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BabyScreen+ newborn screening v1.1 SMN1 Zornitza Stark Tag for review was removed from gene: SMN1.
BabyScreen+ newborn screening v1.1 OAT Zornitza Stark Tag for review was removed from gene: OAT.
BabyScreen+ newborn screening v1.1 MLH1 Zornitza Stark Tag for review was removed from gene: MLH1.
BabyScreen+ newborn screening v1.1 KCNJ2 Zornitza Stark Tag for review was removed from gene: KCNJ2.
Tag treatable tag was added to gene: KCNJ2.
BabyScreen+ newborn screening v1.1 HIBCH Zornitza Stark Tag for review was removed from gene: HIBCH.
BabyScreen+ newborn screening v1.1 NIPAL4 Zornitza Stark Tag for review was removed from gene: NIPAL4.
Tag treatable tag was added to gene: NIPAL4.
Tag dermatological tag was added to gene: NIPAL4.
BabyScreen+ newborn screening v1.1 SAMD9 Zornitza Stark Tag treatable tag was added to gene: SAMD9.
Tag endocrine tag was added to gene: SAMD9.
Tag haematological tag was added to gene: SAMD9.
BabyScreen+ newborn screening v1.1 PDP1 Zornitza Stark Tag treatable tag was added to gene: PDP1.
Tag metabolic tag was added to gene: PDP1.
Phagocyte Defects v1.16 GFI1 Zornitza Stark Tag treatable tag was added to gene: GFI1.
Mendeliome v1.1117 GFI1 Zornitza Stark Tag treatable tag was added to gene: GFI1.
Bone Marrow Failure v1.46 GFI1 Zornitza Stark Tag treatable tag was added to gene: GFI1.
BabyScreen+ newborn screening v1.1 GFI1 Zornitza Stark Tag treatable tag was added to gene: GFI1.
Tag immunological tag was added to gene: GFI1.
BabyScreen+ newborn screening v1.1 DLAT Zornitza Stark Tag treatable tag was added to gene: DLAT.
Tag metabolic tag was added to gene: DLAT.
Severe Combined Immunodeficiency (absent T present B cells) v1.3 CORO1A Zornitza Stark Tag treatable tag was added to gene: CORO1A.
Mendeliome v1.1117 CORO1A Zornitza Stark Tag treatable tag was added to gene: CORO1A.
BabyScreen+ newborn screening v1.1 CORO1A Zornitza Stark Tag treatable tag was added to gene: CORO1A.
Tag immunological tag was added to gene: CORO1A.
Susceptibility to Viral Infections v0.113 CD70 Zornitza Stark Tag treatable tag was added to gene: CD70.
Disorders of immune dysregulation v0.178 CD70 Zornitza Stark Tag treatable tag was added to gene: CD70.
Mendeliome v1.1117 CD70 Zornitza Stark Tag treatable tag was added to gene: CD70.
BabyScreen+ newborn screening v1.1 CD70 Zornitza Stark Tag treatable tag was added to gene: CD70.
Tag immunological tag was added to gene: CD70.
Combined Immunodeficiency v1.43 CD40 Zornitza Stark Tag treatable tag was added to gene: CD40.
Mendeliome v1.1117 CD40 Zornitza Stark Tag treatable tag was added to gene: CD40.
BabyScreen+ newborn screening v1.1 CD40 Zornitza Stark Tag treatable tag was added to gene: CD40.
Tag immunological tag was added to gene: CD40.
BabyScreen+ newborn screening v1.1 BMP1 Zornitza Stark Tag skeletal tag was added to gene: BMP1.
Incidentalome v0.254 ATP7B Bryony Thompson Publications for gene: ATP7B were set to
Incidentalome v0.253 ATP7B Bryony Thompson Tag treatable tag was added to gene: ATP7B.
Incidentalome v0.253 ATP7B Bryony Thompson Mode of inheritance for gene: ATP7B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Incidentalome v0.252 ATP7B Bryony Thompson Phenotypes for gene: ATP7B were changed from to Wilson Disease (MONDO:0010200; MIM #277900)
Incidentalome v0.251 ATP13A2 Bryony Thompson Marked gene: ATP13A2 as ready
Incidentalome v0.251 ATP13A2 Bryony Thompson Gene: atp13a2 has been classified as Green List (High Evidence).
Incidentalome v0.251 ATP13A2 Bryony Thompson Phenotypes for gene: ATP13A2 were changed from to Kufor-Rakeb syndrome, MIM# 606693
Incidentalome v0.250 ATP13A2 Bryony Thompson Mode of inheritance for gene: ATP13A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Incidentalome v0.249 ATP13A2 Bryony Thompson Tag neurological tag was added to gene: ATP13A2.
Incidentalome v0.249 APP Bryony Thompson Marked gene: APP as ready
Incidentalome v0.249 APP Bryony Thompson Gene: app has been classified as Green List (High Evidence).
Incidentalome v0.249 APP Bryony Thompson Phenotypes for gene: APP were changed from to Alzheimer's Disease (MIM#104300)
Incidentalome v0.248 APP Bryony Thompson Publications for gene: APP were set to
Incidentalome v0.247 APP Bryony Thompson Mode of pathogenicity for gene: APP was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Incidentalome v0.246 APP Bryony Thompson Mode of inheritance for gene: APP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.245 APP Bryony Thompson Tag adult onset neurodegenerative tag was added to gene: APP.
Incidentalome v0.245 APOE Bryony Thompson Phenotypes for gene: APOE were changed from Alzheimer disease 2, MIM# 104310 to Alzheimer disease 2, MIM# 104310; Hyperlipoproteinemia, type III (MIM#617347); Sea-blue histiocyte disease (MIM#269600)
Incidentalome v0.244 APOE Bryony Thompson Tag adult onset neurodegenerative tag was added to gene: APOE.
Incidentalome v0.243 APOE Bryony Thompson Phenotypes for gene: APOE were changed from to Alzheimer disease 2, MIM# 104310
Incidentalome v0.242 APOB Bryony Thompson Marked gene: APOB as ready
Incidentalome v0.242 APOB Bryony Thompson Gene: apob has been classified as Green List (High Evidence).
Incidentalome v0.242 APOB Bryony Thompson Mode of inheritance for gene: APOB was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.241 APOB Bryony Thompson Phenotypes for gene: APOB were changed from to Hypercholesterolemia, familial, 2, MIM# 144010
Incidentalome v0.240 APOB Bryony Thompson Mode of inheritance for gene: APOB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.239 APOB Bryony Thompson Tag treatable tag was added to gene: APOB.
Incidentalome v0.238 ANG Bryony Thompson Marked gene: ANG as ready
Incidentalome v0.238 ANG Bryony Thompson Gene: ang has been classified as Amber List (Moderate Evidence).
Incidentalome v0.238 ANG Bryony Thompson Phenotypes for gene: ANG were changed from to Amyotrophic Lateral Sclerosis (MONDO: 0012753; MIM#611895)
Incidentalome v0.237 ANG Bryony Thompson Publications for gene: ANG were set to
Incidentalome v0.236 ANG Bryony Thompson Tag neurological tag was added to gene: ANG.
Incidentalome v0.236 ANG Bryony Thompson Mode of inheritance for gene: ANG was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.235 ANG Bryony Thompson Mode of inheritance for gene: ANG was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.235 ANG Bryony Thompson Classified gene: ANG as Amber List (moderate evidence)
Incidentalome v0.235 ANG Bryony Thompson Gene: ang has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v1.0 Bryony Thompson promoted panel to version 1.0
Motor Neurone Disease v0.194 HNRNPA2B1 Bryony Thompson changed review comment from: Comment on list classification: Assigned amber because HNRNPA2B1 is a multisystem proteinopathy gene, with includes ALS in the spectrum of phenotypes; to: Comment on list classification: Assigned amber because HNRNPA2B1 is a multisystem proteinopathy gene, which includes ALS in the spectrum of phenotypes
Motor Neurone Disease v0.194 HNRNPA2B1 Bryony Thompson Classified gene: HNRNPA2B1 as Amber List (moderate evidence)
Motor Neurone Disease v0.194 HNRNPA2B1 Bryony Thompson Added comment: Comment on list classification: Assigned amber because HNRNPA2B1 is a multisystem proteinopathy gene, which includes ALS in the spectrum of phenotypes
Motor Neurone Disease v0.194 HNRNPA2B1 Bryony Thompson Gene: hnrnpa2b1 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.194 HNRNPA2B1 Bryony Thompson Classified gene: HNRNPA2B1 as Amber List (moderate evidence)
Motor Neurone Disease v0.194 HNRNPA2B1 Bryony Thompson Added comment: Comment on list classification: Assigned amber because HNRNPA2B1 is a multisystem proteinopathy gene, with includes ALS in the spectrum of phenotypes
Motor Neurone Disease v0.194 HNRNPA2B1 Bryony Thompson Gene: hnrnpa2b1 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.193 EWSR1 Bryony Thompson Marked gene: EWSR1 as ready
Motor Neurone Disease v0.193 EWSR1 Bryony Thompson Gene: ewsr1 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.193 ERLIN1 Bryony Thompson Marked gene: ERLIN1 as ready
Motor Neurone Disease v0.193 ERLIN1 Bryony Thompson Gene: erlin1 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.193 DAO Bryony Thompson Marked gene: DAO as ready
Motor Neurone Disease v0.193 DAO Bryony Thompson Gene: dao has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.193 CCNF Bryony Thompson edited their review of gene: CCNF: Changed rating: AMBER
Early-onset Dementia v1.0 Bryony Thompson promoted panel to version 1.0
Early-onset Dementia v0.221 NR4A2 Bryony Thompson Marked gene: NR4A2 as ready
Early-onset Dementia v0.221 NR4A2 Bryony Thompson Gene: nr4a2 has been classified as Red List (Low Evidence).
Early-onset Dementia v0.221 HTRA2 Bryony Thompson Marked gene: HTRA2 as ready
Early-onset Dementia v0.221 HTRA2 Bryony Thompson Gene: htra2 has been classified as Red List (Low Evidence).
Early-onset Dementia v0.221 TIA1 Bryony Thompson Marked gene: TIA1 as ready
Early-onset Dementia v0.221 TIA1 Bryony Thompson Gene: tia1 has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.221 TIA1 Bryony Thompson Classified gene: TIA1 as Amber List (moderate evidence)
Early-onset Dementia v0.221 TIA1 Bryony Thompson Gene: tia1 has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.220 TIA1 Bryony Thompson gene: TIA1 was added
gene: TIA1 was added to Early-onset Dementia. Sources: Literature
Mode of inheritance for gene: TIA1 was set to Other
Publications for gene: TIA1 were set to 36861178; 29599744; 29457785
Phenotypes for gene: TIA1 were set to Multisystem proteinopathy
Review for gene: TIA1 was set to AMBER
Added comment: Digenic variants in SQSTM1 and TIA1 have been reported in multisystem proteinopathy which includes clinical combinations of inclusion body myopathy (IBM), neurodegeneration [motor neuron disorder (MND)/frontotemporal dementia (FTD)], and Paget disease of bone (PDB). FTD has reported in at least one individual with FTD as a feature of the phenotype.
Sources: Literature
Early-onset Dementia v0.219 HNRNPA1 Bryony Thompson Classified gene: HNRNPA1 as Amber List (moderate evidence)
Early-onset Dementia v0.219 HNRNPA1 Bryony Thompson Added comment: Comment on list classification: Included as an amber gene because the gene is associated with multisystem proteinopathy, which FTD can be a feature. No FTD has been reported in association with this gene.
Early-onset Dementia v0.219 HNRNPA1 Bryony Thompson Gene: hnrnpa1 has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.218 GCH1 Bryony Thompson Marked gene: GCH1 as ready
Early-onset Dementia v0.218 GCH1 Bryony Thompson Gene: gch1 has been classified as Red List (Low Evidence).
Early-onset Dementia v0.218 FIG4 Bryony Thompson Marked gene: FIG4 as ready
Early-onset Dementia v0.218 FIG4 Bryony Thompson Gene: fig4 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.193 ANG Bryony Thompson Classified gene: ANG as Amber List (moderate evidence)
Motor Neurone Disease v0.193 ANG Bryony Thompson Gene: ang has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.218 ANG Bryony Thompson Marked gene: ANG as ready
Early-onset Dementia v0.218 ANG Bryony Thompson Gene: ang has been classified as Red List (Low Evidence).
Early-onset Dementia v0.218 ALS2 Bryony Thompson Marked gene: ALS2 as ready
Early-onset Dementia v0.218 ALS2 Bryony Thompson Gene: als2 has been classified as Red List (Low Evidence).
Early-onset Dementia v0.218 SCA17 Bryony Thompson Classified STR: SCA17 as Green List (high evidence)
Early-onset Dementia v0.218 SCA17 Bryony Thompson Str: sca17 has been classified as Green List (High Evidence).
Early-onset Dementia v0.217 SCA17 Bryony Thompson Marked STR: SCA17 as ready
Early-onset Dementia v0.217 SCA17 Bryony Thompson Str: sca17 has been classified as Red List (Low Evidence).
Early-onset Dementia v0.217 SCA17 Bryony Thompson STR: SCA17 was added
STR: SCA17 was added to Early-onset Dementia. Sources: Expert list
Mode of inheritance for STR: SCA17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA17 were set to 10484774; 20301611
Phenotypes for STR: SCA17 were set to Spinocerebellar ataxia 17 MIM#607136
Review for STR: SCA17 was set to GREEN
STR: SCA17 was marked as clinically relevant
Added comment: NM_003194.4:c.172_174[X]
Mechanism of disease expected to be gain of function
Normal: ≤ 40 CAG/CAA repeats
Reduced-penetrance: 41-48 CAG/CAA repeats, individual may or may not develop symptoms.
Full-penetrance: ≥49 CAG/CAA repeats
Dementia is a feature of the condition
Sources: Expert list
Early-onset Dementia v0.216 XK Sangavi Sivagnanasundram Deleted their comment
Early-onset Dementia v0.216 XK Sangavi Sivagnanasundram edited their review of gene: XK: Added comment: McLeod Syndrome (MLS) is multisystem disorder with central nervous system (CNS), neuromuscular, cardiovascular, and hematologic manifestations in males.

Dementia is not a typical feature of MLS but cognitive impairment has been identified in multiple individuals with MLS.

PMID: 12899725
Reported in one individual with McLeod Syndrome (MLS) who developed mild dementia during disease progression (age of onset was later in life). Testing confirmed he has a complete deletion of exon 2.

PMID: 11761473
Approx 15 individuals identified with neurological impact to the central nervous system resulting in cognitive impairment.; Changed rating: GREEN; Changed publications: 12899725, 11761473
Early-onset Dementia v0.216 CCNF Bryony Thompson edited their review of gene: CCNF: Changed rating: AMBER
Skeletal dysplasia v0.248 RAB3GAP2 Ain Roesley Classified gene: RAB3GAP2 as Green List (high evidence)
Skeletal dysplasia v0.248 RAB3GAP2 Ain Roesley Gene: rab3gap2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.248 RAB3GAP2 Ain Roesley Marked gene: RAB3GAP2 as ready
Skeletal dysplasia v0.248 RAB3GAP2 Ain Roesley Gene: rab3gap2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.248 RAB3GAP2 Ain Roesley Mode of inheritance for gene: RAB3GAP2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.248 RAB3GAP2 Ain Roesley Publications for gene: RAB3GAP2 were set to 23420520; 20967465
Skeletal dysplasia v0.247 RAB3GAP2 Ain Roesley Phenotypes for gene: RAB3GAP2 were changed from Warburg micro syndrome 2, MIM# 614225 to Martsolf syndrome 1 MIM#212720
Skeletal dysplasia v0.246 RAB3GAP2 Ain Roesley Phenotypes for gene: RAB3GAP2 were changed from Martsolf syndrome to Warburg micro syndrome 2, MIM# 614225
Skeletal dysplasia v0.246 RAB3GAP2 Ain Roesley Publications for gene: RAB3GAP2 were set to
Skeletal dysplasia v0.246 RAB3GAP2 Ain Roesley Mode of inheritance for gene: RAB3GAP2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.246 RAB3GAP2 Ain Roesley Classified gene: RAB3GAP2 as Green List (high evidence)
Skeletal dysplasia v0.246 RAB3GAP2 Ain Roesley Gene: rab3gap2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.245 PHF6 Ain Roesley Marked gene: PHF6 as ready
Skeletal dysplasia v0.245 PHF6 Ain Roesley Gene: phf6 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.245 PHF6 Ain Roesley Phenotypes for gene: PHF6 were changed from Coffin-Siris syndrome to Borjeson-Forssman-Lehmann syndrome, MIM# 301900
Skeletal dysplasia v0.245 PHF6 Ain Roesley Publications for gene: PHF6 were set to
Skeletal dysplasia v0.244 PHF6 Ain Roesley Mode of inheritance for gene: PHF6 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal dysplasia v0.244 PHF6 Ain Roesley Classified gene: PHF6 as Green List (high evidence)
Skeletal dysplasia v0.244 PHF6 Ain Roesley Gene: phf6 has been classified as Green List (High Evidence).
Mendeliome v1.1117 DDRGK1 Ain Roesley Marked gene: DDRGK1 as ready
Mendeliome v1.1117 DDRGK1 Ain Roesley Gene: ddrgk1 has been classified as Green List (High Evidence).
Mendeliome v1.1117 DDRGK1 Ain Roesley Classified gene: DDRGK1 as Green List (high evidence)
Mendeliome v1.1117 DDRGK1 Ain Roesley Gene: ddrgk1 has been classified as Green List (High Evidence).
Mendeliome v1.1116 DDRGK1 Ain Roesley gene: DDRGK1 was added
gene: DDRGK1 was added to Mendeliome. Sources: Literature
founder tags were added to gene: DDRGK1.
Mode of inheritance for gene: DDRGK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDRGK1 were set to 28263186; 35377455; 35670300; 36243336
Phenotypes for gene: DDRGK1 were set to Spondyloepimetaphyseal dysplasia, Shohat type (MIM#602557)
Review for gene: DDRGK1 was set to GREEN
gene: DDRGK1 was marked as current diagnostic
Added comment: RNA and protein studies performed for the splice variant. These two variants likely represents founder variants

PMID:28263186 reported six individuals from three different families of Iraqi Jewish descent (three patients from family 1 and one individual each from families 2-4) identified with homozygous c.408+1G>A donor splice site loss-of-function mutation in DDRGK1 and presented with Shohat-type spondyloepimetaphyseal dysplasia (SEMD). It is a skeletal dysplasia that affects cartilage development.

PMID: 35670300 reported two unrelated cases of Moroccan descent identified with homozygous missense variant c.406G>A and presented with SEMD. PMID:36243336 reported an Omani female patient identified with the same homozygous variant as the Iraqi cases and was reported with SEMD.

In addition, studies on both zebrafish and mouse models confirms the physiological role of DDRGK1 in the development and maintenance of the growth plate cartilage and deficiency of DDRGK1 recapitulate the clinical phenotype of short stature and joint abnormalities observed in patients with Shohat type SEMD (PMID:28263186; PMID:35377455).
Sources: Literature
Skeletal dysplasia v0.243 DDRGK1 Ain Roesley Marked gene: DDRGK1 as ready
Skeletal dysplasia v0.243 DDRGK1 Ain Roesley Added comment: Comment when marking as ready: RNA and protein studies performed for the splice variant. These two variants likely represents founder variants
Skeletal dysplasia v0.243 DDRGK1 Ain Roesley Gene: ddrgk1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.243 DDRGK1 Ain Roesley Tag founder tag was added to gene: DDRGK1.
Skeletal dysplasia v0.243 DDRGK1 Ain Roesley Classified gene: DDRGK1 as Green List (high evidence)
Skeletal dysplasia v0.243 DDRGK1 Ain Roesley Gene: ddrgk1 has been classified as Green List (High Evidence).
Early-onset Dementia v0.216 NHLRC1 Zornitza Stark Marked gene: NHLRC1 as ready
Early-onset Dementia v0.216 NHLRC1 Zornitza Stark Gene: nhlrc1 has been classified as Green List (High Evidence).
Early-onset Dementia v0.216 NHLRC1 Zornitza Stark Phenotypes for gene: NHLRC1 were changed from to Epilepsy, progressive myoclonic 2B (Lafora Disease) MIM#254780
Early-onset Dementia v0.215 NHLRC1 Zornitza Stark Publications for gene: NHLRC1 were set to
Early-onset Dementia v0.214 NHLRC1 Zornitza Stark Mode of inheritance for gene: NHLRC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.213 NPC2 Zornitza Stark Marked gene: NPC2 as ready
Early-onset Dementia v0.213 NPC2 Zornitza Stark Gene: npc2 has been classified as Green List (High Evidence).
Early-onset Dementia v0.213 NPC2 Zornitza Stark Phenotypes for gene: NPC2 were changed from to Niemann-pick disease, type C2 MIM#607625
Early-onset Dementia v0.212 NPC2 Zornitza Stark Publications for gene: NPC2 were set to
Early-onset Dementia v0.211 NPC2 Zornitza Stark Mode of inheritance for gene: NPC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.210 OPTN Zornitza Stark Marked gene: OPTN as ready
Early-onset Dementia v0.210 OPTN Zornitza Stark Gene: optn has been classified as Green List (High Evidence).
Early-onset Dementia v0.210 OPTN Zornitza Stark Phenotypes for gene: OPTN were changed from to Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia (MIM#613435)
Early-onset Dementia v0.209 OPTN Zornitza Stark Publications for gene: OPTN were set to
Early-onset Dementia v0.208 OPTN Zornitza Stark Mode of inheritance for gene: OPTN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Dementia v0.207 PANK2 Zornitza Stark Marked gene: PANK2 as ready
Early-onset Dementia v0.207 PANK2 Zornitza Stark Gene: pank2 has been classified as Green List (High Evidence).
Early-onset Dementia v0.207 PANK2 Zornitza Stark Phenotypes for gene: PANK2 were changed from to Neurodegeneration with brain iron accumulation 1 (MIM#234200)
Early-onset Dementia v0.206 PANK2 Zornitza Stark Publications for gene: PANK2 were set to
Early-onset Dementia v0.205 PANK2 Zornitza Stark Mode of inheritance for gene: PANK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.204 PRNP Zornitza Stark Marked gene: PRNP as ready
Early-onset Dementia v0.204 PRNP Zornitza Stark Gene: prnp has been classified as Green List (High Evidence).
Early-onset Dementia v0.204 PRNP Zornitza Stark Phenotypes for gene: PRNP were changed from to Prion Disease (MIM#176640); Creutzfeldt-Jakob disease (MIM#123400)
Early-onset Dementia v0.203 PRNP Zornitza Stark Publications for gene: PRNP were set to
Early-onset Dementia v0.202 PRNP Zornitza Stark Mode of inheritance for gene: PRNP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.201 PSEN1 Zornitza Stark Marked gene: PSEN1 as ready
Early-onset Dementia v0.201 PSEN1 Zornitza Stark Gene: psen1 has been classified as Green List (High Evidence).
Early-onset Dementia v0.201 PSEN1 Zornitza Stark Phenotypes for gene: PSEN1 were changed from to Alzheimer disease, type 3 (MIM#607822; MONDO:0011913)
Early-onset Dementia v0.200 PSEN1 Zornitza Stark Publications for gene: PSEN1 were set to
Early-onset Dementia v0.199 PSEN1 Zornitza Stark Mode of inheritance for gene: PSEN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.198 PSEN2 Zornitza Stark Marked gene: PSEN2 as ready
Early-onset Dementia v0.198 PSEN2 Zornitza Stark Gene: psen2 has been classified as Green List (High Evidence).
Early-onset Dementia v0.198 PSEN2 Zornitza Stark Phenotypes for gene: PSEN2 were changed from to Alzheimer disease-4 (MIM#606889)
Early-onset Dementia v0.197 PSEN2 Zornitza Stark Publications for gene: PSEN2 were set to
Early-onset Dementia v0.196 PSEN2 Zornitza Stark Mode of inheritance for gene: PSEN2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.195 SQSTM1 Zornitza Stark Marked gene: SQSTM1 as ready
Early-onset Dementia v0.195 SQSTM1 Zornitza Stark Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.195 SQSTM1 Zornitza Stark Phenotypes for gene: SQSTM1 were changed from to Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 (MIM#616437)
Early-onset Dementia v0.194 SQSTM1 Zornitza Stark Publications for gene: SQSTM1 were set to
Early-onset Dementia v0.193 SQSTM1 Zornitza Stark Mode of inheritance for gene: SQSTM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.192 SQSTM1 Zornitza Stark Classified gene: SQSTM1 as Amber List (moderate evidence)
Early-onset Dementia v0.192 SQSTM1 Zornitza Stark Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.191 TARDBP Zornitza Stark Marked gene: TARDBP as ready
Early-onset Dementia v0.191 TARDBP Zornitza Stark Gene: tardbp has been classified as Green List (High Evidence).
Early-onset Dementia v0.191 TARDBP Zornitza Stark Phenotypes for gene: TARDBP were changed from to Amyotrophic lateral sclerosis 10, with or without FTD (MIM#612069)
Early-onset Dementia v0.190 TARDBP Zornitza Stark Publications for gene: TARDBP were set to
Early-onset Dementia v0.189 TARDBP Zornitza Stark Mode of inheritance for gene: TARDBP was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Dementia v0.188 TBK1 Zornitza Stark Marked gene: TBK1 as ready
Early-onset Dementia v0.188 TBK1 Zornitza Stark Gene: tbk1 has been classified as Green List (High Evidence).
Early-onset Dementia v0.188 TBK1 Zornitza Stark Phenotypes for gene: TBK1 were changed from to Frontotemporal dementia and/or amyotrophic lateral sclerosis 4, MIM# 616439
Early-onset Dementia v0.187 TBK1 Zornitza Stark Publications for gene: TBK1 were set to
Early-onset Dementia v0.186 TBK1 Zornitza Stark Mode of inheritance for gene: TBK1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.185 TYROBP Zornitza Stark Marked gene: TYROBP as ready
Early-onset Dementia v0.185 TYROBP Zornitza Stark Gene: tyrobp has been classified as Green List (High Evidence).
Early-onset Dementia v0.185 TYROBP Zornitza Stark Phenotypes for gene: TYROBP were changed from to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 (MIM#221770)
Early-onset Dementia v0.184 TYROBP Zornitza Stark Publications for gene: TYROBP were set to
Early-onset Dementia v0.183 TYROBP Zornitza Stark Mode of inheritance for gene: TYROBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1115 FBXO31 Zornitza Stark Phenotypes for gene: FBXO31 were changed from Mental retardation, autosomal recessive 45, MIM#615979; Cerebral palsy, MONDO:0006497, FBXO31-related; Spastic-dystonic cerebral palsy, intellectual disability, de novo dominant to Intellectual developmental disorder, autosomal recessive 45 (MIM#615979; Cerebral palsy, MONDO:0006497, FBXO31-related; Spastic-dystonic cerebral palsy, intellectual disability, de novo dominant
Mendeliome v1.1114 FBXO31 Zornitza Stark Phenotypes for gene: FBXO31 were changed from Mental retardation, autosomal recessive 45, MIM#615979; Spastic-dystonic cerebral palsy, intellectual disability, de novo dominant to Mental retardation, autosomal recessive 45, MIM#615979; Cerebral palsy, MONDO:0006497, FBXO31-related; Spastic-dystonic cerebral palsy, intellectual disability, de novo dominant
Mendeliome v1.1113 FBXO31 Zornitza Stark Publications for gene: FBXO31 were set to 24623383; 32989326
Early-onset Dementia v0.182 PLA2G6 Zornitza Stark Marked gene: PLA2G6 as ready
Early-onset Dementia v0.182 PLA2G6 Zornitza Stark Gene: pla2g6 has been classified as Green List (High Evidence).
Early-onset Dementia v0.182 PLA2G6 Zornitza Stark Phenotypes for gene: PLA2G6 were changed from to Parkinson disease 14, autosomal recessive, MIM# 612953
Early-onset Dementia v0.181 PLA2G6 Zornitza Stark Publications for gene: PLA2G6 were set to
Early-onset Dementia v0.180 PLA2G6 Zornitza Stark Mode of inheritance for gene: PLA2G6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.107 DOCK11 Zornitza Stark Marked gene: DOCK11 as ready
Inflammatory bowel disease v0.107 DOCK11 Zornitza Stark Gene: dock11 has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.107 DOCK11 Zornitza Stark Phenotypes for gene: DOCK11 were changed from Inflammatory bowel disease to Autoimmune disease with immune dysregulation, X-linked (ADMIDX), MIM#301109; Inflammatory bowel disease
Inflammatory bowel disease v0.106 DOCK11 Zornitza Stark Classified gene: DOCK11 as Green List (high evidence)
Inflammatory bowel disease v0.106 DOCK11 Zornitza Stark Gene: dock11 has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.105 DOCK11 Zornitza Stark reviewed gene: DOCK11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoimmune disease with immune dysregulation, X-linked (ADMIDX), MIM#301109; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal dysplasia v0.242 Zornitza Stark removed gene:PLK4 from the panel
Skeletal dysplasia v0.241 PLK4 Zornitza Stark changed review comment from: At least 3 unrelated families reported with autosomal recessive developmental disorder characterised by delayed psychomotor development, visual impairment, and microcephaly.; to: At least 3 unrelated families reported with autosomal recessive developmental disorder characterised by delayed psychomotor development, visual impairment, and microcephaly.

Short stature but no specific skeletal abnormalities.
Skeletal dysplasia v0.241 PLK4 Zornitza Stark edited their review of gene: PLK4: Changed rating: RED
Skeletal dysplasia v0.241 PHF6 Zornitza Stark changed review comment from: Clinical features are quite variable, with the most consistent features being initial hypotonia, mild to moderate impaired intellectual development, large fleshy ears, underdeveloped genitalia, gynecomastia, truncal obesity, tapering fingers, and shortening of the fourth and fifth toes. Heterozygous females may have a milder similar clinical phenotype, which can include hypothyroidism; however, many carrier females appear unaffected.

More than 20 families reported.; to: Clinical features are quite variable, with the most consistent features being initial hypotonia, mild to moderate impaired intellectual development, large fleshy ears, underdeveloped genitalia, gynecomastia, truncal obesity, tapering fingers, and shortening of the fourth and fifth toes. Heterozygous females may have a milder similar clinical phenotype, which can include hypothyroidism; however, many carrier females appear unaffected.

More than 20 families reported.

Abnormal skeletal features including thickened calvarium and abnormal vertebrae reported.
Inflammatory bowel disease v0.105 DOCK11 Peter McNaughton gene: DOCK11 was added
gene: DOCK11 was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: DOCK11 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: DOCK11 were set to PMID: 37342957; PMID: 36952639
Phenotypes for gene: DOCK11 were set to Inflammatory bowel disease
Added comment: 12 patients across 2 studies described. Severe gastrointestinal disease was observed in most of the patients, manifested as ulcerative colitis-like or Crohn's disease-like inflammatory bowel disease, unspecified ileitis, and colitis. Oral and anal ulcerations or ileus affected 6 of the patients.
Sources: Literature
Callosome v0.501 ATP6V0C Zornitza Stark Phenotypes for gene: ATP6V0C were changed from neurodevelopmental disorder (MONDO:0700092), ATP6V0C-related to Epilepsy, early-onset, with or without developmental delay, MIM#620465; neurodevelopmental disorder (MONDO:0700092), ATP6V0C-related
Intellectual disability syndromic and non-syndromic v0.5336 ATP6V0C Zornitza Stark Phenotypes for gene: ATP6V0C were changed from Epilepsy; Intellectual Disability; microcephaly to Epilepsy, early-onset, with or without developmental delay, MIM#620465; Epilepsy; Intellectual Disability; microcephaly
Genetic Epilepsy v0.1881 ATP6V0C Zornitza Stark Phenotypes for gene: ATP6V0C were changed from Epilepsy; Intellectual Disability; microcephaly to Epilepsy, early-onset, with or without developmental delay, MIM#620465; Epilepsy; Intellectual Disability; microcephaly
Genetic Epilepsy v0.1880 ATP6V0C Zornitza Stark edited their review of gene: ATP6V0C: Changed phenotypes: Epilepsy, early-onset, with or without developmental delay, MIM#620465, Intellectual disability, seizures
Mendeliome v1.1112 ATP6V0C Zornitza Stark Phenotypes for gene: ATP6V0C were changed from Epilepsy; Intellectual Disability; microcephaly to Epilepsy, early-onset, with or without developmental delay, MIM#620465; Epilepsy; Intellectual Disability; microcephaly
Mendeliome v1.1111 ATP6V0C Zornitza Stark edited their review of gene: ATP6V0C: Changed phenotypes: Epilepsy, early-onset, with or without developmental delay, MIM#620465, Epilepsy, Intellectual Disability, microcephaly
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.24 HNRNPA1 Zornitza Stark changed review comment from: PMID 34722876: single multigenerational family reported with distal myopathy and 160bp deletion involving exon 10.; to: PMID 34722876: single multigenerational family reported with slowly progressive distal myopathy and 160bp deletion involving exon 10.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.24 HNRNPA1 Zornitza Stark Phenotypes for gene: HNRNPA1 were changed from inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3 MONDO:0014179 to Myopathy, distal, 3, MIM# 610099; inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3 MONDO:0014179
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.23 HNRNPA1 Zornitza Stark Publications for gene: HNRNPA1 were set to 23455423; 27066560
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.22 HNRNPA1 Zornitza Stark edited their review of gene: HNRNPA1: Added comment: PMID 34722876: single multigenerational family reported with distal myopathy and 160bp deletion involving exon 10.; Changed publications: 23455423, 34291734, 34722876; Changed phenotypes: Amyotrophic lateral sclerosis 20 MIM#615426, Myopathy, distal, 3, MIM# 610099
Early-onset Dementia v0.179 PLA2G6 Sangavi Sivagnanasundram reviewed gene: PLA2G6: Rating: AMBER; Mode of pathogenicity: None; Publications: 25634434, 26836416, 22406380, 20938027; Phenotypes: Parkinson disease 14, autosomal recessive 612953; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1111 FBXO31 Ain Roesley reviewed gene: FBXO31: Rating: AMBER; Mode of pathogenicity: None; Publications: 35019165, 24623383; Phenotypes: Intellectual developmental disorder, autosomal recessive 45 (MIM#615979); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Early-onset Dementia v0.179 TYROBP Sangavi Sivagnanasundram reviewed gene: TYROBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301376; Phenotypes: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 (MIM#221770); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.179 TBK1 Sangavi Sivagnanasundram reviewed gene: TBK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301623; Phenotypes: Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 616439; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.179 TARDBP Sangavi Sivagnanasundram reviewed gene: TARDBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301761, 21803454; Phenotypes: Amyotrophic lateral sclerosis 10, with or without FTD (MIM#612069); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Dementia v0.179 SQSTM1 Sangavi Sivagnanasundram reviewed gene: SQSTM1: Rating: AMBER; Mode of pathogenicity: None; Publications: 22084127, 22972638; Phenotypes: Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 (MIM#616437); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early-onset Dementia v0.179 PSEN2 Sangavi Sivagnanasundram reviewed gene: PSEN2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 22503161, 20301340, 25323700, 35491795; Phenotypes: Alzheimer disease-4 (MIM#606889); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early-onset Dementia v0.179 PSEN1 Sangavi Sivagnanasundram reviewed gene: PSEN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22503161, 20301340; Phenotypes: Alzheimer disease, type 3 (MIM#607822, MONDO:0011913); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.179 PRNP Sangavi Sivagnanasundram reviewed gene: PRNP: Rating: GREEN; Mode of pathogenicity: None; Publications: 27910931, 19571725, 20301407, 6351815; Phenotypes: Prion Disease (MIM#176640), Creutzfeldt-Jakob disease (MIM#123400); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early-onset Dementia v0.179 PANK2 Sangavi Sivagnanasundram reviewed gene: PANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24600523, 23447832, 19480328; Phenotypes: Neurodegeneration with brain iron accumulation 1 (MIM#234200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.179 OPTN Sangavi Sivagnanasundram reviewed gene: OPTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 31838784, 20428114, 20301623; Phenotypes: Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia (MIM#613435); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Dementia v0.179 NPC2 Sangavi Sivagnanasundram reviewed gene: NPC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27792009, 20525256; Phenotypes: Niemann-pick disease, type C2 MIM#607625; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.179 NPC1 Sangavi Sivagnanasundram edited their review of gene: NPC1: Changed rating: AMBER
Early-onset Dementia v0.179 NPC1 Sangavi Sivagnanasundram changed review comment from: NPC is a slowly progressive lysosomal disorder with subtle cognitive impairment in affected individuals at first which progresses to dementia during the disease course. LoF is the mechanism of disease.

PMID: 11182931
reported in one individual with NPC and dementia as a phenotype.; to: NPC is a slowly progressive lysosomal disorder with subtle cognitive impairment in affected individuals at first which progresses to dementia during the disease course. NPC type 1 is also known as "juvenile alzheimers disease". LoF is the mechanism of disease.

PMID: 11182931
reported in one individual with NPC and dementia as a phenotype.
Early-onset Dementia v0.179 NPC1 Sangavi Sivagnanasundram edited their review of gene: NPC1: Changed rating: GREEN; Changed publications: 20301473, 11182931, 22495346
Early-onset Dementia v0.179 NHLRC1 Sangavi Sivagnanasundram reviewed gene: NHLRC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28556688, 34117373; Phenotypes: Epilepsy, progressive myoclonic 2B (Lafora Disease) MIM#254780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.1 Zornitza Stark Panel name changed from Baby Screen+ newborn screening to BabyScreen+ newborn screening
Hereditary Neuropathy - complex v1.0 Bryony Thompson promoted panel to version 1.0
Hereditary Neuropathy - complex v0.275 SPAST Bryony Thompson Marked gene: SPAST as ready
Hereditary Neuropathy - complex v0.275 SPAST Bryony Thompson Gene: spast has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.275 SPAST Sangavi Sivagnanasundram changed review comment from: Neuropathy is a feature in complex HSP which is caused by autosomal dominant mutations in SPAST or KIF5A.

PMID: 322442913; 22192498
3 unrelated individuals with HSP and polyneuropathy as a clinical feature however their WES remains undiagnosed.; to: Neuropathy is a feature in complex HSP which is caused by autosomal dominant mutations in SPAST or KIF5A.

PMID: 32242913; 22192498
3 unrelated individuals with HSP and polyneuropathy as a clinical feature however their WES remains undiagnosed.
Hereditary Neuropathy - complex v0.275 SPAST Sangavi Sivagnanasundram Deleted their comment
Hereditary Neuropathy - complex v0.275 SPAST Sangavi Sivagnanasundram edited their review of gene: SPAST: Changed publications: 32242913, 22192498, 26374131, 20301339
Hereditary Neuropathy - complex v0.275 HEXA Bryony Thompson Marked gene: HEXA as ready
Hereditary Neuropathy - complex v0.275 HEXA Bryony Thompson Gene: hexa has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.275 PLA2G6 Sangavi Sivagnanasundram edited their review of gene: PLA2G6: Added comment: Established gene-disease associated with neuropathy as a clinical feature.

PMID: 25164370
9 individuals from 6 unrelated families with motor or sensory-motor neuropathy. All individuals were found to share the p.V691del variant which is a founder variant in the North African population.; Changed rating: GREEN; Changed publications: 25164370
Hereditary Neuropathy - complex v0.275 PDHA1 Sangavi Sivagnanasundram edited their review of gene: PDHA1: Added comment: PMID: 33661577
Young boy from China with lethal neuropathy and the presence of a de novo mutation in PDHA1 (c.1167_1170del; p.Ser390LysfsTer33) that is clinically significant for Leigh Syndrome. PDCD is known a biochemical pathway in individuals with Leigh Syndrome.

PMID: 36693417
Multiple reported individual with sensory-motor polyneuropathy and a high serum lactate. One individual identified with a hemizygous mutation (p.Arg88Cys) causative of pyruvate dehydrogenase complex deficiency.; Changed rating: GREEN; Changed publications: 33661577, 36693417, 34138529; Changed phenotypes: Primary Pyruvate Dehydrogenase Complex Deficiency MIM#312170
Hereditary Neuropathy - complex v0.275 MTTP Sangavi Sivagnanasundram edited their review of gene: MTTP: Added comment: Reported in multiple individuals with progressive neuropathy due to the deficiency of fat-soluble vitamins (vitamins E, A, D, K). Neuropathy typically presents due to a lack of vitamin E in individuals.; Changed rating: GREEN; Changed publications: 10679949, 29540175
Hereditary Neuropathy - complex v0.275 HEXA Bryony Thompson Publications for gene: HEXA were set to
Hereditary Neuropathy - complex v0.274 ERCC8 Sangavi Sivagnanasundram edited their review of gene: ERCC8: Added comment: Established gene-disease association with progressive neuropathy a feature in individuals with Cockayne Syndrome.

PMID: 29422660
In vitro minigene assay was conducted to test the splice effect of c.173+1119G>C which showed the introduction of a premature termination codon at the end of exon resulting in loss of function of the ERCC8 protein.; Changed rating: GREEN; Changed publications: 25453614, 29422660, 4320535
Hereditary Neuropathy - complex v0.274 ERCC6 Sangavi Sivagnanasundram edited their review of gene: ERCC6: Added comment: PMID: 25376329
Two siblings from a consanguineous family with bilateral peripheral neuropathy and a homozygous splice variant in ERCC6 (c.1992+3A>G).

PMID: 25453614
Progressive neuropathy has been identified in multiple individuals with Cockayne Syndrome.; Changed rating: GREEN; Changed publications: 25376329, 25453614
Hereditary Neuropathy - complex v0.274 ASAH1 Sangavi Sivagnanasundram edited their review of gene: ASAH1: Added comment: PMID:27026573
Siblings from a consanguineous family with SMA phenotype and a homozygous mutation in ASAH1.

PMID: 22703880
5 individuals from 2 unrelated families with SMA and a homozygous mutation (Thr42Met) in ASAH1.

In vivo functional assay using Zebrafish model showed a loss in motor neuron axonal branching and increased apotheosis in the spinal cord suggesting that ASAH plays an integral role in motor-axonal branching and in the survival of spinal cord neurons.; Changed rating: GREEN; Changed publications: 27026573, 22703880; Changed phenotypes: Spinal muscular atrophy with progressive myoclonic epilepsy (MIM#159950)
Hereditary Neuropathy - complex v0.274 SPAST Sangavi Sivagnanasundram edited their review of gene: SPAST: Added comment: Neuropathy is a feature in complex HSP which is caused by autosomal dominant mutations in SPAST or KIF5A.

PMID: 322442913; 22192498
3 unrelated individuals with HSP and polyneuropathy as a clinical feature however their WES remains undiagnosed.; Changed rating: GREEN; Changed publications: 322442913, 22192498, 26374131, 20301339
Hereditary Neuropathy - complex v0.274 HEXA Sangavi Sivagnanasundram changed review comment from: HEXA is associated with the clinical phenotype known as Tay-Sachs disease.
Evidence of sensory neuropathy was present in two unrelated individuals with tay Sachs disease however genetic testing wasn’t conducted to confirm the presence of a HEXA genetic variant in either individual.; to: PMID: 3159334, 1838393: HEXA is associated with the clinical phenotype known as Tay-Sachs disease.
Evidence of sensory neuropathy was present in two unrelated individuals with tay Sachs disease however genetic testing wasn’t conducted to identify genetic pathogenesis.
Hereditary Neuropathy - complex v0.274 HEXA Sangavi Sivagnanasundram edited their review of gene: HEXA: Added comment: Established gene disease associated with >3 unrelated individuals with neuropathy as a clinical feature.
Mutations in HEXA gene cause juvenile gm2 gangliosidosis (jGM2) and Tay Sachs is a well established form of jGM2.

PMID: 17015493
One individual with variant in HEXA and diagnosis of Tay Sachs

PMID: 18642377
Multiple individuals diagnosed with late onset tay-Sachs and identified to have axonal polyneuropathy in 8 individuals.; Changed rating: GREEN; Changed publications: 17015493, 18642377, 3159334, 1838393
Mendeliome v1.1111 TBL1XR1 Achchuthan Shanmugasundram reviewed gene: TBL1XR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28687524, 37010288; Phenotypes: Pierpont syndrome, OMIM:602342; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1111 NEB Achchuthan Shanmugasundram reviewed gene: NEB: Rating: AMBER; Mode of pathogenicity: None; Publications: 12207937, 21798101, 33376055, 37010288; Phenotypes: Arthrogryposis multiplex congenita 6, OMIM:619334; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1111 ECEL1 Achchuthan Shanmugasundram reviewed gene: ECEL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30131190, 37010288; Phenotypes: Arthrogryposis, distal, type 5D, OMIM:615065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.179 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Early-onset Dementia v0.179 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Early-onset Dementia v0.179 NPC1 Zornitza Stark Phenotypes for gene: NPC1 were changed from to Niemann-Pick disease, type C1 (MIM#257220; MONDO:0009757)
Early-onset Dementia v0.178 NPC1 Zornitza Stark Publications for gene: NPC1 were set to
Early-onset Dementia v0.177 NPC1 Zornitza Stark Mode of inheritance for gene: NPC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.176 UBQLN2 Zornitza Stark Phenotypes for gene: UBQLN2 were changed from Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia (MIM#300857) to Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia (MIM#300857)
Early-onset Dementia v0.175 UBQLN2 Zornitza Stark Marked gene: UBQLN2 as ready
Early-onset Dementia v0.175 UBQLN2 Zornitza Stark Gene: ubqln2 has been classified as Green List (High Evidence).
Early-onset Dementia v0.175 UBQLN2 Zornitza Stark Phenotypes for gene: UBQLN2 were changed from to Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia (MIM#300857)
Early-onset Dementia v0.174 UBQLN2 Zornitza Stark Publications for gene: UBQLN2 were set to
Early-onset Dementia v0.173 UBQLN2 Zornitza Stark Mode of inheritance for gene: UBQLN2 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary Neuropathy - complex v0.274 IFRD1 Zornitza Stark Tag refuted tag was added to gene: IFRD1.
Early-onset Dementia v0.172 VCP Zornitza Stark Marked gene: VCP as ready
Early-onset Dementia v0.172 VCP Zornitza Stark Gene: vcp has been classified as Green List (High Evidence).
Early-onset Dementia v0.172 VCP Zornitza Stark Phenotypes for gene: VCP were changed from to Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia 1 (MIM#167320); Frontotemporal dementia and/or amyotrophic lateral sclerosis 6 (MIM#613954)
Early-onset Dementia v0.171 VCP Zornitza Stark Publications for gene: VCP were set to
Early-onset Dementia v0.170 VCP Zornitza Stark Mode of inheritance for gene: VCP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.169 XK Zornitza Stark Marked gene: XK as ready
Early-onset Dementia v0.169 XK Zornitza Stark Gene: xk has been classified as Green List (High Evidence).
Early-onset Dementia v0.169 XK Zornitza Stark Phenotypes for gene: XK were changed from to McLeod syndrome with or without chronic granulomatous disease (MIM#300842)
Early-onset Dementia v0.168 XK Zornitza Stark Publications for gene: XK were set to
Early-onset Dementia v0.167 XK Zornitza Stark Mode of inheritance for gene: XK was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early-onset Dementia v0.166 XK Zornitza Stark reviewed gene: XK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: McLeod syndrome with or without chronic granulomatous disease (MIM#300842); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early-onset Dementia v0.166 GRN Zornitza Stark Marked gene: GRN as ready
Early-onset Dementia v0.166 GRN Zornitza Stark Gene: grn has been classified as Green List (High Evidence).
Early-onset Dementia v0.166 GRN Zornitza Stark Phenotypes for gene: GRN were changed from to frontotemporal dementia and/or amyotrophic lateral sclerosis MONDO:0030923
Early-onset Dementia v0.165 GRN Zornitza Stark Publications for gene: GRN were set to
Early-onset Dementia v0.164 GRN Zornitza Stark Mode of inheritance for gene: GRN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.163 EPM2A Zornitza Stark Marked gene: EPM2A as ready
Early-onset Dementia v0.163 EPM2A Zornitza Stark Gene: epm2a has been classified as Green List (High Evidence).
Early-onset Dementia v0.163 EPM2A Zornitza Stark Phenotypes for gene: EPM2A were changed from to Epilepsy, progressive myoclonic 2A (Lafora) MIM#254780
Early-onset Dementia v0.162 EPM2A Zornitza Stark Publications for gene: EPM2A were set to
Early-onset Dementia v0.161 EPM2A Zornitza Stark Mode of inheritance for gene: EPM2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.160 NPC1 Sangavi Sivagnanasundram reviewed gene: NPC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 20301473, 11182931; Phenotypes: Niemann-Pick disease, type C1 (MIM#257220, MONDO:0009757); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.274 PEX12 Bryony Thompson Marked gene: PEX12 as ready
Hereditary Neuropathy - complex v0.274 PEX12 Bryony Thompson Gene: pex12 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.274 PEX12 Bryony Thompson Publications for gene: PEX12 were set to 24627108
Hereditary Neuropathy - complex v0.273 PEX12 Bryony Thompson Classified gene: PEX12 as Green List (high evidence)
Hereditary Neuropathy - complex v0.273 PEX12 Bryony Thompson Gene: pex12 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.272 PEX12 Bryony Thompson Deleted their comment
Hereditary Neuropathy - complex v0.272 PEX12 Bryony Thompson edited their review of gene: PEX12: Added comment: Neuropathy as a feature of the conditon in 45% (9/14) families with an Egyptian founder variant ((c.1047_1049del p.(Gln349del)) and also in an additional proband.; Changed rating: GREEN; Changed publications: 24627108, 33123925
Hereditary Neuropathy - complex v0.272 NIPA1 Bryony Thompson Marked gene: NIPA1 as ready
Hereditary Neuropathy - complex v0.272 NIPA1 Bryony Thompson Gene: nipa1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.272 NIPA1 Bryony Thompson Classified gene: NIPA1 as Green List (high evidence)
Hereditary Neuropathy - complex v0.272 NIPA1 Bryony Thompson Gene: nipa1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.271 NIPA1 Bryony Thompson edited their review of gene: NIPA1: Added comment: Neuropathy is not a prominent feature of the complicated HSP sometimes reported associated with this gene. However, it has been reported in 6/110 (5.5%) of NIPA1-associated complicated HSP cases.; Changed rating: GREEN; Changed publications: 34863451
Hereditary Neuropathy - complex v0.271 NIPA1 Bryony Thompson Deleted their comment
Early-onset Dementia v0.160 UBQLN2 Sangavi Sivagnanasundram reviewed gene: UBQLN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 20301623, 31319884, 21857683, 30348461; Phenotypes: Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia (MIM#300857); Mode of inheritance: None
Hereditary Neuropathy - complex v0.271 IFRD1 Bryony Thompson Marked gene: IFRD1 as ready
Hereditary Neuropathy - complex v0.271 IFRD1 Bryony Thompson Gene: ifrd1 has been classified as Red List (Low Evidence).
Hereditary Neuropathy - complex v0.271 DCAF8 Bryony Thompson Marked gene: DCAF8 as ready
Hereditary Neuropathy - complex v0.271 DCAF8 Bryony Thompson Gene: dcaf8 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.271 DCAF8 Bryony Thompson Publications for gene: DCAF8 were set to
Hereditary Neuropathy - complex v0.270 CCT5 Bryony Thompson Marked gene: CCT5 as ready
Hereditary Neuropathy - complex v0.270 CCT5 Bryony Thompson Gene: cct5 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.270 CCT5 Bryony Thompson Publications for gene: CCT5 were set to
Hereditary Neuropathy - complex v0.269 CCT5 Bryony Thompson edited their review of gene: CCT5: Added comment: Now two families reported with two different missense variants (Leu224Val and His147Arg).; Changed publications: 16399879, 25124038, 25345891, 33076433, 37237456
Mendeliome v1.1111 CCT5 Bryony Thompson edited their review of gene: CCT5: Added comment: Now two families reported with two different missense variants (Leu224Val and His147Arg).; Changed publications: 16399879, 25124038, 25345891, 33076433, 37237456
Early-onset Dementia v0.160 VCP Sangavi Sivagnanasundram reviewed gene: VCP: Rating: GREEN; Mode of pathogenicity: None; Publications: 15034582, 30103325, 21145000; Phenotypes: Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia 1 (MIM#167320), Frontotemporal dementia and/or amyotrophic lateral sclerosis 6 (MIM#613954); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.160 XK Sangavi Sivagnanasundram reviewed gene: XK: Rating: RED; Mode of pathogenicity: None; Publications: 12899725; Phenotypes: McLeod syndrome with or without chronic granulomatous disease (MIM#300842); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary Neuropathy - complex v0.269 TYMP Bryony Thompson Marked gene: TYMP as ready
Hereditary Neuropathy - complex v0.269 TYMP Bryony Thompson Gene: tymp has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.269 PMM2 Bryony Thompson Marked gene: PMM2 as ready
Hereditary Neuropathy - complex v0.269 PMM2 Bryony Thompson Gene: pmm2 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.269 PMM2 Bryony Thompson Publications for gene: PMM2 were set to
Hereditary Neuropathy - complex v0.268 PRNP Bryony Thompson Marked gene: PRNP as ready
Hereditary Neuropathy - complex v0.268 PRNP Bryony Thompson Gene: prnp has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.268 PRNP Bryony Thompson Phenotypes for gene: PRNP were changed from Prion diseases to Prion diseases; peripheral neuropathy; chronic diarrhea; dementia
Hereditary Neuropathy - complex v0.267 PRNP Bryony Thompson Publications for gene: PRNP were set to
Hereditary Neuropathy - complex v0.266 PRNP Bryony Thompson reviewed gene: PRNP: Rating: GREEN; Mode of pathogenicity: None; Publications: 31953922, 31907995, 29928661, 27716661, 26926995, 24224623, 26768678; Phenotypes: peripheral neuropathy, chronic diarrhea, dementia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5335 ZFHX4 Ain Roesley Phenotypes for gene: ZFHX4 were changed from Developmental disorders; intellectual disability, dysmorphic features to neurodevelopmental disorder, ZFHX4-related (MONDO:0700092)
Hereditary Neuropathy - complex v0.266 PMM2 Sangavi Sivagnanasundram edited their review of gene: PMM2: Changed rating: GREEN
Mendeliome v1.1111 ZFHX4 Ain Roesley Phenotypes for gene: ZFHX4 were changed from Developmental disorders to neurodevelopmental disorder, ZFHX4-related (MONDO:0700092)
Hereditary Neuropathy - complex v0.266 GLA Bryony Thompson Marked gene: GLA as ready
Hereditary Neuropathy - complex v0.266 GLA Bryony Thompson Gene: gla has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.266 GLA Bryony Thompson Publications for gene: GLA were set to
Hereditary Neuropathy - complex v0.265 EXOSC8 Bryony Thompson Deleted their review
Hereditary Neuropathy - complex v0.265 EXOSC8 Bryony Thompson commented on gene: EXOSC8
Hereditary Neuropathy - complex v0.265 EXOSC8 Bryony Thompson Deleted their review
Early-onset Dementia v0.160 GRN Sangavi Sivagnanasundram reviewed gene: GRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301545, 17436289; Phenotypes: frontotemporal dementia and/or amyotrophic lateral sclerosis MONDO:0030923; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.265 DARS2 Bryony Thompson Marked gene: DARS2 as ready
Hereditary Neuropathy - complex v0.265 DARS2 Bryony Thompson Gene: dars2 has been classified as Green List (High Evidence).
Early-onset Dementia v0.160 EPM2A Sangavi Sivagnanasundram reviewed gene: EPM2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 12019207; Phenotypes: Epilepsy, progressive myoclonic 2A (Lafora) MIM#254780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.531 RNH1 Zornitza Stark Phenotypes for gene: RNH1 were changed from Neurodevelopmental disorder, MONDO:0700092, RNH1-related; encephalopathy, acute, infection-induced (MONDO:0000166), RNH1-related to Neurodevelopmental disorder, MONDO:0700092, RNH1-related; {Encephalopathy, acute, infection-induced, susceptibiliyt to, 12}, MIM# 620461
Genetic Epilepsy v0.1880 RNH1 Zornitza Stark Phenotypes for gene: RNH1 were changed from Neurodevelopmental disorder, MONDO:0700092, RNH1-related; encephalopathy, acute, infection-induced (MONDO:0000166), RNH1-related to Neurodevelopmental disorder, MONDO:0700092, RNH1-related; {Encephalopathy, acute, infection-induced, susceptibiliyt to, 12}, MIM# 620461
Mendeliome v1.1110 RNH1 Zornitza Stark Phenotypes for gene: RNH1 were changed from Neurodevelopmental disorder, MONDO:0700092, RNH1-related; encephalopathy, acute, infection-induced (MONDO:0000166), RNH1-related to Neurodevelopmental disorder, MONDO:0700092, RNH1-related; {Encephalopathy, acute, infection-induced, susceptibiliyt to, 12}, MIM# 620461
Early-onset Dementia v0.160 DNMT1 Sangavi Sivagnanasundram reviewed gene: DNMT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21532572; Phenotypes: Neuropathy, hereditary sensory, type IE (MIM#614116); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early-onset Dementia v0.160 DNAJC5 Sangavi Sivagnanasundram reviewed gene: DNAJC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 6153706, 11489285, 12112194, 12790899; Phenotypes: Ceroid lipofuscinosis, neuronal, 4 (Kufs type), autosomal dominant (MIM#162350); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early-onset Dementia v0.160 CSF1R Sangavi Sivagnanasundram reviewed gene: CSF1R: Rating: GREEN; Mode of pathogenicity: Other; Publications: 22934315, 24336230; Phenotypes: Leukoencephalopathy, diffuse hereditary, with spheroids 1 (MIM#221820); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early-onset Dementia v0.160 CHMP2B Sangavi Sivagnanasundram reviewed gene: CHMP2B: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 20301378, 16041373; Phenotypes: Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (MIM#600795, MONDO:0010936); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mosaic skin disorders v1.12 ACTB Zornitza Stark Phenotypes for gene: ACTB were changed from Becker's naevus to Becker nevus, somatic mosaic, MIM# 604919
Mosaic skin disorders v1.11 ACTB Zornitza Stark reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Becker nevus, somatic mosaic, MIM# 604919; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.160 APP Sangavi Sivagnanasundram reviewed gene: APP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301340, 1671712, 1678058, 1908231, 1302033; Phenotypes: Alzheimer disease (MIM#104300, MONDO:0007088); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary Neuropathy - complex v0.265 SPAST Sangavi Sivagnanasundram reviewed gene: SPAST: Rating: RED; Mode of pathogenicity: None; Publications: 20301339; Phenotypes: Spastic paraplegia 4, autosomal dominant 182601; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.265 PMM2 Sangavi Sivagnanasundram reviewed gene: PMM2: Rating: RED; Mode of pathogenicity: None; Publications: 20301507, 20301289; Phenotypes: Congenital disorder of glycosylation, type Ia (MIM#212065); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Predominantly Antibody Deficiency v0.125 FNIP1 Peter McNaughton gene: FNIP1 was added
gene: FNIP1 was added to Predominantly Antibody Deficiency. Sources: Literature
Mode of inheritance for gene: FNIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FNIP1 were set to PMID: 37522988; PMID: 32181500; PMID: 32905580 (2020)
Phenotypes for gene: FNIP1 were set to Hypertrophic Cardiomyopathy; Primary Immunodeficiency; Agammaglobulinemia; Neutropenia; Immunodeficiency 93 and hypertrophic cardiomyopathy, MIM# 619705
Review for gene: FNIP1 was set to GREEN
Added comment: PMID: 37522988 (2023)- Additional patient with - Peripheral B cell deficiency, severe hypogammaglobulinemia/agammaglobulinemia, intermittent neutropenia responsive to G-CSF treatment, in conjunction with hypertrophic cardiomyopathy of the ventricle associated with Wolff-Parkinson-White Syndrome, and psycho-motor as well as intellectual developmental delay.

PMID: 32181500 (2020) - Three patients from two independent consanguineous families with homozygous variants (c.3353G>A, p.Ser1118Asn and c.1289delA, p.His430Profs7*) in the FNIP1 gene. Both variants segregated with the disease phenotype in each family. Clinically, patients presented with combined immunodeficiency, cardiac findings (hypertrophic cardiomyopathy, Wolff‐Parkinson‐White syndrome), and myopathy of skeletal muscles with motor DD. Authors note phenotypic overlap with the murine model of FNIP1 deficiency, but no functional analyses of the variants or patient cells were performed.

- PMID: 32905580 (2020) - Three cases from unrelated families, all harbouring novel biallelic variants in FNIP1. Clinical manifestations in all patients include hypertrophic cardiomyopathy, severe and/or recurrent infections, absent circulating B-cells, and agammaglobulinemia; as well as either severe or intermittent neutropenia in two cases. Functional studies showed impairment of B-cell metabolism, including disruptions to mitochondrial numbers/activity and the PI3K/AKT pathway.
Sources: Literature
Hereditary Neuropathy - complex v0.265 HEXA Sangavi Sivagnanasundram reviewed gene: HEXA: Rating: RED; Mode of pathogenicity: None; Publications: 3159334, 1838393; Phenotypes: Tay-Sachs disease MIM#272800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.265 ASAH1 Sangavi Sivagnanasundram reviewed gene: ASAH1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Farber lipogranulomatosis (MIM#228000), Spinal muscular atrophy with progressive myoclonic epilepsy (MIM#159950); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1109 HNRNPC Zornitza Stark Marked gene: HNRNPC as ready
Mendeliome v1.1109 HNRNPC Zornitza Stark Gene: hnrnpc has been classified as Green List (High Evidence).
Mendeliome v1.1109 HNRNPC Zornitza Stark Classified gene: HNRNPC as Green List (high evidence)
Mendeliome v1.1109 HNRNPC Zornitza Stark Gene: hnrnpc has been classified as Green List (High Evidence).
Mendeliome v1.1108 HNRNPC Zornitza Stark gene: HNRNPC was added
gene: HNRNPC was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HNRNPC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPC were set to 37541189
Phenotypes for gene: HNRNPC were set to Neurodevelopmental disorder (MONDO:0700092), HNRNPC-related
Review for gene: HNRNPC was set to GREEN
Added comment: 13 individuals with global developmental delay, intellectual disability, behavioral abnormalities, and subtle facial dysmorphology with heterozygous HNRNPC germline variants. Five had an identical in-frame deletion of nine amino acids in the extreme C terminus. Supportive functional data; haploinsufficiency is the mechanism.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5334 HNRNPC Zornitza Stark Marked gene: HNRNPC as ready
Intellectual disability syndromic and non-syndromic v0.5334 HNRNPC Zornitza Stark Gene: hnrnpc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5334 HNRNPC Zornitza Stark Classified gene: HNRNPC as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5334 HNRNPC Zornitza Stark Gene: hnrnpc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5333 HNRNPC Zornitza Stark gene: HNRNPC was added
gene: HNRNPC was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HNRNPC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPC were set to 37541189
Phenotypes for gene: HNRNPC were set to Neurodevelopmental disorder (MONDO:0700092), HNRNPC-related
Review for gene: HNRNPC was set to GREEN
Added comment: 13 individuals with global developmental delay, intellectual disability, behavioral abnormalities, and subtle facial dysmorphology with heterozygous HNRNPC germline variants. Five had an identical in-frame deletion of nine amino acids in the extreme C terminus.

Supportive functional data; haploinsufficiency is the mechanism.
Sources: Literature
Hereditary Neuropathy - complex v0.265 XK Zornitza Stark Marked gene: XK as ready
Hereditary Neuropathy - complex v0.265 XK Zornitza Stark Gene: xk has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.265 XK Zornitza Stark Phenotypes for gene: XK were changed from McLeod syndrome with or without chronic granulomatous disease, 300842; acanthocytes and Huntington-like syndrome, also epilepsy, cardiomyopathy, axonal motor neuropathy to McLeod syndrome with or without chronic granulomatous disease (MIM#300842)
Hereditary Neuropathy - complex v0.264 XK Zornitza Stark Publications for gene: XK were set to
Hereditary Neuropathy - complex v0.263 TWNK Zornitza Stark Marked gene: TWNK as ready
Hereditary Neuropathy - complex v0.263 TWNK Zornitza Stark Gene: twnk has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.263 TWNK Zornitza Stark Phenotypes for gene: TWNK were changed from HMSN; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 to Perrault syndrome (MIM#616138); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, MIM# 609286
Hereditary Neuropathy - complex v0.262 TWNK Zornitza Stark Publications for gene: TWNK were set to 25254289; 25355836; 27650058; 28178980
Hereditary Neuropathy - complex v0.261 TWNK Zornitza Stark Mode of inheritance for gene: TWNK was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.261 TWNK Zornitza Stark Mode of inheritance for gene: TWNK was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.260 TWNK Zornitza Stark reviewed gene: TWNK: Rating: GREEN; Mode of pathogenicity: None; Publications: 35011763; Phenotypes: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, MIM# 609286; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.260 TWNK Zornitza Stark Publications for gene: TWNK were set to
Hereditary Neuropathy - complex v0.259 TWNK Zornitza Stark Mode of inheritance for gene: TWNK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.258 TUBB3 Zornitza Stark Marked gene: TUBB3 as ready
Hereditary Neuropathy - complex v0.258 TUBB3 Zornitza Stark Gene: tubb3 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.258 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from Fibrosis of extraocular muscles, congenital, 3A; HMSN to Fibrosis of extraocular muscles, congenital, 3A (MIM#600638); Neuropathy
Hereditary Neuropathy - complex v0.257 TUBB3 Zornitza Stark Publications for gene: TUBB3 were set to
Hereditary Neuropathy - complex v0.256 TUBB3 Zornitza Stark reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 34652576; Phenotypes: Fibrosis of extraocular muscles, congenital, 3A (MIM#600638), Neuropathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.256 TTR Zornitza Stark Marked gene: TTR as ready
Hereditary Neuropathy - complex v0.256 TTR Zornitza Stark Gene: ttr has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.256 TTR Zornitza Stark Phenotypes for gene: TTR were changed from Cardiomyopathy; Amyloidogenic transthyretin amyloidosis; HSAN/SFN to Amyloidosis, hereditary, transthyretin-related MIM#105210; Cardiomyopathy; Amyloidogenic transthyretin amyloidosis; HSAN/SFN
Hereditary Neuropathy - complex v0.255 TTR Zornitza Stark Publications for gene: TTR were set to
Hereditary Neuropathy - complex v0.254 SUCLA2 Zornitza Stark Marked gene: SUCLA2 as ready
Hereditary Neuropathy - complex v0.254 SUCLA2 Zornitza Stark Gene: sucla2 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.254 SUCLA2 Zornitza Stark Phenotypes for gene: SUCLA2 were changed from ‘Leigh’-like syndrome, deafness, progressive dystonia, mild methylmaolnic acidaemia, peripheral neuropathy to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) (MONDO:0012791; MIM#612073); ‘Leigh’-like syndrome, deafness, progressive dystonia, mild methylmaolnic acidaemia, peripheral neuropathy
Hereditary Neuropathy - complex v0.253 SUCLA2 Zornitza Stark Publications for gene: SUCLA2 were set to
Hereditary Neuropathy - complex v0.252 SUCLA2 Zornitza Stark Classified gene: SUCLA2 as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.252 SUCLA2 Zornitza Stark Gene: sucla2 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.251 SUCLA2 Zornitza Stark reviewed gene: SUCLA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 35235001; Phenotypes: Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) (MONDO:0012791, MIM#612073); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1107 PSMC3 Zornitza Stark Phenotypes for gene: PSMC3 were changed from Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354 to neurodevelopmental disorder, MONDO:0700092, PSMC3-related; Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354
Mendeliome v1.1106 PSMC3 Zornitza Stark Publications for gene: PSMC3 were set to 32500975
Mendeliome v1.1105 PSMC3 Zornitza Stark Mode of inheritance for gene: PSMC3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1104 PSMC3 Zornitza Stark Classified gene: PSMC3 as Green List (high evidence)
Mendeliome v1.1104 PSMC3 Zornitza Stark Gene: psmc3 has been classified as Green List (High Evidence).
Mendeliome v1.1103 PSMC3 Zornitza Stark edited their review of gene: PSMC3: Added comment: PMID:37256937 - 23 individuals with neurodevelopmental disorder was identified with 15 different de novo missense variants. Apart from one child (patient 2), all others had developmental delay characterised by speech delay (19/19) alone or with intellectual disability (16/18) and motor delay (15/19). In addition, structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune program.; Changed rating: GREEN; Changed publications: 32500975, 37256937; Changed phenotypes: neurodevelopmental disorder, MONDO:0700092, PSMC3-related, Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5332 PSMC3 Zornitza Stark Mode of inheritance for gene: PSMC3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5331 PSMC3 Zornitza Stark Mode of inheritance for gene: PSMC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5330 PSMC3 Zornitza Stark Phenotypes for gene: PSMC3 were changed from Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354 to neurodevelopmental disorder, MONDO:0700092, PSMC3-related; Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354
Intellectual disability syndromic and non-syndromic v0.5329 PSMC3 Zornitza Stark Publications for gene: PSMC3 were set to 32500975
Intellectual disability syndromic and non-syndromic v0.5328 PSMC3 Zornitza Stark Mode of inheritance for gene: PSMC3 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5327 PSMC3 Zornitza Stark Classified gene: PSMC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5327 PSMC3 Zornitza Stark Gene: psmc3 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.251 SOX10 Zornitza Stark Marked gene: SOX10 as ready
Hereditary Neuropathy - complex v0.251 SOX10 Zornitza Stark Gene: sox10 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.251 SOX10 Zornitza Stark Phenotypes for gene: SOX10 were changed from PCWH syndrome, 609136; Waardenburg syndrome, type 4C, 613266; Hypopigmentation of the hair and skin, sensory hearing loss, demyelinating neuropathy, dysmyelinating leukodystrophy, developmental delay, spasticity, ataxia, Hirschsprung disease; Waardenburg syndrome, type 2E, with or without neurologic involvement, 611584; HMSN to PCWH Syndrome (MIM#609136; MONDO:0012198); Waardenburg syndrome, type 4C, 613266; Hypopigmentation of the hair and skin, sensory hearing loss, demyelinating neuropathy, dysmyelinating leukodystrophy, developmental delay, spasticity, ataxia, Hirschsprung disease; Waardenburg syndrome, type 2E, with or without neurologic involvement, 611584; HMSN
Hereditary Neuropathy - complex v0.250 SOX10 Zornitza Stark Publications for gene: SOX10 were set to
Hereditary Neuropathy - complex v0.249 SNAP29 Zornitza Stark Marked gene: SNAP29 as ready
Hereditary Neuropathy - complex v0.249 SNAP29 Zornitza Stark Gene: snap29 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.249 SNAP29 Zornitza Stark Phenotypes for gene: SNAP29 were changed from Cerebral Dysgenesis and severe psychomotor retardation, axonal sensory-motor Neuropathy, Ichthyosis, palmoplantar Keratoderma, fatal by second decade of life to Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (CEDNIK) Syndrome (MONDO:0012290) (MIM#609528); Cerebral Dysgenesis and severe psychomotor retardation, axonal sensory-motor Neuropathy, Ichthyosis, palmoplantar Keratoderma, fatal by second decade of life
Hereditary Neuropathy - complex v0.248 SNAP29 Zornitza Stark Publications for gene: SNAP29 were set to
Hereditary Neuropathy - complex v0.247 SLC52A3 Zornitza Stark Marked gene: SLC52A3 as ready
Hereditary Neuropathy - complex v0.247 SLC52A3 Zornitza Stark Gene: slc52a3 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.247 SLC52A3 Zornitza Stark Phenotypes for gene: SLC52A3 were changed from dHMN; Brown-Vialetto-Van Laere syndrome 1; Fazio-Londe disease to Brown-Vialetto-Van Laere syndrome 1 (MIM#211530); dHMN; Brown-Vialetto-Van Laere syndrome 1; Fazio-Londe disease
Hereditary Neuropathy - complex v0.246 SLC52A3 Zornitza Stark Publications for gene: SLC52A3 were set to
Mendeliome v1.1103 EMC1 Zornitza Stark Publications for gene: EMC1 were set to 26942288; 29271071
Mendeliome v1.1102 EMC1 Zornitza Stark Mode of inheritance for gene: EMC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5326 EMC1 Zornitza Stark Publications for gene: EMC1 were set to 26942288; 29271071
Intellectual disability syndromic and non-syndromic v0.5325 EMC1 Zornitza Stark Mode of inheritance for gene: EMC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.245 SLC52A2 Zornitza Stark Marked gene: SLC52A2 as ready
Hereditary Neuropathy - complex v0.245 SLC52A2 Zornitza Stark Gene: slc52a2 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.245 SLC52A2 Zornitza Stark Phenotypes for gene: SLC52A2 were changed from Brown-Vialetto-Van Laere syndrome 2 to Brown-Vialetto-van Laere syndrome 2 (BVVLS2) (MONDO:0013867)
Hereditary Neuropathy - complex v0.244 SLC52A2 Zornitza Stark Publications for gene: SLC52A2 were set to
Hereditary Neuropathy - complex v0.243 SCYL1 Zornitza Stark Marked gene: SCYL1 as ready
Hereditary Neuropathy - complex v0.243 SCYL1 Zornitza Stark Gene: scyl1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.243 SCYL1 Zornitza Stark Phenotypes for gene: SCYL1 were changed from Spinocerebellar ataxia, autosomal recessive 21; Early-onset ataxia (<1 year) with recurrent episodes of liver failure, sensory-motor axonal neuropathy, cerebellar atrophy to Spinocerebellar ataxia, autosomal recessive 21 (MIM#616719); acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome (MONDO:0014744); Spinocerebellar ataxia, autosomal recessive 21; Early-onset ataxia (<1 year) with recurrent episodes of liver failure, sensory-motor axonal neuropathy, cerebellar atrophy
Hereditary Neuropathy - complex v0.242 SCYL1 Zornitza Stark Publications for gene: SCYL1 were set to
Hereditary Neuropathy - complex v0.241 SACS Zornitza Stark Marked gene: SACS as ready
Hereditary Neuropathy - complex v0.241 SACS Zornitza Stark Gene: sacs has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.241 SACS Zornitza Stark Phenotypes for gene: SACS were changed from Spastic ataxia Charlevoix-Saguenay type; HMSN to Charlevoix-Saguenay spastic ataxia (MONDO:0010041; MIM#270550)
Hereditary Neuropathy - complex v0.240 SACS Zornitza Stark Publications for gene: SACS were set to
Hereditary Neuropathy - complex v0.239 SACS Zornitza Stark Tag SV/CNV tag was added to gene: SACS.
Hereditary Neuropathy - complex v0.239 PTRH2 Zornitza Stark Marked gene: PTRH2 as ready
Hereditary Neuropathy - complex v0.239 PTRH2 Zornitza Stark Gene: ptrh2 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.239 PTRH2 Zornitza Stark Phenotypes for gene: PTRH2 were changed from Infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, sensory neuronal hearing loss, hepatomegaly, pancreatic insufficiency, proximal placement of thumb, SNCV neuropathy to Infantile multisystem neurologic, endocrine, and pancreatic disease (IMNPED) (MIM#616263); Infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, sensory neuronal hearing loss, hepatomegaly, pancreatic insufficiency, proximal placement of thumb, SNCV neuropathy
Hereditary Neuropathy - complex v0.238 PTRH2 Zornitza Stark Publications for gene: PTRH2 were set to
Hereditary Neuropathy - complex v0.237 XK Sangavi Sivagnanasundram reviewed gene: XK: Rating: GREEN; Mode of pathogenicity: None; Publications: 11761473; Phenotypes: McLeod syndrome with or without chronic granulomatous disease (MIM#300842); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary Neuropathy - complex v0.237 TWNK Sangavi Sivagnanasundram reviewed gene: TWNK: Rating: GREEN; Mode of pathogenicity: None; Publications: 25254289, 25355836, 27650058, 28178980; Phenotypes: Perrault syndrome (MIM#616138); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.237 TUBB3 Sangavi Sivagnanasundram reviewed gene: TUBB3: Rating: AMBER; Mode of pathogenicity: None; Publications: 20074521; Phenotypes: Fibrosis of extraocular muscles, congenital, 3A (MIM#600638); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary Neuropathy - complex v0.237 TTR Sangavi Sivagnanasundram reviewed gene: TTR: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301373, 8071954, 19180884, 24101130; Phenotypes: Amyloidosis, hereditary, transthyretin-related MIM#105210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.237 SUCLA2 Sangavi Sivagnanasundram reviewed gene: SUCLA2: Rating: RED; Mode of pathogenicity: None; Publications: 20301762; Phenotypes: Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) (MONDO:0012791, MIM#612073); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5324 PSMC3 Achchuthan Shanmugasundram reviewed gene: PSMC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37256937; Phenotypes: neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.237 SOX10 Sangavi Sivagnanasundram reviewed gene: SOX10: Rating: AMBER; Mode of pathogenicity: None; Publications: 15004559; Phenotypes: PCWH Syndrome (MIM#609136, MONDO:0012198); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary Neuropathy - complex v0.237 SNAP29 Sangavi Sivagnanasundram reviewed gene: SNAP29: Rating: AMBER; Mode of pathogenicity: None; Publications: 33977139; Phenotypes: Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (CEDNIK) Syndrome (MONDO:0012290) (MIM#609528); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.237 SLC52A3 Sangavi Sivagnanasundram reviewed gene: SLC52A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20206331; Phenotypes: Brown-Vialetto-Van Laere syndrome 1 (MIM#211530); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1101 EMC1 Chern Lim edited their review of gene: EMC1: Changed rating: GREEN
Mendeliome v1.1101 EMC1 Chern Lim reviewed gene: EMC1: Rating: ; Mode of pathogenicity: None; Publications: 35234901, 26942288; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5324 EMC1 Chern Lim reviewed gene: EMC1: Rating: ; Mode of pathogenicity: None; Publications: 35234901, 26942288; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary Neuropathy - complex v0.237 SLC52A2 Sangavi Sivagnanasundram reviewed gene: SLC52A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22740598, 24253200; Phenotypes: Brown-Vialetto-van Laere syndrome 2 (BVVLS2) (MONDO:0013867); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.237 SCYL1 Sangavi Sivagnanasundram reviewed gene: SCYL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26581903, 30531813; Phenotypes: Spinocerebellar ataxia, autosomal recessive 21 (MIM#616719), acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome (MONDO:0014744); Mode of inheritance: None
BabyScreen+ newborn screening v1.0 Zornitza Stark promoted panel to version 1.0
Hereditary Neuropathy - complex v0.237 SACS Sangavi Sivagnanasundram reviewed gene: SACS: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301432, 20876471; Phenotypes: Charlevoix-Saguenay spastic ataxia (MONDO:0010041, MIM#270550); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.237 PTRH2 Sangavi Sivagnanasundram reviewed gene: PTRH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25574476, 27129381, 28328138; Phenotypes: Infantile multisystem neurologic, endocrine, and pancreatic disease (IMNPED) (MIM#616263); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.186 SYNE1 Zornitza Stark reviewed gene: SYNE1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis multiplex congenita 3, myogenic type MIM#618484, Emery-Dreifuss muscular dystrophy 4, autosomal dominant MIM#612998, Spinocerebellar ataxia, autosomal recessive 8 MIM#610743; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Autoinflammatory Disorders v1.12 RELA Zornitza Stark Marked gene: RELA as ready
Autoinflammatory Disorders v1.12 RELA Zornitza Stark Gene: rela has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.12 RELA Zornitza Stark Phenotypes for gene: RELA were changed from periodic fever, inflammatory bowel disease, JIA to Mucocutaneous ulceration, chronic, MIM# 618287; periodic fever, inflammatory bowel disease, JIA
Autoinflammatory Disorders v1.11 RELA Zornitza Stark Classified gene: RELA as Green List (high evidence)
Autoinflammatory Disorders v1.11 RELA Zornitza Stark Gene: rela has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.10 RELA Zornitza Stark reviewed gene: RELA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucocutaneous ulceration, chronic, MIM# 618287; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v1.43 RELA Zornitza Stark Publications for gene: RELA were set to 28600438; 29305315
Combined Immunodeficiency v1.42 RELA Zornitza Stark Classified gene: RELA as Green List (high evidence)
Combined Immunodeficiency v1.42 RELA Zornitza Stark Gene: rela has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.41 RELA Zornitza Stark edited their review of gene: RELA: Added comment: Additional 6 individuals from five families reported.; Changed rating: GREEN; Changed publications: 28600438, 29305315, 37273177; Changed phenotypes: Mucocutaneous ulceration, chronic, MIM# 618287, Impaired NFkB activation, reduced production of inflammatory cytokines, autoimmune cytopaenias
Mendeliome v1.1101 RELA Zornitza Stark Publications for gene: RELA were set to 28600438; 29305315
Mendeliome v1.1100 RELA Zornitza Stark Classified gene: RELA as Green List (high evidence)
Mendeliome v1.1100 RELA Zornitza Stark Gene: rela has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.105 RELA Zornitza Stark changed review comment from: Additional 6 individuals from two families reported.; to: Additional 6 individuals from five families reported.
Mendeliome v1.1099 RELA Zornitza Stark changed review comment from: Additional 6 individuals from two families reported.; to: Additional 6 individuals from five families reported.
Mendeliome v1.1099 RELA Zornitza Stark edited their review of gene: RELA: Added comment: Additional 6 individuals from two families reported.; Changed rating: GREEN; Changed publications: 28600438, 29305315, 37273177; Changed phenotypes: Mucocutaneous ulceration, chronic, MIM# 618287, Impaired NFkB activation, reduced production of inflammatory cytokines, autoimmune cytopaenias
Inflammatory bowel disease v0.105 RELA Zornitza Stark Marked gene: RELA as ready
Inflammatory bowel disease v0.105 RELA Zornitza Stark Gene: rela has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.105 RELA Zornitza Stark Phenotypes for gene: RELA were changed from Inflammatory bowel disease to Mucocutaneous ulceration, chronic, MIM# 618287; Inflammatory bowel disease
Inflammatory bowel disease v0.104 RELA Zornitza Stark Classified gene: RELA as Green List (high evidence)
Inflammatory bowel disease v0.104 RELA Zornitza Stark Gene: rela has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.103 RELA Zornitza Stark edited their review of gene: RELA: Added comment: Additional 6 individuals from two families reported.; Changed rating: GREEN; Changed publications: 37273177
Inflammatory bowel disease v0.103 RELA Zornitza Stark reviewed gene: RELA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucocutaneous ulceration, chronic, MIM# 618287; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.237 NGLY1 Zornitza Stark Marked gene: NGLY1 as ready
Hereditary Neuropathy - complex v0.237 NGLY1 Zornitza Stark Gene: ngly1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.237 NGLY1 Zornitza Stark Phenotypes for gene: NGLY1 were changed from Developmental delay, choreoathetosis, alacrimia, seizures, microcephaly, transaminitis, neuropathy to Congenital disorder of deglycosylation 1 (CDDG1) (MIM#615273); Developmental delay, choreoathetosis, alacrimia, seizures, microcephaly, transaminitis, neuropathy
Hereditary Neuropathy - complex v0.236 NGLY1 Zornitza Stark Publications for gene: NGLY1 were set to
Hereditary Neuropathy - complex v0.235 OPA1 Zornitza Stark Marked gene: OPA1 as ready
Hereditary Neuropathy - complex v0.235 OPA1 Zornitza Stark Gene: opa1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.235 OPA1 Zornitza Stark Phenotypes for gene: OPA1 were changed from Optic atrophy plus syndrome, 125250; Optic atrophy 1, 165500; HMSN to Optic atrophy plus syndrome (MIM#125250)
Hereditary Neuropathy - complex v0.234 OPA1 Zornitza Stark Publications for gene: OPA1 were set to
Hereditary Neuropathy - complex v0.233 PDYN Zornitza Stark Marked gene: PDYN as ready
Hereditary Neuropathy - complex v0.233 PDYN Zornitza Stark Gene: pdyn has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.233 PDYN Zornitza Stark Phenotypes for gene: PDYN were changed from Cerebellar ataxia, sensory-motor axonal neuropathy; Spinocerebellar ataxia 23 to Spinocerebellar ataxia 23 (MIM#610245); Cerebellar ataxia, sensory-motor axonal neuropathy; Spinocerebellar ataxia 23
Hereditary Neuropathy - complex v0.232 PDYN Zornitza Stark Publications for gene: PDYN were set to
Hereditary Neuropathy - complex v0.231 PDYN Zornitza Stark reviewed gene: PDYN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 23 (MIM#610245); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.231 PEX7 Zornitza Stark Marked gene: PEX7 as ready
Hereditary Neuropathy - complex v0.231 PEX7 Zornitza Stark Gene: pex7 has been classified as Red List (Low Evidence).
Hereditary Neuropathy - complex v0.231 PEX7 Zornitza Stark Publications for gene: PEX7 were set to
Hereditary Neuropathy - complex v0.230 PEX7 Zornitza Stark Classified gene: PEX7 as Red List (low evidence)
Hereditary Neuropathy - complex v0.230 PEX7 Zornitza Stark Gene: pex7 has been classified as Red List (Low Evidence).
Hereditary Neuropathy - complex v0.229 PHYH Zornitza Stark Marked gene: PHYH as ready
Hereditary Neuropathy - complex v0.229 PHYH Zornitza Stark Gene: phyh has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.229 PHYH Zornitza Stark Phenotypes for gene: PHYH were changed from Refsum disease; Phytanic acid storage disease to Refsum Disease MIM#266500
Hereditary Neuropathy - complex v0.228 PHYH Zornitza Stark Publications for gene: PHYH were set to
Hereditary Neuropathy - complex v0.227 PHYH Zornitza Stark reviewed gene: PHYH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Refsum Disease MIM#266500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.227 PLA2G6 Zornitza Stark Marked gene: PLA2G6 as ready
Hereditary Neuropathy - complex v0.227 PLA2G6 Zornitza Stark Gene: pla2g6 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.227 PLA2G6 Zornitza Stark Phenotypes for gene: PLA2G6 were changed from Infantile-onset, progressive neurodegeneration (tetraplegia, dementia, visual loss) and axonal sensory-motor neuropathy, globus pallidus iron deposition on MRI to Infantile neuroaxonal dystrophy 1 (MIM#256600); Neurodegeneration with brain iron accumulation 2B (MIM#610217)
Hereditary Neuropathy - complex v0.226 PLA2G6 Zornitza Stark Publications for gene: PLA2G6 were set to
Hereditary Neuropathy - complex v0.225 PLA2G6 Zornitza Stark reviewed gene: PLA2G6: Rating: GREEN; Mode of pathogenicity: None; Publications: 29859652; Phenotypes: Infantile neuroaxonal dystrophy 1 (MIM#256600), Neurodegeneration with brain iron accumulation 2B (MIM#610217), Parkinson disease 14, autosomal recessive (MIM#612953); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1099 DPP9 Zornitza Stark Phenotypes for gene: DPP9 were changed from Autoinflammatory syndrome MONDO:0019751, DPP9-related; recurrent fevers; repeated infections; herpes susceptibility; cytopenias to Hatipoglu immunodeficiency syndrome MIM#620331; Autoinflammatory syndrome MONDO:0019751, DPP9-related; recurrent fevers; repeated infections; herpes susceptibility; cytopenias
Mendeliome v1.1098 DPP9 Zornitza Stark Phenotypes for gene: DPP9 were changed from Autoinflammatory syndrome MONDO:0019751, DPP9-related; recurrent fevers; repeated infections; herpes susceptibility; cytopenias to Autoinflammatory syndrome MONDO:0019751, DPP9-related; recurrent fevers; repeated infections; herpes susceptibility; cytopenias
Mendeliome v1.1097 DPP9 Zornitza Stark Publications for gene: DPP9 were set to 36112693
Mendeliome v1.1096 DPP9 Zornitza Stark Mode of inheritance for gene: DPP9 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1095 DPP9 Zornitza Stark edited their review of gene: DPP9: Added comment: Amber for mono-allelic association:

