Activity

Filter

Cancel
Date Panel Item Activity
3000 actions
Catecholaminergic Polymorphic Ventricular Tachycardia v0.12 KCNJ2 Zornitza Stark Mode of inheritance for gene: KCNJ2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Catecholaminergic Polymorphic Ventricular Tachycardia v0.11 KCNJ2 Zornitza Stark Classified gene: KCNJ2 as Amber List (moderate evidence)
Catecholaminergic Polymorphic Ventricular Tachycardia v0.11 KCNJ2 Zornitza Stark Gene: kcnj2 has been classified as Amber List (Moderate Evidence).
Cholestasis v0.27 VPS33B Zornitza Stark Marked gene: VPS33B as ready
Cholestasis v0.27 VPS33B Zornitza Stark Gene: vps33b has been classified as Green List (High Evidence).
Cholestasis v0.27 VPS33B Zornitza Stark Phenotypes for gene: VPS33B were changed from to Arthrogryposis, renal dysfunction, and cholestasis 1 (MIM#208085)
Cholestasis v0.26 VPS33B Zornitza Stark Publications for gene: VPS33B were set to
Cholestasis v0.25 VPS33B Zornitza Stark Mode of inheritance for gene: VPS33B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.24 VPS33B Zornitza Stark reviewed gene: VPS33B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31240160, 31777725, 24415890, 15052268; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 1 (MIM#208085); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.52 VPS33B Zornitza Stark Marked gene: VPS33B as ready
Arthrogryposis v0.52 VPS33B Zornitza Stark Gene: vps33b has been classified as Green List (High Evidence).
Arthrogryposis v0.52 VPS33B Zornitza Stark Phenotypes for gene: VPS33B were changed from to Arthrogryposis, renal dysfunction, and cholestasis 1 (MIM#208085)
Arthrogryposis v0.51 VPS33B Zornitza Stark Publications for gene: VPS33B were set to
Arthrogryposis v0.50 VPS33B Zornitza Stark Mode of inheritance for gene: VPS33B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.14 ALX4 Zornitza Stark Marked gene: ALX4 as ready
Craniosynostosis v0.14 ALX4 Zornitza Stark Gene: alx4 has been classified as Green List (High Evidence).
Craniosynostosis v0.14 HUWE1 Bryony Thompson Marked gene: HUWE1 as ready
Craniosynostosis v0.14 HUWE1 Bryony Thompson Gene: huwe1 has been classified as Green List (High Evidence).
Craniosynostosis v0.14 HUWE1 Bryony Thompson Phenotypes for gene: HUWE1 were changed from to Mental retardation, X-linked syndromic, Turner type MIM#309590
Craniosynostosis v0.13 HUWE1 Bryony Thompson Mode of inheritance for gene: HUWE1 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)
Craniosynostosis v0.12 HUWE1 Bryony Thompson reviewed gene: HUWE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29180823; Phenotypes: Mental retardation, X-linked syndromic, Turner type MIM#309590; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Craniosynostosis v0.12 FGF9 Bryony Thompson Marked gene: FGF9 as ready
Craniosynostosis v0.12 FGF9 Bryony Thompson Gene: fgf9 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.12 FGF9 Bryony Thompson Phenotypes for gene: FGF9 were changed from to Multiple synostoses syndrome 3 MIM#612961
Craniosynostosis v0.11 FGF9 Bryony Thompson Mode of inheritance for gene: FGF9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.10 FGF9 Bryony Thompson Classified gene: FGF9 as Amber List (moderate evidence)
Craniosynostosis v0.10 FGF9 Bryony Thompson Gene: fgf9 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.9 FGF9 Bryony Thompson reviewed gene: FGF9: Rating: AMBER; Mode of pathogenicity: None; Publications: 19219044, 28730625; Phenotypes: Multiple synostoses syndrome 3 MIM#612961; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.9 CDC45 Bryony Thompson Marked gene: CDC45 as ready
Craniosynostosis v0.9 CDC45 Bryony Thompson Gene: cdc45 has been classified as Green List (High Evidence).
Craniosynostosis v0.9 CDC45 Bryony Thompson Phenotypes for gene: CDC45 were changed from to Meier-Gorlin syndrome 7 MIM#617063
Craniosynostosis v0.8 CDC45 Bryony Thompson Publications for gene: CDC45 were set to
Craniosynostosis v0.7 CDC45 Bryony Thompson Mode of inheritance for gene: CDC45 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.6 CDC45 Bryony Thompson Mode of inheritance for gene: CDC45 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.6 CDC45 Bryony Thompson Mode of inheritance for gene: CDC45 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.5 CDC45 Bryony Thompson edited their review of gene: CDC45: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.5 CDC45 Bryony Thompson reviewed gene: CDC45: Rating: GREEN; Mode of pathogenicity: None; Publications: 27374770; Phenotypes: Meier-Gorlin syndrome 7 MIM#617063; Mode of inheritance: None
Craniosynostosis v0.5 ALX4 Bryony Thompson Classified gene: ALX4 as Green List (high evidence)
Craniosynostosis v0.5 ALX4 Bryony Thompson Gene: alx4 has been classified as Green List (High Evidence).
Craniosynostosis v0.4 ALX4 Bryony Thompson gene: ALX4 was added
gene: ALX4 was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: ALX4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ALX4 were set to 19692347; 29215649; 22829454
Phenotypes for gene: ALX4 were set to Frontonasal dysplasia 2 MIM#613451; Parietal foramina 2 MIM#609597
Review for gene: ALX4 was set to GREEN
Added comment: Craniosynostosis has been reported in 2 cases with monoallelic likely LoF variants and as a feature of a syndromic condition in 2 consanguineous families with homozygous LoF variants. 2 putative gain of function missense variants were identified in 2 probands with non-syndromic craniosynostosis, but were also identified in unaffected parents.
Sources: Expert list
Arthrogryposis v0.49 VPS33B Crystle Lee reviewed gene: VPS33B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31240160, 31777725, 24415890, 15052268; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 1 (MIM#208085); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 KCNJ2 Ivan Macciocca reviewed gene: KCNJ2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 31020160, 22589293, 26322597; Phenotypes: Andersen Tawil syndrome, LQTS; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 CASQ2 Ivan Macciocca changed review comment from: not curated by ClinGen as at 03/05/2020
Green in PanelApp GEL

Homozygous or compound heterozygous variants have been reported in at least 3 families. Heterozygotes are typically not affected. Functional studies on the variants identified in these families support a deleterious effect. Variants reported in the orgiginal gene discovery papers are either no present, or present at very low frequency (2 or less) in GnomAD/Exac.; to: not curated by ClinGen as at 03/05/2020
Green in PanelApp GEL

Homozygous or compound heterozygous variants have been reported in at least 3 families. Heterozygotes are typically not affected, although there is at least 1 report of a multi-generation family with affected heterozygotes (PMID: 27157848) - this variant is absent from Gnomad as at 03/06/2020). Functional studies on the variants identified in these families support a deleterious effect. Variants reported in the original gene discovery papers are either no present, or present at very low frequency (2 or less) in GnomAD/Exac.
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 CASQ2 Ivan Macciocca changed review comment from: not curated by ClinGen as at 03/05/2020
Green in PanelApp GEL

Homozygous or compound heterozygous variants have been reported in at least 3 families. Heterozygotes are typically not affected. Functional studies on the variants identified in these families support a deleterious effect.; to: not curated by ClinGen as at 03/05/2020
Green in PanelApp GEL

Homozygous or compound heterozygous variants have been reported in at least 3 families. Heterozygotes are typically not affected. Functional studies on the variants identified in these families support a deleterious effect. Variants reported in the orgiginal gene discovery papers are either no present, or present at very low frequency (2 or less) in GnomAD/Exac.
Arthrogryposis v0.49 ZC4H2 Crystle Lee reviewed gene: ZC4H2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23623388, 31885220; Phenotypes: Wieacker-Wolff syndrome (MIM#314580); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 CASQ2 Ivan Macciocca reviewed gene: CASQ2: Rating: GREEN; Mode of pathogenicity: None; Publications: OMID: 611938, 611938; Phenotypes: CPVT; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 CALM2 Ivan Macciocca edited their review of gene: CALM2: Changed publications: PMID: 31170290; Changed phenotypes: LQTS, sudden unexplained death, idopathic VF
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 CALM2 Ivan Macciocca changed review comment from: Not assessed by ClinGen as at 03.05.2020.
Green in PanelApp GEL

Pathogenic and likely pathogenic CALM 1, 2 and 3 variants have been asscoiated with CPVT, LQTS and Idopathic VF (incldundg sudden unexplained death) in a review paper formt he CALM registry (PMID: 31170290). For CPVT at least:
- 7 families have been reported with one of 2 CALM1 P/LP variants, both variants caused overlapping phenotype of LQTS, CPVT and/or SUD
- 8 families have been reported with one of 4 CALM2 P/LP variants, 3 of which caused overlapping phenotype of LQTS, CPVT and/or SUD
- 2 families have been reported with one of 2 CALM3 P/LP variants, both of which caused CPVT exclusively.

Calmodulin is an essential calcium-sensing, signal-transducing protein. Three calmodulin genes, CALM1, CALM2 and CALM3, have unique nucleotide sequences but encode identical 149-amino acid calmodulin proteins with 4 EF-hand calcium-binding loops. (OMIM: https://omim.org/entry/114180?search=CALM1&highlight=calm1#7, accessed 03.05.2020); to: Not assessed by ClinGen as at 03.05.2020.
Green in PanelApp GEL

Pathogenic and likely pathogenic CALM 1, 2 and 3 variants have been asscoiated with CPVT, LQTS and Idopathic VF (incldundg sudden unexplained death) in a review paper formt he CALM registry (PMID: 31170290). For CPVT at least:
- 7 families have been reported with one of 2 CALM1 P/LP variants, both variants caused overlapping phenotype of LQTS, CPVT and/or SUD
- 8 families have been reported with one of 4 CALM2 P/LP variants, 3 of which caused overlapping phenotype of LQTS, CPVT and/or SUD
- 2 families have been reported with one of 2 CALM3 P/LP variants, both of which caused CPVT exclusively.

Calmodulin is an essential calcium-sensing, signal-transducing protein. Three calmodulin genes, CALM1, CALM2 and CALM3, have unique nucleotide sequences but encode identical 149-amino acid calmodulin proteins with 4 EF-hand calcium-binding loops. (OMIM: https://omim.org/entry/114180?search=CALM1&highlight=calm1#7, accessed 03.05.2020)
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 CALM3 Ivan Macciocca reviewed gene: CALM3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 31170290; Phenotypes: LQTS, idiopathic VF, sudden unexplained death; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 CALM2 Ivan Macciocca commented on gene: CALM2
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 CALM1 Ivan Macciocca reviewed gene: CALM1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31170290; Phenotypes: CPVT, LQTS, idiopathic VF; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliary Dyskinesia v0.113 HYDIN Crystle Lee reviewed gene: HYDIN: Rating: GREEN; Mode of pathogenicity: None; Publications: 23022101, 23849777, 28441829, 31116566; Phenotypes: Ciliary dyskinesia, primary, 5 (MIM#608647); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.103 HYDIN Crystle Lee reviewed gene: HYDIN: Rating: RED; Mode of pathogenicity: None; Publications: 23022101, 23849777; Phenotypes: Ciliary dyskinesia, primary, 5 (MIM#08647); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.448 MT-CO3 Chern Lim gene: MT-CO3 was added
gene: MT-CO3 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene gene: MT-CO3 was set to MITOCHONDRIAL
Publications for gene: MT-CO3 were set to 20525945; 9634511; 11063732; 12414820
Phenotypes for gene: MT-CO3 were set to Leigh syndrome; Leigh-like syndrome; Myopathy; Encephalopathy and myopathy
Review for gene: MT-CO3 was set to GREEN
gene: MT-CO3 was marked as current diagnostic
Added comment: Reported in at least 3 unrelated families (PMIDs: 20525945, 9634511, 11063732, 12414820).
Sources: Literature
Heterotaxy v0.103 LRRC56 Elena Savva gene: LRRC56 was added
gene: LRRC56 was added to Heterotaxy. Sources: Expert list
Mode of inheritance for gene: LRRC56 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC56 were set to PMID: 30388400
Phenotypes for gene: LRRC56 were set to Ciliary dyskinesia, primary, 39 618254
Review for gene: LRRC56 was set to GREEN
Added comment: PMID: 30388400 - 3 unrelated families reported with either homozygous splice, missense or chet (nonsense/splice). All patients had dextrocardia, atrial situs inversus and abdominal/thoracic situs inversus
Sources: Expert list
Heterotaxy v0.103 LZTFL1 Crystle Lee gene: LZTFL1 was added
gene: LZTFL1 was added to Heterotaxy. Sources: Expert Review
Mode of inheritance for gene: LZTFL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LZTFL1 were set to 22510444; 23692385; 27312011; 22072986
Phenotypes for gene: LZTFL1 were set to Bardet-Biedl syndrome 17 (MIM#615994)
Review for gene: LZTFL1 was set to AMBER
Added comment: Only 1 family of the 2 currently reported presented with situs invertus

PMID: 22510444; Marion 2012: Hom variant reported in BBS family, presenting with situs invertus. Supporting functional studies performed. Variant not present in gnomad

PMID: 23692385; Schaefer 2014: Compound heterozygous variants reported in twins with BBS, with supporting functional studies. Situs invertus not reported. Variants not in gnomAD at unexpected frquencies.

PMID: 27312011; Jiang 2016: Knockout mice model showed retinal defects and differences in weight compared to wild-type mice.

PMID: 22072986; Seo 2011: LZTFL1 interacts with BBS protein complex and is an important regulator of BBSome ciliary trafficking
Sources: Expert Review
Bardet Biedl syndrome v0.28 LZTFL1 Crystle Lee reviewed gene: LZTFL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22510444, 23692385, 27312011, 22072986; Phenotypes: Bardet-Biedl syndrome 17 (MIM#615994); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Vascular Malformations_Germline v0.94 PTPN14 Zornitza Stark Publications for gene: PTPN14 were set to
Vascular Malformations_Germline v0.93 PTPN11 Zornitza Stark Marked gene: PTPN11 as ready
Vascular Malformations_Germline v0.93 PTPN11 Zornitza Stark Added comment: Comment when marking as ready: No evidence for association between germline variants and vascular malformations.
Vascular Malformations_Germline v0.93 PTPN11 Zornitza Stark Gene: ptpn11 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 PIK3R2 Zornitza Stark Marked gene: PIK3R2 as ready
Vascular Malformations_Germline v0.93 PIK3R2 Zornitza Stark Gene: pik3r2 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 PIK3R1 Zornitza Stark Marked gene: PIK3R1 as ready
Vascular Malformations_Germline v0.93 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 NRAS Zornitza Stark Marked gene: NRAS as ready
Vascular Malformations_Germline v0.93 NRAS Zornitza Stark Gene: nras has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 MTOR Zornitza Stark Marked gene: MTOR as ready
Vascular Malformations_Germline v0.93 MTOR Zornitza Stark Gene: mtor has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 MAP3K3 Zornitza Stark Marked gene: MAP3K3 as ready
Vascular Malformations_Germline v0.93 MAP3K3 Zornitza Stark Gene: map3k3 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 MAP2K1 Zornitza Stark Marked gene: MAP2K1 as ready
Vascular Malformations_Germline v0.93 MAP2K1 Zornitza Stark Gene: map2k1 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 KRAS Zornitza Stark Marked gene: KRAS as ready
Vascular Malformations_Germline v0.93 KRAS Zornitza Stark Gene: kras has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 HRAS Zornitza Stark Marked gene: HRAS as ready
Vascular Malformations_Germline v0.93 HRAS Zornitza Stark Gene: hras has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 GNAQ Zornitza Stark Marked gene: GNAQ as ready
Vascular Malformations_Germline v0.93 GNAQ Zornitza Stark Gene: gnaq has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 GNA14 Zornitza Stark Marked gene: GNA14 as ready
Vascular Malformations_Germline v0.93 GNA14 Zornitza Stark Gene: gna14 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 GNA11 Zornitza Stark Marked gene: GNA11 as ready
Vascular Malformations_Germline v0.93 GNA11 Zornitza Stark Gene: gna11 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 GNA11 Zornitza Stark Mode of pathogenicity for gene: GNA11 was changed from to Other
Vascular Malformations_Germline v0.92 GNA11 Zornitza Stark Mode of inheritance for gene: GNA11 was changed from to Other
Vascular Malformations_Germline v0.91 BRAF Zornitza Stark Marked gene: BRAF as ready
Vascular Malformations_Germline v0.91 BRAF Zornitza Stark Gene: braf has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.91 AKT1 Zornitza Stark Marked gene: AKT1 as ready
Vascular Malformations_Germline v0.91 AKT1 Zornitza Stark Gene: akt1 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.91 KDR Zornitza Stark Marked gene: KDR as ready
Vascular Malformations_Germline v0.91 KDR Zornitza Stark Gene: kdr has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.91 ELMO2 Zornitza Stark Marked gene: ELMO2 as ready
Vascular Malformations_Germline v0.91 ELMO2 Zornitza Stark Gene: elmo2 has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.91 ELMO2 Zornitza Stark Publications for gene: ELMO2 were set to
Vascular Malformations_Germline v0.89 SOS1 Zornitza Stark Marked gene: SOS1 as ready
Vascular Malformations_Germline v0.89 SOS1 Zornitza Stark Added comment: Comment when marking as ready: Somatic variants in Rasopathy genes have been associated with vascular malformations.
Vascular Malformations_Germline v0.89 SOS1 Zornitza Stark Gene: sos1 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.89 SOS1 Zornitza Stark Tag somatic tag was added to gene: SOS1.
Mendeliome v0.2996 DNAL1 Zornitza Stark Marked gene: DNAL1 as ready
Mendeliome v0.2996 DNAL1 Zornitza Stark Gene: dnal1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2996 DNAL1 Zornitza Stark Phenotypes for gene: DNAL1 were changed from to Ciliary dyskinesia, primary, 16, MIM# 614017
Mendeliome v0.2995 DNAL1 Zornitza Stark Publications for gene: DNAL1 were set to
Mendeliome v0.2994 DNAL1 Zornitza Stark Mode of inheritance for gene: DNAL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2993 DNAL1 Zornitza Stark Classified gene: DNAL1 as Amber List (moderate evidence)
Mendeliome v0.2993 DNAL1 Zornitza Stark Gene: dnal1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2992 DNAL1 Zornitza Stark Tag founder tag was added to gene: DNAL1.
Mendeliome v0.2992 DNAL1 Zornitza Stark reviewed gene: DNAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21496787; Phenotypes: Ciliary dyskinesia, primary, 16, MIM# 614017; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.113 DNAL1 Zornitza Stark Tag founder tag was added to gene: DNAL1.
Heterotaxy v0.103 DNAL1 Zornitza Stark Marked gene: DNAL1 as ready
Heterotaxy v0.103 DNAL1 Zornitza Stark Gene: dnal1 has been classified as Amber List (Moderate Evidence).
Heterotaxy v0.103 DNAL1 Zornitza Stark Phenotypes for gene: DNAL1 were changed from to Ciliary dyskinesia, primary, 16, MIM# 614017
Heterotaxy v0.102 DNAL1 Zornitza Stark Publications for gene: DNAL1 were set to
Heterotaxy v0.101 DNAL1 Zornitza Stark Mode of inheritance for gene: DNAL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.100 DNAL1 Zornitza Stark Tag founder tag was added to gene: DNAL1.
Heterotaxy v0.100 DNAL1 Zornitza Stark Classified gene: DNAL1 as Amber List (moderate evidence)
Heterotaxy v0.100 DNAL1 Zornitza Stark Gene: dnal1 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.113 DNAL1 Zornitza Stark changed review comment from: Single family reported with homozygous missense variant, some functional data.; to: Two Bedouin families reported with same homozygous missense variant (founder), some functional data.
Heterotaxy v0.99 DNAL1 Zornitza Stark reviewed gene: DNAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21496787; Phenotypes: Ciliary dyskinesia, primary, 16, MIM# 614017; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.113 DNAL1 Zornitza Stark Marked gene: DNAL1 as ready
Ciliary Dyskinesia v0.113 DNAL1 Zornitza Stark Gene: dnal1 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.113 DNAL1 Zornitza Stark Phenotypes for gene: DNAL1 were changed from to Ciliary dyskinesia, primary, 16, MIM# 614017
Ciliary Dyskinesia v0.112 DNAL1 Zornitza Stark Publications for gene: DNAL1 were set to
Ciliary Dyskinesia v0.111 DNAL1 Zornitza Stark Mode of inheritance for gene: DNAL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.110 DNAL1 Zornitza Stark Classified gene: DNAL1 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.110 DNAL1 Zornitza Stark Gene: dnal1 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.109 DNAL1 Zornitza Stark reviewed gene: DNAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21496787; Phenotypes: Ciliary dyskinesia, primary, 16, MIM# 614017; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2992 DNAH8 Zornitza Stark Marked gene: DNAH8 as ready
Mendeliome v0.2992 DNAH8 Zornitza Stark Gene: dnah8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2992 DNAH8 Zornitza Stark Phenotypes for gene: DNAH8 were changed from to Asthenozoospermia; primary ciliary dyskinesia
Mendeliome v0.2991 DNAH8 Zornitza Stark Publications for gene: DNAH8 were set to
Mendeliome v0.2990 DNAH8 Zornitza Stark Mode of inheritance for gene: DNAH8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2989 DNAH8 Zornitza Stark Classified gene: DNAH8 as Amber List (moderate evidence)
Mendeliome v0.2989 DNAH8 Zornitza Stark Gene: dnah8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2988 DNAH8 Zornitza Stark reviewed gene: DNAH8: Rating: AMBER; Mode of pathogenicity: None; Publications: 31178125, 24307375; Phenotypes: Asthenozoospermia, primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.99 GAS8 Zornitza Stark changed review comment from: Heterotaxy is not part of the phenotype of this PCD.; to: Heterotaxy is not part of the phenotype of this PCD in the individuals reported, though note zebrafish model had LR axis abnormalities.
Heterotaxy v0.99 GAS8 Zornitza Stark edited their review of gene: GAS8: Changed publications: 19043402, 26387594
Heterotaxy v0.99 GAS8 Zornitza Stark Marked gene: GAS8 as ready
Heterotaxy v0.99 GAS8 Zornitza Stark Gene: gas8 has been classified as Red List (Low Evidence).
Heterotaxy v0.99 GAS8 Zornitza Stark Phenotypes for gene: GAS8 were changed from to Ciliary dyskinesia, primary, 33, MIM# 616726
Heterotaxy v0.98 GAS8 Zornitza Stark Mode of inheritance for gene: GAS8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.97 GAS8 Zornitza Stark Classified gene: GAS8 as Red List (low evidence)
Heterotaxy v0.97 GAS8 Zornitza Stark Gene: gas8 has been classified as Red List (Low Evidence).
Heterotaxy v0.96 GAS8 Zornitza Stark reviewed gene: GAS8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 33, MIM# 616726; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2988 TTC5 Zornitza Stark Marked gene: TTC5 as ready
Mendeliome v0.2988 TTC5 Zornitza Stark Gene: ttc5 has been classified as Green List (High Evidence).
Mendeliome v0.2988 TTC5 Zornitza Stark Classified gene: TTC5 as Green List (high evidence)
Mendeliome v0.2988 TTC5 Zornitza Stark Gene: ttc5 has been classified as Green List (High Evidence).
Mendeliome v0.2987 TTC5 Zornitza Stark gene: TTC5 was added
gene: TTC5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TTC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC5 were set to 29302074; 32439809
Phenotypes for gene: TTC5 were set to Central hypotonia; Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; Microcephaly; Abnormality of the face; Behavioral abnormality; Abnormality of the genitourinary system
Review for gene: TTC5 was set to GREEN
Added comment: Eleven individuals from seven families reported.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2660 TTC5 Zornitza Stark Marked gene: TTC5 as ready
Intellectual disability syndromic and non-syndromic v0.2660 TTC5 Zornitza Stark Gene: ttc5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2660 TTC5 Zornitza Stark Classified gene: TTC5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2660 TTC5 Zornitza Stark Gene: ttc5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2659 TTC5 Konstantinos Varvagiannis gene: TTC5 was added
gene: TTC5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TTC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC5 were set to 29302074; 32439809
Phenotypes for gene: TTC5 were set to Central hypotonia; Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; Microcephaly; Abnormality of the face; Behavioral abnormality; Abnormality of the genitourinary system
Penetrance for gene: TTC5 were set to Complete
Review for gene: TTC5 was set to GREEN
Added comment: Hu et al (2019 - PMID: 29302074) reported briefly on 3 individuals from 2 consanguineous families (from Turkey and Iran) with biallelic TTC5 variants. Features included DD (3/3), ID (severe in 2/2 with relevant age), microcephaly (3/3), brain abnormalities, etc. A nonsense and a variant affecting splice site were identified by WES/WGS.

---

In a recent report, Rasheed et al (2020 - PMID: 32439809) report on the phenotype of 8 individuals - belonging to 5 consanguineous families - all 8 harboring homozygous TTC5 mutations.

Frequent features included hypotonia (6/8), motor and speech delay, moderate to severe ID (10/10 of relevant age - inclusion of less severely affected subjects was not considered by study design), brain MRI abnormalities (8/8). Other findings included microcephaly in some (6/11), behavioral abnormalities in few (autistic behavior in 2/8, aggression in 2/8), genitourinary anomalies (2/8), seizures (1/11). Facial phenotype incl. thin V-shaped upper lip, low-set ears (in most) and/or additional features.

TTC5 encodes a 440 aa protein, functioning as a scaffold to stabilise p300-JMY interactions. Apart from this role in nucleus, it has functions in the cytoplasm (inhibiting actin nucleataion, autophagosome formation, etc).

The gene has ubiquitous expression, highest in brain.

All variants were identified following WES - as the best candidates - in affected individuals with compatible Sanger studies in all affected family members and carrier parents.

2 missense and 2 nonsense variants were identified with the 2 missense SNVs localizing within TPR domains. qRT-PCR studies for a nonsense variant localizing 19 nt before the last exon, revealed fourfold decreased expression in affected individuals compared to carriers.

Families from Egypt shared a homozygous ~6.3 Mb haplotype block spanning TTC5, suggesting that p.(Arg263Ter) is likely a founder mutation.

The authors underscore some phenotypic (though not facial) similarities with Rubinstein-Taybi syndrome 2 due to EP300 mutations (in line with the role of TTC5).

Biallelic variants in genes encoding other members of the TTC family (containing a TPR motif), e.g. TTC8 or TTC15 cause disorders with neurologic manifestations (and DD/ID).
Sources: Literature
Vascular Malformations_Germline v0.89 CDKN1C Zornitza Stark Marked gene: CDKN1C as ready
Vascular Malformations_Germline v0.89 CDKN1C Zornitza Stark Gene: cdkn1c has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.89 CDKN1C Zornitza Stark Phenotypes for gene: CDKN1C were changed from Beckwith-Wiedemann syndrome 130650; IMAGE syndrome 614732 to Beckwith-Wiedemann syndrome 130650
Vascular Malformations_Germline v0.88 CDKN1C Zornitza Stark Classified gene: CDKN1C as Amber List (moderate evidence)
Vascular Malformations_Germline v0.88 CDKN1C Zornitza Stark Gene: cdkn1c has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.87 CDKN1C Zornitza Stark reviewed gene: CDKN1C: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Beckwith-Wiedemann syndrome, MIM# 130650; Mode of inheritance: None
Vascular Malformations_Germline v0.85 SOS1 Zornitza Stark Marked gene: SOS1 as ready
Vascular Malformations_Germline v0.85 SOS1 Zornitza Stark Gene: sos1 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.84 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mendeliome v0.2986 ACAD11 Zornitza Stark Marked gene: ACAD11 as ready
Mendeliome v0.2986 ACAD11 Zornitza Stark Gene: acad11 has been classified as Red List (Low Evidence).
Mendeliome v0.2986 ACAD11 Zornitza Stark Classified gene: ACAD11 as Red List (low evidence)
Mendeliome v0.2986 ACAD11 Zornitza Stark Gene: acad11 has been classified as Red List (Low Evidence).
Mendeliome v0.2985 ACAD11 Zornitza Stark reviewed gene: ACAD11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Heterotaxy v0.96 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Long QT Syndrome v0.57 KCNE1 Zornitza Stark Phenotypes for gene: KCNE1 were changed from long QT syndrome; acquired LQTS to Jervell and Lange-Nielsen syndrome 2, MIM# 612347; Long QT syndrome 5, MIM# 613695; Acquired LQTS
Long QT Syndrome v0.56 KCNE1 Zornitza Stark Marked gene: KCNE1 as ready
Long QT Syndrome v0.56 KCNE1 Zornitza Stark Added comment: Comment when marking as ready: Rated as MODERATE by ClinGen for bi-allelic disease. Evidence for mono-allelic disease is limited.
Long QT Syndrome v0.56 KCNE1 Zornitza Stark Gene: kcne1 has been classified as Amber List (Moderate Evidence).
Long QT Syndrome v0.56 SNTA1 Zornitza Stark Marked gene: SNTA1 as ready
Long QT Syndrome v0.56 SNTA1 Zornitza Stark Gene: snta1 has been classified as Red List (Low Evidence).
Long QT Syndrome v0.56 SNTA1 Zornitza Stark Phenotypes for gene: SNTA1 were changed from to Long QT syndrome 12, MIM# 612955
Long QT Syndrome v0.55 SNTA1 Zornitza Stark Publications for gene: SNTA1 were set to
Long QT Syndrome v0.54 SNTA1 Zornitza Stark Mode of inheritance for gene: SNTA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.53 SNTA1 Zornitza Stark Classified gene: SNTA1 as Red List (low evidence)
Long QT Syndrome v0.53 SNTA1 Zornitza Stark Gene: snta1 has been classified as Red List (Low Evidence).
Long QT Syndrome v0.52 SNTA1 Zornitza Stark Tag disputed tag was added to gene: SNTA1.
Long QT Syndrome v0.52 TRDN Zornitza Stark Marked gene: TRDN as ready
Long QT Syndrome v0.52 TRDN Zornitza Stark Gene: trdn has been classified as Green List (High Evidence).
Long QT Syndrome v0.52 TRDN Zornitza Stark Publications for gene: TRDN were set to long QT syndrome
Long QT Syndrome v0.51 TRDN Zornitza Stark Phenotypes for gene: TRDN were changed from PMID: 31983240; 25922419 to Long QT syndrome; Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness, MIM# 615441
Long QT Syndrome v0.50 TRDN Zornitza Stark Classified gene: TRDN as Green List (high evidence)
Long QT Syndrome v0.50 TRDN Zornitza Stark Gene: trdn has been classified as Green List (High Evidence).
Long QT Syndrome v0.49 CALM2 Zornitza Stark Marked gene: CALM2 as ready
Long QT Syndrome v0.49 CALM2 Zornitza Stark Gene: calm2 has been classified as Green List (High Evidence).
Long QT Syndrome v0.49 CALM2 Zornitza Stark Phenotypes for gene: CALM2 were changed from long QT syndrome to Long QT syndrome 15, MIM# 616249
Long QT Syndrome v0.48 CALM2 Zornitza Stark Classified gene: CALM2 as Green List (high evidence)
Long QT Syndrome v0.48 CALM2 Zornitza Stark Gene: calm2 has been classified as Green List (High Evidence).
Long QT Syndrome v0.46 CALM1 Zornitza Stark Marked gene: CALM1 as ready
Long QT Syndrome v0.46 CALM1 Zornitza Stark Gene: calm1 has been classified as Green List (High Evidence).
Long QT Syndrome v0.46 CALM1 Zornitza Stark Phenotypes for gene: CALM1 were changed from long QT syndrome to Long QT syndrome 14, MIM# 616247
Long QT Syndrome v0.45 CALM1 Zornitza Stark Classified gene: CALM1 as Green List (high evidence)
Long QT Syndrome v0.45 CALM1 Zornitza Stark Gene: calm1 has been classified as Green List (High Evidence).
Long QT Syndrome v0.44 SCN4B Zornitza Stark Marked gene: SCN4B as ready
Long QT Syndrome v0.44 SCN4B Zornitza Stark Gene: scn4b has been classified as Red List (Low Evidence).
Long QT Syndrome v0.44 SCN4B Zornitza Stark Phenotypes for gene: SCN4B were changed from to Long QT syndrome 10, MIM# 611819
Long QT Syndrome v0.43 SCN4B Zornitza Stark Publications for gene: SCN4B were set to
Long QT Syndrome v0.42 SCN4B Zornitza Stark Mode of inheritance for gene: SCN4B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.41 SCN4B Zornitza Stark Classified gene: SCN4B as Red List (low evidence)
Long QT Syndrome v0.41 SCN4B Zornitza Stark Gene: scn4b has been classified as Red List (Low Evidence).
Long QT Syndrome v0.40 SCN4B Zornitza Stark Tag disputed tag was added to gene: SCN4B.
Long QT Syndrome v0.40 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Long QT Syndrome v0.39 KCNJ5 Zornitza Stark Marked gene: KCNJ5 as ready
Long QT Syndrome v0.39 KCNJ5 Zornitza Stark Gene: kcnj5 has been classified as Red List (Low Evidence).
Long QT Syndrome v0.39 KCNJ5 Zornitza Stark Phenotypes for gene: KCNJ5 were changed from to Long QT syndrome 13, MIM# 613485
Long QT Syndrome v0.38 KCNJ5 Zornitza Stark Publications for gene: KCNJ5 were set to
Long QT Syndrome v0.37 KCNJ5 Zornitza Stark Mode of inheritance for gene: KCNJ5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.36 KCNJ5 Zornitza Stark Tag disputed tag was added to gene: KCNJ5.
Long QT Syndrome v0.36 KCNJ5 Zornitza Stark Classified gene: KCNJ5 as Red List (low evidence)
Long QT Syndrome v0.36 KCNJ5 Zornitza Stark Gene: kcnj5 has been classified as Red List (Low Evidence).
Heterotaxy v0.95 NPHP4 Zornitza Stark Marked gene: NPHP4 as ready
Heterotaxy v0.95 NPHP4 Zornitza Stark Gene: nphp4 has been classified as Amber List (Moderate Evidence).
Heterotaxy v0.95 NPHP4 Zornitza Stark Mode of inheritance for gene: NPHP4 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Heterotaxy v0.95 NPHP4 Zornitza Stark Mode of inheritance for gene: NPHP4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Heterotaxy v0.94 NPHP4 Zornitza Stark Classified gene: NPHP4 as Amber List (moderate evidence)
Heterotaxy v0.94 NPHP4 Zornitza Stark Gene: nphp4 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.45 NKX2-5 Zornitza Stark Marked gene: NKX2-5 as ready
Congenital Heart Defect v0.45 NKX2-5 Zornitza Stark Gene: nkx2-5 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.45 NKX2-5 Zornitza Stark Phenotypes for gene: NKX2-5 were changed from to Ventricular septal defect 3 (MIM#614432); Tetralogy of Fallot (MIM#187500)
Congenital Heart Defect v0.44 NKX2-5 Zornitza Stark Publications for gene: NKX2-5 were set to
Congenital Heart Defect v0.43 NKX2-5 Zornitza Stark Mode of inheritance for gene: NKX2-5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.43 NKX2-5 Zornitza Stark Mode of inheritance for gene: NKX2-5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Heterotaxy v0.93 CCNO Zornitza Stark Marked gene: CCNO as ready
Heterotaxy v0.93 CCNO Zornitza Stark Gene: ccno has been classified as Red List (Low Evidence).
Heterotaxy v0.93 CCNO Zornitza Stark Phenotypes for gene: CCNO were changed from to Ciliary dyskinesia, primary, 29, MIM# 615872
Heterotaxy v0.92 CCNO Zornitza Stark Publications for gene: CCNO were set to
Heterotaxy v0.91 CCNO Zornitza Stark Mode of inheritance for gene: CCNO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.90 CCNO Zornitza Stark Classified gene: CCNO as Red List (low evidence)
Heterotaxy v0.90 CCNO Zornitza Stark Gene: ccno has been classified as Red List (Low Evidence).
Heterotaxy v0.89 CRELD1 Zornitza Stark Classified gene: CRELD1 as Amber List (moderate evidence)
Heterotaxy v0.89 CRELD1 Zornitza Stark Gene: creld1 has been classified as Amber List (Moderate Evidence).
Heterotaxy v0.88 CRELD1 Zornitza Stark changed review comment from: Three families reported with heterozygous missense variants and heterotaxy phenotype.
Sources: Expert list; to: Three families reported with heterozygous missense variants and heterotaxy phenotype. However, supporting evidence of pathogenicity for some of the variants is relatively weak.
Sources: Expert list
Heterotaxy v0.88 CRELD1 Zornitza Stark edited their review of gene: CRELD1: Changed rating: AMBER
Heterotaxy v0.88 DNAAF2 Zornitza Stark Marked gene: DNAAF2 as ready
Heterotaxy v0.88 DNAAF2 Zornitza Stark Gene: dnaaf2 has been classified as Green List (High Evidence).
Heterotaxy v0.88 DNAAF2 Zornitza Stark Phenotypes for gene: DNAAF2 were changed from to Ciliary dyskinesia, primary, 10 612518
Heterotaxy v0.87 DNAAF2 Zornitza Stark Publications for gene: DNAAF2 were set to
Heterotaxy v0.86 DNAAF2 Zornitza Stark Mode of inheritance for gene: DNAAF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.85 DNAH1 Zornitza Stark Marked gene: DNAH1 as ready
Heterotaxy v0.85 DNAH1 Zornitza Stark Gene: dnah1 has been classified as Red List (Low Evidence).
Heterotaxy v0.85 DNAH1 Zornitza Stark Classified gene: DNAH1 as Red List (low evidence)
Heterotaxy v0.85 DNAH1 Zornitza Stark Gene: dnah1 has been classified as Red List (Low Evidence).
Mendeliome v0.2985 DNAH6 Zornitza Stark Marked gene: DNAH6 as ready
Mendeliome v0.2985 DNAH6 Zornitza Stark Gene: dnah6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2985 DNAH6 Zornitza Stark Classified gene: DNAH6 as Amber List (moderate evidence)
Mendeliome v0.2985 DNAH6 Zornitza Stark Gene: dnah6 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.109 DNAH9 Zornitza Stark Marked gene: DNAH9 as ready
Ciliary Dyskinesia v0.109 DNAH9 Zornitza Stark Gene: dnah9 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.109 DNAH9 Zornitza Stark Phenotypes for gene: DNAH9 were changed from to Ciliary dyskinesia, primary, 40, MIM# 618300
Ciliary Dyskinesia v0.108 DNAH9 Zornitza Stark Publications for gene: DNAH9 were set to
Ciliary Dyskinesia v0.107 DNAH9 Zornitza Stark Mode of inheritance for gene: DNAH9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.106 DNAH9 Zornitza Stark reviewed gene: DNAH9: Rating: GREEN; Mode of pathogenicity: None; Publications: 30471717, 30471718; Phenotypes: Ciliary dyskinesia, primary, 40, MIM# 618300; Mode of inheritance: None
Heterotaxy v0.84 DNAH9 Zornitza Stark Marked gene: DNAH9 as ready
Heterotaxy v0.84 DNAH9 Zornitza Stark Gene: dnah9 has been classified as Green List (High Evidence).
Heterotaxy v0.84 DNAH9 Zornitza Stark Classified gene: DNAH9 as Green List (high evidence)
Heterotaxy v0.84 DNAH9 Zornitza Stark Gene: dnah9 has been classified as Green List (High Evidence).
Mendeliome v0.2984 DRC1 Zornitza Stark Marked gene: DRC1 as ready
Mendeliome v0.2984 DRC1 Zornitza Stark Gene: drc1 has been classified as Green List (High Evidence).
Mendeliome v0.2984 DRC1 Zornitza Stark Phenotypes for gene: DRC1 were changed from to Ciliary dyskinesia, primary, 21, MIM# 615294
Mendeliome v0.2983 DRC1 Zornitza Stark Publications for gene: DRC1 were set to
Mendeliome v0.2982 DRC1 Zornitza Stark Mode of inheritance for gene: DRC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2981 DRC1 Zornitza Stark Tag SV/CNV tag was added to gene: DRC1.
Mendeliome v0.2981 DRC1 Zornitza Stark edited their review of gene: DRC1: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2981 DRC1 Zornitza Stark reviewed gene: DRC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31960620; Phenotypes: Ciliary dyskinesia, primary, 21, MIM# 615294; Mode of inheritance: None
Heterotaxy v0.83 DRC1 Zornitza Stark Marked gene: DRC1 as ready
Heterotaxy v0.83 DRC1 Zornitza Stark Gene: drc1 has been classified as Red List (Low Evidence).
Heterotaxy v0.83 DRC1 Zornitza Stark Phenotypes for gene: DRC1 were changed from to Ciliary dyskinesia, primary, 21, MIM# 615294
Heterotaxy v0.82 DRC1 Zornitza Stark Publications for gene: DRC1 were set to
Heterotaxy v0.81 DRC1 Zornitza Stark Mode of inheritance for gene: DRC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.80 DRC1 Zornitza Stark Classified gene: DRC1 as Red List (low evidence)
Heterotaxy v0.80 DRC1 Zornitza Stark Gene: drc1 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.42 TLL1 Zornitza Stark Marked gene: TLL1 as ready
Congenital Heart Defect v0.42 TLL1 Zornitza Stark Gene: tll1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.42 TLL1 Zornitza Stark Publications for gene: TLL1 were set to
Congenital Heart Defect v0.41 TLL1 Zornitza Stark Mode of inheritance for gene: TLL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.40 TLL1 Zornitza Stark reviewed gene: TLL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18830233, 30538173, 27418595, 31570783; Phenotypes: Atrial septal defect; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2981 TLL1 Zornitza Stark Phenotypes for gene: TLL1 were changed from to Atrial septal defect
Mendeliome v0.2980 TLL1 Zornitza Stark Publications for gene: TLL1 were set to
Mendeliome v0.2979 TLL1 Zornitza Stark Mode of inheritance for gene: TLL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2978 TLL1 Dean Phelan reviewed gene: TLL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18830233, 30538173, 27418595, 31570783; Phenotypes: Atrial septal defect; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2978 HIST1H4J Zornitza Stark Marked gene: HIST1H4J as ready
Mendeliome v0.2978 HIST1H4J Zornitza Stark Gene: hist1h4j has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2978 HIST1H4J Zornitza Stark Classified gene: HIST1H4J as Amber List (moderate evidence)
Mendeliome v0.2978 HIST1H4J Zornitza Stark Gene: hist1h4j has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2977 HIST1H4J Zornitza Stark gene: HIST1H4J was added
gene: HIST1H4J was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIST1H4J was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIST1H4J were set to 31804630
Phenotypes for gene: HIST1H4J were set to microcephaly; intellectual disability; dysmorphic features
Review for gene: HIST1H4J was set to AMBER
Added comment: Single case report but with functional evidence in zebrafish and phenotypic similarity to other HIST1H4C phenotype
Sources: Literature
Mendeliome v0.2976 MCIDAS Zornitza Stark Marked gene: MCIDAS as ready
Mendeliome v0.2976 MCIDAS Zornitza Stark Gene: mcidas has been classified as Green List (High Evidence).
Mendeliome v0.2976 MCIDAS Zornitza Stark Phenotypes for gene: MCIDAS were changed from to Ciliary dyskinesia, primary, 42 (MIM#618695)
Mendeliome v0.2975 MCIDAS Zornitza Stark Publications for gene: MCIDAS were set to
Mendeliome v0.2974 MCIDAS Zornitza Stark Mode of inheritance for gene: MCIDAS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2973 MCIDAS Zornitza Stark reviewed gene: MCIDAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 25048963; Phenotypes: Ciliary dyskinesia, primary, 42 (MIM#618695); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.79 MCIDAS Zornitza Stark Marked gene: MCIDAS as ready
Heterotaxy v0.79 MCIDAS Zornitza Stark Gene: mcidas has been classified as Red List (Low Evidence).
Heterotaxy v0.79 MCIDAS Zornitza Stark Phenotypes for gene: MCIDAS were changed from to Ciliary dyskinesia, primary, 42 (MIM#618695)
Heterotaxy v0.78 MCIDAS Zornitza Stark Publications for gene: MCIDAS were set to
Heterotaxy v0.77 MCIDAS Zornitza Stark Mode of inheritance for gene: MCIDAS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.76 MCIDAS Zornitza Stark Classified gene: MCIDAS as Red List (low evidence)
Heterotaxy v0.76 MCIDAS Zornitza Stark Gene: mcidas has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.106 MCIDAS Zornitza Stark Marked gene: MCIDAS as ready
Ciliary Dyskinesia v0.106 MCIDAS Zornitza Stark Gene: mcidas has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.106 MCIDAS Zornitza Stark Phenotypes for gene: MCIDAS were changed from to Ciliary dyskinesia, primary, 42 (MIM#618695)
Ciliary Dyskinesia v0.105 MCIDAS Zornitza Stark Publications for gene: MCIDAS were set to
Ciliary Dyskinesia v0.104 MCIDAS Zornitza Stark Mode of inheritance for gene: MCIDAS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2973 VWA3B Zornitza Stark Marked gene: VWA3B as ready
Mendeliome v0.2973 VWA3B Zornitza Stark Gene: vwa3b has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.13 TOR1AIP1 Zornitza Stark Marked gene: TOR1AIP1 as ready
Muscular dystrophy and myopathy_Paediatric v0.13 TOR1AIP1 Zornitza Stark Gene: tor1aip1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.13 TOR1AIP1 Zornitza Stark Classified gene: TOR1AIP1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.13 TOR1AIP1 Zornitza Stark Gene: tor1aip1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.12 TOR1AIP1 Zornitza Stark gene: TOR1AIP1 was added
gene: TOR1AIP1 was added to Muscular dystrophy. Sources: Literature
Mode of inheritance for gene: TOR1AIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOR1AIP1 were set to 24856141; 31299614; 30723199; 27342937; 32055997
Phenotypes for gene: TOR1AIP1 were set to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Progeroid appearance; Cataracts; Microcephaly; Deafness; Contractures
Review for gene: TOR1AIP1 was set to GREEN
Added comment: Multiple families reported but highly variable phenotype; muscular dystrophy reported frequently.
Sources: Literature
Arthrogryposis v0.49 TOR1AIP1 Zornitza Stark Marked gene: TOR1AIP1 as ready
Arthrogryposis v0.49 TOR1AIP1 Zornitza Stark Gene: tor1aip1 has been classified as Green List (High Evidence).
Arthrogryposis v0.49 TOR1AIP1 Zornitza Stark Classified gene: TOR1AIP1 as Green List (high evidence)
Arthrogryposis v0.49 TOR1AIP1 Zornitza Stark Gene: tor1aip1 has been classified as Green List (High Evidence).
Arthrogryposis v0.48 TOR1AIP1 Zornitza Stark gene: TOR1AIP1 was added
gene: TOR1AIP1 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: TOR1AIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOR1AIP1 were set to 24856141; 31299614; 30723199; 27342937; 32055997
Phenotypes for gene: TOR1AIP1 were set to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Progeroid appearance; Cataracts; Microcephaly; Deafness; Contractures
Review for gene: TOR1AIP1 was set to GREEN
Added comment: Multiple families reported but highly variable phenotype; joint contractures observed in multiple individuals.
Sources: Literature
Mendeliome v0.2973 TOR1AIP1 Zornitza Stark Phenotypes for gene: TOR1AIP1 were changed from Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Progeroid appearance; Cataracts; Microcephaly; Deafness to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Progeroid appearance; Cataracts; Microcephaly; Deafness; Contractures
Mendeliome v0.2972 TOR1AIP1 Zornitza Stark Phenotypes for gene: TOR1AIP1 were changed from Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072 to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Progeroid appearance; Cataracts; Microcephaly; Deafness
Mendeliome v0.2971 TOR1AIP1 Zornitza Stark Marked gene: TOR1AIP1 as ready
Mendeliome v0.2971 TOR1AIP1 Zornitza Stark Added comment: Comment when marking as ready: Highly variable phenotype. Few of the features are consistently reported across affected individuals.
Mendeliome v0.2971 TOR1AIP1 Zornitza Stark Gene: tor1aip1 has been classified as Green List (High Evidence).
Mendeliome v0.2971 TOR1AIP1 Zornitza Stark Publications for gene: TOR1AIP1 were set to 24856141; 31299614; 30723199; 27342937
Leukodystrophy - paediatric v0.127 CNP Zornitza Stark Marked gene: CNP as ready
Leukodystrophy - paediatric v0.127 CNP Zornitza Stark Gene: cnp has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.127 CNP Zornitza Stark Classified gene: CNP as Amber List (moderate evidence)
Leukodystrophy - paediatric v0.127 CNP Zornitza Stark Gene: cnp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2970 EFEMP1 Zornitza Stark Marked gene: EFEMP1 as ready
Mendeliome v0.2970 EFEMP1 Zornitza Stark Gene: efemp1 has been classified as Green List (High Evidence).
Mendeliome v0.2970 EFEMP1 Zornitza Stark Phenotypes for gene: EFEMP1 were changed from to Doyne honeycomb degeneration of retina, MIM# 126600; EFEMP1-related connective tissue disorder
Mendeliome v0.2969 EFEMP1 Zornitza Stark Publications for gene: EFEMP1 were set to
Mendeliome v0.2968 EFEMP1 Zornitza Stark Mode of inheritance for gene: EFEMP1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2967 ZFYVE27 Bryony Thompson Classified gene: ZFYVE27 as Red List (low evidence)
Mendeliome v0.2967 ZFYVE27 Bryony Thompson Gene: zfyve27 has been classified as Red List (Low Evidence).
Mendeliome v0.2966 ZFYVE27 Bryony Thompson reviewed gene: ZFYVE27: Rating: RED; Mode of pathogenicity: None; Publications: 16826525, 29980238, 18606302; Phenotypes: Spastic paraplegia 33, autosomal dominant MIM#610244; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2966 EFEMP1 Zornitza Stark reviewed gene: EFEMP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32006683, 31792352; Phenotypes: Doyne honeycomb degeneration of retina, MIM# 126600, EFEMP1-related connective tissue disorder; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.25 EFEMP1 Zornitza Stark Marked gene: EFEMP1 as ready
Aortopathy_Connective Tissue Disorders v0.25 EFEMP1 Zornitza Stark Gene: efemp1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.25 EFEMP1 Zornitza Stark Classified gene: EFEMP1 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.25 EFEMP1 Zornitza Stark Gene: efemp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2966 TOR1AIP1 Kristin Rigbye reviewed gene: TOR1AIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32055997; Phenotypes: TOR1AIP1-associated nuclear envelopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.349 SLC12A2 Zornitza Stark Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome; deafness; intellectual disability; dysmorphic features; absent salivation to Kilquist syndrome: deafness, intellectual disability, dysmorphic features, absent salivation; Congenital, severe to profound hearing loss; minor motor developmental delay
Deafness_IsolatedAndComplex v0.348 SLC12A2 Zornitza Stark Publications for gene: SLC12A2 were set to 30740830
Deafness_IsolatedAndComplex v0.347 SLC12A2 Zornitza Stark Mode of inheritance for gene: SLC12A2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2966 USP8 Bryony Thompson Classified gene: USP8 as Green List (high evidence)
Mendeliome v0.2966 USP8 Bryony Thompson Gene: usp8 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.346 SLC12A2 Zornitza Stark Classified gene: SLC12A2 as Green List (high evidence)
Deafness_IsolatedAndComplex v0.346 SLC12A2 Zornitza Stark Gene: slc12a2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.24 EFEMP1 Michelle Torres gene: EFEMP1 was added
gene: EFEMP1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: EFEMP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EFEMP1 were set to 32006683; 31792352
Phenotypes for gene: EFEMP1 were set to EFEMP1-related connective tissue disorder
Review for gene: EFEMP1 was set to AMBER
Added comment: New gene-disease association for EFEMP1: truncating variants (absent in gnomAD):