de novo monoallelic dominant-negative mutation in DPP9 (c.755G>C, R252P) presenting with HLH at ~2m. Functional data supporting dominant negative mechanism.; Changed publications: 36112693, 37544411; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Autoinflammatory Disorders v1.10 DPP9 Zornitza Stark Mode of inheritance for gene: DPP9 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.225 PLP1 Zornitza Stark Marked gene: PLP1 as ready
Hereditary Neuropathy - complex v0.225 PLP1 Zornitza Stark Gene: plp1 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.225 PLP1 Zornitza Stark Phenotypes for gene: PLP1 were changed from Pelizaeus-Merzbacher disease; Infantile-onset, nystagmus, cognitive impairment, spasticity and ataxia, leukodystrophy on MRI, mild multifocal SNCV neuropathy seen with null mutations and more mild phenotype of mild spasticity and ataxia; HMSN to Pelizaeus-Merzbacher disease (MIM#312080)
Hereditary Neuropathy - complex v0.224 PLP1 Zornitza Stark Publications for gene: PLP1 were set to
Hereditary Neuropathy - complex v0.223 PLP1 Zornitza Stark Classified gene: PLP1 as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.223 PLP1 Zornitza Stark Gene: plp1 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.222 PNKP Zornitza Stark Marked gene: PNKP as ready
Hereditary Neuropathy - complex v0.222 PNKP Zornitza Stark Gene: pnkp has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.222 PNKP Zornitza Stark Phenotypes for gene: PNKP were changed from Ataxia-oculomotor apraxia 4, 616267; Microcephaly, global developmental delay, progressive cerebellar ataxia and atrophy, sensory-motor axonal neuropathy; Microcephaly, seizures, and developmental delay, 613402; HMSN to Charcot-Marie-Tooth disease, axonal, type 2B2 (MIM#605589); Ataxia-oculomotor apraxia 4 (MIM#616267)
Hereditary Neuropathy - complex v0.221 PNKP Zornitza Stark Publications for gene: PNKP were set to
Hereditary Neuropathy - complex v0.220 PNPLA6 Zornitza Stark Marked gene: PNPLA6 as ready
Hereditary Neuropathy - complex v0.220 PNPLA6 Zornitza Stark Gene: pnpla6 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.220 PNPLA6 Zornitza Stark Phenotypes for gene: PNPLA6 were changed from progressive distal motor neuropathy beginning in early through late adolescence; Hereditary Neuropathies; Childhood onset of slowly progressive spastic paraplegia to Laurence-Moon Syndrome (LMS) MIM#245800; Spastic Paraplegia Type 39 MIM#612020
Hereditary Neuropathy - complex v0.219 PNPLA6 Zornitza Stark Publications for gene: PNPLA6 were set to
Cerebral Palsy v1.186 ADNP Zornitza Stark Classified gene: ADNP as Green List (high evidence)
Cerebral Palsy v1.186 ADNP Zornitza Stark Gene: adnp has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.218 PRNP Sangavi Sivagnanasundram changed review comment from: Neuropathy not an established feature of CAA - only one reported family.
PMID: 24224623
Multigenerational British family with symptoms of mixed neuropathy (predominantly sensory and autonomic) with a Y163X truncation mutation with the M129V polymorphism.; to: Neuropathy not an established feature of PRNP-related CAA - only one reported family.
PMID: 24224623
Multigenerational British family with symptoms of mixed neuropathy (predominantly sensory and autonomic) with a Y163X truncation mutation with the M129V polymorphism.
Hereditary Neuropathy - complex v0.218 POLG Zornitza Stark Marked gene: POLG as ready
Hereditary Neuropathy - complex v0.218 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.218 POLG Zornitza Stark Phenotypes for gene: POLG were changed from Mitochondrial DNA depletion syndrome 4B (MNGIE type); Mitochondrial DNA depletion syndrome 4A (Alpers type); Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE); Progressive external ophthalmoplegia, autosomal dominant 1; Progressive external ophthalmoplegia, autosomal recessive 1; Cardiomyopathy; sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO); HMSN to Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) 607459
Hereditary Neuropathy - complex v0.217 POLG Zornitza Stark Publications for gene: POLG were set to
Hereditary Neuropathy - complex v0.216 PRNP Sangavi Sivagnanasundram reviewed gene: PRNP: Rating: RED; Mode of pathogenicity: None; Publications: 24224623; Phenotypes: Inherited prion disease, Cerebral amyloid angiopathy, PRNP-related (MIM#137440); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary Neuropathy - complex v0.216 POLG Zornitza Stark Mode of inheritance for gene: POLG was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Pulmonary Arterial Hypertension v1.35 SOX17 Zornitza Stark Phenotypes for gene: SOX17 were changed from Vesicoureteral reflux 3 MIM#613674; Pulmonary arterial hypertension to Heritable pulmonary arterial hypertension, MONDO:0017148, SOX17-related
Pulmonary Arterial Hypertension v1.33 SMAD4 Zornitza Stark Phenotypes for gene: SMAD4 were changed from Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome MIM#175050; Pulmonary arterial hypertension to Pulmonary arterial hypertension MONDO:0015924, SMAD4-related
Pulmonary Arterial Hypertension v1.32 SMAD4 Zornitza Stark Tag disputed tag was added to gene: SMAD4.
Pulmonary Arterial Hypertension v1.32 SMAD4 Zornitza Stark reviewed gene: SMAD4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, SMAD4-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.32 SMAD1 Zornitza Stark Tag disputed tag was added to gene: SMAD1.
Pulmonary Arterial Hypertension v1.32 SMAD1 Zornitza Stark Phenotypes for gene: SMAD1 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension MONDO:0015924, SMAD1-related
Pulmonary Arterial Hypertension v1.31 SMAD1 Zornitza Stark reviewed gene: SMAD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, SMAD1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.31 NOTCH3 Zornitza Stark Phenotypes for gene: NOTCH3 were changed from Pulmonary arterial hypertension, MONDO:0015924 to Pulmonary arterial hypertension MONDO:0015924, NOTCH3-related
Pulmonary Arterial Hypertension v1.30 NOTCH3 Zornitza Stark Tag disputed tag was added to gene: NOTCH3.
Pulmonary Arterial Hypertension v1.30 NOTCH3 Zornitza Stark reviewed gene: NOTCH3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, NOTCH3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.30 BMPR1B Zornitza Stark Tag disputed tag was added to gene: BMPR1B.
Pulmonary Arterial Hypertension v1.30 BMPR1B Zornitza Stark reviewed gene: BMPR1B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, BMPR1B-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1095 PDGFD Zornitza Stark Marked gene: PDGFD as ready
Mendeliome v1.1095 PDGFD Zornitza Stark Gene: pdgfd has been classified as Red List (Low Evidence).
Mendeliome v1.1095 PDGFD Zornitza Stark gene: PDGFD was added
gene: PDGFD was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PDGFD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDGFD were set to 33187088; 33971972
Phenotypes for gene: PDGFD were set to Pulmonary arterial hypertension MONDO:0015924, PDGFD-related
Review for gene: PDGFD was set to RED
Added comment: Rated as LIMITED by ClinGen. 10 unique variants (all missense) that have been reported in 10 probands in 2 publications (PMIDs: 33187088, 33971972) are included in this curation. 9 of these variants were observed in a cohort of 1647 idiopathic pulmonary arterial hypertension (IPAH) patients of European Ancestry as part of a case-control study. Variant aggregation analysis revealed a significant burden (p=0.0000172) of likely gene damaging PDGFD variants in the IPAH cohort as compared to a group of 18,819 European controls (PMID:33971972). Gelinas et al. also reported a missense PDGFD variant in a proband with IPAH (PMID:33187088). There is currently no functional evidence demonstrating a damaging effect of any of the reported PDGFD variants in humans.
Sources: Expert list
Pulmonary Arterial Hypertension v1.30 PDGFD Zornitza Stark Marked gene: PDGFD as ready
Pulmonary Arterial Hypertension v1.30 PDGFD Zornitza Stark Gene: pdgfd has been classified as Red List (Low Evidence).
Pulmonary Arterial Hypertension v1.30 PDGFD Zornitza Stark gene: PDGFD was added
gene: PDGFD was added to Pulmonary Arterial Hypertension. Sources: Expert list
Mode of inheritance for gene: PDGFD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDGFD were set to 33187088; 33971972
Phenotypes for gene: PDGFD were set to Pulmonary arterial hypertension MONDO:0015924, PDGFD-related
Review for gene: PDGFD was set to RED
Added comment: Rated as LIMITED by ClinGen.

10 unique variants (all missense) that have been reported in 10 probands in 2 publications (PMIDs: 33187088, 33971972) are included in this curation. 9 of these variants were observed in a cohort of 1647 idiopathic pulmonary arterial hypertension (IPAH) patients of European Ancestry as part of a case-control study. Variant aggregation analysis revealed a significant burden (p=0.0000172) of likely gene damaging PDGFD variants in the IPAH cohort as compared to a group of 18,819 European controls (PMID:33971972). Gelinas et al. also reported a missense PDGFD variant in a proband with IPAH (PMID:33187088). There is currently no functional evidence demonstrating a damaging effect of any of the reported PDGFD variants in humans.
Sources: Expert list
Mendeliome v1.1094 KLF2 Zornitza Stark Phenotypes for gene: KLF2 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension MONDO:0015924, KLF2-related
Mendeliome v1.1093 KLF2 Zornitza Stark edited their review of gene: KLF2: Changed phenotypes: Pulmonary arterial hypertension MONDO:0015924, KLF2-related
Pulmonary Arterial Hypertension v1.29 KLF2 Zornitza Stark Phenotypes for gene: KLF2 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension MONDO:0015924, KLF2-related
Pulmonary Arterial Hypertension v1.28 KLF2 Zornitza Stark reviewed gene: KLF2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, KLF2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1093 FBLN2 Zornitza Stark Marked gene: FBLN2 as ready
Mendeliome v1.1093 FBLN2 Zornitza Stark Gene: fbln2 has been classified as Red List (Low Evidence).
Mendeliome v1.1093 FBLN2 Zornitza Stark gene: FBLN2 was added
gene: FBLN2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FBLN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBLN2 were set to 33971972
Phenotypes for gene: FBLN2 were set to Pulmonary arterial hypertension MONDO:0015924, FBLN2-related
Review for gene: FBLN2 was set to RED
Added comment: LIMITED by ClinGen. Out of a cohort of 1647 idiopathic PAH cases, 3 rare predicted deleterious missense variants were identified in 6 unrelated individuals with one variant recurrent in four individuals. Gene-disease association also supported by tissue expression data.
Sources: Expert list
Pulmonary Arterial Hypertension v1.28 FBLN2 Zornitza Stark Marked gene: FBLN2 as ready
Pulmonary Arterial Hypertension v1.28 FBLN2 Zornitza Stark Gene: fbln2 has been classified as Red List (Low Evidence).
Pulmonary Arterial Hypertension v1.28 FBLN2 Zornitza Stark gene: FBLN2 was added
gene: FBLN2 was added to Pulmonary Arterial Hypertension. Sources: Expert list
Mode of inheritance for gene: FBLN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBLN2 were set to 33971972
Phenotypes for gene: FBLN2 were set to Pulmonary arterial hypertension MONDO:0015924, FBLN2-related
Review for gene: FBLN2 was set to RED
Added comment: LIMITED by ClinGen. Out of a cohort of 1647 idiopathic PAH cases, 3 rare predicted deleterious missense variants were identified in 6 unrelated individuals with one variant recurrent in four individuals. Gene-disease association also supported by tissue expression data.
Sources: Expert list
Pulmonary Arterial Hypertension v1.27 BMP10 Zornitza Stark Phenotypes for gene: BMP10 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension MONDO:0015924, BMP10-related
Pulmonary Arterial Hypertension v1.26 BMP10 Zornitza Stark Publications for gene: BMP10 were set to 30578383
Pulmonary Arterial Hypertension v1.25 BMP10 Zornitza Stark reviewed gene: BMP10: Rating: AMBER; Mode of pathogenicity: None; Publications: 29843651, 33187088, 31661308, 30578383; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, BMP10-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1092 AQP1 Zornitza Stark Phenotypes for gene: AQP1 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension MONDO:0015924, AQP1-related
Mendeliome v1.1091 AQP1 Zornitza Stark Publications for gene: AQP1 were set to PMID:22683574; 29650961
Mendeliome v1.1090 AQP1 Zornitza Stark Classified gene: AQP1 as Amber List (moderate evidence)
Mendeliome v1.1090 AQP1 Zornitza Stark Gene: aqp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1089 AQP1 Zornitza Stark reviewed gene: AQP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 37007933, 35627312; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, AQP1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.25 AQP1 Zornitza Stark Phenotypes for gene: AQP1 were changed from Pulmonary arterial hypertension MONDO:0015924, AQP2-related to Pulmonary arterial hypertension MONDO:0015924, AQP1-related
Pulmonary Arterial Hypertension v1.24 AQP1 Zornitza Stark edited their review of gene: AQP1: Changed phenotypes: Pulmonary arterial hypertension MONDO:0015924, AQP1-related
Pulmonary Arterial Hypertension v1.24 AQP1 Zornitza Stark Phenotypes for gene: AQP1 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension MONDO:0015924, AQP2-related
Pulmonary Arterial Hypertension v1.23 AQP1 Zornitza Stark Publications for gene: AQP1 were set to 22683574; 29650961
Pulmonary Arterial Hypertension v1.22 AQP1 Zornitza Stark Classified gene: AQP1 as Amber List (moderate evidence)
Pulmonary Arterial Hypertension v1.22 AQP1 Zornitza Stark Gene: aqp1 has been classified as Amber List (Moderate Evidence).
Pulmonary Arterial Hypertension v1.21 AQP1 Zornitza Stark reviewed gene: AQP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 37007933, 35627312; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, AQP2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1089 TET2 Zornitza Stark Phenotypes for gene: TET2 were changed from Dementia; Lymphoma/myeloid malignancy; Immunodeficiency-75 (IMD75), MIM#619126 to Dementia; Lymphoma/myeloid malignancy; Immunodeficiency-75 (IMD75), MIM#619126; Pulmonary arterial hypertension MONDO:0015924, TET2-related
Mendeliome v1.1088 TET2 Zornitza Stark Publications for gene: TET2 were set to 30890702; 31827242; 32330418
Mendeliome v1.1087 TET2 Zornitza Stark changed review comment from: Association with PAH:
MODERATE by ClinGen. TET2 was first reported in relation to autosomal dominant pulmonary arterial hypertension (PAH) in 2020 (Potus et al., PMID: 32192357). Out of a cohort of 2572 cases from the PAH biobank, 6 rare predicted deleterious likely germline variants including missense, nonsense, and frameshift variants were identified in 6 unrelated individuals. The relationship between TET2 and PAH is also supported by experimental evidence including tissue expression in controls and patients, biochemical function as a negative regulator of a proinflammatory response, and knock out TET2 mice exhibiting a PH phenotype.; to: Association with PAH:
MODERATE by ClinGen/Amber rating here. TET2 was first reported in relation to autosomal dominant pulmonary arterial hypertension (PAH) in 2020 (Potus et al., PMID: 32192357). Out of a cohort of 2572 cases from the PAH biobank, 6 rare predicted deleterious likely germline variants including missense, nonsense, and frameshift variants were identified in 6 unrelated individuals. The relationship between TET2 and PAH is also supported by experimental evidence including tissue expression in controls and patients, biochemical function as a negative regulator of a proinflammatory response, and knock out TET2 mice exhibiting a PH phenotype.
Mendeliome v1.1087 TET2 Zornitza Stark edited their review of gene: TET2: Added comment: Association with PAH:
MODERATE by ClinGen. TET2 was first reported in relation to autosomal dominant pulmonary arterial hypertension (PAH) in 2020 (Potus et al., PMID: 32192357). Out of a cohort of 2572 cases from the PAH biobank, 6 rare predicted deleterious likely germline variants including missense, nonsense, and frameshift variants were identified in 6 unrelated individuals. The relationship between TET2 and PAH is also supported by experimental evidence including tissue expression in controls and patients, biochemical function as a negative regulator of a proinflammatory response, and knock out TET2 mice exhibiting a PH phenotype.; Changed publications: 30890702, 31827242, 32330418, 32518946, 32192357; Changed phenotypes: Dementia, Lymphoma/myeloid malignancy, Immunodeficiency-75 (IMD75), MIM#619126, Pulmonary arterial hypertension MONDO:0015924, TET2-related
Pulmonary Arterial Hypertension v1.21 TET2 Zornitza Stark Marked gene: TET2 as ready
Pulmonary Arterial Hypertension v1.21 TET2 Zornitza Stark Gene: tet2 has been classified as Amber List (Moderate Evidence).
Pulmonary Arterial Hypertension v1.21 TET2 Zornitza Stark Classified gene: TET2 as Amber List (moderate evidence)
Pulmonary Arterial Hypertension v1.21 TET2 Zornitza Stark Gene: tet2 has been classified as Amber List (Moderate Evidence).
Pulmonary Arterial Hypertension v1.20 TET2 Zornitza Stark edited their review of gene: TET2: Changed rating: AMBER
Pulmonary Arterial Hypertension v1.20 TET2 Zornitza Stark gene: TET2 was added
gene: TET2 was added to Pulmonary Arterial Hypertension. Sources: Expert list
Mode of inheritance for gene: TET2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TET2 were set to 32192357
Phenotypes for gene: TET2 were set to Pulmonary arterial hypertension MONDO:0015924, TET2-related
Added comment: MODERATE by ClinGen.

TET2 was first reported in relation to autosomal dominant pulmonary arterial hypertension (PAH) in 2020 (Potus et al., PMID: 32192357). Out of a cohort of 2572 cases from the PAH biobank, 6 rare predicted deleterious likely germline variants including missense, nonsense, and frameshift variants were identified in 6 unrelated individuals. The relationship between TET2 and PAH is also supported by experimental evidence including tissue expression in controls and patients, biochemical function as a negative regulator of a proinflammatory response, and knock out TET2 mice exhibiting a PH phenotype.
Sources: Expert list
Pulmonary Arterial Hypertension v1.19 GGCX Zornitza Stark reviewed gene: GGCX: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: pulmonary arterial hypertension MONDO:0015924; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.19 ABCC8 Zornitza Stark reviewed gene: ABCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: pulmonary arterial hypertension MONDO:0015924, ABCC8-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.19 SOX17 Zornitza Stark reviewed gene: SOX17: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Heritable pulmonary arterial hypertension, MONDO:0017148, SOX17-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.19 SMAD9 Zornitza Stark reviewed gene: SMAD9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary hypertension, primary, 2 MIM#615342; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.19 KDR Zornitza Stark commented on gene: KDR: DEFINITIVE by ClinGen.
Pulmonary Arterial Hypertension v1.19 KCNK3 Zornitza Stark reviewed gene: KCNK3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary hypertension, primary, 4 MIM#615344; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.19 GDF2 Zornitza Stark reviewed gene: GDF2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 5 MIM#615506, Pulmonary arterial hypertension; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.215 POLG Sangavi Sivagnanasundram reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301791; Phenotypes: Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) 607459; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.185 ADNP Luisa Weiss edited their review of gene: ADNP: Added comment: In addition to the previous cases, there is one case report of a boy with the full phenotypic picture of Helsmoortel-van der Aa syndrome and hypotonic cerebral palsy. Note that hypotonia is one feature of Helsmoortel-van der Aa syndrome, but hypotonic cerebral palsy seems to be rare.; Changed rating: GREEN; Changed publications: 29780943; Changed phenotypes: Helsmoortel-van der Aa syndrome MIM#615873
Pulmonary Arterial Hypertension v1.19 CAV1 Zornitza Stark reviewed gene: CAV1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary hypertension, primary, 3 MIM#615343; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.19 BMPR2 Zornitza Stark reviewed gene: BMPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary hypertension, familial primary, 1, with or without HHT MIM#178600, Pulmonary hypertension, primary, fenfluramine or dexfenfluramine-associated MIM#178600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.19 ATP13A3 Zornitza Stark commented on gene: ATP13A3: DEFINITIVE by ClinGen.
Hereditary Neuropathy - complex v0.215 PNPLA6 Sangavi Sivagnanasundram reviewed gene: PNPLA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 25299038, 18313024; Phenotypes: Laurence-Moon Syndrome (LMS) MIM#245800, Spastic Paraplegia Type 39 MIM#612020; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.215 PNKP Sangavi Sivagnanasundram reviewed gene: PNKP: Rating: GREEN; Mode of pathogenicity: None; Publications: 30039206, 27066567, 25728773; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2B2 (MIM#605589), Ataxia-oculomotor apraxia 4 (MIM#616267); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.215 PLP1 Sangavi Sivagnanasundram reviewed gene: PLP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 20301361, 11872612; Phenotypes: Pelizaeus-Merzbacher disease (MIM#312080); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Autoinflammatory Disorders v1.9 DPP9 Peter McNaughton edited their review of gene: DPP9: Added comment: de novo monoallelic dominant-negative mutation in DPP9 (c.755G>C, R252P) presenting with HLH at ~2m. Functional data supporting dominant negative mechanism.; Changed publications: PMID: 37544411; Changed phenotypes: HLH; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.215 PLA2G6 Sangavi Sivagnanasundram reviewed gene: PLA2G6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Infantile neuroaxonal dystrophy 1 (MIM#256600), Neurodegeneration with brain iron accumulation 2B (MIM#610217), Parkinson disease 14, autosomal recessive (MIM#612953); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.215 PHYH Sangavi Sivagnanasundram reviewed gene: PHYH: Rating: AMBER; Mode of pathogenicity: None; Publications: 2433405, 20301527; Phenotypes: Adult Refsum Disease MIM#266500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.215 PEX7 Sangavi Sivagnanasundram reviewed gene: PEX7: Rating: RED; Mode of pathogenicity: None; Publications: 20301447, 12325024; Phenotypes: Peroxisome biogenesis disorder 9B (MIM#614879); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.215 PDYN Sangavi Sivagnanasundram reviewed gene: PDYN: Rating: AMBER; Mode of pathogenicity: None; Publications: 21035104; Phenotypes: Spinocerebellar ataxia 23 (MIM#610245); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary Neuropathy - complex v0.215 OPA1 Sangavi Sivagnanasundram reviewed gene: OPA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16240368, 18065439, 20157015, 21112924; Phenotypes: Optic atrophy plus syndrome (MIM#125250); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary Neuropathy - complex v0.215 NGLY1 Sangavi Sivagnanasundram reviewed gene: NGLY1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22581936, 27388694, 29419975; Phenotypes: Congenital disorder of deglycosylation 1 (CDDG1) (MIM#615273); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.103 RELA Peter McNaughton gene: RELA was added
gene: RELA was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: RELA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RELA were set to PMID: 37273177
Phenotypes for gene: RELA were set to Inflammatory bowel disease
Review for gene: RELA was set to GREEN
Added comment: Patients with RELA DN mutations additionally presented periodic fever, inflammatory bowel diseases (IBDs), juvenile idiopathic arthritis (JIA), and skin involvement. Complete penetrance was observed for IBD
Sources: Literature
Autoinflammatory Disorders v1.9 RELA Peter McNaughton gene: RELA was added
gene: RELA was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: RELA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RELA were set to PMID: 37273177
Phenotypes for gene: RELA were set to periodic fever, inflammatory bowel disease, JIA
Review for gene: RELA was set to GREEN
Added comment: Dominant negative RELA mutations in six patients from five unrelated families. Phenotypic overlap with RELA haploinsufficiency - chronic mucocutaneous ulcerations and autoimmune hematological disorders such as immune thrombocytopenia (ITP) and neutropenia. Patients with RELA DN mutations additionally presented periodic fever, inflammatory bowel diseases (IBDs), juvenile idiopathic arthritis (JIA), and skin involvement.
Sources: Literature
Cerebral Palsy v1.185 SYNE1 Luisa Weiss Deleted their comment
Cerebral Palsy v1.185 SYNE1 Luisa Weiss edited their review of gene: SYNE1: Added comment: Two cases each in two larger CP cohort studies, one with ataxic and one with spastic CP, with biallelic SYNE1 mutations.
In addition, one case report of an 18-year-old girl with CP and a heterozygous SYNE1-mutation. Not that this patient had a history of perinatal distress and asphyxia. The SYNE1 mutation was discovered at the age of 18 years due to a hypertrophic cardiomyopathy. It is uncertain whether the SYNE1 mutation is the cause for the CP.; Changed rating: GREEN; Changed publications: 34321325, 34816117, 31110749; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital ophthalmoplegia v1.8 HNRNPA2B1 Zornitza Stark Phenotypes for gene: HNRNPA2B1 were changed from oculopharyngeal muscular dystrophy, MONDO:0008116 to oculopharyngeal muscular dystrophy, MONDO:0008116, OMIM#620460
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.22 HNRNPA2B1 Zornitza Stark Phenotypes for gene: HNRNPA2B1 were changed from inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 MONDO:0014178; oculopharyngeal muscular dystrophy, MONDO:0008116 to oculopharyngeal muscular dystrophy, MONDO:0008116, OMIM#620460
Mendeliome v1.1087 HNRNPA2B1 Zornitza Stark Phenotypes for gene: HNRNPA2B1 were changed from oculopharyngeal muscular dystrophy, MONDO:0008116; Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 MIM#615422 to oculopharyngeal muscular dystrophy, MONDO:0008116, OMIM#620460; Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 MIM#615422
Hereditary Neuropathy - complex v0.215 SURF1 Sangavi Sivagnanasundram reviewed gene: SURF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843204, 9837813; Phenotypes: Charcot-Marie-Tooth disease, type 4K (MIM#616684, MONDO:0014733); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.215 TECPR2 Sangavi Sivagnanasundram reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 36137062, 26542466, 23176824; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay (HSAN) (MIM#615031); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.215 TYMP Sangavi Sivagnanasundram reviewed gene: TYMP: Rating: AMBER; Mode of pathogenicity: Other; Publications: 20301358, 14757860; Phenotypes: Mitochondrial DNA depletion syndrome 1 (MNGIE type) MIM#603041; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1086 AGAP1 Zornitza Stark Phenotypes for gene: AGAP1 were changed from Cerebral palsy to Cerebral palsy, MONDO:0006497, AGAP1-related
Mendeliome v1.1085 AGAP1 Zornitza Stark edited their review of gene: AGAP1: Changed phenotypes: Cerebral palsy, MONDO:0006497, AGAP1-related
Cerebral Palsy v1.184 AGAP1 Zornitza Stark Phenotypes for gene: AGAP1 were changed from Neurodevelopmental disorder, MONDO:0700092, AGAP1-related to Cerebral palsy, MONDO:0006497, AGAP1-related
Cerebral Palsy v1.183 AGAP1 Zornitza Stark Phenotypes for gene: AGAP1 were changed from Cerebral palsy to Neurodevelopmental disorder, MONDO:0700092, AGAP1-related
Cerebral Palsy v1.182 AGAP1 Zornitza Stark Publications for gene: AGAP1 were set to 31700678; 25666757; 30472483
Cerebral Palsy v1.181 AGAP1 Zornitza Stark Tag SV/CNV tag was added to gene: AGAP1.
Cerebral Palsy v1.181 HPDL Zornitza Stark Publications for gene: HPDL were set to 33634263
Cerebral Palsy v1.180 HPDL Zornitza Stark Classified gene: HPDL as Green List (high evidence)
Cerebral Palsy v1.180 HPDL Zornitza Stark Gene: hpdl has been classified as Green List (High Evidence).
Cerebral Palsy v1.179 MAP2K1 Zornitza Stark Marked gene: MAP2K1 as ready
Cerebral Palsy v1.179 MAP2K1 Zornitza Stark Gene: map2k1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.179 MAP2K1 Zornitza Stark Classified gene: MAP2K1 as Green List (high evidence)
Cerebral Palsy v1.179 MAP2K1 Zornitza Stark Gene: map2k1 has been classified as Green List (High Evidence).
Mendeliome v1.1085 PRDM10 Zornitza Stark Phenotypes for gene: PRDM10 were changed from Fibrofolliculoma, HP:0030436; lipomatosis, MONDO:0006574; renal cell carcinoma, MONDO:0005086 to Birt-Hogg-Dube syndrome 2, MIM# 620459
Mendeliome v1.1084 PRDM10 Zornitza Stark reviewed gene: PRDM10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Birt-Hogg-Dube syndrome 2, MIM# 620459; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.136 PLCB4 Zornitza Stark Phenotypes for gene: PLCB4 were changed from Auriculocondylar syndrome 2, MIM# 614669 to Auriculocondylar syndrome 2A, MIM# 614669; Auriculocondylar syndrome 2B, MIM# 620458
Fetal anomalies v1.135 PLCB4 Zornitza Stark reviewed gene: PLCB4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Auriculocondylar syndrome 2A, MIM# 614669, Auriculocondylar syndrome 2B, MIM# 620458; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Clefting disorders v0.240 PLCB4 Zornitza Stark Phenotypes for gene: PLCB4 were changed from Auriculocondylar syndrome 2, MIM# 614669; Cleft palate to Auriculocondylar syndrome 2A, MIM# 614669; Auriculocondylar syndrome 2B, MIM# 620458; Cleft palate
Clefting disorders v0.239 PLCB4 Zornitza Stark edited their review of gene: PLCB4: Changed phenotypes: AAuriculocondylar syndrome 2A, MIM# 614669, Auriculocondylar syndrome 2B, MIM# 620458
Pierre Robin Sequence v0.47 PLCB4 Zornitza Stark edited their review of gene: PLCB4: Changed phenotypes: Auriculocondylar syndrome 2A, MIM# 614669, Auriculocondylar syndrome 2B, MIM# 620458
Pierre Robin Sequence v0.47 PLCB4 Zornitza Stark Phenotypes for gene: PLCB4 were changed from Auriculocondylar syndrome 2, MIM# 614669 to Auriculocondylar syndrome 2A, MIM# 614669; Auriculocondylar syndrome 2B, MIM# 620458
Mendeliome v1.1084 PLCB4 Zornitza Stark Phenotypes for gene: PLCB4 were changed from Auriculocondylar syndrome 2, MIM# 614669 to Auriculocondylar syndrome 2A, MIM# 614669; Auriculocondylar syndrome 2B, MIM# 620458
Mendeliome v1.1083 PLCB4 Zornitza Stark edited their review of gene: PLCB4: Changed phenotypes: Auriculocondylar syndrome 2A, MIM# 614669, Auriculocondylar syndrome 2B, MIM# 620458
Mandibulofacial Acrofacial dysostosis v1.9 PLCB4 Zornitza Stark Phenotypes for gene: PLCB4 were changed from Auriculocondylar syndrome 2, MIM# 614669 to Auriculocondylar syndrome 2A, MIM# 614669; Auriculocondylar syndrome 2B, MIM# 620458
Mandibulofacial Acrofacial dysostosis v1.8 PLCB4 Zornitza Stark edited their review of gene: PLCB4: Changed phenotypes: Auriculocondylar syndrome 2A, MIM# 614669, Auriculocondylar syndrome 2B, MIM# 620458
Cardiomyopathy_Paediatric v0.166 TBX5 Zornitza Stark Marked gene: TBX5 as ready
Cardiomyopathy_Paediatric v0.166 TBX5 Zornitza Stark Gene: tbx5 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.166 TBX5 Zornitza Stark Classified gene: TBX5 as Green List (high evidence)
Cardiomyopathy_Paediatric v0.166 TBX5 Zornitza Stark Gene: tbx5 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.165 TBX5 Zornitza Stark gene: TBX5 was added
gene: TBX5 was added to Cardiomyopathy_Paediatric. Sources: Expert Review
Mode of inheritance for gene: TBX5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBX5 were set to 32449309; 32236096; 25963046; 25725155
Phenotypes for gene: TBX5 were set to Holt-Oram syndrome, MIM# 142900; Dilated cardiomyopathy
Review for gene: TBX5 was set to GREEN
Added comment: DCM is a feature of this congenital disorder.
Sources: Expert Review
Cardiomyopathy_Paediatric v0.164 TBX20 Zornitza Stark Marked gene: TBX20 as ready
Cardiomyopathy_Paediatric v0.164 TBX20 Zornitza Stark Gene: tbx20 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.164 TBX20 Zornitza Stark Classified gene: TBX20 as Green List (high evidence)
Cardiomyopathy_Paediatric v0.164 TBX20 Zornitza Stark Gene: tbx20 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.163 TBX20 Zornitza Stark gene: TBX20 was added
gene: TBX20 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: TBX20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBX20 were set to 26118961; 17668378; 27510170; 35282022
Phenotypes for gene: TBX20 were set to Dilated cardiomyopathy, MONDO:0005021, TBX20-related
Review for gene: TBX20 was set to GREEN
Added comment: Multiple reports in literature, including of children. Also aware of additional four families identified internally, publication pending.
Sources: Literature
Dilated Cardiomyopathy v1.22 TBX20 Zornitza Stark Phenotypes for gene: TBX20 were changed from Dilated cardiomyopathy to Dilated cardiomyopathy, MONDO:0005021, TBX20-related
Dilated Cardiomyopathy v1.21 TBX20 Zornitza Stark Publications for gene: TBX20 were set to 26118961; 17668378; 27510170
Dilated Cardiomyopathy v1.20 TBX20 Zornitza Stark Mode of inheritance for gene: TBX20 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dilated Cardiomyopathy v1.19 TBX20 Zornitza Stark Classified gene: TBX20 as Green List (high evidence)
Dilated Cardiomyopathy v1.19 TBX20 Zornitza Stark Gene: tbx20 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.18 TBX20 Zornitza Stark reviewed gene: TBX20: Rating: GREEN; Mode of pathogenicity: None; Publications: 35282022; Phenotypes: Dilated cardiomyopathy, MONDO:0005021, TBX20-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v0.162 PRDM16 Zornitza Stark Marked gene: PRDM16 as ready
Cardiomyopathy_Paediatric v0.162 PRDM16 Zornitza Stark Gene: prdm16 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.162 PRDM16 Zornitza Stark Classified gene: PRDM16 as Green List (high evidence)
Cardiomyopathy_Paediatric v0.162 PRDM16 Zornitza Stark Gene: prdm16 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.161 PRDM16 Zornitza Stark gene: PRDM16 was added
gene: PRDM16 was added to Cardiomyopathy_Paediatric. Sources: Expert Review
Mode of inheritance for gene: PRDM16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRDM16 were set to 29367541; 29447731; 30847666; 33082984; 32183154; 33500567; 34540771; 34350506; 34935411
Phenotypes for gene: PRDM16 were set to Cardiomyopathy, dilated, 1LL MIM#615373; Left ventricular noncompaction 8 MIM#615373
Review for gene: PRDM16 was set to GREEN
Added comment: Paediatric onset reported.
Sources: Expert Review
Motor Neurone Disease v0.192 LRP12-ALS_CGG Zornitza Stark Marked STR: LRP12-ALS_CGG as ready
Motor Neurone Disease v0.192 LRP12-ALS_CGG Zornitza Stark Str: lrp12-als_cgg has been classified as Green List (High Evidence).
Motor Neurone Disease v0.192 LRP12-ALS_CGG Zornitza Stark Phenotypes for STR: LRP12-ALS_CGG were changed from Amyotrophic lateral sclerosis MONDO:0004976 to Amyotrophic lateral sclerosis MONDO:0004976; Amyotrophic lateral sclerosis 28, MIM# 620452
Mendeliome v1.1083 IL1R1 Zornitza Stark Marked gene: IL1R1 as ready
Mendeliome v1.1083 IL1R1 Zornitza Stark Gene: il1r1 has been classified as Red List (Low Evidence).
Mendeliome v1.1083 IL1R1 Zornitza Stark gene: IL1R1 was added
gene: IL1R1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IL1R1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IL1R1 were set to 37315560
Phenotypes for gene: IL1R1 were set to Chronic recurrent multifocal osteomyelitis 3, MIM# 259680
Review for gene: IL1R1 was set to RED
Added comment: Single individual reported with de novo missense variant in this gene and a phenotype of chronic recurrent multifocal osteomyelitis, auto inflammatory in nature. Some functional data presented.
Sources: Literature
Autoinflammatory Disorders v1.9 IL1R1 Zornitza Stark Marked gene: IL1R1 as ready
Autoinflammatory Disorders v1.9 IL1R1 Zornitza Stark Gene: il1r1 has been classified as Red List (Low Evidence).
Autoinflammatory Disorders v1.9 IL1R1 Zornitza Stark gene: IL1R1 was added
gene: IL1R1 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: IL1R1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IL1R1 were set to 37315560
Phenotypes for gene: IL1R1 were set to Chronic recurrent multifocal osteomyelitis 3, MIM# 259680
Review for gene: IL1R1 was set to RED
Added comment: Single individual reported with de novo missense variant in this gene and a phenotype of chronic recurrent multifocal osteomyelitis, auto inflammatory in nature. Some functional data presented.
Sources: Literature
Mendeliome v1.1082 STAB1 Zornitza Stark Marked gene: STAB1 as ready
Mendeliome v1.1082 STAB1 Zornitza Stark Gene: stab1 has been classified as Green List (High Evidence).
Mendeliome v1.1082 STAB1 Zornitza Stark Classified gene: STAB1 as Green List (high evidence)
Mendeliome v1.1082 STAB1 Zornitza Stark Gene: stab1 has been classified as Green List (High Evidence).
Mendeliome v1.1081 RINT1 Zornitza Stark Phenotypes for gene: RINT1 were changed from Recurrent acute liver failure to Infantile liver failure syndrome 3, MIM# 618641
Hereditary Spastic Paraplegia - paediatric v1.68 RINT1 Zornitza Stark Marked gene: RINT1 as ready
Hereditary Spastic Paraplegia - paediatric v1.68 RINT1 Zornitza Stark Gene: rint1 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia - paediatric v1.68 RINT1 Zornitza Stark Phenotypes for gene: RINT1 were changed from Hereditary spastic paraplegia, MONDO:0019064, RINT1-related to Infantile liver failure syndrome 3, MIM# 618641; Hereditary spastic paraplegia, MONDO:0019064, RINT1-related
Hereditary Spastic Paraplegia - paediatric v1.67 RINT1 Zornitza Stark Classified gene: RINT1 as Amber List (moderate evidence)
Hereditary Spastic Paraplegia - paediatric v1.67 RINT1 Zornitza Stark Gene: rint1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1080 SMARCA4 Zornitza Stark Phenotypes for gene: SMARCA4 were changed from Coffin-Siris syndrome 4, MIM# 614609 to Coffin-Siris syndrome 4, MIM# 614609; Otosclerosis MONDO:0005349, SMARCA4-related
Mendeliome v1.1079 SMARCA4 Zornitza Stark Publications for gene: SMARCA4 were set to 22426308
Deafness_Isolated v1.47 SMARCA4 Zornitza Stark Marked gene: SMARCA4 as ready
Deafness_Isolated v1.47 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Amber List (Moderate Evidence).
Deafness_Isolated v1.47 SMARCA4 Zornitza Stark Classified gene: SMARCA4 as Amber List (moderate evidence)
Deafness_Isolated v1.47 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.115 TBC1D31 Zornitza Stark Marked gene: TBC1D31 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.115 TBC1D31 Zornitza Stark Gene: tbc1d31 has been classified as Red List (Low Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.115 TBC1D31 Zornitza Stark gene: TBC1D31 was added
gene: TBC1D31 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic. Sources: Literature
Mode of inheritance for gene: TBC1D31 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D31 were set to 37468454
Phenotypes for gene: TBC1D31 were set to congenital anomaly of kidney and urinary tract MONDO:0019719, TBC1D31-related
Review for gene: TBC1D31 was set to RED
Added comment: Single paper with homozygous mutations in 3 sibs with CAKUT from consanguineous family
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5324 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5324 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5323 SLC4A10 Krithika Murali Marked gene: SLC4A10 as ready
Intellectual disability syndromic and non-syndromic v0.5323 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Red List (Low Evidence).
Mendeliome v1.1078 TBC1D31 Zornitza Stark Marked gene: TBC1D31 as ready
Mendeliome v1.1078 TBC1D31 Zornitza Stark Gene: tbc1d31 has been classified as Red List (Low Evidence).
Mendeliome v1.1078 TBC1D31 Zornitza Stark Classified gene: TBC1D31 as Red List (low evidence)
Mendeliome v1.1078 TBC1D31 Zornitza Stark Gene: tbc1d31 has been classified as Red List (Low Evidence).
Leukodystrophy - paediatric v0.296 AQP4 Zornitza Stark Marked gene: AQP4 as ready
Leukodystrophy - paediatric v0.296 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.296 AQP4 Zornitza Stark Classified gene: AQP4 as Amber List (moderate evidence)
Leukodystrophy - paediatric v0.296 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.295 AQP4 Zornitza Stark gene: AQP4 was added
gene: AQP4 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: AQP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AQP4 were set to 37143309
Phenotypes for gene: AQP4 were set to Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448
Review for gene: AQP4 was set to AMBER
Added comment: Borderline Amber/Red.

PMID: 37143309 Missense variant in AQP4 seen homozygous in 2 siblings and het in the parents. Patients had macrocephaly, developmental delay, hypotonia, epilepsy, and cognitive deficit.

Western blots on generated MDCK cell lines showed no detectable expression of AQP4 protein from the cells with the patients variant. Immunofluorescence also showed no membrane expression. Overexpression studies in HEK293T cells showed WT was seen as mainly monomers or dimers where as variant protein formed large aggregates- likely due to the saturation of protein degradation pathways because of the overexpression.
Sources: Literature
Early-onset Parkinson disease v0.243 PTPA Zornitza Stark Publications for gene: PTPA were set to 36073231
Early-onset Parkinson disease v0.242 PTPA Zornitza Stark Mode of inheritance for gene: PTPA was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5323 AQP4 Zornitza Stark Marked gene: AQP4 as ready
Intellectual disability syndromic and non-syndromic v0.5323 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5323 AQP4 Zornitza Stark Phenotypes for gene: AQP4 were changed from ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448 to Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448
Intellectual disability syndromic and non-syndromic v0.5322 AQP4 Zornitza Stark Classified gene: AQP4 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5322 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1077 AQP4 Zornitza Stark Marked gene: AQP4 as ready
Mendeliome v1.1077 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1077 AQP4 Zornitza Stark Phenotypes for gene: AQP4 were changed from ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448 to Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448
Mendeliome v1.1076 AQP4 Zornitza Stark Classified gene: AQP4 as Amber List (moderate evidence)
Mendeliome v1.1076 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1879 AQP4 Zornitza Stark Marked gene: AQP4 as ready
Genetic Epilepsy v0.1879 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1879 AQP4 Zornitza Stark Phenotypes for gene: AQP4 were changed from ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448 to Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448
Genetic Epilepsy v0.1878 AQP4 Zornitza Stark Classified gene: AQP4 as Amber List (moderate evidence)
Genetic Epilepsy v0.1878 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1877 AQP4 Zornitza Stark reviewed gene: AQP4: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1075 EZH1 Zornitza Stark Marked gene: EZH1 as ready
Mendeliome v1.1075 EZH1 Zornitza Stark Gene: ezh1 has been classified as Green List (High Evidence).
Mendeliome v1.1075 EZH1 Zornitza Stark Classified gene: EZH1 as Green List (high evidence)
Mendeliome v1.1075 EZH1 Zornitza Stark Gene: ezh1 has been classified as Green List (High Evidence).
Mendeliome v1.1074 EZH1 Zornitza Stark gene: EZH1 was added
gene: EZH1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EZH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EZH1 were set to 37433783
Phenotypes for gene: EZH1 were set to Neurodevelopmental disorder (MONDO:0700092), EZH1-related
Review for gene: EZH1 was set to GREEN
Added comment: PMID: 37433783
Variants were identified 19 individuals from 14 unrelated families, all sharing a clinical phenotype of a neurodevelopmental disorder manifested early in life as global motor, speech and cognitive delay leading to intellectual disability, usually non-progressive and co-occurring with dysmorphic facial features.

Functional studies have shown that some missense EZH1 variants lead to GOF with increased methyltransferase activity and recessive variants impair EZH1 expression causing loss of function effects.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5321 EZH1 Zornitza Stark Marked gene: EZH1 as ready
Intellectual disability syndromic and non-syndromic v0.5321 EZH1 Zornitza Stark Gene: ezh1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5321 EZH1 Zornitza Stark Phenotypes for gene: EZH1 were changed from to Neurodevelopmental disorder (MONDO:0700092), EZH1-related
Intellectual disability syndromic and non-syndromic v0.5320 EZH1 Zornitza Stark Publications for gene: EZH1 were set to
Intellectual disability syndromic and non-syndromic v0.5319 EZH1 Zornitza Stark Classified gene: EZH1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5319 EZH1 Zornitza Stark Gene: ezh1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.66 RINT1 Chern Lim gene: RINT1 was added
gene: RINT1 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: RINT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RINT1 were set to 37463447
Phenotypes for gene: RINT1 were set to Hereditary spastic paraplegia, MONDO:0019064, RINT1-related
Review for gene: RINT1 was set to AMBER
gene: RINT1 was marked as current diagnostic
Added comment: PMID: 37463447
- 3 individuals from 2 unrelated families with biallelic LoF variants - hom canonical spice variant in 1 family, chet stopgain+canonical splice variants in another family.
- Affected individuals presented with early onset spastic paraplegia, ataxia, optic nerve hypoplasia, and dysmorphic features, broadening the previously described phenotype.
- One of the individual died at 14 months due to acute liver failure, probably before the development of a neurological phenotype. The episodic liver dysfunction two other patients was very similar to that previously reported in PMID: 31204009.
- RNA studies showed the splice variants result in aberrant splicing. Other functional and lipidomic analyses supportive of pathogenicity.
Sources: Literature
Mendeliome v1.1073 GPRC5B Zornitza Stark Marked gene: GPRC5B as ready
Mendeliome v1.1073 GPRC5B Zornitza Stark Gene: gprc5b has been classified as Green List (High Evidence).
Mendeliome v1.1073 GPRC5B Zornitza Stark Classified gene: GPRC5B as Green List (high evidence)
Mendeliome v1.1073 GPRC5B Zornitza Stark Gene: gprc5b has been classified as Green List (High Evidence).
Ataxia - adult onset v1.4 RFC1 Dean Phelan Deleted their review
Ataxia - adult onset v1.4 CANVAS Dean Phelan reviewed STR: CANVAS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37450567; Phenotypes: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (MIM:614575); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1072 PHF5A Zornitza Stark Marked gene: PHF5A as ready
Mendeliome v1.1072 PHF5A Zornitza Stark Gene: phf5a has been classified as Green List (High Evidence).
Mendeliome v1.1072 PHF5A Zornitza Stark Classified gene: PHF5A as Green List (high evidence)
Mendeliome v1.1072 PHF5A Zornitza Stark Gene: phf5a has been classified as Green List (High Evidence).
Mendeliome v1.1071 SMARCA4 Paul De Fazio changed review comment from: Additional phenotype reported:

A single missense variant E1610K (M_001128849.3) was reported in 7 affected members of a family with progressive hearing loss due to otosclerosis and no other clinical features. Variant is absent from gnomAD. Note that unaffected members of the family were not tested.

A mouse CRISPR model with the orthologous variant had a similar phenotype.; to: Additional phenotype reported:

A single missense variant E1610K (M_001128849.3) was reported in 7 affected members of a family with progressive hearing loss due to otosclerosis and no other clinical features. Variant is absent from gnomAD. Note that unaffected members of the family were not tested - some obligate carriers were apparently unaffected, reflecting incomplete penetrance.

A mouse CRISPR model with the orthologous variant had a similar phenotype.
Deafness_Isolated v1.46 SMARCA4 Paul De Fazio changed review comment from: A single missense variant E1610K (M_001128849.3) was reported in 7 affected members of a family with progressive hearing loss due to otosclerosis and no other clinical features. Variant is absent from gnomAD. Note that unaffected members of the family were not tested.

A mouse CRISPR model with the orthologous variant had a similar phenotype.
Sources: Literature; to: A single missense variant E1610K (M_001128849.3) was reported in 7 affected members of a family with progressive hearing loss due to otosclerosis and no other clinical features. Variant is absent from gnomAD. Note that unaffected members of the family were not tested - some obligate carriers were apparently unaffected, reflecting incomplete penetrance.

A mouse CRISPR model with the orthologous variant had a similar phenotype.
Sources: Literature
Mendeliome v1.1071 CANVAS Dean Phelan reviewed STR: CANVAS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37450567; Phenotypes: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (MIM:614575); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5318 PHF5A Zornitza Stark Marked gene: PHF5A as ready
Intellectual disability syndromic and non-syndromic v0.5318 PHF5A Zornitza Stark Gene: phf5a has been classified as Green List (High Evidence).
Mendeliome v1.1071 PHF5A Daniel Flanagan gene: PHF5A was added
gene: PHF5A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PHF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PHF5A were set to PMID: 37422718
Phenotypes for gene: PHF5A were set to Neurodevelopmental disorder (MONDO#0700092), PHF5A-related
Review for gene: PHF5A was set to GREEN
Added comment: Nine subjects with congenital malformations, including hypospadias, growth abnormalities, and developmental delay who had de novo PHF5A variants. Prenatally, six subjects had intrauterine growth retardation. All subjects had motor and speech delay and developmental delay. Congenital abnormalities comprised hypospadias in three of four male subjects, and heart defects (3/9), inguinal hernia (3/9), and sacral dimple (3/9). Six of the nine subjects had short stature. Craniofacial dysmorphism is variable in the nine subjects, high forehead and preauricular skin tag(s) in five subjects.
Sources: Expert list
Mendeliome v1.1071 TBC1D31 Lilian Downie gene: TBC1D31 was added
gene: TBC1D31 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TBC1D31 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D31 were set to PMID: 37468454
Phenotypes for gene: TBC1D31 were set to congenital anomaly of kidney and urinary tract MONDO:0019719
Review for gene: TBC1D31 was set to RED
Added comment: Single paper with homozygous mutations in 3 sibs with CAKUT from consanguineous family
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5318 PHF5A Zornitza Stark Classified gene: PHF5A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5318 PHF5A Zornitza Stark Gene: phf5a has been classified as Green List (High Evidence).
Mendeliome v1.1071 AQP4 Lucy Spencer gene: AQP4 was added
gene: AQP4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AQP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AQP4 were set to 37143309
Phenotypes for gene: AQP4 were set to ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448
Review for gene: AQP4 was set to AMBER
Added comment: PMID: 37143309
Cohort of patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). Missense variant in AQP4 seen homozygous in 2 siblings and het in the parents. Patients had macrocephaly, developmental delay, hypotonia, epilepsy, and cognitive deficit.

Western blots on generated MDCK cell lines showed no detectable expression of AQP4 protein from the cells with the patients variant. Immunofluorescence also showed no membrane expression. Overexpression studies in HEK293T cells showed WT was seen as mainly monomers or dimers where as variant protein formed large aggregates- likely due to the saturation of protein degradation pathways because of the overexpression.
Sources: Literature
Fetal anomalies v1.135 PHF5A Zornitza Stark Marked gene: PHF5A as ready
Fetal anomalies v1.135 PHF5A Zornitza Stark Gene: phf5a has been classified as Green List (High Evidence).
Fetal anomalies v1.135 PHF5A Zornitza Stark Phenotypes for gene: PHF5A were changed from PMID: 37422718 to Neurodevelopmental disorder (MONDO#0700092), PHF5A-related
Mitochondrial disease v0.882 COX18 Elena Savva Classified gene: COX18 as Red List (low evidence)
Mitochondrial disease v0.882 COX18 Elena Savva Gene: cox18 has been classified as Red List (Low Evidence).
Mitochondrial disease v0.882 COX18 Elena Savva Classified gene: COX18 as Red List (low evidence)
Mitochondrial disease v0.882 COX18 Elena Savva Gene: cox18 has been classified as Red List (Low Evidence).
Fetal anomalies v1.134 PHF5A Zornitza Stark Publications for gene: PHF5A were set to
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Classified gene: CTNNB1 as Green List (high evidence)
Early-onset Parkinson disease v0.241 PTPA Zornitza Stark Mode of inheritance for gene: PTPA was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Gene: ctnnb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Marked gene: CTNNB1 as ready
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Gene: ctnnb1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.881 COX18 Elena Savva Classified gene: COX18 as Red List (low evidence)
Mitochondrial disease v0.881 COX18 Elena Savva Gene: cox18 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Marked gene: CTNNB1 as ready
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Gene: ctnnb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5317 AQP4 Lucy Spencer gene: AQP4 was added
gene: AQP4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: AQP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AQP4 were set to 37143309
Phenotypes for gene: AQP4 were set to ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448
Review for gene: AQP4 was set to AMBER
Added comment: PMID: 37143309
Cohort patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). Missense variant in AQP4 seen homozygous in 2 siblings and het in the parents. Patients had macrocephaly, developmental delay, hypotonia, epilepsy, and cognitive deficit.

Western blots on generated MDCK cell lines showed no detectable expression of AQP4 protein from the cells with the patients variant. Immunofluorescence also showed no membrane expression. Overexpression studies in HEK293T cells showed WT was seen as mainly monomers or dimers where as variant protein formed large aggregates- likely due to the saturation of protein degradation pathways because of the overexpression.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5317 PHF5A Daniel Flanagan gene: PHF5A was added
gene: PHF5A was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: PHF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PHF5A were set to PMID: 37422718
Phenotypes for gene: PHF5A were set to Neurodevelopmental disorder (MONDO#0700092), PHF5A-related
Review for gene: PHF5A was set to GREEN
Added comment: Nine subjects with congenital malformations, including hypospadias, growth abnormalities, and developmental delay who had de novo PHF5A variants. Prenatally, six subjects had intrauterine growth retardation. All subjects had motor and speech delay and developmental delay. Congenital abnormalities comprised hypospadias in three of four male subjects, and heart defects (3/9), inguinal hernia (3/9), and sacral dimple (3/9). Six of the nine subjects had short stature. Craniofacial dysmorphism is variable in the nine subjects, high forehead and preauricular skin tag(s) in five subjects.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Classified gene: CTNNB1 as Green List (high evidence)
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Gene: ctnnb1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.241 PTPA Zornitza Stark Mode of inheritance for gene: PTPA was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disease v0.881 COX18 Elena Savva Classified gene: COX18 as Red List (low evidence)
Mitochondrial disease v0.881 COX18 Elena Savva Gene: cox18 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Marked gene: GPRC5B as ready
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Fetal anomalies v1.133 PHF5A Zornitza Stark Classified gene: PHF5A as Green List (high evidence)
Fetal anomalies v1.133 PHF5A Zornitza Stark Gene: phf5a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Classified gene: CTNNB1 as Green List (high evidence)
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Gene: ctnnb1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1877 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Genetic Epilepsy v0.1877 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1877 GPRC5B Ain Roesley Marked gene: GPRC5B as ready
Genetic Epilepsy v0.1877 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Mitochondrial disease v0.881 COX18 Elena Savva Classified gene: COX18 as Red List (low evidence)
Mitochondrial disease v0.881 COX18 Elena Savva Gene: cox18 has been classified as Red List (Low Evidence).
Mendeliome v1.1071 GPRC5B Lucy Spencer gene: GPRC5B was added
gene: GPRC5B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPRC5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPRC5B were set to 37143309
Phenotypes for gene: GPRC5B were set to Megalencephalic leukoencephalopathy with subcortical cysts 3 620447
Review for gene: GPRC5B was set to GREEN
Added comment: PMID: 37143309
Cohort of 5 patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). 3 unrelated patients had variants in GPRC5B, 2 have the same inframe dup Ile175dup and the third has an in frame dup of Ala177. All 3 were de novo and unaffected siblings did not have the variants. All patients have macrocephaly, delayed motor development, seizures, all had varying degrees of cognitive deficits. 2 also had spasticity, ataxia and dystonia. MRI showed MLC, abnormal and swollen cerebral white matter.

Patient cell lines showed reduced regulatory volume decrease, and western blot showed a strong increase in GRPC5B levels in patient lymphoblasts. Together, these findings indicate disturbed volume regulation in lymphoblasts from patients with GPRC5B variants, potentially due to increased GPRC5B levels. Transfected cells caused increased volume-regulated anion channel activity.
Sources: Literature
Genetic Epilepsy v0.1877 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Genetic Epilepsy v0.1877 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Mendeliome v1.1071 MAMDC2 Elena Savva Marked gene: MAMDC2 as ready
Mendeliome v1.1071 MAMDC2 Elena Savva Gene: mamdc2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.880 COX18 Elena Savva Marked gene: COX18 as ready
Mitochondrial disease v0.880 COX18 Elena Savva Gene: cox18 has been removed from the panel.
Congenital Heart Defect v0.289 CTNNB1 Zornitza Stark reviewed gene: CTNNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with spastic diplegia and visual defects MIM#615075; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1071 MAMDC2 Elena Savva Classified gene: MAMDC2 as Amber List (moderate evidence)
Mendeliome v1.1071 MAMDC2 Elena Savva Gene: mamdc2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1876 AQP4 Lucy Spencer gene: AQP4 was added
gene: AQP4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: AQP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AQP4 were set to PMID: 37143309
Phenotypes for gene: AQP4 were set to ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448
Review for gene: AQP4 was set to AMBER
Added comment: PMID: 37143309
Cohort of 5 patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). Missense variant in AQP4 seen homozygous in 2 siblings and het in the parents. Patients had macrocephaly, developmental delay, hypotonia, epilepsy, and cognitive deficit.

Western blots on generated MDCK cell lines showed no detectable expression of AQP4 protein from the cells with the patients variant. Immunofluorescence also showed no membrane expression. Overexpression studies in HEK293T cells showed WT was seen as mainly monomers or dimers where as variant protein formed large aggregates- likely due to the saturation of protein degradation pathways because of the overexpression.
Sources: Literature
Mendeliome v1.1070 COX18 Elena Savva Marked gene: COX18 as ready
Mendeliome v1.1070 COX18 Elena Savva Gene: cox18 has been classified as Red List (Low Evidence).
Mendeliome v1.1070 COX18 Elena Savva Classified gene: COX18 as Red List (low evidence)
Mendeliome v1.1070 COX18 Elena Savva Gene: cox18 has been classified as Red List (Low Evidence).
Fetal anomalies v1.132 PHF5A Daniel Flanagan reviewed gene: PHF5A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37422718; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), PHF5A-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy - paediatric v0.294 GPRC5B Ain Roesley Marked gene: GPRC5B as ready
Leukodystrophy - paediatric v0.294 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.294 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Leukodystrophy - paediatric v0.294 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Mendeliome v1.1068 NAA30 Zornitza Stark Marked gene: NAA30 as ready
Mendeliome v1.1068 NAA30 Zornitza Stark Gene: naa30 has been classified as Red List (Low Evidence).
Mendeliome v1.1069 PTPA Zornitza Stark Publications for gene: PTPA were set to 36073231
Intellectual disability syndromic and non-syndromic v0.5316 EZH1 Dean Phelan reviewed gene: EZH1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 37433783; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), EZH1-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1068 MAMDC2 Belinda Chong gene: MAMDC2 was added
gene: MAMDC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAMDC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAMDC2 were set to 37503746
Phenotypes for gene: MAMDC2 were set to Muscular Dystrophy MONDO:0020121, MAMDC2-related
Review for gene: MAMDC2 was set to AMBER
Added comment: 17 individuals with an autosomal dominant muscular dystrophy belonging to two unrelated families in which different heterozygous truncating variants in the last exon of MAMDC2 co-segregate correctly with the disease.
Sources: Literature
Macrocephaly_Megalencephaly v0.127 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Macrocephaly_Megalencephaly v0.127 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.126 GPRC5B Ain Roesley Marked gene: GPRC5B as ready
Macrocephaly_Megalencephaly v0.126 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Mendeliome v1.1068 PTPA Zornitza Stark Mode of inheritance for gene: PTPA was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Macrocephaly_Megalencephaly v0.126 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Macrocephaly_Megalencephaly v0.126 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.293 GPRC5B Lucy Spencer gene: GPRC5B was added
gene: GPRC5B was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: GPRC5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPRC5B were set to 37143309
Phenotypes for gene: GPRC5B were set to Megalencephalic leukoencephalopathy with subcortical cysts 3 MIM#620447
Review for gene: GPRC5B was set to GREEN
Added comment: PMID: 37143309
Cohort of 5 patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). 3 unrelated patients had variants in GPRC5B, 2 have the same inframe dup Ile175dup and the third has an in frame dup of Ala177. All 3 were de novo and unaffected siblings did not have the variants. All patients have macrocephaly, delayed motor development, seizures, all had varying degrees of cognitive deficits. 2 also had spasticity, ataxia and dystonia. MRI showed MLC, abnormal and swollen cerebral white matter.

Patient cell lines showed reduced regulatory volume decrease, and western blot showed a strong increase in GRPC5B levels in patient lymphoblasts. Together, these findings indicate disturbed volume regulation in lymphoblasts from patients with GPRC5B variants, potentially due to increased GPRC5B levels. Transfected cells caused increased volume-regulated anion channel activity.
Sources: Literature
Macrocephaly_Megalencephaly v0.126 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Macrocephaly_Megalencephaly v0.126 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Mendeliome v1.1067 NAA30 Zornitza Stark Phenotypes for gene: NAA30 were changed from to neurodevelopmental disorder, MONDO:0700092, NAA30-related
Autoinflammatory Disorders v1.8 STAT4 Elena Savva Classified gene: STAT4 as Green List (high evidence)
Autoinflammatory Disorders v1.8 STAT4 Elena Savva Gene: stat4 has been classified as Green List (High Evidence).
Mendeliome v1.1066 NAA30 Zornitza Stark Mode of inheritance for gene: NAA30 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoinflammatory Disorders v1.7 STAT4 Elena Savva Classified gene: STAT4 as Green List (high evidence)
Autoinflammatory Disorders v1.7 STAT4 Elena Savva Gene: stat4 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.4 MAMDC2 Elena Savva Classified gene: MAMDC2 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.4 MAMDC2 Elena Savva Gene: mamdc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1065 NAA30 Zornitza Stark Classified gene: NAA30 as Red List (low evidence)
Mendeliome v1.1065 NAA30 Zornitza Stark Gene: naa30 has been classified as Red List (Low Evidence).
Mendeliome v1.1064 COX18 Naomi Baker gene: COX18 was added
gene: COX18 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: COX18 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX18 were set to PMID:37468577
Phenotypes for gene: COX18 were set to Mitochondrial disease (MONDO:0044970), COX18-related
Review for gene: COX18 was set to RED
Added comment: Paper reports a single patient with a homozygous COX18 missense variant, with a neonatal form of mitochondrial hypertrophic cardiomyopathy, lactic acidosis, failure to thrive and neurological involvement associated with severe skeletal muscle COX deficiency. Functional studies demonstrated COX deficiency which could be partially rescued with over-expression of COX18.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.3 MAMDC2 Elena Savva Classified gene: MAMDC2 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.3 MAMDC2 Elena Savva Gene: mamdc2 has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v1.7 STAT4 Elena Savva Classified gene: STAT4 as Green List (high evidence)
Autoinflammatory Disorders v1.7 STAT4 Elena Savva Gene: stat4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5316 NAA30 Zornitza Stark Marked gene: NAA30 as ready
Intellectual disability syndromic and non-syndromic v0.5316 NAA30 Zornitza Stark Gene: naa30 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5316 NAA30 Zornitza Stark Phenotypes for gene: NAA30 were changed from to neurodevelopmental disorder, MONDO:0700092, NAA30-related
Muscular dystrophy and myopathy_Paediatric v1.3 MAMDC2 Elena Savva Classified gene: MAMDC2 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.3 MAMDC2 Elena Savva Gene: mamdc2 has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v1.6 STAT4 Elena Savva Marked gene: STAT4 as ready
Autoinflammatory Disorders v1.6 STAT4 Elena Savva Gene: stat4 has been removed from the panel.
Genetic Epilepsy v0.1876 GPRC5B Lucy Spencer gene: GPRC5B was added
gene: GPRC5B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: GPRC5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPRC5B were set to 37143309
Phenotypes for gene: GPRC5B were set to Megalencephalic leukoencephalopathy with subcortical cysts 3 MIM#620447
Review for gene: GPRC5B was set to GREEN
Added comment: PMID: 37143309
Cohort of 5 patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). 3 unrelated patients had variants in GPRC5B, 2 have the same inframe dup Ile175dup and the third has an in frame dup of Ala177. All 3 were de novo and unaffected siblings did not have the variants. All patients have macrocephaly, delayed motor development, seizures, all had varying degrees of cognitive deficits. 2 also had spasticity, ataxia and dystonia. MRI showed MLC, abnormal and swollen cerebral white matter.

Patient cell lines showed reduced regulatory volume decrease, and western blot showed a strong increase in GRPC5B levels in patient lymphoblasts. Together, these findings indicate disturbed volume regulation in lymphoblasts from patients with GPRC5B variants, potentially due to increased GPRC5B levels. Transfected cells caused increased volume-regulated anion channel activity.
Sources: Literature
Autoinflammatory Disorders v1.6 STAT4 Melanie Marty gene: STAT4 was added
gene: STAT4 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: STAT4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STAT4 were set to PMID: 37256972
Phenotypes for gene: STAT4 were set to Disabling pansclerotic morphea of childhood MIM#620443
Mode of pathogenicity for gene: STAT4 was set to Other
Review for gene: STAT4 was set to GREEN
Added comment: Baghdassarian et al (2023) Four patients from three unrelated families with disabling pansclerotic morphea (DPM, a rare inflammatory disorder), 3 x het missense variants identified, AD inheritance. All 4 patients had disease onset before 5 years of age, with signs of mucosal ulcerations and skin sclerosis. These variants occur in the SH2 domain. Functional studies showed a gain of function effect for these variants.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.2 MAMDC2 Elena Savva Marked gene: MAMDC2 as ready
Muscular dystrophy and myopathy_Paediatric v1.2 MAMDC2 Elena Savva Gene: mamdc2 has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.5315 NAA30 Zornitza Stark Mode of inheritance for gene: NAA30 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Muscular dystrophy and myopathy_Paediatric v1.2 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.2 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.21 MAMDC2 Elena Savva Phenotypes for gene: MAMDC2 were changed from Muscular Dystrophy MONDO:0020121, MAMDC2-related to Muscular Dystrophy MONDO:0020121, MAMDC2-related
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.21 MAMDC2 Elena Savva Marked gene: MAMDC2 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.21 MAMDC2 Elena Savva Gene: mamdc2 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.314 TUFM Ain Roesley Marked gene: TUFM as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.314 TUFM Ain Roesley Gene: tufm has been classified as Red List (Low Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.21 MAMDC2 Elena Savva Phenotypes for gene: MAMDC2 were changed from Muscular Dystrophy to Muscular Dystrophy MONDO:0020121, MAMDC2-related
Muscular dystrophy and myopathy_Paediatric v1.2 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.2 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5314 NAA30 Zornitza Stark Classified gene: NAA30 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5314 NAA30 Zornitza Stark Gene: naa30 has been classified as Red List (Low Evidence).
Mendeliome v1.1064 TUFM Ain Roesley reviewed gene: TUFM: Rating: RED; Mode of pathogenicity: None; Publications: 37461298; Phenotypes: Inherited primary ovarian failure MONDO:0019852, TUFM-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.21 MAMDC2 Elena Savva Classified gene: MAMDC2 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.21 MAMDC2 Elena Savva Gene: mamdc2 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.314 TUFM Ain Roesley edited their review of gene: TUFM: Changed publications: 37461298
Callosome v0.500 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Callosome v0.500 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Mitochondrial disease v0.880 COX18 Naomi Baker gene: COX18 was added
gene: COX18 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: COX18 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX18 were set to PMID:37468577
Phenotypes for gene: COX18 were set to Mitochondrial disease (MONDO:0044970), COX18-related
Review for gene: COX18 was set to RED
Added comment: Paper reports a single patient with a homozygous COX18 missense variant, with a neonatal form of mitochondrial hypertrophic cardiomyopathy, lactic acidosis, failure to thrive and neurological involvement associated with severe skeletal muscle COX deficiency. Functional studies demonstrated COX deficiency which could be partially rescued with over-expression of COX18.
Sources: Literature
Fetal anomalies v1.132 PHF5A Daniel Flanagan Deleted their review
Muscular dystrophy and myopathy_Paediatric v1.2 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.2 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5314 NAA30 Zornitza Stark Classified gene: NAA30 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5314 NAA30 Zornitza Stark Gene: naa30 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.289 CTNNB1 Lilian Downie gene: CTNNB1 was added
gene: CTNNB1 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: CTNNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTNNB1 were set to PMID: 37455656
Phenotypes for gene: CTNNB1 were set to Neurodevelopmental disorder with spastic diplegia and visual defects MIM#615075
Added comment: Paper reviewing 19 patients; five cases presenting with different types of CHDs, including absent pulmonary valve (APV) with intact ventricular septum (IVS),
atrioventricular canal defect (AVCD), tetralogy of Fallot (ToF), and
mitral valve prolapse (MPV).
Lit review summarised about 25% of patients will have a cardiac anomaly as part of the phenotype.
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.20 MAMDC2 Belinda Chong edited their review of gene: MAMDC2: Changed phenotypes: Muscular Dystrophy MONDO:0020121, MAMDC2-related
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.314 TUFM Ain Roesley gene: TUFM was added
gene: TUFM was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature
Mode of inheritance for gene: TUFM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUFM were set to 37468454
Phenotypes for gene: TUFM were set to Inherited primary ovarian failure MONDO:0019852, TUFM-related
Review for gene: TUFM was set to RED
gene: TUFM was marked as current diagnostic
Added comment: 1 family with 1 homozygote with NM_172745.3:c.524G>C: p.Gly175Ala)

in vitro functional: reduction in protein expression, decreased mitochondrial membrane potential and increased reactive oxygen species production, inhibits OXPHOS activity and results in impaired autophagy activation

mouse models recapitulates phenotype
Sources: Literature
Fetal anomalies v1.132 PHF5A Daniel Flanagan gene: PHF5A was added
gene: PHF5A was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: PHF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PHF5A were set to PMID: 37422718
Review for gene: PHF5A was set to GREEN
Added comment: Nine subjects with congenital malformations, including hypospadias, growth abnormalities, and developmental delay who had de novo PHF5A variants. Prenatally, six subjects had intrauterine growth retardation. All subjects had motor and speech delay and developmental delay. Congenital abnormalities comprised hypospadias in three of four male subjects and heart defects, inguinal hernia, and sacral dimple in three subjects. Six of the nine subjects had short stature. Craniofacial dysmorphism is variable in the nine subjects, high forehead and preauricular skin tag(s) in five subjects.
Sources: Expert list
Macrocephaly_Megalencephaly v0.125 GPRC5B Lucy Spencer gene: GPRC5B was added
gene: GPRC5B was added to Macrocephaly_Megalencephaly. Sources: Literature
Mode of inheritance for gene: GPRC5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPRC5B were set to 37143309
Phenotypes for gene: GPRC5B were set to Megalencephalic leukoencephalopathy with subcortical cysts 3 MIM#620447
Review for gene: GPRC5B was set to GREEN
Added comment: PMID: 37143309
Cohort of 5 patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). 3 unrelated patients had variants in GPRC5B, 2 have the same inframe dup Ile175dup and the third has an in frame dup of Ala177. All 3 were de novo and unaffected siblings did not have the variants. All patients have macrocephaly, delayed motor development, spasticity, ataxia and dystonia, seizures, all had varying degrees of cognitive deficits. MRI showed MLC, abnormal and swollen cerebral white matter.