PMID 31792352 reports one man with a pronounced connective tissue phenotype presenting multiple and recurrent abdominal and thoracic herniae, myopia, hypermobile joints, scoliosis, and thin translucent skin. This individual has no clinical signs of retinal dystrophy.

PMID 32006683 reports 2 homozygous siblings (consanguinous) with multiple and recurrent herniae, pelvic and rectal prolapse, huge diverticula, marfanoid habitus, joint laxity, dorsal scoliosis, advanced bone age, pectus excavatum, dysmorphic facial features, and myopia. Both were homozygous for a truncating in VCPKMT, with no gene-disease association in OMIM, not in Panel App.

Both papers mention that studies on EFEMP1−/− mice revealed a phenotypic resemblance.
Sources: Literature
Mendeliome v0.2965 USP8 Bryony Thompson gene: USP8 was added
gene: USP8 was added to Mendeliome. Sources: Expert list
somatic tags were added to gene: USP8.
Mode of inheritance for gene: USP8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: USP8 were set to 25675982; 24482476; 25485838; 25942478
Phenotypes for gene: USP8 were set to Pituitary adenoma 4, ACTH-secreting, somatic MIM#219090; hereditary spastic paraplegia
Review for gene: USP8 was set to GREEN
Added comment: Recurrent somatic gain of function missense variants in pituitary adenomas cause Cushing's disease.
A single family reported with spastic paraplegia with a homozygous variant, and a zebrafish model with a movement disorder.
Sources: Expert list
Deafness_IsolatedAndComplex v0.345 SLC12A2 Zornitza Stark Classified gene: SLC12A2 as Green List (high evidence)
Deafness_IsolatedAndComplex v0.345 SLC12A2 Zornitza Stark Gene: slc12a2 has been classified as Green List (High Evidence).
Mendeliome v0.2964 RIMS2 Zornitza Stark Marked gene: RIMS2 as ready
Mendeliome v0.2964 RIMS2 Zornitza Stark Gene: rims2 has been classified as Green List (High Evidence).
Mendeliome v0.2964 RIMS2 Zornitza Stark Phenotypes for gene: RIMS2 were changed from to nystagmus; retinal dysfunction; autism; night blindness
Mendeliome v0.2963 RIMS2 Zornitza Stark Classified gene: RIMS2 as Green List (high evidence)
Mendeliome v0.2963 RIMS2 Zornitza Stark Gene: rims2 has been classified as Green List (High Evidence).
Mendeliome v0.2962 RIMS2 Zornitza Stark reviewed gene: RIMS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: nystagmus, retinal dysfunction, autism, night blindness; Mode of inheritance: None
Autism v0.97 RIMS2 Zornitza Stark Marked gene: RIMS2 as ready
Autism v0.97 RIMS2 Zornitza Stark Added comment: Comment when marking as ready: Most affected individuals reported as having autism.
Autism v0.97 RIMS2 Zornitza Stark Gene: rims2 has been classified as Green List (High Evidence).
Autism v0.97 RIMS2 Zornitza Stark Classified gene: RIMS2 as Green List (high evidence)
Autism v0.97 RIMS2 Zornitza Stark Gene: rims2 has been classified as Green List (High Evidence).
Congenital Stationary Night Blindness v0.3 RIMS2 Zornitza Stark Marked gene: RIMS2 as ready
Congenital Stationary Night Blindness v0.3 RIMS2 Zornitza Stark Gene: rims2 has been classified as Green List (High Evidence).
Congenital Stationary Night Blindness v0.3 RIMS2 Zornitza Stark Classified gene: RIMS2 as Green List (high evidence)
Congenital Stationary Night Blindness v0.3 RIMS2 Zornitza Stark Gene: rims2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2659 SOX6 Zornitza Stark Marked gene: SOX6 as ready
Intellectual disability syndromic and non-syndromic v0.2659 SOX6 Zornitza Stark Added comment: Comment when marking as ready: Most individuals had ID, ranging from mild to severe.
Intellectual disability syndromic and non-syndromic v0.2659 SOX6 Zornitza Stark Gene: sox6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2659 SOX6 Zornitza Stark Classified gene: SOX6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2659 SOX6 Zornitza Stark Gene: sox6 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.17 TRIM71 Zornitza Stark Marked gene: TRIM71 as ready
Hydrocephalus_Ventriculomegaly v0.17 TRIM71 Zornitza Stark Gene: trim71 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.17 TRIM71 Zornitza Stark Mode of pathogenicity for gene: TRIM71 was changed from Other to None
Leukodystrophy - paediatric v0.126 CNP Kristin Rigbye gene: CNP was added
gene: CNP was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: CNP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNP were set to 32128616; 12590258
Phenotypes for gene: CNP were set to Hypomyelinating leukodystrophy
Review for gene: CNP was set to AMBER
Added comment: Single consanguineous family described with homozygous missense in affected child (additional two affected deceased offspring unavailable for testing; healthy carrier parents and sibling).
Loss of protein by Western blot and defect in F-actin structure and organization observed in patient fibroblasts.
Deficiency of CNP in mouse has previously been shown to cause a lethal white matter neurodegenerative phenotype (PMID: 12590258), similar to the phenotype observed in this family.
Sources: Literature
Mendeliome v0.2962 TRIM71 Seb Lunke Mode of pathogenicity for gene: TRIM71 was changed from Other to None
Hydrocephalus_Ventriculomegaly v0.16 TRIM71 Zornitza Stark Classified gene: TRIM71 as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v0.16 TRIM71 Zornitza Stark Gene: trim71 has been classified as Green List (High Evidence).
Mendeliome v0.2961 TRIM71 Seb Lunke Marked gene: TRIM71 as ready
Mendeliome v0.2961 TRIM71 Seb Lunke Gene: trim71 has been classified as Green List (High Evidence).
Mendeliome v0.2961 TRIM71 Seb Lunke Classified gene: TRIM71 as Green List (high evidence)
Mendeliome v0.2961 TRIM71 Seb Lunke Gene: trim71 has been classified as Green List (High Evidence).
Mendeliome v0.2960 SCYL2 Zornitza Stark Marked gene: SCYL2 as ready
Mendeliome v0.2960 SCYL2 Zornitza Stark Gene: scyl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2960 SCYL2 Zornitza Stark Classified gene: SCYL2 as Amber List (moderate evidence)
Mendeliome v0.2960 SCYL2 Zornitza Stark Gene: scyl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2959 SCYL2 Zornitza Stark gene: SCYL2 was added
gene: SCYL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SCYL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCYL2 were set to 31960134; 26203146
Phenotypes for gene: SCYL2 were set to Arthrogryposis multiplex congenita (AMC); Zain syndrome
Review for gene: SCYL2 was set to AMBER
Added comment: Two unrelated families reported with AMC, variable other features including microcephaly.
Sources: Literature
Ataxia - adult onset v0.54 VWA3B Bryony Thompson Classified gene: VWA3B as Red List (low evidence)
Ataxia - adult onset v0.54 VWA3B Bryony Thompson Gene: vwa3b has been classified as Red List (Low Evidence).
Mendeliome v0.2958 CNP Seb Lunke Marked gene: CNP as ready
Mendeliome v0.2958 CNP Seb Lunke Gene: cnp has been classified as Amber List (Moderate Evidence).
Ataxia - adult onset v0.53 VWA3B Bryony Thompson edited their review of gene: VWA3B: Changed rating: RED
Mendeliome v0.2958 CNP Seb Lunke Classified gene: CNP as Amber List (moderate evidence)
Mendeliome v0.2958 CNP Seb Lunke Gene: cnp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2957 VWA3B Bryony Thompson edited their review of gene: VWA3B: Changed rating: RED
Mendeliome v0.2957 VWA3B Bryony Thompson Classified gene: VWA3B as Red List (low evidence)
Mendeliome v0.2957 VWA3B Bryony Thompson Added comment: Comment on list classification: Single family and in vitro assay only
Mendeliome v0.2957 VWA3B Bryony Thompson Gene: vwa3b has been classified as Red List (Low Evidence).
Congenital Stationary Night Blindness v0.2 RIMS2 Paul De Fazio gene: RIMS2 was added
gene: RIMS2 was added to Congenital Stationary Night Blindness. Sources: Literature
Mode of inheritance for gene: RIMS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIMS2 were set to 32470375
Phenotypes for gene: RIMS2 were set to nystagmus; retinal dysfunction; autism; night blindness
Review for gene: RIMS2 was set to GREEN
Added comment: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant. Several individuals had autism. One had night blindness.
Sources: Literature
Autism v0.96 RIMS2 Paul De Fazio changed review comment from: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant. Several individuals had autism.
Sources: Literature; to: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant. Several individuals had autism. One had night blindness.
Sources: Literature
Mendeliome v0.2956 RIMS2 Paul De Fazio changed review comment from: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant.
Sources: Literature; to: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant. Several individuals had autism. One had night blindness.
Sources: Literature
Arthrogryposis v0.47 SCYL2 Zornitza Stark Marked gene: SCYL2 as ready
Arthrogryposis v0.47 SCYL2 Zornitza Stark Gene: scyl2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.47 SCYL2 Zornitza Stark Classified gene: SCYL2 as Amber List (moderate evidence)
Arthrogryposis v0.47 SCYL2 Zornitza Stark Gene: scyl2 has been classified as Amber List (Moderate Evidence).
Autism v0.96 RIMS2 Paul De Fazio changed review comment from: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant.
Sources: Literature; to: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant. Several individuals had autism.
Sources: Literature
Autism v0.96 RIMS2 Paul De Fazio gene: RIMS2 was added
gene: RIMS2 was added to Autism. Sources: Literature
Mode of inheritance for gene: RIMS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIMS2 were set to 32470375
Phenotypes for gene: RIMS2 were set to nystagmus; retinal dysfunction; autism; night blindness
Review for gene: RIMS2 was set to GREEN
Added comment: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant.
Sources: Literature
Mendeliome v0.2956 VWA3B Bryony Thompson Classified gene: VWA3B as Amber List (moderate evidence)
Mendeliome v0.2956 VWA3B Bryony Thompson Gene: vwa3b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2955 VWA3B Bryony Thompson gene: VWA3B was added
gene: VWA3B was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: VWA3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VWA3B were set to 26157035
Phenotypes for gene: VWA3B were set to Spinocerebellar ataxia, autosomal recessive 22 MIM#616948
Review for gene: VWA3B was set to AMBER
Added comment: A homozygous missense variant was identified in 3 brothers from a single consanguineous Japanese family with autosomal recessive cerebellar ataxia. Transfection of the mutant VWA3B protein into several different cultured cell lines resulted in decreased cell viability.
Sources: Expert list
Deafness_IsolatedAndComplex v0.344 SLC12A2 Ee Ming Wong reviewed gene: SLC12A2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32294086; Phenotypes: Congenital, severe to profound hearing loss, minor motor developmental delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2954 SLC12A2 Zornitza Stark Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome; deafness; intellectual disability; dysmorphic features; absent salivation to Kilquist syndrome: deafness, intellectual disability, dysmorphic features, absent salivation; Congenital, severe to profound hearing loss
Mendeliome v0.2953 SOX6 Paul De Fazio changed review comment from: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me (paper says 19 individuals from 17 families). 12 were de novo.
Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome. Paper says 19 individuals from 17 families. 12 were de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2658 SOX6 Paul De Fazio changed review comment from: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me (paper says 19 individuals from 17 families). 12 were de novo.
Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome. Paper says 19 individuals from 17 families. 12 were de novo.
Sources: Literature
Mendeliome v0.2953 SLC12A2 Zornitza Stark Publications for gene: SLC12A2 were set to 30740830
Mendeliome v0.2952 SOX6 Paul De Fazio changed review comment from: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me (paper says 19 individuals from 17 families). 12 were de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2658 SOX6 Paul De Fazio changed review comment from: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me (paper says 19 individuals from 17 families). 12 were de novo.
Sources: Literature
Mendeliome v0.2952 SLC12A2 Zornitza Stark Mode of inheritance for gene: SLC12A2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2952 PLD3 Bryony Thompson Classified gene: PLD3 as Amber List (moderate evidence)
Mendeliome v0.2952 PLD3 Bryony Thompson Gene: pld3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2951 SLC12A2 Zornitza Stark Classified gene: SLC12A2 as Green List (high evidence)
Mendeliome v0.2951 SLC12A2 Zornitza Stark Gene: slc12a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2658 SOX6 Paul De Fazio gene: SOX6 was added
gene: SOX6 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SOX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX6 were set to 32442410
Phenotypes for gene: SOX6 were set to ADHD; Craniosynostosis; Osteochondromas
Review for gene: SOX6 was set to GREEN
Added comment: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature
Mendeliome v0.2950 PLD3 Bryony Thompson gene: PLD3 was added
gene: PLD3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PLD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLD3 were set to 29053796; 30312375; 30312384
Phenotypes for gene: PLD3 were set to Spinocerebellar ataxia 46 MIM#617770
Review for gene: PLD3 was set to AMBER
Added comment: A heterozygous missense was identified in 8 affected members of a single family with spinocerebellar ataxia, and supporting in vitro functional assays.
Sources: Expert list
Ataxia - adult onset v0.53 PLD3 Bryony Thompson edited their review of gene: PLD3: Changed publications: 29053796, 30312375, 30312384
Mendeliome v0.2949 SOX6 Paul De Fazio changed review comment from: 6 LoF and 4 missense variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature
Mendeliome v0.2949 SPATA13 Zornitza Stark Marked gene: SPATA13 as ready
Mendeliome v0.2949 SPATA13 Zornitza Stark Added comment: Comment when marking as ready: Adult-onset.
Mendeliome v0.2949 SPATA13 Zornitza Stark Gene: spata13 has been classified as Green List (High Evidence).
Mendeliome v0.2949 SPATA13 Zornitza Stark Classified gene: SPATA13 as Green List (high evidence)
Mendeliome v0.2949 SPATA13 Zornitza Stark Gene: spata13 has been classified as Green List (High Evidence).
Mendeliome v0.2948 SPATA13 Zornitza Stark reviewed gene: SPATA13: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Craniosynostosis v0.3 SOX6 Seb Lunke Marked gene: SOX6 as ready
Craniosynostosis v0.3 SOX6 Seb Lunke Gene: sox6 has been classified as Green List (High Evidence).
Craniosynostosis v0.3 SOX6 Seb Lunke Classified gene: SOX6 as Green List (high evidence)
Craniosynostosis v0.3 SOX6 Seb Lunke Gene: sox6 has been classified as Green List (High Evidence).
Craniosynostosis v0.2 SOX6 Seb Lunke gene: SOX6 was added
gene: SOX6 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: SOX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX6 were set to 32442410
Phenotypes for gene: SOX6 were set to ADHD; Craniosynostosis; Osteochondromas
Review for gene: SOX6 was set to GREEN
gene: SOX6 was marked as current diagnostic
Added comment: 6 LoF and 4 missense variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me. Sources: Literature
Sources: Literature
Mendeliome v0.2948 SOX6 Seb Lunke Marked gene: SOX6 as ready
Mendeliome v0.2948 SOX6 Seb Lunke Gene: sox6 has been classified as Green List (High Evidence).
Ciliopathies v0.187 KIF3B Zornitza Stark Marked gene: KIF3B as ready
Ciliopathies v0.187 KIF3B Zornitza Stark Gene: kif3b has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.187 KIF3B Zornitza Stark Classified gene: KIF3B as Amber List (moderate evidence)
Ciliopathies v0.187 KIF3B Zornitza Stark Gene: kif3b has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.186 KIF3B Zornitza Stark gene: KIF3B was added
gene: KIF3B was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: KIF3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF3B were set to 32386558
Phenotypes for gene: KIF3B were set to hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly
Review for gene: KIF3B was set to AMBER
Added comment: Two unrelated families with a ciliopathy phenotype and some functional data.
Sources: Literature
Mendeliome v0.2948 SOX6 Seb Lunke Classified gene: SOX6 as Green List (high evidence)
Mendeliome v0.2948 SOX6 Seb Lunke Gene: sox6 has been classified as Green List (High Evidence).
Mendeliome v0.2947 KIF3B Zornitza Stark Marked gene: KIF3B as ready
Mendeliome v0.2947 KIF3B Zornitza Stark Gene: kif3b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2947 KIF3B Zornitza Stark Publications for gene: KIF3B were set to
Mendeliome v0.2946 KIF3B Zornitza Stark Classified gene: KIF3B as Amber List (moderate evidence)
Mendeliome v0.2946 KIF3B Zornitza Stark Gene: kif3b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2945 KIF3B Zornitza Stark edited their review of gene: KIF3B: Changed rating: AMBER
Mendeliome v0.2945 KIF3B Zornitza Stark reviewed gene: KIF3B: Rating: RED; Mode of pathogenicity: None; Publications: 32386558; Phenotypes: hepatic fibrosis, retinitis pigmentosa, postaxial polydactyly; Mode of inheritance: None
Mendeliome v0.2945 POC5 Bryony Thompson Marked gene: POC5 as ready
Mendeliome v0.2945 POC5 Bryony Thompson Gene: poc5 has been classified as Green List (High Evidence).
Mendeliome v0.2945 POC5 Bryony Thompson Classified gene: POC5 as Green List (high evidence)
Mendeliome v0.2945 POC5 Bryony Thompson Gene: poc5 has been classified as Green List (High Evidence).
Mendeliome v0.2944 POC5 Bryony Thompson gene: POC5 was added
gene: POC5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POC5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POC5 were set to 25642776; 29272404
Phenotypes for gene: POC5 were set to Idiopathic scoliosis; retinitis pigmentosa; short stature; microcephaly; recurrent glomerulonephritis
Review for gene: POC5 was set to GREEN
Added comment: Three heterozygous missense variants identified in three families segregating with idiopathic scoliosis, and supporting zebrafish models for each of the missense variants.
Also, one case reported with retinitis pigmentosa, short stature, microcephaly, and recurrent glomerulonephritis with a homozygous truncating variant and a supporting zebrafish model.
Sources: Literature
Long QT Syndrome v0.35 KCNJ2 Zornitza Stark Marked gene: KCNJ2 as ready
Long QT Syndrome v0.35 KCNJ2 Zornitza Stark Gene: kcnj2 has been classified as Green List (High Evidence).
Long QT Syndrome v0.35 KCNJ2 Zornitza Stark Phenotypes for gene: KCNJ2 were changed from to long QT syndrome; Andersen-Tawil syndrome
Long QT Syndrome v0.34 KCNJ2 Zornitza Stark Publications for gene: KCNJ2 were set to
Long QT Syndrome v0.33 KCNJ2 Zornitza Stark Mode of inheritance for gene: KCNJ2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2943 KIF3B Paul De Fazio gene: KIF3B was added
gene: KIF3B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KIF3B were set to hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly
Review for gene: KIF3B was set to AMBER
Added comment: 2 families reported with missense variants, one de novo and one segregating in a six-generation pedigree. Functional studies in zebrafish showed the variants result in impaired rhodopsin trafficking.
Sources: Literature
Long QT Syndrome v0.32 KCNH2 Zornitza Stark Marked gene: KCNH2 as ready
Long QT Syndrome v0.32 KCNH2 Zornitza Stark Gene: kcnh2 has been classified as Green List (High Evidence).
Long QT Syndrome v0.32 KCNH2 Zornitza Stark Phenotypes for gene: KCNH2 were changed from to long QT syndrome
Long QT Syndrome v0.31 KCNH2 Zornitza Stark Publications for gene: KCNH2 were set to
Long QT Syndrome v0.30 KCNH2 Zornitza Stark Mode of inheritance for gene: KCNH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.29 KCNE2 Zornitza Stark Marked gene: KCNE2 as ready
Long QT Syndrome v0.29 KCNE2 Zornitza Stark Gene: kcne2 has been classified as Amber List (Moderate Evidence).
Long QT Syndrome v0.29 KCNE2 Zornitza Stark Phenotypes for gene: KCNE2 were changed from to Long QT syndrome
Mendeliome v0.2943 SPATA13 Ain Roesley changed review comment from: PMID: 32339198; 10 unrelated probands with missense except for 2 families with inframe del of 9bp.
Sources: Literature; to: PMID: 32339198; 10 unrelated probands with missense except for 2 families with inframe del of 9bp.
Sources: Literature
Long QT Syndrome v0.28 KCNE2 Zornitza Stark Publications for gene: KCNE2 were set to
Mendeliome v0.2943 SPATA13 Ain Roesley gene: SPATA13 was added
gene: SPATA13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPATA13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPATA13 were set to PMID: 32339198
Phenotypes for gene: SPATA13 were set to primary angle-closure glaucoma
Added comment: PMID: 32339198; 10 unrelated probands with missense except for 2 families with inframe del of 9bp.
Sources: Literature
Long QT Syndrome v0.27 KCNE2 Zornitza Stark Classified gene: KCNE2 as Amber List (moderate evidence)
Long QT Syndrome v0.27 KCNE2 Zornitza Stark Gene: kcne2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2943 SOX6 Paul De Fazio gene: SOX6 was added
gene: SOX6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SOX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX6 were set to 32442410
Phenotypes for gene: SOX6 were set to ADHD; Craniosynostosis; Osteochondromas
Added comment: 6 LoF and 4 missense variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature
Long QT Syndrome v0.26 KCNE1 Zornitza Stark Marked gene: KCNE1 as ready
Long QT Syndrome v0.26 KCNE1 Zornitza Stark Gene: kcne1 has been classified as Amber List (Moderate Evidence).
Long QT Syndrome v0.26 KCNE1 Zornitza Stark Publications for gene: KCNE1 were set to
Long QT Syndrome v0.25 KCNE1 Zornitza Stark Phenotypes for gene: KCNE1 were changed from to long QT syndrome; acquired LQTS
Long QT Syndrome v0.24 KCNE1 Zornitza Stark Mode of inheritance for gene: KCNE1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2943 CNP Kristin Rigbye gene: CNP was added
gene: CNP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNP were set to 32128616; 12590258
Phenotypes for gene: CNP were set to Hypomyelinating leukodystrophy
Review for gene: CNP was set to AMBER
Added comment: Single consanguineous family described with homozygous missense in affected child (additional two affected deceased offspring unavailable for testing; healthy carrier parents and sibling).
Loss of protein by Western blot and defect in F-actin structure and organization observed in patient fibroblasts.
Deficiency of CNP in mouse has previously been shown to cause a lethal white matter neurodegenerative phenotype (PMID: 12590258), similar to the phenotype observed in this family.
Sources: Literature
Long QT Syndrome v0.23 KCNE1 Zornitza Stark Classified gene: KCNE1 as Amber List (moderate evidence)
Long QT Syndrome v0.23 KCNE1 Zornitza Stark Gene: kcne1 has been classified as Amber List (Moderate Evidence).
Long QT Syndrome v0.22 CAV3 Zornitza Stark Marked gene: CAV3 as ready
Long QT Syndrome v0.22 CAV3 Zornitza Stark Gene: cav3 has been classified as Amber List (Moderate Evidence).
Long QT Syndrome v0.22 CAV3 Zornitza Stark Phenotypes for gene: CAV3 were changed from to Long QT syndrome 9, MIM# 611818
Long QT Syndrome v0.21 CAV3 Zornitza Stark Publications for gene: CAV3 were set to
Long QT Syndrome v0.20 CAV3 Zornitza Stark Mode of pathogenicity for gene: CAV3 was changed from to None
Long QT Syndrome v0.19 CAV3 Zornitza Stark Mode of inheritance for gene: CAV3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.18 CAV3 Zornitza Stark Classified gene: CAV3 as Amber List (moderate evidence)
Long QT Syndrome v0.18 CAV3 Zornitza Stark Gene: cav3 has been classified as Amber List (Moderate Evidence).
Long QT Syndrome v0.17 CAV3 Zornitza Stark reviewed gene: CAV3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Long QT syndrome 9, MIM# 611818; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2943 SLC12A2 Ee Ming Wong reviewed gene: SLC12A2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32294086; Phenotypes: Congenital, severe to profound hearing loss, minor motor developmental delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.55 Bryony Thompson removed gene:POC5 from the panel
Syndromic Retinopathy v0.72 POC5 Bryony Thompson Phenotypes for gene: POC5 were changed from to retinitis pigmentosa; short stature; microcephaly; recurrent glomerulonephritis
Syndromic Retinopathy v0.71 POC5 Bryony Thompson Publications for gene: POC5 were set to
Syndromic Retinopathy v0.70 POC5 Bryony Thompson Mode of inheritance for gene: POC5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Long QT Syndrome v0.17 CACNA1C Zornitza Stark Marked gene: CACNA1C as ready
Long QT Syndrome v0.17 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Green List (High Evidence).
Long QT Syndrome v0.17 CACNA1C Zornitza Stark Phenotypes for gene: CACNA1C were changed from Long QT syndrome 8, MIM# 618447; Timothy syndrome, MIM# 601005 to Long QT syndrome 8, MIM# 618447; Timothy syndrome, MIM# 601005
Long QT Syndrome v0.16 CACNA1C Zornitza Stark Phenotypes for gene: CACNA1C were changed from to Long QT syndrome 8, MIM# 618447; Timothy syndrome, MIM# 601005
Hydrocephalus_Ventriculomegaly v0.15 TRIM71 Elena Savva gene: TRIM71 was added
gene: TRIM71 was added to Hydrocephalus_Ventriculomegaly. Sources: Literature
Mode of inheritance for gene: TRIM71 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRIM71 were set to PMID: 29983323; 32168371; 30975633
Phenotypes for gene: TRIM71 were set to Hydrocephalus, congenital communicating, 1 618667
Mode of pathogenicity for gene: TRIM71 was set to Other
Review for gene: TRIM71 was set to GREEN
Added comment: PMID: 29983323 - 3 unrelated patients with de novo missense and hydrocephalus with ventriculomegaly (p.Arg608His recurrent). One patient then transmitted the variant to an affected child.

PMID: 32168371 - refers to the gene as an established sources of neurodevelopmental disorder

PMID: 30975633 - identifies and proves by functional studies that TRIM71 is essential for neurodevelopment. Proposes a LOF mechanism.
Sources: Literature
Mendeliome v0.2943 TRIM71 Elena Savva reviewed gene: TRIM71: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 29983323, 32168371, 30975633; Phenotypes: Hydrocephalus, congenital communicating, 1 618667; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.2943 TRIM71 Elena Savva Deleted their review
Mendeliome v0.2943 RIMS2 Paul De Fazio changed review comment from: Segregates with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant.
Sources: Literature; to: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant.
Sources: Literature
Long QT Syndrome v0.15 CACNA1C Zornitza Stark Publications for gene: CACNA1C were set to
Mendeliome v0.2943 TRIM71 Elena Savva gene: TRIM71 was added
gene: TRIM71 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRIM71 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRIM71 were set to PMID: 29983323; 32168371; 30975633
Phenotypes for gene: TRIM71 were set to Hydrocephalus, congenital communicating, 1 618667
Mode of pathogenicity for gene: TRIM71 was set to Other
Added comment: PMID: 29983323 - 3 unrelated patients with de novo missense and hydrocephalus with ventriculomegaly (p.Arg608His recurrent). One patient then transmitted the variant to an affected child.

PMID: 32168371 - refers to the gene as an established sources of neurodevelopmental disorder

PMID: 30975633 - identifies and proves by functional studies that TRIM71 is essential for neurodevelopment. Proposes a LOF mechanism.
Sources: Literature
Long QT Syndrome v0.14 CACNA1C Zornitza Stark Mode of inheritance for gene: CACNA1C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.13 ANK2 Zornitza Stark edited their review of gene: ANK2: Changed phenotypes: Long QT syndrome 4, MIM# 600919
Long QT Syndrome v0.13 ANK2 Zornitza Stark Tag disputed tag was added to gene: ANK2.
Long QT Syndrome v0.13 ANK2 Zornitza Stark Marked gene: ANK2 as ready
Long QT Syndrome v0.13 ANK2 Zornitza Stark Gene: ank2 has been classified as Red List (Low Evidence).
Long QT Syndrome v0.13 ANK2 Zornitza Stark Phenotypes for gene: ANK2 were changed from to Long QT syndrome 4, MIM# 600919
Mendeliome v0.2943 RIMS2 Paul De Fazio gene: RIMS2 was added
gene: RIMS2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RIMS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIMS2 were set to 32470375
Review for gene: RIMS2 was set to GREEN
Added comment: Segregates with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant.
Sources: Literature
Long QT Syndrome v0.12 ANK2 Zornitza Stark Publications for gene: ANK2 were set to
Long QT Syndrome v0.11 ANK2 Zornitza Stark Classified gene: ANK2 as Red List (low evidence)
Long QT Syndrome v0.11 ANK2 Zornitza Stark Gene: ank2 has been classified as Red List (Low Evidence).
Long QT Syndrome v0.10 ANK2 Zornitza Stark reviewed gene: ANK2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Arthrogryposis v0.46 SCYL2 Kristin Rigbye gene: SCYL2 was added
gene: SCYL2 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: SCYL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCYL2 were set to 31960134; 26203146
Phenotypes for gene: SCYL2 were set to Arthrogryposis multiplex congenita (AMC); Zain syndrome
Review for gene: SCYL2 was set to AMBER
Added comment: 2 unrelated consanguineous families reported with AMC (PMID: 31960134).
Constitutive mouse knockout of Scyl2 results in neonatal lethality and severe motor and sensory deficits (PMID: 26203146).
Sources: Literature
Incidentalome v0.31 AKAP9 Zornitza Stark Tag disputed tag was added to gene: AKAP9.
Incidentalome v0.31 AKAP9 Zornitza Stark Marked gene: AKAP9 as ready
Incidentalome v0.31 AKAP9 Zornitza Stark Gene: akap9 has been classified as Red List (Low Evidence).
Incidentalome v0.31 AKAP9 Zornitza Stark Phenotypes for gene: AKAP9 were changed from to Long QT syndrome 11, MIM# 611820
Incidentalome v0.30 AKAP9 Zornitza Stark Publications for gene: AKAP9 were set to
Incidentalome v0.29 AKAP9 Zornitza Stark Mode of inheritance for gene: AKAP9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.28 AKAP9 Zornitza Stark Classified gene: AKAP9 as Red List (low evidence)
Incidentalome v0.28 AKAP9 Zornitza Stark Gene: akap9 has been classified as Red List (Low Evidence).
Incidentalome v0.27 AKAP9 Zornitza Stark reviewed gene: AKAP9: Rating: RED; Mode of pathogenicity: None; Publications: 31983240; Phenotypes: Long QT syndrome 11, MIM# 611820; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.10 AKAP9 Zornitza Stark Tag disputed tag was added to gene: AKAP9.
Long QT Syndrome v0.10 AKAP9 Zornitza Stark Marked gene: AKAP9 as ready
Long QT Syndrome v0.10 AKAP9 Zornitza Stark Gene: akap9 has been classified as Red List (Low Evidence).
Long QT Syndrome v0.10 AKAP9 Zornitza Stark Phenotypes for gene: AKAP9 were changed from to long QT syndrome
Long QT Syndrome v0.9 AKAP9 Zornitza Stark Publications for gene: AKAP9 were set to
Long QT Syndrome v0.8 AKAP9 Zornitza Stark Classified gene: AKAP9 as Red List (low evidence)
Long QT Syndrome v0.8 AKAP9 Zornitza Stark Gene: akap9 has been classified as Red List (Low Evidence).
Mendeliome v0.2943 RBM7 Bryony Thompson Classified gene: RBM7 as Amber List (moderate evidence)
Mendeliome v0.2943 RBM7 Bryony Thompson Gene: rbm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2942 RBM7 Bryony Thompson gene: RBM7 was added
gene: RBM7 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RBM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBM7 were set to 27193168
Phenotypes for gene: RBM7 were set to SMA-like spinal motor neuropathy; dHMN/dSMA
Review for gene: RBM7 was set to AMBER
Added comment: Single case with a homozygote variant, with functional assays in patient fibroblasts. Also, supporting zebrafish model.
Sources: Expert list
Mendeliome v0.2941 SORD Seb Lunke Marked gene: SORD as ready
Mendeliome v0.2941 SORD Seb Lunke Gene: sord has been classified as Green List (High Evidence).
Mendeliome v0.2941 SORD Seb Lunke Classified gene: SORD as Green List (high evidence)
Mendeliome v0.2941 SORD Seb Lunke Gene: sord has been classified as Green List (High Evidence).
Hereditary Neuropathy_CMT - isolated v0.44 SORD Seb Lunke Marked gene: SORD as ready
Hereditary Neuropathy_CMT - isolated v0.44 SORD Seb Lunke Gene: sord has been classified as Green List (High Evidence).
Hereditary Neuropathy_CMT - isolated v0.44 SORD Seb Lunke Classified gene: SORD as Green List (high evidence)
Hereditary Neuropathy_CMT - isolated v0.44 SORD Seb Lunke Gene: sord has been classified as Green List (High Evidence).
Hereditary Neuropathy_CMT - isolated v0.43 SORD Seb Lunke edited their review of gene: SORD: Changed rating: GREEN
Hereditary Neuropathy_CMT - isolated v0.43 SORD Seb Lunke gene: SORD was added
gene: SORD was added to Hereditary Neuropathy_CMT - isolated. Sources: Literature
Mode of inheritance for gene: SORD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SORD were set to 32367058
Phenotypes for gene: SORD were set to isolated hereditary neuropathy
gene: SORD was marked as current diagnostic
Added comment: 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG
(p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state
Sources: Literature
Mendeliome v0.2940 SORD Seb Lunke gene: SORD was added
gene: SORD was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SORD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SORD were set to 32367058
Phenotypes for gene: SORD were set to isolated hereditary neuropathy
Review for gene: SORD was set to GREEN
gene: SORD was marked as current diagnostic
Added comment: 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG
(p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state
Sources: Literature
Brugada syndrome v0.34 KCND3 Zornitza Stark Phenotypes for gene: KCND3 were changed from to Brugada syndrome
Brugada syndrome v0.33 KCND3 Zornitza Stark Tag disputed tag was added to gene: KCND3.
Brugada syndrome v0.33 CACNB2 Zornitza Stark Tag disputed tag was added to gene: CACNB2.
Brugada syndrome v0.33 CACNA2D1 Zornitza Stark Tag disputed tag was added to gene: CACNA2D1.
Brugada syndrome v0.33 CACNA1C Zornitza Stark Tag disputed tag was added to gene: CACNA1C.
Incidentalome v0.27 GPD1L Zornitza Stark Classified gene: GPD1L as Red List (low evidence)
Incidentalome v0.27 GPD1L Zornitza Stark Gene: gpd1l has been classified as Red List (Low Evidence).
Brugada syndrome v0.33 GPD1L Zornitza Stark Publications for gene: GPD1L were set to 17967977; 19666841
Brugada syndrome v0.32 GPD1L Zornitza Stark Classified gene: GPD1L as Red List (low evidence)
Brugada syndrome v0.32 GPD1L Zornitza Stark Gene: gpd1l has been classified as Red List (Low Evidence).
Brugada syndrome v0.31 SCN1B Zornitza Stark Marked gene: SCN1B as ready
Brugada syndrome v0.31 SCN1B Zornitza Stark Gene: scn1b has been classified as Red List (Low Evidence).
Brugada syndrome v0.31 SCN1B Zornitza Stark Publications for gene: SCN1B were set to
Brugada syndrome v0.30 SCN1B Zornitza Stark Classified gene: SCN1B as Red List (low evidence)
Brugada syndrome v0.30 SCN1B Zornitza Stark Gene: scn1b has been classified as Red List (Low Evidence).
Brugada syndrome v0.29 SCN1B Zornitza Stark Tag disputed tag was added to gene: SCN1B.
Brugada syndrome v0.29 SCN10A Zornitza Stark Marked gene: SCN10A as ready
Brugada syndrome v0.29 SCN10A Zornitza Stark Gene: scn10a has been classified as Red List (Low Evidence).
Brugada syndrome v0.29 SCN10A Zornitza Stark Phenotypes for gene: SCN10A were changed from to Brugada syndrome
Brugada syndrome v0.28 SCN10A Zornitza Stark Publications for gene: SCN10A were set to
Brugada syndrome v0.27 SCN10A Zornitza Stark Classified gene: SCN10A as Red List (low evidence)
Brugada syndrome v0.27 SCN10A Zornitza Stark Gene: scn10a has been classified as Red List (Low Evidence).
Brugada syndrome v0.26 SCN10A Zornitza Stark Tag disputed tag was added to gene: SCN10A.
Mendeliome v0.2940 KCNJ8 Zornitza Stark Marked gene: KCNJ8 as ready
Mendeliome v0.2940 KCNJ8 Zornitza Stark Gene: kcnj8 has been classified as Red List (Low Evidence).
Mendeliome v0.2940 KCNJ8 Zornitza Stark Phenotypes for gene: KCNJ8 were changed from to Brugada syndrome
Mendeliome v0.2939 KCNJ8 Zornitza Stark Publications for gene: KCNJ8 were set to
Mendeliome v0.2938 KCNJ8 Zornitza Stark Mode of inheritance for gene: KCNJ8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2937 KCNJ8 Zornitza Stark Classified gene: KCNJ8 as Red List (low evidence)
Mendeliome v0.2937 KCNJ8 Zornitza Stark Gene: kcnj8 has been classified as Red List (Low Evidence).
Mendeliome v0.2936 KCNJ8 Zornitza Stark Tag disputed tag was added to gene: KCNJ8.
Mendeliome v0.2936 KCNJ8 Zornitza Stark reviewed gene: KCNJ8: Rating: RED; Mode of pathogenicity: None; Publications: 29959160; Phenotypes: Brugada syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brugada syndrome v0.26 KCNJ8 Zornitza Stark Phenotypes for gene: KCNJ8 were changed from to Brugada syndrome
Brugada syndrome v0.25 KCNJ8 Zornitza Stark Marked gene: KCNJ8 as ready
Brugada syndrome v0.25 KCNJ8 Zornitza Stark Gene: kcnj8 has been classified as Red List (Low Evidence).
Brugada syndrome v0.25 KCNJ8 Zornitza Stark Tag disputed tag was added to gene: KCNJ8.
Mendeliome v0.2936 KCNE3 Zornitza Stark Marked gene: KCNE3 as ready
Mendeliome v0.2936 KCNE3 Zornitza Stark Gene: kcne3 has been classified as Red List (Low Evidence).
Mendeliome v0.2936 KCNE3 Zornitza Stark Phenotypes for gene: KCNE3 were changed from to Brugada syndrome
Mendeliome v0.2935 KCNE3 Zornitza Stark Publications for gene: KCNE3 were set to
Mendeliome v0.2934 KCNE3 Zornitza Stark Mode of inheritance for gene: KCNE3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brugada syndrome v0.25 KCNJ8 Zornitza Stark Publications for gene: KCNJ8 were set to
Brugada syndrome v0.24 KCNJ8 Zornitza Stark Classified gene: KCNJ8 as Red List (low evidence)
Brugada syndrome v0.24 KCNJ8 Zornitza Stark Gene: kcnj8 has been classified as Red List (Low Evidence).
Brugada syndrome v0.23 KCNE3 Zornitza Stark Marked gene: KCNE3 as ready
Brugada syndrome v0.23 KCNE3 Zornitza Stark Gene: kcne3 has been classified as Red List (Low Evidence).
Brugada syndrome v0.23 KCNE3 Zornitza Stark Tag disputed tag was added to gene: KCNE3.
Mendeliome v0.2933 KCNE3 Zornitza Stark Classified gene: KCNE3 as Red List (low evidence)
Mendeliome v0.2933 KCNE3 Zornitza Stark Gene: kcne3 has been classified as Red List (Low Evidence).
Mendeliome v0.2932 KCNE3 Zornitza Stark reviewed gene: KCNE3: Rating: RED; Mode of pathogenicity: None; Publications: 29959160; Phenotypes: Brugada syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brugada syndrome v0.23 KCNE3 Zornitza Stark Publications for gene: KCNE3 were set to
Brugada syndrome v0.22 KCNE3 Zornitza Stark Classified gene: KCNE3 as Red List (low evidence)
Brugada syndrome v0.22 KCNE3 Zornitza Stark Gene: kcne3 has been classified as Red List (Low Evidence).
Brugada syndrome v0.21 KCND3 Zornitza Stark Marked gene: KCND3 as ready
Brugada syndrome v0.21 KCND3 Zornitza Stark Gene: kcnd3 has been classified as Red List (Low Evidence).
Brugada syndrome v0.21 KCND3 Zornitza Stark Publications for gene: KCND3 were set to
Brugada syndrome v0.20 KCND3 Zornitza Stark Classified gene: KCND3 as Red List (low evidence)
Brugada syndrome v0.20 KCND3 Zornitza Stark Gene: kcnd3 has been classified as Red List (Low Evidence).
Brugada syndrome v0.19 CACNB2 Zornitza Stark Marked gene: CACNB2 as ready
Brugada syndrome v0.19 CACNB2 Zornitza Stark Gene: cacnb2 has been classified as Red List (Low Evidence).
Brugada syndrome v0.19 CACNB2 Zornitza Stark Publications for gene: CACNB2 were set to
Brugada syndrome v0.18 CACNB2 Zornitza Stark Classified gene: CACNB2 as Red List (low evidence)
Brugada syndrome v0.18 CACNB2 Zornitza Stark Gene: cacnb2 has been classified as Red List (Low Evidence).
Brugada syndrome v0.17 CACNA2D1 Zornitza Stark Marked gene: CACNA2D1 as ready
Brugada syndrome v0.17 CACNA2D1 Zornitza Stark Gene: cacna2d1 has been classified as Red List (Low Evidence).
Brugada syndrome v0.17 CACNA2D1 Zornitza Stark Publications for gene: CACNA2D1 were set to
Brugada syndrome v0.16 CACNA2D1 Zornitza Stark Classified gene: CACNA2D1 as Red List (low evidence)
Brugada syndrome v0.16 CACNA2D1 Zornitza Stark Gene: cacna2d1 has been classified as Red List (Low Evidence).
Brugada syndrome v0.15 CACNA1C Zornitza Stark Marked gene: CACNA1C as ready
Brugada syndrome v0.15 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Red List (Low Evidence).
Brugada syndrome v0.15 CACNA1C Zornitza Stark Publications for gene: CACNA1C were set to
Brugada syndrome v0.14 CACNA1C Zornitza Stark Classified gene: CACNA1C as Red List (low evidence)
Brugada syndrome v0.14 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.103 MCIDAS Crystle Lee reviewed gene: MCIDAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 25048963; Phenotypes: Ciliary dyskinesia, primary, 42 (MIM#618695); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.75 MCIDAS Crystle Lee changed review comment from: PCD without situs invertus (OMIM)

PMID: 25048963: 3 different homozygous variants reported in 4 unrelated families. Situs invertus not observed in any of the 9 individuals reported. Functional studies showed reduction of cilia; to: PCD without situs invertus (OMIM)

PMID: 25048963: 3 different homozygous variants reported in 4 unrelated families. Situs invertus not observed in any of the 9 individuals reported. Functional studies showed reduction of cilia. None of the variants identified were observed in gnomAD at unexpected frequency for a recessive condition.
Heterotaxy v0.75 MCIDAS Crystle Lee reviewed gene: MCIDAS: Rating: RED; Mode of pathogenicity: None; Publications: 25048963; Phenotypes: Ciliary dyskinesia, primary, 42 (MIM#618695); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2658 HIST1H4J Sue White Classified gene: HIST1H4J as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2658 HIST1H4J Sue White Gene: hist1h4j has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2657 HIST1H4J Sue White Marked gene: HIST1H4J as ready
Intellectual disability syndromic and non-syndromic v0.2657 HIST1H4J Sue White Gene: hist1h4j has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2657 HIST1H4J Sue White gene: HIST1H4J was added
gene: HIST1H4J was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HIST1H4J was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIST1H4J were set to 31804630
Phenotypes for gene: HIST1H4J were set to microcephaly; intellectual disability; dysmorphic features
Penetrance for gene: HIST1H4J were set to Complete
Review for gene: HIST1H4J was set to AMBER
Added comment: single case report but with functional evidence in zebrafish and phenotypic similarity to other HIST1H4C phenotype
Sources: Literature
Chronic granulomatous disease v0.9 Bryony Thompson Panel status changed from internal to public
Panel types changed to Royal Melbourne Hospital; Rare Disease
Chronic granulomatous disease v0.8 NCF4 Bryony Thompson Classified gene: NCF4 as Green List (high evidence)
Chronic granulomatous disease v0.8 NCF4 Bryony Thompson Gene: ncf4 has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.7 NCF4 Bryony Thompson reviewed gene: NCF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 19692703, 16880254, 29969437; Phenotypes: Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III MIM#613960; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.75 DRC1 Elena Savva reviewed gene: DRC1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 31960620, 32108610; Phenotypes: Ciliary dyskinesia, primary, 21, MIM# 615294; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Chronic granulomatous disease v0.7 C17orf62 Bryony Thompson edited their review of gene: C17orf62: Changed publications: 28600779, 30361506, 28351984, 30312704
Chronic granulomatous disease v0.7 C17orf62 Bryony Thompson Classified gene: C17orf62 as Green List (high evidence)
Chronic granulomatous disease v0.7 C17orf62 Bryony Thompson Gene: c17orf62 has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.6 C17orf62 Bryony Thompson reviewed gene: C17orf62: Rating: GREEN; Mode of pathogenicity: None; Publications: 28600779, 30361506, 28351984; Phenotypes: Chronic granulomatous disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Chronic granulomatous disease v0.6 NOD2 Bryony Thompson Classified gene: NOD2 as Green List (high evidence)
Chronic granulomatous disease v0.6 NOD2 Bryony Thompson Gene: nod2 has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.5 NCF2 Bryony Thompson Classified gene: NCF2 as Green List (high evidence)
Chronic granulomatous disease v0.5 NCF2 Bryony Thompson Gene: ncf2 has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.4 NCF1 Bryony Thompson Classified gene: NCF1 as Green List (high evidence)
Chronic granulomatous disease v0.4 NCF1 Bryony Thompson Gene: ncf1 has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.3 G6PD Bryony Thompson Classified gene: G6PD as Green List (high evidence)
Chronic granulomatous disease v0.3 G6PD Bryony Thompson Gene: g6pd has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.2 CYBB Bryony Thompson Classified gene: CYBB as Green List (high evidence)
Chronic granulomatous disease v0.2 CYBB Bryony Thompson Gene: cybb has been classified as Green List (High Evidence).
Congenital Heart Defect v0.40 MYH6 Crystle Lee reviewed gene: MYH6: Rating: GREEN; Mode of pathogenicity: Other; Publications: 20656787, 29969989, 15735645; Phenotypes: Atrial septal defect 3 (MIM#614089); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Chronic granulomatous disease v0.1 CYBA Bryony Thompson Classified gene: CYBA as Green List (high evidence)
Chronic granulomatous disease v0.1 CYBA Bryony Thompson Gene: cyba has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.0 NOD2 Bryony Thompson gene: NOD2 was added
gene: NOD2 was added to Chronic granulomatous disease. Sources: Expert list
Mode of inheritance for gene: NOD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NOD2 were set to Blau syndrome MIM#186580
Chronic granulomatous disease v0.0 NCF4 Bryony Thompson gene: NCF4 was added
gene: NCF4 was added to Chronic granulomatous disease. Sources: Expert list
Mode of inheritance for gene: NCF4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NCF4 were set to Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III MIM#613960
Chronic granulomatous disease v0.0 NCF2 Bryony Thompson gene: NCF2 was added
gene: NCF2 was added to Chronic granulomatous disease. Sources: Expert list
Mode of inheritance for gene: NCF2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NCF2 were set to Chronic granulomatous disease due to deficiency of NCF-2 MIM#233710
Chronic granulomatous disease v0.0 NCF1 Bryony Thompson gene: NCF1 was added
gene: NCF1 was added to Chronic granulomatous disease. Sources: Expert list
Mode of inheritance for gene: NCF1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NCF1 were set to Chronic granulomatous disease due to deficiency of NCF-1 MIM#233700
Chronic granulomatous disease v0.0 G6PD Bryony Thompson gene: G6PD was added
gene: G6PD was added to Chronic granulomatous disease. Sources: Expert list
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 Hemolytic anemia, G6PD deficient (favism) MIM#300908
Chronic granulomatous disease v0.0 CYBB Bryony Thompson gene: CYBB was added
gene: CYBB was added to Chronic granulomatous disease. Sources: Expert list
Mode of inheritance for gene: CYBB was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: CYBB were set to Chronic granulomatous disease, X-linked MIM#306400
Chronic granulomatous disease v0.0 CYBA Bryony Thompson gene: CYBA was added
gene: CYBA was added to Chronic granulomatous disease. Sources: Expert list
Mode of inheritance for gene: CYBA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYBA were set to Chronic granulomatous disease, autosomal, due to deficiency of CYBA MIM#233690
Chronic granulomatous disease v0.0 C17orf62 Bryony Thompson gene: C17orf62 was added
gene: C17orf62 was added to Chronic granulomatous disease. Sources: Expert list
Mode of inheritance for gene: C17orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf62 were set to 30361506; 30312704
Phenotypes for gene: C17orf62 were set to Chronic granulomatous disease
Chronic granulomatous disease v0.0 Bryony Thompson Added panel Chronic granulomatous disease
Heterotaxy v0.75 DNAH9 Elena Savva gene: DNAH9 was added
gene: DNAH9 was added to Heterotaxy. Sources: Expert list
Mode of inheritance for gene: DNAH9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH9 were set to PMID: 30471717; 30471718
Phenotypes for gene: DNAH9 were set to Ciliary dyskinesia, primary, 40 618300
Review for gene: DNAH9 was set to GREEN
Added comment: OMIM: Situs inversus of the heart

PMID: 30471717 - 4 patients (3 families) all with PCD and situs inversus.