Patient cell lines showed reduced regulatory volume decrease, and western blot showed a strong increase in GRPC5B levels in patient lymphoblasts. Together, these findings indicate disturbed volume regulation in lymphoblasts from patients with GPRC5B variants, potentially due to increased GPRC5B levels. Transfected cells caused increased volume-regulated anion channel activity.
Sources: Literature
Mendeliome v1.1064 STAT4 Elena Savva Publications for gene: STAT4 were set to
Mendeliome v1.1064 STAB1 Chern Lim gene: STAB1 was added
gene: STAB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: STAB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAB1 were set to 37490907; 28052375
Phenotypes for gene: STAB1 were set to Iron metabolism disease (MONDO:0002279), STAB1-related
Review for gene: STAB1 was set to GREEN
gene: STAB1 was marked as current diagnostic
Added comment: PMID: 37490907
- Biallelic variants identified in 10 individuals from 7 families with unexplained hyperferritinaemia without iron overload. All of them were in good health and had no dysmorphologies, psycho-motor development abnormalities, hearing or vision disorders, or other pathologies.
- Homozygous/compound heterozygous variants: missense, frameshift, stopgain, inframe del of 3 AAs, one synonymous.
- Samples from three of the patients from two families showed no immunoreactivity with anti-stabilin-1 compared to control liver where high signal was detected in the liver sinusoids (immunohistochemistry analysis).
- Patients’ peripheral monocytes and monocyte-derived macrophages showed very little expression of stabilin-1 on CD14+ monocytes and macrophages compared to control subjects (flow cytometry analysis).
- These families have also been published in PMID: 28052375.
Sources: Literature
Mendeliome v1.1064 STAT4 Elena Savva Phenotypes for gene: STAT4 were changed from to Disabling pansclerotic morphea of childhood MIM#620443
Callosome v0.499 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Callosome v0.499 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Mendeliome v1.1064 STAT4 Melanie Marty edited their review of gene: STAT4: Changed phenotypes: Disabling pansclerotic morphea of childhood MIM#620443
Mendeliome v1.1064 STAT4 Elena Savva Mode of inheritance for gene: STAT4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.1064 STAT4 Elena Savva Classified gene: STAT4 as Green List (high evidence)
Mendeliome v1.1064 STAT4 Elena Savva Gene: stat4 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.2 MAMDC2 Belinda Chong gene: MAMDC2 was added
gene: MAMDC2 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: MAMDC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAMDC2 were set to 37503746
Phenotypes for gene: MAMDC2 were set to Muscular Dystrophy MONDO:0020121, MAMDC2-related
Review for gene: MAMDC2 was set to AMBER
Added comment: 17 individuals with an autosomal dominant muscular dystrophy belonging to two unrelated families in which different heterozygous truncating variants in the last exon of MAMDC2 co-segregate correctly with the disease.
Sources: Literature
Callosome v0.499 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Callosome v0.499 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Callosome v0.498 SLC4A10 Krithika Murali Marked gene: SLC4A10 as ready
Callosome v0.498 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.240 PTPA Ee Ming Wong reviewed gene: PTPA: Rating: AMBER; Mode of pathogenicity: None; Publications: 37448355; Phenotypes: Intellectual disability, MONDO: 36073231, PTPA-related, Parkisonism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1063 PTPA Ee Ming Wong changed review comment from: - Six individuals with later-onset Parkinson disease with no atypical features eg intellectual disability or early cognitive dysfunction
- All were heterozygous for missense variants, a second hit not identified: authors suggests these are monoallelic cases
- Three of the 5 missense variants have multiple heterozygotes in gnomAD, two of the missense variants have homozygotes in gnomAD, including one with 7 homozygotes.; to: - Six individuals with later-onset Parkinson disease with no atypical features eg intellectual disability or early cognitive dysfunction
- All were heterozygous for missense variants, a second hit not identified: authors suggests these are monoallelic cases
- Three of the 5 missense variants have multiple heterozygotes in gnomAD, two of the missense variants have homozygotes in gnomAD, including one with 7 homozygotes.
Intellectual disability syndromic and non-syndromic v0.5313 GPRC5B Lucy Spencer gene: GPRC5B was added
gene: GPRC5B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GPRC5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPRC5B were set to PMID: 37143309
Phenotypes for gene: GPRC5B were set to Megalencephalic leukoencephalopathy with subcortical cysts 3 MIM#620447
Review for gene: GPRC5B was set to GREEN
Added comment: PMID: 37143309
Cohort of 5 patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). 3 unrelated patients had variants in GPRC5B, 2 have the same inframe dup Ile175dup and the third has an in frame dup of Ala177. All 3 were de novo and unaffected siblings did not have the variants. All patients have macrocephaly, delayed motor development, spasticity, ataxia and dystonia, seizures, all had varying degrees of cognitive deficits. MRI showed MLC, abnormal and swollen cerebral white matter.

Patient cell lines showed reduced regulatory volume decrease, and western blot showed a strong increase in GRPC5B levels in patient lymphoblasts. Together, these findings indicate disturbed volume regulation in lymphoblasts from patients with GPRC5B variants, potentially due to increased GPRC5B levels. Transfected cells caused increased volume-regulated anion channel activity.
Sources: Literature
Ataxia - adult onset v1.4 RFC1 Dean Phelan reviewed gene: RFC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37450567; Phenotypes: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (MIM:614575); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v1.2 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.2 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Microcephaly v1.224 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Microcephaly v1.224 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Metal Metabolism Disorders v0.35 STAB1 Zornitza Stark Marked gene: STAB1 as ready
Metal Metabolism Disorders v0.35 STAB1 Zornitza Stark Gene: stab1 has been classified as Green List (High Evidence).
Metal Metabolism Disorders v0.35 STAB1 Zornitza Stark Phenotypes for gene: STAB1 were changed from Iron metabolism metabolism, MONDO:0002279, STAB1; Hyperferritinaemia without iron overload to Iron metabolism metabolism, MONDO:0002279, STAB1-related; Hyperferritinaemia without iron overload
Muscular dystrophy and myopathy_Paediatric v1.1 SLC4A10 Krithika Murali Marked gene: SLC4A10 as ready
Muscular dystrophy and myopathy_Paediatric v1.1 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Red List (Low Evidence).
Mendeliome v1.1063 PTPA Ee Ming Wong reviewed gene: PTPA: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 37448355; Phenotypes: Intellectual disability, MONDO: 36073231, PTPA-related, Parkisonism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Metal Metabolism Disorders v0.34 STAB1 Zornitza Stark Phenotypes for gene: STAB1 were changed from Hyperferritinaemia without iron overload to Iron metabolism metabolism, MONDO:0002279, STAB1; Hyperferritinaemia without iron overload
Microcephaly v1.223 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Microcephaly v1.223 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Microcephaly v1.223 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Microcephaly v1.223 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Metal Metabolism Disorders v0.33 STAB1 Zornitza Stark Classified gene: STAB1 as Green List (high evidence)
Metal Metabolism Disorders v0.33 STAB1 Zornitza Stark Gene: stab1 has been classified as Green List (High Evidence).
Microcephaly v1.222 SLC4A10 Krithika Murali Marked gene: SLC4A10 as ready
Microcephaly v1.222 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Red List (Low Evidence).
Mendeliome v1.1063 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Mendeliome v1.1063 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Mendeliome v1.1062 SLC4A10 Krithika Murali Marked gene: SLC4A10 as ready
Mendeliome v1.1062 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Red List (Low Evidence).
Mendeliome v1.1062 NAA30 Sarah Pantaleo edited their review of gene: NAA30: Changed phenotypes: neurodevelopmental disorder, MONDO:0700092, NAA30-related
Autism v0.191 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Autism v0.191 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5313 NAA30 Sarah Pantaleo edited their review of gene: NAA30: Changed phenotypes: neurodevelopmental disorder, MONDO:0700092, NAA30-related
Autism v0.190 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Autism v0.190 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Autism v0.190 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Autism v0.190 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Autism v0.189 SLC4A10 Krithika Murali Marked gene: SLC4A10 as ready
Autism v0.189 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Red List (Low Evidence).
Mendeliome v1.1062 SMARCA4 Paul De Fazio reviewed gene: SMARCA4: Rating: AMBER; Mode of pathogenicity: None; Publications: 37399313; Phenotypes: Otosclerosis MONDO:0005349, SMARCA4-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Callosome v0.498 SLC4A10 Krithika Murali gene: SLC4A10 was added
gene: SLC4A10 was added to Callosome. Sources: Literature
Mode of inheritance for gene: SLC4A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A10 were set to PMID: 37459438
Phenotypes for gene: SLC4A10 were set to Neurodevelopmental disorderMONDO:0700092, SLC4A10-related
Review for gene: SLC4A10 was set to GREEN
Added comment: PMID: 37459438 Fasham et al 2023 (Brain) report 10 affected individuals from 5 unrelated families with biallelic LoF variants in this gene with a novel neurodevelopmental disorder.

Phenotypic features include hypotonia in infancy, delayed psychomotor development, typically severe ID, progressive postnatal microcephaly, ASD traits, corpus callosal abnormalities and 'slit-like' lateral ventricles. These phenotypic features were recapitulated in knockout mice with additional supportive functional studies.

Isolated seizures was reported in 2/10 cases.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5313 SLC4A10 Krithika Murali gene: SLC4A10 was added
gene: SLC4A10 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SLC4A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A10 were set to PMID: 37459438
Phenotypes for gene: SLC4A10 were set to Neurodevelopmental disorderMONDO:0700092, SLC4A10-related
Review for gene: SLC4A10 was set to GREEN
Added comment: PMID: 37459438 Fasham et al 2023 (Brain) report 10 affected individuals from 5 unrelated families with biallelic LoF variants in this gene with a novel neurodevelopmental disorder.

Phenotypic features include hypotonia in infancy, delayed psychomotor development, typically severe ID, progressive postnatal microcephaly, ASD traits, corpus callosal abnormalities and 'slit-like' lateral ventricles. These phenotypic features were recapitulated in knockout mice with additional supportive functional studies.

Isolated seizures was reported in 2/10 cases.
Sources: Literature
Peroxisomal Disorders v0.47 PEX14 Zornitza Stark Phenotypes for gene: PEX14 were changed from peroxisome biogenesis disorder due to PEX14 defect MONDO:0100268 to peroxisome biogenesis disorder due to PEX14 defect MONDO:0100268
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.20 MAMDC2 Belinda Chong gene: MAMDC2 was added
gene: MAMDC2 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for gene: MAMDC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAMDC2 were set to 37503746
Phenotypes for gene: MAMDC2 were set to Muscular Dystrophy
Review for gene: MAMDC2 was set to AMBER
Added comment: 17 individuals with an autosomal dominant muscular dystrophy belonging to two unrelated families in which different heterozygous truncating variants in the last exon of MAMDC2 co-segregate correctly with the disease.
Sources: Literature
Autism v0.189 SLC4A10 Krithika Murali gene: SLC4A10 was added
gene: SLC4A10 was added to Autism. Sources: Literature
Mode of inheritance for gene: SLC4A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A10 were set to PMID: 37459438
Phenotypes for gene: SLC4A10 were set to Neurodevelopmental disorderMONDO:0700092, SLC4A10-related
Review for gene: SLC4A10 was set to GREEN
Added comment: PMID: 37459438 Fasham et al 2023 (Brain) report 10 affected individuals from 5 unrelated families with biallelic LoF variants in this gene with a novel neurodevelopmental disorder.

Phenotypic features include hypotonia in infancy, delayed psychomotor development, typically severe ID, progressive postnatal microcephaly, ASD traits, corpus callosal abnormalities and 'slit-like' lateral ventricles. These phenotypic features were recapitulated in knockout mice with additional supportive functional studies.

Isolated seizures was reported in 2/10 cases.
Sources: Literature
Mendeliome v1.1062 NAA30 Sarah Pantaleo gene: NAA30 was added
gene: NAA30 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NAA30 was set to Unknown
Publications for gene: NAA30 were set to PMID: 37387332
Penetrance for gene: NAA30 were set to unknown
Added comment: Report a de novo heterozygous NAA30 nonsense variant c.244C>T, p.(Gln82*) in a 5yo boy with GDD, ASD, hypotonia, seizures, tracheal cleft and recurrent respiratory infections. Seizures resolved after two weeks of life. Family history of ASD in older sister. Epilepsy in mother, childhood onset.

Biochemical studies performed to assess the functional impact of the premature stop codon on catalytic activity. The variant was found to completely disrupt N-terminal acetyltransferase activity using an in vitro acetylation assay.

Variant de novo, “in a gene sensitive to loss of heterozygosity”. Limitation of study - have not established whether this gene variant acts in a dominant or recessive manner.
Sources: Literature
Peroxisomal Disorders v0.46 PEX14 Zornitza Stark Marked gene: PEX14 as ready
Peroxisomal Disorders v0.46 PEX14 Zornitza Stark Gene: pex14 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5312 SLC4A10 Krithika Murali gene: SLC4A10 was added
gene: SLC4A10 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SLC4A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A10 were set to PMID: 37459438
Phenotypes for gene: SLC4A10 were set to Neurodevelopmental disorderMONDO:0700092, SLC4A10-related
Review for gene: SLC4A10 was set to GREEN
Added comment: PMID: 37459438 Fasham et al 2023 (Brain) report 10 affected individuals from 5 unrelated families with biallelic LoF variants in this gene with a novel neurodevelopmental disorder.

Phenotypic features include hypotonia in infancy, delayed psychomotor development, typically severe ID, progressive postnatal microcephaly, ASD traits, corpus callosal abnormalities and 'slit-like' lateral ventricles. These phenotypic features were recapitulated in knockout mice with additional supportive functional studies.

Isolated seizures was reported in 2/10 cases.
Sources: Literature
Deafness_Isolated v1.46 SMARCA4 Paul De Fazio gene: SMARCA4 was added
gene: SMARCA4 was added to Deafness_Isolated. Sources: Literature
Mode of inheritance for gene: SMARCA4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SMARCA4 were set to 37399313
Phenotypes for gene: SMARCA4 were set to Otosclerosis MONDO:0005349, SMARCA4-related
Review for gene: SMARCA4 was set to AMBER
gene: SMARCA4 was marked as current diagnostic
Added comment: A single missense variant E1610K (M_001128849.3) was reported in 7 affected members of a family with progressive hearing loss due to otosclerosis and no other clinical features. Variant is absent from gnomAD. Note that unaffected members of the family were not tested.

A mouse CRISPR model with the orthologous variant had a similar phenotype.
Sources: Literature
Peroxisomal Disorders v0.46 PEX14 Zornitza Stark Phenotypes for gene: PEX14 were changed from to peroxisome biogenesis disorder due to PEX14 defect MONDO:0100268
Intellectual disability syndromic and non-syndromic v0.5312 PIP5K1C Elena Savva Publications for gene: PIP5K1C were set to 37451268
Intellectual disability syndromic and non-syndromic v0.5311 NAA30 Sarah Pantaleo gene: NAA30 was added
gene: NAA30 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NAA30 was set to Unknown
Publications for gene: NAA30 were set to PMID: 37387332
Penetrance for gene: NAA30 were set to unknown
Review for gene: NAA30 was set to RED
Added comment: Report a de novo heterozygous NAA30 nonsense variant c.244C>T, p.(Gln82*) in a 5yo boy with GDD, ASD, hypotonia, seizures, tracheal cleft and recurrent respiratory infections. Seizures resolved after two weeks of life. Family history of ASD in older sister. Epilepsy in mother, childhood onset.

Biochemical studies performed to assess the functional impact of the premature stop codon on catalytic activity. The variant was found to completely disrupt N-terminal acetyltransferase activity using an in vitro acetylation assay.

Variant de novo, “in a gene sensitive to loss of heterozygosity”. Limitation of study - have not established whether this gene variant acts in a dominant or recessive manner.
Sources: Literature
Peroxisomal Disorders v0.46 PEX14 Zornitza Stark Publications for gene: PEX14 were set to 37493040
Microcephaly v1.222 PIP5K1C Elena Savva Publications for gene: PIP5K1C were set to 37451268
Mendeliome v1.1062 STAT4 Melanie Marty changed review comment from: Baghdassarian et al (2023) Four patients from three unrelated families with disabling pansclerotic morphea (DPM, a rare inflammatory disorder), 3 x het missense variants identified, AD inheritance. All 4 patients had disease onset before 5 years of age, with signs of mucosal ulcerations and skin sclerosis. All variants occur in the SH2 domain. Functional studies showed a gain of function effect for these variants.; to: Baghdassarian et al (2023) Four patients from three unrelated families with disabling pansclerotic morphea (DPM, a rare inflammatory disorder), 3 x het missense variants identified, AD inheritance. All 4 patients had disease onset before 5 years of age, with signs of mucosal ulcerations and skin sclerosis. These variants occur in the SH2 domain. Functional studies showed a gain of function effect for these variants.
Cerebral Palsy v1.178 HPDL Clare van Eyk reviewed gene: HPDL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35985664, PMID: 33634263, PMID: 32707086; Phenotypes: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities MIM#619026; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5311 PIP5K1C Elena Savva Publications for gene: PIP5K1C were set to
Mendeliome v1.1062 STAT4 Melanie Marty Deleted their comment
Microcephaly v1.222 PIP5K1C Elena Savva Publications for gene: PIP5K1C were set to
Peroxisomal Disorders v0.45 PEX14 Zornitza Stark Publications for gene: PEX14 were set to
Mendeliome v1.1062 STAT4 Melanie Marty commented on gene: STAT4: Baghdassarian et al (2023) Four patients from three unrelated families with disabling pansclerotic morphea (DPM, a rare inflammatory disorder), 3 x het missense variants identified, AD inheritance. All 4 patients had disease onset before 5 years of age, with signs of mucosal ulcerations and skin sclerosis. All variants occur in the SH2 domain. Functional studies showed a gain of function effect for these variants.
Mendeliome v1.1062 STAT4 Melanie Marty edited their review of gene: STAT4: Changed phenotypes: Disabling pansclerotic morphea, inflammatory disorder, poor wound healing, fibrosis, cytopenias, hypogammaglobulinemia, squamous-cell carcinoma
Multiple pterygium syndrome_Fetal akinesia sequence v1.4 PIP5K1C Elena Savva Publications for gene: PIP5K1C were set to 17701898
Peroxisomal Disorders v0.45 PEX14 Zornitza Stark Mode of inheritance for gene: PEX14 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1062 PIP5K1C Elena Savva Publications for gene: PIP5K1C were set to 17701898
Mendeliome v1.1061 PEX14 Lilian Downie reviewed gene: PEX14: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37493040; Phenotypes: peroxisome biogenesis disorder due to PEX14 defect MONDO:0100268; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Peroxisomal Disorders v0.44 PEX14 Zornitza Stark Mode of inheritance for gene: PEX14 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phagocyte Defects v1.16 SENP7 Elena Savva Classified gene: SENP7 as Amber List (moderate evidence)
Phagocyte Defects v1.16 SENP7 Elena Savva Gene: senp7 has been classified as Amber List (Moderate Evidence).
Phagocyte Defects v1.16 SENP7 Elena Savva Classified gene: SENP7 as Amber List (moderate evidence)
Phagocyte Defects v1.16 SENP7 Elena Savva Gene: senp7 has been classified as Amber List (Moderate Evidence).
Peroxisomal Disorders v0.43 PEX14 Zornitza Stark reviewed gene: PEX14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: peroxisome biogenesis disorder due to PEX14 defect MONDO:0100268; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phagocyte Defects v1.16 SENP7 Elena Savva Classified gene: SENP7 as Amber List (moderate evidence)
Phagocyte Defects v1.16 SENP7 Elena Savva Gene: senp7 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.401 SENP7 Elena Savva Classified gene: SENP7 as Amber List (moderate evidence)
Arthrogryposis v0.401 SENP7 Elena Savva Gene: senp7 has been classified as Amber List (Moderate Evidence).
Phagocyte Defects v1.15 SENP7 Elena Savva Marked gene: SENP7 as ready
Phagocyte Defects v1.15 SENP7 Elena Savva Gene: senp7 has been classified as Red List (Low Evidence).
Arthrogryposis v0.400 SENP7 Elena Savva Marked gene: SENP7 as ready
Arthrogryposis v0.400 SENP7 Elena Savva Gene: senp7 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.400 SENP7 Elena Savva Classified gene: SENP7 as Amber List (moderate evidence)
Arthrogryposis v0.400 SENP7 Elena Savva Gene: senp7 has been classified as Amber List (Moderate Evidence).
Metal Metabolism Disorders v0.32 STAB1 Chern Lim gene: STAB1 was added
gene: STAB1 was added to Iron metabolism disorders. Sources: Literature
Mode of inheritance for gene: STAB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAB1 were set to 37490907; 28052375
Phenotypes for gene: STAB1 were set to Hyperferritinaemia without iron overload
Review for gene: STAB1 was set to GREEN
gene: STAB1 was marked as current diagnostic
Added comment: PMID: 37490907
- Biallelic variants identified in 10 individuals from 7 families with unexplained hyperferritinaemia without iron overload. All of them were in good health and had no dysmorphologies, psycho-motor development abnormalities, hearing or vision disorders, or other pathologies.
- Homozygous/compound heterozygous variants: missense, frameshift, stopgain, inframe del of 3 AAs, one synonymous.
- Samples from three of the patients from two families showed no immunoreactivity with anti-stabilin-1 compared to control liver where high signal was detected in the liver sinusoids (immunohistochemistry analysis).
- Patients’ peripheral monocytes and monocyte-derived macrophages showed very little expression of stabilin-1 on CD14+ monocytes and macrophages compared to control subjects (flow cytometry analysis).
- These families have also been published in PMID: 28052375.
Sources: Literature
Phagocyte Defects v1.15 SENP7 Elena Savva gene: SENP7 was added
gene: SENP7 was added to Phagocyte Defects. Sources: Literature
Mode of inheritance for gene: SENP7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SENP7 were set to PMID: 37460201
Phenotypes for gene: SENP7 were set to Arthrogryposis multiplex congenita, MONDO:0015168, SENP7-related
Review for gene: SENP7 was set to AMBER
Added comment: PMID: 37460201
- 1 family (4 affecteds, sibling pair and 1st cousin) with fatal arthrogryposis multiplex congenita, early respiratory failure and neutropenia. Fetus could not be tested, so 3 confirmed genetically.
- Homozygous for a PTC, decreased mRNA from one sample supports an NMD outcome.
- Additional studies performed supporting downstream proteins expression being affected
- Neutropenia observed in 2/3 patients
Sources: Literature
Mendeliome v1.1061 SENP7 Elena Savva Classified gene: SENP7 as Amber List (moderate evidence)
Mendeliome v1.1061 SENP7 Elena Savva Gene: senp7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1060 SENP7 Elena Savva Marked gene: SENP7 as ready
Mendeliome v1.1060 SENP7 Elena Savva Gene: senp7 has been classified as Red List (Low Evidence).
Mendeliome v1.1060 STAT4 Melanie Marty reviewed gene: STAT4: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 37256972; Phenotypes: Disabling pansclerotic morphea, inflammatory disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1060 SENP7 Elena Savva gene: SENP7 was added
gene: SENP7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SENP7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SENP7 were set to PMID: 37460201
Phenotypes for gene: SENP7 were set to Arthrogryposis multiplex congenita, MONDO:0015168, SENP7-related
Review for gene: SENP7 was set to AMBER
Added comment: PMID: 37460201
- 1 family (4 affecteds, sibling pair and 1st cousin) with fatal arthrogryposis multiplex congenita, early respiratory failure and neutropenia. Fetus could not be tested, so 3 confirmed genetically.
- Homozygous for a PTC, decreased mRNA from one sample supports an NMD outcome.
- Additional studies performed supporting downstream proteins expression being affected
- Neutropenia observed in 2/3 patients
Sources: Literature
Fetal anomalies v1.132 SENP7 Elena Savva Marked gene: SENP7 as ready
Fetal anomalies v1.132 SENP7 Elena Savva Gene: senp7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.132 SENP7 Elena Savva Classified gene: SENP7 as Amber List (moderate evidence)
Fetal anomalies v1.132 SENP7 Elena Savva Gene: senp7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.131 SENP7 Elena Savva gene: SENP7 was added
gene: SENP7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SENP7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SENP7 were set to PMID: 37460201
Phenotypes for gene: SENP7 were set to Arthrogryposis multiplex congenita, MONDO:0015168, SENP7-related
Review for gene: SENP7 was set to AMBER
Added comment: PMID: 37460201
- 1 family (4 affecteds, sibling pair and 1st cousin) with fatal arthrogryposis multiplex congenita, early respiratory failure and neutropenia. Fetus could not be tested, so 3 confirmed genetically.
- Homozygous for a PTC, decreased mRNA from one sample supports an NMD outcome.
- Additional studies performed supporting downstream proteins expression being affected
- Neutropenia observed in 2/3 patients
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.1 SLC4A10 Krithika Murali gene: SLC4A10 was added
gene: SLC4A10 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: SLC4A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A10 were set to PMID: 37459438
Phenotypes for gene: SLC4A10 were set to Neurodevelopmental disorderMONDO:0700092, SLC4A10-related
Review for gene: SLC4A10 was set to GREEN
Added comment: PMID: 37459438 Fasham et al 2023 (Brain) report 10 affected individuals from 5 unrelated families with biallelic LoF variants in this gene with a novel neurodevelopmental disorder.

Phenotypic features include hypotonia in infancy, delayed psychomotor development, typically severe ID, progressive postnatal microcephaly, ASD traits, corpus callosal abnormalities and 'slit-like' lateral ventricles. These phenotypic features were recapitulated in knockout mice with additional supportive functional studies.

Isolated seizures was reported in 2/10 cases.
Sources: Literature
Peroxisomal Disorders v0.43 PEX14 Lilian Downie reviewed gene: PEX14: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 37493040; Phenotypes: peroxisome biogenesis disorder due to PEX14 defect MONDO:0100268; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Arthrogryposis v0.399 SENP7 Elena Savva gene: SENP7 was added
gene: SENP7 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: SENP7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SENP7 were set to PMID: 37460201
Phenotypes for gene: SENP7 were set to Arthrogryposis multiplex congenita, MONDO:0015168, SENP7-related
Review for gene: SENP7 was set to AMBER
Added comment: PMID: 37460201
- 1 family (4 affecteds, sibling pair and 1st cousin) with fatal arthrogryposis multiplex congenita, early respiratory failure and neutropenia. Fetus could not be tested, so 3 confirmed genetically.
- Homozygous for a PTC, decreased mRNA from one sample supports an NMD outcome.
- Additional studies performed supporting downstream proteins expression being affected
- Neutropenia observed in 2/3 patients
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.176 ALPK3 Zornitza Stark Publications for gene: ALPK3 were set to 26846950; 27106955; 32480058
Microcephaly v1.221 SLC4A10 Krithika Murali gene: SLC4A10 was added
gene: SLC4A10 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SLC4A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A10 were set to PMID: 37459438
Phenotypes for gene: SLC4A10 were set to Neurodevelopmental disorderMONDO:0700092, SLC4A10-related
Review for gene: SLC4A10 was set to GREEN
Added comment: PMID: 37459438 Fasham et al 2023 (Brain) report 10 affected individuals from 5 unrelated families with biallelic LoF variants in this gene with a novel neurodevelopmental disorder.

Phenotypic features include hypotonia in infancy, delayed psychomotor development, typically severe ID, progressive postnatal microcephaly, ASD traits, corpus callosal abnormalities and 'slit-like' lateral ventricles. These phenotypic features were recapitulated in knockout mice with additional supportive functional studies.

Isolated seizures was reported in 2/10 cases.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.313 CLPB Zornitza Stark Marked gene: CLPB as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.313 CLPB Zornitza Stark Gene: clpb has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.313 CLPB Zornitza Stark Phenotypes for gene: CLPB were changed from syndromic premature ovarian insufficiency; neutropenia; cataracts; 3-methylglutaconic aciduria; neurological dysfunction to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271 3-methylglutaconic aciduria, type VIIB, autosomal recessive, MIM# 616271; syndromic premature ovarian insufficiency; neutropenia; cataracts; 3-methylglutaconic aciduria; neurological dysfunction
Congenital Disorders of Glycosylation v1.35 STX5 Ain Roesley Marked gene: STX5 as ready
Congenital Disorders of Glycosylation v1.35 STX5 Ain Roesley Gene: stx5 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.312 CLPB Zornitza Stark Classified gene: CLPB as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.312 CLPB Zornitza Stark Gene: clpb has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v1.35 STX5 Ain Roesley Classified gene: STX5 as Amber List (moderate evidence)
Congenital Disorders of Glycosylation v1.35 STX5 Ain Roesley Gene: stx5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.130 STX5 Ain Roesley Marked gene: STX5 as ready
Fetal anomalies v1.130 STX5 Ain Roesley Gene: stx5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1059 STX5 Ain Roesley Marked gene: STX5 as ready
Mendeliome v1.1059 STX5 Ain Roesley Gene: stx5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.130 STX5 Ain Roesley Classified gene: STX5 as Amber List (moderate evidence)
Fetal anomalies v1.130 STX5 Ain Roesley Gene: stx5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1059 STX5 Ain Roesley Publications for gene: STX5 were set to
Mendeliome v1.1058 STX5 Ain Roesley Classified gene: STX5 as Amber List (moderate evidence)
Mendeliome v1.1058 STX5 Ain Roesley Gene: stx5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1057 SLC4A10 Krithika Murali gene: SLC4A10 was added
gene: SLC4A10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC4A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A10 were set to PMID: 37459438
Phenotypes for gene: SLC4A10 were set to Neurodevelopmental disorderMONDO:0700092, SLC4A10-related
Review for gene: SLC4A10 was set to GREEN
Added comment: PMID: 37459438 Fasham et al 2023 (Brain) report 10 affected individuals from 5 unrelated families with biallelic LoF variants in this gene with a novel neurodevelopmental disorder.

Phenotypic features include hypotonia in infancy, delayed psychomotor development, typically severe ID, progressive postnatal microcephaly, ASD traits, corpus callosal abnormalities and 'slit-like' lateral ventricles. These phenotypic features were recapitulated in knockout mice with additional supportive functional studies.

Isolated seizures was reported in 2/10 cases.
Sources: Literature
Dystonia - complex v0.231 SHQ1 Zornitza Stark Publications for gene: SHQ1 were set to 34542157; 29178645
Congenital Disorders of Glycosylation v1.34 STX5 Ain Roesley gene: STX5 was added
gene: STX5 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: STX5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STX5 were set to 34711829
Phenotypes for gene: STX5 were set to congenital disorder of glycosylation MONDO#0015286, STX5-related
Review for gene: STX5 was set to AMBER
gene: STX5 was marked as current diagnostic
Added comment: 1x family with 3x deceased shortly after death + 3x spontaneous abortions + 2x abortions due to abnormal fatal ultrasound (US).
Hom for NM_003164.4:c.163 A > G p.(Met55Val), which results in complete loss of short isoform (which uses Met55 as the start)

phenotype: short long bones on US, dysmorphism, skeletal dysplasia, profound hypotonia, hepatomegaly elevated cholesterol.
Post-natally they died of progressive liver failure with cholestasis and hyperinsulinemic hypoglycemias

Primary human dermal fibroblasts isolated from these patients show defective glycosylation, altered Golgi morphology as measured by electron microscopy, mislocalization of glycosyltransferases, and compromised ER-Golgi trafficking
Sources: Literature
Dystonia - complex v0.230 SHQ1 Zornitza Stark Classified gene: SHQ1 as Green List (high evidence)
Dystonia - complex v0.230 SHQ1 Zornitza Stark Gene: shq1 has been classified as Green List (High Evidence).
Dystonia - complex v0.229 SHQ1 Zornitza Stark edited their review of gene: SHQ1: Added comment: Two more individuals with dystonia reported.; Changed rating: GREEN; Changed publications: 34542157, 29178645, 36847845, 37475611
Mendeliome v1.1056 KDM4B Sarah Pantaleo reviewed gene: KDM4B: Rating: ; Mode of pathogenicity: None; Publications: PMID: 37526414; Phenotypes: Intellectual developmental disorder, autosomal dominant 65, MIM#619320; Mode of inheritance: None
Fetal anomalies v1.129 STX5 Ain Roesley gene: STX5 was added
gene: STX5 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: STX5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STX5 were set to 34711829
Phenotypes for gene: STX5 were set to congenital disorder of glycosylation MONDO#0015286, STX5-related
Review for gene: STX5 was set to AMBER
gene: STX5 was marked as current diagnostic
Added comment: 1x family with 3x deceased shortly after death + 3x spontaneous abortions + 2x abortions due to abnormal fatal ultrasound (US).
Hom for NM_003164.4:c.163 A > G p.(Met55Val), which results in complete loss of short isoform (which uses Met55 as the start)

phenotype: short long bones on US, dysmorphism, skeletal dysplasia, profound hypotonia, hepatomegaly elevated cholesterol.
Post-natally they died of progressive liver failure with cholestasis and hyperinsulinemic hypoglycemias

Primary human dermal fibroblasts isolated from these patients show defective glycosylation, altered Golgi morphology as measured by electron microscopy, mislocalization of glycosyltransferases, and compromised ER-Golgi trafficking
Sources: Literature
Mendeliome v1.1056 STX5 Ain Roesley edited their review of gene: STX5: Changed publications: 34711829
Mendeliome v1.1056 SHQ1 Zornitza Stark Publications for gene: SHQ1 were set to 34542157; 29178645; 36847845
Intellectual disability syndromic and non-syndromic v0.5310 KDM4B Sarah Pantaleo reviewed gene: KDM4B: Rating: ; Mode of pathogenicity: None; Publications: PMID: 37526414; Phenotypes: Intellectual developmental disorder, autosomal dominant 65, MIM#619320; Mode of inheritance: None
Mendeliome v1.1055 SHQ1 Zornitza Stark Classified gene: SHQ1 as Green List (high evidence)
Mendeliome v1.1055 SHQ1 Zornitza Stark Gene: shq1 has been classified as Green List (High Evidence).
Mendeliome v1.1054 SHQ1 Zornitza Stark edited their review of gene: SHQ1: Added comment: Additional individual with isolated, early-onset dystonia reported.

It is likely these clinical presentations are part of a spectrum.; Changed rating: GREEN; Changed publications: 34542157, 29178645, 36847845, 37475611
Mendeliome v1.1054 STX5 Ain Roesley gene: STX5 was added
gene: STX5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: STX5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STX5 were set to congenital disorder of glycosylation MONDO#0015286, STX5-related
Review for gene: STX5 was set to AMBER
gene: STX5 was marked as current diagnostic
Added comment: 1x family with 3x deceased shortly after death + 3x spontaneous abortions + 2x abortions due to abnormal fatal ultrasound (US).
Hom for NM_003164.4:c.163 A > G p.(Met55Val), which results in complete loss of short isoform (which uses Met55 as the start)

phenotype: short long bones on US, dysmorphism, skeletal dysplasia, profound hypotonia, hepatomegaly elevated cholesterol.
Post-natally they died of progressive liver failure with cholestasis and hyperinsulinemic hypoglycemias

Primary human dermal fibroblasts isolated from these patients show defective glycosylation, altered Golgi morphology as measured by electron microscopy, mislocalization of glycosyltransferases, and compromised ER-Golgi trafficking
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5310 EZH1 Dean Phelan gene: EZH1 was added
gene: EZH1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EZH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dystonia - isolated/combined v1.34 SHQ1 Zornitza Stark Publications for gene: SHQ1 were set to 34542157
Dystonia - isolated/combined v1.33 SHQ1 Zornitza Stark Classified gene: SHQ1 as Green List (high evidence)
Dystonia - isolated/combined v1.33 SHQ1 Zornitza Stark Gene: shq1 has been classified as Green List (High Evidence).
Dystonia - isolated/combined v1.32 SHQ1 Zornitza Stark edited their review of gene: SHQ1: Added comment: Additional individual with isolated dystonia, early-onset, reported. Compound het variants including one LoF and one missense.; Changed rating: GREEN; Changed publications: 34542157, 37475611
Cerebral Palsy v1.178 AGAP1 Clare van Eyk changed review comment from: An additional three patients with heterozygous microdeletions and phenotypic overlap with previously described patients, but none with a CP diagnosis (PMID:36778426). Overall 4/10 patients with an AGAP1 variant have CP, however not all of these were classified as pathogenic and 2/3 of the new microdeletions are inherited suggesting incomplete penetrance. Authors show that mutant Drosophila have increased lethality from exposure to environmental insult.; to: An additional three patients with heterozygous microdeletions and phenotypic overlap with previously described patients, but none with a CP diagnosis (PMID:36778426, PMID: 37470098). Overall 4/10 patients with an AGAP1 variant have CP, however not all of these were classified as pathogenic and 2/3 of the new microdeletions are inherited suggesting incomplete penetrance. Authors show that mutant Drosophila have increased lethality from exposure to environmental insult.
Cerebral Palsy v1.178 AGAP1 Clare van Eyk reviewed gene: AGAP1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 36778426; Phenotypes: cerebral palsy, intellectual disability, autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.175 ALPK3 Sarah Pantaleo reviewed gene: ALPK3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34263907, 35783621; Phenotypes: Cardiomyopathy, familial hypertrophic 27 MIM#618052; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2180 KCNQ1 Zornitza Stark Phenotypes for gene: KCNQ1 were changed from Long QT syndrome 1, MIM# 192500 to Jervell and Lange-Nielsen syndrome MIM#220400; Long QT syndrome 1, MIM# 192500
BabyScreen+ newborn screening v0.2179 KCNQ1 Zornitza Stark Mode of inheritance for gene: KCNQ1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2178 KCNQ1 Zornitza Stark Tag deafness tag was added to gene: KCNQ1.
BabyScreen+ newborn screening v0.2178 DMD Zornitza Stark Classified gene: DMD as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2178 DMD Zornitza Stark Gene: dmd has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2177 DMD Zornitza Stark Tag for review was removed from gene: DMD.
BabyScreen+ newborn screening v0.2177 DMD Zornitza Stark edited their review of gene: DMD: Added comment: Reviewed with RCH Neurology team: treatments currently not approved by the TGA. Downgrade to Amber, can be upgraded when this changes.; Changed rating: AMBER
Macrocephaly_Megalencephaly v0.125 KDM6B Elena Savva Classified gene: KDM6B as Green List (high evidence)
Macrocephaly_Megalencephaly v0.125 KDM6B Elena Savva Gene: kdm6b has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.124 KDM6B Elena Savva Classified gene: KDM6B as Green List (high evidence)
Macrocephaly_Megalencephaly v0.124 KDM6B Elena Savva Gene: kdm6b has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.123 KDM6B Elena Savva Marked gene: KDM6B as ready
Macrocephaly_Megalencephaly v0.123 KDM6B Elena Savva Gene: kdm6b has been classified as Red List (Low Evidence).
Macrocephaly_Megalencephaly v0.123 KDM6B Elena Savva gene: KDM6B was added
gene: KDM6B was added to Macrocephaly_Megalencephaly. Sources: Literature
Mode of inheritance for gene: KDM6B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KDM6B were set to PMID: 37196654
Phenotypes for gene: KDM6B were set to Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities MIM#618505
Review for gene: KDM6B was set to GREEN
Added comment: Rots (2023): 17/65 probands were macrocephalic
Sources: Literature
BabyScreen+ newborn screening v0.2177 KCNQ1 Lilian Downie reviewed gene: KCNQ1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301579; Phenotypes: Jervell and Lange-Nielsen syndrome MIM#220400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.215 MTTP Zornitza Stark Marked gene: MTTP as ready
Hereditary Neuropathy - complex v0.215 MTTP Zornitza Stark Gene: mttp has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.215 MTTP Zornitza Stark Phenotypes for gene: MTTP were changed from Young onset; Abetalipoproteinaemia; hypocholesterloaemia leading to malabsorption of fat-soluble vitamins (vitamin E), acanthocytes, retinitis pigmentosa, progressive sensory axonal neuropathy to Abetalipoproteinemia (MIM#200100); Young onset; Abetalipoproteinaemia; hypocholesterloaemia leading to malabsorption of fat-soluble vitamins (vitamin E), acanthocytes, retinitis pigmentosa, progressive sensory axonal neuropathy
Hereditary Neuropathy - complex v0.214 MTTP Zornitza Stark Publications for gene: MTTP were set to
Hereditary Neuropathy - complex v0.213 MTTP Zornitza Stark reviewed gene: MTTP: Rating: GREEN; Mode of pathogenicity: None; Publications: 33994405; Phenotypes: Abetalipoproteinemia (MIM#200100); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.213 C12orf65 Zornitza Stark Marked gene: C12orf65 as ready
Hereditary Neuropathy - complex v0.213 C12orf65 Zornitza Stark Gene: c12orf65 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.213 C12orf65 Zornitza Stark Publications for gene: C12orf65 were set to
Hereditary Neuropathy - complex v0.212 C12orf65 Zornitza Stark Tag new gene name tag was added to gene: C12orf65.
Hereditary Neuropathy - complex v0.212 ATM Zornitza Stark Marked gene: ATM as ready
Hereditary Neuropathy - complex v0.212 ATM Zornitza Stark Gene: atm has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.212 ATM Zornitza Stark Phenotypes for gene: ATM were changed from Childhood-onset progressive ataxia, conjunctival telangiectasia, sensory axonal neuropathy, chorea and dystonia, immunodeficiency and increased risk of malignancy, elevated α-fetoprotein; Ataxia-telangiectasia syndrome to Ataxia-telangiectasia, MIM#208900; Childhood-onset progressive ataxia, conjunctival telangiectasia, sensory axonal neuropathy, chorea and dystonia, immunodeficiency and increased risk of malignancy, elevated α-fetoprotein; Ataxia-telangiectasia syndrome
Hereditary Neuropathy - complex v0.211 ATM Zornitza Stark Publications for gene: ATM were set to
Hereditary Neuropathy - complex v0.210 ATM Zornitza Stark Classified gene: ATM as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.210 ATM Zornitza Stark Gene: atm has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.209 ATM Zornitza Stark reviewed gene: ATM: Rating: AMBER; Mode of pathogenicity: None; Publications: 32259893; Phenotypes: Ataxia-telangiectasia, MIM#208900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.209 AP1S1 Zornitza Stark Marked gene: AP1S1 as ready
Hereditary Neuropathy - complex v0.209 AP1S1 Zornitza Stark Gene: ap1s1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.209 AP1S1 Zornitza Stark Phenotypes for gene: AP1S1 were changed from Congenital-onset, Mental retardation, Enteropathy (severe congenital diarrhoea), Deafness, sensory-motor Neuropathy with intermediate conduction velocities, Ichthyosis, Keratoderma to MEDNIK Syndrome (MONDO:0012251, MIM#609313); Congenital-onset, Mental retardation, Enteropathy (severe congenital diarrhoea), Deafness, sensory-motor Neuropathy with intermediate conduction velocities, Ichthyosis, Keratoderma
Hereditary Neuropathy - complex v0.208 AP1S1 Zornitza Stark Publications for gene: AP1S1 were set to
Hereditary Neuropathy - complex v0.207 AP1S1 Zornitza Stark reviewed gene: AP1S1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30244301; Phenotypes: MEDNIK syndrome (MIM#609313); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.207 ABCA1 Zornitza Stark Marked gene: ABCA1 as ready
Hereditary Neuropathy - complex v0.207 ABCA1 Zornitza Stark Gene: abca1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.207 ABCA1 Zornitza Stark Phenotypes for gene: ABCA1 were changed from HMSN; Tangier disease to Tangier Disease (MONDO:0008783; MIM#205400)
Hereditary Neuropathy - complex v0.206 ABCA1 Zornitza Stark Publications for gene: ABCA1 were set to
Hereditary Neuropathy - complex v0.205 ABCA1 Zornitza Stark changed review comment from: Neuropathy is a key feature of this metabolic disorder.; to: Neuropathy is a feature of this metabolic disorder. 54 individuals with neuropathy summarised in PMID 29582519.
Hereditary Neuropathy - complex v0.205 ABCA1 Zornitza Stark edited their review of gene: ABCA1: Changed publications: 29582519
Hereditary Neuropathy - complex v0.205 ABCA1 Zornitza Stark reviewed gene: ABCA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tangier Disease (MONDO:0008783, MIM#205400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.178 TSC1 Zornitza Stark Marked gene: TSC1 as ready
Cerebral Palsy v1.178 TSC1 Zornitza Stark Gene: tsc1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.178 TSC1 Zornitza Stark Phenotypes for gene: TSC1 were changed from Focal cortical dysplasia, type II, somatic MIM#607341; Lymphangioleiomyomatosis MIM#606690; Tuberous sclerosis-1 MIM#191100 to Tuberous sclerosis-1 MIM#191100
Cerebral Palsy v1.177 TSC1 Zornitza Stark Classified gene: TSC1 as Amber List (moderate evidence)
Cerebral Palsy v1.177 TSC1 Zornitza Stark Gene: tsc1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.176 TRAPPC9 Zornitza Stark Marked gene: TRAPPC9 as ready
Cerebral Palsy v1.176 TRAPPC9 Zornitza Stark Gene: trappc9 has been classified as Green List (High Evidence).
Cerebral Palsy v1.176 TRAPPC9 Zornitza Stark Classified gene: TRAPPC9 as Green List (high evidence)
Cerebral Palsy v1.176 TRAPPC9 Zornitza Stark Gene: trappc9 has been classified as Green List (High Evidence).
Cerebral Palsy v1.175 TMX2 Zornitza Stark Marked gene: TMX2 as ready
Cerebral Palsy v1.175 TMX2 Zornitza Stark Gene: tmx2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.175 TMX2 Zornitza Stark Classified gene: TMX2 as Green List (high evidence)
Cerebral Palsy v1.175 TMX2 Zornitza Stark Gene: tmx2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.174 TMX2 Zornitza Stark reviewed gene: TMX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity MIM#618730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.174 TH Zornitza Stark Marked gene: TH as ready
Cerebral Palsy v1.174 TH Zornitza Stark Gene: th has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.205 MTTP Sangavi Sivagnanasundram reviewed gene: MTTP: Rating: RED; Mode of pathogenicity: None; Publications: 30358967; Phenotypes: Abetalipoproteinemia (MIM#200100); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.174 TH Zornitza Stark Classified gene: TH as Amber List (moderate evidence)
Cerebral Palsy v1.174 TH Zornitza Stark Gene: th has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1053 TEP1 Zornitza Stark Marked gene: TEP1 as ready
Mendeliome v1.1053 TEP1 Zornitza Stark Gene: tep1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1053 TEP1 Zornitza Stark Classified gene: TEP1 as Amber List (moderate evidence)
Mendeliome v1.1053 TEP1 Zornitza Stark Gene: tep1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1052 TEP1 Zornitza Stark gene: TEP1 was added
gene: TEP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TEP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TEP1 were set to 34543729
Phenotypes for gene: TEP1 were set to Cerebral palsy, MONDO:0006497, TEP1-related
Review for gene: TEP1 was set to AMBER
Added comment: Wang et al. screened a large cohort of more than 600 CP patients from China and found several variants in TEP1, 11 of which were LoF, while no LoF variant was found in the control cohort. These children all had spastic CP. Among these 11 children, 6 children had birth asphyxia and neonatal encephalopathy. Compared to the total group with birth asphyxia (71/667), 6 patients with TEP1 LOF mutations had a significantly greater risk of birth asphyxia. They confirmed TEP1 as a risk factor for CP by cytological and animal models.

Uncertain if these are risk alleles vs indicative of a monogenic disorder. Note LoF variants in gnomad. As this was a cohort study, inheritance of these variants is unknown.
Sources: Literature
Cerebral Palsy v1.173 TEP1 Zornitza Stark Phenotypes for gene: TEP1 were changed from to Cerebral palsy, MONDO:0006497, TEP1-related
Cerebral Palsy v1.172 TEP1 Zornitza Stark Classified gene: TEP1 as Amber List (moderate evidence)
Cerebral Palsy v1.172 TEP1 Zornitza Stark Gene: tep1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.171 TEP1 Zornitza Stark commented on gene: TEP1: Uncertain if these are risk alleles vs indicative of a monogenic disorder. Note LoF variants in gnomad. As this was a cohort study, inheritance of these variants is unknown.
Cerebral Palsy v1.171 TEP1 Zornitza Stark reviewed gene: TEP1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral palsy, MONDO:0006497, TEP1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.171 TEP1 Zornitza Stark Classified gene: TEP1 as Green List (high evidence)
Cerebral Palsy v1.171 TEP1 Zornitza Stark Gene: tep1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.170 TANGO2 Zornitza Stark Marked gene: TANGO2 as ready
Cerebral Palsy v1.170 TANGO2 Zornitza Stark Gene: tango2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.170 TANGO2 Zornitza Stark Classified gene: TANGO2 as Amber List (moderate evidence)
Cerebral Palsy v1.170 TANGO2 Zornitza Stark Gene: tango2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.169 TANGO2 Zornitza Stark reviewed gene: TANGO2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration MIM#616878; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.205 HEXB Sangavi Sivagnanasundram reviewed gene: HEXB: Rating: GREEN; Mode of pathogenicity: None; Publications: 17251047, 14722612, 35420740; Phenotypes: Sandhoff disease, infantile, juvenile, and adult forms (MIM#268800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.169 SYNGAP1 Zornitza Stark Marked gene: SYNGAP1 as ready
Cerebral Palsy v1.169 SYNGAP1 Zornitza Stark Gene: syngap1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.169 SYNGAP1 Zornitza Stark Classified gene: SYNGAP1 as Green List (high evidence)
Cerebral Palsy v1.169 SYNGAP1 Zornitza Stark Gene: syngap1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.168 SYNE1 Zornitza Stark Marked gene: SYNE1 as ready
Cerebral Palsy v1.168 SYNE1 Zornitza Stark Gene: syne1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.168 SYNE1 Zornitza Stark Classified gene: SYNE1 as Amber List (moderate evidence)
Cerebral Palsy v1.168 SYNE1 Zornitza Stark Gene: syne1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.167 SUOX Zornitza Stark Marked gene: SUOX as ready
Cerebral Palsy v1.167 SUOX Zornitza Stark Gene: suox has been classified as Green List (High Evidence).
Cerebral Palsy v1.167 SUOX Zornitza Stark Classified gene: SUOX as Green List (high evidence)
Cerebral Palsy v1.167 SUOX Zornitza Stark Gene: suox has been classified as Green List (High Evidence).
Cerebral Palsy v1.166 STAMBP Zornitza Stark Marked gene: STAMBP as ready
Cerebral Palsy v1.166 STAMBP Zornitza Stark Gene: stambp has been classified as Green List (High Evidence).
Cerebral Palsy v1.166 STAMBP Zornitza Stark Classified gene: STAMBP as Green List (high evidence)
Cerebral Palsy v1.166 STAMBP Zornitza Stark Gene: stambp has been classified as Green List (High Evidence).
Cerebral Palsy v1.165 ST3GAL5 Zornitza Stark Marked gene: ST3GAL5 as ready
Cerebral Palsy v1.165 ST3GAL5 Zornitza Stark Gene: st3gal5 has been classified as Green List (High Evidence).
Cerebral Palsy v1.165 ST3GAL5 Zornitza Stark Classified gene: ST3GAL5 as Green List (high evidence)
Cerebral Palsy v1.165 ST3GAL5 Zornitza Stark Gene: st3gal5 has been classified as Green List (High Evidence).
Cerebral Palsy v1.164 SPTBN2 Zornitza Stark Marked gene: SPTBN2 as ready
Cerebral Palsy v1.164 SPTBN2 Zornitza Stark Gene: sptbn2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.164 SPTBN2 Zornitza Stark Classified gene: SPTBN2 as Green List (high evidence)
Cerebral Palsy v1.164 SPTBN2 Zornitza Stark Gene: sptbn2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.163 SPR Zornitza Stark Marked gene: SPR as ready
Cerebral Palsy v1.163 SPR Zornitza Stark Gene: spr has been classified as Green List (High Evidence).
Cerebral Palsy v1.163 SPR Zornitza Stark Classified gene: SPR as Green List (high evidence)
Cerebral Palsy v1.163 SPR Zornitza Stark Gene: spr has been classified as Green List (High Evidence).
Cerebral Palsy v1.162 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Cerebral Palsy v1.162 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Cerebral Palsy v1.162 SPATA5 Zornitza Stark Classified gene: SPATA5 as Green List (high evidence)
Cerebral Palsy v1.162 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Cerebral Palsy v1.161 SON Zornitza Stark Marked gene: SON as ready
Cerebral Palsy v1.161 SON Zornitza Stark Gene: son has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.161 SON Zornitza Stark Classified gene: SON as Amber List (moderate evidence)
Cerebral Palsy v1.161 SON Zornitza Stark Gene: son has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.160 SNX14 Zornitza Stark Marked gene: SNX14 as ready
Cerebral Palsy v1.160 SNX14 Zornitza Stark Gene: snx14 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.160 SNX14 Zornitza Stark Classified gene: SNX14 as Amber List (moderate evidence)
Cerebral Palsy v1.160 SNX14 Zornitza Stark Gene: snx14 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.159 SMARCB1 Zornitza Stark Classified gene: SMARCB1 as Amber List (moderate evidence)
Cerebral Palsy v1.159 SMARCB1 Zornitza Stark Gene: smarcb1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.158 SLITRK2 Zornitza Stark Marked gene: SLITRK2 as ready
Cerebral Palsy v1.158 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.158 SLITRK2 Zornitza Stark Classified gene: SLITRK2 as Green List (high evidence)
Cerebral Palsy v1.158 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.157 SLC5A6 Zornitza Stark Marked gene: SLC5A6 as ready
Cerebral Palsy v1.157 SLC5A6 Zornitza Stark Gene: slc5a6 has been classified as Green List (High Evidence).
Cerebral Palsy v1.157 SLC5A6 Zornitza Stark Classified gene: SLC5A6 as Green List (high evidence)
Cerebral Palsy v1.157 SLC5A6 Zornitza Stark Gene: slc5a6 has been classified as Green List (High Evidence).
Cerebral Palsy v1.156 SLC16A2 Zornitza Stark Marked gene: SLC16A2 as ready
Cerebral Palsy v1.156 SLC16A2 Zornitza Stark Gene: slc16a2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.156 SLC16A2 Zornitza Stark Classified gene: SLC16A2 as Green List (high evidence)
Cerebral Palsy v1.156 SLC16A2 Zornitza Stark Gene: slc16a2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.155 SLC13A5 Zornitza Stark Marked gene: SLC13A5 as ready
Cerebral Palsy v1.155 SLC13A5 Zornitza Stark Gene: slc13a5 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.155 SLC13A5 Zornitza Stark Classified gene: SLC13A5 as Amber List (moderate evidence)
Cerebral Palsy v1.155 SLC13A5 Zornitza Stark Gene: slc13a5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1051 Bryony Thompson removed gene:DUSP7 from the panel
Hereditary Neuropathy - complex v0.205 GLA Sangavi Sivagnanasundram changed review comment from: Systemic disease manifesting a range of phenotypes including small-fibre neuropathy.
Neuropathy is not a specific feature of Fabry Disease however is shown to progress with age.; to: Systemic disease manifesting a range of phenotypes including small-fibre neuropathy.
Neuropathy is not a specific feature of Fabry Disease however is shown to progress with age.
Variants in GLA have been reported in individuals with neuropathy pain.
Hereditary Neuropathy - complex v0.205 GLA Sangavi Sivagnanasundram reviewed gene: GLA: Rating: AMBER; Mode of pathogenicity: None; Publications: 19318041, 22497776; Phenotypes: Fabry Disease (MIM#301500); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary Neuropathy - complex v0.205 C19orf12 Sangavi Sivagnanasundram reviewed gene: C19orf12: Rating: GREEN; Mode of pathogenicity: None; Publications: 21981780; Phenotypes: Neurodegeneration with brain iron accumulation 4 (NBIA) (MONDO:0013674); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dystonia - complex v0.229 EIF4A2 Zornitza Stark Phenotypes for gene: EIF4A2 were changed from Neurodevelopmental disorder (MONDO:0700092), EIF4A2-related to Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures, MIM# 620455
Intellectual disability syndromic and non-syndromic v0.5310 EIF4A2 Zornitza Stark Phenotypes for gene: EIF4A2 were changed from Neurodevelopmental disorder (MONDO:0700092), EIF4A2-related to Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures, MIM# 620455
Genetic Epilepsy v0.1876 EIF4A2 Zornitza Stark Phenotypes for gene: EIF4A2 were changed from Neurodevelopmental disorder (MONDO:0700092), EIF4A2-related to Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures, MIM# 620455
Mendeliome v1.1050 EIF4A2 Zornitza Stark Phenotypes for gene: EIF4A2 were changed from Neurodevelopmental disorder (MONDO:0700092), EIF4A2-related to Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures, MIM# 620455
Mendeliome v1.1049 TINF2 Sangavi Sivagnanasundram reviewed gene: TINF2: Rating: AMBER; Mode of pathogenicity: None; Publications: https://doi.org/10.1016/j.xhgg.2023.100225; Phenotypes: Multiple Primary Melanomas (MPM); Mode of inheritance: Unknown
Cerebral Palsy v1.154 SHANK3 Zornitza Stark Publications for gene: SHANK3 were set to 17173049
Cerebral Palsy v1.153 SHANK3 Zornitza Stark Classified gene: SHANK3 as Amber List (moderate evidence)
Cerebral Palsy v1.153 SHANK3 Zornitza Stark Gene: shank3 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.152 SEPSECS Zornitza Stark Marked gene: SEPSECS as ready
Cerebral Palsy v1.152 SEPSECS Zornitza Stark Gene: sepsecs has been classified as Green List (High Evidence).
Cerebral Palsy v1.152 SEPSECS Zornitza Stark Classified gene: SEPSECS as Green List (high evidence)
Cerebral Palsy v1.152 SEPSECS Zornitza Stark Gene: sepsecs has been classified as Green List (High Evidence).
Cerebral Palsy v1.151 SATB2 Zornitza Stark Marked gene: SATB2 as ready
Cerebral Palsy v1.151 SATB2 Zornitza Stark Gene: satb2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.151 SATB2 Zornitza Stark Classified gene: SATB2 as Green List (high evidence)
Cerebral Palsy v1.151 SATB2 Zornitza Stark Gene: satb2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.150 SACS Zornitza Stark Marked gene: SACS as ready
Cerebral Palsy v1.150 SACS Zornitza Stark Gene: sacs has been classified as Green List (High Evidence).
Cerebral Palsy v1.150 SACS Zornitza Stark Classified gene: SACS as Green List (high evidence)
Cerebral Palsy v1.150 SACS Zornitza Stark Gene: sacs has been classified as Green List (High Evidence).
Cerebral Palsy v1.149 SACS Zornitza Stark Tag SV/CNV tag was added to gene: SACS.
Cerebral Palsy v1.149 RARS2 Zornitza Stark Marked gene: RARS2 as ready
Cerebral Palsy v1.149 RARS2 Zornitza Stark Gene: rars2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.149 RARS2 Zornitza Stark Classified gene: RARS2 as Green List (high evidence)
Cerebral Palsy v1.149 RARS2 Zornitza Stark Gene: rars2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.148 RAB3GAP1 Zornitza Stark Marked gene: RAB3GAP1 as ready
Cerebral Palsy v1.148 RAB3GAP1 Zornitza Stark Gene: rab3gap1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.148 RAB3GAP1 Zornitza Stark Classified gene: RAB3GAP1 as Green List (high evidence)
Cerebral Palsy v1.148 RAB3GAP1 Zornitza Stark Gene: rab3gap1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.147 PTPN23 Zornitza Stark Marked gene: PTPN23 as ready
Cerebral Palsy v1.147 PTPN23 Zornitza Stark Gene: ptpn23 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.147 PTPN23 Zornitza Stark Classified gene: PTPN23 as Amber List (moderate evidence)
Cerebral Palsy v1.147 PTPN23 Zornitza Stark Gene: ptpn23 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.46 CLPB Zornitza Stark Marked gene: CLPB as ready
Bone Marrow Failure v1.46 CLPB Zornitza Stark Gene: clpb has been classified as Green List (High Evidence).
Bone Marrow Failure v1.46 CLPB Zornitza Stark Phenotypes for gene: CLPB were changed from congenital neutropenia, 3-methylglutaconic aciduria, cataracts, severe psychomotor regression during febrile episodes, epilepsy to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271; 3-methylglutaconic aciduria, type VIIB, autosomal recessive, MIM# 616271; congenital neutropenia, 3-methylglutaconic aciduria, cataracts, severe psychomotor regression during febrile episodes, epilepsy
Bone Marrow Failure v1.45 CLPB Zornitza Stark Classified gene: CLPB as Green List (high evidence)
Bone Marrow Failure v1.45 CLPB Zornitza Stark Gene: clpb has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.4 Bryony Thompson HPO terms changed from Increased susceptibility to fractures, HP:0002659 to
Panel status changed from internal to public
Panel types changed to Melbourne Genomics; Royal Melbourne Hospital
Mendeliome v1.1049 LAMA3 Sangavi Sivagnanasundram changed review comment from: Zhou et al. (2023) - Two heterozygous nonsense variants identified in two individuals of the same family [p.Arg1126Ter and p.Gln1507Ter] that was shown to segregate in the family with reduced penetrance.

The authors hypothesize that function of laminin 𝛼3 is altered as it changes its ability to form heterotrimeric laminins.

In vivo functional study using CRISPR/Cas-9 mediated LAMA3 knockout mice. Results of the functional assay showed development of tricuspid valve and right ventricle abnormalities in the presence of a homozygous LoF variant in LAMA3.; to: Novel gene-disease association
Zhou et al. (2023) - Two heterozygous nonsense variants identified in two individuals of the same family [p.Arg1126Ter and p.Gln1507Ter] that was shown to segregate in the family with reduced penetrance.

The authors hypothesize that function of laminin 𝛼3 is altered as it changes its ability to form heterotrimeric laminins.