PMID: 30471718 - 5 families with situs inversus totalis and/or heterotaxy
Sources: Expert list
Mendeliome v0.2932 DNAH6 Elena Savva gene: DNAH6 was added
gene: DNAH6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNAH6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH6 were set to PMID: 26918822
Phenotypes for gene: DNAH6 were set to Heterotaxy, Azoospermia
Review for gene: DNAH6 was set to AMBER
Added comment: PMID: 26918822 - zebrafish model has disrupted motile cilia and cilia length, with some body axis defects within embryos. Transfected human cells also had defective motile cilia and cilia width.
Two patients with heterotaxy, one homozygous (missense), the other heterozygous (missense), but the heterozygous carrier has an additional known PCD mutation in DNA1.

Summary: 1 convincing patient with animal model
Sources: Literature
Heterotaxy v0.75 DNAH1 Elena Savva gene: DNAH1 was added
gene: DNAH1 was added to Heterotaxy. Sources: Expert list
Mode of inheritance for gene: DNAH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH1 were set to PMID: 25927852; 24360805
Phenotypes for gene: DNAH1 were set to ?Ciliary dyskinesia, primary, 37 617577
Review for gene: DNAH1 was set to RED
Added comment: PMID: 25927852 - 2 homozygous siblings with a missense variant and PCD. Proband had situs invertus, sibling details unavailable.

PMID: 24360805 - 7 patients (4 different variants) with homozygous variants and infertility due to defective sperm. No mention of patients and situs inversus "Apart from infertility, none of the 20 individuals declared suffering from any of the principal PCD symptoms"

Summary: single report but emerging gene with limited reports
Sources: Expert list
Heterotaxy v0.75 DNAAF2 Elena Savva reviewed gene: DNAAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19052621, 31107948; Phenotypes: Ciliary dyskinesia, primary, 10 612518; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.75 CCNO Elena Savva reviewed gene: CCNO: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 24747639, 24824133, 31765523; Phenotypes: Ciliary dyskinesia, primary, 29 615872; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.40 NKX2-5 Crystle Lee reviewed gene: NKX2-5: Rating: GREEN; Mode of pathogenicity: None; Publications: 25742962, 26805889; Phenotypes: Ventricular septal defect 3 (MIM#614432), Tetralogy of Fallot (MIM#187500); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Heterotaxy v0.75 NPHP4 Crystle Lee gene: NPHP4 was added
gene: NPHP4 was added to Heterotaxy. Sources: Expert Review
Mode of inheritance for gene: NPHP4 was set to Unknown
Publications for gene: NPHP4 were set to 22550138
Phenotypes for gene: NPHP4 were set to Pleiotropic Heart Malformations (PMID: 22550138)
Review for gene: NPHP4 was set to AMBER
Added comment: Single publication in 2012 reported biallelic variants in a consanguineous family and additional heterozygous variants in sporadic patients with cardiac laterality defects. Knockdown nphp4 expression in zebrafish caused laterality defects.

PMID: 22550138; Frenh 2012: Hom missense reported in a consang family with with cardiac laterality defects. 9 additional het sporadic cases reported with features of heterotaxy. p.(Ala1110Val) reported in one patient with abdominal situs inversus but variant is present in gnomAD (1007 hets and 3 hom), another missense, p.(Pro541Leu), reported in patient with midline liver and asplenia (variant is present 228x in gnomAD). Most of the variants in the sporadic cases either many hets or present in homozygosity.
Sources: Expert Review
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 RYR2 Ivan Macciocca changed review comment from: rated as definitive by ClinGen; to: rated as definitive by ClinGen 03/08/2017
Long QT Syndrome v0.7 TRDN Ivan Macciocca gene: TRDN was added
gene: TRDN was added to Long QT Syndrome. Sources: Expert list
Mode of inheritance for gene: TRDN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRDN were set to long QT syndrome
Phenotypes for gene: TRDN were set to PMID: 31983240; 25922419
Review for gene: TRDN was set to GREEN
gene: TRDN was marked as current diagnostic
Added comment: definitive as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group:
Evidence for involvement of TRDN in LQTS was based mainly on a single publication demonstrating 5 cases with homozygous or compound heterozygous frameshift variants. All cases presented during early childhood (up to the age of 3 years) with QT prolongation, negative T waves in precordial leads, and exercise-induced arrhythmias, although typical
torsades de pointes was demonstrated only in 1 case. Experimental evidence demonstrated that TRDN loss of function may lead to arrhythmogenesis but did not specifically show prolongation of repolarization, which is the hallmark of LQTS. Accordingly, there was a debate
within the panel as to whether the TRDN-related cardiac phenotype should be classified as CPVT or as a unique syndrome, referred in the literature as triadin knockout syndrome. Because QT prolongation was the most easily discernable abnormality, it was decided to consider these cases as having an atypical LQTS phenotype. Furthermore, it was agreed that there was strong evidence for TRDN’s disease association.
Sources: Expert list
Long QT Syndrome v0.7 SNTA1 Ivan Macciocca reviewed gene: SNTA1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.7 SCN5A Ivan Macciocca reviewed gene: SCN5A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome, Brugada syndrome, dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Long QT Syndrome v0.7 SCN4B Ivan Macciocca reviewed gene: SCN4B: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.7 KCNQ1 Ivan Macciocca reviewed gene: KCNQ1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Long QT Syndrome v0.7 KCNJ5 Ivan Macciocca reviewed gene: KCNJ5: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.7 KCNJ2 Ivan Macciocca reviewed gene: KCNJ2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome, Andersen-Tawil syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Long QT Syndrome v0.7 KCNE2 Ivan Macciocca edited their review of gene: KCNE2: Set current diagnostic: yes
Long QT Syndrome v0.7 KCNH2 Ivan Macciocca reviewed gene: KCNH2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Long QT Syndrome v0.7 KCNE2 Ivan Macciocca reviewed gene: KCNE2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 31983240, 28794082; Phenotypes: ; Mode of inheritance: None
Long QT Syndrome v0.7 KCNE1 Ivan Macciocca reviewed gene: KCNE1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: long QT syndrome, acquired LQTS; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Long QT Syndrome v0.7 CAV3 Ivan Macciocca reviewed gene: CAV3: Rating: AMBER; 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: PMID: 31983240, 17060380; Phenotypes: long QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Long QT Syndrome v0.7 CALM2 Ivan Macciocca gene: CALM2 was added
gene: CALM2 was added to Long QT Syndrome. Sources: Expert list
Mode of inheritance for gene: CALM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CALM2 were set to PMID: 31983240
Phenotypes for gene: CALM2 were set to long QT syndrome
Penetrance for gene: CALM2 were set to unknown
Review for gene: CALM2 was set to GREEN
gene: CALM2 was marked as current diagnostic
Added comment: strong evidence for causality in LQTS with atypical features presenting in childhood - presentation typically in infancy or early childhood (up to 5 years) with marked bradycardia or atrioventricular block associated with severe QT prolongation, a presentation that is seen only rarely in LQTS related to SCN5A and KCNH2 genetic defects as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group
Sources: Expert list
Long QT Syndrome v0.7 CALM1 Ivan Macciocca gene: CALM1 was added
gene: CALM1 was added to Long QT Syndrome. Sources: Expert Review
Mode of inheritance for gene: CALM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CALM1 were set to long QT syndrome
Penetrance for gene: CALM1 were set to unknown
Review for gene: CALM1 was set to GREEN
gene: CALM1 was marked as current diagnostic
Added comment: strong evidence for causality in LQTS with atypical features presenting in childhood - presentation typically in infancy or early childhood (up to 5 years) with marked bradycardia or atrioventricular block associated with severe QT prolongation, a presentation that is seen only rarely in LQTS related to SCN5A and KCNH2 genetic defects as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group
Sources: Expert Review
Long QT Syndrome v0.7 CALM3 Ivan Macciocca reviewed gene: CALM3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Long QT Syndrome v0.7 CACNA1C Ivan Macciocca reviewed gene: CACNA1C: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome, Timothy syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Long QT Syndrome v0.7 ANK2 Ivan Macciocca reviewed gene: ANK2: Rating: ; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: ; Mode of inheritance: None
Long QT Syndrome v0.7 AKAP9 Ivan Macciocca reviewed gene: AKAP9: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome; Mode of inheritance: None
Brugada syndrome v0.13 SCN3B Ivan Macciocca reviewed gene: SCN3B: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: Brugada syndrome; Mode of inheritance: None
Brugada syndrome v0.13 GPD1L Ivan Macciocca reviewed gene: GPD1L: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Brugada syndrome v0.13 SCN5A Ivan Macciocca reviewed gene: SCN5A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: Brugada syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Brugada syndrome v0.13 SCN1B Ivan Macciocca reviewed gene: SCN1B: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Brugada syndrome v0.13 SCN10A Ivan Macciocca reviewed gene: SCN10A: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Brugada syndrome v0.13 KCNJ8 Ivan Macciocca reviewed gene: KCNJ8: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Brugada syndrome v0.13 KCNE3 Ivan Macciocca reviewed gene: KCNE3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Brugada syndrome v0.13 CACNB2 Ivan Macciocca changed review comment from: disputed by ClinGen (21/11/2017) and recent publication: Circulation. 2018;138:1195–1205 (PMID: 29959160); to: disputed by ClinGen (21/11/2017) and as reported in Circulation. 2018;138:1195–1205 (PMID: 29959160)
Brugada syndrome v0.13 CACNA2D1 Ivan Macciocca changed review comment from: disputed by ClinGen (21/11/2017) and recent publication: Circulation. 2018;138:1195–1205; to: disputed by ClinGen (21/11/2017) and as reported in Circulation. 2018;138:1195–1205 (PMID: 29959160)
Brugada syndrome v0.13 CACNA1C Ivan Macciocca changed review comment from: disputed by ClinGen (21/11/2017) and recent publication: Circulation. 2018;138:1195–1205; to: disputed by ClinGen (21/11/2017) and as reported in Circulation. 2018;138:1195–1205 (PMID: 29959160)
Brugada syndrome v0.13 KCND3 Ivan Macciocca reviewed gene: KCND3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Brugada syndrome v0.13 CACNB2 Ivan Macciocca reviewed gene: CACNB2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Brugada syndrome v0.13 CACNA2D1 Ivan Macciocca reviewed gene: CACNA2D1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Brugada syndrome v0.13 CACNA1C Ivan Macciocca reviewed gene: CACNA1C: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Malformations of cortical development_Superpanel v0.85 Bryony Thompson Panel name changed from Malformations of cortical development Superpanel to Malformations of cortical development
Malformations of cortical development_Superpanel v0.84 Bryony Thompson Panel types changed to Royal Melbourne Hospital; Rare Disease
Malformations of cortical development_Superpanel v0.83 Bryony Thompson Changed child panels to: Polymicrogyria and Schizencephaly; Lissencephaly and Band Heterotopia; Tuberous Sclerosis_Cortical Dysplasia_Hemimegalencephaly; Tubulinopathies; Cobblestone Malformations; Periventricular Grey Matter Heterotopia
Malformations of cortical development_Superpanel v0.82 Bryony Thompson Changed child panels to: Microcephaly; Polymicrogyria and Schizencephaly; Lissencephaly and Band Heterotopia; Tuberous Sclerosis_Cortical Dysplasia_Hemimegalencephaly; Tubulinopathies; Cobblestone Malformations; Periventricular Grey Matter Heterotopia
Microcephaly v0.125 CSNK2A1 Zornitza Stark Marked gene: CSNK2A1 as ready
Microcephaly v0.125 CSNK2A1 Zornitza Stark Gene: csnk2a1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.83 GPSM2 Bryony Thompson Marked gene: GPSM2 as ready
Polymicrogyria and Schizencephaly v0.83 GPSM2 Bryony Thompson Gene: gpsm2 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.83 GPSM2 Bryony Thompson Classified gene: GPSM2 as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.83 GPSM2 Bryony Thompson Gene: gpsm2 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.82 GPSM2 Bryony Thompson gene: GPSM2 was added
gene: GPSM2 was added to Polymicrogyria and Schizencephaly. Sources: Expert list
Mode of inheritance for gene: GPSM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPSM2 were set to 22578326
Phenotypes for gene: GPSM2 were set to Chudley-McCullough syndrome MIM#604213
Review for gene: GPSM2 was set to GREEN
Added comment: Polymicrogyria is a prominent feature of the condtion, reported in at least 10/10 families.
Sources: Expert list
Malformations of cortical development_Superpanel v0.79 Bryony Thompson Changed child panels to: Microcephaly; Polymicrogyria and Schizencephaly; Lissencephaly and Band Heterotopia; Tuberous Sclerosis_Cortical Dysplasia_Hemimegalencephaly; Cobblestone Malformations; Periventricular Grey Matter Heterotopia
Microcephaly v0.125 CSNK2A1 Bryony Thompson Classified gene: CSNK2A1 as Green List (high evidence)
Microcephaly v0.125 CSNK2A1 Bryony Thompson Gene: csnk2a1 has been classified as Green List (High Evidence).
Microcephaly v0.124 CSNK2A1 Bryony Thompson gene: CSNK2A1 was added
gene: CSNK2A1 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: CSNK2A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CSNK2A1 were set to 29240241
Phenotypes for gene: CSNK2A1 were set to Okur-Chung neurodevelopmental syndrome MIM#617062
Review for gene: CSNK2A1 was set to GREEN
Added comment: Microcephaly is a feature of the condition in 8/14 cases with de novo variants.
Sources: Expert list
Polymicrogyria and Schizencephaly v0.81 CCND2 Bryony Thompson Marked gene: CCND2 as ready
Polymicrogyria and Schizencephaly v0.81 CCND2 Bryony Thompson Gene: ccnd2 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.81 CCND2 Bryony Thompson Classified gene: CCND2 as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.81 CCND2 Bryony Thompson Gene: ccnd2 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.80 CCND2 Bryony Thompson gene: CCND2 was added
gene: CCND2 was added to Polymicrogyria and Schizencephaly. Sources: Expert list
Mode of inheritance for gene: CCND2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCND2 were set to 24705253
Phenotypes for gene: CCND2 were set to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 MIM#615938
Mode of pathogenicity for gene: CCND2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: CCND2 was set to GREEN
Added comment: Polymicrogyria is a prominent feature of the condition. At least 12 cases with de novo or parental mosaic missense with expected gain of function.
Sources: Expert list
Malformations of cortical development_Superpanel v0.74 Bryony Thompson Changed child panels to: Microcephaly; Polymicrogyria and Schizencephaly; Lissencephaly and Band Heterotopia; Tuberous Sclerosis_Cortical Dysplasia_Hemimegalencephaly; Cobblestone Malformations
Intellectual disability syndromic and non-syndromic v0.2656 ADAM22 Zornitza Stark Classified gene: ADAM22 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2656 ADAM22 Zornitza Stark Gene: adam22 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 ADAM22 Zornitza Stark Marked gene: ADAM22 as ready
Intellectual disability syndromic and non-syndromic v0.2655 ADAM22 Zornitza Stark Gene: adam22 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 RAX Zornitza Stark Marked gene: RAX as ready
Intellectual disability syndromic and non-syndromic v0.2655 RAX Zornitza Stark Gene: rax has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 TUBA8 Zornitza Stark Marked gene: TUBA8 as ready
Intellectual disability syndromic and non-syndromic v0.2655 TUBA8 Zornitza Stark Gene: tuba8 has been classified as Red List (Low Evidence).
Mendeliome v0.2932 XIST Zornitza Stark Marked gene: XIST as ready
Mendeliome v0.2932 XIST Zornitza Stark Gene: xist has been classified as Green List (High Evidence).
Mendeliome v0.2932 XIST Zornitza Stark Phenotypes for gene: XIST were changed from to X-inactivation, familial skewed, MIM# 300087
Mendeliome v0.2931 XIST Zornitza Stark Mode of inheritance for gene: XIST was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2930 XIST Zornitza Stark reviewed gene: XIST: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: X-inactivation, familial skewed, MIM# 300087; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2655 XIST Zornitza Stark Marked gene: XIST as ready
Intellectual disability syndromic and non-syndromic v0.2655 XIST Zornitza Stark Gene: xist has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 WFS1 Zornitza Stark Marked gene: WFS1 as ready
Intellectual disability syndromic and non-syndromic v0.2655 WFS1 Zornitza Stark Gene: wfs1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 RBM10 Zornitza Stark Marked gene: RBM10 as ready
Intellectual disability syndromic and non-syndromic v0.2655 RBM10 Zornitza Stark Gene: rbm10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 RBM10 Zornitza Stark Phenotypes for gene: RBM10 were changed from to TARP syndrome, 311900 (3), X-linked recessive
Intellectual disability syndromic and non-syndromic v0.2654 RBM10 Zornitza Stark Publications for gene: RBM10 were set to
Intellectual disability syndromic and non-syndromic v0.2653 RBM10 Zornitza Stark Mode of inheritance for gene: RBM10 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2930 SYNE2 Zornitza Stark Marked gene: SYNE2 as ready
Mendeliome v0.2930 SYNE2 Zornitza Stark Gene: syne2 has been classified as Red List (Low Evidence).
Mendeliome v0.2930 SYNE2 Zornitza Stark Phenotypes for gene: SYNE2 were changed from to Emery-Dreifuss muscular dystrophy 5, autosomal dominant MIM#612999
Mendeliome v0.2929 SYNE2 Zornitza Stark Publications for gene: SYNE2 were set to
Intellectual disability syndromic and non-syndromic v0.2652 RBM10 Michelle Torres reviewed gene: RBM10: Rating: GREEN; Mode of pathogenicity: None; Publications: 24259342, 24000153, 30462380; Phenotypes: TARP syndrome, 311900 (3), X-linked recessive; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Rhabdomyolysis and Metabolic Myopathy v0.53 YARS2 Bryony Thompson Marked gene: YARS2 as ready
Rhabdomyolysis and Metabolic Myopathy v0.53 YARS2 Bryony Thompson Gene: yars2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.53 YARS2 Bryony Thompson Classified gene: YARS2 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.53 YARS2 Bryony Thompson Gene: yars2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.52 YARS2 Bryony Thompson gene: YARS2 was added
gene: YARS2 was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: YARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YARS2 were set to 28395030
Phenotypes for gene: YARS2 were set to Myopathy, lactic acidosis, and sideroblastic anemia 2 MIM#613561
Review for gene: YARS2 was set to GREEN
Added comment: Exercise intolerance is a prominent presenting feature of the condition.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.51 TYMP Bryony Thompson changed review comment from: Cannot find any evidence that rhabdomyolysis is a feature of the condition. This condition has features of a visceral myopathy.; to: Cannot find any evidence that rhabdomyolysis is a feature of the condition. One case reported with exercise intolerance as a presenting feature of the condition.
Rhabdomyolysis and Metabolic Myopathy v0.51 TYMP Bryony Thompson edited their review of gene: TYMP: Changed publications: 24199812
Rhabdomyolysis and Metabolic Myopathy v0.51 TTN Bryony Thompson gene: TTN was added
gene: TTN was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: TTN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTN were set to 31353864
Phenotypes for gene: TTN were set to Congenital titinopathy; exercise intolerance
Review for gene: TTN was set to RED
Added comment: Exercise intolerance only reported in two cases.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.50 TSFM Bryony Thompson edited their review of gene: TSFM: Changed rating: RED
Rhabdomyolysis and Metabolic Myopathy v0.50 TSFM Bryony Thompson edited their review of gene: TSFM: Changed rating: AMBER; Changed publications: 31267352, 17033963
Rhabdomyolysis and Metabolic Myopathy v0.50 TSEN54 Bryony Thompson edited their review of gene: TSEN54: Changed publications: 23177318; Changed phenotypes: Pontocerebellar hypoplasia type 2A MIM#277470
Rhabdomyolysis and Metabolic Myopathy v0.50 TSEN54 Bryony Thompson changed review comment from: Cannot find any evidence that rhabdomyolysis is a feature of the condition. Hypertonia reported which is neurogenic.; to: Single case reported with recurrent rhabdomyolysis and PCH with a homozygous variant.
Rhabdomyolysis and Metabolic Myopathy v0.50 TNNT1 Bryony Thompson Marked gene: TNNT1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.50 TNNT1 Bryony Thompson Gene: tnnt1 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.50 TNNT1 Bryony Thompson Classified gene: TNNT1 as Amber List (moderate evidence)
Rhabdomyolysis and Metabolic Myopathy v0.50 TNNT1 Bryony Thompson Gene: tnnt1 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.49 TNNT1 Bryony Thompson gene: TNNT1 was added
gene: TNNT1 was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: TNNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNNT1 were set to 31970803
Phenotypes for gene: TNNT1 were set to Nemaline myopathy 5, Amish type MIM#605355
Review for gene: TNNT1 was set to AMBER
Added comment: 4 individuals belonging to 3 apparently unrelated families of French Canadian ancestry
harbouring a novel homozygous TNNT1 (NM_003283.6:c.287T>C; p.Leu96Pro) missense with recurrent episodes of rhabdomyolysis.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.48 TAZ Bryony Thompson Classified gene: TAZ as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.48 TAZ Bryony Thompson Gene: taz has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.47 TAZ Bryony Thompson gene: TAZ was added
gene: TAZ was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: TAZ was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TAZ were set to 26845103
Phenotypes for gene: TAZ were set to Barth syndrome MIM#302060
Review for gene: TAZ was set to GREEN
Added comment: Exercise intolerance is a prominent feature of the condition.
Sources: Expert list
Mendeliome v0.2928 SYNE2 Bryony Thompson Classified gene: SYNE2 as Red List (low evidence)
Mendeliome v0.2928 SYNE2 Bryony Thompson Gene: syne2 has been classified as Red List (Low Evidence).
Mendeliome v0.2927 SYNE2 Bryony Thompson reviewed gene: SYNE2: Rating: RED; Mode of pathogenicity: None; Publications: 32184094, 17761684; Phenotypes: Emery-Dreifuss muscular dystrophy 5, autosomal dominant MIM#612999; Mode of inheritance: None
Rhabdomyolysis and Metabolic Myopathy v0.46 SLC25A20 Bryony Thompson gene: SLC25A20 was added
gene: SLC25A20 was added to Rhabdomyolysis RMH. Sources: Literature
Mode of inheritance for gene: SLC25A20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A20 were set to 24088670
Phenotypes for gene: SLC25A20 were set to Carnitine-acylcarnitine translocase deficiency MIM#212138
Review for gene: SLC25A20 was set to RED
Added comment: Single case with rhabdomyolysis with biallelic variants.
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v0.45 SLC25A4 Bryony Thompson Marked gene: SLC25A4 as ready
Rhabdomyolysis and Metabolic Myopathy v0.45 SLC25A4 Bryony Thompson Gene: slc25a4 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.45 SLC25A4 Bryony Thompson Classified gene: SLC25A4 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.45 SLC25A4 Bryony Thompson Gene: slc25a4 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.44 SLC25A4 Bryony Thompson gene: SLC25A4 was added
gene: SLC25A4 was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: SLC25A4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A4 were set to 28823815
Phenotypes for gene: SLC25A4 were set to Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR MIM#615418
Review for gene: SLC25A4 was set to GREEN
Added comment: Five unrelated cases reported with exercise intolerance as a presenting feature of the condition.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.43 SGCA Bryony Thompson Marked gene: SGCA as ready
Rhabdomyolysis and Metabolic Myopathy v0.43 SGCA Bryony Thompson Gene: sgca has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.43 SGCA Bryony Thompson Classified gene: SGCA as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.43 SGCA Bryony Thompson Gene: sgca has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.42 SGCA Bryony Thompson gene: SGCA was added
gene: SGCA was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: SGCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGCA were set to 27297959; 26453141; 23989969
Phenotypes for gene: SGCA were set to Muscular dystrophy, limb-girdle, autosomal recessive 3 MIM#608099
Review for gene: SGCA was set to GREEN
Added comment: Four unrelated cases reported with rhabdomyolysis or exercise intolerance.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.41 KCNJ11 Bryony Thompson gene: KCNJ11 was added
gene: KCNJ11 was added to Rhabdomyolysis RMH. Sources: Literature
Mode of inheritance for gene: KCNJ11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KCNJ11 were set to Hyperinsulinemic hypoglycemia, familial, 2 MIM#601820
Review for gene: KCNJ11 was set to RED
Added comment: Single consanguineous family reported with congenital hyperinsulinism and rhabdomyolysis
Sources: Literature
Mendeliome v0.2927 PRKAG3 Bryony Thompson Classified gene: PRKAG3 as Amber List (moderate evidence)
Mendeliome v0.2927 PRKAG3 Bryony Thompson Gene: prkag3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2926 PRKAG3 Bryony Thompson reviewed gene: PRKAG3: Rating: AMBER; 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: 17878938, 10818001; Phenotypes: increased glycogen content in skeletal muscle; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2926 PAH Elena Savva reviewed gene: PAH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Phenylketonuria 261600, [Hyperphenylalaninemia, non-PKU mild] 261600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and Metabolic Myopathy v0.40 HMBS Bryony Thompson Marked gene: HMBS as ready
Rhabdomyolysis and Metabolic Myopathy v0.40 HMBS Bryony Thompson Gene: hmbs has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.40 HMBS Bryony Thompson Classified gene: HMBS as Amber List (moderate evidence)
Rhabdomyolysis and Metabolic Myopathy v0.40 HMBS Bryony Thompson Gene: hmbs has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.39 HMBS Bryony Thompson gene: HMBS was added
gene: HMBS was added to Rhabdomyolysis RMH. Sources: Literature
Mode of inheritance for gene: HMBS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HMBS were set to 25389600; 18647325
Phenotypes for gene: HMBS were set to Porphyria, acute intermittent MIM#176000
Review for gene: HMBS was set to AMBER
Added comment: Two cases reported with rhabdomyolysis.
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v0.38 FDX2 Bryony Thompson Marked gene: FDX2 as ready
Rhabdomyolysis and Metabolic Myopathy v0.38 FDX2 Bryony Thompson Gene: fdx2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.38 FDX2 Bryony Thompson Classified gene: FDX2 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.38 FDX2 Bryony Thompson Gene: fdx2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.37 FDX2 Bryony Thompson gene: FDX2 was added
gene: FDX2 was added to Rhabdomyolysis RMH. Sources: Literature
Mode of inheritance for gene: FDX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDX2 were set to 24281368; 30010796; 28803783
Phenotypes for gene: FDX2 were set to Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy MIM#251900
Review for gene: FDX2 was set to GREEN
Added comment: Three unrelated cases reported with rhabdomyolysis/myoglobinuria.
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v0.36 DGUOK Bryony Thompson gene: DGUOK was added
gene: DGUOK was added to Rhabdomyolysis RMH. Sources: Literature
Mode of inheritance for gene: DGUOK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DGUOK were set to 23043144
Phenotypes for gene: DGUOK were set to Rhabdomyolisis; lower limb weakness
Review for gene: DGUOK was set to RED
Added comment: Single case reported with rhabdomyolysis
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v0.35 CASQ1 Bryony Thompson Marked gene: CASQ1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.35 CASQ1 Bryony Thompson Gene: casq1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.35 CASQ1 Bryony Thompson Classified gene: CASQ1 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.35 CASQ1 Bryony Thompson Gene: casq1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.34 CASQ1 Bryony Thompson gene: CASQ1 was added