In vivo functional study using CRISPR/Cas-9 mediated LAMA3 knockout mice. Results of the functional assay showed development of tricuspid valve and right ventricle abnormalities in the presence of a homozygous LoF variant in LAMA3.
Mendeliome v1.1049 LAMA3 Sangavi Sivagnanasundram reviewed gene: LAMA3: Rating: AMBER; Mode of pathogenicity: None; Publications: https://doi.org/10.1016/j.xhgg.2023.100227; Phenotypes: Ebstein’s anomaly (MIM#224700); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Transplant Co-Morbidity Superpanel v0.3 SUFU Bryony Thompson Classified gene: SUFU as Green List (high evidence)
Transplant Co-Morbidity Superpanel v0.3 SUFU Bryony Thompson Gene: sufu has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.2 PTCH1 Bryony Thompson Classified gene: PTCH1 as Green List (high evidence)
Transplant Co-Morbidity Superpanel v0.2 PTCH1 Bryony Thompson Gene: ptch1 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.1 FAM46A Bryony Thompson Classified gene: FAM46A as Green List (high evidence)
Transplant Co-Morbidity Superpanel v0.1 FAM46A Bryony Thompson Gene: fam46a has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.0 XYLT2 Bryony Thompson gene: XYLT2 was added
gene: XYLT2 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: XYLT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XYLT2 were set to 26987875; 26027496
Phenotypes for gene: XYLT2 were set to Spondyloocular syndrome MIM#605822
Transplant Co-Morbidity Superpanel v0.0 WT1 Bryony Thompson gene: WT1 was added
gene: WT1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: WT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WT1 were set to 35802134
Phenotypes for gene: WT1 were set to Wilms' tumor MIM#194070
Transplant Co-Morbidity Superpanel v0.0 WNT1 Bryony Thompson gene: WNT1 was added
gene: WNT1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: WNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WNT1 were set to 23499310; 23499309; 23656646; 26671912
Phenotypes for gene: WNT1 were set to Osteogenesis imperfecta, type XV, MIM# 615220
Transplant Co-Morbidity Superpanel v0.0 WIPF1 Bryony Thompson gene: WIPF1 was added
gene: WIPF1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: WIPF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WIPF1 were set to 11869681; 14757742; 9405671; 27742395; 22231303
Phenotypes for gene: WIPF1 were set to Wiskott-Aldrich syndrome 2, MIM# 614493
Transplant Co-Morbidity Superpanel v0.0 WFS1 Bryony Thompson gene: WFS1 was added
gene: WFS1 was added to Transplant Co-Morbidity Superpanel. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: WFS1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: WFS1 were set to 27217304; 27185633
Phenotypes for gene: WFS1 were set to diabetes insipidus or optic atrophy; ?Cataract 41,116400; Wolfram syndrome, 222300; Deafness,autosomal dominant 6/14/38, 600965; {Diabetes mellitus, noninsulin-dependent, association with}, 125853; {Diabetes mellitus, noninsulin-dependent,association with}; Deafness, autosomal dominant 6/14/38, 600965; Wolfram-like syndrome, autosomal dominant, 614296
Transplant Co-Morbidity Superpanel v0.0 WAS Bryony Thompson gene: WAS was added
gene: WAS was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: WAS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: WAS were set to Wiskott-Aldrich syndrome, MIM# 301000; Thrombocytopenia, X-linked, MIM# 313900
Transplant Co-Morbidity Superpanel v0.0 VWF Bryony Thompson gene: VWF was added
gene: VWF was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: VWF was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: VWF were set to von Willebrand disease, type 1, MIM#193400; von Willibrand disease, type 3, MIM#277480; von Willebrand disease, types 2A, 2B, 2M, and 2N, MIM#613554
Transplant Co-Morbidity Superpanel v0.0 VPS33B Bryony Thompson gene: VPS33B was added
gene: VPS33B was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: VPS33B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS33B were set to 26399659; 16896922
Phenotypes for gene: VPS33B were set to Arthrogryposis, renal dysfunction, and cholestasis 1, MIM# 208085
Transplant Co-Morbidity Superpanel v0.0 VKORC1 Bryony Thompson gene: VKORC1 was added
gene: VKORC1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: VKORC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VKORC1 were set to 14765194
Phenotypes for gene: VKORC1 were set to Vitamin K-dependent clotting factors, combined deficiency of, 2, MIM# 607473
Transplant Co-Morbidity Superpanel v0.0 VIPAS39 Bryony Thompson gene: VIPAS39 was added
gene: VIPAS39 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: VIPAS39 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VIPAS39 were set to Arthrogryposis, renal dysfunction, and cholestasis 2, MIM# 613404
Transplant Co-Morbidity Superpanel v0.0 VHL Bryony Thompson gene: VHL was added
gene: VHL was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: VHL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: VHL were set to von Hippel-Lindau syndrome , MIM#193300
Transplant Co-Morbidity Superpanel v0.0 VCL Bryony Thompson gene: VCL was added
gene: VCL was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: VCL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCL were set to 11815424; 26458567; 17785437; 31983221; 32516855; 26406308; 24062880
Phenotypes for gene: VCL were set to Cardiomyopathy, dilated, 1W, MIM# 611407
Transplant Co-Morbidity Superpanel v0.0 UQCRFS1 Bryony Thompson gene: UQCRFS1 was added
gene: UQCRFS1 was added to Transplant Co-Morbidity Superpanel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: UQCRFS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UQCRFS1 were set to 31883641
Phenotypes for gene: UQCRFS1 were set to fetal bradycardia; Mitochondrial Complex III deficiency; hypertrophic cardiomyopathy; lactic acidosis; alopecia totalis
Transplant Co-Morbidity Superpanel v0.0 TULP3 Bryony Thompson gene: TULP3 was added
gene: TULP3 was added to Transplant Co-Morbidity Superpanel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: TULP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TULP3 were set to PMID: 35397207
Phenotypes for gene: TULP3 were set to Hepatorenocardiac degenerative fibrosis, MIM# 619902
Transplant Co-Morbidity Superpanel v0.0 TUBB1 Bryony Thompson gene: TUBB1 was added
gene: TUBB1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: TUBB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB1 were set to 31565851; 29333906; 32757236; 18849486
Phenotypes for gene: TUBB1 were set to Macrothrombocytopenia, autosomal dominant, TUBB1-related, MIM# 613112
Transplant Co-Morbidity Superpanel v0.0 TTR Bryony Thompson gene: TTR was added
gene: TTR was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TTR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TTR were set to 28475415; 35802134; 31554435
Phenotypes for gene: TTR were set to Amyloidosis, hereditary, transthyretin-related MIM#105210
Transplant Co-Morbidity Superpanel v0.0 TTN Bryony Thompson gene: TTN was added
gene: TTN was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TTN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TTN were set to 25589632; 28045975; 22335739; 33947203; 34012068
Phenotypes for gene: TTN were set to Cardiomyopathy, dilated, 1G, MIM#604145
Transplant Co-Morbidity Superpanel v0.0 TSC2 Bryony Thompson gene: TSC2 was added
gene: TSC2 was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: TSC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TSC2 were set to Tuberous sclerosis-2, MIM# 613254
Transplant Co-Morbidity Superpanel v0.0 TSC1 Bryony Thompson gene: TSC1 was added
gene: TSC1 was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: TSC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TSC1 were set to Tuberous sclerosis-1, MIM# 191100
Transplant Co-Morbidity Superpanel v0.0 TRPV6 Bryony Thompson gene: TRPV6 was added
gene: TRPV6 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TRPV6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPV6 were set to 29861107
Phenotypes for gene: TRPV6 were set to Hyperparathyroidism, transient neonatal, MIM# 618188
Transplant Co-Morbidity Superpanel v0.0 TRIM63 Bryony Thompson gene: TRIM63 was added
gene: TRIM63 was added to Transplant Co-Morbidity Superpanel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: TRIM63 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM63 were set to 32451364; 30681346
Phenotypes for gene: TRIM63 were set to Hypertrophic cardiomyopathy, MONDO:0005045
Transplant Co-Morbidity Superpanel v0.0 TRDN Bryony Thompson gene: TRDN was added
gene: TRDN was added to Transplant Co-Morbidity Superpanel. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: TRDN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRDN were set to 22422768; 31983240; 30649896; 25922419
Phenotypes for gene: TRDN were set to Long QT syndrome; Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness, MIM# 615441
Transplant Co-Morbidity Superpanel v0.0 TPM4 Bryony Thompson gene: TPM4 was added
gene: TPM4 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: TPM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TPM4 were set to 28134622; 21153663; 31249973
Phenotypes for gene: TPM4 were set to Macrothrombocytopenia
Transplant Co-Morbidity Superpanel v0.0 TPM1 Bryony Thompson gene: TPM1 was added
gene: TPM1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TPM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TPM1 were set to 11273725; 30681346; 15249230; 31270709; 21483645; 31983221; 23147248; 20117437; 28600229; 20215591
Phenotypes for gene: TPM1 were set to Left ventricular noncompaction 9, MIM# 611878; Cardiomyopathy, hypertrophic, 3, MIM# 115196; Cardiomyopathy, dilated, 1Y, MIM# 611878
Transplant Co-Morbidity Superpanel v0.0 TP53 Bryony Thompson gene: TP53 was added
gene: TP53 was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: TP53 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TP53 were set to Li-Fraumeni syndrome, MIM# 151623
Transplant Co-Morbidity Superpanel v0.0 TNXB Bryony Thompson gene: TNXB was added
gene: TNXB was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: TNXB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TNXB were set to Ehlers-Danlos syndrome, classic-like, 1, MIM# 606408
Transplant Co-Morbidity Superpanel v0.0 TNNT2 Bryony Thompson gene: TNNT2 was added
gene: TNNT2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TNNT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNNT2 were set to 20031601; 33947203; 17556660, 30681346; 20978592; 15542288; 11106718
Phenotypes for gene: TNNT2 were set to Cardiomyopathy, familial restrictive, 3, MIM# 612422; Cardiomyopathy, dilated, 1D, MIM# 601494; Left ventricular noncompaction 6, MIM# 601494; Cardiomyopathy, hypertrophic, 2, MIM# 115195
Transplant Co-Morbidity Superpanel v0.0 TNNI3K Bryony Thompson gene: TNNI3K was added
gene: TNNI3K was added to Transplant Co-Morbidity Superpanel. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: TNNI3K was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNNI3K were set to 29355681; 30010057
Phenotypes for gene: TNNI3K were set to Cardiac conduction disease with or without dilated cardiomyopathy, MIM# 616117
Transplant Co-Morbidity Superpanel v0.0 TNNI3 Bryony Thompson gene: TNNI3 was added
gene: TNNI3 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TNNI3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TNNI3 were set to 2226790; 19590045; 30681346; 31568572; 22464770; 21846512; 15607392; 20215591
Phenotypes for gene: TNNI3 were set to Cardiomyopathy, dilated, 1FF, MIM# 613286; Cardiomyopathy, hypertrophic, 7 , MIM#613690; Cardiomyopathy, familial restrictive, MIM#1 115210
Mode of pathogenicity for gene: TNNI3 was set to Other
Transplant Co-Morbidity Superpanel v0.0 TNNC1 Bryony Thompson gene: TNNC1 was added
gene: TNNC1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TNNC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNNC1 were set to 17977476; 33947203; 31983221; 19808376
Phenotypes for gene: TNNC1 were set to MONDO:0012745; Cardiomyopathy, dilated, 1Z, MIM# 611879
Transplant Co-Morbidity Superpanel v0.0 TMEM43 Bryony Thompson gene: TMEM43 was added
gene: TMEM43 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TMEM43 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM43 were set to 22725725; 21214875; 29980933; 24598986; 18313022; 23812740; 33831308
Phenotypes for gene: TMEM43 were set to Arrhythmogenic right ventricular dysplasia 5, MIM# 604400
Transplant Co-Morbidity Superpanel v0.0 TMEM38B Bryony Thompson gene: TMEM38B was added
gene: TMEM38B was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TMEM38B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM38B were set to 23054245; 28323974
Phenotypes for gene: TMEM38B were set to Osteogenesis imperfecta, type XIV , MIM#615066
Transplant Co-Morbidity Superpanel v0.0 TMEM127 Bryony Thompson gene: TMEM127 was added
gene: TMEM127 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: TMEM127 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM127 were set to 34012068
Phenotypes for gene: TMEM127 were set to {Pheochromocytoma, susceptibility to} 171300
Transplant Co-Morbidity Superpanel v0.0 THPO Bryony Thompson gene: THPO was added
gene: THPO was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: THPO was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THPO were set to 10583217; 9425899
Phenotypes for gene: THPO were set to Thrombocythemia 1, MIM# 187950
Transplant Co-Morbidity Superpanel v0.0 THBD Bryony Thompson gene: THBD was added
gene: THBD was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: THBD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THBD were set to 28267383; 25564403; 10627464; 32935436; 25049278; 32634856; 27436851
Phenotypes for gene: THBD were set to Bleeding disorder
Transplant Co-Morbidity Superpanel v0.0 TGFBR2 Bryony Thompson gene: TGFBR2 was added
gene: TGFBR2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TGFBR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TGFBR2 were set to Loeys-Dietz syndrome 2, MIM# 610168
Transplant Co-Morbidity Superpanel v0.0 TGFBR1 Bryony Thompson gene: TGFBR1 was added
gene: TGFBR1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TGFBR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TGFBR1 were set to Loeys-Dietz syndrome 1, MIM# 609192
Transplant Co-Morbidity Superpanel v0.0 TGFB3 Bryony Thompson gene: TGFB3 was added
gene: TGFB3 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TGFB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TGFB3 were set to Loeys-Dietz syndrome 5, MIM# 615582
Transplant Co-Morbidity Superpanel v0.0 TGFB2 Bryony Thompson gene: TGFB2 was added
gene: TGFB2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TGFB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TGFB2 were set to Loeys-Dietz syndrome 4, MIM# 614816
Transplant Co-Morbidity Superpanel v0.0 TECRL Bryony Thompson gene: TECRL was added
gene: TECRL was added to Transplant Co-Morbidity Superpanel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: TECRL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TECRL were set to 33367594; 17666061; 30790670; 27861123
Phenotypes for gene: TECRL were set to Ventricular tachycardia, catecholaminergic polymorphic, 3, MIM# 614021
Transplant Co-Morbidity Superpanel v0.0 TBXAS1 Bryony Thompson gene: TBXAS1 was added
gene: TBXAS1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: TBXAS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBXAS1 were set to 18264100
Phenotypes for gene: TBXAS1 were set to Ghosal hematodiaphyseal syndrome, MIM# 231095
Transplant Co-Morbidity Superpanel v0.0 TBX5 Bryony Thompson gene: TBX5 was added
gene: TBX5 was added to Transplant Co-Morbidity Superpanel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: TBX5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBX5 were set to 25725155; 32236096; 32449309; 25963046
Phenotypes for gene: TBX5 were set to Holt-Oram syndrome, MIM# 142900; Dilated cardiomyopathy
Transplant Co-Morbidity Superpanel v0.0 SUFU Bryony Thompson gene: SUFU was added
gene: SUFU was added to Transplant Co-Morbidity Superpanel. Sources: Expert List
Mode of inheritance for gene: SUFU was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: SUFU were set to SUFU-related neurodevelopmental disorder
Transplant Co-Morbidity Superpanel v0.0 STIM1 Bryony Thompson gene: STIM1 was added
gene: STIM1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: STIM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: STIM1 were set to Stormorken syndrome, MIM# 185070
Transplant Co-Morbidity Superpanel v0.0 SRC Bryony Thompson gene: SRC was added
gene: SRC was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SRC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRC were set to 31204551; 26936507
Phenotypes for gene: SRC were set to Thrombocytopaenia 6, MIM# 616937
Transplant Co-Morbidity Superpanel v0.0 SPARC Bryony Thompson gene: SPARC was added
gene: SPARC was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SPARC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPARC were set to 34462290; 26027498
Phenotypes for gene: SPARC were set to Osteogenesis imperfecta, type XVII, MIM# 616507
Transplant Co-Morbidity Superpanel v0.0 SP7 Bryony Thompson gene: SP7 was added
gene: SP7 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SP7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SP7 were set to 32413570; 29382611; 34091789; 20579626; 35367406
Phenotypes for gene: SP7 were set to Osteogenesis imperfecta type 12, MONDO:0013460; Osteogenesis imperfecta, type XII, OMIM:613849
Transplant Co-Morbidity Superpanel v0.0 SMAD4 Bryony Thompson gene: SMAD4 was added
gene: SMAD4 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SMAD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD4 were set to 30809044
Phenotypes for gene: SMAD4 were set to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, MIM# 175050; Thoracic aortic aneurysm
Transplant Co-Morbidity Superpanel v0.0 SMAD3 Bryony Thompson gene: SMAD3 was added
gene: SMAD3 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SMAD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMAD3 were set to Loeys-Dietz syndrome 3, MIM# 613795
Transplant Co-Morbidity Superpanel v0.0 SLFN14 Bryony Thompson gene: SLFN14 was added
gene: SLFN14 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SLFN14 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLFN14 were set to 26280575; 26769223
Phenotypes for gene: SLFN14 were set to Bleeding disorder, platelet-type, 20, MIM# 616913
Transplant Co-Morbidity Superpanel v0.0 SLC40A1 Bryony Thompson gene: SLC40A1 was added
gene: SLC40A1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review,Expert Review Green
Mode of inheritance for gene: SLC40A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SLC40A1 were set to Hemochromatosis, type 4 606069
Transplant Co-Morbidity Superpanel v0.0 SLC37A4 Bryony Thompson gene: SLC37A4 was added
gene: SLC37A4 was added to Transplant Co-Morbidity Superpanel. Sources: Literature,Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC37A4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SLC37A4 were set to 33964207
Phenotypes for gene: SLC37A4 were set to liver dysfunction; Congenital disorder of glycosylation; coagulation deficiency
Transplant Co-Morbidity Superpanel v0.0 SLC2A10 Bryony Thompson gene: SLC2A10 was added
gene: SLC2A10 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC2A10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC2A10 were set to Arterial tortuosity syndrome, MIM# 208050
Transplant Co-Morbidity Superpanel v0.0 SKI Bryony Thompson gene: SKI was added
gene: SKI was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SKI was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SKI were set to Shprintzen-Goldberg syndrome, MIM# 182212
Transplant Co-Morbidity Superpanel v0.0 SGMS2 Bryony Thompson gene: SGMS2 was added
gene: SGMS2 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGMS2 were set to 32028018; 30779713
Phenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia MIM#126550
Transplant Co-Morbidity Superpanel v0.0 SERPINH1 Bryony Thompson gene: SERPINH1 was added
gene: SERPINH1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SERPINH1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SERPINH1 were set to Osteogenesis imperfecta
Transplant Co-Morbidity Superpanel v0.0 SERPINF2 Bryony Thompson gene: SERPINF2 was added
gene: SERPINF2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SERPINF2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SERPINF2 were set to 10583218; 31441040; 29656168; 31282989; 2572590
Phenotypes for gene: SERPINF2 were set to Alpha-2-plasmin inhibitor deficiency, MIM# 262850
Transplant Co-Morbidity Superpanel v0.0 SERPINF1 Bryony Thompson gene: SERPINF1 was added
gene: SERPINF1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SERPINF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERPINF1 were set to 28689307
Phenotypes for gene: SERPINF1 were set to Osteogenesis imperfecta, type VI, MIM# 613982
Transplant Co-Morbidity Superpanel v0.0 SERPINE1 Bryony Thompson gene: SERPINE1 was added
gene: SERPINE1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SERPINE1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SERPINE1 were set to 15650551; 9207454
Phenotypes for gene: SERPINE1 were set to Plasminogen activator inhibitor-1 deficiency, MIM# 613329
Transplant Co-Morbidity Superpanel v0.0 SEC24D Bryony Thompson gene: SEC24D was added
gene: SEC24D was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SEC24D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEC24D were set to 26467156; 27942778; 30462379; 25683121
Phenotypes for gene: SEC24D were set to Cole-Carpenter syndrome 2, MIM# 616294
Transplant Co-Morbidity Superpanel v0.0 SDHD Bryony Thompson gene: SDHD was added
gene: SDHD was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: SDHD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHD were set to Pheochromocytoma, MIM# 171300; Paragangliomas 1, with or without deafness, MIM# 168000
Transplant Co-Morbidity Superpanel v0.0 SDHC Bryony Thompson gene: SDHC was added
gene: SDHC was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: SDHC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHC were set to Paragangliomas 3, MIM# 605373
Transplant Co-Morbidity Superpanel v0.0 SDHB Bryony Thompson gene: SDHB was added
gene: SDHB was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: SDHB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHB were set to Paragangliomas 4, MIM# 115310
Transplant Co-Morbidity Superpanel v0.0 SDHAF2 Bryony Thompson gene: SDHAF2 was added
gene: SDHAF2 was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: SDHAF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHAF2 were set to Paragangliomas 2, MIM# 601650
Transplant Co-Morbidity Superpanel v0.0 SCN5A Bryony Thompson gene: SCN5A was added
gene: SCN5A was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SCN5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN5A were set to 21824921; 22766342; 22675453; 31520233; 29506689; 19808398; 15671429; 21596231; 29871609; 17512504; 31514951; 22999724; 31930659; 20458009; 30218094
Phenotypes for gene: SCN5A were set to Heart block, nonprogressive; Atrial fibrillation, familial, 10; Long QT syndrome 3; Ventricular fibrillation, familial, 1; Cardiomyopathy, dilated, 1E, MIM# 601154; Sick sinus syndrome 1; Heart block, progressive, type IA; Brugada syndrome 1; {Sudden infant death syndrome, susceptibility to}
Transplant Co-Morbidity Superpanel v0.0 RYR2 Bryony Thompson gene: RYR2 was added
gene: RYR2 was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: RYR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RYR2 were set to Ventricular tachycardia, catecholaminergic polymorphic, 1, MIM# 604772; Arrhythmogenic right ventricular dysplasia 2 , MIM#600996
Transplant Co-Morbidity Superpanel v0.0 RYR1 Bryony Thompson gene: RYR1 was added
gene: RYR1 was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: RYR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RYR1 were set to {Malignant hyperthermia susceptibility 1}, MIM#145600
Transplant Co-Morbidity Superpanel v0.0 RUNX1 Bryony Thompson gene: RUNX1 was added
gene: RUNX1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: RUNX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RUNX1 were set to 10508512
Phenotypes for gene: RUNX1 were set to Platelet disorder, familial, with associated myeloid malignancy, MIM# 601399
Transplant Co-Morbidity Superpanel v0.0 RET Bryony Thompson gene: RET was added
gene: RET was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: RET was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RET were set to Multiple endocrine neoplasia IIB, MIM# 162300; Multiple endocrine neoplasia IIA, MIM# 171400
Transplant Co-Morbidity Superpanel v0.0 RBM8A Bryony Thompson gene: RBM8A was added
gene: RBM8A was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: RBM8A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RBM8A were set to Thrombocytopenia-absent radius syndrome, MIM# 274000
Transplant Co-Morbidity Superpanel v0.0 RBM20 Bryony Thompson gene: RBM20 was added
gene: RBM20 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: RBM20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBM20 were set to 33947203; 30871351; 35802134
Phenotypes for gene: RBM20 were set to Cardiomyopathy, dilated, 1DD MIM#613172 AD
Transplant Co-Morbidity Superpanel v0.0 RB1 Bryony Thompson gene: RB1 was added
gene: RB1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: RB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RB1 were set to Retinoblastoma MONDO:0008380
Transplant Co-Morbidity Superpanel v0.0 RASGRP2 Bryony Thompson gene: RASGRP2 was added
gene: RASGRP2 was added to Transplant Co-Morbidity Superpanel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: RASGRP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RASGRP2 were set to 32041177; 24958846; 30849270; 32609603; 31724816
Phenotypes for gene: RASGRP2 were set to Bleeding disorder, platelet-type, 18, MIM# 615888
Transplant Co-Morbidity Superpanel v0.0 PTPN11 Bryony Thompson gene: PTPN11 was added
gene: PTPN11 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: PTPN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PTPN11 were set to Noonan syndrome 1, MIM# 163950
Mode of pathogenicity for gene: PTPN11 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Transplant Co-Morbidity Superpanel v0.0 PTEN Bryony Thompson gene: PTEN was added
gene: PTEN was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: PTEN was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Phenotypes for gene: PTEN were set to Cowden syndrome 1, MIM# 158350
Transplant Co-Morbidity Superpanel v0.0 PTCH1 Bryony Thompson gene: PTCH1 was added
gene: PTCH1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert List
Mode of inheritance for gene: PTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PTCH1 were set to Holoprosencephaly 7, MIM# 610828
Transplant Co-Morbidity Superpanel v0.0 PRKG1 Bryony Thompson gene: PRKG1 was added
gene: PRKG1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: PRKG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PRKG1 were set to Aortic aneurysm, familial thoracic 8, MIM# 615436
Transplant Co-Morbidity Superpanel v0.0 PRKAG2 Bryony Thompson gene: PRKAG2 was added
gene: PRKAG2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: PRKAG2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRKAG2 were set to 30681346
Phenotypes for gene: PRKAG2 were set to Cardiomyopathy, hypertrophic 6, MIM# 600858
Transplant Co-Morbidity Superpanel v0.0 PRDM16 Bryony Thompson gene: PRDM16 was added
gene: PRDM16 was added to Transplant Co-Morbidity Superpanel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: PRDM16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRDM16 were set to 34540771; 34935411; 29367541; 24387995; 32183154; 33500567; 33082984; 34350506; 31965688; 29447731; PMID: 23768516; 30847666
Phenotypes for gene: PRDM16 were set to Left ventricular noncompaction 8 MIM#615373; Cardiomyopathy, dilated, 1LL MIM#615373
Transplant Co-Morbidity Superpanel v0.0 PPIB Bryony Thompson gene: PPIB was added
gene: PPIB was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: PPIB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPIB were set to 32392875; 19781681
Phenotypes for gene: PPIB were set to Osteogenesis imperfecta, type IX, MIM# 259440
Transplant Co-Morbidity Superpanel v0.0 PPARG Bryony Thompson gene: PPARG was added
gene: PPARG was added to Transplant Co-Morbidity Superpanel. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: PPARG was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PPARG were set to FPLD3; Lipodystrophy, familial partial, type 3; LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 3; Insulin resistance, severe, digenic; Obesity, severe, 601665; Carotid intimal medial thickness 1, 609338; Lipodystrophy, familial partial, type 3, 604367; {Diabetes, type 2}, 125853; Lipodystrophy, familial partial, type 3 604367; [Obesity, resistance to]; Insulin resistance, severe, digenic 604367; Diabetes Mellitus, Noninsulin-Dependent, with Acanthosis Nigricans and Hypertension; Insulin resistance, severe, digenic, 604367
Transplant Co-Morbidity Superpanel v0.0 PMS2 Bryony Thompson gene: PMS2 was added
gene: PMS2 was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: PMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PMS2 were set to Colorectal cancer, hereditary nonpolyposis, type 4, MIM# 614337
Transplant Co-Morbidity Superpanel v0.0 PLS3 Bryony Thompson gene: PLS3 was added
gene: PLS3 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: PLS3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: PLS3 were set to Bone mineral density QTL18, osteoporosis
Transplant Co-Morbidity Superpanel v0.0 PLOD2 Bryony Thompson gene: PLOD2 was added
gene: PLOD2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: PLOD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLOD2 were set to 12881513; 22689593; 15523624
Phenotypes for gene: PLOD2 were set to Bruck syndrome 2, MIM# 609220
Transplant Co-Morbidity Superpanel v0.0 PLN Bryony Thompson gene: PLN was added
gene: PLN was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: PLN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLN were set to 33947203; 30681346
Phenotypes for gene: PLN were set to Cardiomyopathy, hypertrophic, 18 (MIM #613874); Cardiomyopathy, dilated, 1P, MIM# 609909
Transplant Co-Morbidity Superpanel v0.0 PLAU Bryony Thompson gene: PLAU was added
gene: PLAU was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: PLAU was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLAU were set to 20007542
Phenotypes for gene: PLAU were set to Quebec platelet disorder, MIM# 601709
Transplant Co-Morbidity Superpanel v0.0 PLA2G4A Bryony Thompson gene: PLA2G4A was added
gene: PLA2G4A was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: PLA2G4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLA2G4A were set to 23268370; 25102815; 18451993
Phenotypes for gene: PLA2G4A were set to Gastrointestinal ulceration, recurrent, with dysfunctional platelets, MIM# 618372
Transplant Co-Morbidity Superpanel v0.0 PKP2 Bryony Thompson gene: PKP2 was added
gene: PKP2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: PKP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PKP2 were set to 33831308
Phenotypes for gene: PKP2 were set to Arrhythmogenic right ventricular dysplasia 9, MIM# 609040
Transplant Co-Morbidity Superpanel v0.0 PCSK9 Bryony Thompson gene: PCSK9 was added
gene: PCSK9 was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: PCSK9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PCSK9 were set to Hypercholesterolemia, familial, 3, MIM# 603776
Transplant Co-Morbidity Superpanel v0.0 PAX6 Bryony Thompson gene: PAX6 was added
gene: PAX6 was added to Transplant Co-Morbidity Superpanel. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: PAX6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PAX6 were set to diabetes; Aniridia 106210
Transplant Co-Morbidity Superpanel v0.0 PALB2 Bryony Thompson gene: PALB2 was added
gene: PALB2 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: PALB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PALB2 were set to 34012068
Phenotypes for gene: PALB2 were set to {Breast cancer, susceptibility to} 114480
Transplant Co-Morbidity Superpanel v0.0 P4HB Bryony Thompson gene: P4HB was added
gene: P4HB was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: P4HB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: P4HB were set to 25683117; 30063094; 29384951; 29263160
Phenotypes for gene: P4HB were set to Cole-Carpenter syndrome 1, MIM#112240
Transplant Co-Morbidity Superpanel v0.0 P3H1 Bryony Thompson gene: P3H1 was added
gene: P3H1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: P3H1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: P3H1 were set to 18566967; 17277775
Phenotypes for gene: P3H1 were set to Osteogenesis imperfecta, type VIII, (MIM# 610915)
Transplant Co-Morbidity Superpanel v0.0 P2RY12 Bryony Thompson gene: P2RY12 was added
gene: P2RY12 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: P2RY12 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: P2RY12 were set to 29117459; 11196645; 12578987; 19237732
Phenotypes for gene: P2RY12 were set to MONDO:0012354; Bleeding disorder, platelet-type, 8, MIM# 609821
Transplant Co-Morbidity Superpanel v0.0 NOTCH2 Bryony Thompson gene: NOTCH2 was added
gene: NOTCH2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: NOTCH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH2 were set to 21378989; 21378985; 16773578
Phenotypes for gene: NOTCH2 were set to Hajdu-Cheney syndrome (MIM#102500)
Transplant Co-Morbidity Superpanel v0.0 NOTCH1 Bryony Thompson gene: NOTCH1 was added
gene: NOTCH1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: NOTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH1 were set to 26820064; 25963545; 16729972; 16025100
Phenotypes for gene: NOTCH1 were set to Aortic aneurysm
Transplant Co-Morbidity Superpanel v0.0 NF2 Bryony Thompson gene: NF2 was added
gene: NF2 was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: NF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NF2 were set to Neurofibromatosis, type 2, MIM# 101000
Transplant Co-Morbidity Superpanel v0.0 NEXN Bryony Thompson gene: NEXN was added
gene: NEXN was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: NEXN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NEXN were set to 28416588; 27532257; 19881492; 24503780; 29540472; 25163546; 26659360
Phenotypes for gene: NEXN were set to Cardiomyopathy, dilated, 1CC, MIM# 613122
Transplant Co-Morbidity Superpanel v0.0 NEUROD1 Bryony Thompson gene: NEUROD1 was added
gene: NEUROD1 was added to Transplant Co-Morbidity Superpanel. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: NEUROD1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NEUROD1 were set to 10545951; 26773576; 26669242; 20573748
Phenotypes for gene: NEUROD1 were set to MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 6; Maturity-Onset Diabetes Of The Young; Permanent neonatal diabetes and cerebellar agenesis; MODY6; Maturity Onset Diabetes of the Young; {Diabetes mellitus, noninsulin-dependent}, 125853; Maturity-onset diabetes of the young 6, 606394
Transplant Co-Morbidity Superpanel v0.0 NBEAL2 Bryony Thompson gene: NBEAL2 was added
gene: NBEAL2 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: NBEAL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NBEAL2 were set to 21765412; 21765411; 21765413
Phenotypes for gene: NBEAL2 were set to Gray platelet syndrome, MIM# 139090
Transplant Co-Morbidity Superpanel v0.0 NBAS Bryony Thompson gene: NBAS was added
gene: NBAS was added to Transplant Co-Morbidity Superpanel. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: NBAS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NBAS were set to 29955634; 27789416
Phenotypes for gene: NBAS were set to Short stature, optic nerve atrophy, and Pelger-Huet anomaly, MIM# 614800; immunodeficiency; short stature; bone fragility; developmental delay; autism
Transplant Co-Morbidity Superpanel v0.0 MYLK Bryony Thompson gene: MYLK was added
gene: MYLK was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: MYLK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MYLK were set to Aortic aneurysm, familial thoracic 7, MIM# 613780
Transplant Co-Morbidity Superpanel v0.0 MYL3 Bryony Thompson gene: MYL3 was added
gene: MYL3 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: MYL3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYL3 were set to 30681346
Phenotypes for gene: MYL3 were set to Cardiomyopathy, hypertrophic, 8, MIM# 608751
Transplant Co-Morbidity Superpanel v0.0 MYL2 Bryony Thompson gene: MYL2 was added
gene: MYL2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: MYL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYL2 were set to 30681346
Phenotypes for gene: MYL2 were set to Cardiomyopathy, hypertrophic, 10, MIM# 608758
Transplant Co-Morbidity Superpanel v0.0 MYH9 Bryony Thompson gene: MYH9 was added
gene: MYH9 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: MYH9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MYH9 were set to Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, MIM# 155100
Transplant Co-Morbidity Superpanel v0.0 MYH7 Bryony Thompson gene: MYH7 was added
gene: MYH7 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: MYH7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYH7 were set to 30874888; 25935763; 30384889; 30681346; 24119082; 21483645; 27000522; 24558114; 21846512; 33947203; 31179125; 27965028
Phenotypes for gene: MYH7 were set to MONDO:0013262; Cardiomyopathy, dilated, 1S, MIM# 613426; Cardiomyopathy, hypertrophic, 1, MIM# 192600
Transplant Co-Morbidity Superpanel v0.0 MYH11 Bryony Thompson gene: MYH11 was added
gene: MYH11 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: MYH11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MYH11 were set to Aortic aneurysm, familial thoracic 4, MIM# 132900
Transplant Co-Morbidity Superpanel v0.0 MYBPC3 Bryony Thompson gene: MYBPC3 was added
gene: MYBPC3 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: MYBPC3 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: MYBPC3 were set to 30681346; 20378854
Phenotypes for gene: MYBPC3 were set to Cardiomyopathy, dilated, 1MM, MIM# 615396; Left ventricular noncompaction 10, MIM# 615396; Cardiomyopathy, hypertrophic, 4, MIM# 115197
Transplant Co-Morbidity Superpanel v0.0 MTTP Bryony Thompson gene: MTTP was added
gene: MTTP was added to Transplant Co-Morbidity Superpanel. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: MTTP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTTP were set to 30720493; 27604308; 8533758
Phenotypes for gene: MTTP were set to Inherited hypolipidaemias; Abetalipoproteinemia MIM#200100
Transplant Co-Morbidity Superpanel v0.0 MSH6 Bryony Thompson gene: MSH6 was added
gene: MSH6 was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: MSH6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MSH6 were set to Colorectal cancer, hereditary nonpolyposis, type 5, MIM# 614350
Transplant Co-Morbidity Superpanel v0.0 MSH2 Bryony Thompson gene: MSH2 was added
gene: MSH2 was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: MSH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MSH2 were set to Colorectal cancer, hereditary nonpolyposis, type 1, MIM# 120435
Transplant Co-Morbidity Superpanel v0.0 MPL Bryony Thompson gene: MPL was added
gene: MPL was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: MPL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPL were set to 11133753
Phenotypes for gene: MPL were set to Thrombocytopenia, congenital amegakaryocytic, MIM# 604498
Transplant Co-Morbidity Superpanel v0.0 MPIG6B Bryony Thompson gene: MPIG6B was added
gene: MPIG6B was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: MPIG6B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPIG6B were set to 29898956; 31276734; 27743390
Phenotypes for gene: MPIG6B were set to Thrombocytopenia, anemia, and myelofibrosis, MIM# 617441
Transplant Co-Morbidity Superpanel v0.0 MPI Bryony Thompson gene: MPI was added
gene: MPI was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review,Expert Review Green
Mode of inheritance for gene: MPI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPI were set to 32266963; 10980531; 12414827; 33098580; 32905087; 30242110; 33204592; 9585601
Phenotypes for gene: MPI were set to MPI-CDG MONDO:0011257; Congenital disorder of glycosylation, type Ib, MIM# 602579
Transplant Co-Morbidity Superpanel v0.0 MLH1 Bryony Thompson gene: MLH1 was added
gene: MLH1 was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: MLH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MLH1 were set to Colorectal cancer, hereditary nonpolyposis, type 2, MIM# 609310
Transplant Co-Morbidity Superpanel v0.0 MESD Bryony Thompson gene: MESD was added
gene: MESD was added to Transplant Co-Morbidity Superpanel. Sources: Other,Expert Review Green
Mode of inheritance for gene: MESD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MESD were set to 31564437
Phenotypes for gene: MESD were set to Osteogenesis imperfecta, type XX, MIM# 618644
Transplant Co-Morbidity Superpanel v0.0 MEN1 Bryony Thompson gene: MEN1 was added
gene: MEN1 was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: MEN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MEN1 were set to Multiple endocrine neoplasia 1, MIM# 131100
Transplant Co-Morbidity Superpanel v0.0 MED12 Bryony Thompson gene: MED12 was added
gene: MED12 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: MED12 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: MED12 were set to Lujan-Fryns syndrome, MIM# 309520
Transplant Co-Morbidity Superpanel v0.0 MECOM Bryony Thompson gene: MECOM was added
gene: MECOM was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: MECOM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MECOM were set to Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, MIM# 616738
Transplant Co-Morbidity Superpanel v0.0 MCFD2 Bryony Thompson gene: MCFD2 was added
gene: MCFD2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: MCFD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCFD2 were set to 16304051; 18391077; 12717434
Phenotypes for gene: MCFD2 were set to Factor V and factor VIII, combined deficiency of, MIM# 613625; MONDO:0013331
Transplant Co-Morbidity Superpanel v0.0 MAX Bryony Thompson gene: MAX was added
gene: MAX was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to 34012068
Phenotypes for gene: MAX were set to {Pheochromocytoma, susceptibility to} 171300
Transplant Co-Morbidity Superpanel v0.0 LYST Bryony Thompson gene: LYST was added
gene: LYST was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: LYST was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LYST were set to Chediak-Higashi syndrome, MIM# 214500
Transplant Co-Morbidity Superpanel v0.0 LRP5 Bryony Thompson gene: LRP5 was added
gene: LRP5 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: LRP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: LRP5 were set to Osteopetrosis, autosomal dominant 1, MIM# 607634
Transplant Co-Morbidity Superpanel v0.0 LPL Bryony Thompson gene: LPL was added
gene: LPL was added to Transplant Co-Morbidity Superpanel. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: LPL was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: LPL were set to Lipoprotein lipase deficiency, Hyperlipoproteinemia, Combined hyperlipidemia, familial
Transplant Co-Morbidity Superpanel v0.0 LOX Bryony Thompson gene: LOX was added
gene: LOX was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: LOX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LOX were set to 30675029; 30071989; 26838787
Phenotypes for gene: LOX were set to Aortic aneurysm, familial thoracic 10, MIM# 617168
Transplant Co-Morbidity Superpanel v0.0 LMNA Bryony Thompson gene: LMNA was added
gene: LMNA was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: LMNA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LMNA were set to 33947203
Phenotypes for gene: LMNA were set to Cardiomyopathy, dilated, 1A, MIM# 115200
Transplant Co-Morbidity Superpanel v0.0 LMF1 Bryony Thompson gene: LMF1 was added
gene: LMF1 was added to Transplant Co-Morbidity Superpanel. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: LMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LMF1 were set to Combined lipase deficiency
Transplant Co-Morbidity Superpanel v0.0 LMAN1 Bryony Thompson gene: LMAN1 was added
gene: LMAN1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: LMAN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LMAN1 were set to 16304051; 9546392
Phenotypes for gene: LMAN1 were set to MONDO:0009206; Combined factor V and VIII deficiency, MIM# 227300
Transplant Co-Morbidity Superpanel v0.0 LIPC Bryony Thompson gene: LIPC was added
gene: LIPC was added to Transplant Co-Morbidity Superpanel. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: LIPC was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: LIPC were set to 1671786; 12777476; 23219720; 26423094; 1883393; 22464213
Phenotypes for gene: LIPC were set to Inherited mixed hyperlipidaemias; Hepatic lipase deficiency MIM#614025; hyperalphalipoproteinemia
Transplant Co-Morbidity Superpanel v0.0 LIPA Bryony Thompson gene: LIPA was added
gene: LIPA was added to Transplant Co-Morbidity Superpanel. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: LIPA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LIPA were set to Wolman disease, Cholesterol ester storage disease
Transplant Co-Morbidity Superpanel v0.0 LDLRAP1 Bryony Thompson gene: LDLRAP1 was added
gene: LDLRAP1 was added to Transplant Co-Morbidity Superpanel. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: LDLRAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LDLRAP1 were set to 4351242
Phenotypes for gene: LDLRAP1 were set to Hypercholesterolemia, familial, 4, MIM# 603813
Transplant Co-Morbidity Superpanel v0.0 LDLR Bryony Thompson gene: LDLR was added
gene: LDLR was added to Transplant Co-Morbidity Superpanel. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: LDLR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: LDLR were set to Hypercholesterolemia, familial, 1, MIM# 143890
Transplant Co-Morbidity Superpanel v0.0 LCAT Bryony Thompson gene: LCAT was added
gene: LCAT was added to Transplant Co-Morbidity Superpanel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: LCAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LCAT were set to 30720493; 6624548
Phenotypes for gene: LCAT were set to Disorders of high density lipoprotein metabolism; Norum disease MIM#245900; Fish-eye disease MIM#136120
Transplant Co-Morbidity Superpanel v0.0 LAMP2 Bryony Thompson gene: LAMP2 was added
gene: LAMP2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: LAMP2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: LAMP2 were set to 25228319; 27165304; 30681346
Phenotypes for gene: LAMP2 were set to Danon disease, MIM#300257
Transplant Co-Morbidity Superpanel v0.0 KLHL24 Bryony Thompson gene: KLHL24 was added
gene: KLHL24 was added to Transplant Co-Morbidity Superpanel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: KLHL24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KLHL24 were set to 27798626; 30715372; 27889062
Phenotypes for gene: KLHL24 were set to Cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies, MIM# 620236
Transplant Co-Morbidity Superpanel v0.0 KDSR Bryony Thompson gene: KDSR was added
gene: KDSR was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: KDSR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KDSR were set to 28774589; 30467204
Phenotypes for gene: KDSR were set to Erythrokeratodermia variabilis et progressiva 4, MIM# 617526; severe thrombocytopaenia
Transplant Co-Morbidity Superpanel v0.0 KDELR2 Bryony Thompson gene: KDELR2 was added
gene: KDELR2 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review,Expert Review Green
Mode of inheritance for gene: KDELR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KDELR2 were set to 33053334
Phenotypes for gene: KDELR2 were set to Increased susceptibility to fractures; Bowing of the legs; Osteogenesis imperfecta 21, MIM# 619131; joint hypermobility; Bowing of the arms; Scoliosis
Transplant Co-Morbidity Superpanel v0.0 KCNQ1 Bryony Thompson gene: KCNQ1 was added
gene: KCNQ1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: KCNQ1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: KCNQ1 were set to 20301308; 34557911
Phenotypes for gene: KCNQ1 were set to Jervell and Lange-Nielsen syndrome 220400; Long QT syndrome 1, MIM# 192500; Long QT syndrome 1, 192500; Atrial fibrillation, familial, 3 607554; Short QT syndrome 2 609621
Transplant Co-Morbidity Superpanel v0.0 KCNJ2 Bryony Thompson gene: KCNJ2 was added
gene: KCNJ2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: KCNJ2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ2 were set to 31983240; 34557911
Phenotypes for gene: KCNJ2 were set to Short QT syndrome; long QT syndrome; Andersen-Tawil syndrome
Transplant Co-Morbidity Superpanel v0.0 KCNJ11 Bryony Thompson gene: KCNJ11 was added
gene: KCNJ11 was added to Transplant Co-Morbidity Superpanel. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: KCNJ11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KCNJ11 were set to Diabetes mellitus, trans; Maturity Onset Diabetes of the Young (Dominant); Diabetes Mellitus, Permanent Neonatal; Transient Neonatal diabetes mellitus (Dominant); {Diabetes mellitus, type 2, susceptibility to}, 125853; Transient Neonatal Diabetes, Dominant; Diabetes mellitus, permanent neonatal, with neurologic features, 606176; Diabetes, permanent neonatal, 606176; Diabetes mellitus, transient neonatal, 3, 610582; Diabetes Mellitus, Transient Neonatal, 3; Diabetes Mellitus, Permanent Neonatal diabetes mellitus (Dominant and recessive); Hyperinsulinemic hypoglycemia, familial, 2, 601820Diabetes, permanent neonatal, 606176Diabetes mellitus, permanent neonatal, with neurologic features, 606176{Diabetes mellitus, type 2, susceptibility to}, 125853Diabetes mellitus, transient neonatal, 3, 610582; Maturity Onset Diabetes of the Young; Transient Neonatal, 3; Hyperinsulinemic hypoglycemia, familial, 2, 601820
Mode of pathogenicity for gene: KCNJ11 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Transplant Co-Morbidity Superpanel v0.0 KCNH2 Bryony Thompson gene: KCNH2 was added
gene: KCNH2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: KCNH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNH2 were set to 31983240
Phenotypes for gene: KCNH2 were set to Long QT syndrome 2, MIM# 613688; Short QT syndrome
Transplant Co-Morbidity Superpanel v0.0 JUP Bryony Thompson gene: JUP was added
gene: JUP was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: JUP was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: JUP were set to 17924338; 33831308; 16722579
Phenotypes for gene: JUP were set to Arrhythmogenic right ventricular dysplasia 12 MIM# 611528; Naxos disease MIM# 601214
Transplant Co-Morbidity Superpanel v0.0 ITGB3 Bryony Thompson gene: ITGB3 was added
gene: ITGB3 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ITGB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ITGB3 were set to 19336737; 20081061; 18065693; 23253071
Phenotypes for gene: ITGB3 were set to Bleeding disorder, platelet-type, 24, MIM#619271; MONDO:0008552
Transplant Co-Morbidity Superpanel v0.0 ITGA2B Bryony Thompson gene: ITGA2B was added
gene: ITGA2B was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ITGA2B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ITGA2B were set to 21454453; 8282784; 1638023; 16463284
Phenotypes for gene: ITGA2B were set to Glanzmann thrombasthaenia 1, MIM# 273800; MONDO:000855; Bleeding disorder, platelet-type, 16, MIM# 187800
Transplant Co-Morbidity Superpanel v0.0 INSR Bryony Thompson gene: INSR was added
gene: INSR was added to Transplant Co-Morbidity Superpanel. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: INSR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: INSR were set to 8288049
Phenotypes for gene: INSR were set to Pineal Hyperplasia, Insulin-Resistant Diabetes Mellitus, And Somatic Abnormalities; Diabetes Mellitus, Insulin-Resistant, With Acanthosis Nigricans; OMIM 610549; Rabson-Mendenhall syndrome, 262190; Pineal Hyperplasia,Insulin- Resistant Diabetes Mellitus, and Somatic Abnormalities; Diabetes Mellitus, Insulin Resistant, with Acanthosis Nigricans; Diabetes mellitus, insulin-resistant, with acanthosis nigricans, 610549; Diabetes mellitus, insulin-resistant, with acanthosis nigricans; Hyperinsulinemic hypoglycemia, familial, 5, 609968; Leprechaunism, 246200; DIABETES MELLITUS, INSULIN-RESISTANT, WITH ACANTHOSIS NIGRICANS
Transplant Co-Morbidity Superpanel v0.0 INS Bryony Thompson gene: INS was added
gene: INS was added to Transplant Co-Morbidity Superpanel. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: INS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: INS were set to Maturity Onset Diabetes of the Young (Dominant); Diabetes mellitus, type 1, 125852; Diabetes mellitus, insulin-dependent, 2, 125852; Transient Neonatal Diabetes, Dominant/Recessive; MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 10; Maturity-onset diabetes of the young, type 10, 613370; Diabetes mellitus, permanent neonatal, 606176; Hyperproinsulinemia, familial, with or without diabetes; Permanent Neonatal diabetes mellitus; Maturity Onset Diabetes of the Young; MODY10
Transplant Co-Morbidity Superpanel v0.0 IKZF5 Bryony Thompson gene: IKZF5 was added
gene: IKZF5 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review,Expert Review Green
Mode of inheritance for gene: IKZF5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKZF5 were set to 31217188
Phenotypes for gene: IKZF5 were set to Thrombocytopaenia 7, MIM#619130
Transplant Co-Morbidity Superpanel v0.0 IFITM5 Bryony Thompson gene: IFITM5 was added
gene: IFITM5 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: IFITM5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IFITM5 were set to 22863195; 22863190; 32383316; 24519609
Phenotypes for gene: IFITM5 were set to Osteogenesis imperfecta type V, MIM#610967
Mode of pathogenicity for gene: IFITM5 was set to Other
Transplant Co-Morbidity Superpanel v0.0 HRG Bryony Thompson gene: HRG was added
gene: HRG was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review,Expert Review Green
Mode of inheritance for gene: HRG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HRG were set to 11057869; 8236132; 29108964
Phenotypes for gene: HRG were set to Thrombophilia 11 due to HRG deficiency, MIM# 613116
Transplant Co-Morbidity Superpanel v0.0 HPS6 Bryony Thompson gene: HPS6 was added
gene: HPS6 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: HPS6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPS6 were set to 12548288; 19843503; 17041891
Phenotypes for gene: HPS6 were set to Hermansky-Pudlak syndrome 6, MIM# 614075; MONDO:0013558
Transplant Co-Morbidity Superpanel v0.0 HPS5 Bryony Thompson gene: HPS5 was added
gene: HPS5 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: HPS5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPS5 were set to 28296950; 32725903
Phenotypes for gene: HPS5 were set to Hermansky-Pudlak syndrome 5 (MIM#614074)
Transplant Co-Morbidity Superpanel v0.0 HPS4 Bryony Thompson gene: HPS4 was added
gene: HPS4 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: HPS4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPS4 were set to 12664304; 11836498
Phenotypes for gene: HPS4 were set to Hermansky-Pudlak syndrome 4, MIM# 614073; MONDO:0013556
Transplant Co-Morbidity Superpanel v0.0 HPS3 Bryony Thompson gene: HPS3 was added
gene: HPS3 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: HPS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPS3 were set to 30990103; 11455388; 31621111; 31880485
Phenotypes for gene: HPS3 were set to Hermansky-Pudlak syndrome 3, MIM# 614072; MONDO:0013555
Transplant Co-Morbidity Superpanel v0.0 HPS1 Bryony Thompson gene: HPS1 was added
gene: HPS1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: HPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPS1 were set to 9497254
Phenotypes for gene: HPS1 were set to MONDO:0008748; Hermansky-Pudlak syndrome 1, MIM# 203300
Transplant Co-Morbidity Superpanel v0.0 HNF4A Bryony Thompson gene: HNF4A was added
gene: HNF4A was added to Transplant Co-Morbidity Superpanel. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: HNF4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNF4A were set to 28242437
Phenotypes for gene: HNF4A were set to Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young 616026; MODY1, 125850; {Diabetes mellitus, noninsulin-dependent}, 125853; Maturity-Onset Diabetes Of The Young, Type 1
Transplant Co-Morbidity Superpanel v0.0 HNF1B Bryony Thompson gene: HNF1B was added
gene: HNF1B was added to Transplant Co-Morbidity Superpanel. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: HNF1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: HNF1B were set to Transient neonatal diabetes; RCAD; RENAL CYSTS AND DIABETES SYNDROME; Maturity-Onset Diabetes Of The Young; renal malformation; {Renal cell carcinoma}, 144700; Renal cysts and diabetes syndrome, 137920; Diabetes mellitus, noninsulin-dependent, 125853; Renal Cysts and Diabetes Syndrome
Transplant Co-Morbidity Superpanel v0.0 HNF1A Bryony Thompson gene: HNF1A was added
gene: HNF1A was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: HNF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNF1A were set to 34012068
Phenotypes for gene: HNF1A were set to MODY, type III , MIM#600496
Transplant Co-Morbidity Superpanel v0.0 HFE Bryony Thompson gene: HFE was added
gene: HFE was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: HFE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HFE were set to Haemochromatosis, MIM# 235200
Transplant Co-Morbidity Superpanel v0.0 HCN4 Bryony Thompson gene: HCN4 was added
gene: HCN4 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: HCN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HCN4 were set to 15123648; 16407510; 12750403; 25145518; 17646576
Phenotypes for gene: HCN4 were set to Sick sinus syndrome 2, MIM# 163800
Transplant Co-Morbidity Superpanel v0.0 GPIHBP1 Bryony Thompson gene: GPIHBP1 was added
gene: GPIHBP1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Royal Melbourne Hospital,Expert list
Mode of inheritance for gene: GPIHBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GPIHBP1 were set to Hyperlipoproteinemia, type ID
Transplant Co-Morbidity Superpanel v0.0 GP9 Bryony Thompson gene: GP9 was added
gene: GP9 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: GP9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GP9 were set to 32030720; 8049428; 33553065; 31484196
Phenotypes for gene: GP9 were set to Bernard-Soulier syndrome, type C, MIM# 231200
Transplant Co-Morbidity Superpanel v0.0 GP6 Bryony Thompson gene: GP6 was added
gene: GP6 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: GP6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GP6 were set to 19549989; 23815599; 19552682
Phenotypes for gene: GP6 were set to Bleeding disorder, platelet-type, 11, MIM# 614201; MONDO:0013623
Transplant Co-Morbidity Superpanel v0.0 GP1BB Bryony Thompson gene: GP1BB was added
gene: GP1BB was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: GP1BB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GP1BB were set to 33813986; 33657022; 11222377; 8703016; 10887115; 9116284; 33216977; 1730088; 31997307
Phenotypes for gene: GP1BB were set to Macrothrombocytopaenia; Bernard-Soulier syndrome, type B, MIM# 231200
Transplant Co-Morbidity Superpanel v0.0 GP1BA Bryony Thompson gene: GP1BA was added
gene: GP1BA was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: GP1BA was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GP1BA were set to 24934643
Phenotypes for gene: GP1BA were set to MONDO:0007930; MONDO:0008332; Bernard-Soulier syndrome, type A1 (recessive), (MIM#231200), AR (AR BSS); von Willebrand disease, platelet-type, (MIM#177820), AD (VWD); Bernard-Soulier syndrome, type A2 (dominant), (MIM#153670) (AD BSS)
Transplant Co-Morbidity Superpanel v0.0 GORAB Bryony Thompson gene: GORAB was added
gene: GORAB was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GORAB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GORAB were set to Geroderma osteodysplasticum, MIM# 231070
Transplant Co-Morbidity Superpanel v0.0 GNE Bryony Thompson gene: GNE was added
gene: GNE was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GNE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNE were set to 30171045; 25257349; 32505938; 29941673
Phenotypes for gene: GNE were set to Thrombocytopaenia; Myopathy
Transplant Co-Morbidity Superpanel v0.0 GLA Bryony Thompson gene: GLA was added
gene: GLA was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: GLA was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: GLA were set to 30681346
Phenotypes for gene: GLA were set to Fabry disease (MIM# 301500)
Transplant Co-Morbidity Superpanel v0.0 GGCX Bryony Thompson gene: GGCX was added
gene: GGCX was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GGCX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GGCX were set to 32785662; 26758921; 30531603
Phenotypes for gene: GGCX were set to Vitamin K-dependent clotting factors, combined deficiency of, 1, MIM# 277450
Transplant Co-Morbidity Superpanel v0.0 GFI1B Bryony Thompson gene: GFI1B was added
gene: GFI1B was added to Transplant Co-Morbidity Superpanel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: GFI1B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GFI1B were set to 24325358; 28041820; 11825872; 23927492
Phenotypes for gene: GFI1B were set to Bleeding disorder, platelet-type, 17 MIM#187900
Transplant Co-Morbidity Superpanel v0.0 GCK Bryony Thompson gene: GCK was added
gene: GCK was added to Transplant Co-Morbidity Superpanel. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: GCK was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: GCK were set to 19790256
Phenotypes for gene: GCK were set to Hyperinsulinemic hypoglycemia, familial, 3, AD (MIM#602485); MODY, type II, AD (MIM#125851); Diabetes mellitus, permanent neonatal 1, AR (MIM#606176); Diabetes mellitus, noninsulin-dependent, late onset, AD (MIM#125853)
Transplant Co-Morbidity Superpanel v0.0 GBA Bryony Thompson gene: GBA was added
gene: GBA was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GBA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GBA were set to Gaucher disease
Transplant Co-Morbidity Superpanel v0.0 GATA6 Bryony Thompson gene: GATA6 was added
gene: GATA6 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green
Mode of inheritance for gene: GATA6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: GATA6 were set to Pancreatic agenesis and congenital heart defects, 600001; Persistent truncus arteriosus, 217095; Tetralogy of Fallot, 187500; Atrial septal defect 9, 614475; Atrioventricular septal defect 5, 614474
Transplant Co-Morbidity Superpanel v0.0 GATA4 Bryony Thompson gene: GATA4 was added
gene: GATA4 was added to Transplant Co-Morbidity Superpanel. Sources: NHS GMS,UKGTN,Expert Review Green
Mode of inheritance for gene: GATA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GATA4 were set to 20854389; 27810688; 24696446
Transplant Co-Morbidity Superpanel v0.0 GATA1 Bryony Thompson gene: GATA1 was added
gene: GATA1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GATA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: GATA1 were set to Thrombocytopenia, X-linked, with or without dyserythropoietic anemia, MIM# 300367
Transplant Co-Morbidity Superpanel v0.0 G6PD Bryony Thompson gene: G6PD was added
gene: G6PD was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green
Mode of inheritance for gene: G6PD was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: G6PD were set to Haemolytic anaemia
Transplant Co-Morbidity Superpanel v0.0 FLNC Bryony Thompson gene: FLNC was added
gene: FLNC was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review,Expert Review Green
Mode of inheritance for gene: FLNC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FLNC were set to 28356264; 30411535; 31924696
Phenotypes for gene: FLNC were set to Cardiomyopathy, familial hypertrophic, 26; Arrhythmogenic right ventricular cardiomyopathy; Dilated cardiomyopathy
Transplant Co-Morbidity Superpanel v0.0 FLNA Bryony Thompson gene: FLNA was added
gene: FLNA was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: FLNA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FLNA were set to 32299270
Phenotypes for gene: FLNA were set to Macrothrombocytopaenia
Transplant Co-Morbidity Superpanel v0.0 FLI1 Bryony Thompson gene: FLI1 was added
gene: FLI1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: FLI1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: FLI1 were set to 28255014; 24100448; 26316623
Phenotypes for gene: FLI1 were set to Bleeding disorder, platelet-type, 21, MIM# 617443
Transplant Co-Morbidity Superpanel v0.0 FKRP Bryony Thompson gene: FKRP was added
gene: FKRP was added to Transplant Co-Morbidity Superpanel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: FKRP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FKRP were set to PMID: 32914449
Phenotypes for gene: FKRP were set to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5, 607155
Transplant Co-Morbidity Superpanel v0.0 FKBP10 Bryony Thompson gene: FKBP10 was added
gene: FKBP10 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: FKBP10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FKBP10 were set to Osteogenesis imperfecta, type XI, 610968
Transplant Co-Morbidity Superpanel v0.0 FHOD3 Bryony Thompson gene: FHOD3 was added
gene: FHOD3 was added to Transplant Co-Morbidity Superpanel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: FHOD3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FHOD3 were set to 30442288; 33586461; 32335906; 31742804
Phenotypes for gene: FHOD3 were set to Cardiomyopathy, familial hypertrophic, 28, MIM# 619402
Transplant Co-Morbidity Superpanel v0.0 FHL1 Bryony Thompson gene: FHL1 was added
gene: FHL1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: FHL1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: FHL1 were set to Emery-Dreifuss muscular dystrophy 6, X-linked, MIM# 300696
Transplant Co-Morbidity Superpanel v0.0 FGG Bryony Thompson gene: FGG was added
gene: FGG was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: FGG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FGG were set to 3337908; 11001903; 11001902
Phenotypes for gene: FGG were set to Afibrinogenaemia, congenital, MIM# 202400; Hypofibrinogenaemia, congenital, MIM# 202400; Dysfibrinogenemia, congenital, MIM# 616004
Transplant Co-Morbidity Superpanel v0.0 FGB Bryony Thompson gene: FGB was added
gene: FGB was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: FGB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FGB were set to 12393540; 16195396
Phenotypes for gene: FGB were set to Afibrinogenaemia, congenital, MIM# 202400; Hypofibrinogenaemia, congenital, MIM# 202400; Dysfibrinogenemia, congenital, MIM# 616004
Transplant Co-Morbidity Superpanel v0.0 FGA Bryony Thompson gene: FGA was added
gene: FGA was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: FGA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FGA were set to 17295221; 11739173; 19073821; 31064749
Phenotypes for gene: FGA were set to Afibrinogenemia, congenital (MIM#202400)
Transplant Co-Morbidity Superpanel v0.0 FERMT3 Bryony Thompson gene: FERMT3 was added
gene: FERMT3 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: FERMT3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FERMT3 were set to Leukocyte adhesion deficiency, type III, MIM# 612840
Transplant Co-Morbidity Superpanel v0.0 FBN1 Bryony Thompson gene: FBN1 was added
gene: FBN1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: FBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FBN1 were set to Marfan syndrome, MIM# 154700
Transplant Co-Morbidity Superpanel v0.0 FAM46A Bryony Thompson gene: FAM46A was added
gene: FAM46A was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green, Victorian Clinical Genetics Services
Mode of inheritance for gene: FAM46A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FAM46A were set to Osteogenesis imperfecta, type XVIII, MIM# 617952
Transplant Co-Morbidity Superpanel v0.0 F9 Bryony Thompson gene: F9 was added
gene: F9 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: F9 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: F9 were set to 33656538; 34015304; 19846852
Phenotypes for gene: F9 were set to Haemophilia B, MIM# 306900; Thrombophilia, X-linked, due to factor IX defect, MIM# 300807; MONDO:0010432; MONDO:0010604
Transplant Co-Morbidity Superpanel v0.0 F8 Bryony Thompson gene: F8 was added
gene: F8 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: F8 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: F8 were set to 2986011; 3097553
Phenotypes for gene: F8 were set to Thrombophilia 13, X-linked, due to factor VIII defect, MIM# 301071; MONDO:0010602; Haemophilia A, MIM# 306700
Transplant Co-Morbidity Superpanel v0.0 F7 Bryony Thompson gene: F7 was added
gene: F7 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: F7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: F7 were set to 12181036
Phenotypes for gene: F7 were set to MONDO:0009211; Factor VII deficiency, MIM# 227500
Transplant Co-Morbidity Superpanel v0.0 F5 Bryony Thompson gene: F5 was added
gene: F5 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: F5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: F5 were set to MONDO:0009210; Factor V deficiency, MIM# 227400; {Thrombophilia, susceptibility to, due to factor V Leiden}, MIM# 188055; MONDO:0008560; Thrombophilia due to activated protein C resistance, MIM# 188055
Transplant Co-Morbidity Superpanel v0.0 F2 Bryony Thompson gene: F2 was added
gene: F2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: F2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: F2 were set to 30297698
Phenotypes for gene: F2 were set to {Pregnancy loss, recurrent, susceptibility to, 2} 614390 AD; Dysprothrombinemia 613679 AR; Hypoprothrombinemia 613679 AR; Thrombophilia due to thrombin defect 188050 AD; {Stroke, ischemic, susceptibility to} 601367 Mu
Mode of pathogenicity for gene: F2 was set to Other
Transplant Co-Morbidity Superpanel v0.0 F13B Bryony Thompson gene: F13B was added
gene: F13B was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: F13B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: F13B were set to 26247044; 20331752
Phenotypes for gene: F13B were set to Factor XIIIB deficiency, MIM#613235
Transplant Co-Morbidity Superpanel v0.0 F13A1 Bryony Thompson gene: F13A1 was added
gene: F13A1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: F13A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: F13A1 were set to 1644910; 10027709; 7727776; 32060721; 33802692
Phenotypes for gene: F13A1 were set to Factor XIIIA deficiency, MIM# 613225; MONDO:0013187
Transplant Co-Morbidity Superpanel v0.0 F11 Bryony Thompson gene: F11 was added
gene: F11 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: F11 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: F11 were set to 18446632; 15026311
Phenotypes for gene: F11 were set to Factor XI deficiency, autosomal dominant 612416; Factor XI deficiency, autosomal recessive, MIM#612416
Transplant Co-Morbidity Superpanel v0.0 F10 Bryony Thompson gene: F10 was added
gene: F10 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: F10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: F10 were set to 2567188; 10746568; 2790181; 12028042
Phenotypes for gene: F10 were set to Factor X deficiency, MIM# 227600; MONDO:0009212
Transplant Co-Morbidity Superpanel v0.0 ETV6 Bryony Thompson gene: ETV6 was added
gene: ETV6 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ETV6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ETV6 were set to 25807284; 25581430
Phenotypes for gene: ETV6 were set to Thrombocytopaenia 5, MIM# 616216
Transplant Co-Morbidity Superpanel v0.0 ENG Bryony Thompson gene: ENG was added
gene: ENG was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ENG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ENG were set to 34012068
Phenotypes for gene: ENG were set to Telangiectasia, hereditary hemorrhagic, type 1, MIM# 187300
Transplant Co-Morbidity Superpanel v0.0 EIF2B1 Bryony Thompson gene: EIF2B1 was added
gene: EIF2B1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review,Expert Review Green
Mode of inheritance for gene: EIF2B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF2B1 were set to 31882561
Phenotypes for gene: EIF2B1 were set to Neonatal diabetes mellitus, MONDO:0016391, EIF2B1-related
Transplant Co-Morbidity Superpanel v0.0 DTNBP1 Bryony Thompson gene: DTNBP1 was added
gene: DTNBP1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: DTNBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DTNBP1 were set to 23364359; 30990103; 12923531; 28259707
Phenotypes for gene: DTNBP1 were set to MONDO:0013559; Hermansky-Pudlak syndrome 7, MIM# 614076
Transplant Co-Morbidity Superpanel v0.0 DSP Bryony Thompson gene: DSP was added
gene: DSP was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: DSP was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: DSP were set to 24938629; 20864495; 22240500; 25765472; 11063735; 24108106; 31073624; 15941723; 31983221; 21397041; 23954618; 30345701; 33831308
Phenotypes for gene: DSP were set to Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis, MIM# 615821; Carvajal syndrome; Arrhythmogenic right ventricular dysplasia 8, MIM# 607450; Cardiomyopathy, dilated, with woolly hair and keratoderma, MIM# 605676
Transplant Co-Morbidity Superpanel v0.0 DSG2 Bryony Thompson gene: DSG2 was added
gene: DSG2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: DSG2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DSG2 were set to 33831308
Phenotypes for gene: DSG2 were set to Arrhythmogenic right ventricular dysplasia 10, MIM# 610193
Transplant Co-Morbidity Superpanel v0.0 DSC2 Bryony Thompson gene: DSC2 was added
gene: DSC2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: DSC2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: DSC2 were set to 28339476; 18957847; 23863954; 17963498; 17033975; 17186466; 21062920; 33831308
Phenotypes for gene: DSC2 were set to Arrhythmogenic right ventricular dysplasia 11, MIM# 610476; Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, MIM# 610476
Transplant Co-Morbidity Superpanel v0.0 DMD Bryony Thompson gene: DMD was added
gene: DMD was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: DMD was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: DMD were set to 26066469
Phenotypes for gene: DMD were set to Cardiomyopathy, dilated, 3B (MIM#302045)
Transplant Co-Morbidity Superpanel v0.0 DIAPH1 Bryony Thompson gene: DIAPH1 was added
gene: DIAPH1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: DIAPH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIAPH1 were set to 27808407]; 26912466
Phenotypes for gene: DIAPH1 were set to Deafness, autosomal dominant 1, with or without thrombocytopenia, MIM# 124900
Transplant Co-Morbidity Superpanel v0.0 DES Bryony Thompson gene: DES was added
gene: DES was added to Transplant Co-Morbidity Superpanel. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: DES was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DES were set to 23168288; 20423733; 20829228; 19879535; 22395865; 24200904; 29212896
Phenotypes for gene: DES were set to Arrhythmogenic right ventricular cardiomyopathy; Cardiomyopathy, dilated, 1I, MIM# 604765; Myopathy, myofibrillar, 1 , MIM#601419
Transplant Co-Morbidity Superpanel v0.0 CYP27A1 Bryony Thompson gene: CYP27A1 was added
gene: CYP27A1 was added to Transplant Co-Morbidity Superpanel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: CYP27A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP27A1 were set to 30720493; 20301583; 2019602
Phenotypes for gene: CYP27A1 were set to Cerebrotendinous xanthomatosis MIM#213700
Transplant Co-Morbidity Superpanel v0.0 CYCS Bryony Thompson gene: CYCS was added
gene: CYCS was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CYCS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CYCS were set to 24326104; 30051457; 18345000
Phenotypes for gene: CYCS were set to Thrombocytopenia 4, MIM# 612004
Transplant Co-Morbidity Superpanel v0.0 CSRP3 Bryony Thompson gene: CSRP3 was added
gene: CSRP3 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CSRP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CSRP3 were set to 18505755; 30681346
Phenotypes for gene: CSRP3 were set to Cardiomyopathy, hypertrophic, 12, MIM# 612124
Transplant Co-Morbidity Superpanel v0.0 CRTAP Bryony Thompson gene: CRTAP was added
gene: CRTAP was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CRTAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRTAP were set to 21955071; 17192541; 19846465
Phenotypes for gene: CRTAP were set to Osteogenesis imperfecta, type VII MIM#610682
Transplant Co-Morbidity Superpanel v0.0 CREB3L1 Bryony Thompson gene: CREB3L1 was added
gene: CREB3L1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CREB3L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CREB3L1 were set to 24079343; 29936144; 30657919; 28817112
Phenotypes for gene: CREB3L1 were set to Osteogenesis imperfecta, type XVI, 616229
Transplant Co-Morbidity Superpanel v0.0 COPB2 Bryony Thompson gene: COPB2 was added
gene: COPB2 was added to Transplant Co-Morbidity Superpanel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: COPB2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COPB2 were set to 34450031
Phenotypes for gene: COPB2 were set to Osteoporosis, childhood- or juvenile-onset, with developmental delay, MIM# 619884
Transplant Co-Morbidity Superpanel v0.0 COL3A1 Bryony Thompson gene: COL3A1 was added
gene: COL3A1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: COL3A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: COL3A1 were set to Ehlers-Danlos syndrome, vascular type, MIM# 130050
Transplant Co-Morbidity Superpanel v0.0 COL1A2 Bryony Thompson gene: COL1A2 was added
gene: COL1A2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: COL1A2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: COL1A2 were set to Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2, MIM# 619120
Transplant Co-Morbidity Superpanel v0.0 COL1A1 Bryony Thompson gene: COL1A1 was added
gene: COL1A1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: COL1A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: COL1A1 were set to Osteogenesis imperfecta
Transplant Co-Morbidity Superpanel v0.0 CHST14 Bryony Thompson gene: CHST14 was added
gene: CHST14 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CHST14 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CHST14 were set to Ehlers-Danlos syndrome, musculocontractural type 1, MIM# 601776
Transplant Co-Morbidity Superpanel v0.0 CDKN2A Bryony Thompson gene: CDKN2A was added
gene: CDKN2A was added to Transplant Co-Morbidity Superpanel. Sources: SA Pathology,Expert Review Green
Mode of inheritance for gene: CDKN2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Transplant Co-Morbidity Superpanel v0.0 CDK4 Bryony Thompson gene: CDK4 was added
gene: CDK4 was added to Transplant Co-Morbidity Superpanel. Sources: SA Pathology,Expert Review Green
Mode of inheritance for gene: CDK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CDK4 were set to Melanoma, cutaneous malignant, MIM#609408
Transplant Co-Morbidity Superpanel v0.0 CDC42 Bryony Thompson gene: CDC42 was added
gene: CDC42 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CDC42 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDC42 were set to 29394990
Phenotypes for gene: CDC42 were set to Takenouchi-Kosaki syndrome, MIM#616737
Transplant Co-Morbidity Superpanel v0.0 CCDC134 Bryony Thompson gene: CCDC134 was added
gene: CCDC134 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CCDC134 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC134 were set to 32181939; 35019224; 34204301
Phenotypes for gene: CCDC134 were set to Osteogenesis imperfecta, type XXII, MIM#619795
Transplant Co-Morbidity Superpanel v0.0 CASR Bryony Thompson gene: CASR was added
gene: CASR was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CASR was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CASR were set to 22620673
Phenotypes for gene: CASR were set to severe hypercalcemia, bone demineralization, multiple fractures; Hyperparathyroidism, neonatal, MIM# 239200
Transplant Co-Morbidity Superpanel v0.0 CASQ2 Bryony Thompson gene: CASQ2 was added
gene: CASQ2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CASQ2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CASQ2 were set to 16908766; 11704930; 34012068
Phenotypes for gene: CASQ2 were set to Ventricular tachycardia, catecholaminergic polymorphic, 2, MIM# 611938
Transplant Co-Morbidity Superpanel v0.0 CALM3 Bryony Thompson gene: CALM3 was added
gene: CALM3 was added to Transplant Co-Morbidity Superpanel. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: CALM3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CALM3 were set to 25460178; 31454269
Phenotypes for gene: CALM3 were set to Long QT syndrome 16, MIM# 618782
Transplant Co-Morbidity Superpanel v0.0 CALM2 Bryony Thompson gene: CALM2 was added
gene: CALM2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CALM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CALM2 were set to 31983240; 31170290
Phenotypes for gene: CALM2 were set to Long QT syndrome 15 616249; idopathic VF; sudden unexplained death
Transplant Co-Morbidity Superpanel v0.0 CALM1 Bryony Thompson gene: CALM1 was added
gene: CALM1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CALM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CALM1 were set to 31170290
Phenotypes for gene: CALM1 were set to Long QT syndrome 14 616247; Ventricular tachycardia, catecholaminergic polymorphic, 4 614916
Transplant Co-Morbidity Superpanel v0.0 CACNA1S Bryony Thompson gene: CACNA1S was added
gene: CACNA1S was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: CACNA1S was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CACNA1S were set to Malignant hyperthermia susceptibility 5, MIM# 601887
Transplant Co-Morbidity Superpanel v0.0 CACNA1C Bryony Thompson gene: CACNA1C was added
gene: CACNA1C was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CACNA1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1C were set to 31983240
Phenotypes for gene: CACNA1C were set to Long QT syndrome 8, MIM# 618447; Timothy syndrome, MIM# 601005
Transplant Co-Morbidity Superpanel v0.0 C1QBP Bryony Thompson gene: C1QBP was added
gene: C1QBP was added to Transplant Co-Morbidity Superpanel. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: C1QBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C1QBP were set to 28942965
Phenotypes for gene: C1QBP were set to Combined oxidative phosphorylation deficiency 33, MIM#617713
Transplant Co-Morbidity Superpanel v0.0 BRCA2 Bryony Thompson gene: BRCA2 was added
gene: BRCA2 was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: BRCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BRCA2 were set to Breast-ovarian cancer, familial, 2, MIM#612555
Transplant Co-Morbidity Superpanel v0.0 BRCA1 Bryony Thompson gene: BRCA1 was added
gene: BRCA1 was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: BRCA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BRCA1 were set to Breast-ovarian cancer, familial, 1, MIM# 604370
Transplant Co-Morbidity Superpanel v0.0 BMPR1A Bryony Thompson gene: BMPR1A was added
gene: BMPR1A was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: BMPR1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BMPR1A were set to Polyposis, juvenile intestinal, MIM# 174900
Transplant Co-Morbidity Superpanel v0.0 BMP1 Bryony Thompson gene: BMP1 was added
gene: BMP1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: BMP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BMP1 were set to 25214535; 25402547; 22052668; 22482805
Phenotypes for gene: BMP1 were set to Osteogenesis imperfecta, type XIII , MIM#614856
Transplant Co-Morbidity Superpanel v0.0 BLOC1S6 Bryony Thompson gene: BLOC1S6 was added
gene: BLOC1S6 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: BLOC1S6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BLOC1S6 were set to 29054114; 33543539; 22461475; 26575419; 32245340; 10610180
Phenotypes for gene: BLOC1S6 were set to Hermansky-pudlak syndrome 9, MIM# 614171
Transplant Co-Morbidity Superpanel v0.0 BLOC1S5 Bryony Thompson gene: BLOC1S5 was added
gene: BLOC1S5 was added to Transplant Co-Morbidity Superpanel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: BLOC1S5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BLOC1S5 were set to PMID: 32565547
Phenotypes for gene: BLOC1S5 were set to Hermansky Pudlak syndrome type 11, MIM#619172
Transplant Co-Morbidity Superpanel v0.0 BLOC1S3 Bryony Thompson gene: BLOC1S3 was added
gene: BLOC1S3 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: BLOC1S3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BLOC1S3 were set to 32687635; 16385460; 22709368
Phenotypes for gene: BLOC1S3 were set to Hermansky-Pudlak syndrome 8, MIM# 614077; MONDO:0013560
Transplant Co-Morbidity Superpanel v0.0 BAP1 Bryony Thompson gene: BAP1 was added
gene: BAP1 was added to Transplant Co-Morbidity Superpanel. Sources: SA Pathology,Expert Review Green
Mode of inheritance for gene: BAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BAP1 were set to Tumour predisposition syndrome, MIM#614327
Transplant Co-Morbidity Superpanel v0.0 BAG5 Bryony Thompson gene: BAG5 was added
gene: BAG5 was added to Transplant Co-Morbidity Superpanel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: BAG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BAG5 were set to 35044787
Phenotypes for gene: BAG5 were set to Cardiomyopathy, dilated, 2F, MIM# 619747
Transplant Co-Morbidity Superpanel v0.0 BAG3 Bryony Thompson gene: BAG3 was added
gene: BAG3 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: BAG3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAG3 were set to 25448463; 24623017; 21353195; 29323723; 28737513; 27391596; 25008357; 35802134; 30442290; 31983221; 33947203; 28211974
Phenotypes for gene: BAG3 were set to Cardiomyopathy, dilated, 1HH, MIM# 613881; MONDO:0013479; Myopathy, myofibrillar, 6, MIM# 612954
Transplant Co-Morbidity Superpanel v0.0 B4GALT7 Bryony Thompson gene: B4GALT7 was added
gene: B4GALT7 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: B4GALT7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B4GALT7 were set to 26940150
Phenotypes for gene: B4GALT7 were set to Ehlers-Danlos syndrome, spondylodysplastic type, 1, MIM# 130070
Transplant Co-Morbidity Superpanel v0.0 B3GALT6 Bryony Thompson gene: B3GALT6 was added
gene: B3GALT6 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: B3GALT6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B3GALT6 were set to 23664118; 23664117
Phenotypes for gene: B3GALT6 were set to Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures, MIM# 271640, MONDO:0010075
Transplant Co-Morbidity Superpanel v0.0 ATP7B Bryony Thompson gene: ATP7B was added
gene: ATP7B was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: ATP7B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATP7B were set to Wilson disease, MIM# 277900
Transplant Co-Morbidity Superpanel v0.0 ARPC1B Bryony Thompson gene: ARPC1B was added
gene: ARPC1B was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ARPC1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARPC1B were set to 29127144; 27965109; 28368018; 30254128
Phenotypes for gene: ARPC1B were set to Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia, MIM# 617718
Transplant Co-Morbidity Superpanel v0.0 APOE Bryony Thompson gene: APOE was added
gene: APOE was added to Transplant Co-Morbidity Superpanel. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: APOE was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: APOE were set to Sea-blue histiocyte disease, Dysbetalipoproteinemia, familial (Hyperlipoproteinemia), Lipoprotein glomerulopathy
Transplant Co-Morbidity Superpanel v0.0 APOC2 Bryony Thompson gene: APOC2 was added
gene: APOC2 was added to Transplant Co-Morbidity Superpanel. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: APOC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APOC2 were set to 32280258; 32292609; PMID: 32562799; 26044956
Phenotypes for gene: APOC2 were set to Hyperlipoproteinemia, type Ib MIM#207750
Transplant Co-Morbidity Superpanel v0.0 APOB Bryony Thompson gene: APOB was added
gene: APOB was added to Transplant Co-Morbidity Superpanel. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: APOB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: APOB were set to Hypobetalipoproteinemia, Hypercholesterolemia
Transplant Co-Morbidity Superpanel v0.0 APOA5 Bryony Thompson gene: APOA5 was added
gene: APOA5 was added to Transplant Co-Morbidity Superpanel. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: APOA5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: APOA5 were set to Hyperchylomicronemia
Transplant Co-Morbidity Superpanel v0.0 APOA1 Bryony Thompson gene: APOA1 was added
gene: APOA1 was added to Transplant Co-Morbidity Superpanel. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: APOA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: APOA1 were set to 16023124
Phenotypes for gene: APOA1 were set to Hypoalphalipoproteinaemia, primary, 2, intermediate, MIM# 619836
Transplant Co-Morbidity Superpanel v0.0 APC Bryony Thompson gene: APC was added
gene: APC was added to Transplant Co-Morbidity Superpanel. Sources: Melbourne Genomics Health Alliance,Expert Review Green
Mode of inheritance for gene: APC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: APC were set to Adenomatous polyposis coli, MIM# 175100
Transplant Co-Morbidity Superpanel v0.0 AP3B1 Bryony Thompson gene: AP3B1 was added
gene: AP3B1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: AP3B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP3B1 were set to 10024875; 11809908; 14566336
Phenotypes for gene: AP3B1 were set to Hermansky-Pudlak syndrome 2, MIM# 608233; MONDO:0011997
Transplant Co-Morbidity Superpanel v0.0 ANO6 Bryony Thompson gene: ANO6 was added
gene: ANO6 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ANO6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANO6 were set to 21107324; 27879994; 11895776; 27634832
Phenotypes for gene: ANO6 were set to MONDO:0009885; Scott syndrome, MIM# 262890
Transplant Co-Morbidity Superpanel v0.0 ANO5 Bryony Thompson gene: ANO5 was added
gene: ANO5 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ANO5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANO5 were set to 30712070; 29175271; 15124103; 30641283
Phenotypes for gene: ANO5 were set to Gnathodiaphyseal dysplasia MIM#166260
Transplant Co-Morbidity Superpanel v0.0 ANKRD26 Bryony Thompson gene: ANKRD26 was added
gene: ANKRD26 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ANKRD26 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANKRD26 were set to 21211618
Phenotypes for gene: ANKRD26 were set to Thrombocytopaenia 2, MIM# 188000
Transplant Co-Morbidity Superpanel v0.0 ALPL Bryony Thompson gene: ALPL was added
gene: ALPL was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ALPL was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: ALPL were set to disorder of bone metabolism; Hypophosphatasia
Transplant Co-Morbidity Superpanel v0.0 ALPK3 Bryony Thompson gene: ALPK3 was added
gene: ALPK3 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ALPK3 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ALPK3 were set to 27106955; 26846950; 32480058
Phenotypes for gene: ALPK3 were set to Cardiomyopathy, familial hypertrophic 27, MIM#618052
Transplant Co-Morbidity Superpanel v0.0 ALMS1 Bryony Thompson gene: ALMS1 was added
gene: ALMS1 was added to Transplant Co-Morbidity Superpanel. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: ALMS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ALMS1 were set to Alstrom syndrome
Transplant Co-Morbidity Superpanel v0.0 AKT2 Bryony Thompson gene: AKT2 was added
gene: AKT2 was added to Transplant Co-Morbidity Superpanel. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: AKT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AKT2 were set to 17327441; 15166380; 17576055
Phenotypes for gene: AKT2 were set to Diabetes mellitus, type II, 125853; Severe insulin resistance, partial lipodystrophy and diabetes
Transplant Co-Morbidity Superpanel v0.0 ADAMTS13 Bryony Thompson gene: ADAMTS13 was added
gene: ADAMTS13 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ADAMTS13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS13 were set to 30312976; 11586351
Phenotypes for gene: ADAMTS13 were set to Thrombotic thrombocytopenic purpura, hereditary, MIM# 274150
Transplant Co-Morbidity Superpanel v0.0 ACVRL1 Bryony Thompson gene: ACVRL1 was added
gene: ACVRL1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ACVRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACVRL1 were set to 34012068
Phenotypes for gene: ACVRL1 were set to Telangiectasia, hereditary hemorrhagic, type 2, MIM# 600376
Transplant Co-Morbidity Superpanel v0.0 ACTN1 Bryony Thompson gene: ACTN1 was added
gene: ACTN1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ACTN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACTN1 were set to 23434115
Phenotypes for gene: ACTN1 were set to Bleeding disorder, platelet-type, 15, MIM# 615193
Transplant Co-Morbidity Superpanel v0.0 ACTC1 Bryony Thompson gene: ACTC1 was added
gene: ACTC1 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ACTC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACTC1 were set to 26432839; 20600154; 30384889; 14605248; 31430208; 9563954
Phenotypes for gene: ACTC1 were set to Cardiomyopathy, dilated, 1R, MIM# 613424; Cardiomyopathy, hypertrophic, 11, MIM# 612098; Left ventricular noncompaction 4, MIM# 613424
Transplant Co-Morbidity Superpanel v0.0 ACTB Bryony Thompson gene: ACTB was added
gene: ACTB was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ACTB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACTB were set to 30315159
Phenotypes for gene: ACTB were set to Syndromic thrombocytopaenia
Transplant Co-Morbidity Superpanel v0.0 ACTA2 Bryony Thompson gene: ACTA2 was added
gene: ACTA2 was added to Transplant Co-Morbidity Superpanel. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ACTA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ACTA2 were set to Aortic aneurysm, familial thoracic 6, MIM# 611788
Transplant Co-Morbidity Superpanel v0.0 ABCG8 Bryony Thompson gene: ABCG8 was added
gene: ABCG8 was added to Transplant Co-Morbidity Superpanel. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ABCG8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCG8 were set to 32546081; 23556150
Phenotypes for gene: ABCG8 were set to Sitosterolemia 1, MIM# 210250
Transplant Co-Morbidity Superpanel v0.0 ABCG5 Bryony Thompson gene: ABCG5 was added
gene: ABCG5 was added to Transplant Co-Morbidity Superpanel. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: ABCG5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ABCG5 were set to Sitosterolaemia 2, MIM# 618666
Transplant Co-Morbidity Superpanel v0.0 ABCC8 Bryony Thompson gene: ABCC8 was added
gene: ABCC8 was added to Transplant Co-Morbidity Superpanel. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: ABCC8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: ABCC8 were set to Diabetes mellitus, permanent neonatal, 6; Hyperinsulinemic hypoglycemia, familial, 1, 256450; DIABETES MELLITUS, NONINSULIN-DEPENDENT; transient neonatal diabetes (Dominant); Transient Neonatal Diabetes, Dominant; Diabetes mellitus, transient neonatal 2, 610374; Permanent Neonatal Diabetes Mellitus; Hypoglycemia of infancy, leucine-sensitive, 240800; Permanent Neonatal Diabetes Mellitus (recessive); Diabetes mellitus, noninsulin-dependent, 125853; Permanent neonatal diabetes mellitus; Hyperinsulinemic hypoglycemia, familial, 1, 256450Hypoglycemia of infancy, leucine-sensitive, 240800Diabetes mellitus, transient neonatal 2, 610374Diabetes mellitus, noninsulin-dependent, 125853Diabetes mellitus, permanent neonatal, 6
Mode of pathogenicity for gene: ABCC8 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Transplant Co-Morbidity Superpanel v0.0 ABCA1 Bryony Thompson gene: ABCA1 was added
gene: ABCA1 was added to Transplant Co-Morbidity Superpanel. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: ABCA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ABCA1 were set to 10431237; 10431236
Phenotypes for gene: ABCA1 were set to HDL deficiency, familial, 1, MIM# 604091; Tangier disease, MIM# 205400
Transplant Co-Morbidity Superpanel v0.0 Bryony Thompson Added panel Transplant Co-Morbidity Superpanel
Mendeliome v1.1049 DUSP7 Sangavi Sivagnanasundram gene: DUSP7 was added
gene: DUSP7 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: DUSP7 was set to Unknown
Publications for gene: DUSP7 were set to https://doi.org/10.1155/2023/4348290
Phenotypes for gene: DUSP7 were set to Acute Myeloid Leukemia (AML)
Review for gene: DUSP7 was set to RED
Added comment: New gene with an association in AML prognosis.

Gao (2023) - Recruitment from three public AML cohorts - GSE71014, TARGET-AML, and TCGA-AML.
The study results suggest that with an DUSP7 may affect AML progression in individuals by affecting the recruitment of local immune cells.
Sources: Other
Hereditary Neuropathy - complex v0.205 C12orf65 Sangavi Sivagnanasundram reviewed gene: C12orf65: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301682, 23188110, 3479531, 24198383; Phenotypes: Spastic paraplegia 55 (MIM#615035); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1049 PYROXD2 Zornitza Stark Classified gene: PYROXD2 as Red List (low evidence)
Mendeliome v1.1049 PYROXD2 Zornitza Stark Gene: pyroxd2 has been classified as Red List (Low Evidence).
Mendeliome v1.1048 PYROXD2 Zornitza Stark Tag disputed tag was added to gene: PYROXD2.
Mendeliome v1.1048 PYROXD2 Zornitza Stark edited their review of gene: PYROXD2: Added comment: Alternative diagnosis identified in proband, downgrade.; Changed rating: RED
Mitochondrial disease v0.880 PYROXD2 Zornitza Stark Classified gene: PYROXD2 as Red List (low evidence)
Mitochondrial disease v0.880 PYROXD2 Zornitza Stark Gene: pyroxd2 has been classified as Red List (Low Evidence).
Mitochondrial disease v0.879 PYROXD2 Zornitza Stark Tag disputed tag was added to gene: PYROXD2.
Mitochondrial disease v0.879 PYROXD2 Zornitza Stark edited their review of gene: PYROXD2: Added comment: Alternative diagnosis identified in proband, downgrade.; Changed rating: RED
Hereditary Neuropathy - complex v0.205 ATM Sangavi Sivagnanasundram reviewed gene: ATM: Rating: RED; Mode of pathogenicity: None; Publications: 20301790; Phenotypes: Ataxia-telangiectasia, MIM#208900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.205 AP1S1 Sangavi Sivagnanasundram reviewed gene: AP1S1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23423674; Phenotypes: MEDNIK Syndrome (MONDO:0012251, MIM#609313); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.205 ABCA1 Sangavi Sivagnanasundram reviewed gene: ABCA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 4165386, 31751110; Phenotypes: Tangier Disease (MONDO:0008783, MIM#205400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.146 TSC1 Luisa Weiss gene: TSC1 was added
gene: TSC1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TSC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TSC1 were set to 29706646; 34788679; 25817843
Phenotypes for gene: TSC1 were set to Focal cortical dysplasia, type II, somatic MIM#607341; Lymphangioleiomyomatosis MIM#606690; Tuberous sclerosis-1 MIM#191100
Review for gene: TSC1 was set to AMBER
Added comment: Two patients in large cohort studies of children with cryptogenic CP and maternally inherited mutation in TSC1, parents were mildly affected. In addition, one patient with a VUS in TSC1 with cortical and movement abnormalities, but no clinical diagnosis of TS.
Sources: Literature
Cerebral Palsy v1.146 TRAPPC9 Luisa Weiss gene: TRAPPC9 was added
gene: TRAPPC9 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TRAPPC9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC9 were set to 33528536; 34540776; 36475161
Phenotypes for gene: TRAPPC9 were set to Intellectual developmental disorder, autosomal recessive MIM#13 613192
Review for gene: TRAPPC9 was set to GREEN
Added comment: Two larger CP cohort studies with one patient each harboring biallelic TRAPPC9 mutations. No phenotypic information is given. In addition, one case report of a girl with CP and intellectual disability and biallelic TRAPPC9 mutations.
Sources: Literature
Cerebral Palsy v1.146 TMX2 Luisa Weiss gene: TMX2 was added
gene: TMX2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TMX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMX2 were set to 31735293
Phenotypes for gene: TMX2 were set to Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity MIM#618730
Added comment: Vandervore et al. published a larger study of several patients with neurological impariment and biallelic TMX2 mutations. 8 individuals out of 5 families had previously been diagnosed with CP. Most patients had severely impaired development and epilepsy.
Sources: Literature
Cerebral Palsy v1.146 TH Luisa Weiss gene: TH was added
gene: TH was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TH were set to 34788679
Phenotypes for gene: TH were set to Segawa syndrome, recessive MIM#605407
Review for gene: TH was set to AMBER
Added comment: 2 individual cases in one large Chinese CP cohort study, both with compound heterozygous mutations.
Sources: Literature
Cerebral Palsy v1.146 TEP1 Luisa Weiss gene: TEP1 was added
gene: TEP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TEP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TEP1 were set to 34543729
Review for gene: TEP1 was set to GREEN
Added comment: Wang et al. screened a large cohort of more than 600 CP patients from China and found several variants in TEP1, 11 of which were LoF, while no LoF variant was found in the control cohort. These children all had spastic CP. Among these 11 children, 6 children had birth asphyxia and neonatal encephalopathy. Compared to the total group with birth asphyxia (71/667), 6 patients with TEP1 LOF mutations had a significantly greater risk of birth asphyxia. They confirmed TEP1 as a risk factor for CP by cytological and animal models.
Sources: Literature
Cerebral Palsy v1.146 TANGO2 Luisa Weiss gene: TANGO2 was added
gene: TANGO2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TANGO2 were set to 33528536; 34364746
Phenotypes for gene: TANGO2 were set to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration MIM#616878
Review for gene: TANGO2 was set to GREEN
Added comment: 3 individual patients in two large CP cohort study, both with biallelic larger deletions encompassing TANGO2. Phenotypic information is only given for one patient, this one showed slowly progressive spastic paraplegia and ataxia.
Sources: Literature
Cerebral Palsy v1.146 SYNGAP1 Luisa Weiss gene: SYNGAP1 was added
gene: SYNGAP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SYNGAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SYNGAP1 were set to 33528536; 31700678
Phenotypes for gene: SYNGAP1 were set to Intellectual developmental disorder, autosomal dominant 5 MIM#612621
Review for gene: SYNGAP1 was set to GREEN
Added comment: Moreno de Luca et al. found 3 heterozygous de novo SYNGAP1 mutations in a large CP cohort study. In addition, van Eyk et al. found one non-maternally inherited VUS in a child with CP in a cohort study.
Sources: Literature
Cerebral Palsy v1.146 SYNE1 Luisa Weiss gene: SYNE1 was added
gene: SYNE1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SYNE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SYNE1 were set to 34321325; 34816117
Phenotypes for gene: SYNE1 were set to Arthrogryposis multiplex congenita 3, myogenic type MIM#618484; Emery-Dreifuss muscular dystrophy 4, autosomal dominant MIM#612998; Spinocerebellar ataxia, autosomal recessive 8 MIM#610743
Review for gene: SYNE1 was set to AMBER
Added comment: Two cases each in two larger CP cohort studies, one with ataxic and one with spastic CP, with biallelic SYNE1 mutations.
Sources: Literature
Cerebral Palsy v1.146 SUOX Luisa Weiss gene: SUOX was added
gene: SUOX was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SUOX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUOX were set to 27289259; 34540776
Phenotypes for gene: SUOX were set to Sulfite oxidase deficiency MIM#272300
Review for gene: SUOX was set to GREEN
Added comment: Zaki et al. presented 3 individual cases in a larger cohort study harboring biallelic SUOX mutations and presenting with spastic quadriparesis, even though no formal CP diagnosis was given. In addition, two additional cases of patients with homozygous mutations in SUOX from a larger cohort study from Iran.
Sources: Literature
Cerebral Palsy v1.146 STAMBP Luisa Weiss gene: STAMBP was added
gene: STAMBP was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: STAMBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAMBP were set to 33528536; 23542699
Phenotypes for gene: STAMBP were set to Microcephaly-capillary malformation syndrome MIM#614261
Review for gene: STAMBP was set to GREEN
Added comment: 2 cases in a larger CP cohort study with homozygous missense mutations in STAMBP, no phenotypic information is given.
McDonnell et al. (23542699) presented a large cohort of previously published and unpublished patients with microcephaly-capillary malformation syndrome, which all had cutaneous abnormalities, developmental delay and epilepsy, but 8 of which presented with spastic quadriparesis. Overlap with CP is possible; however, additional phenotypic features seem to be present in any case.
Sources: Literature
Cerebral Palsy v1.146 ST3GAL5 Luisa Weiss gene: ST3GAL5 was added
gene: ST3GAL5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ST3GAL5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ST3GAL5 were set to 34540776; 30185102; 25131622; 24026681
Phenotypes for gene: ST3GAL5 were set to Salt and pepper developmental regression syndrome MIM#609056
Review for gene: ST3GAL5 was set to GREEN
Added comment: Several reports on patients with different forms of CP (dystonic, quadriplegic or spastic) later found to harbor biallelic ST3GAL5 mutations. One patient in a larger CP cohort (34540776) with a homozygous VUS, others with pathogenic mutations. Note that the patients which were presented with photographs all showed cutaneous abnormalities as well.
Sources: Literature
Cerebral Palsy v1.146 SPTBN2 Luisa Weiss reviewed gene: SPTBN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31066025, 25981959, 31721007; Phenotypes: Spinocerebellar ataxia 5 MIM#600224, Spinocerebellar ataxia, autosomal recessive 14 MIM#615386; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cerebral Palsy v1.146 SPTBN2 Luisa Weiss Deleted their review
Cerebral Palsy v1.146 SPTBN2 Luisa Weiss gene: SPTBN2 was added
gene: SPTBN2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SPTBN2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SPTBN2 were set to 31066025; 25981959; 31721007
Phenotypes for gene: SPTBN2 were set to Spinocerebellar ataxia 5 MIM#600224; Spinocerebellar ataxia, autosomal recessive 14 MIM#615386
Added comment: 5 patients presented in an overview study with ataxic CP and heterozygous (4/5) or biallelic SPTBN2 (1/5) mutations. In addition, one more case report and another case in a larger CP cohort study, all children presenting with ataxic CP.
Note both heterozygous and biallelic mutations have been reported to cause ataxic CP in children, even though heterozygous mutations have previously been associated with adult onset spinocerebellar ataxia.
Sources: Literature
Dystonia - complex v0.228 EIF4A2 Zornitza Stark Marked gene: EIF4A2 as ready
Dystonia - complex v0.228 EIF4A2 Zornitza Stark Gene: eif4a2 has been classified as Green List (High Evidence).
Dystonia - complex v0.228 EIF4A2 Zornitza Stark Phenotypes for gene: EIF4A2 were changed from DYSTONIA; TREMOR to Neurodevelopmental disorder (MONDO:0700092), EIF4A2-related
Dystonia - complex v0.227 EIF4A2 Zornitza Stark Classified gene: EIF4A2 as Green List (high evidence)
Dystonia - complex v0.227 EIF4A2 Zornitza Stark Gene: eif4a2 has been classified as Green List (High Evidence).
Dystonia - complex v0.226 EIF4A2 Zornitza Stark edited their review of gene: EIF4A2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.226 EIF4A2 Zornitza Stark reviewed gene: EIF4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), EIF4A2-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v1.146 PTPN11 Zornitza Stark Phenotypes for gene: PTPN11 were changed from LEOPARD syndrome 1 MIM#151100; Leukemia, juvenile myelomonocytic, somatic MIM#607785; Metachondromatosis MIM#156250; Noonan syndrome MIM#163950 to LEOPARD syndrome 1 MIM#151100; Noonan syndrome MIM#163950
Cerebral Palsy v1.145 PTPN11 Zornitza Stark Marked gene: PTPN11 as ready
Cerebral Palsy v1.145 PTPN11 Zornitza Stark Added comment: Comment when marking as ready: Very little phenotypic overlap between NS and CP.
Cerebral Palsy v1.145 PTPN11 Zornitza Stark Gene: ptpn11 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.145 PTPN11 Zornitza Stark Classified gene: PTPN11 as Amber List (moderate evidence)
Cerebral Palsy v1.145 PTPN11 Zornitza Stark Gene: ptpn11 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1875 TMEM63B Zornitza Stark Marked gene: TMEM63B as ready
Genetic Epilepsy v0.1875 TMEM63B Zornitza Stark Gene: tmem63b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1875 TMEM63B Zornitza Stark Classified gene: TMEM63B as Green List (high evidence)
Genetic Epilepsy v0.1875 TMEM63B Zornitza Stark Gene: tmem63b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1874 TMEM63B Zornitza Stark gene: TMEM63B was added
gene: TMEM63B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TMEM63B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM63B were set to 37421948
Phenotypes for gene: TMEM63B were set to developmental and epileptic encephalopathy, MONDO:0100062, TMEM63B-related
Review for gene: TMEM63B was set to GREEN
Added comment: 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment were identified with ten distinct heterozygous variants inTMEM63B. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense or in-frame. All individuals had global developmental delay, with moderate-to-profound intellectual disability and severe motor impairment. All individuals had early-onset drug-resistant epilepsy, whose onset ranged from birth to 3 years but occurred within the first year in 14/17 (82%) and in the first month of life in 6/17 (35%).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5309 TMEM63B Zornitza Stark Marked gene: TMEM63B as ready
Intellectual disability syndromic and non-syndromic v0.5309 TMEM63B Zornitza Stark Gene: tmem63b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5309 TMEM63B Zornitza Stark Classified gene: TMEM63B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5309 TMEM63B Zornitza Stark Gene: tmem63b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5308 TMEM63B Zornitza Stark gene: TMEM63B was added
gene: TMEM63B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TMEM63B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM63B were set to 37421948
Phenotypes for gene: TMEM63B were set to developmental and epileptic encephalopathy, MONDO:0100062, TMEM63B-related
Review for gene: TMEM63B was set to GREEN
Added comment: 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment were identified with ten distinct heterozygous variants inTMEM63B. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense or in-frame. All individuals had global developmental delay, with moderate-to-profound intellectual disability and severe motor impairment. All individuals had early-onset drug-resistant epilepsy, whose onset ranged from birth to 3 years but occurred within the first year in 14/17 (82%) and in the first month of life in 6/17 (35%).
Sources: Literature
Mendeliome v1.1048 TMEM63B Zornitza Stark Marked gene: TMEM63B as ready
Mendeliome v1.1048 TMEM63B Zornitza Stark Gene: tmem63b has been classified as Green List (High Evidence).
Mendeliome v1.1048 TMEM63B Zornitza Stark Phenotypes for gene: TMEM63B were changed from developmental and epileptic encephalopathy, MONDO:0100062 to developmental and epileptic encephalopathy, MONDO:0100062, TMEM63B-related
Mendeliome v1.1047 TMEM63B Zornitza Stark Classified gene: TMEM63B as Green List (high evidence)
Mendeliome v1.1047 TMEM63B Zornitza Stark Gene: tmem63b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5307 DHX9 Zornitza Stark Marked gene: DHX9 as ready
Intellectual disability syndromic and non-syndromic v0.5307 DHX9 Zornitza Stark Added comment: Comment when marking as ready: LoF variants caused mild NDD phenotypes and nuclear localization signal (NLS) missense variants caused severe NDD. CMT2-associated missense variants caused aberrant nucleolar DHX9 accumulation, a phenomenon previously associated with cellular stress.
Intellectual disability syndromic and non-syndromic v0.5307 DHX9 Zornitza Stark Gene: dhx9 has been classified as Green List (High Evidence).
Mendeliome v1.1046 DHX9 Zornitza Stark Marked gene: DHX9 as ready
Mendeliome v1.1046 DHX9 Zornitza Stark Added comment: Comment when marking as ready: LoF variants caused mild NDD phenotypes and nuclear localization signal (NLS) missense variants caused severe NDD. CMT2-associated missense variants caused aberrant nucleolar DHX9 accumulation, a phenomenon previously associated with cellular stress.
Mendeliome v1.1046 DHX9 Zornitza Stark Gene: dhx9 has been classified as Green List (High Evidence).
Hereditary Neuropathy_CMT - isolated v1.31 DHX9 Zornitza Stark Marked gene: DHX9 as ready
Hereditary Neuropathy_CMT - isolated v1.31 DHX9 Zornitza Stark Gene: dhx9 has been classified as Green List (High Evidence).
Hereditary Neuropathy_CMT - isolated v1.31 DHX9 Zornitza Stark Classified gene: DHX9 as Green List (high evidence)
Hereditary Neuropathy_CMT - isolated v1.31 DHX9 Zornitza Stark Gene: dhx9 has been classified as Green List (High Evidence).
Hereditary Neuropathy_CMT - isolated v1.30 DHX9 Zornitza Stark gene: DHX9 was added
gene: DHX9 was added to Hereditary Neuropathy_CMT - isolated. Sources: Literature
Mode of inheritance for gene: DHX9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX9 were set to 37467750
Phenotypes for gene: DHX9 were set to Charcot-Marie-Tooth disease, MONDO:0015626, DHX9-related
Review for gene: DHX9 was set to GREEN
Added comment: PMID:37467750 - 17 unrelated individuals were identified with de novo, ultra-rare, heterozygous missense or loss-of-function DHX9 variants, of which 14 individuals were reported with a neurodevelopmental disorder (NDD) and three were reported with Charcot-Marie-Tooth disease (CMT). All 14 cases with NDD had developmental delay, of which eight were reported with intellectual disability (4 severe, 1 moderate, 3 mild). Two cases did not have ID, one had borderline ID and three cases were too young (0-5 years old). The three cases with CMT presented with adult-onset axonal neuropathy.

LoF variants caused mild NDD phenotypes and nuclear localization signal (NLS) missense variants caused severe NDD. CMT2-associated missense variants caused aberrant nucleolar DHX9 accumulation, a phenomenon previously associated with cellular stress.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5307 DHX9 Zornitza Stark Marked gene: DHX9 as ready
Intellectual disability syndromic and non-syndromic v0.5307 DHX9 Zornitza Stark Gene: dhx9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5307 DHX9 Zornitza Stark Classified gene: DHX9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5307 DHX9 Zornitza Stark Gene: dhx9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5306 DHX9 Zornitza Stark gene: DHX9 was added
gene: DHX9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DHX9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX9 were set to 37467750
Phenotypes for gene: DHX9 were set to Neurodevelopmental disorder, MONDO:0700092, DHX9-related
Review for gene: DHX9 was set to GREEN
Added comment: PMID:37467750 - 17 unrelated individuals were identified with de novo, ultra-rare, heterozygous missense or loss-of-function DHX9 variants, of which 14 individuals were reported with a neurodevelopmental disorder (NDD) and three were reported with Charcot-Marie-Tooth disease (CMT). All 14 cases with NDD had developmental delay, of which eight were reported with intellectual disability (4 severe, 1 moderate, 3 mild). Two cases did not have ID, one had borderline ID and three cases were too young (0-5 years old). The three cases with CMT presented with adult-onset axonal neuropathy.
Sources: Literature
Mendeliome v1.1046 DHX9 Zornitza Stark Marked gene: DHX9 as ready
Mendeliome v1.1046 DHX9 Zornitza Stark Gene: dhx9 has been classified as Green List (High Evidence).
Mendeliome v1.1046 DHX9 Zornitza Stark Classified gene: DHX9 as Green List (high evidence)
Mendeliome v1.1046 DHX9 Zornitza Stark Gene: dhx9 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.111 CASR Zornitza Stark Marked gene: CASR as ready
Paroxysmal Dyskinesia v0.111 CASR Zornitza Stark Gene: casr has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.111 CASR Zornitza Stark Phenotypes for gene: CASR were changed from Hypocalciuric Hypercalcemic; Hyperparathyroidism; paroxysmal dyskinesia; brain calcification to Hypocalciuric hypercalcemia, type I, MIM# 145980; Hypocalciuric Hypercalcemic; Hyperparathyroidism; paroxysmal dyskinesia; brain calcification
Paroxysmal Dyskinesia v0.110 CASR Zornitza Stark Classified gene: CASR as Green List (high evidence)
Paroxysmal Dyskinesia v0.110 CASR Zornitza Stark Gene: casr has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.207 MCOLN1 Zornitza Stark Marked gene: MCOLN1 as ready
Syndromic Retinopathy v0.207 MCOLN1 Zornitza Stark Gene: mcoln1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.207 MCOLN1 Zornitza Stark Classified gene: MCOLN1 as Green List (high evidence)
Syndromic Retinopathy v0.207 MCOLN1 Zornitza Stark Gene: mcoln1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.206 MCOLN1 Zornitza Stark gene: MCOLN1 was added
gene: MCOLN1 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: MCOLN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCOLN1 were set to 17239335; 25156245; 35205297
Phenotypes for gene: MCOLN1 were set to Mucolipidosis IV, MIM# 252650; MONDO:0009653
Review for gene: MCOLN1 was set to GREEN
Added comment: patients with MCOLN1-associated mucolipidosis IV present with ocular phenotypes including retinal dystrophy.

Mucolipidosis type IV caused by biallelic variants in MCOLN1 gene ism a lysosomal disease that primarily affects the central nervous system. It manifests with severely impaired psychomotor development, and later onset, gradual neurological decline paralleled by cerebellar degeneration and neuroaxonal injury. In addition, they also manifest retinal dystrophy, which develops in the first years of life and rapidly progresses in adolescence, leaving patients legally blind by the second decade (PMID:33965501).

The following are some of the reported cases:
PMID:17239335 - Compound heterozygous variants in MCOLN1 were identified in a patient with mucolipidosis type IV (ML IV), who had low visual acuity and cloudy corneas since 2 years of age, progressive decrease in visual acuity since the age of 9 years.
PMID:25156245 - An Italian child with ML IV was identified with homozygous MCOLN1 variants (c.395_397delCTG & c.468_474dupTTGGACC), while his parents were heterozygous for the same variants. Ophthalmological manifestations included esotropia, bilateral corneal clouding and severe myopia.
PMID:35205297 - Six patients from two Omani families with ML IV were identified with a novel variant (c.237+5G>A) in MCOLN1 gene, which is not present in control subjects screened with a high-resolution melting (HRM) assay. The patients displayed ophthalmic manifestations including corneal haziness, pigmentary retinopathy and ERG-rod cone dysfunction.
Sources: Expert list
Cerebral Palsy v1.144 SPR Luisa Weiss gene: SPR was added
gene: SPR was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SPR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SPR were set to 33528536; 34540776; 22522443
Phenotypes for gene: SPR were set to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency MIM#612716
Review for gene: SPR was set to GREEN
Added comment: Two large CP cohort studies with one case each presenting with CP and biallelic SPR mutations. In one large study from 2012, 43 individuals with Sepiapterin reductase deficiency (SRD) were clinically analyzed, diagnoses of cerebral palsy (CP) were common, both hypotonic and dystonic.
Sources: Literature
Cerebral Palsy v1.144 SPATA5 Luisa Weiss gene: SPATA5 was added
gene: SPATA5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SPATA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5 were set to 33528536
Phenotypes for gene: SPATA5 were set to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities MIM#616577
Review for gene: SPATA5 was set to GREEN
Added comment: 4 individual cases in one large CP cohort study with biallelic SPATA5 mutations. Spasticity has been described in other patients as well while developmental delay seems to be mostly present.
Sources: Literature
Cerebral Palsy v1.144 SON Luisa Weiss gene: SON was added
gene: SON was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SON was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SON were set to 33528536
Phenotypes for gene: SON were set to ZTTK syndrome MIM#617140
Review for gene: SON was set to AMBER
Added comment: 2 individual cases in one large CP cohort study. However, usually ZITK syndrome is a multisystem disorder and intellectual disabilities, and organ malformations seem to be leading phenotypic features.
Sources: Literature
Cerebral Palsy v1.144 SNX14 Luisa Weiss gene: SNX14 was added
gene: SNX14 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SNX14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNX14 were set to 34540776; 29997391
Phenotypes for gene: SNX14 were set to Spinocerebellar ataxia, autosomal recessive 20 MIM#616354
Review for gene: SNX14 was set to AMBER
Added comment: One case in a large CP cohort study. In addition, one patient in a large cohort study on congenital ataxia, which can present as dystonic cerebral palsy.
Sources: Literature
Cerebral Palsy v1.144 SMARCB1 Luisa Weiss reviewed gene: SMARCB1: Rating: AMBER; Mode of pathogenicity: None; Publications: 33528536, 34114234; Phenotypes: Coffin-Siris syndrome 3 MIM#614608, Rhabdoid tumors, somatic MIM#609322; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.144 SLITRK2 Luisa Weiss gene: SLITRK2 was added
gene: SLITRK2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLITRK2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SLITRK2 were set to 35840571
Phenotypes for gene: SLITRK2 were set to Intellectual developmental disorder, X-linked MIM#301107
Review for gene: SLITRK2 was set to GREEN
Added comment: Case study of several patients harboring SLITRK2 variants and neurodevelopmental delay. Three patients reported with spasticity, diplegic cerebral palsy and dystonic diplegia, respectively. Functional tests show impaired neuronal function and knock-out mice showed abnormal gait.
Sources: Literature
Cerebral Palsy v1.144 SLC5A6 Luisa Weiss gene: SLC5A6 was added
gene: SLC5A6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLC5A6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC5A6 were set to 33528536; 21112253; 33098801
Phenotypes for gene: SLC5A6 were set to Parkinsonism-dystonia, infantile, 1 MIM#613135
Review for gene: SLC5A6 was set to GREEN
Added comment: 21112253 presents a clinical overview of 11 children with biallelic SLC6A3 mutations, 7 of which were initially diagnosed with CP. In addition, two more CP cohort studies with one patient each harboring SLC6A3 mutations.
Sources: Literature
Cerebral Palsy v1.144 SLC16A2 Luisa Weiss gene: SLC16A2 was added
gene: SLC16A2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLC16A2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SLC16A2 were set to 33528536; 35076175; 25280894
Phenotypes for gene: SLC16A2 were set to Allan-Herndon-Dudley syndrome MIM#300523
Review for gene: SLC16A2 was set to GREEN
Added comment: Four individual cases in three large CP cohort studies presenting as dystonic or spastic CP. Mutations described were both nonsense and missense mutations and could be inherited maternally or de novo.
Sources: Literature
Cerebral Palsy v1.144 SLC13A5 Luisa Weiss gene: SLC13A5 was added
gene: SLC13A5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLC13A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A5 were set to 34364746; 34540776
Phenotypes for gene: SLC13A5 were set to Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta MIM#615905
Review for gene: SLC13A5 was set to AMBER
Added comment: Two large case studies with one patient described each harboring homozygous SLC13A5 variants, however, in PMID 34540776 this variant was defined as a VUS rather than a pathogenic mutation.
In other described cases epilepsy and ID seem to be the main phenotypic features, while ataxia and spasticity have been desribed.
Sources: Literature
Cerebral Palsy v1.144 SHANK3 Luisa Weiss reviewed gene: SHANK3: Rating: AMBER; Mode of pathogenicity: None; Publications: 33528536, 33098801; Phenotypes: Phelan-McDermid syndrome MIM#606232; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.144 SEPSECS Luisa Weiss gene: SEPSECS was added
gene: SEPSECS was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SEPSECS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEPSECS were set to 33528536; 35252561; 34540776; 36085396
Phenotypes for gene: SEPSECS were set to Pontocerebellar hypoplasia type 2D MIM#613811
Review for gene: SEPSECS was set to GREEN
Added comment: Biallelic SEPSECS mutations have been described to cause Pontocerebellar hypoplasia type 2D, which usually presents with progressive microcephaly, progressive brain atrophy, ID and variable seizures and movement disorders.
There have been two cases in two large CP cohort studies (33528536, 34540776) which have been proven to harbor biallelic SEPSECS variants, however, in PMID 34540776 these can only be formally classified as VUS. In addition, there is a case report (PMID 35252561) of a man presenting with no CP but spastic paraparesis and only slow disease progression in adult life (patient 48 years old at time of presentation). PMID 36085396 provides a literature review of described PCD2D patients, 72.7% of which have presented with spastic or dystonic quadriplegia, so there is significant phenotypic overlap with CP.
Sources: Literature
Cerebral Palsy v1.144 SATB2 Luisa Weiss gene: SATB2 was added
gene: SATB2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SATB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SATB2 were set to 33528536; 35076175
Phenotypes for gene: SATB2 were set to Glass syndrome MIM#612313
Review for gene: SATB2 was set to GREEN
Added comment: 4 patients in 3 large CP cohort studies were found to have heterozygous de novo SATB2 mutations, three of which were nonsense and one was a missense mutation. Note that in one patient an additional acute perinatal event (neonatal compartment syndrome, intracranial hemorrhage) was present which might have added to the CP phenotype.
Sources: Literature
Cerebral Palsy v1.144 SACS Luisa Weiss gene: SACS was added
gene: SACS was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SACS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SACS were set to 33528536; 34816117; 29997391
Phenotypes for gene: SACS were set to Spastic ataxia, Charlevoix-Saguenay type MIM#270550
Review for gene: SACS was set to GREEN
Added comment: Multiple large and small cohort studies with more than 3 individual patients initially diagnosed as cerebral palsy and later diagnosed with biallelic SACS mutations. SACS is a known disease gene for spastic ataxia of Charlevoix-Saguenay, which can resemble CP but usually has a progressive course of disease.
Sources: Literature
Cerebral Palsy v1.144 RARS2 Luisa Weiss gene: RARS2 was added
gene: RARS2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RARS2 were set to 34077496; 34717047
Phenotypes for gene: RARS2 were set to Pontocerebellar hypoplasia, type 6 MIM#611523
Review for gene: RARS2 was set to GREEN
Added comment: Two male patients in a large CP cohort study with either spastic quadriplegic or dyskinetic CP. Both frameshift and missense mutations have been described.
PMID 34717047 presents a good overview of published cases with RARS2 mutations. Even though none of them were officially diagnosed with cerebral palsy, many showed progressive movement disorders like spastic quadriplegia, thus possibly presenting as CP.
Sources: Literature
Cerebral Palsy v1.144 RAB3GAP1 Luisa Weiss gene: RAB3GAP1 was added
gene: RAB3GAP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RAB3GAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB3GAP1 were set to 33528536; 16532399; 27081543
Phenotypes for gene: RAB3GAP1 were set to Martsolf syndrome 2 MIM#619420; Warburg micro syndrome MIM#600118
Review for gene: RAB3GAP1 was set to GREEN
Added comment: Multiple case reports of patients with either Martsolf syndrome or Warburg micro syndrome and spastic diplegia or cerebral palsy, but all patients also presented with eye phenotype. In addition, two individuals in a large CP cohort study (no additional phenotypic information given).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5305 NLGN4X Zornitza Stark Publications for gene: NLGN4X were set to 12669065; 18231125; 10071191; 29428674
Intellectual disability syndromic and non-syndromic v0.5304 NLGN4X Zornitza Stark Classified gene: NLGN4X as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5304 NLGN4X Zornitza Stark Gene: nlgn4x has been classified as Green List (High Evidence).
Cerebral Palsy v1.144 PTPN23 Luisa Weiss gene: PTPN23 was added
gene: PTPN23 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PTPN23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPN23 were set to 31395947; 25558065; 34064836
Phenotypes for gene: PTPN23 were set to Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity MIM#618890
Review for gene: PTPN23 was set to AMBER
Added comment: Biallelic PTPN23 mutations have been associated with neurodevelopmental delay and structural brain abnormalities in an initial study of 7 patients. In this cohort, one had the initial diagnosis of cerebral palsy (patient 6), but one other patient (patient 4) showed spasticity and contractures and thus phenotypic overlap. In addition, this study referred to another study (25558065), in which a family with PTPN23 mutations was described. Even though in PMID:31395947 this family was described as having CP, this cannot be confirmed in the initial report. Note that final exon frameshift mutations in PTPN23 have been associated complex hereditary spastic paraplegia which might hint to a phenotypic overlap to CP.
Sources: Literature
Bone Marrow Failure v1.44 CLPB Pasquale Barbaro gene: CLPB was added
gene: CLPB was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: CLPB was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CLPB were set to PMID: 34115842, 25597510, 25597511
Phenotypes for gene: CLPB were set to congenital neutropenia, 3-methylglutaconic aciduria, cataracts, severe psychomotor regression during febrile episodes, epilepsy
Penetrance for gene: CLPB were set to unknown
Mode of pathogenicity for gene: CLPB was set to Other
Review for gene: CLPB was set to GREEN
Added comment: Biallelic variants identified have been loss of function, and cause a severe syndrome associated with 3-MGA, cataracts, developmental delay, epilepsy. Heterozygous variants have been found in one paper (Warren et al) in 10 patients with non-syndromic congenital neutropenia and appear to cause a dominant negative effect.
Sources: Expert list
Cerebral Palsy v1.144 PTPN11 Luisa Weiss gene: PTPN11 was added
gene: PTPN11 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PTPN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN11 were set to 33528536; 23799168
Phenotypes for gene: PTPN11 were set to LEOPARD syndrome 1 MIM#151100; Leukemia, juvenile myelomonocytic, somatic MIM#607785; Metachondromatosis MIM#156250; Noonan syndrome MIM#163950
Review for gene: PTPN11 was set to GREEN
Added comment: One case report of a girl with hearing loss and CP later diagnosed as having a heterozygous de novo missense mutation in PTPN11. In addition, two individuals in a large CP cohort study with heterozygous missense PTPN11 mutations. No information about inheritance is given in these cases. Note that there is no information about additional phenotypic features in these two cases, but the girl in the case report presented with the typical clinical picture of Noonan Syndrome with multiple lentigines (NSML, formerly known as Leopard syndrome).
Sources: Literature
Dystonia - complex v0.226 EIF4A2 Shekeeb Mohammad gene: EIF4A2 was added
gene: EIF4A2 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: EIF4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF4A2 were set to 37485550
Phenotypes for gene: EIF4A2 were set to DYSTONIA; TREMOR
Penetrance for gene: EIF4A2 were set to unknown
Review for gene: EIF4A2 was set to GREEN
Added comment: Sources: Literature
Mendeliome v1.1045 TMEM63B Achchuthan Shanmugasundram changed review comment from: There is sufficient evidence for this gene to be included with green rating in intellectual disability and epilepsy panels.

17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment were identified with ten distinct heterozygous variants inTMEM63B. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense or in-frame.

All individuals had global developmental delay, with moderate-to-profound intellectual disability and severe motor impairment.

All individuals had early-onset drug-resistant epilepsy, whose onset ranged from birth to 3 years but occurred within the first year in 14/17 (82%) and in the first month of life in 6/17 (35%).
Sources: Literature; to: There is sufficient evidence for this gene to be included with green rating in 'Intellectual disability syndromic and non-syndromic' and 'Genetic epilepsy' panels.

17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment were identified with ten distinct heterozygous variants inTMEM63B. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense or in-frame.

All individuals had global developmental delay, with moderate-to-profound intellectual disability and severe motor impairment.

All individuals had early-onset drug-resistant epilepsy, whose onset ranged from birth to 3 years but occurred within the first year in 14/17 (82%) and in the first month of life in 6/17 (35%).
Sources: Literature
Mendeliome v1.1045 TMEM63B Achchuthan Shanmugasundram gene: TMEM63B was added
gene: TMEM63B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM63B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM63B were set to 37421948
Phenotypes for gene: TMEM63B were set to developmental and epileptic encephalopathy, MONDO:0100062
Review for gene: TMEM63B was set to GREEN
Added comment: There is sufficient evidence for this gene to be included with green rating in intellectual disability and epilepsy panels.

17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment were identified with ten distinct heterozygous variants inTMEM63B. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense or in-frame.

All individuals had global developmental delay, with moderate-to-profound intellectual disability and severe motor impairment.

All individuals had early-onset drug-resistant epilepsy, whose onset ranged from birth to 3 years but occurred within the first year in 14/17 (82%) and in the first month of life in 6/17 (35%).
Sources: Literature
Mendeliome v1.1045 DHX9 Achchuthan Shanmugasundram gene: DHX9 was added
gene: DHX9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DHX9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX9 were set to 37467750
Phenotypes for gene: DHX9 were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071; Charcot-Marie-Tooth disease, MONDO:0015626
Review for gene: DHX9 was set to GREEN
Added comment: PMID:37467750 - 17 unrelated individuals were identified with de novo, ultra-rare, heterozygous missense or loss-of-function DHX9 variants, of which 14 individuals were reported with a neurodevelopmental disorder (NDD) and three were reported with Charcot-Marie-Tooth disease (CMT). All 14 cases with NDD had developmental delay, of which eight were reported with intellectual disability (4 severe, 1 moderate, 3 mild). Two cases did not have ID, one had borderline ID and three cases were too young (0-5 years old). The three cases with CMT presented with adult-onset axonal neuropathy.
Sources: Literature
Paroxysmal Dyskinesia v0.109 CASR Shekeeb Mohammad gene: CASR was added
gene: CASR was added to Paroxysmal Dyskinesia. Sources: Literature
Mode of inheritance for gene: CASR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CASR were set to 34913197
Phenotypes for gene: CASR were set to Hypocalciuric Hypercalcemic; Hyperparathyroidism; paroxysmal dyskinesia; brain calcification
Review for gene: CASR was set to GREEN
Added comment: Sources: Literature
Mendeliome v1.1045 MCOLN1 Achchuthan Shanmugasundram reviewed gene: MCOLN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17239335, 25156245, 33965501, 35205297; Phenotypes: Mucolipidosis IV, OMIM:252650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.144 GRIN1 Zornitza Stark Marked gene: GRIN1 as ready
Cerebral Palsy v1.144 GRIN1 Zornitza Stark Gene: grin1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.144 GRIN1 Zornitza Stark Classified gene: GRIN1 as Green List (high evidence)
Cerebral Palsy v1.144 GRIN1 Zornitza Stark Gene: grin1 has been classified as Green List (High Evidence).
Mendeliome v1.1045 KLK1 Zornitza Stark Phenotypes for gene: KLK1 were changed from [Kallikrein, decreased urinary activity of] 615953 to [Kallikrein, decreased urinary activity of] 615953; Pulmonary arterial hypertension MONDO:0015924
Mendeliome v1.1044 KLK1 Zornitza Stark Publications for gene: KLK1 were set to
Mendeliome v1.1043 KLK1 Zornitza Stark Mode of inheritance for gene: KLK1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1042 KLK1 Zornitza Stark edited their review of gene: KLK1: Added comment: Association with PAH:

PMID: 31727138
screening of the biobank - 12 individuals with genetic variant in KLK1 relevant to PAH (not all were found to be hereditary). Assay showed that carriers of variants in KLK1 are less clinically severe compared to those who carry variants in BMPR2.

PMID: 17573418
Functional study using sensitive and specific type ELISAs to assay multiple panels of human tissue. KLK1 tissue was abundantly expressed in the pancreas and salivary gland and moderately expressed in the lungs.

Reviewed by ClinGen Pulmonary Hypertension GCEP on 30/8/2022 with LIMITED evidence supporting gene-disease validity; Changed publications: 31727138, 17573418; Changed phenotypes: [Kallikrein, decreased urinary activity of] 615953, Pulmonary arterial hypertension MONDO:0015924; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.19 KLK1 Zornitza Stark Marked gene: KLK1 as ready
Pulmonary Arterial Hypertension v1.19 KLK1 Zornitza Stark Gene: klk1 has been classified as Red List (Low Evidence).
Pulmonary Arterial Hypertension v1.19 KLK1 Zornitza Stark Classified gene: KLK1 as Red List (low evidence)
Pulmonary Arterial Hypertension v1.19 KLK1 Zornitza Stark Gene: klk1 has been classified as Red List (Low Evidence).
Pulmonary Arterial Hypertension v1.18 KLK1 Zornitza Stark reviewed gene: KLK1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary arterial hypertension MONDO:0015924; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.143 PRUNE1 Zornitza Stark Marked gene: PRUNE1 as ready
Cerebral Palsy v1.143 PRUNE1 Zornitza Stark Gene: prune1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.143 PRUNE1 Zornitza Stark Classified gene: PRUNE1 as Green List (high evidence)
Cerebral Palsy v1.143 PRUNE1 Zornitza Stark Gene: prune1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.142 PROC Zornitza Stark Phenotypes for gene: PROC were changed from Thrombophilia due to protein C deficiency, autosomal recessive, MIM# 612304 to Thrombophilia 3 due to protein C deficiency MIM#176860; Thrombophilia 3 due to protein C deficiency MIM#612304
Cerebral Palsy v1.141 PROC Zornitza Stark Publications for gene: PROC were set to 31700678; 20187890
Cerebral Palsy v1.140 PROC Zornitza Stark Mode of inheritance for gene: PROC was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v1.139 PROC Zornitza Stark Classified gene: PROC as Green List (high evidence)
Cerebral Palsy v1.139 PROC Zornitza Stark Gene: proc has been classified as Green List (High Evidence).
Cerebral Palsy v1.138 POMGNT1 Zornitza Stark Marked gene: POMGNT1 as ready
Cerebral Palsy v1.138 POMGNT1 Zornitza Stark Gene: pomgnt1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.138 POMGNT1 Zornitza Stark Phenotypes for gene: POMGNT1 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 MIM# 253280; Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 3 MIM#613151; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3 MIM#613157; Retinitis pigmentosa 76 MIM#617123 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 MIM# 253280; Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 3 MIM#613151; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3 MIM#613157
Cerebral Palsy v1.137 POMGNT1 Zornitza Stark Classified gene: POMGNT1 as Green List (high evidence)
Cerebral Palsy v1.137 POMGNT1 Zornitza Stark Gene: pomgnt1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.205 PDHA1 Zornitza Stark Marked gene: PDHA1 as ready
Hereditary Neuropathy - complex v0.205 PDHA1 Zornitza Stark Gene: pdha1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.205 PDHA1 Zornitza Stark Phenotypes for gene: PDHA1 were changed from Pyruvate dehydrogenase E1-alpha deficiency; HMSN to Primary Pyruvate Dehydrogenase Complex Deficiency MIM 312170
Hereditary Neuropathy - complex v0.204 PDHA1 Zornitza Stark Publications for gene: PDHA1 were set to
Hereditary Neuropathy - complex v0.203 PDHA1 Zornitza Stark reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36693417, 33661577; Phenotypes: Primary Pyruvate Dehydrogenase Complex Deficiency MIM 312170; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.136 POGZ Zornitza Stark Marked gene: POGZ as ready
Cerebral Palsy v1.136 POGZ Zornitza Stark Gene: pogz has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.136 POGZ Zornitza Stark Classified gene: POGZ as Amber List (moderate evidence)
Cerebral Palsy v1.136 POGZ Zornitza Stark Gene: pogz has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.203 NTRK1 Zornitza Stark Marked gene: NTRK1 as ready
Hereditary Neuropathy - complex v0.203 NTRK1 Zornitza Stark Gene: ntrk1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.203 NTRK1 Zornitza Stark Phenotypes for gene: NTRK1 were changed from HSAN/SFN; Hereditary Neuropathies; Insensitivity to pain, congenital, with anhidrosis to hereditary sensory and autonomic neuropathy type 4 MONDO:0009746
Hereditary Neuropathy - complex v0.202 NTRK1 Zornitza Stark Publications for gene: NTRK1 were set to
Cerebral Palsy v1.135 PNPLA6 Zornitza Stark Marked gene: PNPLA6 as ready
Cerebral Palsy v1.135 PNPLA6 Zornitza Stark Gene: pnpla6 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.135 PNPLA6 Zornitza Stark Phenotypes for gene: PNPLA6 were changed from Boucher-Neuhauser syndrome MIM#215470; Oliver-McFarlane syndrome MIM#275400; Spastic paraplegia 39 MIM#612020 to Spastic paraplegia 39 MIM#612020
Cerebral Palsy v1.134 PNPLA6 Zornitza Stark Classified gene: PNPLA6 as Amber List (moderate evidence)
Cerebral Palsy v1.134 PNPLA6 Zornitza Stark Gene: pnpla6 has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.133 TBX6 Zornitza Stark Marked gene: TBX6 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.133 TBX6 Zornitza Stark Gene: tbx6 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.133 TBX6 Zornitza Stark Phenotypes for gene: TBX6 were changed from Mayer-Rokitansky-Küster-Hauser syndrome; Combined skeletal-kidney dysplasia syndrome to Mayer-Rokitansky-Küster-Hauser syndrome, MONDO:0017771, TBX6-related; Combined skeletal-kidney dysplasia syndrome
Mendeliome v1.1042 TBX6 Zornitza Stark Phenotypes for gene: TBX6 were changed from Spondylocostal dysostosis 5, 122600 to Spondylocostal dysostosis 5, 122600; Mayer-Rokitansky-Küster-Hauser syndrome, MONDO:0017771, TBX6-related
Mendeliome v1.1041 WBP4 Zornitza Stark Marked gene: WBP4 as ready
Mendeliome v1.1041 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Mendeliome v1.1041 WBP4 Zornitza Stark Phenotypes for gene: WBP4 were changed from Neurodevelopmental disorder, MONDO:0700092, WBP4-related to Neurodevelopmental disorder, MONDO:0700092, WBP4-related
Intellectual disability syndromic and non-syndromic v0.5303 WBP4 Zornitza Stark Marked gene: WBP4 as ready
Intellectual disability syndromic and non-syndromic v0.5303 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5303 WBP4 Zornitza Stark Phenotypes for gene: WBP4 were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, WBP4-related
Mendeliome v1.1040 WBP4 Zornitza Stark Marked gene: WBP4 as ready
Mendeliome v1.1040 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Mendeliome v1.1040 WBP4 Zornitza Stark Phenotypes for gene: WBP4 were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, WBP4-related
Intellectual disability syndromic and non-syndromic v0.5302 KDM2A Zornitza Stark Marked gene: KDM2A as ready
Intellectual disability syndromic and non-syndromic v0.5302 KDM2A Zornitza Stark Gene: kdm2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5302 KDM2A Zornitza Stark Phenotypes for gene: KDM2A were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, KDM2A-related
Mendeliome v1.1039 KDM2A Zornitza Stark Marked gene: KDM2A as ready
Mendeliome v1.1039 KDM2A Zornitza Stark Gene: kdm2a has been classified as Green List (High Evidence).
Mendeliome v1.1039 KDM2A Zornitza Stark Phenotypes for gene: KDM2A were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, KDM2A-related
Intellectual disability syndromic and non-syndromic v0.5301 PIP5K1C Zornitza Stark Marked gene: PIP5K1C as ready
Intellectual disability syndromic and non-syndromic v0.5301 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5301 PIP5K1C Zornitza Stark Phenotypes for gene: PIP5K1C were changed from Neurodevelopmental disorder and microcephaly to Neurodevelopmental disorder and microcephaly, MONDO:0700092, PIP5K1C-related
Microcephaly v1.220 PIP5K1C Zornitza Stark Marked gene: PIP5K1C as ready
Microcephaly v1.220 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Green List (High Evidence).
Microcephaly v1.220 PIP5K1C Zornitza Stark Phenotypes for gene: PIP5K1C were changed from Neurodevelopmental disorder and microcephaly to Neurodevelopmental disorder and microcephaly, MONDO:0700092, PIP5K1C-related
Mendeliome v1.1038 PIP5K1C Zornitza Stark Phenotypes for gene: PIP5K1C were changed from Lethal congenital contractural syndrome 3, MIM# 611369 to Neurodevelopmental disorder and microcephaly, MONDO:0700092, PIP5K1C-related; Lethal congenital contractural syndrome 3, MIM# 611369
Mendeliome v1.1037 PIP5K1C Zornitza Stark Mode of inheritance for gene: PIP5K1C was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1036 PIP5K1C Zornitza Stark Mode of inheritance for gene: PIP5K1C was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.128 INTS13 Zornitza Stark Marked gene: INTS13 as ready
Fetal anomalies v1.128 INTS13 Zornitza Stark Gene: ints13 has been classified as Green List (High Evidence).
Fetal anomalies v1.128 INTS13 Zornitza Stark Phenotypes for gene: INTS13 were changed from Oral-facial-digital syndrome to Oral-facial-digital syndrome, MONDO:0015375, INTS13-related
Clefting disorders v0.239 INTS13 Zornitza Stark Marked gene: INTS13 as ready
Clefting disorders v0.239 INTS13 Zornitza Stark Gene: ints13 has been classified as Green List (High Evidence).
Clefting disorders v0.239 INTS13 Zornitza Stark Phenotypes for gene: INTS13 were changed from Oral-facial-digital syndrome to Oral-facial-digital syndrome, MONDO:0015375, INTS13-related
Intellectual disability syndromic and non-syndromic v0.5300 INTS13 Zornitza Stark Marked gene: INTS13 as ready
Intellectual disability syndromic and non-syndromic v0.5300 INTS13 Zornitza Stark Gene: ints13 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5300 INTS13 Zornitza Stark Phenotypes for gene: INTS13 were changed from Oral-facial-digital syndrome to Oral-facial-digital syndrome, MONDO:0015375, INTS13-related
Ciliopathies v1.44 INTS13 Zornitza Stark Marked gene: INTS13 as ready
Ciliopathies v1.44 INTS13 Zornitza Stark Gene: ints13 has been classified as Green List (High Evidence).
Ciliopathies v1.44 INTS13 Zornitza Stark Phenotypes for gene: INTS13 were changed from Oral-facial-digital syndrome to Oral-facial-digital syndrome, MONDO:0015375, INTS13-related
Mendeliome v1.1035 INTS13 Zornitza Stark Marked gene: INTS13 as ready
Mendeliome v1.1035 INTS13 Zornitza Stark Gene: ints13 has been classified as Green List (High Evidence).
Mendeliome v1.1035 INTS13 Zornitza Stark Phenotypes for gene: INTS13 were changed from Oral-facial-digital syndrome to Oral-facial-digital syndrome, MONDO:0015375, INTS13-related
BabyScreen+ newborn screening v0.2177 PLG Zornitza Stark Mode of inheritance for gene: PLG was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Pulmonary Arterial Hypertension v1.18 KLK1 Sangavi Sivagnanasundram gene: KLK1 was added
gene: KLK1 was added to Pulmonary Arterial Hypertension. Sources: Other
Mode of inheritance for gene: KLK1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KLK1 were set to 31727138; 17573418
Phenotypes for gene: KLK1 were set to Pulmonary arterial hypertension MONDO:0015924
Review for gene: KLK1 was set to AMBER
Added comment: PMID: 31727138
screening of the biobank - 12 individuals with genetic variant in KLK1 relevant to PAH (not all were found to be hereditary). Assay showed that carriers of variants in KLK1 are less clinically severe compared to those who carry variants in BMPR2.

PMID: 17573418
Functional study using sensitive and specific type ELISAs to assay multiple panels of human tissue. KLK1 tissue was abundantly expressed in the pancreas and salivary gland and moderately expressed in the lungs.

Reviewed by ClinGen Pulmonary Hypertension GCEP on 30/8/2022 with limited evidence supporting gene-disease validation
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5299 TEFM Zornitza Stark Marked gene: TEFM as ready
Intellectual disability syndromic and non-syndromic v0.5299 TEFM Zornitza Stark Gene: tefm has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5299 TEFM Zornitza Stark Classified gene: TEFM as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5299 TEFM Zornitza Stark Gene: tefm has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5298 TEFM Zornitza Stark gene: TEFM was added
gene: TEFM was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TEFM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TEFM were set to 36823193
Phenotypes for gene: TEFM were set to Combined oxidative phosphorylation deficiency 58, MIM# 620451
Review for gene: TEFM was set to GREEN
Added comment: Seven individuals from 5 families reported. Presentation predominantly with encephalopathy, seizures and ID, in addition to lactic acidosis.
Sources: Literature
Genetic Epilepsy v0.1873 TEFM Zornitza Stark Marked gene: TEFM as ready
Genetic Epilepsy v0.1873 TEFM Zornitza Stark Gene: tefm has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1873 TEFM Zornitza Stark Classified gene: TEFM as Green List (high evidence)
Genetic Epilepsy v0.1873 TEFM Zornitza Stark Gene: tefm has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1872 TEFM Zornitza Stark gene: TEFM was added
gene: TEFM was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TEFM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TEFM were set to 36823193
Phenotypes for gene: TEFM were set to Combined oxidative phosphorylation deficiency 58, MIM# 620451
Review for gene: TEFM was set to GREEN
Added comment: Seven individuals from 5 families reported. Presentation predominantly with encephalopathy, seizures and ID, in addition to lactic acidosis.
Sources: Literature
Mitochondrial disease v0.879 TEFM Zornitza Stark Phenotypes for gene: TEFM were changed from Combined oxidative phosphorylation deficiency 58, MIM# 620451 to Combined oxidative phosphorylation deficiency 58, MIM# 620451
Mitochondrial disease v0.878 TEFM Zornitza Stark Phenotypes for gene: TEFM were changed from Combined oxidative phosphorylation deficiency 58, MIM# 620451 to Combined oxidative phosphorylation deficiency 58, MIM# 620451
Mitochondrial disease v0.878 TEFM Zornitza Stark Phenotypes for gene: TEFM were changed from Mitochondrial disease (MONDO#0044970), TEFM-related to Combined oxidative phosphorylation deficiency 58, MIM# 620451
Mendeliome v1.1034 TEFM Zornitza Stark Phenotypes for gene: TEFM were changed from Mitochondrial disease (MONDO#0044970), TEFM-related to Combined oxidative phosphorylation deficiency 58, MIM# 620451
Common Variable Immunodeficiency v1.5 MAP3K14 Zornitza Stark Phenotypes for gene: MAP3K14 were changed from hypogammaglobulinemia; recurrent infections to Immunodeficiency 112, MIM# 620449
Combined Immunodeficiency v1.41 MAP3K14 Zornitza Stark Phenotypes for gene: MAP3K14 were changed from NIK deficiency; Poor T cell proliferation to antigen; Low B-cell numbers; Low NK number and function; recurrent bacterial/viral/ cryptosporidium infections; hypogammaglobulinaemia; decreased immunoglobulin levels to Immunodeficiency 112, MIM# 620449; NIK deficiency; Poor T cell proliferation to antigen; Low B-cell numbers; Low NK number and function; recurrent bacterial/viral/ cryptosporidium infections; hypogammaglobulinaemia; decreased immunoglobulin levels
Mendeliome v1.1033 MAP3K14 Zornitza Stark Phenotypes for gene: MAP3K14 were changed from NIK deficiency; Poor T cell proliferation to antigen; Low B-cell numbers; Low NK number and function; recurrent bacterial/viral/ cryptosporidium infections; hypogammaglobulinaemia; decreased immunoglobulin levels to Immunodeficiency 112, MIM# 620449; NIK deficiency; Poor T cell proliferation to antigen; Low B-cell numbers; Low NK number and function; recurrent bacterial/viral/ cryptosporidium infections; hypogammaglobulinaemia; decreased immunoglobulin levels
Mendeliome v1.1032 MAP3K14 Zornitza Stark edited their review of gene: MAP3K14: Changed phenotypes: Immunodeficiency 112, MIM# 620449, NIK deficiency, Poor T cell proliferation to antigen, Low B-cell numbers, Low NK number and function, recurrent bacterial/viral/ cryptosporidium infections, hypogammaglobulinaemia, decreased immunoglobulin levels
Fetal anomalies v1.127 SLC20A1 Zornitza Stark Phenotypes for gene: SLC20A1 were changed from Bladder-Exstrophy-Epispadias Complex (BEEC) to Bladder-Exstrophy-Epispadias Complex (BEEC), MONDO:0017919, SLC20A1-related
Mendeliome v1.1032 SLC20A1 Zornitza Stark Phenotypes for gene: SLC20A1 were changed from Bladder-Exstrophy-Epispadias Complex (BEEC) to Bladder-Exstrophy-Epispadias Complex (BEEC), MONDO:0017919, SLC20A1-related
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.114 SLC20A1 Zornitza Stark Phenotypes for gene: SLC20A1 were changed from Bladder-Exstrophy-Epispadias Complex (BEEC) to Bladder-Exstrophy-Epispadias Complex (BEEC), MONDO:0017919, SLC20A1-related
Differences of Sex Development v0.280 SLC20A1 Zornitza Stark Marked gene: SLC20A1 as ready
Differences of Sex Development v0.280 SLC20A1 Zornitza Stark Gene: slc20a1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.280 SLC20A1 Zornitza Stark Phenotypes for gene: SLC20A1 were changed from Bladder-Exstrophy-Epispadias Complex (BEEC) to Bladder-Exstrophy-Epispadias Complex (BEEC), MONDO:0017919, SLC20A1-related
Syndromic Retinopathy v0.205 TUBB4B Zornitza Stark Phenotypes for gene: TUBB4B were changed from Leber congenital amaurosis with early-onset deafness MIM#617879 to Leber congenital amaurosis with early-onset deafness MIM#617879; Primary ciliary dyskinesia, MONDO:0016575, TUBB4B-related
Ciliary Dyskinesia v1.34 TUBB4B Zornitza Stark Marked gene: TUBB4B as ready
Ciliary Dyskinesia v1.34 TUBB4B Zornitza Stark Gene: tubb4b has been classified as Green List (High Evidence).
Ciliary Dyskinesia v1.34 TUBB4B Zornitza Stark Phenotypes for gene: TUBB4B were changed from Primary ciliary dyskinesia to Primary ciliary dyskinesia, MONDO:0016575, TUBB4B-related
Mendeliome v1.1031 TUBB4B Zornitza Stark Phenotypes for gene: TUBB4B were changed from Leber congenital amaurosis with early onset deafness, LCAEOD, OMIM #617879; MONDO:0060650 to Leber congenital amaurosis with early onset deafness, LCAEOD, OMIM #617879; MONDO:0060650; Primary ciliary dyskinesia, MONDO:0016575, TUBB4B-related
Mendeliome v1.1030 CYHR1 Zornitza Stark Marked gene: CYHR1 as ready
Mendeliome v1.1030 CYHR1 Zornitza Stark Gene: cyhr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1030 CYHR1 Zornitza Stark Phenotypes for gene: CYHR1 were changed from Neurodevelopmental disorder and microcephaly to Neurodevelopmental disorder and microcephaly, MONDO:0700092, CYHR1-related
Microcephaly v1.219 CYHR1 Zornitza Stark Marked gene: CYHR1 as ready
Microcephaly v1.219 CYHR1 Zornitza Stark Gene: cyhr1 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.219 CYHR1 Zornitza Stark Phenotypes for gene: CYHR1 were changed from Neurodevelopmental disorder and microcephaly to Neurodevelopmental disorder and microcephaly, MONDO:0700092, CYHR1-related
Intellectual disability syndromic and non-syndromic v0.5297 CYHR1 Zornitza Stark Marked gene: CYHR1 as ready
Intellectual disability syndromic and non-syndromic v0.5297 CYHR1 Zornitza Stark Gene: cyhr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5297 CYHR1 Zornitza Stark Phenotypes for gene: CYHR1 were changed from Neurodevelopmental disorder and microcephaly to Neurodevelopmental disorder and microcephaly, MONDO:0700092, CYHR1-related
BabyScreen+ newborn screening v0.2176 ABCD4 Zornitza Stark Tag metabolic tag was added to gene: ABCD4.
Hereditary Spastic Paraplegia - adult onset v1.7 TSPOAP1 Zornitza Stark Phenotypes for gene: TSPOAP1 were changed from Dystonia, intellectual disability and cerebellar atrophy to Dystonia 22, MIM# 620453
Hereditary Spastic Paraplegia - adult onset v1.6 TSPOAP1 Zornitza Stark reviewed gene: TSPOAP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia 22, MIM# 620453; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.226 TSPOAP1 Zornitza Stark Marked gene: TSPOAP1 as ready
Dystonia - complex v0.226 TSPOAP1 Zornitza Stark Gene: tspoap1 has been classified as Green List (High Evidence).
Dystonia - complex v0.226 TSPOAP1 Zornitza Stark Phenotypes for gene: TSPOAP1 were changed from dystonia; intellectual disability; cerebellar atrophy to Dystonia 22, MIM# 620453
Dystonia - complex v0.225 TSPOAP1 Zornitza Stark Classified gene: TSPOAP1 as Green List (high evidence)
Dystonia - complex v0.225 TSPOAP1 Zornitza Stark Gene: tspoap1 has been classified as Green List (High Evidence).
Dystonia - complex v0.224 TSPOAP1 Zornitza Stark reviewed gene: TSPOAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia 22, MIM# 620453; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5296 TSPOAP1 Zornitza Stark Phenotypes for gene: TSPOAP1 were changed from Dystonia, intellectual disability and cerebellar atrophy to Dystonia 22, MIM# 620453
Intellectual disability syndromic and non-syndromic v0.5295 TSPOAP1 Zornitza Stark reviewed gene: TSPOAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia 22, MIM# 620453; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1029 TSPOAP1 Zornitza Stark Phenotypes for gene: TSPOAP1 were changed from Dystonia, intellectual disability and cerebellar atrophy to Dystonia 22, MIM# 620453
Mendeliome v1.1028 TSPOAP1 Zornitza Stark reviewed gene: TSPOAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia 22, MIM# 620453; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5295 TAF4 Zornitza Stark Phenotypes for gene: TAF4 were changed from Neurodevelopmental disorder, MONDO:0700092, TAF4-related to Intellectual developmental disorder, autosomal dominant 73, MIM# 620450
Intellectual disability syndromic and non-syndromic v0.5294 TAF4 Zornitza Stark edited their review of gene: TAF4: Changed phenotypes: Intellectual developmental disorder, autosomal dominant 73, MIM# 620450
Mendeliome v1.1028 TAF4 Zornitza Stark Phenotypes for gene: TAF4 were changed from Neurodevelopmental disorder, MONDO:0700092, TAF4-related to Intellectual developmental disorder, autosomal dominant 73, MIM# 620450
Mendeliome v1.1027 TAF4 Zornitza Stark edited their review of gene: TAF4: Changed phenotypes: Intellectual developmental disorder, autosomal dominant 73, MIM# 620450
Regression v0.530 NAA60 Zornitza Stark Marked gene: NAA60 as ready
Regression v0.530 NAA60 Zornitza Stark Gene: naa60 has been classified as Green List (High Evidence).
Regression v0.530 NAA60 Zornitza Stark Classified gene: NAA60 as Green List (high evidence)
Regression v0.530 NAA60 Zornitza Stark Gene: naa60 has been classified as Green List (High Evidence).
Regression v0.529 NAA60 Zornitza Stark gene: NAA60 was added
gene: NAA60 was added to Regression. Sources: Other
Mode of inheritance for gene: NAA60 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NAA60 were set to Basal ganglia calcification, MONDO:0008947, NAA60-related
Review for gene: NAA60 was set to GREEN
Added comment: ESHG 2023:
10 individuals from 7 families with biallelic variants in NAA60 (missense and framshift).
All with primary brain calcification - 4/10 childhood onset (DD, ID), 6/10 adult onset (cerebellar and pyramidal dysfunction, dystonia, parkinsonism, cognitive impairment, psychiatric manifestations).

NAA60 catalyses N-terminal acetylation of transmembrane proteins and localises to Golgi apparatus. In vitro assay of variants showed reduced capacity of Nt acetylation. Fibroblast studies showed significantly reduced levels of phosphate importer (SLC20A2). Loss of function variants in SLC20A2 (~50% of PFBC cases) lead to increased extracellular phosphate (which is thought to lead to calcium deposits in brain).
Sources: Other
Mendeliome v1.1027 NAA60 Zornitza Stark Marked gene: NAA60 as ready
Mendeliome v1.1027 NAA60 Zornitza Stark Gene: naa60 has been classified as Green List (High Evidence).
Mendeliome v1.1027 NAA60 Zornitza Stark Phenotypes for gene: NAA60 were changed from Basal ganglia calcification to Basal ganglia calcification, MONDO:0008947, NAA60-related
Brain Calcification v1.94 NAA60 Zornitza Stark Marked gene: NAA60 as ready
Brain Calcification v1.94 NAA60 Zornitza Stark Gene: naa60 has been classified as Green List (High Evidence).
Brain Calcification v1.94 NAA60 Zornitza Stark Phenotypes for gene: NAA60 were changed from Basal ganglia calcification to Basal ganglia calcification, MONDO:0008947, NAA60-related
Mendeliome v1.1026 POPDC2 Zornitza Stark Marked gene: POPDC2 as ready
Mendeliome v1.1026 POPDC2 Zornitza Stark Gene: popdc2 has been classified as Green List (High Evidence).
Mendeliome v1.1026 POPDC2 Zornitza Stark Phenotypes for gene: POPDC2 were changed from Sinus node dysfunction to Sinoatrial node disorder, MONDO:0000469, POPDC2-related
Sick sinus syndrome v1.4 POPDC2 Zornitza Stark Marked gene: POPDC2 as ready
Sick sinus syndrome v1.4 POPDC2 Zornitza Stark Gene: popdc2 has been classified as Green List (High Evidence).
Sick sinus syndrome v1.4 POPDC2 Zornitza Stark Phenotypes for gene: POPDC2 were changed from Sinus node dysfunction to Sinoatrial node disorder, MONDO:0000469, POPDC2-related
Syndromic Retinopathy v0.204 GPATCH11 Zornitza Stark Marked gene: GPATCH11 as ready
Syndromic Retinopathy v0.204 GPATCH11 Zornitza Stark Gene: gpatch11 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.204 GPATCH11 Zornitza Stark Phenotypes for gene: GPATCH11 were changed from Leber congenital amaurosis and developmental delay to Neurodevelopmental disorder, MONDO:0700092, GPATCH11-related; Leber congenital amaurosis and developmental delay
Intellectual disability syndromic and non-syndromic v0.5294 GPATCH11 Zornitza Stark Marked gene: GPATCH11 as ready
Intellectual disability syndromic and non-syndromic v0.5294 GPATCH11 Zornitza Stark Gene: gpatch11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5294 GPATCH11 Zornitza Stark Phenotypes for gene: GPATCH11 were changed from Leber congenital amaurosis and developmental delay to Neurodevelopmental disorder, MONDO:0700092, GPATCH11-related; Leber congenital amaurosis and developmental delay
Intellectual disability syndromic and non-syndromic v0.5293 GPATCH11 Zornitza Stark Classified gene: GPATCH11 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5293 GPATCH11 Zornitza Stark Gene: gpatch11 has been classified as Green List (High Evidence).
Mendeliome v1.1025 GPATCH11 Zornitza Stark Marked gene: GPATCH11 as ready
Mendeliome v1.1025 GPATCH11 Zornitza Stark Gene: gpatch11 has been classified as Green List (High Evidence).
Mendeliome v1.1025 GPATCH11 Zornitza Stark Phenotypes for gene: GPATCH11 were changed from Leber congenital amaurosis and developmental delay to Neurodevelopmental disorder, MONDO:0700092, GPATCH11-related; Leber congenital amaurosis and developmental delay
Intellectual disability syndromic and non-syndromic v0.5292 KCNA3 Zornitza Stark Marked gene: KCNA3 as ready
Intellectual disability syndromic and non-syndromic v0.5292 KCNA3 Zornitza Stark Gene: kcna3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5292 KCNA3 Zornitza Stark Phenotypes for gene: KCNA3 were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, KCNA3-related
Genetic Epilepsy v0.1871 KCNA3 Zornitza Stark Marked gene: KCNA3 as ready
Genetic Epilepsy v0.1871 KCNA3 Zornitza Stark Gene: kcna3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1871 KCNA3 Zornitza Stark Phenotypes for gene: KCNA3 were changed from Neurodevelopmental disorder with epilepsy to Neurodevelopmental disorder, MONDO:0700092, KCNA3-related
Mendeliome v1.1024 KCNA3 Zornitza Stark Marked gene: KCNA3 as ready
Mendeliome v1.1024 KCNA3 Zornitza Stark Gene: kcna3 has been classified as Green List (High Evidence).
Mendeliome v1.1024 KCNA3 Zornitza Stark Phenotypes for gene: KCNA3 were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, KCNA3-related
Mendeliome v1.1023 FSD1L Zornitza Stark Marked gene: FSD1L as ready
Mendeliome v1.1023 FSD1L Zornitza Stark Gene: fsd1l has been classified as Green List (High Evidence).
Mendeliome v1.1023 FSD1L Zornitza Stark Phenotypes for gene: FSD1L were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, FSD1L-related
Intellectual disability syndromic and non-syndromic v0.5291 FSD1L Zornitza Stark Marked gene: FSD1L as ready
Intellectual disability syndromic and non-syndromic v0.5291 FSD1L Zornitza Stark Gene: fsd1l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5291 FSD1L Zornitza Stark Phenotypes for gene: FSD1L were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, FSD1L-related
Mendeliome v1.1022 DENND5B Zornitza Stark Marked gene: DENND5B as ready
Mendeliome v1.1022 DENND5B Zornitza Stark Gene: dennd5b has been classified as Green List (High Evidence).
Mendeliome v1.1022 DENND5B Zornitza Stark Phenotypes for gene: DENND5B were changed from Neurodevelopmental disorder with white matter anomalies to Neurodevelopmental disorder with white matter anomalies, MONDO:0700092, DENND5B-related
Intellectual disability syndromic and non-syndromic v0.5290 DENND5B Zornitza Stark Marked gene: DENND5B as ready
Intellectual disability syndromic and non-syndromic v0.5290 DENND5B Zornitza Stark Gene: dennd5b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5290 DENND5B Zornitza Stark Phenotypes for gene: DENND5B were changed from Neurodevelopmental disorder with white matter anomalies to Neurodevelopmental disorder with white matter anomalies, MONDO:0700092, DENND5B-related
Leukodystrophy - paediatric v0.293 DENND5B Zornitza Stark Marked gene: DENND5B as ready
Leukodystrophy - paediatric v0.293 DENND5B Zornitza Stark Gene: dennd5b has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.293 DENND5B Zornitza Stark Phenotypes for gene: DENND5B were changed from Neurodevelopmental disorder with white matter anomalies to Neurodevelopmental disorder with white matter anomalies, MONDO:0700092, DENND5B-related
Intellectual disability syndromic and non-syndromic v0.5289 DMAP1 Zornitza Stark Marked gene: DMAP1 as ready
Intellectual disability syndromic and non-syndromic v0.5289 DMAP1 Zornitza Stark Gene: dmap1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5289 DMAP1 Zornitza Stark Phenotypes for gene: DMAP1 were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, DMAP1-related
Mendeliome v1.1021 DMAP1 Zornitza Stark Marked gene: DMAP1 as ready
Mendeliome v1.1021 DMAP1 Zornitza Stark Gene: dmap1 has been classified as Green List (High Evidence).
Mendeliome v1.1021 DMAP1 Zornitza Stark Phenotypes for gene: DMAP1 were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, DMAP1-related
Mendeliome v1.1020 VGLL2 Zornitza Stark Marked gene: VGLL2 as ready
Mendeliome v1.1020 VGLL2 Zornitza Stark Gene: vgll2 has been classified as Green List (High Evidence).
Mendeliome v1.1020 VGLL2 Zornitza Stark Phenotypes for gene: VGLL2 were changed from Syngnathia to Syngnathia, MONDO:0015409, VGLL2-related
Mandibulofacial Acrofacial dysostosis v1.8 VGLL2 Zornitza Stark Marked gene: VGLL2 as ready
Mandibulofacial Acrofacial dysostosis v1.8 VGLL2 Zornitza Stark Gene: vgll2 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v1.8 VGLL2 Zornitza Stark Phenotypes for gene: VGLL2 were changed from Syngnathia to Syngnathia, MONDO:0015409, VGLL2-related
Regression v0.528 ZIC1 Zornitza Stark Marked gene: ZIC1 as ready
Regression v0.528 ZIC1 Zornitza Stark Gene: zic1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2176 COL4A6 Zornitza Stark Classified gene: COL4A6 as Red List (low evidence)
BabyScreen+ newborn screening v0.2176 COL4A6 Zornitza Stark Gene: col4a6 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2175 COL4A6 Zornitza Stark edited their review of gene: COL4A6: Added comment: Further review of PMID:33840813;

Family A:
- Proband is hemi for COL4A6 and het for GJB2. Mother is het for COL4A6
- hypothesised that in the proband is more severe than the parents due to additive effects of his two variants however, mother's audiometric data was unavailable to confirm this.

Family B:
- Variant does not segregate within family with the proband being WT in this gene
- NM_001287758.1: c.3272G>C is the mutation however, it appears to be an annotation error as it corresponds to NC_000023.11:g.108171443 in GRCh38. At that position, the c. is T not G and the amino acid residue is Val, not Gly.

In addition, there is a missense affecting Gly of GXY in gnomad v3 with 38 hemis.; Changed rating: RED; Changed publications: 33840813; Changed phenotypes: Deafness, X-linked 6 MIM#300914; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Deafness_IsolatedAndComplex v1.158 COL4A6 Zornitza Stark Classified gene: COL4A6 as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v1.158 COL4A6 Zornitza Stark Gene: col4a6 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.157 COL4A6 Zornitza Stark edited their review of gene: COL4A6: Changed rating: AMBER
Deafness_IsolatedAndComplex v1.157 COL4A6 Zornitza Stark edited their review of gene: COL4A6: Added comment: Further review of PMID:33840813

Family A:
- Proband is hemi for COL4A6 and het for GJB2. Mother is het for COL4A6
- hypothesised that in the proband is more severe than the parents due to additive effects of his two variants however, mother's audiometric data was unavailable to confirm this.

Family B:
- Variant does not segregate within family with the proband being WT in this gene
- NM_001287758.1: c.3272G>C is the mutation however, it appears to be an annotation error as it corresponds to NC_000023.11:g.108171443 in GRCh38. At that position, the c. is T not G and the amino acid residue is Val, not Gly.

In addition, there is a missense affecting Gly of GXY in gnomad v3 with 38 hemis.; Changed publications: 23714752, 33840813
Mendeliome v1.1019 COL4A6 Zornitza Stark Publications for gene: COL4A6 were set to 23714752; 12784310
Mendeliome v1.1018 COL4A6 Zornitza Stark Classified gene: COL4A6 as Amber List (moderate evidence)
Mendeliome v1.1018 COL4A6 Zornitza Stark Gene: col4a6 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1017 HCN2 Zornitza Stark Phenotypes for gene: HCN2 were changed from Febrile seizures, familial, 2, MIM# 602477; Genetic epilepsy with febrile seizures plus; Other seizure disorders to Febrile seizures, familial, 2, MIM# 602477; Genetic epilepsy with febrile seizures plus; Other seizure disorders; Neurodevelopmental disorder (MONDO#0700092), HCN2-related
Mendeliome v1.1016 HCN2 Zornitza Stark edited their review of gene: HCN2: Added comment: ICG congress 2023: cohort presented with ID as key feature.; Changed phenotypes: Febrile seizures, familial, 2, MIM# 602477, Genetic epilepsy with febrile seizures plus, Other seizure disorders, Neurodevelopmental disorder (MONDO#0700092), HCN2-related
Intellectual disability syndromic and non-syndromic v0.5288 HCN2 Zornitza Stark Marked gene: HCN2 as ready
Intellectual disability syndromic and non-syndromic v0.5288 HCN2 Zornitza Stark Gene: hcn2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5288 HCN2 Zornitza Stark Phenotypes for gene: HCN2 were changed from Febrile seizures, familial, 2 MIM#602477; Generalized epilepsy with febrile seizures plus, type 11 MIM#602477; {Epilepsy, idiopathic generalized, susceptibility to, 17} MIM#602477; Neurodevelopmental disorder (MONDO#0700092), HCN2-related to Neurodevelopmental disorder (MONDO#0700092), HCN2-related
Intellectual disability syndromic and non-syndromic v0.5287 HCN2 Zornitza Stark Classified gene: HCN2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5287 HCN2 Zornitza Stark Gene: hcn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1016 SLC4A3 Zornitza Stark Publications for gene: SLC4A3 were set to PMID: 29167417; 34557911
Mendeliome v1.1015 SLC4A3 Zornitza Stark Classified gene: SLC4A3 as Green List (high evidence)
Mendeliome v1.1015 SLC4A3 Zornitza Stark Gene: slc4a3 has been classified as Green List (High Evidence).
Short QT syndrome v1.7 SLC4A3 Zornitza Stark Publications for gene: SLC4A3 were set to PMID: 29167417; 34557911
Short QT syndrome v1.6 SLC4A3 Zornitza Stark Classified gene: SLC4A3 as Green List (high evidence)
Short QT syndrome v1.6 SLC4A3 Zornitza Stark Gene: slc4a3 has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.103 SOCS1 Zornitza Stark Marked gene: SOCS1 as ready
Inflammatory bowel disease v0.103 SOCS1 Zornitza Stark Gene: socs1 has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.103 SOCS1 Zornitza Stark Phenotypes for gene: SOCS1 were changed from Enteropathy to Autoinflammatory syndrome, familial, with or without immunodeficiency, MIM# 619375; Enteropathy
Inflammatory bowel disease v0.102 SOCS1 Zornitza Stark Classified gene: SOCS1 as Green List (high evidence)
Inflammatory bowel disease v0.102 SOCS1 Zornitza Stark Gene: socs1 has been classified as Green List (High Evidence).
Mendeliome v1.1014 PLCG1 Zornitza Stark Marked gene: PLCG1 as ready
Mendeliome v1.1014 PLCG1 Zornitza Stark Gene: plcg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1014 PLCG1 Zornitza Stark Classified gene: PLCG1 as Amber List (moderate evidence)
Mendeliome v1.1014 PLCG1 Zornitza Stark Gene: plcg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1013 PLCG1 Zornitza Stark gene: PLCG1 was added
gene: PLCG1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: PLCG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLCG1 were set to 37422272
Phenotypes for gene: PLCG1 were set to Autoinflammatory syndrome, MONDO:0019751, PLCG1-related; Immune dysregulation
Mode of pathogenicity for gene: PLCG1 was set to Other
Review for gene: PLCG1 was set to AMBER
Added comment: Single 7yo proband presented with thrombocytopaenia and lymphadenopathy. De Novo , c.3062C>T, p.S1021F with functional testing supportive of GOF mechanism of disease
Sources: Expert Review
Disorders of immune dysregulation v0.178 PLCG1 Zornitza Stark Marked gene: PLCG1 as ready
Disorders of immune dysregulation v0.178 PLCG1 Zornitza Stark Gene: plcg1 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.178 PLCG1 Zornitza Stark Phenotypes for gene: PLCG1 were changed from Immune dysregulation to Autoinflammatory syndrome, MONDO:0019751, PLCG1-related; Immune dysregulation
Disorders of immune dysregulation v0.177 PLCG1 Zornitza Stark Classified gene: PLCG1 as Amber List (moderate evidence)
Disorders of immune dysregulation v0.177 PLCG1 Zornitza Stark Gene: plcg1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.133 PRUNE1 Luisa Weiss gene: PRUNE1 was added
gene: PRUNE1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PRUNE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRUNE1 were set to 33528536; 35379233
Phenotypes for gene: PRUNE1 were set to Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies MIM#617481
Review for gene: PRUNE1 was set to GREEN
Added comment: Case report of one consanguineous Iranian family with two children affected with spastic quadriplegic CP and a homozygous start loss of PRUNE1. The children also showed hypotonia and cerebellar atrophy. In addition, two additional cases in one large CP cohort study, one with homozygous mutation the other with compound heterozygous mutation/deletion.
Sources: Literature
Cerebral Palsy v1.133 PROC Luisa Weiss reviewed gene: PROC: Rating: GREEN; Mode of pathogenicity: None; Publications: 31700678, 20187890, 34531397; Phenotypes: Thrombophilia 3 due to protein C deficiency MIM#176860, Thrombophilia 3 due to protein C deficiency MIM#612304; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia - paediatric v1.9 TTI1 Zornitza Stark Phenotypes for gene: TTI1 were changed from Neurodevelopmental disorder, MONDO:0700092, TTI1-related to Neurodevelopmental disorder with microcephaly and movement abnormalities, MIM# 620445
Ataxia - paediatric v1.8 TTI1 Zornitza Stark Publications for gene: TTI1 were set to
Ataxia - paediatric v1.7 TTI1 Zornitza Stark reviewed gene: TTI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36724785; Phenotypes: Neurodevelopmental disorder with microcephaly and movement abnormalities, MIM# 620445; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5286 TTI1 Zornitza Stark Phenotypes for gene: TTI1 were changed from Neurodevelopmental disorder, MONDO:0700092, TTI1-related to Neurodevelopmental disorder with microcephaly and movement abnormalities, MIM# 620445
Intellectual disability syndromic and non-syndromic v0.5285 TTI1 Zornitza Stark Publications for gene: TTI1 were set to 26539891; 30315573
Microcephaly v1.218 TTI1 Zornitza Stark Publications for gene: TTI1 were set to DOI:https://doi.org/10.1016/j.ajhg.2023.01.006
Microcephaly v1.217 TTI1 Zornitza Stark reviewed gene: TTI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36724785; Phenotypes: Neurodevelopmental disorder with microcephaly and movement abnormalities, MIM# 620445; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.217 TTI1 Zornitza Stark Phenotypes for gene: TTI1 were changed from Neurodevelopmental disorder with microcephaly and movement abnormalities, MIM# 620445 to Neurodevelopmental disorder with microcephaly and movement abnormalities, MIM# 620445
Microcephaly v1.217 TTI1 Zornitza Stark Phenotypes for gene: TTI1 were changed from Neurodevelopmental disorder, MONDO:0700092, TTI1-related to to Neurodevelopmental disorder with microcephaly and movement abnormalities, MIM# 620445
Mendeliome v1.1012 TTI1 Zornitza Stark Phenotypes for gene: TTI1 were changed from Neurodevelopmental disorder, MONDO:0700092, TTI1-related to Neurodevelopmental disorder with microcephaly and movement abnormalities, MIM# 620445
Fetal anomalies v1.126 DCAF15 Zornitza Stark Marked gene: DCAF15 as ready
Fetal anomalies v1.126 DCAF15 Zornitza Stark Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.126 DCAF15 Zornitza Stark Phenotypes for gene: DCAF15 were changed from Cornelia de Lange syndrome to Cornelia de Lange syndrome, MONDO:0016033, DCAF15-related
Growth failure v1.67 DCAF15 Zornitza Stark Marked gene: DCAF15 as ready
Growth failure v1.67 DCAF15 Zornitza Stark Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Growth failure v1.67 DCAF15 Zornitza Stark Phenotypes for gene: DCAF15 were changed from Cornelia de Lange syndrome to Cornelia de Lange syndrome, MONDO:0016033, DCAF15-related
Intellectual disability syndromic and non-syndromic v0.5284 DCAF15 Zornitza Stark Marked gene: DCAF15 as ready
Intellectual disability syndromic and non-syndromic v0.5284 DCAF15 Zornitza Stark Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5284 DCAF15 Zornitza Stark Phenotypes for gene: DCAF15 were changed from Cornelia de Lange syndrome to Cornelia de Lange syndrome, MONDO:0016033, DCAF15-related
Mendeliome v1.1011 DCAF15 Zornitza Stark Marked gene: DCAF15 as ready
Mendeliome v1.1011 DCAF15 Zornitza Stark Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1011 DCAF15 Zornitza Stark Phenotypes for gene: DCAF15 were changed from Cornelia de Lange syndrome to Cornelia de Lange syndrome, MONDO:0016033, DCAF15-related
Hypertrichosis syndromes v0.43 DCAF15 Zornitza Stark Phenotypes for gene: DCAF15 were changed from Cornelia de Lange syndrome to Cornelia de Lange syndrome, MONDO:0016033, DCAF15-related
Microcephaly v1.216 DCAF15 Zornitza Stark Marked gene: DCAF15 as ready
Microcephaly v1.216 DCAF15 Zornitza Stark Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.216 DCAF15 Zornitza Stark Phenotypes for gene: DCAF15 were changed from Cornelia de Lange syndrome to Cornelia de Lange syndrome, MONDO:0016033, DCAF15-related
Microcephaly v1.215 DCAF15 Zornitza Stark Classified gene: DCAF15 as Amber List (moderate evidence)
Microcephaly v1.215 DCAF15 Zornitza Stark Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Hypertrichosis syndromes v0.42 DCAF15 Zornitza Stark Marked gene: DCAF15 as ready
Hypertrichosis syndromes v0.42 DCAF15 Zornitza Stark Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Hypertrichosis syndromes v0.42 DCAF15 Zornitza Stark Classified gene: DCAF15 as Amber List (moderate evidence)
Hypertrichosis syndromes v0.42 DCAF15 Zornitza Stark Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.133 POMGNT1 Luisa Weiss gene: POMGNT1 was added
gene: POMGNT1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: POMGNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMGNT1 were set to 33528536; 17881266; 34077496
Phenotypes for gene: POMGNT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 MIM# 253280; Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 3 MIM#613151; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3 MIM#613157; Retinitis pigmentosa 76 MIM#617123
Review for gene: POMGNT1 was set to GREEN
Added comment: One case report of two brothers diagnosed with CP and later found to have POMGnt1 biallelic mutations. In addition, two additional cases in two large CP cohort studies presenting with biallelic POMGnT1 mutations.
Sources: Literature
Differences of Sex Development v0.279 PTCH1 Zornitza Stark Marked gene: PTCH1 as ready
Differences of Sex Development v0.279 PTCH1 Zornitza Stark Gene: ptch1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.279 PTCH1 Zornitza Stark Classified gene: PTCH1 as Amber List (moderate evidence)
Differences of Sex Development v0.279 PTCH1 Zornitza Stark Gene: ptch1 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.201 PDHA1 Sangavi Sivagnanasundram reviewed gene: PDHA1: Rating: RED; Mode of pathogenicity: None; Publications: 34138529; Phenotypes: Primary Pyruvate Dehydrogenase Complex Deficiency MIM 312170; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.133 POGZ Luisa Weiss gene: POGZ was added
gene: POGZ was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: POGZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POGZ were set to 33528536
Phenotypes for gene: POGZ were set to White-Sutton syndrome MIM#616364
Review for gene: POGZ was set to AMBER
Added comment: 2 cases in one large cohort study, one with a likely pathogenic mutation and one with a pathogenic mutation.
Sources: Literature
Hereditary Neuropathy - complex v0.201 NTRK1 Sangavi Sivagnanasundram reviewed gene: NTRK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301726, 11310631; Phenotypes: hereditary sensory and autonomic neuropathy type 4 MONDO:0009746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.133 PNPLA6 Luisa Weiss changed review comment from: 2 case reports of patients initially reported as having CP but later re-diagnosed as having spastic paraplegia Type 39 due to biallelic PNPLA6 mutations. Significant phenotypic overlap with childhood onset of sometimes very slowly progressive motor disease
Sources: Literature; to: 2 case reports of patients initially reported as having CP but later re-diagnosed as having spastic paraplegia Type 39 due to biallelic PNPLA6 mutations. Significant phenotypic overlap with HSP 39: childhood onset of potentially very slowly progressive motor disease
Sources: Literature
Cerebral Palsy v1.133 PNPLA6 Luisa Weiss gene: PNPLA6 was added
gene: PNPLA6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PNPLA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA6 were set to 34816117; 34364746
Phenotypes for gene: PNPLA6 were set to Boucher-Neuhauser syndrome MIM#215470; Oliver-McFarlane syndrome MIM#275400; Spastic paraplegia 39 MIM#612020
Review for gene: PNPLA6 was set to AMBER
Added comment: 2 case reports of patients initially reported as having CP but later re-diagnosed as having spastic paraplegia Type 39 due to biallelic PNPLA6 mutations. Significant phenotypic overlap with childhood onset of sometimes very slowly progressive motor disease
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.132 TBX6 Chirag Patel Classified gene: TBX6 as Green List (high evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.132 TBX6 Chirag Patel Gene: tbx6 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.131 TBX6 Chirag Patel gene: TBX6 was added
gene: TBX6 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Literature
Mode of inheritance for gene: TBX6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBX6 were set to PMID: 36112137, 36161696
Phenotypes for gene: TBX6 were set to Mayer-Rokitansky-Küster-Hauser syndrome; Combined skeletal-kidney dysplasia syndrome
Review for gene: TBX6 was set to GREEN
gene: TBX6 was marked as current diagnostic
Added comment: TBX6 encodes transcription-factor box 6, a transcription factor critical to paraxial mesoderm segmentation and somitogenesis during embryonic development. TBX6 haploinsufficiency is believed to drive the skeletal and kidney phenotypes associated with the 16p11.2 deletion syndrome.

Ma et al (2022) reported 16 rare variants in TBX6 from Mayer-Rokitansky-Küster-Hauser syndrome cohort (1 truncating, 15 VUS). They observed a significant mutational burden of TBX6 in affected individuals vs controls. Of the 15 variants with uncertain effects, 7 were shown to induce a loss-of-function effect through various mechanisms (i.e. impaired normal splicing of TBX6 messenger RNA, decreased protein expression, perturbed transcriptional activity, and protein mislocalization). There was observed incomplete penetrance and variable expressivity in families carrying deleterious variants.

Li et al (2022) reported 7 individuals with vertebral and rib malformations and structural kidney differences associated with heterozygous TBX6 gene deletion in trans with a hypomorphic TBX6 allele or biallelic TBX6 variants.
Sources: Literature
Mendeliome v1.1010 TBX6 Chirag Patel reviewed gene: TBX6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36112137, 36161696; Phenotypes: Mayer-Rokitansky-Küster-Hauser syndrome, Combined skeletal-kidney dysplasia syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5283 WBP4 Chirag Patel Classified gene: WBP4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5283 WBP4 Chirag Patel Gene: wbp4 has been classified as Green List (High Evidence).
Mendeliome v1.1010 WBP4 Chirag Patel Classified gene: WBP4 as Green List (high evidence)
Mendeliome v1.1010 WBP4 Chirag Patel Gene: wbp4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5282 WBP4 Chirag Patel gene: WBP4 was added
gene: WBP4 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: WBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WBP4 were set to Neurodevelopmental disorder
Review for gene: WBP4 was set to GREEN
gene: WBP4 was marked as current diagnostic
Added comment: ESHG 2023:
11 individuals from 8 families with homozygous LOF variants in WBP4 gene (4 different variants). Presentation of severe DD and ID, hypotonia, abnormal outer ears, and varying congenital anomalies. WBP4 is spliceosome protein which binds/interacts with SNRNP200. In vivo and in vitro studies previously showed WBP4 enhances splicing and regulates alternative splicing. Patient fibroblasts showed loss of expression of WBP4. RNA sequencing analysis showed abnormal splicing patterns. Proposed spliceosomopathy.
Sources: Other
Mendeliome v1.1009 WBP4 Chirag Patel gene: WBP4 was added
gene: WBP4 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: WBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WBP4 were set to Neurodevelopmental disorder
Review for gene: WBP4 was set to GREEN
gene: WBP4 was marked as current diagnostic
Added comment: ESHG 2023:
11 individuals from 8 families with homozygous LOF variants in WBP4 gene (4 different variants). Presentation of severe DD and ID, hypotonia, abnormal outer ears, and varying congenital anomalies. WBP4 is spliceosome protein which binds/interacts with SNRNP200. In vivo and in vitro studies previously showed WBP4 enhances splicing and regulates alternative splicing. Patient fibroblasts showed loss of expression of WBP4. RNA sequencing analysis showed abnormal splicing patterns. Proposed spliceosomopathy.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5281 KDM2A Chirag Patel Classified gene: KDM2A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5281 KDM2A Chirag Patel Gene: kdm2a has been classified as Green List (High Evidence).
Mendeliome v1.1008 KDM2A Chirag Patel Classified gene: KDM2A as Green List (high evidence)
Mendeliome v1.1008 KDM2A Chirag Patel Gene: kdm2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5280 KDM2A Chirag Patel gene: KDM2A was added
gene: KDM2A was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: KDM2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KDM2A were set to Neurodevelopmental disorder
Review for gene: KDM2A was set to GREEN
gene: KDM2A was marked as current diagnostic
Added comment: ESHG 2023:
14 patients with de novo HTZ variants in KDM2A (5 x truncating, 9 x missense)
Presentation with DD, ID (mild), seizures, growth retardation, and dysmorphism.

Functional studies:
-patient blood showed aberrant genome wide methylation profile - potential episignature
-HEK293T cells showed altered subcellular localisation of KDM2A
-Drosophila models showed variants caused neurotoxicity
Sources: Other
Mendeliome v1.1007 KDM2A Chirag Patel gene: KDM2A was added
gene: KDM2A was added to Mendeliome. Sources: Other
Mode of inheritance for gene: KDM2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KDM2A were set to Neurodevelopmental disorder
Review for gene: KDM2A was set to GREEN
gene: KDM2A was marked as current diagnostic
Added comment: ESHG 2023:
14 patients with de novo HTZ variants in KDM2A (5 x truncating, 9 x missense)
Presentation with DD, ID (mild), seizures, growth retardation, and dysmorphism.

Functional studies:
-patient blood showed aberrant genome wide methylation profile - potential episignature
-HEK293T cells showed altered subcellular localisation of KDM2A
-Drosophila models showed variants caused neurotoxicity
Sources: Other
Microcephaly v1.214 PIP5K1C Chirag Patel Classified gene: PIP5K1C as Green List (high evidence)
Microcephaly v1.214 PIP5K1C Chirag Patel Gene: pip5k1c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5279 PIP5K1C Chirag Patel Classified gene: PIP5K1C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5279 PIP5K1C Chirag Patel Gene: pip5k1c has been classified as Green List (High Evidence).
Microcephaly v1.213 PIP5K1C Chirag Patel gene: PIP5K1C was added
gene: PIP5K1C was added to Microcephaly. Sources: Other
Mode of inheritance for gene: PIP5K1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PIP5K1C were set to Neurodevelopmental disorder and microcephaly
Review for gene: PIP5K1C was set to GREEN
gene: PIP5K1C was marked as current diagnostic
Added comment: ESHG 2023:
9 unrelated patients with de novo missense variants in PIP5K1C (3 x recurrent variants).
Presentation with DD/ID (mod-profound), microcephaly, seizures, visual impairment, and dysmorphism.

PIP5K1C is one of the phosphoinositolides, which control membrane composition of organelles and varying cellular processes. Patient fibroblasts showed increased PI(4,5)P2 levels, altered PI(4,5)P2 composition of early endosomes, and impaired endocytosis trafficking. Drosophila models showed microcephaly and ocular phenotype.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5278 PIP5K1C Chirag Patel gene: PIP5K1C was added
gene: PIP5K1C was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: PIP5K1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PIP5K1C were set to Neurodevelopmental disorder and microcephaly
Review for gene: PIP5K1C was set to GREEN
gene: PIP5K1C was marked as current diagnostic
Added comment: ESHG 2023:
9 unrelated patients with de novo missense variants in PIP5K1C (3 x recurrent variants).
Presentation with DD/ID (mod-profound), microcephaly, seizures, visual impairment, and dysmorphism.

PIP5K1C is one of the phosphoinositolides, which control membrane composition of organelles and varying cellular processes. Patient fibroblasts showed increased PI(4,5)P2 levels, altered PI(4,5)P2 composition of early endosomes, and impaired endocytosis trafficking. Drosophila models showed microcephaly and ocular phenotype.
Sources: Other
Mendeliome v1.1006 PIP5K1C Chirag Patel Classified gene: PIP5K1C as Green List (high evidence)
Mendeliome v1.1006 PIP5K1C Chirag Patel Gene: pip5k1c has been classified as Green List (High Evidence).
Mendeliome v1.1005 PIP5K1C Chirag Patel reviewed gene: PIP5K1C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder and microcephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5277 NSUN6 Chirag Patel changed review comment from: Sufficient evidence for upgrade; to: Drosophila KO showed locomotion defects and reduced learning ability. Sufficient evidence for upgrade
Mendeliome v1.1005 NSUN6 Chirag Patel changed review comment from: Sufficient evidence for upgrade; to: Drosophila KO showed locomotion defects and reduced learning ability. Sufficient evidence for upgrade
Intellectual disability syndromic and non-syndromic v0.5277 NSUN6 Chirag Patel Classified gene: NSUN6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5277 NSUN6 Chirag Patel Gene: nsun6 has been classified as Green List (High Evidence).
Mendeliome v1.1005 NSUN6 Chirag Patel Classified gene: NSUN6 as Green List (high evidence)
Mendeliome v1.1005 NSUN6 Chirag Patel Gene: nsun6 has been classified as Green List (High Evidence).
Mendeliome v1.1004 NSUN6 Chirag Patel reviewed gene: NSUN6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.5276 NSUN6 Chirag Patel reviewed gene: NSUN6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5276 INTS13 Chirag Patel Classified gene: INTS13 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5276 INTS13 Chirag Patel Gene: ints13 has been classified as Green List (High Evidence).
Ciliopathies v1.43 INTS13 Chirag Patel Classified gene: INTS13 as Green List (high evidence)
Ciliopathies v1.43 INTS13 Chirag Patel Gene: ints13 has been classified as Green List (High Evidence).
Clefting disorders v0.238 INTS13 Chirag Patel Classified gene: INTS13 as Green List (high evidence)
Clefting disorders v0.238 INTS13 Chirag Patel Gene: ints13 has been classified as Green List (High Evidence).
Fetal anomalies v1.125 INTS13 Chirag Patel Classified gene: INTS13 as Green List (high evidence)
Fetal anomalies v1.125 INTS13 Chirag Patel Gene: ints13 has been classified as Green List (High Evidence).
Mendeliome v1.1004 INTS13 Chirag Patel Classified gene: INTS13 as Green List (high evidence)
Mendeliome v1.1004 INTS13 Chirag Patel Gene: ints13 has been classified as Green List (High Evidence).
Ciliopathies v1.42 INTS13 Chirag Patel gene: INTS13 was added
gene: INTS13 was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: INTS13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS13 were set to PMID: 36229431
Phenotypes for gene: INTS13 were set to Oral-facial-digital syndrome
Review for gene: INTS13 was set to GREEN
gene: INTS13 was marked as current diagnostic
Added comment: 2 families with 4 affected individuals with Oral-facial-digital (OFD) phenotype. Homozygosity mapping and WES found 2 homozygous variants in INTS13 gene. This is a subunit of the Integrator complex, which associates with RNA Polymerase II and cleaves nascent RNA to modulate gene expression. Variants segregated with disease. Depletion of INTS13 disrupts ciliogenesis in human cultured cells and causes dysregulation of a broad collection of ciliary genes. Knockdown in Xenopus embryos leads to motile cilia anomalies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5275 INTS13 Chirag Patel gene: INTS13 was added
gene: INTS13 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: INTS13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS13 were set to PMID: 36229431
Phenotypes for gene: INTS13 were set to Oral-facial-digital syndrome
Review for gene: INTS13 was set to GREEN
Added comment: 2 families with 4 affected individuals with Oral-facial-digital (OFD) phenotype. Homozygosity mapping and WES found 2 homozygous variants in INTS13 gene. This is a subunit of the Integrator complex, which associates with RNA Polymerase II and cleaves nascent RNA to modulate gene expression. Variants segregated with disease. Depletion of INTS13 disrupts ciliogenesis in human cultured cells and causes dysregulation of a broad collection of ciliary genes. Knockdown in Xenopus embryos leads to motile cilia anomalies.
Sources: Literature
Fetal anomalies v1.124 INTS13 Chirag Patel gene: INTS13 was added
gene: INTS13 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: INTS13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS13 were set to PMID: 36229431
Phenotypes for gene: INTS13 were set to Oral-facial-digital syndrome
Review for gene: INTS13 was set to GREEN
gene: INTS13 was marked as current diagnostic
Added comment: 2 families with 4 affected individuals with Oral-facial-digital (OFD) phenotype. Homozygosity mapping and WES found 2 homozygous variants in INTS13 gene. This is a subunit of the Integrator complex, which associates with RNA Polymerase II and cleaves nascent RNA to modulate gene expression. Variants segregated with disease. Depletion of INTS13 disrupts ciliogenesis in human cultured cells and causes dysregulation of a broad collection of ciliary genes. Knockdown in Xenopus embryos leads to motile cilia anomalies.
Sources: Literature
Clefting disorders v0.237 INTS13 Chirag Patel gene: INTS13 was added
gene: INTS13 was added to Clefting disorders. Sources: Literature
Mode of inheritance for gene: INTS13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS13 were set to PMID: 36229431
Phenotypes for gene: INTS13 were set to Oral-facial-digital syndrome
Review for gene: INTS13 was set to GREEN
gene: INTS13 was marked as current diagnostic
Added comment: 2 families with 4 affected individuals with Oral-facial-digital (OFD) phenotype. Homozygosity mapping and WES found 2 homozygous variants in INTS13 gene. This is a subunit of the Integrator complex, which associates with RNA Polymerase II and cleaves nascent RNA to modulate gene expression. Variants segregated with disease. Depletion of INTS13 disrupts ciliogenesis in human cultured cells and causes dysregulation of a broad collection of ciliary genes. Knockdown in Xenopus embryos leads to motile cilia anomalies.
Sources: Literature
Mendeliome v1.1003 INTS13 Chirag Patel gene: INTS13 was added
gene: INTS13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: INTS13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS13 were set to PMID: 36229431
Phenotypes for gene: INTS13 were set to Oral-facial-digital syndrome
Review for gene: INTS13 was set to GREEN
gene: INTS13 was marked as current diagnostic
Added comment: 2 families with 4 affected individuals with Oral-facial-digital (OFD) phenotype. Homozygosity mapping and WES found 2 homozygous variants in INTS13 gene. This is a subunit of the Integrator complex, which associates with RNA Polymerase II and cleaves nascent RNA to modulate gene expression. Variants segregated with disease. Depletion of INTS13 disrupts ciliogenesis in human cultured cells and causes dysregulation of a broad collection of ciliary genes. Knockdown in Xenopus embryos leads to motile cilia anomalies.
Sources: Literature
Differences of Sex Development v0.278 SLC20A1 Chirag Patel Classified gene: SLC20A1 as Green List (high evidence)
Differences of Sex Development v0.278 SLC20A1 Chirag Patel Gene: slc20a1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.277 SLC20A1 Chirag Patel gene: SLC20A1 was added
gene: SLC20A1 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: SLC20A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC20A1 were set to PMID: 32850778, 27013921
Phenotypes for gene: SLC20A1 were set to Bladder-Exstrophy-Epispadias Complex (BEEC)
Review for gene: SLC20A1 was set to GREEN
gene: SLC20A1 was marked as current diagnostic
Added comment: Three individuals with BEEC and animal model supporting role of this gene in urinary tract and urorectal development.
Sources: Literature
Ciliary Dyskinesia v1.33 TUBB4B Chirag Patel Classified gene: TUBB4B as Green List (high evidence)
Ciliary Dyskinesia v1.33 TUBB4B Chirag Patel Gene: tubb4b has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.203 TUBB4B Chirag Patel reviewed gene: TUBB4B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary ciliary dyskinesia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v1.157 TUBB4B Chirag Patel reviewed gene: TUBB4B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary ciliary dyskinesia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliary Dyskinesia v1.32 TUBB4B Chirag Patel gene: TUBB4B was added
gene: TUBB4B was added to Ciliary Dyskinesia. Sources: Other
Mode of inheritance for gene: TUBB4B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TUBB4B were set to Primary ciliary dyskinesia
Review for gene: TUBB4B was set to GREEN
Added comment: ESHG 2023:
De novo heterozygous TUBB4B variants found in:
-8 patients with recurrent respiratory infections (PCD phenotype), irregular corpus callosum, and dilated ventricles (suggesting motile cilia anomaly)
-3 patients with retinal dystrophy, SNHL, and PCD respiratory issues

Functional studies:
-variants showed decreased cilia number and length, and mislocalisation of dyenin motors
-mouse models had decreased cilia number and length in trachea, and reduction in cilia in choroid plexus cells leading to hydrocephaly
Sources: Other
Mendeliome v1.1002 TUBB4B Chirag Patel reviewed gene: TUBB4B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary ciliary dyskinesia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.113 PTCH1 Chirag Patel Classified gene: PTCH1 as Amber List (moderate evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.113 PTCH1 Chirag Patel Gene: ptch1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.276 PTCH1 Chirag Patel gene: PTCH1 was added
gene: PTCH1 was added to Differences of Sex Development. Sources: Other
Mode of inheritance for gene: PTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PTCH1 were set to Bladder exstrophy and epispadias complex (BEEC)
Review for gene: PTCH1 was set to AMBER
Added comment: ESHG 2023:
9 individuals with BEEC (WES/Sanger) with 9 x rare HTZ variants in PTCH1 (2 de novo, 7 inherited unaffected parent). No clinical features of Gorlin syndrome and variants not seen in Gorlin syndrome.

Zebrafish models:
a) knock out and knock in (1 missense variant) models showed no phenotype
b) co-injection of WT and missense variant led to altered cloaca on D5.
Proposed mechanism is dominant negative effect.
Sources: Other
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.112 PTCH1 Chirag Patel gene: PTCH1 was added
gene: PTCH1 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic. Sources: Other
Mode of inheritance for gene: PTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PTCH1 were set to Bladder exstrophy and epispadias complex (BEEC)
Review for gene: PTCH1 was set to AMBER
Added comment: ESHG 2023:
9 individuals with BEEC (WES/Sanger) with 9 x rare HTZ variants in PTCH1 (2 de novo, 7 inherited unaffected parent). No clinical features of Gorlin syndrome and variants not seen in Gorlin syndrome.

Zebrafish models:
a) knock out and knock in (1 missense variant) models showed no phenotype
b) co-injection of WT and missense variant led to altered cloaca on D5.
Proposed mechanism is dominant negative effect.
Sources: Other
Differences of Sex Development v0.276 PTCH1 Chirag Patel gene: PTCH1 was added
gene: PTCH1 was added to Differences of Sex Development. Sources: Other
Mode of inheritance for gene: PTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PTCH1 were set to Bladder exstrophy and epispadias complex (BEEC)
Review for gene: PTCH1 was set to AMBER
Added comment: ESHG 2023:
9 individuals with BEEC (WES/Sanger) with 9 x rare HTZ variants in PTCH1 (2 de novo, 7 inherited unaffected parent). No clinical features of Gorlin syndrome and variants not seen in Gorlin syndrome.

Zebrafish models:
a) knock out and knock in (1 missense variant) models showed no phenotype
b) co-injection of WT and missense variant led to altered cloaca on D5.
Proposed mechanism is dominant negative effect.
Sources: Other
Mendeliome v1.1002 PTCH1 Chirag Patel reviewed gene: PTCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bladder exstrophy and epispadias complex (BEEC); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.123 PTCH1 Chirag Patel reviewed gene: PTCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bladder exstrophy and epispadias complex (BEEC); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5274 DCAF15 Chirag Patel Classified gene: DCAF15 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5274 DCAF15 Chirag Patel Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5274 DCAF15 Chirag Patel Classified gene: DCAF15 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5274 DCAF15 Chirag Patel Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.212 DCAF15 Chirag Patel gene: DCAF15 was added
gene: DCAF15 was added to Microcephaly. Sources: Other
Mode of inheritance for gene: DCAF15 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DCAF15 were set to Cornelia de Lange syndrome
Review for gene: DCAF15 was set to AMBER
Added comment: ESHG 2023:
3 unrelated cases with CdLS (1 x TOP with MCA, 1 x death @20mths, 1 x living child)
Features suggestive of CdLS - DD, microcephaly, CHD, dysmorphism, visual/hearing impairment.

WES identified recurrent de novo variant (p.Ser470Phe) in DCAF15 gene. This mediates ubiquitination and degradation of target proteins, and interacts with cohesin complex members (SMC1/SMC3).

Protein analysis from individuals showed increased accumulation of ubiquitination-modified proteins and SM3 (GOF mechanism). EpiSign analysis showed same DNA methylation pattern as other CdLS cases/genes. Zebrafish model showed reduced body length, reduced head size, reduced oligodendrocytes, heart defect, aberrant motor neurons, and abnormal response to visual/auditory stimuli.
Sources: Other
Hypertrichosis syndromes v0.41 DCAF15 Chirag Patel gene: DCAF15 was added
gene: DCAF15 was added to Hypertrichosis syndromes. Sources: Other
Mode of inheritance for gene: DCAF15 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DCAF15 were set to Cornelia de Lange syndrome
Review for gene: DCAF15 was set to AMBER
Added comment: ESHG 2023:
3 unrelated cases with CdLS (1 x TOP with MCA, 1 x death @20mths, 1 x living child)
Features suggestive of CdLS - DD, microcephaly, CHD, dysmorphism, visual/hearing impairment.

WES identified recurrent de novo variant (p.Ser470Phe) in DCAF15 gene. This mediates ubiquitination and degradation of target proteins, and interacts with cohesin complex members (SMC1/SMC3).

Protein analysis from individuals showed increased accumulation of ubiquitination-modified proteins and SM3 (GOF mechanism). EpiSign analysis showed same DNA methylation pattern as other CdLS cases/genes. Zebrafish model showed reduced body length, reduced head size, reduced oligodendrocytes, heart defect, aberrant motor neurons, and abnormal response to visual/auditory stimuli.
Sources: Other
Hypertrichosis syndromes v0.41 DCAF15 Chirag Patel gene: DCAF15 was added
gene: DCAF15 was added to Hypertrichosis syndromes. Sources: Other
Mode of inheritance for gene: DCAF15 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DCAF15 were set to Cornelia de Lange syndrome
Review for gene: DCAF15 was set to AMBER
Added comment: ESHG 2023:
3 unrelated cases with CdLS (1 x TOP with MCA, 1 x death @20mths, 1 x living child)
Features suggestive of CdLS - DD, microcephaly, CHD, dysmorphism, visual/hearing impairment.

WES identified recurrent de novo variant (p.Ser470Phe) in DCAF15 gene. This mediates ubiquitination and degradation of target proteins, and interacts with cohesin complex members (SMC1/SMC3).

Protein analysis from individuals showed increased accumulation of ubiquitination-modified proteins and SM3 (GOF mechanism). EpiSign analysis showed same DNA methylation pattern as other CdLS cases/genes. Zebrafish model showed reduced body length, reduced head size, reduced oligodendrocytes, heart defect, aberrant motor neurons, and abnormal response to visual/auditory stimuli.
Sources: Other
Mendeliome v1.1002 DCAF15 Chirag Patel Classified gene: DCAF15 as Amber List (moderate evidence)
Mendeliome v1.1002 DCAF15 Chirag Patel Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.212 DCAF15 Chirag Patel gene: DCAF15 was added
gene: DCAF15 was added to Microcephaly. Sources: Other
Mode of inheritance for gene: DCAF15 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DCAF15 were set to Cornelia de Lange syndrome
Review for gene: DCAF15 was set to AMBER
Added comment: ESHG 2023:
3 unrelated cases with CdLS (1 x TOP with MCA, 1 x death @20mths, 1 x living child)
Features suggestive of CdLS - DD, microcephaly, CHD, dysmorphism, visual/hearing impairment.

WES identified recurrent de novo variant (p.Ser470Phe) in DCAF15 gene. This mediates ubiquitination and degradation of target proteins, and interacts with cohesin complex members (SMC1/SMC3).

Protein analysis from individuals showed increased accumulation of ubiquitination-modified proteins and SM3 (GOF mechanism). EpiSign analysis showed same DNA methylation pattern as other CdLS cases/genes. Zebrafish model showed reduced body length, reduced head size, reduced oligodendrocytes, heart defect, aberrant motor neurons, and abnormal response to visual/auditory stimuli.
Sources: Other
Fetal anomalies v1.123 DCAF15 Chirag Patel Classified gene: DCAF15 as Amber List (moderate evidence)
Fetal anomalies v1.123 DCAF15 Chirag Patel Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Growth failure v1.66 DCAF15 Chirag Patel Classified gene: DCAF15 as Amber List (moderate evidence)
Growth failure v1.66 DCAF15 Chirag Patel Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5273 DCAF15 Chirag Patel gene: DCAF15 was added
gene: DCAF15 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: DCAF15 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DCAF15 were set to Cornelia de Lange syndrome
Review for gene: DCAF15 was set to AMBER
Added comment: ESHG 2023:
3 unrelated cases with CdLS (1 x TOP with MCA, 1 x death @20mths, 1 x living child)
Features suggestive of CdLS - DD, microcephaly, CHD, dysmorphism, visual/hearing impairment.

WES identified recurrent de novo variant (p.Ser470Phe) in DCAF15 gene. This mediates ubiquitination and degradation of target proteins, and interacts with cohesin complex members (SMC1/SMC3).

Protein analysis from individuals showed increased accumulation of ubiquitination-modified proteins and SM3 (GOF mechanism). EpiSign analysis showed same DNA methylation pattern as other CdLS cases/genes. Zebrafish model showed reduced body length, reduced head size, reduced oligodendrocytes, heart defect, aberrant motor neurons, and abnormal response to visual/auditory stimuli.
Sources: Other
Mendeliome v1.1001 DCAF15 Chirag Patel gene: DCAF15 was added
gene: DCAF15 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: DCAF15 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DCAF15 were set to Cornelia de Lange syndrome
Review for gene: DCAF15 was set to AMBER
Added comment: ESHG 2023:
3 unrelated cases with CdLS (1 x TOP with MCA, 1 x death @20mths, 1 x living child)
Features suggestive of CdLS - DD, microcephaly, CHD, dysmorphism, visual/hearing impairment.

WES identified recurrent de novo variant (p.Ser470Phe) in DCAF15 gene. This mediates ubiquitination and degradation of target proteins, and interacts with cohesin complex members (SMC1/SMC3).

Protein analysis from individuals showed increased accumulation of ubiquitination-modified proteins and SM3 (GOF mechanism). EpiSign analysis showed same DNA methylation pattern as other CdLS cases/genes. Zebrafish model showed reduced body length, reduced head size, reduced oligodendrocytes, heart defect, aberrant motor neurons, and abnormal response to visual/auditory stimuli.
Sources: Other
Growth failure v1.65 DCAF15 Chirag Patel gene: DCAF15 was added
gene: DCAF15 was added to Growth failure. Sources: Other
Mode of inheritance for gene: DCAF15 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DCAF15 were set to Cornelia de Lange syndrome
Review for gene: DCAF15 was set to AMBER
Added comment: ESHG 2023:
3 unrelated cases with CdLS (1 x TOP with MCA, 1 x death @20mths, 1 x living child)
Features suggestive of CdLS - DD, microcephaly, CHD, dysmorphism, visual/hearing impairment.

WES identified recurrent de novo variant (p.Ser470Phe) in DCAF15 gene. This mediates ubiquitination and degradation of target proteins, and interacts with cohesin complex members (SMC1/SMC3).

Protein analysis from individuals showed increased accumulation of ubiquitination-modified proteins and SM3 (GOF mechanism). EpiSign analysis showed same DNA methylation pattern as other CdLS cases/genes. Zebrafish model showed reduced body length, reduced head size, reduced oligodendrocytes, heart defect, aberrant motor neurons, and abnormal response to visual/auditory stimuli.
Sources: Other
Fetal anomalies v1.122 DCAF15 Chirag Patel gene: DCAF15 was added
gene: DCAF15 was added to Fetal anomalies. Sources: Other
Mode of inheritance for gene: DCAF15 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DCAF15 were set to Cornelia de Lange syndrome
Review for gene: DCAF15 was set to AMBER
Added comment: ESHG 2023:
3 unrelated cases with CdLS (1 x TOP with MCA, 1 x death @20mths, 1 x living child)
Features suggestive of CdLS - DD, microcephaly, CHD, dysmorphism, visual/hearing impairment.

WES identified recurrent de novo variant (p.Ser470Phe) in DCAF15 gene. This mediates ubiquitination and degradation of target proteins, and interacts with cohesin complex members (SMC1/SMC3).

Protein analysis from individuals showed increased accumulation of ubiquitination-modified proteins and SM3 (GOF mechanism). EpiSign analysis showed same DNA methylation pattern as other CdLS cases/genes. Zebrafish model showed reduced body length, reduced head size, reduced oligodendrocytes, heart defect, aberrant motor neurons, and abnormal response to visual/auditory stimuli.
Sources: Other
Hereditary Neuropathy - complex v0.201 MFF Zornitza Stark Marked gene: MFF as ready
Hereditary Neuropathy - complex v0.201 MFF Zornitza Stark Gene: mff has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.201 MFF Zornitza Stark Phenotypes for gene: MFF were changed from Leigh-like syndrome, developmental delay, optic atrophy, seizures, sensory-motor neuropathy with SNCV, Leigh syndrome-like MRI brain (T2 high signal of basal ganglia and subthalamic nucleus) to Encephalopathy due to defective mitochondrial and peroxisomal fission 2 MIM# 617086
Hereditary Neuropathy - complex v0.200 MFF Zornitza Stark Publications for gene: MFF were set to
Hereditary Neuropathy - complex v0.199 MFF Zornitza Stark Classified gene: MFF as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.199 MFF Zornitza Stark Gene: mff has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.198 LYST Zornitza Stark Marked gene: LYST as ready
Hereditary Neuropathy - complex v0.198 LYST Zornitza Stark Gene: lyst has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.198 LYST Zornitza Stark Phenotypes for gene: LYST were changed from Partial albinism, immunodeficiency, cerebellar atrophy, sensory-motor axonal neuropathy; Chediak-Higashi syndrome, 214500 to Chediak-Higashi syndrome MIM#214500; MONDO:0008963
Hereditary Neuropathy - complex v0.197 LYST Zornitza Stark Publications for gene: LYST were set to
Hereditary Neuropathy - complex v0.196 KARS Zornitza Stark Marked gene: KARS as ready
Hereditary Neuropathy - complex v0.196 KARS Zornitza Stark Gene: kars has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.196 KARS Zornitza Stark Phenotypes for gene: KARS were changed from HMSN; Charcot Marie Tooth disease, recessive intermediate, B, 613641; Deafness, autosomal recessive 89, 613916 to Charcot-Marie-Tooth disease, recessive intermediate, B (MIM#613641; MONDO:0013338)
Hereditary Neuropathy - complex v0.195 KARS Zornitza Stark Publications for gene: KARS were set to
Hereditary Neuropathy - complex v0.194 KARS Zornitza Stark Classified gene: KARS as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.194 KARS Zornitza Stark Gene: kars has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.193 HMBS Zornitza Stark Marked gene: HMBS as ready
Hereditary Neuropathy - complex v0.193 HMBS Zornitza Stark Gene: hmbs has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.193 HMBS Zornitza Stark Phenotypes for gene: HMBS were changed from Acute intermittent porphyria; dHMN/dSMA to Porphyria, acute intermittent MIM#176000; MONDO:0008294
Hereditary Neuropathy - complex v0.192 HMBS Zornitza Stark Publications for gene: HMBS were set to
Hereditary Neuropathy - complex v0.191 HMBS Zornitza Stark reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31205461; Phenotypes: Porphyria, acute intermittent MIM#176000, MONDO:0008294; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.191 HADHB Zornitza Stark Marked gene: HADHB as ready
Hereditary Neuropathy - complex v0.191 HADHB Zornitza Stark Gene: hadhb has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.191 HADHB Zornitza Stark Phenotypes for gene: HADHB were changed from Trifunctional protein deficiency, 609015; HMSN to Mitochondrial Trifunctional Protein Deficiency 2 with Myopathy and Neuropathy MIM#320300
Hereditary Neuropathy - complex v0.190 HADHB Zornitza Stark Publications for gene: HADHB were set to
Hereditary Neuropathy - complex v0.189 HADHB Zornitza Stark reviewed gene: HADHB: Rating: AMBER; Mode of pathogenicity: None; Publications: 37388542; Phenotypes: Mitochondrial Trifunctional Protein Deficiency 2 with Myopathy and Neuropathy MIM#320300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.189 HADHB Zornitza Stark Classified gene: HADHB as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.189 HADHB Zornitza Stark Gene: hadhb has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.188 HADHA Zornitza Stark Marked gene: HADHA as ready
Hereditary Neuropathy - complex v0.188 HADHA Zornitza Stark Gene: hadha has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.188 HADHA Zornitza Stark Phenotypes for gene: HADHA were changed from Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency to LCHAD deficiency MIM#609016; Mitochondrial trifunctional protein deficiency MIM#609015
Hereditary Neuropathy - complex v0.187 HADHA Zornitza Stark Publications for gene: HADHA were set to
Hereditary Neuropathy - complex v0.186 GSN Zornitza Stark Marked gene: GSN as ready
Hereditary Neuropathy - complex v0.186 GSN Zornitza Stark Gene: gsn has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.186 GSN Zornitza Stark Phenotypes for gene: GSN were changed from Amyloidosis, Finnish type; HMSN to Amyloidosis, Finnish type MIM#105120
Hereditary Neuropathy - complex v0.185 GSN Zornitza Stark Publications for gene: GSN were set to
Hereditary Neuropathy - complex v0.184 GSN Zornitza Stark Mode of inheritance for gene: GSN was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.183 GBE1 Zornitza Stark Marked gene: GBE1 as ready
Hereditary Neuropathy - complex v0.183 GBE1 Zornitza Stark Gene: gbe1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.183 GBE1 Zornitza Stark Phenotypes for gene: GBE1 were changed from Late-onset, cognitive impairment, spasticity, sensory-motor axonal neuropathy, bladder dysfunction, cerebellar and extrapyramidal signs also seen, periventricular white matter abnormalities on MRI to Polyglucosan body disease, adult form MIM#263570; Late-onset, cognitive impairment, spasticity, sensory-motor axonal neuropathy, bladder dysfunction, cerebellar and extrapyramidal signs also seen, periventricular white matter abnormalities on MRI
Hereditary Neuropathy - complex v0.182 GBE1 Zornitza Stark Publications for gene: GBE1 were set to
Mendeliome v1.1000 PMVK Zornitza Stark Phenotypes for gene: PMVK were changed from Porokeratosis 1, multiple types, MIM# 175800 to Porokeratosis 1, multiple types, MIM# 175800; Autoinflammatory syndrome, MONDO:0019751, PMVK-related
Mendeliome v1.999 PMVK Zornitza Stark Publications for gene: PMVK were set to 26202976
Mendeliome v1.998 PMVK Zornitza Stark Mode of inheritance for gene: PMVK was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.997 PMVK Zornitza Stark changed review comment from: Association with auto inflammatory syndrome:

Five-year-old girl with recurring hyperinflammatory episodes initially presenting at 9mo with fever, arthritis, aphthous stomatitis and maculopapular rash with homozygous variant in PMVK p.Val131Ala (NM_006556.4: c.392T>C) with clinical overlap with MVK deficiency. Supportive functional data. Second patient, 6yo boy with compound heterozygous c.329G >A (p. Arg110Gln) and c.316G >A (p. Val106Met) mutations in trans configuration with similar phenotype.; to: Association with auto inflammatory syndrome:

Five-year-old girl with recurring hyperinflammatory episodes initially presenting at 9mo with fever, arthritis, aphthous stomatitis and maculopapular rash with homozygous variant in PMVK p.Val131Ala (NM_006556.4: c.392T>C) with clinical overlap with MVK deficiency. Supportive functional data. Second patient, 6yo boy with compound heterozygous c.329G >A (p. Arg110Gln) and c.316G >A (p. Val106Met) mutations in trans configuration with similar phenotype.

Amber for bi-allelic disease association.
Mendeliome v1.997 PMVK Zornitza Stark edited their review of gene: PMVK: Added comment: Association with auto inflammatory syndrome:

Five-year-old girl with recurring hyperinflammatory episodes initially presenting at 9mo with fever, arthritis, aphthous stomatitis and maculopapular rash with homozygous variant in PMVK p.Val131Ala (NM_006556.4: c.392T>C) with clinical overlap with MVK deficiency. Supportive functional data. Second patient, 6yo boy with compound heterozygous c.329G >A (p. Arg110Gln) and c.316G >A (p. Val106Met) mutations in trans configuration with similar phenotype.; Changed publications: 26202976, 37364720, 36410683; Changed phenotypes: Porokeratosis 1, multiple types, MIM# 175800, Autoinflammatory syndrome, MONDO:0019751, PMVK-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Autoinflammatory Disorders v1.6 PMVK Zornitza Stark Phenotypes for gene: PMVK were changed from Autoinflammation to Autoinflammatory syndrome, MONDO:0019751, PMVK-related
Autoinflammatory Disorders v1.5 PMVK Zornitza Stark Classified gene: PMVK as Amber List (moderate evidence)
Autoinflammatory Disorders v1.5 PMVK Zornitza Stark Gene: pmvk has been classified as Amber List (Moderate Evidence).
Susceptibility to Viral Infections v0.113 TNFRSF9 Zornitza Stark Marked gene: TNFRSF9 as ready
Susceptibility to Viral Infections v0.113 TNFRSF9 Zornitza Stark Gene: tnfrsf9 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.113 TNFRSF9 Zornitza Stark Phenotypes for gene: TNFRSF9 were changed from EBV associated lymphoproliferative disease to Immunodeficiency 109 with lymphoproliferation, MIM# 620282
Susceptibility to Viral Infections v0.112 TNFRSF9 Zornitza Stark Classified gene: TNFRSF9 as Green List (high evidence)
Susceptibility to Viral Infections v0.112 TNFRSF9 Zornitza Stark Gene: tnfrsf9 has been classified as Green List (High Evidence).
Mendeliome v1.997 RIPK3 Zornitza Stark Marked gene: RIPK3 as ready
Mendeliome v1.997 RIPK3 Zornitza Stark Gene: ripk3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.997 RIPK3 Zornitza Stark Classified gene: RIPK3 as Amber List (moderate evidence)
Mendeliome v1.997 RIPK3 Zornitza Stark Gene: ripk3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.996 RIPK3 Zornitza Stark gene: RIPK3 was added
gene: RIPK3 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: RIPK3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIPK3 were set to 37083451
Phenotypes for gene: RIPK3 were set to Hereditary susceptibility to infections, MONDO:0015979, RIPK3-related; Recurrent HSV encephalitis
Review for gene: RIPK3 was set to AMBER
Added comment: Single female patient with independent episodes of HSE at 6 and 17 months of age and with autoimmune encephalitis 1 month after the second episode of HSE with two heterozygous mutations of RIPK3 predicted to be loss of function (pLOF): p. Arg422* (c.1264 C > T, MAF 0.001568, CADD 35) and p. Pro493fs9* (c.1475 C > CC, MAF 0.002611, CADD 24.2). Extensive supportive functional data including RIPK3 knockout human pluripotent stem cell–derived cortical neurons.
Sources: Expert Review
Susceptibility to Viral Infections v0.111 RIPK3 Zornitza Stark Marked gene: RIPK3 as ready
Susceptibility to Viral Infections v0.111 RIPK3 Zornitza Stark Gene: ripk3 has been classified as Amber List (Moderate Evidence).
Susceptibility to Viral Infections v0.111 RIPK3 Zornitza Stark Phenotypes for gene: RIPK3 were changed from Recurrent HSV encephalitis to Hereditary susceptibility to infections, MONDO:0015979, RIPK3-related; Recurrent HSV encephalitis
Susceptibility to Viral Infections v0.110 RIPK3 Zornitza Stark Classified gene: RIPK3 as Amber List (moderate evidence)
Susceptibility to Viral Infections v0.110 RIPK3 Zornitza Stark Gene: ripk3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.995 SMAD1 Zornitza Stark Tag disputed tag was added to gene: SMAD1.
Hereditary Neuropathy - complex v0.181 GBA2 Zornitza Stark Marked gene: GBA2 as ready
Hereditary Neuropathy - complex v0.181 GBA2 Zornitza Stark Gene: gba2 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.181 GBA2 Zornitza Stark Publications for gene: GBA2 were set to
Hereditary Neuropathy - complex v0.180 EXOSC3 Zornitza Stark Marked gene: EXOSC3 as ready
Hereditary Neuropathy - complex v0.180 EXOSC3 Zornitza Stark Gene: exosc3 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.180 EXOSC3 Zornitza Stark Classified gene: EXOSC3 as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.180 EXOSC3 Zornitza Stark Gene: exosc3 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.179 ERCC8 Zornitza Stark Marked gene: ERCC8 as ready
Hereditary Neuropathy - complex v0.179 ERCC8 Zornitza Stark Gene: ercc8 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.179 ERCC8 Zornitza Stark Phenotypes for gene: ERCC8 were changed from Dwarfism, optic atrophy, mental retardation, cutaneous photosensitivity, pigmentary retinopathy, deafness, neuropathy with slow conduction velocities to Cockayne syndrome, type A MIM#216400
Hereditary Neuropathy - complex v0.178 ERCC8 Zornitza Stark reviewed gene: ERCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cockayne syndrome, type A MIM#216400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1870 SART3 Zornitza Stark Classified gene: SART3 as Green List (high evidence)
Genetic Epilepsy v0.1870 SART3 Zornitza Stark Gene: sart3 has been classified as Green List (High Evidence).
Fetal anomalies v1.121 ERI1 Zornitza Stark Marked gene: ERI1 as ready
Fetal anomalies v1.121 ERI1 Zornitza Stark Gene: eri1 has been classified as Green List (High Evidence).
Fetal anomalies v1.121 ERI1 Zornitza Stark Classified gene: ERI1 as Green List (high evidence)
Fetal anomalies v1.121 ERI1 Zornitza Stark Gene: eri1 has been classified as Green List (High Evidence).
Fetal anomalies v1.120 ERI1 Zornitza Stark gene: ERI1 was added
gene: ERI1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ERI1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 37352860
Phenotypes for gene: ERI1 were set to Spondyloepimetaphyseal dysplasia (MONDO#0100510)
Review for gene: ERI1 was set to GREEN
Added comment: PMID: 37352860 - 8 individuals from 7 unrelated families
- Patients with biallelic missense show a MORE severe spondyloepimetaphyseal dysplasia, syndactyly, brachydactyly/clinodactyly/camptodactyly
- Patients with biallelic null/whole gene deletion had mild ID and digit anomalies including brachydactyly/clinodactyly/camptodactyly
- Patient chet for a missense and PTC variant has a blended phenotype with short stature, syndactyly, brachydactyly/clinodactyly/camptodactyly, mild ID and failure to thrive

- Missense variants were functionally shown to not be able to rescue 5.8S rRNA processing in KO HeLa cells
- K/O mice had neonatal lethality with growth defects, brachydactyly. Skeletal-specific K/O had mild platyspondyly, had more in keeping with patients with null variants than missense

More severe phenotype hypothesised due to "exonuclease-dead proteins may compete for the target RNA molecules with other exonucleases that have functional redundancy
with ERI1, staying bound to those RNA molecules"
Sources: Literature
Skeletal dysplasia v0.241 Zornitza Stark removed gene:DRG1 from the panel
Mendeliome v1.995 ANO1 Zornitza Stark Phenotypes for gene: ANO1 were changed from Intestinal dysmotility syndrome, MIM# 620045; Impaired intestinal peristalsis; haemorrhagic diarrhoea; dysmorphic features to Intestinal dysmotility syndrome, MIM# 620045; Moyamoya disease, MONDO:0016820, ANO1 related
Mendeliome v1.994 ANO1 Zornitza Stark Publications for gene: ANO1 were set to 32487539
Mendeliome v1.993 ANO1 Zornitza Stark Mode of inheritance for gene: ANO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.992 ANO1 Zornitza Stark edited their review of gene: ANO1: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.992 ANO1 Zornitza Stark edited their review of gene: ANO1: Added comment: PMID 37253099: screening analysis of Moyamoya disease (MMD) cohort revealed 8 individuals with variants in the ANO1 gene. Two families had the same rare variant p.Met658Val. The ANO1 rare variants were assessed using patch-clamp recordings, and the majority of variants, including ANO1 p.Met658Val, displayed increased sensitivity to intracellular Ca2+. Patients harboring these gain-of-function ANO1 variants had classic features of MMD, but also had aneurysm, stenosis, and/or occlusion in the posterior circulation. Amber rating due to somewhat conflicting segregation and functional data presented.; Changed publications: 37253099; Changed phenotypes: Intestinal dysmotility syndrome, MIM# 620045, Moyamoya disease, MONDO:0016820, ANO1 related
Hereditary Neuropathy - complex v0.178 ERCC6 Zornitza Stark Marked gene: ERCC6 as ready
Hereditary Neuropathy - complex v0.178 ERCC6 Zornitza Stark Gene: ercc6 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.178 ERCC6 Zornitza Stark Phenotypes for gene: ERCC6 were changed from Dwarfism, optic atrophy, mental retardation, cutaneous photosensitivity, pigmentary retinopathy, deafness, neuropathy with slow conduction velocities to Cockayne syndrome, type B MIM#133540
Hereditary Neuropathy - complex v0.177 ERCC6 Zornitza Stark Publications for gene: ERCC6 were set to
Hereditary Neuropathy - complex v0.176 ERCC6 Zornitza Stark reviewed gene: ERCC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 25453614; Phenotypes: Cockayne syndrome, type B MIM#133540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.176 GALC Zornitza Stark Marked gene: GALC as ready
Hereditary Neuropathy - complex v0.176 GALC Zornitza Stark Gene: galc has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.176 GALC Zornitza Stark Phenotypes for gene: GALC were changed from Galactosylceramide beta-galactosidase deficiency; HMSN to Krabbe Disease MIM#245200
Hereditary Neuropathy - complex v0.175 GALC Zornitza Stark Publications for gene: GALC were set to
Hereditary Neuropathy - complex v0.174 GALC Zornitza Stark Classified gene: GALC as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.174 GALC Zornitza Stark Gene: galc has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.173 FAM126A Zornitza Stark Marked gene: FAM126A as ready
Hereditary Neuropathy - complex v0.173 FAM126A Zornitza Stark Added comment: Comment when marking as ready: Peripheral and central involvement reported.
Hereditary Neuropathy - complex v0.173 FAM126A Zornitza Stark Gene: fam126a has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.173 FAM126A Zornitza Stark Classified gene: FAM126A as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.173 FAM126A Zornitza Stark Gene: fam126a has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.172 FAM126A Zornitza Stark Classified gene: FAM126A as Red List (low evidence)
Hereditary Neuropathy - complex v0.172 FAM126A Zornitza Stark Gene: fam126a has been classified as Red List (Low Evidence).
Hereditary Neuropathy - complex v0.171 ZFYVE26 Zornitza Stark Marked gene: ZFYVE26 as ready
Hereditary Neuropathy - complex v0.171 ZFYVE26 Zornitza Stark Gene: zfyve26 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.171 ZFYVE26 Zornitza Stark Phenotypes for gene: ZFYVE26 were changed from HMSN; Spastic paraplegia 15 to Spastic paraplegia 15 MIM#270700
Hereditary Neuropathy - complex v0.170 ZFYVE26 Zornitza Stark Publications for gene: ZFYVE26 were set to
Mendeliome v1.992 CYHR1 Chirag Patel Classified gene: CYHR1 as Amber List (moderate evidence)
Mendeliome v1.992 CYHR1 Chirag Patel Gene: cyhr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.991 CYHR1 Chirag Patel gene: CYHR1 was added
gene: CYHR1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: CYHR1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYHR1 were set to Neurodevelopmental disorder and microcephaly
Review for gene: CYHR1 was set to AMBER
Added comment: ESHG 2023:
5 individuals from 3 families with biallelic LOF variants in CYHR1 (aka ZTRAF1). Presentation with microcephaly, hypotonia, DD, and ID. Expression studies showed mislocalisation of CYHR1. Mutant fibroblasts showed increased lysosomal markers and upregulated lysosomal proteins, leading to impaired autophagy. Zebrafish KO however did not show a phenotype.
Sources: Other
Microcephaly v1.211 CYHR1 Chirag Patel Classified gene: CYHR1 as Amber List (moderate evidence)
Microcephaly v1.211 CYHR1 Chirag Patel Gene: cyhr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5272 CYHR1 Chirag Patel Classified gene: CYHR1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5272 CYHR1 Chirag Patel Gene: cyhr1 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.210 CYHR1 Chirag Patel gene: CYHR1 was added
gene: CYHR1 was added to Microcephaly. Sources: Other
Mode of inheritance for gene: CYHR1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYHR1 were set to Neurodevelopmental disorder and microcephaly
Review for gene: CYHR1 was set to AMBER
gene: CYHR1 was marked as current diagnostic
Added comment: ESHG 2023:
5 individuals from 3 families with biallelic LOF variants in CYHR1 (aka ZTRAF1). Presentation with microcephaly, hypotonia, DD, and ID. Expression studies showed mislocalisation of CYHR1. Mutant fibroblasts showed increased lysosomal markers and upregulated lysosomal proteins, leading to impaired autophagy. Zebrafish KO however did not show a phenotype.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5271 CYHR1 Chirag Patel gene: CYHR1 was added
gene: CYHR1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: CYHR1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYHR1 were set to Neurodevelopmental disorder and microcephaly
Review for gene: CYHR1 was set to AMBER
gene: CYHR1 was marked as current diagnostic
Added comment: ESHG 2023:
5 individuals from 3 families with biallelic LOF variants in CYHR1 (aka ZTRAF1). Presentation with microcephaly, hypotonia, DD, and ID. Expression studies showed mislocalisation of CYHR1. Mutant fibroblasts showed increased lysosomal markers and upregulated lysosomal proteins, leading to impaired autophagy. Zebrafish KO however did not show a phenotype.
Sources: Other
Prepair 1000+ v1.1 SCN1B Crystle Lee gene: SCN1B was added
gene: SCN1B was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: SCN1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCN1B were set to 36291443; 31709768
Phenotypes for gene: SCN1B were set to Developmental and epileptic encephalopathy 52, MIM#617350
Review for gene: SCN1B was set to AMBER
Added comment: Bi-allelic variants cause EE/ID. Heterozygous variants linked to cardiac phenotypes and to GEFS+
Sources: Literature
Brain Calcification v1.93 NAA60 Chirag Patel Classified gene: NAA60 as Green List (high evidence)
Brain Calcification v1.93 NAA60 Chirag Patel Gene: naa60 has been classified as Green List (High Evidence).
Brain Calcification v1.93 NAA60 Chirag Patel Classified gene: NAA60 as Green List (high evidence)
Brain Calcification v1.93 NAA60 Chirag Patel Gene: naa60 has been classified as Green List (High Evidence).
Mendeliome v1.990 NAA60 Chirag Patel Classified gene: NAA60 as Green List (high evidence)
Mendeliome v1.990 NAA60 Chirag Patel Gene: naa60 has been classified as Green List (High Evidence).
Mendeliome v1.989 NAA60 Chirag Patel reviewed gene: NAA60: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary familial brain calcification; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.989 NAA60 Chirag Patel Deleted their review
Brain Calcification v1.92 NAA60 Chirag Patel reviewed gene: NAA60: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary familial brain calcification; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Brain Calcification v1.92 NAA60 Chirag Patel Deleted their review
Mendeliome v1.989 NAA60 Chirag Patel gene: NAA60 was added
gene: NAA60 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: NAA60 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NAA60 were set to Basal ganglia calcification
Review for gene: NAA60 was set to GREEN
gene: NAA60 was marked as current diagnostic
Added comment: ESHG 2023:
10 individuals from 7 families with biallelic variants in NAA60 (missense and framshift).
All with primary brain calcification - 4/10 childhood onset (DD, ID), 6/10 adult onset (cerebellar and pyramidal dysfunction, dystonia, parkinsonism, cognitive impairment, psychiatric manifestations).

NAA60 catalyses N-terminal acetylation of transmembrane proteins and localises to Golgi apparatus. In vitro assay of variants showed reduced capacity of Nt acetylation. Fibroblast studies showed significantly reduced levels of phosphate importer (SLC20A2). Loss of function variants in SLC20A2 (~50% of PFBC cases) lead to increased extracellular phosphate (which is thought to lead to calcium deposits in brain).
Sources: Other
Brain Calcification v1.92 NAA60 Chirag Patel gene: NAA60 was added
gene: NAA60 was added to Brain Calcification. Sources: Other
Mode of inheritance for gene: NAA60 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NAA60 were set to Basal ganglia calcification
Review for gene: NAA60 was set to GREEN
gene: NAA60 was marked as current diagnostic
Added comment: ESHG 2023:
10 individuals from 7 families with biallelic variants in NAA60 (missense and framshift).
All with primary brain calcification - 4/10 childhood onset (DD, ID), 6/10 adult onset (cerebellar and pyramidal dysfunction, dystonia, parkinsonism, cognitive impairment, psychiatric manifestations).

NAA60 catalyses N-terminal acetylation of transmembrane proteins and localises to Golgi apparatus. In vitro assay of variants showed reduced capacity of Nt acetylation. Fibroblast studies showed significantly reduced levels of phosphate importer (SLC20A2). Loss of function variants in SLC20A2 (~50% of PFBC cases) lead to increased extracellular phosphate (which is thought to lead to calcium deposits in brain).
Sources: Other
Mendeliome v1.988 POPDC2 Chirag Patel Classified gene: POPDC2 as Green List (high evidence)
Mendeliome v1.988 POPDC2 Chirag Patel Gene: popdc2 has been classified as Green List (High Evidence).
Mendeliome v1.987 POPDC2 Chirag Patel gene: POPDC2 was added
gene: POPDC2 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: POPDC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POPDC2 were set to Sinus node dysfunction
Review for gene: POPDC2 was set to GREEN
gene: POPDC2 was marked as current diagnostic
Added comment: ESHG 2023:
3 families with 7 affected with sinus node dysfunction (bradycardia) and AV block (2/7 HCM).

3 x HMZ variants found in POPDC2 (2 x missense, 1 x indel). Variants predicted to diminish cAMP binding of POPDC2, and shown to disrupt regulation of TREK1 channels (lowering of outward K+ current).

POPDC2 is highly expressed in cardiac myocytes, sinoatrial node, and atrioventricular node. Knockdown in zebrafish leads to AV block, and knockout in mice leads to sinus node dysfunction. Sources: Other
Sources: Other
Sick sinus syndrome v1.3 POPDC2 Chirag Patel Classified gene: POPDC2 as Green List (high evidence)
Sick sinus syndrome v1.3 POPDC2 Chirag Patel Gene: popdc2 has been classified as Green List (High Evidence).
Sick sinus syndrome v1.2 POPDC2 Chirag Patel gene: POPDC2 was added
gene: POPDC2 was added to Sick sinus syndrome. Sources: Other
Mode of inheritance for gene: POPDC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POPDC2 were set to Sinus node dysfunction
Review for gene: POPDC2 was set to GREEN
gene: POPDC2 was marked as current diagnostic
Added comment: ESHG 2023:
3 families with 7 affected with sinus node dysfunction (bradycardia) and AV block (2/7 HCM).

3 x HMZ variants found in POPDC2 (2 x missense, 1 x indel). Variants predicted to diminish cAMP binding of POPDC2, and shown to disrupt regulation of TREK1 channels (lowering of outward K+ current).

POPDC2 is highly expressed in cardiac myocytes, sinoatrial node, and atrioventricular node.
Knockdown in zebrafish leads to AV block, and knockout in mice leads to sinus node dysfunction.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5270 GPATCH11 Chirag Patel gene: GPATCH11 was added
gene: GPATCH11 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: GPATCH11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GPATCH11 were set to Leber congenital amaurosis and developmental delay
Review for gene: GPATCH11 was set to GREEN
gene: GPATCH11 was marked as current diagnostic
Added comment: ESHG 2023:
3 families with 8 individuals with leber congenital amaurosis, developmental delay, language disorder, and behavioural issues.
GPATCH11 localises to nucleus and basal body of primary cilium (similar to other LCA genes).
Biallelic variants found in GPATCH11 - 1 splice variant common to all 3 families (1 other variant in 3rd family). Splice variant leads to loss of exon 4 (mRNA studies).
Mouse models showed i) abnormal rod/cone responses on ERG; ii) decreased outer nuclear layer in retina, and iii) abnormal associate/episodic memory
Sources: Other
Syndromic Retinopathy v0.203 GPATCH11 Chirag Patel Classified gene: GPATCH11 as Green List (high evidence)
Syndromic Retinopathy v0.203 GPATCH11 Chirag Patel Gene: gpatch11 has been classified as Green List (High Evidence).
Mendeliome v1.986 GPATCH11 Chirag Patel Classified gene: GPATCH11 as Green List (high evidence)
Mendeliome v1.986 GPATCH11 Chirag Patel Gene: gpatch11 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.202 GPATCH11 Chirag Patel gene: GPATCH11 was added
gene: GPATCH11 was added to Syndromic Retinopathy. Sources: Other
Mode of inheritance for gene: GPATCH11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GPATCH11 were set to Leber congenital amaurosis and developmental delay
Review for gene: GPATCH11 was set to GREEN
gene: GPATCH11 was marked as current diagnostic
Added comment: ESHG 2023:
3 families with 8 individuals with leber congenital amaurosis, developmental delay, language disorder, and behavioural issues.
GPATCH11 localises to nucleus and basal body of primary cilium (similar to other LCA genes).
Biallelic variants found in GPATCH11 - 1 splice variant common to all 3 families (1 other variant in 3rd family). Splice variant leads to loss of exon 4 (mRNA studies).
Mouse models showed i) abnormal rod/cone responses on ERG; ii) decreased outer nuclear layer in retina, and iii) abnormal associate/episodic memory
Sources: Other
Mendeliome v1.985 GPATCH11 Chirag Patel gene: GPATCH11 was added
gene: GPATCH11 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: GPATCH11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GPATCH11 were set to Leber congenital amaurosis and developmental delay
Review for gene: GPATCH11 was set to GREEN
gene: GPATCH11 was marked as current diagnostic
Added comment: ESHG 2023:
3 families with 8 individuals with leber congenital amaurosis, developmental delay, language disorder, and behavioural issues.
GPATCH11 localises to nucleus and basal body of primary cilium (similar to other LCA genes).
Biallelic variants found in GPATCH11 - 1 splice variant common to all 3 families (1 other variant in 3rd family). Splice variant leads to loss of exon 4 (mRNA studies).
Mouse models showed i) abnormal rod/cone responses on ERG; ii) decreased outer nuclear layer in retina, and iii) abnormal associate/episodic memory
Sources: Other
Genetic Epilepsy v0.1869 KCNA3 Chirag Patel Classified gene: KCNA3 as Green List (high evidence)
Genetic Epilepsy v0.1869 KCNA3 Chirag Patel Gene: kcna3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1869 KCNA3 Chirag Patel Classified gene: KCNA3 as Green List (high evidence)
Genetic Epilepsy v0.1869 KCNA3 Chirag Patel Gene: kcna3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5269 KCNA3 Chirag Patel Classified gene: KCNA3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5269 KCNA3 Chirag Patel Gene: kcna3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1869 KCNA3 Chirag Patel Classified gene: KCNA3 as Green List (high evidence)
Genetic Epilepsy v0.1869 KCNA3 Chirag Patel Gene: kcna3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5268 KCNA3 Chirag Patel Classified gene: KCNA3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5268 KCNA3 Chirag Patel Gene: kcna3 has been classified as Green List (High Evidence).
Mendeliome v1.984 KCNA3 Chirag Patel Classified gene: KCNA3 as Green List (high evidence)
Mendeliome v1.984 KCNA3 Chirag Patel Gene: kcna3 has been classified as Green List (High Evidence).
Mendeliome v1.983 KCNA3 Chirag Patel Classified gene: KCNA3 as Green List (high evidence)
Mendeliome v1.983 KCNA3 Chirag Patel Gene: kcna3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1868 KCNA3 Chirag Patel gene: KCNA3 was added
gene: KCNA3 was added to Genetic Epilepsy. Sources: Other
Mode of inheritance for gene: KCNA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KCNA3 were set to Neurodevelopmental disorder with epilepsy
Review for gene: KCNA3 was set to GREEN
gene: KCNA3 was marked as current diagnostic
Added comment: ESHG 2023:
10 individuals with de novo missense variants in KCNA3 (K+ channel)
Variable electrophysiology studies of effect of variants (5 x LOF, 4 x GOF, 1 no change)
Presentation: abnormal speech development (8/8), ID (6/8), epilepsy (5/8), and ASD (7/8)
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5267 KCNA3 Chirag Patel gene: KCNA3 was added
gene: KCNA3 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: KCNA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KCNA3 were set to Neurodevelopmental disorder
Review for gene: KCNA3 was set to GREEN
gene: KCNA3 was marked as current diagnostic
Added comment: ESHG 2023:
10 individuals with de novo missense variants in KCNA3 (K+ channel)
Variable electrophysiology studies of effect of variants (5 x LOF, 4 x GOF, 1 no change)
Presentation: abnormal speech development (8/8), ID (6/8), epilepsy (5/8), and ASD (7/8)
Sources: Other
Mendeliome v1.982 KCNA3 Chirag Patel gene: KCNA3 was added
gene: KCNA3 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: KCNA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KCNA3 were set to Neurodevelopmental disorder
Review for gene: KCNA3 was set to GREEN
gene: KCNA3 was marked as current diagnostic
Added comment: ESHG 2023:
10 individuals with de novo missense variants in KCNA3 (K+ channel)
Variable electrophysiology studies of effect of variants (5 x LOF, 4 x GOF, 1 no change)
Presentation: abnormal speech development (8/8), ID (6/8), epilepsy (5/8), and ASD (7/8)
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5266 FSD1L Chirag Patel Classified gene: FSD1L as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5266 FSD1L Chirag Patel Gene: fsd1l has been classified as Green List (High Evidence).
Mendeliome v1.981 FSD1L Chirag Patel Classified gene: FSD1L as Green List (high evidence)
Mendeliome v1.981 FSD1L Chirag Patel Gene: fsd1l has been classified as Green List (High Evidence).
Mendeliome v1.980 FSD1L Chirag Patel gene: FSD1L was added
gene: FSD1L was added to Mendeliome. Sources: Other
Mode of inheritance for gene: FSD1L was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FSD1L were set to Neurodevelopmental disorder
Review for gene: FSD1L was set to GREEN
gene: FSD1L was marked as current diagnostic
Added comment: ESHG 2023:
8 families with biallelic missense/nonsense variants
Presentation only described 1 family/2 affecteds with DD, ID, spastic paraparesis, epilepsy, corpus callosum hypoplasia, and optic nerve hypoplasia

Functional assays:
-reduced expression of FSD1L in mature neurons (RNA studies)
-very low % mature neurons (neuronal differentiation)
-reduced neuronal migration
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5265 FSD1L Chirag Patel gene: FSD1L was added
gene: FSD1L was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: FSD1L was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FSD1L were set to Neurodevelopmental disorder
Review for gene: FSD1L was set to GREEN
gene: FSD1L was marked as current diagnostic
Added comment: ESHG 2023:
8 families with biallelic missense/nonsense variants
Presentation only described 1 family/2 affecteds with DD, ID, spastic paraparesis, epilepsy, corpus callosum hypoplasia, and optic nerve hypoplasia

Functional assays:
-reduced expression of FSD1L in mature neurons (RNA studies)
-very low % mature neurons (neuronal differentiation)
-reduced neuronal migration
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5264 DENND5B Chirag Patel Classified gene: DENND5B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5264 DENND5B Chirag Patel Gene: dennd5b has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.292 DENND5B Chirag Patel Classified gene: DENND5B as Green List (high evidence)
Leukodystrophy - paediatric v0.292 DENND5B Chirag Patel Gene: dennd5b has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.291 DENND5B Chirag Patel Classified gene: DENND5B as Green List (high evidence)
Leukodystrophy - paediatric v0.291 DENND5B Chirag Patel Gene: dennd5b has been classified as Green List (High Evidence).
Mendeliome v1.979 DENND5B Chirag Patel Classified gene: DENND5B as Green List (high evidence)
Mendeliome v1.979 DENND5B Chirag Patel Gene: dennd5b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5263 DENND5B Chirag Patel gene: DENND5B was added
gene: DENND5B was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: DENND5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DENND5B were set to Neurodevelopmental disorder with white matter anomalies
Review for gene: DENND5B was set to GREEN
gene: DENND5B was marked as current diagnostic
Added comment: ESHG 2023:
7 patients/7 families with de novo DENND5B variants (6 missense, 1 splice)
DD/ID (mod/profound)(7/7), white matter anomalies (6/7) hypotonia, epilepsy (3/7)

DENND5B acts as:
-GEF for activation of RAB proteins which are involved in membrane trafficking and neurotransmitter release
-regulator of lipid absorption and homeostasis

Functional studies showed loss of expression of DENND5B in fibroblasts, abnormal vesicle trafficking, and impaired lipid uptake and intracellular distribution
Sources: Other
Mendeliome v1.978 DENND5B Chirag Patel gene: DENND5B was added
gene: DENND5B was added to Mendeliome. Sources: Other
Mode of inheritance for gene: DENND5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DENND5B were set to Neurodevelopmental disorder with white matter anomalies
Review for gene: DENND5B was set to GREEN
gene: DENND5B was marked as current diagnostic
Added comment: ESHG 2023:
7 patients/7 families with de novo DENND5B variants (6 missense, 1 splice)
DD/ID (mod/profound)(7/7), white matter anomalies (6/7) hypotonia, epilepsy (3/7)

DENND5B acts as:
-GEF for activation of RAB proteins which are involved in membrane trafficking and neurotransmitter release
-regulator of lipid absorption and homeostasis

Functional studies showed loss of expression of DENND5B in fibroblasts, abnormal vesicle trafficking, and impaired lipid uptake and intracellular distribution
Sources: Other
Leukodystrophy - paediatric v0.290 DENND5B Chirag Patel gene: DENND5B was added
gene: DENND5B was added to Leukodystrophy - paediatric. Sources: Other
Mode of inheritance for gene: DENND5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DENND5B were set to Neurodevelopmental disorder with white matter anomalies
Review for gene: DENND5B was set to GREEN
gene: DENND5B was marked as current diagnostic
Added comment: ESHG 2023:
7 patients/7 families with de novo DENND5B variants (6 missense, 1 splice)
DD/ID (mod/profound)(7/7), white matter anomalies (6/7) hypotonia, epilepsy (3/7)

DENND5B acts as:
-GEF for activation of RAB proteins which are involved in membrane trafficking and neurotransmitter release
-regulator of lipid absorption and homeostasis

Functional studies showed loss of expression of DENND5B in fibroblasts, abnormal vesicle trafficking, and impaired lipid uptake and intracellular distribution
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5262 DMAP1 Chirag Patel Classified gene: DMAP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5262 DMAP1 Chirag Patel Gene: dmap1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5261 DMAP1 Chirag Patel Classified gene: DMAP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5261 DMAP1 Chirag Patel Gene: dmap1 has been classified as Green List (High Evidence).
Mendeliome v1.977 DMAP1 Chirag Patel Classified gene: DMAP1 as Green List (high evidence)
Mendeliome v1.977 DMAP1 Chirag Patel Gene: dmap1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5260 DMAP1 Chirag Patel gene: DMAP1 was added
gene: DMAP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: DMAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DMAP1 were set to Neurodevelopmental disorder
Review for gene: DMAP1 was set to GREEN
gene: DMAP1 was marked as current diagnostic
Added comment: ESHG 2023:
9 patients/8 families with bilallelic variants in DMAP1 (3 missense, 7 LOF)
All with DD, speech delay, hypotonia, and ID
Some with epilepsy (4/6), FTT (4/5), and brain malformations (3/5)
Drosophila showed abnormal behaviour pattern and bang sensitivity
Specific methylation episignature also seen
Sources: Other
Mendeliome v1.976 DMAP1 Chirag Patel gene: DMAP1 was added
gene: DMAP1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: DMAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DMAP1 were set to Neurodevelopmental disorder
Review for gene: DMAP1 was set to GREEN
gene: DMAP1 was marked as current diagnostic
Added comment: ESHG 2023:
9 patients/8 families with bilallelic variants in DMAP1 (3 missense, 7 LOF)
All with DD, speech delay, hypotonia, and ID
Some with epilepsy (4/6), FTT (4/5), and brain malformations (3/5)
Drosophila showed abnormal behaviour pattern and bang sensitivity
Specific methylation episignature also seen
Sources: Other
Mandibulofacial Acrofacial dysostosis v1.7 VGLL2 Chirag Patel Classified gene: VGLL2 as Green List (high evidence)
Mandibulofacial Acrofacial dysostosis v1.7 VGLL2 Chirag Patel Gene: vgll2 has been classified as Green List (High Evidence).
Mendeliome v1.975 VGLL2 Chirag Patel Classified gene: VGLL2 as Green List (high evidence)
Mendeliome v1.975 VGLL2 Chirag Patel Gene: vgll2 has been classified as Green List (High Evidence).
Mendeliome v1.974 VGLL2 Chirag Patel gene: VGLL2 was added
gene: VGLL2 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: VGLL2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VGLL2 were set to Syngnathia
Review for gene: VGLL2 was set to GREEN
gene: VGLL2 was marked as current diagnostic
Added comment: ESHG 2023:
4 families/7 affected individuals with isolated unilateral/bilateral syngnathia
biallelic truncating variants in VGLL2
But not phenotype in KO mouse or zebrafish models
Sources: Other
Mandibulofacial Acrofacial dysostosis v1.6 VGLL2 Chirag Patel gene: VGLL2 was added
gene: VGLL2 was added to Mandibulofacial Acrofacial dysostosis. Sources: Other
Mode of inheritance for gene: VGLL2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VGLL2 were set to Syngnathia
Review for gene: VGLL2 was set to GREEN
Added comment: ESHG 2023:
4 families/7 affected individuals with isolated unilateral/bilateral syngnathia
biallelic truncating variants in VGLL2
But not phenotype in KO mouse or zebrafish models
Sources: Other
Regression v0.528 ZIC1 Chirag Patel Classified gene: ZIC1 as Red List (low evidence)
Regression v0.528 ZIC1 Chirag Patel Added comment: Comment on list classification: No evidence of regression
Regression v0.528 ZIC1 Chirag Patel Gene: zic1 has been classified as Red List (Low Evidence).
Regression v0.528 ZIC1 Chirag Patel Classified gene: ZIC1 as Red List (low evidence)
Regression v0.528 ZIC1 Chirag Patel Added comment: Comment on list classification: No evidence of regression
Regression v0.528 ZIC1 Chirag Patel Gene: zic1 has been classified as Red List (Low Evidence).
Regression v0.527 ZIC1 Chirag Patel reviewed gene: ZIC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.973 ITFG2 Chirag Patel Classified gene: ITFG2 as Green List (high evidence)
Mendeliome v1.973 ITFG2 Chirag Patel Gene: itfg2 has been classified as Green List (High Evidence).
Mendeliome v1.972 ITFG2 Chirag Patel reviewed gene: ITFG2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5259 ITFG2 Chirag Patel Classified gene: ITFG2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5259 ITFG2 Chirag Patel Gene: itfg2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5258 ITFG2 Chirag Patel reviewed gene: ITFG2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.972 COL4A6 Ain Roesley reviewed gene: COL4A6: Rating: AMBER; Mode of pathogenicity: None; Publications: 33840813; Phenotypes: Deafness, X-linked 6 MIM#300914; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Cerebral Palsy v1.133 PMM2 Zornitza Stark Marked gene: PMM2 as ready
Cerebral Palsy v1.133 PMM2 Zornitza Stark Gene: pmm2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.133 PMM2 Zornitza Stark Classified gene: PMM2 as Red List (low evidence)
Cerebral Palsy v1.133 PMM2 Zornitza Stark Gene: pmm2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.132 PLP1 Zornitza Stark Marked gene: PLP1 as ready
Cerebral Palsy v1.132 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.132 PLP1 Zornitza Stark Phenotypes for gene: PLP1 were changed from Pelizaeus-Merzbacher disease MIM#312080; Spastic paraplegia 2, X-linked MIM#312920 to Spastic paraplegia 2, X-linked MIM#312920
Cerebral Palsy v1.131 PLP1 Zornitza Stark Classified gene: PLP1 as Green List (high evidence)
Cerebral Palsy v1.131 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.130 PLA2G6 Zornitza Stark Marked gene: PLA2G6 as ready
Cerebral Palsy v1.130 PLA2G6 Zornitza Stark Gene: pla2g6 has been classified as Green List (High Evidence).
Cerebral Palsy v1.130 PLA2G6 Zornitza Stark Phenotypes for gene: PLA2G6 were changed from Infantile neuroaxonal dystrophy 1 MIM#256600; Neurodegeneration with brain iron accumulation 2B MIM#610217; Parkinson disease 14, autosomal recessive MIM#612953 to Neurodegeneration with brain iron accumulation 2B MIM#610217
Cerebral Palsy v1.129 PLA2G6 Zornitza Stark Classified gene: PLA2G6 as Green List (high evidence)
Cerebral Palsy v1.129 PLA2G6 Zornitza Stark Gene: pla2g6 has been classified as Green List (High Evidence).
Cerebral Palsy v1.128 PIGA Zornitza Stark Marked gene: PIGA as ready
Cerebral Palsy v1.128 PIGA Zornitza Stark Gene: piga has been classified as Green List (High Evidence).
Cerebral Palsy v1.128 PIGA Zornitza Stark Phenotypes for gene: PIGA were changed from Multiple congenital anomalies-hypotonia-seizures syndrome 2 MIM#300868; Neurodevelopmental disorder with epilepsy and hemochromatosis MIM#301072; Paroxysmal nocturnal hemoglobinuria, somatic MIM#300818 to Multiple congenital anomalies-hypotonia-seizures syndrome 2 MIM#300868; Neurodevelopmental disorder with epilepsy and haemochromatosis MIM#301072
Cerebral Palsy v1.127 PIGA Zornitza Stark Classified gene: PIGA as Green List (high evidence)
Cerebral Palsy v1.127 PIGA Zornitza Stark Gene: piga has been classified as Green List (High Evidence).
Cerebral Palsy v1.126 PDHX Zornitza Stark Marked gene: PDHX as ready
Cerebral Palsy v1.126 PDHX Zornitza Stark Gene: pdhx has been classified as Green List (High Evidence).
Cerebral Palsy v1.126 PDHX Zornitza Stark Classified gene: PDHX as Green List (high evidence)
Cerebral Palsy v1.126 PDHX Zornitza Stark Gene: pdhx has been classified as Green List (High Evidence).
Cerebral Palsy v1.125 PDHA1 Zornitza Stark Marked gene: PDHA1 as ready
Cerebral Palsy v1.125 PDHA1 Zornitza Stark Gene: pdha1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.125 PDHA1 Zornitza Stark Classified gene: PDHA1 as Green List (high evidence)
Cerebral Palsy v1.125 PDHA1 Zornitza Stark Gene: pdha1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.124 PANK2 Zornitza Stark Publications for gene: PANK2 were set to PMID: 33098801
Cerebral Palsy v1.123 PANK2 Zornitza Stark Classified gene: PANK2 as Green List (high evidence)
Cerebral Palsy v1.123 PANK2 Zornitza Stark Gene: pank2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.122 PAK3 Zornitza Stark Publications for gene: PAK3 were set to 25666757
Cerebral Palsy v1.121 PAK3 Zornitza Stark Classified gene: PAK3 as Green List (high evidence)
Cerebral Palsy v1.121 PAK3 Zornitza Stark Gene: pak3 has been classified as Green List (High Evidence).
Cerebral Palsy v1.120 PAFAH1B1 Zornitza Stark Marked gene: PAFAH1B1 as ready
Cerebral Palsy v1.120 PAFAH1B1 Zornitza Stark Gene: pafah1b1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.120 PAFAH1B1 Zornitza Stark Classified gene: PAFAH1B1 as Green List (high evidence)
Cerebral Palsy v1.120 PAFAH1B1 Zornitza Stark Gene: pafah1b1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.119 NFIX Zornitza Stark Marked gene: NFIX as ready
Cerebral Palsy v1.119 NFIX Zornitza Stark Gene: nfix has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.119 NFIX Zornitza Stark Classified gene: NFIX as Amber List (moderate evidence)
Cerebral Palsy v1.119 NFIX Zornitza Stark Gene: nfix has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.118 NAA10 Zornitza Stark Marked gene: NAA10 as ready
Cerebral Palsy v1.118 NAA10 Zornitza Stark Gene: naa10 has been classified as Green List (High Evidence).
Cerebral Palsy v1.118 NAA10 Zornitza Stark Phenotypes for gene: NAA10 were changed from Microphthalmia, syndromic MIM#309800; Ogden syndrome MIM#300855 to Ogden syndrome MIM#300855
Cerebral Palsy v1.117 NAA10 Zornitza Stark Classified gene: NAA10 as Green List (high evidence)
Cerebral Palsy v1.117 NAA10 Zornitza Stark Gene: naa10 has been classified as Green List (High Evidence).
Cerebral Palsy v1.116 MT-TL1 Zornitza Stark Marked gene: MT-TL1 as ready
Cerebral Palsy v1.116 MT-TL1 Zornitza Stark Added comment: Comment when marking as ready: Note only detectable by appropriate assays (WGS, mtDNA sequencing).
Cerebral Palsy v1.116 MT-TL1 Zornitza Stark Gene: mt-tl1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.116 MT-TL1 Zornitza Stark Marked gene: MT-TL1 as ready
Cerebral Palsy v1.116 MT-TL1 Zornitza Stark Gene: mt-tl1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.116 MT-TL1 Zornitza Stark Phenotypes for gene: MT-TL1 were changed from MYOCLONIC EPILEPSY ASSOCIATED WITH RAGGED-RED FIBERS MERRF MIM#545000; CYCLIC VOMITING SYNDROME WITH NEUROMUSCULAR DISEASE, INCLUDED CYCLIC VOMITING SYNDROME-PLUS, INCLUDED CVS-PLUS, INCLUDED MIM#500007; MITOCHONDRIAL MYOPATHY, ENCEPHALOPATHY, LACTIC ACIDOSIS, AND STROKE-LIKE EPISODES MELAS MIM#540000; DIABETES AND DEAFNESS, MATERNALLY INHERITED MIDD MIM#520000 to MELAS MIM#540000
Cerebral Palsy v1.115 MT-TL1 Zornitza Stark Tag mtDNA tag was added to gene: MT-TL1.
Cerebral Palsy v1.115 MT-TL1 Zornitza Stark Classified gene: MT-TL1 as Green List (high evidence)
Cerebral Palsy v1.115 MT-TL1 Zornitza Stark Gene: mt-tl1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.114 MT-TL1 Zornitza Stark Classified gene: MT-TL1 as Green List (high evidence)
Cerebral Palsy v1.114 MT-TL1 Zornitza Stark Gene: mt-tl1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.114 MT-TL1 Zornitza Stark Classified gene: MT-TL1 as Green List (high evidence)
Cerebral Palsy v1.114 MT-TL1 Zornitza Stark Gene: mt-tl1 has been classified as Green List (High Evidence).
Clefting disorders v0.236 UBE3B Zornitza Stark Marked gene: UBE3B as ready
Clefting disorders v0.236 UBE3B Zornitza Stark Gene: ube3b has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.236 UBE3B Zornitza Stark Classified gene: UBE3B as Amber List (moderate evidence)
Clefting disorders v0.236 UBE3B Zornitza Stark Gene: ube3b has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.235 UBE3B Zornitza Stark gene: UBE3B was added
gene: UBE3B was added to Clefting disorders. Sources: Expert Review
Mode of inheritance for gene: UBE3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBE3B were set to 23200864; 23687348; 37010288
Phenotypes for gene: UBE3B were set to Kaufman oculocerebrofacial syndrome, OMIM:244450
Review for gene: UBE3B was set to AMBER
Added comment: Although there are three unrelated cases associated with biallelic variants in UBE3B gene and reported with clefting, clefting has only been reported as a minor clinical indication.

PMID:23687348 - One of two patients reported with biallelic variants in UBE3B in this study and one of four patients reported in PMID:23200864 and reviewed here had submucous cleft palate.

DECIPHER database - One of three patients with homozygous sequence variants in UBE3B had median cleft palate.
Sources: Expert Review
Clefting disorders v0.234 SMARCB1 Zornitza Stark Marked gene: SMARCB1 as ready
Clefting disorders v0.234 SMARCB1 Zornitza Stark Gene: smarcb1 has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.234 SMARCB1 Zornitza Stark Classified gene: SMARCB1 as Amber List (moderate evidence)
Clefting disorders v0.234 SMARCB1 Zornitza Stark Gene: smarcb1 has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.233 SMARCB1 Zornitza Stark gene: SMARCB1 was added
gene: SMARCB1 was added to Clefting disorders. Sources: Expert Review
Mode of inheritance for gene: SMARCB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCB1 were set to 25168959; 37010288
Phenotypes for gene: SMARCB1 were set to Coffin-Siris syndrome 3, OMIM:614608
Review for gene: SMARCB1 was set to AMBER
Added comment: Although there are 3 unrelated cases reported with cleft palate in total, these represent only a minor fraction of patients (from total of 23) reported with SMARCB1 variants.

PMID:25168959 - Two of ten patients reported with Coffin-Siris syndrome and heterozygous variants in SMARCB1 had cleft palate.

DECIPHER database - One of 13 patients identified with heterozygous sequence variants in SMARCB1 had cleft palate.
Sources: Expert Review
Clefting disorders v0.232 NOTCH2 Zornitza Stark Marked gene: NOTCH2 as ready
Clefting disorders v0.232 NOTCH2 Zornitza Stark Gene: notch2 has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.232 NOTCH2 Zornitza Stark Classified gene: NOTCH2 as Amber List (moderate evidence)
Clefting disorders v0.232 NOTCH2 Zornitza Stark Gene: notch2 has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.231 NOTCH2 Zornitza Stark gene: NOTCH2 was added
gene: NOTCH2 was added to Clefting disorders. Sources: Expert Review
Mode of inheritance for gene: NOTCH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH2 were set to 9188663; 30329210; 37010288
Phenotypes for gene: NOTCH2 were set to Hajdu-Cheney syndrome, OMIM:102500
Review for gene: NOTCH2 was set to AMBER
Added comment: Although there are three cases reported with cleft lip/ palate or cleft of uvula, these are reported only in a minor proportion of patients.

PMID:9188663 - An 8.5-year-old boy with NOTCH2 variant and Hajdu-Cheney syndrome was reported with cleft lip and palate.

PMID:30329210 - A 32-year-old male patient with a de novo truncating variant in NOTCH2 and presenting with Hajdu-Cheney syndrome had high arched palate and cleft of uvula.

DECIPHER database - One of seven patients with heterozygous sequence variants in NOTCH2 was identified with submucous cleft hard palate.
Sources: Expert Review
Clefting disorders v0.230 AUTS2 Zornitza Stark Marked gene: AUTS2 as ready
Clefting disorders v0.230 AUTS2 Zornitza Stark Gene: auts2 has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.230 AUTS2 Zornitza Stark Classified gene: AUTS2 as Amber List (moderate evidence)
Clefting disorders v0.230 AUTS2 Zornitza Stark Gene: auts2 has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.229 AUTS2 Zornitza Stark gene: AUTS2 was added
gene: AUTS2 was added to Clefting disorders. Sources: Expert Review
Mode of inheritance for gene: AUTS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AUTS2 were set to 31788251; 37010288
Phenotypes for gene: AUTS2 were set to Intellectual developmental disorder, autosomal dominant 26, MIM# 615834
Review for gene: AUTS2 was set to AMBER
Added comment: There are a total of five cases reported with cleft lip/ palate. However, clefting has only been reported in less than 10% of patients with monoalellic variants in AUTS2 from the DECIPHER database.

PMID:31788251 - A patient identified with a de novo heterozygous AUTS2 variant (c.1464_1467del ACTC/ p.Tyr488Ter) was reported with autism and cleft lip and palate.

DECIPHER database - Of 44 patients reported with heterozygous sequence variants, 4 patients had cleft lip or cleft palate (2 - cleft palate; 1 - cleft soft palate; 1 - unilateral cleft lip).
Sources: Expert Review
Cancer Predisposition_Paediatric v0.130 ATRX Zornitza Stark Marked gene: ATRX as ready
Cancer Predisposition_Paediatric v0.130 ATRX Zornitza Stark Gene: atrx has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.130 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Osteosarcoma, mild to severe intellectual disability, facial, skeletal, urogenital, and hematopoietic anomalies. to Intellectual disability-hypotonic facies syndrome, X-linked, MIM# 309580; Osteosarcoma, mild to severe intellectual disability, facial, skeletal, urogenital, and hematopoietic anomalies.
Cancer Predisposition_Paediatric v0.129 ATRX Zornitza Stark Classified gene: ATRX as Green List (high evidence)
Cancer Predisposition_Paediatric v0.129 ATRX Zornitza Stark Gene: atrx has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.175 CACNA1C Zornitza Stark Phenotypes for gene: CACNA1C were changed from Hypertrophic cardiomyopathy; congenital heart defects; conduction abnormalities to Hypertrophic cardiomyopathy, MONDO:0005045, CACNA1C-related
Hypertrophic cardiomyopathy_HCM v0.174 CACNA1C Zornitza Stark Classified gene: CACNA1C as Amber List (moderate evidence)
Hypertrophic cardiomyopathy_HCM v0.174 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.173 CACNA1C Zornitza Stark edited their review of gene: CACNA1C: Added comment: Evidence only of association of a specific missense with HCM.; Changed rating: AMBER
Cancer Predisposition_Paediatric v0.128 ATRX Laura Raiti gene: ATRX was added
gene: ATRX was added to Cancer Predisposition_Paediatric. Sources: Literature
Mode of inheritance for gene: ATRX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ATRX were set to PMID: 28371217, 29706636, 28371197
Phenotypes for gene: ATRX were set to Osteosarcoma, mild to severe intellectual disability, facial, skeletal, urogenital, and hematopoietic anomalies.
Penetrance for gene: ATRX were set to unknown
Review for gene: ATRX was set to GREEN
Added comment: Early onset osteosarcoma and development of metachronous osteosarcoma tumours suggestive of cancer predisposition.
Small numbers but at least 3 unrelated individuals reported in literature.
Sources: Literature
Mendeliome v1.972 RDH11 Elena Savva reviewed gene: RDH11: Rating: AMBER; Mode of pathogenicity: None; Publications: 24916380, 15634683, 30731079, 18326732, 34988992; Phenotypes: Retinal dystrophy, juvenile cataracts, and short stature syndrome, MIM# 616108; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5258 HCN2 Elena Savva gene: HCN2 was added
gene: HCN2 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: HCN2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: HCN2 were set to Febrile seizures, familial, 2 MIM#602477; Generalized epilepsy with febrile seizures plus, type 11 MIM#602477; {Epilepsy, idiopathic generalized, susceptibility to, 17} MIM#602477; Neurodevelopmental disorder (MONDO#0700092), HCN2-related
Review for gene: HCN2 was set to AMBER
Added comment: ICG 2023 conference
- cohort of 20 individuals where >80% had a form of intellectual disability (half were severe) and/or seizures. Some had isolated intellectual disability, especially those with a recurring de novo p.E478del.
- Patients were both mono- and biallelic.
- Monoallelic individuals had de novo missense and an inframe deletion. Biallelic individuals had a mix of missense and PTC
Sources: Other
Miscellaneous Metabolic Disorders v1.29 ALDOB Zornitza Stark Marked gene: ALDOB as ready
Miscellaneous Metabolic Disorders v1.29 ALDOB Zornitza Stark Gene: aldob has been classified as Green List (High Evidence).
Miscellaneous Metabolic Disorders v1.29 ALDOB Zornitza Stark Classified gene: ALDOB as Green List (high evidence)
Miscellaneous Metabolic Disorders v1.29 ALDOB Zornitza Stark Gene: aldob has been classified as Green List (High Evidence).
Miscellaneous Metabolic Disorders v1.28 ALDOB Zornitza Stark gene: ALDOB was added
gene: ALDOB was added to Miscellaneous Metabolic Disorders. Sources: Expert Review
Mode of inheritance for gene: ALDOB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ALDOB were set to Fructose intolerance, hereditary, MIM# 229600
Review for gene: ALDOB was set to GREEN
Added comment: Well established gene-disease association.

Clinical symptoms of HFI include gastrointestinal distress (nausea, vomiting, diarrhea, abdominal pain, anorexia), jaundice, bleeding tendency, renal tubular dysfunction and metabolic disturbances following dietary exposure to fructose, sucrose, or sorbitol. If large quantities of fructose are ingested, lethargy, seizures, and/or progressive coma may ensue. Persistent fructose exposure can result in chronic growth restriction, failure to thrive, renal and hepatic failure, and risk of death.

Symptoms appear in infancy at the time of weaning.

Treatment: Lifelong dietary restriction of fructose, sucrose, and sorbitol.

Assessed as 'strong actionability' by ClinGen.

Of particular note, a 24% sucrose solution (routinely administered to hospitalized neonates for minor procedures) should not be given to neonates known to have HFI. This recommendation is supported by case reports of reported accidental and iatrogenic fructose infusion-related serious organ failure events and/or deaths.

Alerts should be placed in the patient's chart or medical record to notify practitioners to the HFI diagnosis and to the medical risks associated with exposures to fructose and related metabolites. The patient is advised to wear at all times a medically approved alert bracelet/necklace that provides information about the diagnosis of HFI.

Evidence from 50 patients presenting with confirmed and symptomatic HFI shows that upon dietary restriction of fructose, the improvement observed is dramatic: vomiting and gastrointestinal symptoms resolved nearly immediately, bleeding tendency resolves in ~24 hours, renal tubular dysfunction can resolve in as little as 3 days, and clinical and biological findings, with the exception of hepatomegaly, resolved within a few weeks. Normal growth occurred in 2-3 years. In the 50 symptomatic patients and 5 patients who received treatment from birth, liver enlargement persisted in spite of treatment and resolution of fibrosis.
Sources: Expert Review
Mendeliome v1.972 SLC4A3 Chern Lim reviewed gene: SLC4A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 36806574; Phenotypes: Short QT syndrome 7, MIM#620231; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Short QT syndrome v1.5 SLC4A3 Chern Lim reviewed gene: SLC4A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 36806574; Phenotypes: Short QT syndrome 7, MIM#620231; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Clefting disorders v0.228 ARID1A Zornitza Stark Marked gene: ARID1A as ready
Clefting disorders v0.228 ARID1A Zornitza Stark Gene: arid1a has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.228 ARID1A Zornitza Stark Classified gene: ARID1A as Amber List (moderate evidence)
Clefting disorders v0.228 ARID1A Zornitza Stark Gene: arid1a has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.227 ARID1A Zornitza Stark gene: ARID1A was added
gene: ARID1A was added to Clefting disorders. Sources: Expert Review
Mode of inheritance for gene: ARID1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARID1A were set to 25168959; 37010288
Phenotypes for gene: ARID1A were set to Coffin-Siris syndrome 2 (MIM#614607)
Review for gene: ARID1A was set to AMBER
Added comment: Clefting is a minor feature on patients with monoallelic variants in ARID1A gene.

PMID:25168959 - Two of eight patients with heterozygous variants in ARID1A gene had cleft palate.

DECIPHER database - One of 26 patients with heterozygous sequence variants in ARID1A gene had cleft palate.
Sources: Expert Review
Clefting disorders v0.226 ZC4H2 Zornitza Stark Marked gene: ZC4H2 as ready
Clefting disorders v0.226 ZC4H2 Zornitza Stark Gene: zc4h2 has been classified as Green List (High Evidence).
Clefting disorders v0.226 ZC4H2 Zornitza Stark Classified gene: ZC4H2 as Green List (high evidence)
Clefting disorders v0.226 ZC4H2 Zornitza Stark Gene: zc4h2 has been classified as Green List (High Evidence).
Clefting disorders v0.225 ZC4H2 Zornitza Stark gene: ZC4H2 was added
gene: ZC4H2 was added to Clefting disorders. Sources: Expert Review
Mode of inheritance for gene: ZC4H2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ZC4H2 were set to 31206972; 37010288
Phenotypes for gene: ZC4H2 were set to Wieacker-Wolff syndrome, MIM# 314580
Review for gene: ZC4H2 was set to GREEN
Added comment: There are ten unrelated patients reported with cleft palate.

PMID:31206972 - Of 42 families identified with de novo and inherited variants in ZC4H2 gene, eight patients had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with sequence variants, three patients had cleft palate.

Cleft palate has been recorded as one of the clinical presentations of female-restricted Wieacker-Wolff syndrome (MIM #301041) in OMIM.
Sources: Expert Review
Clefting disorders v0.224 STAG2 Zornitza Stark Marked gene: STAG2 as ready
Clefting disorders v0.224 STAG2 Zornitza Stark Gene: stag2 has been classified as Green List (High Evidence).
Clefting disorders v0.224 STAG2 Zornitza Stark Publications for gene: STAG2 were set to
Clefting disorders v0.223 STAG2 Zornitza Stark edited their review of gene: STAG2: Changed publications: 28296084, 29263825, 30158690, 31334757, 33014403, 37010288
Clefting disorders v0.223 STAG2 Zornitza Stark Classified gene: STAG2 as Green List (high evidence)
Clefting disorders v0.223 STAG2 Zornitza Stark Gene: stag2 has been classified as Green List (High Evidence).
Clefting disorders v0.222 STAG2 Zornitza Stark gene: STAG2 was added
gene: STAG2 was added to Clefting disorders. Sources: Expert Review
Mode of inheritance for gene: STAG2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: STAG2 were set to Mullegama-Klein-Martinez syndrome, MIM#301022
Review for gene: STAG2 was set to GREEN
Added comment: There are eight unrelated cases identified with cleft lip/ palate and two cases were identified with cleft soft palate or submucous cleft soft palate.

PMID:33014403 - Two female patients identified with de novo variants in STAG2. One had cleft lip/ palate and other had cleft palate. In addition, five additional cases with cleft lip/ palate were also reported from literature review in this publication.

DECIPHER database - Of ten patients with sequence variants in STAG2 gene, one each was identified with cleft palate, cleft soft palate and submucous cleft soft palate (PMID:37010288).
Sources: Expert Review
Clefting disorders v0.221 SMARCA4 Zornitza Stark Marked gene: SMARCA4 as ready
Clefting disorders v0.221 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Green List (High Evidence).
Clefting disorders v0.221 SMARCA4 Zornitza Stark Classified gene: SMARCA4 as Green List (high evidence)
Clefting disorders v0.221 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Green List (High Evidence).
Clefting disorders v0.220 SMARCA4 Zornitza Stark gene: SMARCA4 was added
gene: SMARCA4 was added to Clefting disorders. Sources: Expert Review
Mode of inheritance for gene: SMARCA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCA4 were set to 25168959; 37010288
Phenotypes for gene: SMARCA4 were set to Coffin-Siris syndrome 4, MIM# 614609
Review for gene: SMARCA4 was set to GREEN
Added comment: There are five unrelated cases with cleft plate and one case each with submucous cleft palate and bifid uvula.

PMID:25168959 - 4 of 12 patients with variants in SMARCA4 had cleft palate and another patient had submucous cleft palate.

DECIPHER database - One of 22 patients with heterozygous sequence variants had cleft palate and another patient had bifid uvula (PMID:37010288)
Sources: Expert Review
Clefting disorders v0.219 POGZ Zornitza Stark Marked gene: POGZ as ready
Clefting disorders v0.219 POGZ Zornitza Stark Gene: pogz has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.219 POGZ Zornitza Stark Classified gene: POGZ as Amber List (moderate evidence)
Clefting disorders v0.219 POGZ Zornitza Stark Gene: pogz has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.218 POGZ Zornitza Stark gene: POGZ was added
gene: POGZ was added to Clefting disorders. Sources: Expert Review
Mode of inheritance for gene: POGZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POGZ were set to 26942287; 26739615
Phenotypes for gene: POGZ were set to White-Sutton syndrome, MIM# 616364
Review for gene: POGZ was set to AMBER
Added comment: Although there are more than three unrelated cases reported with either cleft palate or bifid uvula in total, this phenotype is not consistently present in patients with monoallelic variants in POGZ gene.

PMID:26739615 - Five unrelated individuals were identified with de novo truncating variants in POGZ gene, of which one individual had cleft palate and another one had bifid uvula.

PMID:31782611 - In this cohort of 22 individuals with 21 different loss of function variants in POGZ, two patients were reported with bifid uvula.

DECIPHER database - Of 42 patients with heterozygous sequence variants, one had cleft palate and another one had bifid uvula (PMID:37010288).
Sources: Expert Review
Cerebral Palsy v1.113 TUBB2A Zornitza Stark Marked gene: TUBB2A as ready
Cerebral Palsy v1.113 TUBB2A Zornitza Stark Gene: tubb2a has been classified as Green List (High Evidence).
Cerebral Palsy v1.113 TUBB2A Zornitza Stark Classified gene: TUBB2A as Green List (high evidence)
Cerebral Palsy v1.113 TUBB2A Zornitza Stark Gene: tubb2a has been classified as Green List (High Evidence).
Cerebral Palsy v1.112 TUBB3 Zornitza Stark Marked gene: TUBB3 as ready
Cerebral Palsy v1.112 TUBB3 Zornitza Stark Gene: tubb3 has been classified as Green List (High Evidence).
Cerebral Palsy v1.112 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from Cortical dysplasia, complex, with other brain malformations MIM#614039; Fibrosis of extraocular muscles, congenital MIM#600638 to Cortical dysplasia, complex, with other brain malformations MIM#614039
Cerebral Palsy v1.111 TUBB3 Zornitza Stark Classified gene: TUBB3 as Green List (high evidence)
Cerebral Palsy v1.111 TUBB3 Zornitza Stark Gene: tubb3 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.109 TNFRSF9 Peter McNaughton gene: TNFRSF9 was added
gene: TNFRSF9 was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: TNFRSF9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNFRSF9 were set to PMID: 37144041
Phenotypes for gene: TNFRSF9 were set to EBV associated lymphoproliferative disease
Review for gene: TNFRSF9 was set to GREEN
Added comment: Patient with novel biallelic variants (c.208 + 1>AT and p.T151K) with EBV induced lymphoproliferative disease and chronic active EBV. Multiple previous patients reported with EBV associated disease (table1).
Sources: Literature
Inflammatory bowel disease v0.101 SOCS1 Peter McNaughton gene: SOCS1 was added
gene: SOCS1 was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: SOCS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOCS1 were set to PMID: 37156989
Phenotypes for gene: SOCS1 were set to Enteropathy
Review for gene: SOCS1 was set to GREEN
Added comment: 2x patients 1x presenting with treatment refractory Crohn-like disease and 1 with lymphocytic leiomyositis. Potential for targeted therapies leading to remission so important to differentiate from polygenic IBD.
Sources: Literature
Disorders of immune dysregulation v0.176 PLCG1 Peter McNaughton gene: PLCG1 was added
gene: PLCG1 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: PLCG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLCG1 were set to PMID: 37422272
Phenotypes for gene: PLCG1 were set to Immune dysregulation
Mode of pathogenicity for gene: PLCG1 was set to Other
Review for gene: PLCG1 was set to AMBER
Added comment: Single 7yo proband presented with thrombocytopaenia and lymphadenopathy. De Novo , c.3062C>T, p.S1021F with functional testing supportive of GOF mechanism of disease
Sources: Literature
Mendeliome v1.972 C1GALT1C1 Zornitza Stark commented on gene: C1GALT1C1: Two maternal half-brothers with missense variant and aHUS phenotype reported, increasing evidence for association.
Mendeliome v1.972 C1GALT1C1 Zornitza Stark reviewed gene: C1GALT1C1: Rating: AMBER; Mode of pathogenicity: None; Publications: 37216524; Phenotypes: Haemolytic uraemic syndrome, atypical, 8, with rhizomelic short stature, MIM# 301110; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Atypical Haemolytic Uraemic Syndrome_MPGN v0.53 C1GALT1C1 Zornitza Stark Phenotypes for gene: C1GALT1C1 were changed from atypical hemolytic-uremic syndrome MONDO#0016244, C1GALT1C1-related to Haemolytic uraemic syndrome, atypical, 8, with rhizomelic short stature, MIM# 301110
Atypical Haemolytic Uraemic Syndrome_MPGN v0.52 C1GALT1C1 Zornitza Stark Publications for gene: C1GALT1C1 were set to 36599939
Atypical Haemolytic Uraemic Syndrome_MPGN v0.51 C1GALT1C1 Zornitza Stark edited their review of gene: C1GALT1C1: Changed publications: 37216524
Atypical Haemolytic Uraemic Syndrome_MPGN v0.51 C1GALT1C1 Zornitza Stark Mode of inheritance for gene: C1GALT1C1 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Atypical Haemolytic Uraemic Syndrome_MPGN v0.50 C1GALT1C1 Zornitza Stark Classified gene: C1GALT1C1 as Amber List (moderate evidence)
Atypical Haemolytic Uraemic Syndrome_MPGN v0.50 C1GALT1C1 Zornitza Stark Gene: c1galt1c1 has been classified as Amber List (Moderate Evidence).
Atypical Haemolytic Uraemic Syndrome_MPGN v0.49 C1GALT1C1 Zornitza Stark reviewed gene: C1GALT1C1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature, MIM# 301110; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5257 ZMYM3 Zornitza Stark Phenotypes for gene: ZMYM3 were changed from Neurodevelopmental disorder, MONDO:0700092, ZMYM3-related to Intellectual developmental disorder, X-linked 112, MIM# 301111
Intellectual disability syndromic and non-syndromic v0.5256 ZMYM3 Zornitza Stark reviewed gene: ZMYM3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, X-linked 112, MIM# 301111; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.972 ZMYM3 Zornitza Stark Phenotypes for gene: ZMYM3 were changed from Neurodevelopmental disorder, MONDO:0700092, ZMYM3-related to Intellectual developmental disorder, X-linked 112, MIM# 301111
Mendeliome v1.971 ZMYM3 Zornitza Stark reviewed gene: ZMYM3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, X-linked 112, MIM# 301111; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary Neuropathy - complex v0.169 MFF Sangavi Sivagnanasundram reviewed gene: MFF: Rating: RED; Mode of pathogenicity: None; Publications: 26783368; Phenotypes: Encephalopathy due to defective mitochondrial and peroxisomal fission 2 MIM# 617086; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.169 LYST Sangavi Sivagnanasundram reviewed gene: LYST: Rating: AMBER; Mode of pathogenicity: None; Publications: 24521565, 15790783, 20301751; Phenotypes: Chediak-Higashi syndrome MIM#214500, MONDO:0008963; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.169 KARS Sangavi Sivagnanasundram reviewed gene: KARS: Rating: AMBER; Mode of pathogenicity: None; Publications: 20920668; Phenotypes: Charcot-Marie-Tooth disease, recessive intermediate, B (MIM#613641, MONDO:0013338); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.169 HMBS Sangavi Sivagnanasundram reviewed gene: HMBS: Rating: AMBER; Mode of pathogenicity: None; Publications: 20301372, 8563760; Phenotypes: Porphyria, acute intermittent MIM#176000, MONDO:0008294; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary Neuropathy - complex v0.169 HADHB Sangavi Sivagnanasundram reviewed gene: HADHB: Rating: RED; Mode of pathogenicity: None; Publications: 36063482, 24664533; Phenotypes: Mitochondrial Trifunctional Protein Deficiency 2 with Myopathy and Neuropathy MIM#320300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.169 HADHA Sangavi Sivagnanasundram reviewed gene: HADHA: Rating: AMBER; Mode of pathogenicity: None; Publications: 8871579, 23868323, 33744096, 12838198, 36063482; Phenotypes: LCHAD deficiency MIM#609016, Mitochondrial trifunctional protein deficiency MIM#609015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.169 GSN Sangavi Sivagnanasundram reviewed gene: GSN: Rating: AMBER; Mode of pathogenicity: None; Publications: 8684801, 228009, 3513049; Phenotypes: Amyloidosis, Finnish type MIM#105120; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.169 GBE1 Sangavi Sivagnanasundram reviewed gene: GBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23034915, 1763891, 8494336, 20301758; Phenotypes: Polyglucosan body disease, adult form MIM#263570; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Autoinflammatory Disorders v1.4 PMVK Peter McNaughton gene: PMVK was added
gene: PMVK was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: PMVK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PMVK were set to PMID: 37364720; 36410683
Phenotypes for gene: PMVK were set to Autoinflammation
Review for gene: PMVK was set to AMBER
Added comment: Five-year-old girl with recurring hyperinflammatory episodes initially presenting at 9mo with fever, arthritis, aphthous stomatitis and maculopapular rash with homozygous variant in PMVK p.Val131Ala (NM_006556.4: c.392T>C) with clinical overlap with MVK deficiency. Supportive functional data. Second patient, 6yo boy with compound heterozygous c.329G >A (p. Arg110Gln) and c.316G >A (p. Val106Met) mutations in trans configuration with similar phenotype.
Sources: Literature
Susceptibility to Viral Infections v0.109 RIPK3 Peter McNaughton gene: RIPK3 was added
gene: RIPK3 was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: RIPK3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIPK3 were set to PMID: 37083451
Phenotypes for gene: RIPK3 were set to Recurrent HSV encephalitis
Review for gene: RIPK3 was set to AMBER
Added comment: Single female patient with independent episodes of HSE at 6 and 17 months of age and with autoimmune encephalitis 1 month after the second episode of HSE with two heterozygous mutations of RIPK3 predicted to be loss of function (pLOF): p. Arg422* (c.1264 C > T, MAF 0.001568, CADD 35) and p. Pro493fs9* (c.1475 C > CC, MAF 0.002611, CADD 24.2).
Extensive supportive functional data including RIPK3 knockout human pluripotent stem cell–derived cortical neurons.
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.173 ACTN2 Zornitza Stark Classified gene: ACTN2 as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.173 ACTN2 Zornitza Stark Gene: actn2 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.172 ACTN2 Zornitza Stark reviewed gene: ACTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, hypertrophic, 23, with or without LVNC, MIM# 612158; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dilated Cardiomyopathy v1.18 ACTN2 Zornitza Stark Phenotypes for gene: ACTN2 were changed from Intrinsic cardiomyopathy to Cardiomyopathy, dilated, 1AA, with or without LVNC, MIM# 612158
Dilated Cardiomyopathy v1.17 ACTN2 Zornitza Stark Classified gene: ACTN2 as Green List (high evidence)
Dilated Cardiomyopathy v1.17 ACTN2 Zornitza Stark Gene: actn2 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.16 ACTN2 Zornitza Stark reviewed gene: ACTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, dilated, 1AA, with or without LVNC, MIM# 612158; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.971 ACTN2 Zornitza Stark Classified gene: ACTN2 as Green List (high evidence)
Mendeliome v1.971 ACTN2 Zornitza Stark Gene: actn2 has been classified as Green List (High Evidence).
Mendeliome v1.970 NFE2L2 Zornitza Stark Mode of inheritance for gene: NFE2L2 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.969 NFE2L2 Zornitza Stark edited their review of gene: NFE2L2: Changed phenotypes: Immunodeficiency, developmental delay, and hypohomocysteinemia, MIM# 617744, Recurrent respiratory and skin infection, Growth retardation, Developmental delay, borderline ID, White matter cerebral lesions; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.969 SMAD1 Bryony Thompson Classified gene: SMAD1 as Red List (low evidence)
Mendeliome v1.969 SMAD1 Bryony Thompson Added comment: Comment on list classification: Disputed gene-disease validity curation by ClinGen PH VCEP 21/11/2022 - Only two probands reported to have PAH and SMAD1 variants. The variants are missense variants without functional data at the time of curation. Thus, SMAD1 is classified as disputed for PAH based upon insufficient genetic evidence over multiple years of research.
Mendeliome v1.969 SMAD1 Bryony Thompson Gene: smad1 has been classified as Red List (Low Evidence).
Repeat Disorders v0.157 OPDM1 Bryony Thompson Phenotypes for STR: OPDM1 were changed from Oculopharyngodistal myopathy 1 MIM#164310 to Oculopharyngodistal myopathy 1 MIM#164310; Amyotrophic lateral sclerosis MONDO:0004976
Repeat Disorders v0.156 OPDM1 Bryony Thompson Publications for STR: OPDM1 were set to 31332380; 34047774
Repeat Disorders v0.155 OPDM1 Bryony Thompson edited their review of STR: OPDM1: Changed publications: 31332380, 34047774, 37339631
Repeat Disorders v0.155 OPDM1 Bryony Thompson edited their review of STR: OPDM1: Added comment: The CGG repeat expansion in the 5’UTR of LRP12 was identified in 5 ALS families and 2 simplex cases. 61-100 repeats associated with ALS, whereas >100 repeats causes OPDM. Toxic gain-of-function is the mechanism of disease. Authors’ suggest the differences in the levels of toxic RNA and MBNL1 dysfunction, in turn dependent on repeat length, may determine whether the affected individual develops ALS or OPDM; Changed phenotypes: Oculopharyngodistal myopathy 1 MIM#164310, Amyotrophic lateral sclerosis MONDO:0004976
Motor Neurone Disease v0.191 LRP12-ALS_CGG Bryony Thompson Classified STR: LRP12-ALS_CGG as Green List (high evidence)
Motor Neurone Disease v0.191 LRP12-ALS_CGG Bryony Thompson Str: lrp12-als_cgg has been classified as Green List (High Evidence).
Motor Neurone Disease v0.190 LRP12-ALS_CGG Bryony Thompson STR: LRP12-ALS_CGG was added
STR: LRP12-ALS_CGG was added to Motor Neurone Disease. Sources: Literature
Mode of inheritance for STR: LRP12-ALS_CGG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: LRP12-ALS_CGG were set to 37339631
Phenotypes for STR: LRP12-ALS_CGG were set to Amyotrophic lateral sclerosis MONDO:0004976
Review for STR: LRP12-ALS_CGG was set to GREEN
STR: LRP12-ALS_CGG was marked as clinically relevant
Added comment: The CGG repeat expansion in the 5’UTR of LRP12 was identified in 5 ALS families and 2 simplex cases. 61-100 repeats associated with ALS, whereas >100 repeats causes OPDM. Toxic gain-of-function is the mechanism of disease. Authors’ suggest the differences in the levels of toxic RNA and MBNL1 dysfunction, in turn dependent on repeat length, may determine whether the affected individual develops ALS or OPDM.
Sources: Literature
Neurodegeneration with brain iron accumulation v0.28 ATP7B Zornitza Stark Marked gene: ATP7B as ready
Neurodegeneration with brain iron accumulation v0.28 ATP7B Zornitza Stark Gene: atp7b has been classified as Amber List (Moderate Evidence).
Neurodegeneration with brain iron accumulation v0.28 ATP7B Zornitza Stark Phenotypes for gene: ATP7B were changed from dystonia; parkinsonism; psychosis; liver failure; pancreatitis; renal tubular acidosis; dysarthria; dysphagia to Wilson disease, MIM# 277900
Neurodegeneration with brain iron accumulation v0.27 ATP7B Zornitza Stark Classified gene: ATP7B as Amber List (moderate evidence)
Neurodegeneration with brain iron accumulation v0.27 ATP7B Zornitza Stark Gene: atp7b has been classified as Amber List (Moderate Evidence).
Neurodegeneration with brain iron accumulation v0.26 ATP7B Zornitza Stark reviewed gene: ATP7B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Wilson disease, MIM# 277900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neurodegeneration with brain iron accumulation v0.26 AP4M1 Zornitza Stark Marked gene: AP4M1 as ready
Neurodegeneration with brain iron accumulation v0.26 AP4M1 Zornitza Stark Gene: ap4m1 has been classified as Amber List (Moderate Evidence).
Neurodegeneration with brain iron accumulation v0.26 AP4M1 Zornitza Stark Phenotypes for gene: AP4M1 were changed from progressive spastic tetraparesis; microcephaly; intellectual disabiliy; growth retardation; epilepsy; peripheral neuropathy; brain iron deposition to Spastic paraplegia 50, autosomal recessive, MIM# 612936
Neurodegeneration with brain iron accumulation v0.25 AP4M1 Zornitza Stark Classified gene: AP4M1 as Amber List (moderate evidence)
Neurodegeneration with brain iron accumulation v0.25 AP4M1 Zornitza Stark Gene: ap4m1 has been classified as Amber List (Moderate Evidence).
Neurodegeneration with brain iron accumulation v0.24 AP4M1 Zornitza Stark changed review comment from: Brain iron accumulation is not a consistent/common feature of this condition.; to: Brain iron accumulation is a rarely reported feature.
Neurodegeneration with brain iron accumulation v0.24 AP4M1 Zornitza Stark reviewed gene: AP4M1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 50, autosomal recessive, MIM# 612936; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neurodegeneration with brain iron accumulation v0.24 AP1S2 Zornitza Stark Marked gene: AP1S2 as ready
Neurodegeneration with brain iron accumulation v0.24 AP1S2 Zornitza Stark Gene: ap1s2 has been classified as Amber List (Moderate Evidence).
Neurodegeneration with brain iron accumulation v0.24 AP1S2 Zornitza Stark Phenotypes for gene: AP1S2 were changed from spasticity; hypotonia; intellectual disability; posterior fossa malformation; brain iron deposition to Pettigrew syndrome, MIM# 304340
Neurodegeneration with brain iron accumulation v0.23 AP1S2 Zornitza Stark Classified gene: AP1S2 as Amber List (moderate evidence)
Neurodegeneration with brain iron accumulation v0.23 AP1S2 Zornitza Stark Gene: ap1s2 has been classified as Amber List (Moderate Evidence).
Neurodegeneration with brain iron accumulation v0.22 AP1S2 Zornitza Stark reviewed gene: AP1S2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23756445; Phenotypes: Pettigrew syndrome, MIM# 304340; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Clefting disorders v0.217 PGAP3 Zornitza Stark Marked gene: PGAP3 as ready
Clefting disorders v0.217 PGAP3 Zornitza Stark Gene: pgap3 has been classified as Green List (High Evidence).
Clefting disorders v0.217 PGAP3 Zornitza Stark Classified gene: PGAP3 as Green List (high evidence)
Clefting disorders v0.217 PGAP3 Zornitza Stark Gene: pgap3 has been classified as Green List (High Evidence).
Clefting disorders v0.216 PGAP3 Zornitza Stark gene: PGAP3 was added
gene: PGAP3 was added to Clefting disorders. Sources: Expert Review
Mode of inheritance for gene: PGAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGAP3 were set to 28390064; 37010288
Phenotypes for gene: PGAP3 were set to Hyperphosphatasia with impaired intellectual development syndrome 4, OMIM:615716
Review for gene: PGAP3 was set to GREEN
Added comment: PMID:28390064 - 10 individuals from eight families presented with developmental delay, severe intellectual disability, distinct facial dysmorphism and increased alkaline phosphatase. Nine individuals from seven families were homozygous for the same variant (c.402dupC/ p.M135Hfs*28), while one had a different homozygous variant ( c.817_820delGACT/ p.D273Sfs*37). Of nine individuals with p.M135Hfs*28 variant, eight from seven families (except one of the two patients from family 7) had cleft palate. But, the only patient with the different variant did not have cleft palate.

DECIPHER database - Of seven individuals reported with biallelic sequence variants, three with homozygous variants were reported with cleft palate and two with compound heterozygous variants were reported with cleft soft palate (PMID:37010288).
Sources: Expert Review
Clefting disorders v0.215 KMT2A Zornitza Stark Marked gene: KMT2A as ready
Clefting disorders v0.215 KMT2A Zornitza Stark Gene: kmt2a has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.215 KMT2A Zornitza Stark Classified gene: KMT2A as Amber List (moderate evidence)
Clefting disorders v0.215 KMT2A Zornitza Stark Gene: kmt2a has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.214 KMT2A Zornitza Stark gene: KMT2A was added
gene: KMT2A was added to Clefting disorders. Sources: Expert Review
Mode of inheritance for gene: KMT2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT2A were set to 25929198; 30305169; 31710778; 37010288
Phenotypes for gene: KMT2A were set to Wiedemann-Steiner syndrome, OMIM:605130
Review for gene: KMT2A was set to AMBER
Added comment: Although there are more than three cases reported with clefting, it is only present in a very small subsection of patients with KMT2A monoallelic variants.

PMID:25929198 - De novo KMT2A variant (p.Arg1083Ter) in monozygotic twins and they had submucosal cleft palate.

PMID:30305169 - Two of 14 patients with KMT2A variants and presenting with Wiedemann–Steiner syndrome had cleft palate.

PMID:31710778 - Both patients reported with KMT2A variants had only high arched palate and not cleft palate.

DECIPHER database - None of the reported patients had cleft lip/ palate and only one of 115 had bifid uvula (PMID:37010288)
Sources: Expert Review
Clefting disorders v0.213 KAT6B Zornitza Stark Marked gene: KAT6B as ready
Clefting disorders v0.213 KAT6B Zornitza Stark Gene: kat6b has been classified as Green List (High Evidence).
Clefting disorders v0.213 KAT6B Zornitza Stark Phenotypes for gene: KAT6B were changed from Genitopatellar syndrome, 606170; GTPTS to Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736
Clefting disorders v0.212 KAT6B Zornitza Stark Publications for gene: KAT6B were set to 20182757; 27031267
Clefting disorders v0.211 KAT6B Zornitza Stark Mode of inheritance for gene: KAT6B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting disorders v0.210 KAT6B Zornitza Stark Classified gene: KAT6B as Green List (high evidence)
Clefting disorders v0.210 KAT6B Zornitza Stark Gene: kat6b has been classified as Green List (High Evidence).
Clefting disorders v0.209 GLI2 Zornitza Stark Marked gene: GLI2 as ready
Clefting disorders v0.209 GLI2 Zornitza Stark Gene: gli2 has been classified as Green List (High Evidence).
Clefting disorders v0.209 GLI2 Zornitza Stark Classified gene: GLI2 as Green List (high evidence)
Clefting disorders v0.209 GLI2 Zornitza Stark Gene: gli2 has been classified as Green List (High Evidence).
Clefting disorders v0.208 GLI2 Zornitza Stark gene: GLI2 was added
gene: GLI2 was added to Clefting disorders. Sources: Expert Review
Mode of inheritance for gene: GLI2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLI2 were set to 24744436; 37010288
Phenotypes for gene: GLI2 were set to Culler-Jones syndrome, OMIM:615849; Holoprosencephaly 9, OMIM:610829
Review for gene: GLI2 was set to GREEN
Added comment: Although clefting is a minor feature in patients reported with monoallelic GLI2 variants, it has been reported in more than 15 cases.

In ~400 screened individuals with HPE spectrum disorders, 112 individuals were identified with variants in GLI2 gene, of which 16 cases had cleft lip/ palate (PMID:24744436).

Three out of 17 patients reported with heterozygous GLI2 sequence variants in the DECIPHER database presented with cleft lip/ palate as one of the phenotypes (PMID:37010288).
Sources: Expert Review
Cerebral Palsy v1.110 MSL3 Zornitza Stark Marked gene: MSL3 as ready
Cerebral Palsy v1.110 MSL3 Zornitza Stark Gene: msl3 has been classified as Green List (High Evidence).
Cerebral Palsy v1.110 MSL3 Zornitza Stark Classified gene: MSL3 as Green List (high evidence)
Cerebral Palsy v1.110 MSL3 Zornitza Stark Gene: msl3 has been classified as Green List (High Evidence).
Cerebral Palsy v1.109 MOCS2 Zornitza Stark Marked gene: MOCS2 as ready
Cerebral Palsy v1.109 MOCS2 Zornitza Stark Gene: mocs2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.109 MOCS2 Zornitza Stark Classified gene: MOCS2 as Green List (high evidence)
Cerebral Palsy v1.109 MOCS2 Zornitza Stark Gene: mocs2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.108 MEF2C Zornitza Stark Marked gene: MEF2C as ready
Cerebral Palsy v1.108 MEF2C Zornitza Stark Gene: mef2c has been classified as Green List (High Evidence).
Cerebral Palsy v1.108 MEF2C Zornitza Stark Classified gene: MEF2C as Green List (high evidence)
Cerebral Palsy v1.108 MEF2C Zornitza Stark Gene: mef2c has been classified as Green List (High Evidence).
Cerebral Palsy v1.107 MOCS1 Zornitza Stark Marked gene: MOCS1 as ready
Cerebral Palsy v1.107 MOCS1 Zornitza Stark Gene: mocs1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.107 MOCS1 Zornitza Stark Classified gene: MOCS1 as Amber List (moderate evidence)
Cerebral Palsy v1.107 MOCS1 Zornitza Stark Gene: mocs1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.106 MCOLN1 Zornitza Stark Marked gene: MCOLN1 as ready
Cerebral Palsy v1.106 MCOLN1 Zornitza Stark Gene: mcoln1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.106 MCOLN1 Zornitza Stark Classified gene: MCOLN1 as Green List (high evidence)
Cerebral Palsy v1.106 MCOLN1 Zornitza Stark Gene: mcoln1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.105 MAST1 Zornitza Stark Marked gene: MAST1 as ready
Cerebral Palsy v1.105 MAST1 Zornitza Stark Gene: mast1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.105 MAST1 Zornitza Stark Classified gene: MAST1 as Amber List (moderate evidence)
Cerebral Palsy v1.105 MAST1 Zornitza Stark Gene: mast1 has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.207 FGFR3 Zornitza Stark Marked gene: FGFR3 as ready
Clefting disorders v0.207 FGFR3 Zornitza Stark Gene: fgfr3 has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.207 FGFR3 Zornitza Stark Classified gene: FGFR3 as Amber List (moderate evidence)
Clefting disorders v0.207 FGFR3 Zornitza Stark Gene: fgfr3 has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.206 FGFR3 Zornitza Stark gene: FGFR3 was added
gene: FGFR3 was added to Clefting disorders. Sources: Expert Review
Mode of inheritance for gene: FGFR3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGFR3 were set to 22565872; 29150894; 37010288
Phenotypes for gene: FGFR3 were set to Muenke syndrome, OMIM:602849; Hypochondroplasia, OMIM:146000
Review for gene: FGFR3 was set to AMBER
Added comment: Although there are more than three unrelated cases reported with cleft lip and/or palate, this is not consistently found in individuals with monoallelic variants in FGFR3 gene.

PMID:22565872 included 21 individuals with variants in FGFR3 and presenting with Muenke syndrome in this study, of which 16 had structural anomaly of the palate. However, only one patient had cleft lip and palate.

PMID:29150894 reported a father and two children with FGFR3 variant and presenting with hypochondroplasia, of which only the daughter had cleft palate.

2 out of 15 individuals reported in DECIPHER database with monoallelic sequence variants had cleft palate.
Sources: Expert Review
Clefting disorders v0.205 CNTNAP1 Zornitza Stark Marked gene: CNTNAP1 as ready
Clefting disorders v0.205 CNTNAP1 Zornitza Stark Gene: cntnap1 has been classified as Green List (High Evidence).
Clefting disorders v0.205 CNTNAP1 Zornitza Stark Classified gene: CNTNAP1 as Green List (high evidence)
Clefting disorders v0.205 CNTNAP1 Zornitza Stark Gene: cntnap1 has been classified as Green List (High Evidence).
Clefting disorders v0.204 CNTNAP1 Zornitza Stark gene: CNTNAP1 was added
gene: CNTNAP1 was added to Clefting disorders. Sources: Expert Review
Mode of inheritance for gene: CNTNAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNTNAP1 were set to 28374019; 29511323; 29882456; 37010288
Phenotypes for gene: CNTNAP1 were set to Hypomyelinating neuropathy, congenital, 3, OMIM:618186
Review for gene: CNTNAP1 was set to GREEN
Added comment: There is sufficient evidence (3 unrelated cases) for the association of biallelic variants in this gene with cleft palate.

PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - There is one individual reported with compound heterozygous stop gain variants in CNTNAP1 (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Expert Review
Clefting disorders v0.203 ARID1B Zornitza Stark Marked gene: ARID1B as ready
Clefting disorders v0.203 ARID1B Zornitza Stark Gene: arid1b has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.203 ARID1B Zornitza Stark Classified gene: ARID1B as Amber List (moderate evidence)
Clefting disorders v0.203 ARID1B Zornitza Stark Gene: arid1b has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.202 ARID1B Zornitza Stark gene: ARID1B was added
gene: ARID1B was added to Clefting disorders. Sources: Expert Review
Mode of inheritance for gene: ARID1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARID1B were set to 30349098; 37010288
Phenotypes for gene: ARID1B were set to Coffin-Siris syndrome 1, OMIM:135900
Review for gene: ARID1B was set to AMBER
Added comment: Although there are more than three unrelated cases with ARID1B monoallelic variants reported with either cleft palate, cleft uvula or bifid uvula, clefting is not consistently present in individuals with ARID1B variants.

PMID:30349098 - On this web-based survey based on previously reported features of individuals with variants in ARID1B gene (143 in total), which also included submissions to DECIPHER database, two individuals were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available.

Of >100 patients with ARID1B variants in the DECIPHER database, only one patient (c.3183_3184​insT/ p.Tyr1062LeufsTer10) was reported with submucous cleft soft palate and two patients (c.4155_4156​insA/ p.Asn1386LysfsTer18 & c.2620+5G​>A) were reported with bifid uvula.
Sources: Expert Review
Clefting disorders v0.201 CHD4 Zornitza Stark Marked gene: CHD4 as ready
Clefting disorders v0.201 CHD4 Zornitza Stark Gene: chd4 has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.201 CHD4 Zornitza Stark Classified gene: CHD4 as Amber List (moderate evidence)
Clefting disorders v0.201 CHD4 Zornitza Stark Gene: chd4 has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.200 CHD4 Zornitza Stark gene: CHD4 was added
gene: CHD4 was added to Clefting disorders. Sources: Expert Review
Mode of inheritance for gene: CHD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD4 were set to 31388190; 37010288
Phenotypes for gene: CHD4 were set to Sifrim-Hitz-Weiss syndrome, MIM 617159
Review for gene: CHD4 was set to AMBER
Added comment: Although there are four unrelated cases presenting with either cleft palate and/or bifid uvula, this phenotype is not consistent among patients identified with monoallelic variants in CHD4 gene.

PMID:31388190 reported 32 patients with heterozygous variants in CHD4 gene, of which one individual (p.Gln715Ter) had cleft palate and Pierre Robin sequence. In addition, another individual identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, 2 out of 10 individuals with pathogenic/ likely pathogenic heterozygous variants from the DDD study were reported with cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288).
Sources: Expert Review
Clefting disorders v0.199 B4GALT7 Zornitza Stark Marked gene: B4GALT7 as ready
Clefting disorders v0.199 B4GALT7 Zornitza Stark Gene: b4galt7 has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.199 B4GALT7 Zornitza Stark Phenotypes for gene: B4GALT7 were changed from EHLERS-DANLOS SYNDROME WITH SHORT STATURE AND LIMB ANOMALIES; EDSSLA to Ehlers-Danlos syndrome, spondylodysplastic type, 1, MIM# 130070
Clefting disorders v0.198 B4GALT7 Zornitza Stark reviewed gene: B4GALT7: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, spondylodysplastic type, 1, MIM# 130070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.169 DNAJC3 Zornitza Stark Marked gene: DNAJC3 as ready
Hereditary Neuropathy - complex v0.169 DNAJC3 Zornitza Stark Gene: dnajc3 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.169 DNAJC3 Zornitza Stark Phenotypes for gene: DNAJC3 were changed from Cerebellar ataxia, neuropathy with SNCV, hearing loss, diabetes mellitus to Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, MIM# 616192
Hereditary Neuropathy - complex v0.168 DNAJC3 Zornitza Stark Publications for gene: DNAJC3 were set to 25466870
Hereditary Neuropathy - complex v0.167 DDHD1 Zornitza Stark Marked gene: DDHD1 as ready
Hereditary Neuropathy - complex v0.167 DDHD1 Zornitza Stark Gene: ddhd1 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.167 DDHD1 Zornitza Stark Classified gene: DDHD1 as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.167 DDHD1 Zornitza Stark Gene: ddhd1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.104 MLC1 Zornitza Stark Marked gene: MLC1 as ready
Cerebral Palsy v1.104 MLC1 Zornitza Stark Gene: mlc1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.104 MLC1 Zornitza Stark Classified gene: MLC1 as Red List (low evidence)
Cerebral Palsy v1.104 MLC1 Zornitza Stark Gene: mlc1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.103 WDR26 Zornitza Stark Marked gene: WDR26 as ready
Cerebral Palsy v1.103 WDR26 Zornitza Stark Gene: wdr26 has been classified as Green List (High Evidence).
Cerebral Palsy v1.103 WDR26 Zornitza Stark Classified gene: WDR26 as Green List (high evidence)
Cerebral Palsy v1.103 WDR26 Zornitza Stark Gene: wdr26 has been classified as Green List (High Evidence).
Cerebral Palsy v1.102 WWOX Zornitza Stark Marked gene: WWOX as ready
Cerebral Palsy v1.102 WWOX Zornitza Stark Gene: wwox has been classified as Green List (High Evidence).
Cerebral Palsy v1.102 WWOX Zornitza Stark Classified gene: WWOX as Green List (high evidence)
Cerebral Palsy v1.102 WWOX Zornitza Stark Gene: wwox has been classified as Green List (High Evidence).
Callosome v0.497 MLH1 Zornitza Stark Marked gene: MLH1 as ready
Callosome v0.497 MLH1 Zornitza Stark Gene: mlh1 has been classified as Red List (Low Evidence).
Callosome v0.497 MSH2 Zornitza Stark Marked gene: MSH2 as ready
Callosome v0.497 MSH2 Zornitza Stark Gene: msh2 has been classified as Red List (Low Evidence).
Callosome v0.497 MSH6 Zornitza Stark Marked gene: MSH6 as ready
Callosome v0.497 MSH6 Zornitza Stark Gene: msh6 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.101 KMT2B Zornitza Stark Phenotypes for gene: KMT2B were changed from Dystonia 28, childhood-onset - #617284 to Dystonia 28, childhood-onset MIM#617284; Intellectual developmental disorder, autosomal dominant MIM#619934
Cerebral Palsy v1.100 KMT2B Zornitza Stark Publications for gene: KMT2B were set to 29697234
Cerebral Palsy v1.99 KMT2B Zornitza Stark Classified gene: KMT2B as Green List (high evidence)
Cerebral Palsy v1.99 KMT2B Zornitza Stark Gene: kmt2b has been classified as Green List (High Evidence).
Cerebral Palsy v1.98 KCNT1 Zornitza Stark Marked gene: KCNT1 as ready
Cerebral Palsy v1.98 KCNT1 Zornitza Stark Gene: kcnt1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.98 KCNT1 Zornitza Stark Classified gene: KCNT1 as Green List (high evidence)
Cerebral Palsy v1.98 KCNT1 Zornitza Stark Gene: kcnt1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.97 KCNB1 Zornitza Stark Marked gene: KCNB1 as ready
Cerebral Palsy v1.97 KCNB1 Zornitza Stark Gene: kcnb1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.97 KCNB1 Zornitza Stark Classified gene: KCNB1 as Red List (low evidence)
Cerebral Palsy v1.97 KCNB1 Zornitza Stark Gene: kcnb1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.96 KAT6A Zornitza Stark Marked gene: KAT6A as ready
Cerebral Palsy v1.96 KAT6A Zornitza Stark Gene: kat6a has been classified as Green List (High Evidence).
Cerebral Palsy v1.96 KAT6A Zornitza Stark Classified gene: KAT6A as Green List (high evidence)
Cerebral Palsy v1.96 KAT6A Zornitza Stark Gene: kat6a has been classified as Green List (High Evidence).
Cerebral Palsy v1.95 IRF2BPL Zornitza Stark Marked gene: IRF2BPL as ready
Cerebral Palsy v1.95 IRF2BPL Zornitza Stark Gene: irf2bpl has been classified as Green List (High Evidence).
Cerebral Palsy v1.95 IRF2BPL Zornitza Stark Classified gene: IRF2BPL as Green List (high evidence)
Cerebral Palsy v1.95 IRF2BPL Zornitza Stark Gene: irf2bpl has been classified as Green List (High Evidence).
Cerebral Palsy v1.94 IQSEC2 Zornitza Stark Publications for gene: IQSEC2 were set to 33368194; 20473311; 23674175
Cerebral Palsy v1.93 IQSEC2 Zornitza Stark Classified gene: IQSEC2 as Amber List (moderate evidence)
Cerebral Palsy v1.93 IQSEC2 Zornitza Stark Gene: iqsec2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.92 IFIH1 Zornitza Stark Marked gene: IFIH1 as ready
Cerebral Palsy v1.92 IFIH1 Zornitza Stark Gene: ifih1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.92 IFIH1 Zornitza Stark Phenotypes for gene: IFIH1 were changed from Aicardi-Goutieres syndrome 7 MIM#615846; Immunodeficiency 95 MIM#619773; Singleton-Merten syndrome MIM#182250 to Aicardi-Goutieres syndrome 7 MIM#615846
Cerebral Palsy v1.91 IFIH1 Zornitza Stark Classified gene: IFIH1 as Green List (high evidence)
Cerebral Palsy v1.91 IFIH1 Zornitza Stark Gene: ifih1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.90 HUWE1 Zornitza Stark Marked gene: HUWE1 as ready
Cerebral Palsy v1.90 HUWE1 Zornitza Stark Gene: huwe1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.90 HUWE1 Zornitza Stark Classified gene: HUWE1 as Red List (low evidence)
Cerebral Palsy v1.90 HUWE1 Zornitza Stark Gene: huwe1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.89 HPRT1 Zornitza Stark Marked gene: HPRT1 as ready
Cerebral Palsy v1.89 HPRT1 Zornitza Stark Gene: hprt1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.89 HPRT1 Zornitza Stark Classified gene: HPRT1 as Green List (high evidence)
Cerebral Palsy v1.89 HPRT1 Zornitza Stark Gene: hprt1 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.176 DOCK11 Zornitza Stark Phenotypes for gene: DOCK11 were changed from autoimmune disease MONDO:0007179, DOCK11-related to Autoimmune disease with immune dysregulation, X-linked (ADMIDX), MIM#301109
Mendeliome v1.968 DOCK11 Zornitza Stark Phenotypes for gene: DOCK11 were changed from autoimmune disease MONDO:0007179, DOCK11-related to Autoimmune disease with immune dysregulation, X-linked (ADMIDX), MIM#301109
Monogenic Diabetes v0.40 ZNF808 Krithika Murali Marked gene: ZNF808 as ready
Monogenic Diabetes v0.40 ZNF808 Krithika Murali Gene: znf808 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.40 ZNF808 Krithika Murali Classified gene: ZNF808 as Green List (high evidence)
Monogenic Diabetes v0.40 ZNF808 Krithika Murali Gene: znf808 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.39 ZNF808 Krithika Murali gene: ZNF808 was added
gene: ZNF808 was added to Monogenic Diabetes. Sources: Literature
Mode of inheritance for gene: ZNF808 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF808 were set to PMID: 37308312
Phenotypes for gene: ZNF808 were set to non-syndromic neonatal diabetes; MONDO:0016391
Review for gene: ZNF808 was set to GREEN
Added comment: PMID: 37308312; Alqahtani, MA. et al. (2023) Clin Genet. doi: 10.1111/cge.14389. Three siblings in one consanguineous Saudi Arabian family with non-syndromic neonatal diabetes, all with a homozygous frameshift variant, NM_001321425.2:c.1448dupA, p.(Tyr483*), in ZNF808. (Same nucleotide and amino acid numbering as for the MANE SELECT transcript, NM_001039886.4). This variant has been entered as likely pathogenic in ClinVar by this group. This variant occurs in the last exon of the gene and is therefore not NMD-predicted. Instead it is predicted to cause a truncated protein. This paper shows a diagram with several other truncating variants in this exon, which were reported in the paper by De Franco, E. et al. (2021). (These patients also had low vitamin D levels, suggesting an association, and is consistent with other studies looking into loci that are associated with vitamin D). De Franco, E. et al. (2021) medRxiv 08.23.21262262. (Exeter, UK): Firstly, this group found a homozygous variant NM_001039886.3:c.637del, p.(Leu213*) that is predicted to cause a truncated protein, and also a homozygous CNV Chr19(GRCh37):g.53057128_53100968del (predicted to cause a deletion of exons 4 and 5) in two unrelated affected individuals. These patients had pancreatic agenesis, defined as insulin-dependent diabetes in the first 6 months of life (neonatal diabetes) and exocrine pancreatic insufficiency. Both were from consanguineous families. Parents were subsequently tested and shown to be heterozygous carriers. They then investigated 232 additional patients who had been diagnosed with neonatal diabetes before the age of 6 months and found ten more homozygous ZNF808 variants. Six were nonsense: p.(Gln194*), p.(Cys233*), p.(Tyr427*), p.(Lys458*), p.(Tyr528*) and p.(Arg727*), and three were frameshift variants: p.(Ala379Valfs*157), p.(Leu588Profs*118), p.(Asn770Ilefs*98) and one was a whole-gene deletion. All the frameshift and nonsense variants occurred in the last exon of the gene, which contains all 23 zinc finger domains; and therefore all of these variants are predicted to result in truncated proteins, and removal of some, if not all, those domains. This group also carried out functional studies using an in vitro model of pancreas development and showed an aberrant activation of many transposable elements (mostly MER11 elements) that would be normally be repressed during early pancreas development.
Sources: Literature
Mendeliome v1.967 ZNF808 Krithika Murali Marked gene: ZNF808 as ready
Mendeliome v1.967 ZNF808 Krithika Murali Gene: znf808 has been classified as Green List (High Evidence).
Mendeliome v1.967 ZNF808 Krithika Murali Classified gene: ZNF808 as Green List (high evidence)
Mendeliome v1.967 ZNF808 Krithika Murali Added comment: Comment on list classification: Green in Genomics England PanelApp neonatal diabetes panel with both of these papers cited in their review. Note that De Franco et al has not been peer-reviewed, however, the evidence provided is strong and from a reputable source.
Mendeliome v1.967 ZNF808 Krithika Murali Gene: znf808 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.166 GBA2 Sangavi Sivagnanasundram reviewed gene: GBA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301682, 23332917, 29524657; Phenotypes: Spastic paraplegia 46 MIM#614409; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.166 EXOSC3 Sangavi Sivagnanasundram reviewed gene: EXOSC3: Rating: AMBER; Mode of pathogenicity: None; Publications: 25144110, 22544365; Phenotypes: Pontocerebellar hypoplasia, type 1B, MIM#614678; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.166 ERCC6 Sangavi Sivagnanasundram edited their review of gene: ERCC6: Changed rating: RED
Hereditary Neuropathy - complex v0.166 ERCC6 Sangavi Sivagnanasundram changed review comment from: Peripheral neuropathy with nerve conduction study confirmation is a minor criteria for suspected individuals with Cockayne Syndrome.

No reports of neuropathy as a phenotype in a confirmed diagnosis of Cockayne Syndrome.; to: No established gene-disease association

Peripheral neuropathy with nerve conduction study confirmation is a minor criteria for suspected individuals with Cockayne Syndrome.

No reports of neuropathy as a phenotype in a confirmed diagnosis of Cockayne Syndrome.
Hereditary Neuropathy - complex v0.166 ERCC8 Sangavi Sivagnanasundram reviewed gene: ERCC8: Rating: RED; Mode of pathogenicity: None; Publications: 4320535; Phenotypes: Cockayne syndrome, type A MIM#216400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.166 ERCC6 Sangavi Sivagnanasundram edited their review of gene: ERCC6: Changed rating: AMBER
Mendeliome v1.966 ZNF808 Hazel Phillimore gene: ZNF808 was added
gene: ZNF808 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF808 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF808 were set to PMID: 37308312
Phenotypes for gene: ZNF808 were set to non-syndromic neonatal diabetes; MONDO:0016391
Review for gene: ZNF808 was set to GREEN
Added comment: PMID: 37308312; Alqahtani, MA. et al. (2023) Clin Genet. doi: 10.1111/cge.14389.
Three siblings in one consanguineous Saudi Arabian family with non-syndromic neonatal diabetes, all with a homozygous frameshift variant, NM_001321425.2:c.1448dupA, p.(Tyr483*), in ZNF808. (Same nucleotide and amino acid numbering as for the MANE SELECT transcript, NM_001039886.4).
This variant has been entered as likely pathogenic in ClinVar by this group.
This variant occurs in the last exon of the gene and is therefore not NMD-predicted. Instead it is predicted to cause a truncated protein.
This paper shows a diagram with several other truncating variants in this exon, which were reported in the paper by De Franco, E. et al. (2021).
(These patients also had low vitamin D levels, suggesting an association, and is consistent with other studies looking into loci that are associated with vitamin D).

De Franco, E. et al. (2021) medRxiv 08.23.21262262. (Exeter, UK):
Firstly, this group found a homozygous variant NM_001039886.3:c.637del, p.(Leu213*) that is predicted to cause a truncated protein, and also a homozygous CNV Chr19(GRCh37):g.53057128_53100968del (predicted to cause a deletion of exons 4 and 5) in two unrelated affected individuals. These patients had pancreatic agenesis, defined as insulin-dependent diabetes in the first 6 months of life (neonatal diabetes) and exocrine pancreatic insufficiency. Both were from consanguineous families. Parents were subsequently tested and shown to be heterozygous carriers.
They then investigated 232 additional patients who had been diagnosed with neonatal diabetes before the age of 6 months and found ten more homozygous ZNF808 variants. Six were nonsense: p.(Gln194*), p.(Cys233*), p.(Tyr427*), p.(Lys458*), p.(Tyr528*) and p.(Arg727*), and three were frameshift variants: p.(Ala379Valfs*157), p.(Leu588Profs*118), p.(Asn770Ilefs*98) and one was a whole-gene deletion.
All the frameshift and nonsense variants occurred in the last exon of the gene, which contains all 23 zinc finger domains; and therefore all of these variants are predicted to result in truncated proteins, and removal of some, if not all, those domains.
This group also carried out functional studies using an in vitro model of pancreas development and showed an aberrant activation of many transposable elements (mostly MER11 elements) that would be normally be repressed during early pancreas development.
Sources: Literature
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.9 IFT74 Krithika Murali Classified gene: IFT74 as Green List (high evidence)
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.9 IFT74 Krithika Murali Gene: ift74 has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.8 IFT74 Krithika Murali Marked gene: IFT74 as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.8 IFT74 Krithika Murali Gene: ift74 has been removed from the panel.
Congenital Heart Defect v0.289 IFT74 Krithika Murali Marked gene: IFT74 as ready
Congenital Heart Defect v0.289 IFT74 Krithika Murali Gene: ift74 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.289 IFT74 Krithika Murali Classified gene: IFT74 as Green List (high evidence)
Congenital Heart Defect v0.289 IFT74 Krithika Murali Gene: ift74 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.288 IFT74 Naomi Baker gene: IFT74 was added
gene: IFT74 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: IFT74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT74 were set to PMID: 37315079
Phenotypes for gene: IFT74 were set to Jeune syndrome (MONDO:0018770), IFT74-related
Added comment: Five individuals from four families reported. A homozygous exon 2 deletion was identified in two families, and splice variants were identified in the other two families (with minigene experiments demonstrating an effect on splicing of the non-canonical/deep intronic splice variants).

Four of the five individuals had heart defects, including ASD, AVSD, patent ductus arteriosus, double outlet right ventricle, hypoplastic left heart, aortic atresia, and hypoplastic left
ventricle.

Authors also characterised three mouse Ift74 alleles, with phenotypes ranging from a severe mid gestational lethal phenotype in the Ift74Tm1d out of frame exon 3 deletion allele, a post-natal lethal phenotype in the Ift74Tm1a exon 2 skip allele, to no detectable phenotype in Ift74Tm1b in frame exon 3 deletion allele.
Sources: Literature
Skeletal dysplasia v0.240 IFT74 Krithika Murali Classified gene: IFT74 as Green List (high evidence)
Skeletal dysplasia v0.240 IFT74 Krithika Murali Gene: ift74 has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.8 IFT74 Naomi Baker gene: IFT74 was added
gene: IFT74 was added to Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy. Sources: Literature
Mode of inheritance for gene: IFT74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT74 were set to PMID: 37315079
Phenotypes for gene: IFT74 were set to Jeune syndrome (MONDO:0018770), IFT74-related
Review for gene: IFT74 was set to GREEN
Added comment: Five individuals from four families reported. A homozygous exon 2 deletion was identified in two families, and splice variants were identified in the other two families (with minigene experiments demonstrating an effect on splicing of the non-canonical/deep intronic splice variants).

Authors also characterised three mouse Ift74 alleles, with phenotypes ranging from a severe mid gestational lethal phenotype in the Ift74Tm1d out of frame exon 3 deletion allele, a post-natal lethal phenotype in the Ift74Tm1a exon 2 skip allele, to no detectable phenotype in Ift74Tm1b in frame exon 3 deletion allele.
Sources: Literature
Skeletal dysplasia v0.239 IFT74 Krithika Murali Classified gene: IFT74 as Green List (high evidence)
Skeletal dysplasia v0.239 IFT74 Krithika Murali Gene: ift74 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.238 IFT74 Krithika Murali Marked gene: IFT74 as ready
Skeletal dysplasia v0.238 IFT74 Krithika Murali Gene: ift74 has been removed from the panel.
Renal Ciliopathies and Nephronophthisis v1.20 IFT74 Krithika Murali Classified gene: IFT74 as Green List (high evidence)
Renal Ciliopathies and Nephronophthisis v1.20 IFT74 Krithika Murali Gene: ift74 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.205 IFT74 Krithika Murali Marked gene: IFT74 as ready
Skeletal Dysplasia_Fetal v0.205 IFT74 Krithika Murali Gene: ift74 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.205 IFT74 Krithika Murali Classified gene: IFT74 as Green List (high evidence)
Skeletal Dysplasia_Fetal v0.205 IFT74 Krithika Murali Gene: ift74 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v1.19 IFT74 Naomi Baker reviewed gene: IFT74: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37315079; Phenotypes: Jeune syndrome (MONDO:0018770), IFT74-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.204 IFT74 Naomi Baker gene: IFT74 was added
gene: IFT74 was added to Skeletal Dysplasia_Fetal. Sources: Literature
Mode of inheritance for gene: IFT74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT74 were set to PMID: 37315079
Phenotypes for gene: IFT74 were set to Jeune syndrome (MONDO:0018770), IFT74-related
Review for gene: IFT74 was set to GREEN
Added comment: Five individuals from four families reported. A homozygous exon 2 deletion was identified in two families, and splice variants were identified in the other two families (with minigene experiments demonstrating an effect on splicing of the non-canonical/deep intronic splice variants).

Authors also characterised three mouse Ift74 alleles, with phenotypes ranging from a severe mid gestational lethal phenotype in the Ift74Tm1d out of frame exon 3 deletion allele, a post-natal lethal phenotype in the Ift74Tm1a exon 2 skip allele, to no detectable phenotype in Ift74Tm1b in frame exon 3 deletion allele.
Sources: Literature
Skeletal dysplasia v0.238 IFT74 Naomi Baker gene: IFT74 was added
gene: IFT74 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: IFT74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT74 were set to PMID:37315079
Phenotypes for gene: IFT74 were set to Jeune syndrome (MONDO:0018770), IFT74-related
Review for gene: IFT74 was set to GREEN
Added comment: Five individuals from four families reported. A homozygous exon 2 deletion was identified in two families, and splice variants were identified in the other two families (with minigene experiments demonstrating an effect on splicing of the non-canonical/deep intronic splice variants).

Authors also characterised three mouse Ift74 alleles, with phenotypes ranging from a severe mid gestational lethal phenotype in the Ift74Tm1d out of frame exon 3 deletion allele, a post-natal lethal phenotype in the Ift74Tm1a exon 2 skip allele, to no detectable phenotype in Ift74Tm1b in frame exon 3 deletion allele.
Sources: Literature
Stroke v1.10 ANO1 Krithika Murali Marked gene: ANO1 as ready
Stroke v1.10 ANO1 Krithika Murali Gene: ano1 has been classified as Amber List (Moderate Evidence).
Stroke v1.10 ANO1 Krithika Murali Classified gene: ANO1 as Amber List (moderate evidence)
Stroke v1.10 ANO1 Krithika Murali Gene: ano1 has been classified as Amber List (Moderate Evidence).
Stroke v1.9 ANO1 Krithika Murali Classified gene: ANO1 as Amber List (moderate evidence)
Stroke v1.9 ANO1 Krithika Murali Added comment: Comment on list classification: Conflicting functional studies, mechanistic uncertainty, high gnomAD frequency for some variants and incomplete penetrance in family pedigrees noted favouring Amber classification until further supportive evidence available.
Stroke v1.9 ANO1 Krithika Murali Gene: ano1 has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.101 DKC1 Krithika Murali Classified gene: DKC1 as Green List (high evidence)
Inflammatory bowel disease v0.101 DKC1 Krithika Murali Gene: dkc1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1867 SART3 Krithika Murali Marked gene: SART3 as ready
Genetic Epilepsy v0.1867 SART3 Krithika Murali Added comment: Comment when marking as ready: PMID: 37296101 - 3 individuals from 3 unrelated families reported with seizures.
Genetic Epilepsy v0.1867 SART3 Krithika Murali Gene: sart3 has been removed from the panel.
Mendeliome v1.966 SART3 Krithika Murali Classified gene: SART3 as Green List (high evidence)
Mendeliome v1.966 SART3 Krithika Murali Gene: sart3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.275 SART3 Krithika Murali Classified gene: SART3 as Green List (high evidence)
Differences of Sex Development v0.275 SART3 Krithika Murali Gene: sart3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.274 SART3 Krithika Murali Marked gene: SART3 as ready
Differences of Sex Development v0.274 SART3 Krithika Murali Gene: sart3 has been removed from the panel.
Differences of Sex Development v0.274 SART3 Daniel Flanagan gene: SART3 was added
gene: SART3 was added to Differences of Sex Development. Sources: Expert list
Mode of inheritance for gene: SART3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SART3 were set to PMID: 37296101
Phenotypes for gene: SART3 were set to Neurodevelopmental disorder (MONDO#0700092), SART3-related; 46,XY disorder of sex development (MONDO:0020040), SART3-related
Review for gene: SART3 was set to GREEN
Added comment: Nine individuals from six families presenting with intellectual disability, global developmental delay, a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Additionally, two individuals had seizures and two had epileptiform activity reported on EEG.

Human induced pluripotent stem cells carrying patient variants in SART3 show disruption to multiple signalling pathways, upregulation of spliceosome components and demonstrate aberrant gonadal and neuronal differentiation in vitro.
Sources: Expert list
Mendeliome v1.965 SART3 Daniel Flanagan gene: SART3 was added
gene: SART3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SART3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SART3 were set to PMID: 37296101
Phenotypes for gene: SART3 were set to Neurodevelopmental disorder (MONDO#0700092), SART3-related; 46,XY disorder of sex development (MONDO:0020040), SART3-related
Review for gene: SART3 was set to GREEN
Added comment: Nine individuals from six families presenting with intellectual disability, global developmental delay, a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Additionally, two individuals had seizures and two had epileptiform activity reported on EEG.

Human induced pluripotent stem cells carrying patient variants in SART3 show disruption to multiple signalling pathways, upregulation of spliceosome components and demonstrate aberrant gonadal and neuronal differentiation in vitro.
Sources: Expert list
Combined Immunodeficiency v1.40 ARPC5 Elena Savva Classified gene: ARPC5 as Green List (high evidence)
Combined Immunodeficiency v1.40 ARPC5 Elena Savva Gene: arpc5 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.40 ARPC5 Elena Savva Classified gene: ARPC5 as Green List (high evidence)
Combined Immunodeficiency v1.40 ARPC5 Elena Savva Gene: arpc5 has been classified as Green List (High Evidence).
Mendeliome v1.965 ARPC5 Elena Savva Classified gene: ARPC5 as Green List (high evidence)
Mendeliome v1.965 ARPC5 Elena Savva Gene: arpc5 has been classified as Green List (High Evidence).
Mendeliome v1.964 ARPC5 Elena Savva Classified gene: ARPC5 as Green List (high evidence)
Mendeliome v1.964 ARPC5 Elena Savva Gene: arpc5 has been classified as Green List (High Evidence).
Mendeliome v1.963 ARPC5 Elena Savva Marked gene: ARPC5 as ready
Mendeliome v1.963 ARPC5 Elena Savva Gene: arpc5 has been removed from the panel.
Combined Immunodeficiency v1.39 ARPC5 Elena Savva Marked gene: ARPC5 as ready
Combined Immunodeficiency v1.39 ARPC5 Elena Savva Gene: arpc5 has been removed from the panel.
Mendeliome v1.963 NUDCD2 Krithika Murali Marked gene: NUDCD2 as ready
Mendeliome v1.963 NUDCD2 Krithika Murali Gene: nudcd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.963 NUDCD2 Seb Lunke Marked gene: NUDCD2 as ready
Mendeliome v1.963 NUDCD2 Seb Lunke Gene: nudcd2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1867 SART3 Daniel Flanagan gene: SART3 was added
gene: SART3 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: SART3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SART3 were set to PMID: 37296101
Phenotypes for gene: SART3 were set to Neurodevelopmental disorder (MONDO#0700092), SART3-related; 46,XY disorder of sex development (MONDO:0020040), SART3-related
Review for gene: SART3 was set to GREEN
Added comment: Nine individuals from six families presenting with intellectual disability, global developmental delay, a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Additionally, two individuals had seizures and two had epileptiform activity reported on EEG.

Human induced pluripotent stem cells carrying patient variants in SART3 show disruption to multiple signalling pathways, upregulation of spliceosome components and demonstrate aberrant gonadal and neuronal differentiation in vitro.
Sources: Expert list
Mendeliome v1.963 NUDCD2 Seb Lunke Classified gene: NUDCD2 as Amber List (moderate evidence)
Mendeliome v1.963 NUDCD2 Seb Lunke Gene: nudcd2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5256 SART3 Krithika Murali Classified gene: SART3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5256 SART3 Krithika Murali Gene: sart3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1867 RPH3A Elena Savva Classified gene: RPH3A as Green List (high evidence)
Genetic Epilepsy v0.1867 RPH3A Elena Savva Gene: rph3a has been classified as Green List (High Evidence).
Mendeliome v1.962 NUDCD2 Ee Ming Wong gene: NUDCD2 was added
gene: NUDCD2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUDCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDCD2 were set to 37272762
Phenotypes for gene: NUDCD2 were set to Multiple congenital anomalies (MONDO:0019042), NUDCD2-related
Penetrance for gene: NUDCD2 were set to unknown
Review for gene: NUDCD2 was set to AMBER
gene: NUDCD2 was marked as current diagnostic
Added comment: - Two unrelated probands, each biallelic for two variants in NUDCD2 (total 3x LoF variants, 1x missense variant)
- Immunoblotting of proteins extracted from the primary fibroblasts of one proband with 2x LoF variants demonstrated markedly reduced NUDCD2 levels compared to healthy individuals
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5255 SART3 Krithika Murali Marked gene: SART3 as ready
Intellectual disability syndromic and non-syndromic v0.5255 SART3 Krithika Murali Gene: sart3 has been removed from the panel.
Genetic Epilepsy v0.1866 RPH3A Elena Savva Classified gene: RPH3A as Green List (high evidence)
Genetic Epilepsy v0.1866 RPH3A Elena Savva Gene: rph3a has been classified as Green List (High Evidence).
Fetal anomalies v1.119 NUDCD2 Seb Lunke Marked gene: NUDCD2 as ready
Fetal anomalies v1.119 NUDCD2 Seb Lunke Gene: nudcd2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5255 RPH3A Elena Savva Classified gene: RPH3A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5255 RPH3A Elena Savva Gene: rph3a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1866 RPH3A Elena Savva Classified gene: RPH3A as Green List (high evidence)
Genetic Epilepsy v0.1866 RPH3A Elena Savva Gene: rph3a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5255 RPH3A Elena Savva Classified gene: RPH3A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5255 RPH3A Elena Savva Gene: rph3a has been classified as Green List (High Evidence).
Fetal anomalies v1.119 NUDCD2 Seb Lunke Classified gene: NUDCD2 as Amber List (moderate evidence)
Fetal anomalies v1.119 NUDCD2 Seb Lunke Gene: nudcd2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1865 RPH3A Elena Savva Marked gene: RPH3A as ready
Genetic Epilepsy v0.1865 RPH3A Elena Savva Gene: rph3a has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.5254 RPH3A Elena Savva Marked gene: RPH3A as ready
Intellectual disability syndromic and non-syndromic v0.5254 RPH3A Elena Savva Gene: rph3a has been removed from the panel.
Callosome v0.497 RAB34 Elena Savva Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Fetal anomalies v1.118 NUDCD2 Ee Ming Wong gene: NUDCD2 was added
gene: NUDCD2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NUDCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDCD2 were set to 37272762
Phenotypes for gene: NUDCD2 were set to Multiple congenital anomalies (MONDO:0019042), NUDCD2-related
Penetrance for gene: NUDCD2 were set to unknown
Review for gene: NUDCD2 was set to AMBER
gene: NUDCD2 was marked as current diagnostic
Added comment: - Two unrelated probands, each biallelic for two variants in NUDCD2 (total 3x LoF variants, 1x missense variant)
- Immunoblotting of proteins extracted from the primary fibroblasts of one proband with 2x LoF variants demonstrated markedly reduced NUDCD2 levels compared to healthy individuals
Sources: Literature
Callosome v0.497 RAB34 Elena Savva Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Mendeliome v1.962 DCAF13 Seb Lunke Marked gene: DCAF13 as ready
Mendeliome v1.962 DCAF13 Seb Lunke Gene: dcaf13 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.238 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Skeletal dysplasia v0.238 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Mendeliome v1.962 RAB34 Elena Savva Marked gene: RAB34 as ready
Mendeliome v1.962 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Mendeliome v1.962 RAB34 Elena Savva Phenotypes for gene: RAB34 were changed from Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Mendeliome v1.962 DCAF13 Seb Lunke Classified gene: DCAF13 as Red List (low evidence)
Mendeliome v1.962 DCAF13 Seb Lunke Gene: dcaf13 has been classified as Red List (Low Evidence).
Callosome v0.496 RAB34 Elena Savva Phenotypes for gene: RAB34 were changed from Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Mendeliome v1.962 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Mendeliome v1.962 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Fetal anomalies v1.118 RAB34 Elena Savva Marked gene: RAB34 as ready
Fetal anomalies v1.118 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Growth failure v1.64 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Growth failure v1.64 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Fetal anomalies v1.118 RAB34 Elena Savva Phenotypes for gene: RAB34 were changed from Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Fetal anomalies v1.117 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Fetal anomalies v1.117 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.237 DRG1 Krithika Murali Marked gene: DRG1 as ready
Skeletal dysplasia v0.237 DRG1 Krithika Murali Gene: drg1 has been removed from the panel.
Clefting disorders v0.198 RAB34 Elena Savva Marked gene: RAB34 as ready
Clefting disorders v0.198 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Clefting disorders v0.198 RAB34 Elena Savva Phenotypes for gene: RAB34 were changed from Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Callosome v0.496 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Callosome v0.496 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Clefting disorders v0.197 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Clefting disorders v0.197 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Callosome v0.495 RAB34 Elena Savva Marked gene: RAB34 as ready
Callosome v0.495 RAB34 Elena Savva Gene: rab34 has been removed from the panel.
Radial Ray Abnormalities v1.9 RAB34 Elena Savva Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Growth failure v1.63 DRG1 Krithika Murali Marked gene: DRG1 as ready
Growth failure v1.63 DRG1 Krithika Murali Gene: drg1 has been removed from the panel.
Skeletal dysplasia v0.237 DRG1 Dean Phelan gene: DRG1 was added
gene: DRG1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRG1 were set to PMID: 37179472
Phenotypes for gene: DRG1 were set to Neurodevelopmental disorder (MONDO:0700092), DRG1-related
Review for gene: DRG1 was set to GREEN
Added comment: PMID: 37179472
- Biallelic variants were identified in four affected individuals from three distinct families with neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature and craniofacial anomalies. Functional studies show the variants result in a loss of function.
Sources: Literature
Radial Ray Abnormalities v1.8 RAB34 Elena Savva Phenotypes for gene: RAB34 were changed from Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Radial Ray Abnormalities v1.7 RAB34 Elena Savva Marked gene: RAB34 as ready
Radial Ray Abnormalities v1.7 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Growth failure v1.63 DRG1 Krithika Murali Marked gene: DRG1 as ready
Growth failure v1.63 DRG1 Krithika Murali Gene: drg1 has been removed from the panel.
Radial Ray Abnormalities v1.7 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Radial Ray Abnormalities v1.7 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Microcephaly v1.209 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Microcephaly v1.209 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Microcephaly v1.209 DRG1 Krithika Murali Marked gene: DRG1 as ready
Microcephaly v1.209 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Microcephaly v1.209 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Microcephaly v1.209 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Microcephaly v1.208 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Microcephaly v1.208 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Radial Ray Abnormalities v1.6 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Radial Ray Abnormalities v1.6 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Microcephaly v1.208 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Microcephaly v1.208 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Microcephaly v1.207 DRG1 Dean Phelan gene: DRG1 was added
gene: DRG1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRG1 were set to PMID: 37179472
Phenotypes for gene: DRG1 were set to Neurodevelopmental disorder (MONDO:0700092), DRG1-related
Review for gene: DRG1 was set to GREEN
Added comment: PMID: 37179472
- Biallelic variants were identified in four affected individuals from three distinct families with neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature and craniofacial anomalies. Functional studies show the variants result in a loss of function.
Sources: Literature
Mendeliome v1.961 ARPC5 Paul De Fazio gene: ARPC5 was added
gene: ARPC5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARPC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARPC5 were set to 37349293; 37382373
Phenotypes for gene: ARPC5 were set to Combined immunodeficiency, ARPC5-related MONDO:0015131
Review for gene: ARPC5 was set to GREEN
gene: ARPC5 was marked as current diagnostic
Added comment: 4 individuals from 3 families reported with homozygous LoF variants. All had recurrent and severe infections. Other developmental anomalies were present but seemed variable.

PMID:37349293 reports 2 unrelated patients. Both had scoliosis. One had neurodevelopmental delay and brain atrophy. Patient 1 died at 15yo after a sudden episode of hemoptysis and hematochezia. Patient 2 died at 1yo because of progressive neurologic and respiratory disease; an autopsy was not performed.

PMID:37382373 reports 2 patients from the same family. One had multiple congenital anomalies including a congenital heart defect (CHD) (patent foramen ovale), cleft palate, and hypoplastic corpus callosum. The sibling also had CHD (moderate pulmonary stenosis and atrial septal defect).

Functional studies and a mouse model were supportive of the disease association.
Sources: Literature
Stroke v1.8 ANO1 Suliman Khan changed review comment from: Sources: Literature; to: PMID: 37253099: screening analysis of Moyamoya disease (MMD) cohort revealed 8 patients with variants in the ANO1 gene. Two families had the same rare variant p.Met658Val in ANO1 gene. The ANO1 rare variants were assessed using patch-clamp recordings, and the majority of variants, including ANO1 p.Met658Val, displayed increased sensitivity to intracellular Ca2+. Patients harboring these gain-of-function ANO1 variants had classic features of MMD, but also had aneurysm, stenosis, and/or occlusion in the posterior circulation.
Mendeliome v1.961 RPH3A Seb Lunke Marked gene: RPH3A as ready
Mendeliome v1.961 RPH3A Seb Lunke Gene: rph3a has been classified as Green List (High Evidence).
Stroke v1.8 ANO1 Suliman Khan gene: ANO1 was added
gene: ANO1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: ANO1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ANO1 were set to PMID: 37253099
Phenotypes for gene: ANO1 were set to moyamoya; cerebral arteriopathy; stroke; MONDO:0016820
Penetrance for gene: ANO1 were set to unknown
Review for gene: ANO1 was set to AMBER
Added comment: Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5254 SART3 Daniel Flanagan edited their review of gene: SART3: Changed phenotypes: Neurodevelopmental disorder (MONDO#0700092), SART3-related, 46,XY disorder of sex development (MONDO:0020040), SART3-related
Mendeliome v1.961 DRG1 Krithika Murali Marked gene: DRG1 as ready
Mendeliome v1.961 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Mendeliome v1.961 RPH3A Seb Lunke Classified gene: RPH3A as Green List (high evidence)
Mendeliome v1.961 RPH3A Seb Lunke Gene: rph3a has been classified as Green List (High Evidence).
Mendeliome v1.961 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Mendeliome v1.961 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.51 MIR204 Elena Savva Marked gene: MIR204 as ready
Cone-rod Dystrophy v0.51 MIR204 Elena Savva Gene: mir204 has been classified as Amber List (Moderate Evidence).
Growth failure v1.63 DRG1 Dean Phelan gene: DRG1 was added
gene: DRG1 was added to Growth failure. Sources: Literature
Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRG1 were set to PMID: 37179472
Phenotypes for gene: DRG1 were set to Neurodevelopmental disorder (MONDO:0700092), DRG1-related
Review for gene: DRG1 was set to GREEN
Added comment: PMID: 37179472
- Biallelic variants were identified in four affected individuals from three distinct families with neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature and craniofacial anomalies. Functional studies show the variants result in a loss of function.
Sources: Literature
Cone-rod Dystrophy v0.51 MIR204 Elena Savva Classified gene: MIR204 as Amber List (moderate evidence)
Cone-rod Dystrophy v0.51 MIR204 Elena Savva Gene: mir204 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.116 DRG1 Krithika Murali Marked gene: DRG1 as ready
Fetal anomalies v1.116 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Mendeliome v1.960 MIR204 Elena Savva Classified gene: MIR204 as Amber List (moderate evidence)
Mendeliome v1.960 MIR204 Elena Savva Gene: mir204 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.39 ARPC5 Paul De Fazio gene: ARPC5 was added
gene: ARPC5 was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: ARPC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARPC5 were set to 37349293; 37382373
Phenotypes for gene: ARPC5 were set to Combined immunodeficiency, ARPC5-related MONDO:0015131
Review for gene: ARPC5 was set to GREEN
gene: ARPC5 was marked as current diagnostic
Added comment: 4 individuals from 3 families reported with homozygous LoF variants. All had recurrent and severe infections. Other developmental anomalies were present but seemed variable.

PMID:37349293 reports 2 unrelated patients. Both had scoliosis. One had neurodevelopmental delay and brain atrophy. Patient 1 died at 15yo after a sudden episode of hemoptysis and hematochezia. Patient 2 died at 1yo because of progressive neurologic and respiratory disease; an autopsy was not performed.

PMID:37382373 reports 2 patients from the same family. One had multiple congenital anomalies including a congenital heart defect (CHD) (patent foramen ovale), cleft palate, and hypoplastic corpus callosum. The sibling also had CHD (moderate pulmonary stenosis and atrial septal defect).

Functional studies and a mouse model were supportive of the disease association.
Sources: Literature
Fetal anomalies v1.116 DRG1 Krithika Murali Publications for gene: DRG1 were set to PMID: 37179472
Mendeliome v1.959 MIR204 Elena Savva Classified gene: MIR204 as Amber List (moderate evidence)
Mendeliome v1.959 MIR204 Elena Savva Gene: mir204 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.958 MIR204 Elena Savva Marked gene: MIR204 as ready
Mendeliome v1.958 MIR204 Elena Savva Gene: mir204 has been removed from the panel.
Fetal anomalies v1.115 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Fetal anomalies v1.115 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.50 MIR204 Chern Lim gene: MIR204 was added
gene: MIR204 was added to Cone-rod Dystrophy. Sources: Literature
Mode of inheritance for gene: MIR204 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MIR204 were set to 26056285; 37321975
Phenotypes for gene: MIR204 were set to Retinal dystrophy and iris coloboma with or without cataract (MIM#616722)
Mode of pathogenicity for gene: MIR204 was set to Other
Review for gene: MIR204 was set to AMBER
gene: MIR204 was marked as current diagnostic
Added comment: PMID: 26056285
- Bilateral coloboma and rod-cone dystrophy with or without cataract in nine individuals of a five-generation family.
- Heterozygous n.37C>T segregates with the disease in all affected individuals.
- Functional analysis including transcriptome analysis showed this variant resulted in significant alterations of miR-204 targeting capabilities. In vivo injection, in medaka fish (Oryzias latipes), of the mutated miR-204 caused a phenotype consistent with that observed in the family.
- Authors suggested gain of function is the likely disease mechanism.

PMID: 37321975
- Four members of a three-generation family with early-onset chorioretinal dystrophy, heterozygous for n.37C>T.
- Additionally, four family members were shown to be affected by albinism resulting from biallelic pathogenic OCA2 variants.
- Haplotype analysis excluded relatedness with the family reported in PMID: 26056285.
- In silico analysis of the MIR204 n.37C>T variant reveals profound changes to its target mRNAs and suggests a gain-of-function mechanism of miR 204 variant.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5254 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5254 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Optic Atrophy v1.18 MIR204 Elena Savva Marked gene: MIR204 as ready
Optic Atrophy v1.18 MIR204 Elena Savva Gene: mir204 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5253 DRG1 Krithika Murali Marked gene: DRG1 as ready
Intellectual disability syndromic and non-syndromic v0.5253 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Fetal anomalies v1.114 DRG1 Dean Phelan gene: DRG1 was added
gene: DRG1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRG1 were set to PMID: 37179472
Phenotypes for gene: DRG1 were set to Neurodevelopmental disorder (MONDO:0700092), DRG1-related
Review for gene: DRG1 was set to GREEN
Added comment: PMID: 37179472
- Biallelic variants were identified in four affected individuals from three distinct families with neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature and craniofacial anomalies. Functional studies show the variants result in a loss of function.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5253 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5253 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Optic Atrophy v1.18 MIR204 Elena Savva Classified gene: MIR204 as Amber List (moderate evidence)
Optic Atrophy v1.18 MIR204 Elena Savva Gene: mir204 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v0.34 ANO1 Seb Lunke changed review comment from: Comment on list classification: This paper that indicates a predisposition, with both functional data and segregation data somewhat conflicting. Keep at amber for now as clear causality (consistent with author views) remains to be established.; to: Comment on list classification: This paper indicates a predisposition, with both functional data and segregation data somewhat conflicting. Keep at amber for now as clear causality (consistent with author views) remains to be established.
Cerebral vascular malformations v0.34 ANO1 Seb Lunke Marked gene: ANO1 as ready
Cerebral vascular malformations v0.34 ANO1 Seb Lunke Gene: ano1 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v0.34 ANO1 Seb Lunke Phenotypes for gene: ANO1 were changed from moyamoya; cerebral arteriopathy to Moyamoya disease, MONDO:0016820, ANO1 related
Cerebral vascular malformations v0.33 ANO1 Seb Lunke Classified gene: ANO1 as Amber List (moderate evidence)
Cerebral vascular malformations v0.33 ANO1 Seb Lunke Added comment: Comment on list classification: This paper that indicates a predisposition, with both functional data and segregation data somewhat conflicting. Keep at amber for now as clear causality (consistent with author views) remains to be established.
Cerebral vascular malformations v0.33 ANO1 Seb Lunke Gene: ano1 has been classified as Amber List (Moderate Evidence).
Radial Ray Abnormalities v1.5 RAB34 Sarah Pantaleo gene: RAB34 was added
gene: RAB34 was added to Radial Ray Abnormalities. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to PMID: 37384395
Phenotypes for gene: RAB34 were set to Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies
Penetrance for gene: RAB34 were set to Complete
Review for gene: RAB34 was set to GREEN
Added comment: Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogenous disorders characterised by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in >20 genes encoding ciliary proteins have been found to cause OFDS.

Identified by WES biallelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families (aided by GeneMatcher).

Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects.

RAB34 encodes a member of the Lab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Protein products of pathogenic variants clustered near the RAB34 C-terminus exhibit a strong loss of function.

Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, brain malformations), resulting in medical termination for three probands.

In the fourth, the only one alive at birth, proband born at 39+5 weeks, normal growth parameters after pregnancy with polyhydramnios, corpus callosum agenesis and polydactyly. Respiratory distress at birth.

All four probands presented typical features of ciliopathy disorders, overlapping with oral, facial and digital abnormalities.

All with homozygous missense variants. All absent in gnomAD (in homozygous state). Sanger sequencing confirmed mode of inheritance.
Sources: Literature
Mendeliome v1.958 DCAF13 Michelle Torres gene: DCAF13 was added
gene: DCAF13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DCAF13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DCAF13 were set to 36797467
Phenotypes for gene: DCAF13 were set to Neuromuscular disease (MONDO#0019056), DCAF13-related
Review for gene: DCAF13 was set to RED
Added comment: One consanguineous family, 4x individuals homozygous NM_015420.7(DCAF13)c.907 G > A; p.(Asp303Asn) (3x via WES and 1x via Sanger) with a neuromuscular disorder characterized by a waddling gait, limb deformities, muscular weakness and facial palsy.

In silicos analysis of mutant DCAF13 suggests that the amino acid change is deleterious and affects a ß-hairpin turn, within a WD40 domain of the protein which may decrease protein stability. Functional studies were not performed.

Previously, a heterozygous variant in DCAF13 with or without a heterozygous missense variant in CCN3, was suggested to cause inherited cortical myoclonic tremor with epilepsy. In addition, a heterozygous DCAF13 variant has been associated with autism spectrum disorder.
Sources: Literature
Mendeliome v1.958 ERI1 Elena Savva Marked gene: ERI1 as ready
Mendeliome v1.958 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Mendeliome v1.958 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Mendeliome v1.958 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Mendeliome v1.957 ERI1 Elena Savva gene: ERI1 was added
gene: ERI1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 37352860
Phenotypes for gene: ERI1 were set to Spondyloepimetaphyseal dysplasia (MONDO#0100510), ERI1-related, Intellectual disability (MONDO#0001071), ERI1-related
Review for gene: ERI1 was set to GREEN
Added comment: PMID: 37352860 - 8 individuals from 7 unrelated families
- Patients with biallelic missense show a MORE severe spondyloepimetaphyseal dysplasia, syndactyly, brachydactyly/clinodactyly/camptodactyly
- Patients with biallelic null/whole gene deletion had mild ID and digit anomalies including brachydactyly/clinodactyly/camptodactyly
- Patient chet for a missense and PTC variant has a blended phenotype with short stature, syndactyly, brachydactyly/clinodactyly/camptodactyly, mild ID and failure to thrive

- Missense variants were functionally shown to not be able to rescue 5.8S rRNA processing in KO HeLa cells
- K/O mice had neonatal lethality with growth defects, brachydactyly. Skeletal-specific K/O had mild platyspondyly, had more in keeping with patients with null variants than missense

More severe phenotype hypothesised due to "exonuclease-dead proteins may compete for the target RNA molecules with other exonucleases that have functional redundancy
with ERI1, staying bound to those RNA molecules"
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5252 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5252 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5252 SART3 Daniel Flanagan gene: SART3 was added
gene: SART3 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: SART3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SART3 were set to PMID: 37296101
Phenotypes for gene: SART3 were set to Neurodevelopmental disorder (MONDO#0700092), SART3-related, with 46,XY gonadal dysgenesis
Review for gene: SART3 was set to GREEN
Added comment: Nine individuals from six families presenting with intellectual disability, global developmental delay, a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Additionally, two individuals had seizures and two had epileptiform activity reported on EEG.

Human induced pluripotent stem cells carrying patient variants in SART3 show disruption to multiple signalling pathways, upregulation of spliceosome components and demonstrate aberrant gonadal and neuronal differentiation in vitro.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5252 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5252 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5251 ERI1 Elena Savva Marked gene: ERI1 as ready
Intellectual disability syndromic and non-syndromic v0.5251 ERI1 Elena Savva Gene: eri1 has been classified as Red List (Low Evidence).
Skeletal Dysplasia_Fetal v0.204 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Skeletal Dysplasia_Fetal v0.204 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.204 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Skeletal Dysplasia_Fetal v0.204 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.203 ERI1 Elena Savva Marked gene: ERI1 as ready
Skeletal Dysplasia_Fetal v0.203 ERI1 Elena Savva Gene: eri1 has been classified as Red List (Low Evidence).
Mendeliome v1.956 RAB34 Sarah Pantaleo gene: RAB34 was added
gene: RAB34 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to PMID: 37384395
Phenotypes for gene: RAB34 were set to Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies
Penetrance for gene: RAB34 were set to Complete
Review for gene: RAB34 was set to GREEN
Added comment: Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogenous disorders characterised by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in >20 genes encoding ciliary proteins have been found to cause OFDS.

Identified by WES biallelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families (aided by GeneMatcher).

Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects.

RAB34 encodes a member of the Lab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Protein products of pathogenic variants clustered near the RAB34 C-terminus exhibit a strong loss of function.

Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, brain malformations), resulting in medical termination for three probands.

In the fourth, the only one alive at birth, proband born at 39+5 weeks, normal growth parameters after pregnancy with polyhydramnios, corpus callosum agenesis and polydactyly. Respiratory distress at birth.

All four probands presented typical features of ciliopathy disorders, overlapping with oral, facial and digital abnormalities.

All with homozygous missense variants. All absent in gnomAD (in homozygous state). Sanger sequencing confirmed mode of inheritance.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5251 ERI1 Elena Savva gene: ERI1 was added
gene: ERI1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 37352860
Phenotypes for gene: ERI1 were set to Intellectual disability (MONDO#0001071), ERI1-related
Review for gene: ERI1 was set to GREEN
Added comment: PMID: 37352860 - 8 individuals from 7 unrelated families
- Patients with biallelic missense show a MORE severe spondyloepimetaphyseal dysplasia, syndactyly, brachydactyly/clinodactyly/camptodactyly
- Patients with biallelic null/whole gene deletion had mild ID and digit anomalies including brachydactyly/clinodactyly/camptodactyly
- Patient chet for a missense and PTC variant has a blended phenotype with short stature, syndactyly, brachydactyly/clinodactyly/camptodactyly, mild ID and failure to thrive

- Missense variants were functionally shown to not be able to rescue 5.8S rRNA processing in KO HeLa cells
- K/O mice had neonatal lethality with growth defects, brachydactyly. Skeletal-specific K/O had mild platyspondyly, had more in keeping with patients with null variants than missense

More severe phenotype hypothesised due to "exonuclease-dead proteins may compete for the target RNA molecules with other exonucleases that have functional redundancy
with ERI1, staying bound to those RNA molecules"
Sources: Literature
Skeletal Dysplasia_Fetal v0.203 ERI1 Elena Savva gene: ERI1 was added
gene: ERI1 was added to Skeletal Dysplasia_Fetal. Sources: Literature
Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 37352860
Phenotypes for gene: ERI1 were set to Spondyloepimetaphyseal dysplasia (MONDO#0100510), ERI1-related
Review for gene: ERI1 was set to GREEN
Added comment: PMID: 37352860 - 8 individuals from 7 unrelated families
- Patients with biallelic missense show a MORE severe spondyloepimetaphyseal dysplasia, syndactyly, brachydactyly/clinodactyly/camptodactyly
- Patients with biallelic null/whole gene deletion had mild ID and digit anomalies including brachydactyly/clinodactyly/camptodactyly
- Patient chet for a missense and PTC variant has a blended phenotype with short stature, syndactyly, brachydactyly/clinodactyly/camptodactyly, mild ID and failure to thrive

- Missense variants were functionally shown to not be able to rescue 5.8S rRNA processing in KO HeLa cells
- K/O mice had neonatal lethality with growth defects, brachydactyly. Skeletal-specific K/O had mild platyspondyly, had more in keeping with patients with null variants than missense

More severe phenotype hypothesised due to "exonuclease-dead proteins may compete for the target RNA molecules with other exonucleases that have functional redundancy
with ERI1, staying bound to those RNA molecules"
Sources: Literature
Multiple epiphyseal dysplasia and pseudoachondroplasia v0.10 ERI1 Elena Savva Marked gene: ERI1 as ready
Multiple epiphyseal dysplasia and pseudoachondroplasia v0.10 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Multiple epiphyseal dysplasia and pseudoachondroplasia v0.10 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Multiple epiphyseal dysplasia and pseudoachondroplasia v0.10 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Callosome v0.495 RAB34 Sarah Pantaleo gene: RAB34 was added
gene: RAB34 was added to Callosome. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to PMID: 37384395
Phenotypes for gene: RAB34 were set to Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies
Penetrance for gene: RAB34 were set to Complete
Review for gene: RAB34 was set to GREEN
Added comment: Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogenous disorders characterised by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in >20 genes encoding ciliary proteins have been found to cause OFDS.

Identified by WES biallelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families (aided by GeneMatcher).

Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects.

RAB34 encodes a member of the Lab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Protein products of pathogenic variants clustered near the RAB34 C-terminus exhibit a strong loss of function.

Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, brain malformations), resulting in medical termination for three probands.

In the fourth, the only one alive at birth, proband born at 39+5 weeks, normal growth parameters after pregnancy with polyhydramnios, corpus callosum agenesis and polydactyly. Respiratory distress at birth.

All four probands presented typical features of ciliopathy disorders, overlapping with oral, facial and digital abnormalities.

All with homozygous missense variants. All absent in gnomAD (in homozygous state). Sanger sequencing confirmed mode of inheritance.
Sources: Literature
Multiple epiphyseal dysplasia and pseudoachondroplasia v0.9 ERI1 Elena Savva gene: ERI1 was added
gene: ERI1 was added to Multiple epiphyseal dysplasia and pseudoachondroplasia. Sources: Literature
Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 37352860
Review for gene: ERI1 was set to GREEN
Added comment: PMID: 37352860 - 8 individuals from 7 unrelated families
- Patients with biallelic missense show a MORE severe spondyloepimetaphyseal dysplasia, syndactyly, brachydactyly/clinodactyly/camptodactyly
- Patients with biallelic null/whole gene deletion had mild ID and digit anomalies including brachydactyly/clinodactyly/camptodactyly
- Patient chet for a missense and PTC variant has a blended phenotype with short stature, syndactyly, brachydactyly/clinodactyly/camptodactyly, mild ID and failure to thrive

- Missense variants were functionally shown to not be able to rescue 5.8S rRNA processing in KO HeLa cells
- K/O mice had neonatal lethality with growth defects, brachydactyly. Skeletal-specific K/O had mild platyspondyly, had more in keeping with patients with null variants than missense

More severe phenotype hypothesised due to "exonuclease-dead proteins may compete for the target RNA molecules with other exonucleases that have functional redundancy
with ERI1, staying bound to those RNA molecules"
Sources: Literature
Skeletal dysplasia v0.237 ERI1 Elena Savva Phenotypes for gene: ERI1 were changed from Spondyloepimetaphyseal dysplasia (MONDO#0100510), ERI1-related, Intellectual disability (MONDO#0001071), ERI1-related to Spondyloepimetaphyseal dysplasia (MONDO#0100510), ERI1-related
Inflammatory bowel disease v0.100 DKC1 Krithika Murali reviewed gene: DKC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32554502; Phenotypes: DKC1-related disorder - MONDO: 0100152; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Clefting disorders v0.196 RAB34 Sarah Pantaleo gene: RAB34 was added
gene: RAB34 was added to Clefting disorders. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to PMID: 37384395
Phenotypes for gene: RAB34 were set to Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies
Penetrance for gene: RAB34 were set to Complete
Review for gene: RAB34 was set to GREEN
Added comment: Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogenous disorders characterised by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in >20 genes encoding ciliary proteins have been found to cause OFDS.

Identified by WES biallelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families (aided by GeneMatcher).

Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects.

RAB34 encodes a member of the Lab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Protein products of pathogenic variants clustered near the RAB34 C-terminus exhibit a strong loss of function.

Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, brain malformations), resulting in medical termination for three probands.

In the fourth, the only one alive at birth, proband born at 39+5 weeks, normal growth parameters after pregnancy with polyhydramnios, corpus callosum agenesis and polydactyly. Respiratory distress at birth.

All four probands presented typical features of ciliopathy disorders, overlapping with oral, facial and digital abnormalities.

All with homozygous missense variants. All absent in gnomAD (in homozygous state). Sanger sequencing confirmed mode of inheritance.
Sources: Literature
Genetic Epilepsy v0.1865 RPH3A Lucy Spencer gene: RPH3A was added
gene: RPH3A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RPH3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPH3A were set to 37403762; 29441694
Phenotypes for gene: RPH3A were set to Neurodevelopmental disorder (MONDO#0700092), RPH3A-related
Review for gene: RPH3A was set to GREEN
Added comment: PMID: 37403762- 6 patients with RPH3A variant. All 6 have ID, 4 have epilepsy, 2 with obesity, 1 with dysmorphic features. All 6 have missense variants, 3 shown to be de novo, the other 3 parents were not available for testing. I patient also had language and motor impairment, breathing issues and mixed hypo/hypertonia- he also had variants in CUL4B, PRKAG2, SCN4A, none of these genes cause seizures (which he had).

Patch clamp studies on 2 of the missense showed they increased either the number of NMDA receptors on neuron membrane surface or increased their conductance. Study suggests that the variants interrupt the normal role of RPH3A activity at the synaptic NMDAR complex which is needed for the induction of synaptic plasticity and NMDAR-dependant behaviours

Also previously 1 biallelic patient was reported, PMID: 29441694- 1 girl with learning disabilities, tremors, ataxia, hyperglycemia and muscle fatigability. Chet for 2 RPH3A missense. Functional analysis showed strong and marginal impairment of protein binding for each variant.
Sources: Literature
Mendeliome v1.956 DRG1 Dean Phelan gene: DRG1 was added
gene: DRG1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRG1 were set to PMID: 37179472
Phenotypes for gene: DRG1 were set to Neurodevelopmental disorder (MONDO:0700092), DRG1-related
Review for gene: DRG1 was set to GREEN
Added comment: PMID: 37179472
- Biallelic variants were identified in four affected individuals from three distinct families with neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature and craniofacial anomalies. Functional studies show the variants result in a loss of function.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5250 RPH3A Lucy Spencer gene: RPH3A was added
gene: RPH3A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RPH3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPH3A were set to 37403762; 29441694
Phenotypes for gene: RPH3A were set to Neurodevelopmental disorder (MONDO#0700092), RPH3A-related
Review for gene: RPH3A was set to GREEN
Added comment: PMID: 37403762- 6 patients with RPH3A variant. All 6 have ID, 4 have epilepsy, 2 with obesity, 1 with dysmorphic features. All 6 have missense variants, 3 shown to be de novo, the other 3 parents were not available for testing. I patient also had language and motor impairment, breathing issues and mixed hypo/hypertonia- he also had variants in CUL4B, PRKAG2, SCN4A, none of these genes cause seizures (which he had).

Patch clamp studies on 2 of the missense showed they increased either the number of NMDA receptors on neuron membrane surface or increased their conductance. Study suggests that the variants interrupt the normal role of RPH3A activity at the synaptic NMDAR complex which is needed for the induction of synaptic plasticity and NMDAR-dependant behaviours

Also previously 1 biallelic patient was reported, PMID: 29441694- 1 girl with learning disabilities, tremors, ataxia, hyperglycemia and muscle fatigability. Chet for 2 RPH3A missense. Functional analysis showed strong and marginal impairment of protein binding for each variant.
Sources: Literature
Fetal anomalies v1.114 RAB34 Sarah Pantaleo gene: RAB34 was added
gene: RAB34 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to PMID: 37384395
Phenotypes for gene: RAB34 were set to Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies
Penetrance for gene: RAB34 were set to Complete
Review for gene: RAB34 was set to GREEN
Added comment: Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogenous disorders characterised by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in >20 genes encoding ciliary proteins have been found to cause OFDS.

Identified by WES biallelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families (aided by GeneMatcher).

Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects.

RAB34 encodes a member of the Lab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Protein products of pathogenic variants clustered near the RAB34 C-terminus exhibit a strong loss of function.

Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, brain malformations), resulting in medical termination for three probands.

In the fourth, the only one alive at birth, proband born at 39+5 weeks, normal growth parameters after pregnancy with polyhydramnios, corpus callosum agenesis and polydactyly. Respiratory distress at birth.

All four probands presented typical features of ciliopathy disorders, overlapping with oral, facial and digital abnormalities.

All with homozygous missense variants. All absent in gnomAD (in homozygous state). Sanger sequencing confirmed mode of inheritance.
Sources: Literature
Mendeliome v1.956 RPH3A Lucy Spencer gene: RPH3A was added
gene: RPH3A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPH3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPH3A were set to 37403762; 29441694
Phenotypes for gene: RPH3A were set to Neurodevelopmental disorder (MONDO#0700092), RPH3A-related
Review for gene: RPH3A was set to GREEN
Added comment: PMID: 37403762- 6 patients with RPH3A variant. All 6 have ID, 4 have epilepsy, 2 with obesity, 1 with dysmorphic features. All 6 have missense variants, 3 shown to be de novo, the other 3 parents were not available for testing. I patient also had language and motor impairment, breathing issues and mixed hypo/hypertonia- he also had variants in CUL4B, PRKAG2, SCN4A, none of these genes cause seizures (which he had).

Patch clamp studies on 2 of the missense showed they increased either the number of NMDA receptors on neuron membrane surface or increased their conductance. Study suggests that the variants interrupt the normal role of RPH3A activity at the synaptic NMDAR complex which is needed for the induction of synaptic plasticity and NMDAR-dependant behaviours

Previously this gene was reported in PMID: 29441694- 1 girl with learning disabilities, tremors, ataxia, hyperglycemia and muscle fatigability. Chet for 2 RPH3A missense. Functional analysis showed strong and marginal impairment of protein binding for each variant. this is the only biallelic report currently.
Sources: Literature
Mendeliome v1.956 MIR204 Chern Lim gene: MIR204 was added
gene: MIR204 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MIR204 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MIR204 were set to 26056285; 37321975
Phenotypes for gene: MIR204 were set to Retinal dystrophy and iris coloboma with or without cataract (MIM#616722)
Mode of pathogenicity for gene: MIR204 was set to Other
Review for gene: MIR204 was set to GREEN
gene: MIR204 was marked as current diagnostic
Added comment: PMID: 26056285
- Bilateral coloboma and rod-cone dystrophy with or without cataract in nine individuals of a five-generation family.
- Heterozygous n.37C>T segregates with the disease in all affected individuals.
- Functional analysis including transcriptome analysis showed this variant resulted in significant alterations of miR-204 targeting capabilities. In vivo injection, in medaka fish (Oryzias latipes), of the mutated miR-204 caused a phenotype consistent with that observed in the family.
- Authors suggested gain of function is the likely disease mechanism.

PMID: 37321975
- Four members of a three-generation family with early-onset chorioretinal dystrophy, heterozygous for n.37C>T.
- Additionally, four family members were shown to be affected by albinism resulting from biallelic pathogenic OCA2 variants.
- Haplotype analysis excluded relatedness with the family reported in PMID: 26056285.
- In silico analysis of the MIR204 n.37C>T variant reveals profound changes to its target mRNAs and suggests a gain-of-function mechanism of miR 204 variant.
Sources: Literature
Optic Atrophy v1.17 MIR204 Chern Lim gene: MIR204 was added
gene: MIR204 was added to Optic Atrophy. Sources: Literature
Mode of inheritance for gene: MIR204 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MIR204 were set to 26056285; 37321975
Phenotypes for gene: MIR204 were set to Retinal dystrophy and iris coloboma with or without cataract (MIM#616722)
Mode of pathogenicity for gene: MIR204 was set to Other
Review for gene: MIR204 was set to GREEN
gene: MIR204 was marked as current diagnostic
Added comment: PMID: 26056285
- Bilateral coloboma and rod-cone dystrophy with or without cataract in nine individuals of a five-generation family.
- Heterozygous n.37C>T segregates with the disease in all affected individuals.
- Functional analysis including transcriptome analysis showed this variant resulted in significant alterations of miR-204 targeting capabilities. In vivo injection, in medaka fish (Oryzias latipes), of the mutated miR-204 caused a phenotype consistent with that observed in the family.
- Authors suggested gain of function is the likely disease mechanism.

PMID: 37321975
- Four members of a three-generation family with early-onset chorioretinal dystrophy, heterozygous for n.37C>T.
- Additionally, four family members were shown to be affected by albinism resulting from biallelic pathogenic OCA2 variants.
- Haplotype analysis excluded relatedness with the family reported in PMID: 26056285.
- In silico analysis of the MIR204 n.37C>T variant reveals profound changes to its target mRNAs and suggests a gain-of-function mechanism of miR 204 variant.
Sources: Literature
Skeletal dysplasia v0.236 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Skeletal dysplasia v0.236 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.235 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Skeletal dysplasia v0.235 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.234 ERI1 Elena Savva Marked gene: ERI1 as ready
Skeletal dysplasia v0.234 ERI1 Elena Savva Gene: eri1 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.234 ERI1 Elena Savva gene: ERI1 was added
gene: ERI1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 37352860
Phenotypes for gene: ERI1 were set to Spondyloepimetaphyseal dysplasia (MONDO#0100510), ERI1-related, Intellectual disability (MONDO#0001071), ERI1-related
Review for gene: ERI1 was set to GREEN
Added comment: PMID: 37352860 - 8 individuals from 7 unrelated families
- Patients with biallelic missense show a MORE severe spondyloepimetaphyseal dysplasia, syndactyly, brachydactyly/clinodactyly/camptodactyly
- Patients with biallelic null/whole gene deletion had mild ID and digit anomalies including brachydactyly/clinodactyly/camptodactyly
- Patient chet for a missense and PTC variant has a blended phenotype with short stature, syndactyly, brachydactyly/clinodactyly/camptodactyly, mild ID and failure to thrive

- Missense variants were functionally shown to not be able to rescue 5.8S rRNA processing in KO HeLa cells
- K/O mice had neonatal lethality with growth defects, brachydactyly. Skeletal-specific K/O had mild platyspondyly, had more in keeping with patients with null variants than missense

More severe phenotype hypothesised due to "exonuclease-dead proteins may compete for the target RNA molecules with other exonucleases that have functional redundancy
with ERI1, staying bound to those RNA molecules"
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5250 DRG1 Dean Phelan gene: DRG1 was added
gene: DRG1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRG1 were set to PMID: 37179472
Phenotypes for gene: DRG1 were set to Neurodevelopmental disorder (MONDO:0700092), DRG1-related
Review for gene: DRG1 was set to GREEN
Added comment: PMID: 37179472
- Biallelic variants were identified in four affected individuals from three distinct families with neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature and craniofacial anomalies. Functional studies show the variants result in a loss of function.
Sources: Literature
Cerebral vascular malformations v0.32 ANO1 Suliman Khan gene: ANO1 was added
gene: ANO1 was added to Cerebral vascular malformations. Sources: Literature
Mode of inheritance for gene: ANO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANO1 were set to PMID: 37253099
Phenotypes for gene: ANO1 were set to moyamoya; cerebral arteriopathy
Review for gene: ANO1 was set to GREEN
Added comment: PMID: 37253099: screening analysis of Moyamoya disease (MMD) cohort revealed 8 patients with variants in the ANO1 gene. Two families had the same rare variant p.Met658Val in ANO1 gene. The ANO1 rare variants were assessed using patch-clamp recordings, and the majority of variants, including ANO1 p.Met658Val, displayed increased sensitivity to intracellular Ca2+. Patients harboring these gain-of-function ANO1 variants had classic features of MMD, but also had aneurysm, stenosis, and/or occlusion in the posterior circulation.
Sources: Literature
Hereditary Neuropathy - complex v0.166 ERCC6 Sangavi Sivagnanasundram reviewed gene: ERCC6: Rating: RED; Mode of pathogenicity: None; Publications: 20301516; Phenotypes: Cockayne syndrome, type B MIM#133540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neuromuscular Superpanel v1.28 Zornitza Stark Panel types changed to Superpanel; Victorian Clinical Genetics Services; Royal Melbourne Hospital
Hereditary Neuropathy - complex v0.166 GALC Sangavi Sivagnanasundram reviewed gene: GALC: Rating: AMBER; Mode of pathogenicity: None; Publications: 20301416, 21070211; Phenotypes: Krabbe Disease MIM#245200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.166 FAM126A Sangavi Sivagnanasundram reviewed gene: FAM126A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 5 MIM#610532; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.166 ZFYVE26 Sangavi Sivagnanasundram reviewed gene: ZFYVE26: Rating: GREEN; Mode of pathogenicity: None; Publications: 17661097, 19438933; Phenotypes: Spastic paraplegia 15 MIM#270700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuria v0.220 CD2AP Bryony Thompson Phenotypes for gene: CD2AP were changed from focal segmental glomerulosclerosis 3, susceptibility to MONDO:0011917 to focal segmental glomerulosclerosis 3, susceptibility to MONDO:0011917
Proteinuria v0.219 CD2AP Bryony Thompson Phenotypes for gene: CD2AP were changed from Glomerulosclerosis, focal segmental, 3, OMIM #607832 to focal segmental glomerulosclerosis 3, susceptibility to MONDO:0011917
Proteinuria v0.218 CD2AP Bryony Thompson Publications for gene: CD2AP were set to 30612599; 17713465
Proteinuria v0.217 CD2AP Bryony Thompson Mode of inheritance for gene: CD2AP was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Proteinuria v0.216 CD2AP Bryony Thompson Classified gene: CD2AP as Green List (high evidence)
Proteinuria v0.216 CD2AP Bryony Thompson Added comment: Comment on list classification: Comment on list classification: Definitive gene-disease assessment by ClinGen Glomerulopathy GCEP - classified 13/12/2021
Proteinuria v0.216 CD2AP Bryony Thompson Gene: cd2ap has been classified as Green List (High Evidence).
Mendeliome v1.956 CD2AP Bryony Thompson Phenotypes for gene: CD2AP were changed from Glomerulosclerosis, focal segmental, 3, OMIM #607832 to focal segmental glomerulosclerosis 3, susceptibility to MONDO:0011917
Mendeliome v1.955 CD2AP Bryony Thompson Publications for gene: CD2AP were set to 30612599; 17713465; 10997929; 12764198; 15951437
Mendeliome v1.954 CD2AP Bryony Thompson Publications for gene: CD2AP were set to 30612599; 17713465
Mendeliome v1.953 CD2AP Bryony Thompson Mode of inheritance for gene: CD2AP was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.952 CD2AP Bryony Thompson Classified gene: CD2AP as Green List (high evidence)
Mendeliome v1.952 CD2AP Bryony Thompson Added comment: Comment on list classification: Definitive gene-disease assessment by ClinGen Glomerulopathy GCEP - classified 13/12/2021
Mendeliome v1.952 CD2AP Bryony Thompson Gene: cd2ap has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.175 CBLB Zornitza Stark Phenotypes for gene: CBLB were changed from Autoimmune disease, MONDO:0007179 to Autoimmune disease, multisystem, infantile-onset, 3, MIM# 620430
Mendeliome v1.951 CBLB Zornitza Stark Phenotypes for gene: CBLB were changed from Autoimmune disease, MONDO:0007179 to Autoimmune disease, multisystem, infantile-onset, 3, MIM# 620430
Syndromic Retinopathy v0.201 INTS11 Zornitza Stark Marked gene: INTS11 as ready
Syndromic Retinopathy v0.201 INTS11 Zornitza Stark Gene: ints11 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.201 INTS11 Zornitza Stark Classified gene: INTS11 as Green List (high evidence)
Syndromic Retinopathy v0.201 INTS11 Zornitza Stark Gene: ints11 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.200 INTS11 Zornitza Stark gene: INTS11 was added
gene: INTS11 was added to Syndromic Retinopathy. Sources: Expert Review
Mode of inheritance for gene: INTS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS11 were set to 37054711
Phenotypes for gene: INTS11 were set to Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, MIM# 620428
Review for gene: INTS11 was set to GREEN
Added comment: PMID: 37054711 - 15 individuals from 10 unrelated families with bi-allelic variants in INTS11 with global developmental and language delay, intellectual disability, impaired motor development, and brain atrophy. Functional studies in Drosophila showed that dIntS11 (fly ortholog of INTS11) is essential and expressed in the central nervous systems in a subset of neurons and most glia in larval and adult stages.

Retinal dystrophy reported.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5250 INTS11 Zornitza Stark Phenotypes for gene: INTS11 were changed from intellectual disability, MONDO:0001071 to Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, MIM# 620428
Mendeliome v1.950 INTS11 Zornitza Stark Phenotypes for gene: INTS11 were changed from intellectual disability, MONDO:0001071 to Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, MIM# 620428
Intellectual disability syndromic and non-syndromic v0.5249 SRRM2 Zornitza Stark Publications for gene: SRRM2 were set to 33057194
Intellectual disability syndromic and non-syndromic v0.5248 SRRM2 Zornitza Stark Phenotypes for gene: SRRM2 were changed from neurodevelopmental disorder MONDO:0700092 SRRM2-related to Intellectual developmental disorder, autosomal dominant 72, MIM# 620439
Mendeliome v1.949 SRRM2 Zornitza Stark Phenotypes for gene: SRRM2 were changed from Neurodevelopmental disorder MONDO:0700092 SRRM2-related to Intellectual developmental disorder, autosomal dominant 72, MIM# 620439
Early-onset Parkinson disease v0.240 ATP7B Sangavi Sivagnanasundram reviewed gene: ATP7B: Rating: AMBER; Mode of pathogenicity: None; Publications: 31426520, 33972609, 36553628, 16737839; Phenotypes: Wilson disease (MONDO:0010200); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Dystonia - complex v0.224 NUP54 Zornitza Stark Phenotypes for gene: NUP54 were changed from Striatonigral degeneration, MONDO:0003122, NUP54-related; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia to Dystonia 37, early-onset, with striatal lesions, MIM# 620427; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia
Mendeliome v1.948 NUP54 Zornitza Stark Phenotypes for gene: NUP54 were changed from Striatonigral degeneration, MONDO:0003122, NUP54-related; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia to Dystonia 37, early-onset, with striatal lesions, MIM# 620427; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia
BabyScreen+ newborn screening v0.2175 MT-RNR1 Zornitza Stark changed review comment from: The following variants have been associated with aminoglycoside-induced deafness:
m.1555A>G
m.1005T>C
m.1095T>C

Alerts can be placed in medical records to avoid aminoglycoside administration.
Sources: Expert Review; to: The following variants have been associated with aminoglycoside-induced deafness:
m.1555A>G and m.1494C>T

Alerts can be placed in medical records to avoid aminoglycoside administration.
Sources: Expert Review
Fetal anomalies v1.114 BRWD1 Zornitza Stark Phenotypes for gene: BRWD1 were changed from Situs inversus; primary ciliary dyskinesia like to Situs inversus; Ciliary dyskinesia, primary, 51, MIM# 620438
Mendeliome v1.947 BRWD1 Zornitza Stark Phenotypes for gene: BRWD1 were changed from Asthenoteratozoospermia, likely primary ciliary dyskinesia to Ciliary dyskinesia, primary, 51, MIM# 620438
Ciliary Dyskinesia v1.31 BRWD1 Zornitza Stark Phenotypes for gene: BRWD1 were changed from Primary ciliary dyskinesia, asthenoteratozoospermia to Ciliary dyskinesia, primary, 51, MIM# 620438
Ciliary Dyskinesia v1.30 BRWD1 Zornitza Stark edited their review of gene: BRWD1: Changed phenotypes: Ciliary dyskinesia, primary, 51, MIM# 620438
Epidermolysis bullosa v1.15 SPINK5 Bryony Thompson Marked gene: SPINK5 as ready
Epidermolysis bullosa v1.15 SPINK5 Bryony Thompson Gene: spink5 has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.15 SPINK5 Bryony Thompson Mode of pathogenicity for gene: SPINK5 was changed from Other to None
Epidermolysis bullosa v1.14 SPINK5 Bryony Thompson Classified gene: SPINK5 as Green List (high evidence)
Epidermolysis bullosa v1.14 SPINK5 Bryony Thompson Gene: spink5 has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.13 KRT6C Bryony Thompson Marked gene: KRT6C as ready
Epidermolysis bullosa v1.13 KRT6C Bryony Thompson Gene: krt6c has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.13 KRT6C Bryony Thompson Classified gene: KRT6C as Green List (high evidence)
Epidermolysis bullosa v1.13 KRT6C Bryony Thompson Gene: krt6c has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.12 KRT6B Bryony Thompson Marked gene: KRT6B as ready
Epidermolysis bullosa v1.12 KRT6B Bryony Thompson Gene: krt6b has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.12 KRT6B Bryony Thompson Classified gene: KRT6B as Green List (high evidence)
Epidermolysis bullosa v1.12 KRT6B Bryony Thompson Gene: krt6b has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.11 KRT6A Bryony Thompson Marked gene: KRT6A as ready
Epidermolysis bullosa v1.11 KRT6A Bryony Thompson Gene: krt6a has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.11 KRT6A Bryony Thompson Classified gene: KRT6A as Green List (high evidence)
Epidermolysis bullosa v1.11 KRT6A Bryony Thompson Gene: krt6a has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.10 KRT17 Bryony Thompson Marked gene: KRT17 as ready
Epidermolysis bullosa v1.10 KRT17 Bryony Thompson Gene: krt17 has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.10 KRT17 Bryony Thompson Classified gene: KRT17 as Green List (high evidence)
Epidermolysis bullosa v1.10 KRT17 Bryony Thompson Gene: krt17 has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.9 KRT17 Bryony Thompson Mode of pathogenicity for gene: KRT17 was changed from None to Other
Epidermolysis bullosa v1.8 KRT16 Bryony Thompson Marked gene: KRT16 as ready
Epidermolysis bullosa v1.8 KRT16 Bryony Thompson Gene: krt16 has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.8 KRT16 Bryony Thompson Classified gene: KRT16 as Green List (high evidence)
Epidermolysis bullosa v1.8 KRT16 Bryony Thompson Gene: krt16 has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.7 FLG2 Bryony Thompson Deleted their review
Epidermolysis bullosa v1.7 FLG2 Bryony Thompson commented on gene: FLG2
Epidermolysis bullosa v1.7 FLG2 Bryony Thompson Classified gene: FLG2 as Green List (high evidence)
Epidermolysis bullosa v1.7 FLG2 Bryony Thompson Gene: flg2 has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.6 FLG2 Bryony Thompson Deleted their review
Cerebral Palsy v1.88 PMM2 Luisa Weiss gene: PMM2 was added
gene: PMM2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PMM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PMM2 were set to 34788679
Phenotypes for gene: PMM2 were set to Congenital disorder of glycosylation, type Ia MIM#212065
Review for gene: PMM2 was set to AMBER
Added comment: One patient in a large CP cohort study was found to have biallelic mutations ins PMM2, but usually PMM2-CDG presents as a progressive multisystem disease with dysmorphism.
Sources: Literature
Cerebral Palsy v1.88 PLP1 Luisa Weiss gene: PLP1 was added
gene: PLP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PLP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PLP1 were set to 33528536; 25280894; 34816117
Phenotypes for gene: PLP1 were set to Pelizaeus-Merzbacher disease MIM#312080; Spastic paraplegia 2, X-linked MIM#312920
Review for gene: PLP1 was set to GREEN
Added comment: Three large cohort studies with patients initially presenting as CP found three individuals with hemizygous mutations in PLP1. Note that individuals ins PMID 33528536 and 34816117 had different base pair exchanges at the same splice site location (NM_000533:c.191+1G>T and c.191+1G>A, respectively). The other mutation was a PLP1 gene duplication. One patient also had a affected brother.
Sources: Literature
Cerebral Palsy v1.88 PLA2G6 Luisa Weiss gene: PLA2G6 was added
gene: PLA2G6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PLA2G6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLA2G6 were set to 33528536; 34540776; 34788679
Phenotypes for gene: PLA2G6 were set to Infantile neuroaxonal dystrophy 1 MIM#256600; Neurodegeneration with brain iron accumulation 2B MIM#610217; Parkinson disease 14, autosomal recessive MIM#612953
Review for gene: PLA2G6 was set to GREEN
Added comment: Three different individuals from three large CP cohort studies presenting with biallelic PLA2G6 mutations.
Sources: Literature
Cerebral Palsy v1.88 PIGA Luisa Weiss gene: PIGA was added
gene: PIGA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PIGA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PIGA were set to 33528536; 24706016
Phenotypes for gene: PIGA were set to Multiple congenital anomalies-hypotonia-seizures syndrome 2 MIM#300868; Neurodevelopmental disorder with epilepsy and hemochromatosis MIM#301072; Paroxysmal nocturnal hemoglobinuria, somatic MIM#300818
Review for gene: PIGA was set to GREEN
Added comment: One case in a large CP cohort study with maternally inherited PIGA mutation predicted to be likely pathogenic.
In addition, Kato (PMID 24706016) reviewed 7 cases of boys with hemizygous PIGA mutations and encephalopathies, two of which had non-progressive hypotonic quadriplegia and one had spastic quadriplegia. They also showed intellectual disability and seizures. No CP diagnoses was given, but phenotypic overlap is present.
Sources: Literature
Cerebral Palsy v1.88 PDHX Luisa Weiss gene: PDHX was added
gene: PDHX was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PDHX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDHX were set to 33528536; 35076175; 34540776
Phenotypes for gene: PDHX were set to Lacticacidemia due to PDX1 deficiency MIM#245349
Review for gene: PDHX was set to GREEN
Added comment: Three individual patients from three large CP cohort studies with homozygous PDHX mutations. Note that in one case (PMID 35076175) the patient had both homozygous PDHX and homozygous ACADM mutations, but his phenotype was more consistent with PDHX mutations.
Sources: Literature
Cerebral Palsy v1.88 PDHA1 Luisa Weiss gene: PDHA1 was added
gene: PDHA1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PDHA1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: PDHA1 were set to 33528536; 10486093
Phenotypes for gene: PDHA1 were set to Pyruvate dehydrogenase E1-alpha deficiency MIM#312170
Review for gene: PDHA1 was set to GREEN
Added comment: 2 patients in 1 large CP cohort presented with heterozygous likely pathogenic missense mutations, one of them confirmed de novo.
In an older case report (PMID:10486093) two unrelated girls were presented with cerebral palsy which were found to harbor heterozygous PDHA mutations. In one case, parental DNA wasn't analyzed, in the other case the mutation wasn't found in the healthy mother and the healthy brother of the patient. Both girls showed skewed X-Inactivation.
Note that in X-linked PDH deficiency it has been shown that a high proportion of heterozygous females manifest severe symptoms.
Sources: Literature
Cerebral Palsy v1.88 PANK2 Luisa Weiss reviewed gene: PANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33098801, 34114234, 25131622; Phenotypes: HARP syndrome MIM#607236, Neurodegeneration with brain iron accumulation MIM#234200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.88 PAK3 Luisa Weiss reviewed gene: PAK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31444167, 30542205, 25666757; Phenotypes: Intellectual developmental disorder, X-linked MIM#300558; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.88 PAFAH1B1 Luisa Weiss gene: PAFAH1B1 was added
gene: PAFAH1B1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PAFAH1B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAFAH1B1 were set to 19667223
Phenotypes for gene: PAFAH1B1 were set to Lissencephaly MIM#607432; Subcortical laminar heterotopia MIM#607432
Review for gene: PAFAH1B1 was set to GREEN
Added comment: Saillour reviewed 63 patients with posteriorly predominant lissencephaly, 40 of which were proven to have a LIS1 mutation. None of them were officially diagnosed with cerebral palsy, however, 24 of those 40 patients presented with "severe motor impairment including axial hypotonia and spastic quadriparesis". A high percentage of patients also showed severe developmental delay and epilepsy.
Sources: Literature
Cerebral Palsy v1.88 NFIX Luisa Weiss gene: NFIX was added
gene: NFIX was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NFIX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFIX were set to 34788679
Phenotypes for gene: NFIX were set to Malan syndrome MIM#614753; Marshall-Smith syndrome MIM#602535
Review for gene: NFIX was set to AMBER
Added comment: Two patients in a large CP cohort study, one with a nonsense mutation without information on inheritance and one with a de novo missense mutation predicted to be likely pathogenic. Normally, NFIX mutation cause accelerated bone maturation with overgrwowth, dysmorphism and mental retardation, so there is a low possibility for phenotypic overlap.
Sources: Literature
Cerebral Palsy v1.88 NAA10 Luisa Weiss gene: NAA10 was added
gene: NAA10 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NAA10 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: NAA10 were set to 33528536; 30542205
Phenotypes for gene: NAA10 were set to Microphthalmia, syndromic MIM#309800; Ogden syndrome MIM#300855
Review for gene: NAA10 was set to GREEN
Added comment: Four individual cases in two large CP cohort studies. Note that in one publication (33528536) 2/3 mutations occurred de novo.
Sources: Literature
Cerebral Palsy v1.88 MT-TL1 Luisa Weiss gene: MT-TL1 was added
gene: MT-TL1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene gene: MT-TL1 was set to MITOCHONDRIAL
Publications for gene: MT-TL1 were set to 34531397; 34077496; 25280894
Phenotypes for gene: MT-TL1 were set to MYOCLONIC EPILEPSY ASSOCIATED WITH RAGGED-RED FIBERS MERRF MIM#545000; CYCLIC VOMITING SYNDROME WITH NEUROMUSCULAR DISEASE, INCLUDED CYCLIC VOMITING SYNDROME-PLUS, INCLUDED CVS-PLUS, INCLUDED MIM#500007; MITOCHONDRIAL MYOPATHY, ENCEPHALOPATHY, LACTIC ACIDOSIS, AND STROKE-LIKE EPISODES MELAS MIM#540000; DIABETES AND DEAFNESS, MATERNALLY INHERITED MIDD MIM#520000
Review for gene: MT-TL1 was set to GREEN
Added comment: Three individual cases in three different large CP cohort publications. In one case, heteroplasmy was 8% in another it was 58% with a low level detectable also in the mother. The third does not state the heteroplasmy level. Note very high intra- and interfamilial variability, partly due to heteroplasmy level in different tissues.
Sources: Literature
Mendeliome v1.946 UBE3B Achchuthan Shanmugasundram reviewed gene: UBE3B: Rating: AMBER; Mode of pathogenicity: None; Publications: 23200864, 23687348, 37010288; Phenotypes: Kaufman oculocerebrofacial syndrome, OMIM:244450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.946 SMARCB1 Achchuthan Shanmugasundram reviewed gene: SMARCB1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25168959, 37010288; Phenotypes: Coffin-Siris syndrome 3, OMIM:614608; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.946 NOTCH2 Achchuthan Shanmugasundram reviewed gene: NOTCH2: Rating: AMBER; Mode of pathogenicity: None; Publications: 9188663, 30329210, 37010288; Phenotypes: Hajdu-Cheney syndrome, OMIM:102500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.946 AUTS2 Achchuthan Shanmugasundram reviewed gene: AUTS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 31788251, 37010288; Phenotypes: Intellectual developmental disorder, autosomal dominant 26, OMIM:615834; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.946 ARID1A Achchuthan Shanmugasundram reviewed gene: ARID1A: Rating: AMBER; Mode of pathogenicity: None; Publications: 25168959, 37010288; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Epidermolysis bullosa v1.5 SPINK5 Sangavi Sivagnanasundram gene: SPINK5 was added
gene: SPINK5 was added to Epidermolysis bullosa. Sources: Other
Mode of inheritance for gene: SPINK5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPINK5 were set to 19683336
Phenotypes for gene: SPINK5 were set to Netherton syndrome (MIM#256500)
Mode of pathogenicity for gene: SPINK5 was set to Other
Review for gene: SPINK5 was set to GREEN
Added comment: Characterized by congenital erythroderma, a specific hair-shaft abnormality, and atopic manifestations with high IgE levels.
Typically caused by either homozygous or compound heterozygous mutations.

PMID: 19683336
9 unrelated children with Comel-Netherton syndrome with homozygous mutations in SPINK5.
Sources: Other
Epidermolysis bullosa v1.5 KRT17 Sangavi Sivagnanasundram gene: KRT17 was added
gene: KRT17 was added to Epidermolysis bullosa. Sources: Other
Mode of inheritance for gene: KRT17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRT17 were set to 11886499; 21326300
Phenotypes for gene: KRT17 were set to Pachyonychia congenita 2 (MIM#167210)
Review for gene: KRT17 was set to GREEN
Added comment: Also reported as Jackson-Lawler type syndrome

PMID: 11886499
4 unrelated individuals with pachyonychia congenita like phenotype

PMID: 21326300
Heterozygous pathogenic mutations have a dominant-negative effect on the KRT17 protein
Sources: Other
Epidermolysis bullosa v1.5 KRT16 Sangavi Sivagnanasundram gene: KRT16 was added
gene: KRT16 was added to Epidermolysis bullosa. Sources: Other
Mode of inheritance for gene: KRT16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRT16 were set to 16250206
Phenotypes for gene: KRT16 were set to Pachyonychia congenita 1 (MIM#167200)
Mode of pathogenicity for gene: KRT16 was set to Other
Review for gene: KRT16 was set to GREEN
Added comment: PMID: 16250206
Typically identified by nail bed, palmoplantar epidermis (widespread), epidermal appendages, oral mucosa and wound healing.
>5 unrelated families with a consistent phenotype of PC and a heterozygous missense variant in KRT16.
Sources: Other
Epidermolysis bullosa v1.5 KRT6C Sangavi Sivagnanasundram gene: KRT6C was added
gene: KRT6C was added to Epidermolysis bullosa. Sources: Other
Mode of inheritance for gene: KRT6C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRT6C were set to 31823354; 23662636
Phenotypes for gene: KRT6C were set to Palmoplantar keratoderma, nonepidermolytic, focal or diffuse (MIM#615735)
Mode of pathogenicity for gene: KRT6C was set to Other
Review for gene: KRT6C was set to GREEN
Added comment: Phenotype overlap with Pachyonychia congenita (PC)

PMID: 31823354
Approx 23 unrelated families with mutation in KRT6C with phenotypes consistent with pachyonchia congenita

PMID: 23662636
In vitro assay in HaCaT cells showed the overexpression of mutant keratin 6c showed a collapse of the keratin filament network suggestive of dominant negative effect pathogenicity.
Sources: Other
Epidermolysis bullosa v1.5 KRT6B Sangavi Sivagnanasundram gene: KRT6B was added
gene: KRT6B was added to Epidermolysis bullosa. Sources: Other
Mode of inheritance for gene: KRT6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRT6B were set to 24611874; 21326300
Phenotypes for gene: KRT6B were set to Pachyonychia congenita 4 MIM#615728
Mode of pathogenicity for gene: KRT6B was set to Other
Review for gene: KRT6B was set to GREEN
Added comment: Previously known as Jadassohn-Lewandowsky PC type 1 and Jackson-Lawler PC type 2
Mutants are found to have a dominant-negative most of pathogenicity.

PMID: 24611874
Multiple families with either plantar keratoderma or palmopantar keratoderma phenotypes with a mutation in KRT6B

PMID: 21326300
The most common reported mutation K6b p.Glu472Lys in families with KRT6B-related Pachyonychia congenita
Sources: Other
Epidermolysis bullosa v1.5 KRT6A Sangavi Sivagnanasundram gene: KRT6A was added
gene: KRT6A was added to Epidermolysis bullosa. Sources: Other
Mode of inheritance for gene: KRT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRT6A were set to 32017015; 21326300
Phenotypes for gene: KRT6A were set to Pachyonychia congenita 3 MIM#615726
Mode of pathogenicity for gene: KRT6A was set to Other
Review for gene: KRT6A was set to GREEN
Added comment: Well established gene-disease association.

Multiple families reported with hyperkeratotic disorders with skin fragility like symptoms.
p.Asn172del is the most common mutation identified in families with Pachyonychia congenita
Sources: Other
Mendeliome v1.946 ZC4H2 Achchuthan Shanmugasundram changed review comment from: There are ten unrelated patients reported with cleft palate. Hence, this gene should be added with green rating to 'clefting disorders' panel.

PMID:31206972 - Of 42 families identified with variants in de novo and inherited heterozygous variants in ZC4H2 gene, eight patients had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with monoallelic sequence variants, three patients had cleft palate.

Cleft palate has been recorded as one of the clinical presentations of female-restricted Wieacker-Wolff syndrome (MIM #301041) in OMIM.; to: There are ten unrelated patients reported with cleft palate. Hence, this gene should be added with green rating to 'clefting disorders' panel.

PMID:31206972 - Of 42 families identified with de novo and inherited variants in ZC4H2 gene, eight patients had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with sequence variants, three patients had cleft palate.

Cleft palate has been recorded as one of the clinical presentations of female-restricted Wieacker-Wolff syndrome (MIM #301041) in OMIM.
Mendeliome v1.946 ZC4H2 Achchuthan Shanmugasundram edited their review of gene: ZC4H2: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.946 ZC4H2 Achchuthan Shanmugasundram edited their review of gene: ZC4H2: Changed publications: 31206972, 37010288; Changed phenotypes: Wieacker-Wolff syndrome, female-restricted, OMIM:301041
Mendeliome v1.946 ZC4H2 Achchuthan Shanmugasundram reviewed gene: ZC4H2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mitochondrial disease v0.877 GCSH Zornitza Stark Marked gene: GCSH as ready
Mitochondrial disease v0.877 GCSH Zornitza Stark Gene: gcsh has been classified as Green List (High Evidence).
Mitochondrial disease v0.877 GCSH Zornitza Stark Classified gene: GCSH as Green List (high evidence)
Mitochondrial disease v0.877 GCSH Zornitza Stark Gene: gcsh has been classified as Green List (High Evidence).
Mitochondrial disease v0.876 GCSH Zornitza Stark gene: GCSH was added
gene: GCSH was added to Mitochondrial disease. Sources: Expert Review
Mode of inheritance for gene: GCSH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCSH were set to 33890291; 36190515
Phenotypes for gene: GCSH were set to Multiple mitochondrial dysfunctions syndrome 7, MIM# 620423
Review for gene: GCSH was set to GREEN
Added comment: 7 unrelated families reported. Phenotype ranges from neonatal fatal glycine encephalopathy to an attenuated phenotype of developmental delay, behavioral problems, limited epilepsy and variable movement problems.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5247 GCSH Zornitza Stark Phenotypes for gene: GCSH were changed from Glycine encephalopathy MIM#605899; neurodevelopmental disorder MONDO#0700092, GCHS-related to Multiple mitochondrial dysfunctions syndrome 7, MIM# 620423
Callosome v0.495 GCSH Zornitza Stark Phenotypes for gene: GCSH were changed from Glycine encephalopathy, MIM#605899 to Multiple mitochondrial dysfunctions syndrome 7, MIM# 620423
Genetic Epilepsy v0.1865 GCSH Zornitza Stark Phenotypes for gene: GCSH were changed from Glycine encephalopathy MIM#605899; neurodevelopmental disorder MONDO#0700092, GCHS-related to Multiple mitochondrial dysfunctions syndrome 7, MIM# 620423
Mendeliome v1.946 GCSH Zornitza Stark Phenotypes for gene: GCSH were changed from Glycine encephalopathy MIM#605899; neurodevelopmental disorder MONDO#0700092, GCHS-related to Multiple mitochondrial dysfunctions syndrome 7, MIM# 620423
Motor Neurone Disease v0.189 SCA2 Bryony Thompson Marked STR: SCA2 as ready
Motor Neurone Disease v0.189 SCA2 Bryony Thompson Str: sca2 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.189 SCA2 Bryony Thompson Classified STR: SCA2 as Green List (high evidence)
Motor Neurone Disease v0.189 SCA2 Bryony Thompson Str: sca2 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.188 SCA2 Bryony Thompson STR: SCA2 was added
STR: SCA2 was added to Motor Neurone Disease. Sources: Literature
Mode of inheritance for STR: SCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA2 were set to 20301452
Phenotypes for STR: SCA2 were set to Spinocerebellar ataxia 2 MIM#183090
Review for STR: SCA2 was set to GREEN
STR: SCA2 was marked as clinically relevant
Added comment: NM_002973​.3:c.496_498CAG[X]
Toxic protein aggregation is mechanism of disease
Benign: ≤31 repeats (homozygous 31/31 repeats reported for recessive SCA2)
Uncertain: 32 repeats
ALS risk allele: 30-32 repeats
Reduced penetrance: 33-34 repeats, may not develop symptoms or only very late in life
Full penetrance: ≥35 repeats
Interruption of a CAG expanded allele by a CAA repeat does not mitigate the pathogenicity of the repeat size, but may enhance the meiotic stability of the repeat
Sources: Literature
Motor Neurone Disease v0.187 LGALSL Bryony Thompson Marked gene: LGALSL as ready
Motor Neurone Disease v0.187 LGALSL Bryony Thompson Gene: lgalsl has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.187 LGALSL Bryony Thompson Classified gene: LGALSL as Amber List (moderate evidence)
Motor Neurone Disease v0.187 LGALSL Bryony Thompson Gene: lgalsl has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.186 LGALSL Bryony Thompson gene: LGALSL was added
gene: LGALSL was added to Motor Neurone Disease. Sources: ClinGen
Mode of inheritance for gene: LGALSL was set to Unknown
Publications for gene: LGALSL were set to 30940688
Phenotypes for gene: LGALSL were set to amyotrophic lateral sclerosis MONDO:0004976
Review for gene: LGALSL was set to AMBER
Added comment: Limited gene-disease validity assessment by ClinGen ALS spectrum disorder GCEP - 14/02/2023. Significant enrichment in a cohort of 3,239 ALS cases compared to 11,808 controls - OR = 14.63; P = 2.29e-6.
Sources: ClinGen
Motor Neurone Disease v0.185 HNRNPA2B1 Bryony Thompson Marked gene: HNRNPA2B1 as ready
Motor Neurone Disease v0.185 HNRNPA2B1 Bryony Thompson Gene: hnrnpa2b1 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.185 HNRNPA2B1 Bryony Thompson gene: HNRNPA2B1 was added
gene: HNRNPA2B1 was added to Motor Neurone Disease. Sources: ClinGen
Mode of inheritance for gene: HNRNPA2B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPA2B1 were set to 25299611
Phenotypes for gene: HNRNPA2B1 were set to amyotrophic lateral sclerosis MONDO:0004976
Review for gene: HNRNPA2B1 was set to RED
Added comment: Limited gene-disease validity assessment by ALS spectrum disorder GCEP - 15/12/2021. Only one variant in a single ALS proband scored.
Sources: ClinGen
Motor Neurone Disease v0.184 GRN Bryony Thompson Marked gene: GRN as ready
Motor Neurone Disease v0.184 GRN Bryony Thompson Gene: grn has been classified as Green List (High Evidence).
Motor Neurone Disease v0.184 GRN Bryony Thompson Classified gene: GRN as Green List (high evidence)
Motor Neurone Disease v0.184 GRN Bryony Thompson Gene: grn has been classified as Green List (High Evidence).
Motor Neurone Disease v0.183 GRN Bryony Thompson gene: GRN was added
gene: GRN was added to Motor Neurone Disease. Sources: ClinGen
Mode of inheritance for gene: GRN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRN were set to 18184915; 23596077
Phenotypes for gene: GRN were set to frontotemporal dementia and/or amyotrophic lateral sclerosis MONDO:0030923
Review for gene: GRN was set to GREEN
gene: GRN was marked as current diagnostic
Added comment: Well-established FTD gene. ALS has been reported in association with some GRN variants, but appears to be a rare occurrence.
Sources: ClinGen
Motor Neurone Disease v0.182 GLT8D1 Bryony Thompson Marked gene: GLT8D1 as ready
Motor Neurone Disease v0.182 GLT8D1 Bryony Thompson Gene: glt8d1 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.182 GLT8D1 Bryony Thompson Classified gene: GLT8D1 as Amber List (moderate evidence)
Motor Neurone Disease v0.182 GLT8D1 Bryony Thompson Gene: glt8d1 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.181 FIG4 Bryony Thompson Marked gene: FIG4 as ready
Motor Neurone Disease v0.181 FIG4 Bryony Thompson Gene: fig4 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.181 FIG4 Bryony Thompson Phenotypes for gene: FIG4 were changed from to Amyotrophic Lateral Sclerosis Type 11 (MONDO: 0012945; MIM#612577)
Motor Neurone Disease v0.180 FIG4 Bryony Thompson Mode of inheritance for gene: FIG4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.179 FIG4 Bryony Thompson Classified gene: FIG4 as Amber List (moderate evidence)
Motor Neurone Disease v0.179 FIG4 Bryony Thompson Added comment: Comment on list classification: Limited gene-disease validity assessment by ClinGen ALS spectrum disorders GCEP - 09/08/2022
Motor Neurone Disease v0.179 FIG4 Bryony Thompson Gene: fig4 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.178 EWSR1 Bryony Thompson Classified gene: EWSR1 as Red List (low evidence)
Motor Neurone Disease v0.178 EWSR1 Bryony Thompson Added comment: Comment on list classification: Disputed gene-disease validity assessment by ClinGen ALS spectrum disorders GCEP - 11/10/2022
Motor Neurone Disease v0.178 EWSR1 Bryony Thompson Gene: ewsr1 has been classified as Red List (Low Evidence).
Mendeliome v1.945 EWSR1 Bryony Thompson Classified gene: EWSR1 as Red List (low evidence)
Mendeliome v1.945 EWSR1 Bryony Thompson Added comment: Comment on list classification: Disputed gene-disease validity assessment by ClinGen ALS spectrum disorders GCEP - 11/10/2022
Mendeliome v1.945 EWSR1 Bryony Thompson Gene: ewsr1 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.177 ERBB4 Bryony Thompson Classified gene: ERBB4 as Amber List (moderate evidence)
Motor Neurone Disease v0.177 ERBB4 Bryony Thompson Added comment: Comment on list classification: Limited gene-disease validity assessment by ClinGen ALS spectrum disorder GCEP - 30/09/2021
Motor Neurone Disease v0.177 ERBB4 Bryony Thompson Gene: erbb4 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.176 DAO Bryony Thompson Deleted their comment
Motor Neurone Disease v0.176 DAO Bryony Thompson Classified gene: DAO as Red List (low evidence)
Motor Neurone Disease v0.176 DAO Bryony Thompson Added comment: Comment on list classification: Refuted gene-disease validity assessment by ClinGen ALS spectrum disorders GCEP - 21/04/2022
Motor Neurone Disease v0.176 DAO Bryony Thompson Gene: dao has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.176 DAO Bryony Thompson Classified gene: DAO as Red List (low evidence)
Motor Neurone Disease v0.176 DAO Bryony Thompson Added comment: Comment on list classification: Refuted gene-disease vailidity assessment by ClinGen ALS spectrum disorders GCEP - 21/04/2022
Motor Neurone Disease v0.176 DAO Bryony Thompson Gene: dao has been classified as Red List (Low Evidence).
Early-onset Dementia v0.160 CCNF Bryony Thompson Classified gene: CCNF as Amber List (moderate evidence)
Early-onset Dementia v0.160 CCNF Bryony Thompson Added comment: Comment on list classification: Limited gene-disease validity assessment by ClinGen ALS spectrum disorders GCEP - 05/04/2022
Early-onset Dementia v0.160 CCNF Bryony Thompson Gene: ccnf has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.175 CCNF Bryony Thompson Classified gene: CCNF as Amber List (moderate evidence)
Motor Neurone Disease v0.175 CCNF Bryony Thompson Added comment: Comment on list classification: Limited gene-disease validity assessment by ClinGen ALS spectrum disorders GCEP - 05/04/2022
Motor Neurone Disease v0.175 CCNF Bryony Thompson Gene: ccnf has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.174 ARPP21 Bryony Thompson gene: ARPP21 was added
gene: ARPP21 was added to Motor Neurone Disease. Sources: ClinGen
Mode of inheritance for gene: ARPP21 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARPP21 were set to 30811981; 31653410; 35525134
Phenotypes for gene: ARPP21 were set to amyotrophic lateral sclerosis MONDO:0004976
Review for gene: ARPP21 was set to RED
Added comment: Limited gene-disease validity classification by ClinGen ALS spectrum disorders GCEP - 10/01/2023
Sources: ClinGen
Motor Neurone Disease v0.173 ANG Bryony Thompson Classified gene: ANG as Red List (low evidence)
Motor Neurone Disease v0.173 ANG Bryony Thompson Gene: ang has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.172 ANG Bryony Thompson Deleted their comment
Motor Neurone Disease v0.172 ANG Bryony Thompson Classified gene: ANG as Amber List (moderate evidence)
Motor Neurone Disease v0.172 ANG Bryony Thompson Added comment: Comment on list classification: Limited gene-disease validity classification by ClinGen ALS GCEP - 08/02/2022
Motor Neurone Disease v0.172 ANG Bryony Thompson Gene: ang has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.171 ANG Bryony Thompson Classified gene: ANG as Amber List (moderate evidence)
Motor Neurone Disease v0.171 ANG Bryony Thompson Added comment: Comment on list classification: Limited gene-disease validity classification by ClinGen ALS GCEP - 08/02/2022
Motor Neurone Disease v0.171 ANG Bryony Thompson Gene: ang has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.170 SPTLC1 Bryony Thompson Marked gene: SPTLC1 as ready
Motor Neurone Disease v0.170 SPTLC1 Bryony Thompson Gene: sptlc1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.170 SPTLC1 Bryony Thompson Classified gene: SPTLC1 as Green List (high evidence)
Motor Neurone Disease v0.170 SPTLC1 Bryony Thompson Gene: sptlc1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.169 SPTLC1 Bryony Thompson gene: SPTLC1 was added
gene: SPTLC1 was added to Motor Neurone Disease. Sources: Literature
Mode of inheritance for gene: SPTLC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTLC1 were set to 34059824; 35900868; 34459874
Phenotypes for gene: SPTLC1 were set to juvenile amyotrophic lateral sclerosis MONDO:0017593
Mode of pathogenicity for gene: SPTLC1 was set to Other
Review for gene: SPTLC1 was set to GREEN
Added comment: At least 10 unrelated probands/families reported with typically juvenile-onset ALS with missense or in-frame indels. Supporting in vitro functional assays demonstrate the mechanism of disease results in unregulated SPT activity and elevated levels of canonical SPT products, in contrast to the mechanism of disease for SPTLC1 variants that cause hereditary sensory and autonomic neuropathy (shift SPT amino acid usage from serine to alanine, resulting in elevated levels of deoxysphingolipids).
Sources: Literature
Mendeliome v1.944 STAG2 Achchuthan Shanmugasundram reviewed gene: STAG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28296084, 29263825, 30158690, 31334757, 33014403, 37010288; Phenotypes: Holoprosencephaly 13, X-linked, OMIM:301043, Mullegama-Klein-Martinez syndrome, OMIM:301022; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.944 SMARCA4 Achchuthan Shanmugasundram reviewed gene: SMARCA4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25168959, 37010288; Phenotypes: Coffin-Siris syndrome 4, OMIM:614609; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.168 SMN1 Bryony Thompson Marked gene: SMN1 as ready
Motor Neurone Disease v0.168 SMN1 Bryony Thompson Gene: smn1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.168 SMN1 Bryony Thompson Classified gene: SMN1 as Green List (high evidence)
Motor Neurone Disease v0.168 SMN1 Bryony Thompson Gene: smn1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.166 SMN1 Bryony Thompson gene: SMN1 was added
gene: SMN1 was added to Motor Neurone Disease. Sources: Literature
Mode of inheritance for gene: SMN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMN1 were set to 20301623
Phenotypes for gene: SMN1 were set to Spinal muscular atrophy-1, MIM# 253300
Added comment: Differential diagnosis for ALS
Sources: Literature
Mendeliome v1.944 XYLT1 Elena Savva Mode of inheritance for gene: XYLT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.943 POGZ Achchuthan Shanmugasundram changed review comment from: Although there are more than three unrelated cases reported with either cleft palate or bifid uvula in total, this phenotype is not consistently present in patients with monoallelic variants in POGZ gene. Hence, this gene should only be added with amber rating in 'Clefting disorders panel'.

PMID:26739615 - Five unrelated individuals were identified with de novo truncating variants in POGZ gene, of which one individual had cleft palate and another one had bifid uvula.

PMID:31782611 - In this cohort of 22 individuals with 21 different loss of function variants in POGZ, two patients were reported with bifid uvula.

DECIPHER database - Of 42 patients with heterozygous sequence variants, one had cleft palate and another one had bifid uvula (PMID:37010288).

The OMIM entry for White-Sutton syndrome (MIM #616364) does not currently include cleft lip/ palate as one of the clinical manifestations of this syndrome.; to: Although there are more than three unrelated cases reported with either cleft palate or bifid uvula in total, this phenotype is not consistently present in patients with monoallelic variants in POGZ gene. Hence, this gene should only be added with amber rating in 'Clefting disorders' panel.

PMID:26739615 - Five unrelated individuals were identified with de novo truncating variants in POGZ gene, of which one individual had cleft palate and another one had bifid uvula.

PMID:31782611 - In this cohort of 22 individuals with 21 different loss of function variants in POGZ, two patients were reported with bifid uvula.

DECIPHER database - Of 42 patients with heterozygous sequence variants, one had cleft palate and another one had bifid uvula (PMID:37010288).

The OMIM entry for White-Sutton syndrome (MIM #616364) does not currently include cleft lip/ palate as one of the clinical manifestations of this syndrome.
Mendeliome v1.943 POGZ Achchuthan Shanmugasundram reviewed gene: POGZ: Rating: AMBER; Mode of pathogenicity: None; Publications: 26739615, 31782611, 37010288; Phenotypes: White-Sutton syndrome, OMIM:616364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.88 TUBB2A Luisa Weiss gene: TUBB2A was added
gene: TUBB2A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TUBB2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB2A were set to 33528536; 24702957
Phenotypes for gene: TUBB2A were set to Cortical dysplasia, complex, with other brain malformations MIM# 615763
Review for gene: TUBB2A was set to GREEN
Added comment: 4 individual cases in one large CP cohort study, all of them with de novo missense mutations, Note that 2/4 mutations are p.A248V, which has also been described in a nonverbal and nonambulatory girl with generalized hypotonia and mild brain malformations (dysmorphic corpus callosum). Cushion et al. (PMID 24702957) also did functional work on this variant showing is had an impaired ability to coassemble with endogenous alpha-tubulin subunits and integrate into microtubule polymers.
Sources: Literature
Cerebral Palsy v1.88 TUBB3 Luisa Weiss gene: TUBB3 was added
gene: TUBB3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TUBB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB3 were set to 33528536
Phenotypes for gene: TUBB3 were set to Cortical dysplasia, complex, with other brain malformations MIM#614039; Fibrosis of extraocular muscles, congenital MIM#600638
Review for gene: TUBB3 was set to GREEN
Added comment: 4 individual cases in one large CP cohort study, all with de novo missense mutations predicted to be pathogenic.
Sources: Literature
Neurodegeneration with brain iron accumulation v0.22 ATP7B Shekeeb Mohammad gene: ATP7B was added
gene: ATP7B was added to Neuroferritinopathies. Sources: Literature,Expert list
Mode of inheritance for gene: ATP7B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP7B were set to 27543917; 28376267
Phenotypes for gene: ATP7B were set to dystonia; parkinsonism; psychosis; liver failure; pancreatitis; renal tubular acidosis; dysarthria; dysphagia
gene: ATP7B was marked as current diagnostic
Neurodegeneration with brain iron accumulation v0.22 AP4M1 Shekeeb Mohammad gene: AP4M1 was added
gene: AP4M1 was added to Neuroferritinopathies. Sources: Literature,Expert list
Mode of inheritance for gene: AP4M1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP4M1 were set to 29473051
Phenotypes for gene: AP4M1 were set to progressive spastic tetraparesis; microcephaly; intellectual disabiliy; growth retardation; epilepsy; peripheral neuropathy; brain iron deposition
Review for gene: AP4M1 was set to GREEN
gene: AP4M1 was marked as current diagnostic
Added comment: Sources: Literature, Expert list
Neurodegeneration with brain iron accumulation v0.22 AP1S2 Shekeeb Mohammad gene: AP1S2 was added
gene: AP1S2 was added to Neuroferritinopathies. Sources: Expert list,Literature
Mode of inheritance for gene: AP1S2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: AP1S2 were set to 23756445
Phenotypes for gene: AP1S2 were set to spasticity; hypotonia; intellectual disability; posterior fossa malformation; brain iron deposition
Penetrance for gene: AP1S2 were set to Complete
Review for gene: AP1S2 was set to GREEN
Added comment: Sources: Expert list, Literature
Facial papules v1.0 Bryony Thompson promoted panel to version 1.0
Facial papules v0.49 Bryony Thompson Panel status changed from internal to public
Panel types changed to Royal Melbourne Hospital; Rare Disease
Mendeliome v1.943 PGAP3 Achchuthan Shanmugasundram reviewed gene: PGAP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28390064, 37010288; Phenotypes: Hyperphosphatasia with impaired intellectual development syndrome 4, OMIM:615716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.943 KMT2A Achchuthan Shanmugasundram reviewed gene: KMT2A: Rating: AMBER; Mode of pathogenicity: None; Publications: 25929198, 30305169, 31710778, 37010288; Phenotypes: Wiedemann-Steiner syndrome, OMIM:605130; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting disorders v0.196 KAT6B Achchuthan Shanmugasundram reviewed gene: KAT6B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32424177, 37010288; Phenotypes: Genitopatellar syndrome, OMIM:606170, SBBYSS syndrome, OMIM:603736; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.943 GLI2 Achchuthan Shanmugasundram reviewed gene: GLI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24744436, 37010288; Phenotypes: Culler-Jones syndrome, OMIM:615849, Holoprosencephaly 9, OMIM:610829; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.18 SMAD4 Bryony Thompson Classified gene: SMAD4 as Red List (low evidence)
Pulmonary Arterial Hypertension v1.18 SMAD4 Bryony Thompson Added comment: Comment on list classification: Disputed classification by ClinGen PH GCEP 21/11/2022
Pulmonary Arterial Hypertension v1.18 SMAD4 Bryony Thompson Gene: smad4 has been classified as Red List (Low Evidence).
Pulmonary Arterial Hypertension v1.17 SMAD1 Bryony Thompson Classified gene: SMAD1 as Red List (low evidence)
Pulmonary Arterial Hypertension v1.17 SMAD1 Bryony Thompson Added comment: Comment on list classification: Disputed gene curation by ClinGen PH VCEP 21/11/2022
Pulmonary Arterial Hypertension v1.17 SMAD1 Bryony Thompson Gene: smad1 has been classified as Red List (Low Evidence).
Pulmonary Arterial Hypertension v1.16 GGCX Bryony Thompson Marked gene: GGCX as ready
Pulmonary Arterial Hypertension v1.16 GGCX Bryony Thompson Gene: ggcx has been classified as Amber List (Moderate Evidence).
Pulmonary Arterial Hypertension v1.16 GGCX Bryony Thompson Classified gene: GGCX as Amber List (moderate evidence)
Pulmonary Arterial Hypertension v1.16 GGCX Bryony Thompson Gene: ggcx has been classified as Amber List (Moderate Evidence).
Pulmonary Arterial Hypertension v1.15 GGCX Bryony Thompson gene: GGCX was added
gene: GGCX was added to Pulmonary Arterial Hypertension. Sources: ClinGen
Mode of inheritance for gene: GGCX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GGCX were set to 31727138
Phenotypes for gene: GGCX were set to pulmonary arterial hypertension MONDO:0015924
Review for gene: GGCX was set to AMBER
Added comment: Moderate gene-disease validity classification by the pulmonary hypertension GCEP (4/11/2022). All the genetic evidence is based on one study conducting a gene-based association analysis using 812 European IPAH cases and 12,771 European controls. There were 18 probands with GGCX variants identified.
Sources: ClinGen
Facial papules v0.48 ANTXR2 Bryony Thompson Marked gene: ANTXR2 as ready
Facial papules v0.48 ANTXR2 Bryony Thompson Gene: antxr2 has been classified as Green List (High Evidence).
Facial papules v0.48 ANTXR2 Bryony Thompson Classified gene: ANTXR2 as Green List (high evidence)
Facial papules v0.48 ANTXR2 Bryony Thompson Gene: antxr2 has been classified as Green List (High Evidence).
Facial papules v0.47 ANTXR2 Bryony Thompson gene: ANTXR2 was added
gene: ANTXR2 was added to Facial papules. Sources: Literature
Mode of inheritance for gene: ANTXR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANTXR2 were set to 20301698
Phenotypes for gene: ANTXR2 were set to hyaline fibromatosis syndrome MONDO:0009229
Review for gene: ANTXR2 was set to GREEN
gene: ANTXR2 was marked as current diagnostic
Added comment: Coarse facies and pearly papules on the face are common features of the condition.
Sources: Literature