gene: CASQ1 was added to Rhabdomyolysis RMH. Sources: Literature
Mode of inheritance for gene: CASQ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CASQ1 were set to 30258016
Phenotypes for gene: CASQ1 were set to Myopathy, vacuolar, with CASQ1 aggregates MIM#616231
Review for gene: CASQ1 was set to GREEN
Added comment: Exercise intolerance has been reported as the presenting symptom in at least 5 cases, mainly with the described founder mutation (p.Asp244Gly).
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v0.33 PNPLA2 Bryony Thompson Marked gene: PNPLA2 as ready
Rhabdomyolysis and Metabolic Myopathy v0.33 PNPLA2 Bryony Thompson Gene: pnpla2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.33 PNPLA2 Bryony Thompson Classified gene: PNPLA2 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.33 PNPLA2 Bryony Thompson Gene: pnpla2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.32 PNPLA2 Bryony Thompson gene: PNPLA2 was added
gene: PNPLA2 was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: PNPLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA2 were set to 18952067; 25287355; 25956450
Phenotypes for gene: PNPLA2 were set to Neutral lipid storage disease with myopathy MIM#610717
Review for gene: PNPLA2 was set to GREEN
Added comment: Three unrelated families reported with exercise intolerance as a presenting feature of the condition.
Sources: Expert list
Mendeliome v0.2926 ANO5 Zornitza Stark Marked gene: ANO5 as ready
Mendeliome v0.2926 ANO5 Zornitza Stark Gene: ano5 has been classified as Green List (High Evidence).
Mendeliome v0.2926 ANO5 Zornitza Stark Publications for gene: ANO5 were set to
Mendeliome v0.2925 ANO5 Zornitza Stark Phenotypes for gene: ANO5 were changed from to Gnathodiaphyseal dysplasia MIM#166260; Miyoshi muscular dystrophy 3 MIM#613319; Muscular dystrophy, limb-girdle, autosomal recessive 12 MIM#611307
Rhabdomyolysis and Metabolic Myopathy v0.31 AMACR Bryony Thompson gene: AMACR was added
gene: AMACR was added to Rhabdomyolysis RMH. Sources: Literature
Mode of inheritance for gene: AMACR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMACR were set to 20921516
Phenotypes for gene: AMACR were set to rhabdomyolysis
Review for gene: AMACR was set to RED
Added comment: Single case with rahbdomyolysis reported, with a homozygous missense
Sources: Literature
Mendeliome v0.2924 ANO5 Zornitza Stark Mode of inheritance for gene: ANO5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2923 CPT1B Zornitza Stark Marked gene: CPT1B as ready
Mendeliome v0.2923 CPT1B Zornitza Stark Gene: cpt1b has been classified as Red List (Low Evidence).
Mendeliome v0.2923 CPT1B Zornitza Stark Publications for gene: CPT1B were set to
Mendeliome v0.2922 CPT1B Zornitza Stark Mode of inheritance for gene: CPT1B was changed from Unknown to Unknown
Rhabdomyolysis and Metabolic Myopathy v0.30 MYH3 Bryony Thompson gene: MYH3 was added
gene: MYH3 was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: MYH3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYH3 were set to 28779239
Phenotypes for gene: MYH3 were set to paresthesia; rhabdomyolysis
Review for gene: MYH3 was set to RED
Added comment: Single case with rhabdomyolysis reported.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.29 TWNK Bryony Thompson Classified gene: TWNK as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.29 TWNK Bryony Thompson Gene: twnk has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.28 TWNK Bryony Thompson gene: TWNK was added
gene: TWNK was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: TWNK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TWNK were set to 20880070
Phenotypes for gene: TWNK were set to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 MIM#609286
Review for gene: TWNK was set to GREEN
Added comment: Exercise intolerance reported as a presenting feature of the condition in at least 5 cases.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.27 AHCY Bryony Thompson gene: AHCY was added
gene: AHCY was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: AHCY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AHCY were set to 28779239
Phenotypes for gene: AHCY were set to Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase MIM#613752
Review for gene: AHCY was set to RED
Added comment: Single case reported with rhabdomyolysis
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.26 COQ8A Bryony Thompson Marked gene: COQ8A as ready
Rhabdomyolysis and Metabolic Myopathy v0.26 COQ8A Bryony Thompson Gene: coq8a has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.26 COQ8A Bryony Thompson Classified gene: COQ8A as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.26 COQ8A Bryony Thompson Gene: coq8a has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.25 COQ8A Bryony Thompson gene: COQ8A was added
gene: COQ8A was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: COQ8A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ8A were set to 32337771
Phenotypes for gene: COQ8A were set to Coenzyme Q10 deficiency, primary, 4 MIM#612016
Review for gene: COQ8A was set to GREEN
gene: COQ8A was marked as current diagnostic
Added comment: Exercise intolerance is a presenting feature in 25% of cases (out of 59 total).
Sources: Expert list
Mendeliome v0.2921 MYF6 Bryony Thompson Classified gene: MYF6 as Red List (low evidence)
Mendeliome v0.2921 MYF6 Bryony Thompson Gene: myf6 has been classified as Red List (Low Evidence).
Mendeliome v0.2920 MYF6 Bryony Thompson reviewed gene: MYF6: Rating: RED; Mode of pathogenicity: None; Publications: 11053684; Phenotypes: Centronuclear myopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2920 MTMR14 Bryony Thompson Classified gene: MTMR14 as Red List (low evidence)
Mendeliome v0.2920 MTMR14 Bryony Thompson Added comment: Comment on list classification: No evidence of Mendelian disease
Mendeliome v0.2920 MTMR14 Bryony Thompson Gene: mtmr14 has been classified as Red List (Low Evidence).
Mendeliome v0.2919 MTMR14 Bryony Thompson reviewed gene: MTMR14: Rating: RED; Mode of pathogenicity: None; Publications: 17008356; Phenotypes: {Centronuclear myopathy, autosomal, modifier of} MIM#160150; Mode of inheritance: Unknown
Rhabdomyolysis and Metabolic Myopathy v0.22 GMPPB Bryony Thompson Marked gene: GMPPB as ready
Rhabdomyolysis and Metabolic Myopathy v0.22 GMPPB Bryony Thompson Gene: gmppb has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.22 GMPPB Bryony Thompson Classified gene: GMPPB as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.22 GMPPB Bryony Thompson Gene: gmppb has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.21 GMPPB Bryony Thompson gene: GMPPB was added
gene: GMPPB was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: GMPPB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GMPPB were set to 28456886; 27874200; 25681410
Phenotypes for gene: GMPPB were set to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 MIM#615352; Limb myalgia; exercise intolerance; myoglobinuria
Review for gene: GMPPB was set to GREEN
Added comment: Three unrelated cases reported with rhabdomyolysis.
Sources: Expert list
Hereditary Spastic Paraplegia Superpanel v0.94 Bryony Thompson Panel types changed to Royal Melbourne Hospital; Rare Disease
Leukodystrophy - adult onset v0.60 Bryony Thompson Panel types changed to Royal Melbourne Hospital; Rare Disease
Rhabdomyolysis and Metabolic Myopathy v0.20 DNA2 Bryony Thompson gene: DNA2 was added
gene: DNA2 was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: DNA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNA2 were set to 31636600
Phenotypes for gene: DNA2 were set to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 6 MIM#615156
Review for gene: DNA2 was set to RED
Added comment: Single case reported with rhabdomyolysis
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.19 Bryony Thompson removed gene:CYP2C8 from the panel
Rhabdomyolysis and Metabolic Myopathy v0.18 CYP2C8 Bryony Thompson Classified gene: CYP2C8 as No list
Rhabdomyolysis and Metabolic Myopathy v0.18 CYP2C8 Bryony Thompson Gene: cyp2c8 has been removed from the panel.
Mendeliome v0.2919 CPT1B Bryony Thompson Classified gene: CPT1B as Red List (low evidence)
Mendeliome v0.2919 CPT1B Bryony Thompson Gene: cpt1b has been classified as Red List (Low Evidence).
Mendeliome v0.2918 CPT1B Bryony Thompson reviewed gene: CPT1B: Rating: RED; Mode of pathogenicity: None; Publications: 18023382; Phenotypes: ; Mode of inheritance: Unknown
Rhabdomyolysis and Metabolic Myopathy v0.17 COL4A1 Bryony Thompson gene: COL4A1 was added
gene: COL4A1 was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A1 were set to 31540749
Phenotypes for gene: COL4A1 were set to Recurrent rhabdomyolysis; infections; hypertrophic cardiomyopathy.
Review for gene: COL4A1 was set to RED
Added comment: Single case reported with rhabdomyolysis
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.16 CHKB Bryony Thompson Marked gene: CHKB as ready
Rhabdomyolysis and Metabolic Myopathy v0.16 CHKB Bryony Thompson Gene: chkb has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.16 CHKB Bryony Thompson gene: CHKB was added
gene: CHKB was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: CHKB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHKB were set to 26782016
Phenotypes for gene: CHKB were set to Muscular dystrophy, congenital, megaconial type MIM#602541
Review for gene: CHKB was set to RED
Added comment: Single family reported with rhbdomyolysis
Sources: Expert list
Mendeliome v0.2918 ANO5 Bryony Thompson reviewed gene: ANO5: Rating: GREEN; Mode of pathogenicity: None; Publications: 32112655; Phenotypes: Gnathodiaphyseal dysplasia MIM#166260, Miyoshi muscular dystrophy 3 MIM#613319, Muscular dystrophy, limb-girdle, autosomal recessive 12 MIM#611307; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.31 SEC63 Zornitza Stark edited their review of gene: SEC63: Changed rating: RED
Renal Macrocystic Disease v0.31 PRKCSH Zornitza Stark Classified gene: PRKCSH as Amber List (moderate evidence)
Renal Macrocystic Disease v0.31 PRKCSH Zornitza Stark Gene: prkcsh has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.30 PRKCSH Zornitza Stark edited their review of gene: PRKCSH: Changed rating: AMBER
Renal Macrocystic Disease v0.30 ALG9 Zornitza Stark Marked gene: ALG9 as ready
Renal Macrocystic Disease v0.30 ALG9 Zornitza Stark Gene: alg9 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.30 ALG9 Zornitza Stark Classified gene: ALG9 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.30 ALG9 Zornitza Stark Gene: alg9 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.29 ALG9 Zornitza Stark gene: ALG9 was added
gene: ALG9 was added to Renal Macrocystic Disease. Sources: Literature
Mode of inheritance for gene: ALG9 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ALG9 were set to 31395617
Phenotypes for gene: ALG9 were set to Congenital disorder of glycosylation, type Il, MIM# 608776; Gillessen-Kaesbach-Nishimura syndrome, MIM#263210; Polycystic kidney disease
Review for gene: ALG9 was set to AMBER
Added comment: Two individuals with mono-allelic variants reported with polycystic kidney disease, and ALG9 LOF variants over-represented in a population-based cohort. However, penetrance and expressivity seem variable, and also it is unclear whether parents of children affected by the AR CDG have renal cysts. Bi-allelic variants cause CDG: kidney cysts reported as part of phenotype but note this is generally a severe multi-system disorder.
Sources: Literature
Renal Macrocystic Disease v0.28 PRKCSH Zornitza Stark changed review comment from: Well established gene-disease relationship, >50 reported families.; to: Well established gene-disease relationship, >50 reported families. Liver cystic disease predominates the clinical presentation, generally a small number of kidney cysts.
Renal Macrocystic Disease v0.28 PRKCSH Zornitza Stark Phenotypes for gene: PRKCSH were changed from Polycystic liver disease 1, MIM# 174050, with or without kidney cysts to Polycystic liver disease 1, MIM# 174050, with or without kidney cysts
Renal Macrocystic Disease v0.28 PRKCSH Zornitza Stark Marked gene: PRKCSH as ready
Renal Macrocystic Disease v0.28 PRKCSH Zornitza Stark Gene: prkcsh has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.28 PRKCSH Zornitza Stark Phenotypes for gene: PRKCSH were changed from to Polycystic liver disease 1, MIM# 174050, with or without kidney cysts
Renal Macrocystic Disease v0.27 PRKCSH Zornitza Stark Publications for gene: PRKCSH were set to
Renal Macrocystic Disease v0.26 PRKCSH Zornitza Stark Mode of inheritance for gene: PRKCSH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.25 PRKCSH Zornitza Stark reviewed gene: PRKCSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 12577059; Phenotypes: Polycystic liver disease 1, MIM# 174050, with or without kidney cysts; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2918 DNAJB11 Zornitza Stark Marked gene: DNAJB11 as ready
Mendeliome v0.2918 DNAJB11 Zornitza Stark Gene: dnajb11 has been classified as Green List (High Evidence).
Mendeliome v0.2918 DNAJB11 Zornitza Stark Phenotypes for gene: DNAJB11 were changed from to Polycystic kidney disease 6 with or without polycystic liver disease, MIM#618061
Mendeliome v0.2917 DNAJB11 Zornitza Stark Publications for gene: DNAJB11 were set to
Mendeliome v0.2916 DNAJB11 Zornitza Stark Mode of inheritance for gene: DNAJB11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2915 DNAJB11 Zornitza Stark reviewed gene: DNAJB11: Rating: GREEN; Mode of pathogenicity: None; Publications: 29706351, 29777155; Phenotypes: Polycystic kidney disease 6 with or without polycystic liver disease, MIM#618061; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polymicrogyria and Schizencephaly v0.79 RAB3GAP1 Zornitza Stark Marked gene: RAB3GAP1 as ready
Polymicrogyria and Schizencephaly v0.79 RAB3GAP1 Zornitza Stark Gene: rab3gap1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.79 RAB3GAP1 Zornitza Stark Phenotypes for gene: RAB3GAP1 were changed from to Warburg micro syndrome 1, MIM# 600118
Polymicrogyria and Schizencephaly v0.78 RAB3GAP1 Zornitza Stark Publications for gene: RAB3GAP1 were set to
Polymicrogyria and Schizencephaly v0.77 RAB3GAP1 Zornitza Stark Mode of inheritance for gene: RAB3GAP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.76 RAB18 Zornitza Stark Marked gene: RAB18 as ready
Polymicrogyria and Schizencephaly v0.76 RAB18 Zornitza Stark Gene: rab18 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.76 RAB18 Zornitza Stark Phenotypes for gene: RAB18 were changed from to Warburg micro syndrome 3, MIM# 614222
Polymicrogyria and Schizencephaly v0.75 RAB18 Zornitza Stark Publications for gene: RAB18 were set to
Polymicrogyria and Schizencephaly v0.74 RAB18 Zornitza Stark Mode of inheritance for gene: RAB18 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.10 PTEN Zornitza Stark Marked gene: PTEN as ready
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.10 PTEN Zornitza Stark Gene: pten has been classified as Green List (High Evidence).
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.10 PTEN Zornitza Stark Phenotypes for gene: PTEN were changed from to Cowden syndrome 1 158350; Lhermitte-Duclos syndrome 158350; Macrocephaly/autism syndrome 605309
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.9 PTEN Zornitza Stark Publications for gene: PTEN were set to
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.8 PTEN Zornitza Stark Mode of inheritance for gene: PTEN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.28 ANO5 Zornitza Stark Marked gene: ANO5 as ready
Skeletal dysplasia v0.28 ANO5 Zornitza Stark Gene: ano5 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.28 ANO5 Zornitza Stark Publications for gene: ANO5 were set to
Skeletal dysplasia v0.27 ANO5 Zornitza Stark Mode of pathogenicity for gene: ANO5 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
Skeletal dysplasia v0.26 ANO5 Zornitza Stark Mode of inheritance for gene: ANO5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.26 ANO5 Zornitza Stark Mode of inheritance for gene: ANO5 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.25 ANO5 Zornitza Stark Mode of inheritance for gene: ANO5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.25 ANO5 Zornitza Stark Mode of inheritance for gene: ANO5 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2915 GPR143 Zornitza Stark Marked gene: GPR143 as ready
Mendeliome v0.2915 GPR143 Zornitza Stark Gene: gpr143 has been classified as Green List (High Evidence).
Mendeliome v0.2915 GPR143 Zornitza Stark Phenotypes for gene: GPR143 were changed from to congenital nystagmus 6, MIM 300814; type I ocular albinism, Nettleship-Falls type, MIM 300500
Mendeliome v0.2914 GPR143 Zornitza Stark Publications for gene: GPR143 were set to
Mendeliome v0.2913 GPR143 Zornitza Stark Mode of inheritance for gene: GPR143 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cancer Predisposition_Paediatric v0.12 ELP1 Zornitza Stark Marked gene: ELP1 as ready
Cancer Predisposition_Paediatric v0.12 ELP1 Zornitza Stark Gene: elp1 has been classified as Green List (High Evidence).
Mendeliome v0.2912 ELP1 Zornitza Stark Marked gene: ELP1 as ready
Mendeliome v0.2912 ELP1 Zornitza Stark Gene: elp1 has been classified as Green List (High Evidence).
Mendeliome v0.2912 ELP1 Zornitza Stark Phenotypes for gene: ELP1 were changed from to Dysautonomia, familial MIM#223900; paediatric medulloblastoma
Mendeliome v0.2911 ELP1 Zornitza Stark Publications for gene: ELP1 were set to
Mendeliome v0.2910 ELP1 Zornitza Stark Mode of inheritance for gene: ELP1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.73 RAB3GAP2 Lauren Akesson reviewed gene: RAB3GAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23420520, 20967465; Phenotypes: Warburg micro syndrome 2 614225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.73 RAB3GAP1 Lauren Akesson reviewed gene: RAB3GAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23420520; Phenotypes: Warburg micro syndrome 1 600118; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.73 RAB18 Lauren Akesson reviewed gene: RAB18: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21473985, 23420520; Phenotypes: Warburg micro syndrome 3 614222; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.7 PTEN Lauren Akesson reviewed gene: PTEN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32162846; Phenotypes: Cowden syndrome 1 158350, Lhermitte-Duclos syndrome 158350, Macrocephaly/autism syndrome 605309; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.24 ANO5 Bryony Thompson reviewed gene: ANO5: 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: 28176803, 32112655; Phenotypes: Gnathodiaphyseal dysplasia MIM#166260; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2909 GPR143 Teresa Zhao reviewed gene: GPR143: Rating: GREEN; Mode of pathogenicity: None; Publications: 30555098, 29761529; Phenotypes: congenital nystagmus 6, MIM 300814, ty[e I ocular albinism, Nettleship-Falls type, MIM 300500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cancer Predisposition_Paediatric v0.12 ELP1 Bryony Thompson Classified gene: ELP1 as Green List (high evidence)
Cancer Predisposition_Paediatric v0.12 ELP1 Bryony Thompson Gene: elp1 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.11 ELP1 Bryony Thompson gene: ELP1 was added
gene: ELP1 was added to Cancer Predisposition_Paediatric. Sources: Literature
Mode of inheritance for gene: ELP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELP1 were set to 32296180
Phenotypes for gene: ELP1 were set to Paediatric medulloblastoma sonic hedgehog subtype
Review for gene: ELP1 was set to GREEN
Added comment: Medulloblastoma predisposition: association identified for heterozygous ELP1 loss of function variants with paediatric medulloblastoma with exome-wide significance, specifically associated with the sonic hedgehog (SHH) subtype. Association was validated in additional paediatric cohorts. Monoallelic germline loss of function variants identified in 29/202 paediatric medulloblastoma SHH cases (absent from adult patients) and loss of heterozygosity of the ELP1 wild-type allele was present in all tumours. Segregation was reported in one family and expected in another.
Sources: Literature
Mendeliome v0.2909 ELP1 Bryony Thompson reviewed gene: ELP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11179008, 32296180; Phenotypes: Dysautonomia, familial MIM#223900, paediatric medulloblastoma; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2909 SNRNP200 Zornitza Stark Marked gene: SNRNP200 as ready
Mendeliome v0.2909 SNRNP200 Zornitza Stark Gene: snrnp200 has been classified as Green List (High Evidence).
Mendeliome v0.2909 SNRNP200 Zornitza Stark Phenotypes for gene: SNRNP200 were changed from to Retinitis pigmentosa 33 (MIM# 610359)
Mendeliome v0.2908 SNRNP200 Zornitza Stark Publications for gene: SNRNP200 were set to
Mendeliome v0.2907 SNRNP200 Zornitza Stark Mode of inheritance for gene: SNRNP200 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Heterotaxy v0.75 PKD1L1 Zornitza Stark Marked gene: PKD1L1 as ready
Heterotaxy v0.75 PKD1L1 Zornitza Stark Gene: pkd1l1 has been classified as Amber List (Moderate Evidence).
Heterotaxy v0.75 PKD1L1 Zornitza Stark Publications for gene: PKD1L1 were set to
Heterotaxy v0.74 PKD1L1 Zornitza Stark Phenotypes for gene: PKD1L1 were changed from to Heterotaxy, visceral, 8, autosomal (MIM#617205)
Heterotaxy v0.73 PKD1L1 Zornitza Stark Mode of inheritance for gene: PKD1L1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.72 PKD1L1 Zornitza Stark Classified gene: PKD1L1 as Amber List (moderate evidence)
Heterotaxy v0.72 PKD1L1 Zornitza Stark Gene: pkd1l1 has been classified as Amber List (Moderate Evidence).
Heterotaxy v0.71 RPGR Zornitza Stark Marked gene: RPGR as ready
Heterotaxy v0.71 RPGR Zornitza Stark Gene: rpgr has been classified as Red List (Low Evidence).
Heterotaxy v0.71 RPGR Zornitza Stark Phenotypes for gene: RPGR were changed from to Retinitis pigmentosa 3 (MIM#300029)
Heterotaxy v0.70 RPGR Zornitza Stark Publications for gene: RPGR were set to
Heterotaxy v0.69 RPGR Zornitza Stark Mode of inheritance for gene: RPGR was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Heterotaxy v0.68 RPGR Zornitza Stark Classified gene: RPGR as Red List (low evidence)
Heterotaxy v0.68 RPGR Zornitza Stark Gene: rpgr has been classified as Red List (Low Evidence).
Heterotaxy v0.67 RSPH1 Zornitza Stark Marked gene: RSPH1 as ready
Heterotaxy v0.67 RSPH1 Zornitza Stark Gene: rsph1 has been classified as Red List (Low Evidence).
Heterotaxy v0.67 RSPH1 Zornitza Stark Phenotypes for gene: RSPH1 were changed from to Ciliary dyskinesia, primary, 24 (MIM#615481)
Heterotaxy v0.66 RSPH1 Zornitza Stark Publications for gene: RSPH1 were set to
Heterotaxy v0.65 RSPH1 Zornitza Stark Mode of inheritance for gene: RSPH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.64 RSPH1 Zornitza Stark Classified gene: RSPH1 as Red List (low evidence)
Heterotaxy v0.64 RSPH1 Zornitza Stark Gene: rsph1 has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.103 RSPH1 Zornitza Stark Marked gene: RSPH1 as ready
Ciliary Dyskinesia v0.103 RSPH1 Zornitza Stark Gene: rsph1 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.103 RSPH1 Zornitza Stark Phenotypes for gene: RSPH1 were changed from to Ciliary dyskinesia, primary, 24 (MIM#615481)
Ciliary Dyskinesia v0.102 RSPH1 Zornitza Stark Publications for gene: RSPH1 were set to
Ciliary Dyskinesia v0.101 RSPH1 Zornitza Stark Mode of inheritance for gene: RSPH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.63 RSPH3 Zornitza Stark Marked gene: RSPH3 as ready
Heterotaxy v0.63 RSPH3 Zornitza Stark Gene: rsph3 has been classified as Red List (Low Evidence).
Heterotaxy v0.63 RSPH3 Zornitza Stark Phenotypes for gene: RSPH3 were changed from to Ciliary dyskinesia, primary, 32 (MIM#616481)
Heterotaxy v0.62 RSPH3 Zornitza Stark Publications for gene: RSPH3 were set to
Heterotaxy v0.61 RSPH3 Zornitza Stark Mode of inheritance for gene: RSPH3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.60 RSPH3 Zornitza Stark Classified gene: RSPH3 as Red List (low evidence)
Heterotaxy v0.60 RSPH3 Zornitza Stark Gene: rsph3 has been classified as Red List (Low Evidence).
Heterotaxy v0.59 RSPH4A Zornitza Stark Marked gene: RSPH4A as ready
Heterotaxy v0.59 RSPH4A Zornitza Stark Gene: rsph4a has been classified as Red List (Low Evidence).
Heterotaxy v0.59 RSPH4A Zornitza Stark Phenotypes for gene: RSPH4A were changed from to Ciliary dyskinesia, primary, 11 (MIM#612649)
Heterotaxy v0.58 RSPH4A Zornitza Stark Publications for gene: RSPH4A were set to
Heterotaxy v0.57 RSPH4A Zornitza Stark Mode of inheritance for gene: RSPH4A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.56 RSPH4A Zornitza Stark Classified gene: RSPH4A as Red List (low evidence)
Heterotaxy v0.56 RSPH4A Zornitza Stark Gene: rsph4a has been classified as Red List (Low Evidence).
Heterotaxy v0.55 RSPH9 Zornitza Stark Marked gene: RSPH9 as ready
Heterotaxy v0.55 RSPH9 Zornitza Stark Gene: rsph9 has been classified as Red List (Low Evidence).
Heterotaxy v0.55 RSPH9 Zornitza Stark Phenotypes for gene: RSPH9 were changed from to Ciliary dyskinesia, primary, 12 (MIM#612650)
Heterotaxy v0.54 RSPH9 Zornitza Stark Publications for gene: RSPH9 were set to
Heterotaxy v0.53 RSPH9 Zornitza Stark Mode of inheritance for gene: RSPH9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.52 RSPH9 Zornitza Stark Classified gene: RSPH9 as Red List (low evidence)
Heterotaxy v0.52 RSPH9 Zornitza Stark Gene: rsph9 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.24 RUNX2 Zornitza Stark Marked gene: RUNX2 as ready
Skeletal dysplasia v0.24 RUNX2 Zornitza Stark Gene: runx2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.24 MMP9 Zornitza Stark Marked gene: MMP9 as ready
Skeletal dysplasia v0.24 MMP9 Zornitza Stark Gene: mmp9 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.24 SRP54 Zornitza Stark Marked gene: SRP54 as ready
Skeletal dysplasia v0.24 SRP54 Zornitza Stark Gene: srp54 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.24 DNAJC21 Zornitza Stark Marked gene: DNAJC21 as ready
Skeletal dysplasia v0.24 DNAJC21 Zornitza Stark Gene: dnajc21 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.24 EFL1 Zornitza Stark Marked gene: EFL1 as ready
Skeletal dysplasia v0.24 EFL1 Zornitza Stark Gene: efl1 has been classified as Green List (High Evidence).
Mendeliome v0.2906 SNRNP200 Ain Roesley changed review comment from: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD)

PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling

PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA)

PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister

PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.4Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo; to: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD)

PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling

PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA)

PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister

PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.1Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo
Mendeliome v0.2906 SNRNP200 Ain Roesley changed review comment from: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD)

PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling

PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA)

PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister

PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.1Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo; to: PMID: 31260034; more than 20 families reported with either de novo or AD with RP or retinal dystrophy (RD)

PMID: 29320387; p.(Arg1090Gln) in a proband with RP from a consag family with unaffected het parents and sibling

PMID: 23847139; p.(Pro1045Thr) homozygous in a patient with Leber congenital amaurosis (LCA)

PMID: 31260034: p.(Arg545His) homozygous in a patient with RP with asymptomatic het parents and sister

PMID: 27735924: in a patient with RP who is cHet for p.(Pro105Thr) in SNRNP200 and a 1.4Mb deletion spanning SNRNP200. Father is a carrier of the missense and is unaffected and the deletion was de novo
Mendeliome v0.2906 SNRNP200 Ain Roesley reviewed gene: SNRNP200: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31260034, 29320387, 23847139, 27735924; Phenotypes: Retinitis pigmentosa 33 (MIM# 610359); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Heterotaxy v0.51 PKD1L1 Crystle Lee reviewed gene: PKD1L1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27616478, 30664273, 20080492; Phenotypes: Heterotaxy, visceral, 8, autosomal (MIM#617205); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.51 RPGR Crystle Lee reviewed gene: RPGR: Rating: RED; Mode of pathogenicity: None; Publications: 26093275, 31775781; Phenotypes: Retinitis pigmentosa 3 (MIM#300029); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Heterotaxy v0.51 RSPH1 Crystle Lee reviewed gene: RSPH1: Rating: RED; Mode of pathogenicity: None; Publications: 23993197; Phenotypes: Ciliary dyskinesia, primary, 24 (MIM#615481); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.100 RSPH1 Crystle Lee reviewed gene: RSPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23993197; Phenotypes: Ciliary dyskinesia, primary, 24 (MIM#615481); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.51 RSPH3 Crystle Lee reviewed gene: RSPH3: Rating: RED; Mode of pathogenicity: None; Publications: 26073779; Phenotypes: Ciliary dyskinesia, primary, 32 (MIM#616481); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.51 RSPH4A Crystle Lee reviewed gene: RSPH4A: Rating: RED; Mode of pathogenicity: None; Publications: 25789548; Phenotypes: Ciliary dyskinesia, primary, 11 (MIM#612649); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brugada syndrome v0.13 SCN3B Zornitza Stark Phenotypes for gene: SCN3B were changed from Brugada syndrome 7 MIM#613120 to Brugada syndrome 7 MIM#613120
Brugada syndrome v0.13 SCN3B Zornitza Stark Marked gene: SCN3B as ready
Brugada syndrome v0.13 SCN3B Zornitza Stark Gene: scn3b has been classified as Red List (Low Evidence).
Brugada syndrome v0.13 SCN3B Zornitza Stark Phenotypes for gene: SCN3B were changed from to Brugada syndrome 7 MIM#613120
Brugada syndrome v0.12 SCN3B Zornitza Stark Mode of inheritance for gene: SCN3B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brugada syndrome v0.11 SCN3B Zornitza Stark Classified gene: SCN3B as Red List (low evidence)
Brugada syndrome v0.11 SCN3B Zornitza Stark Gene: scn3b has been classified as Red List (Low Evidence).
Brugada syndrome v0.10 SCN3B Zornitza Stark Tag disputed tag was added to gene: SCN3B.
Heterotaxy v0.51 RSPH9 Crystle Lee reviewed gene: RSPH9: Rating: RED; Mode of pathogenicity: None; Publications: 19200523; Phenotypes: Ciliary dyskinesia, primary, 12 (MIM#612650); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Multiple epiphyseal dysplasia and pseudoachondroplasia v0.3 CANT1 Tiong Tan Classified gene: CANT1 as Amber List (moderate evidence)
Multiple epiphyseal dysplasia and pseudoachondroplasia v0.3 CANT1 Tiong Tan Gene: cant1 has been classified as Amber List (Moderate Evidence).
Metaphyseal dysplasias v0.2 SRP54 Tiong Tan Classified gene: SRP54 as Amber List (moderate evidence)
Metaphyseal dysplasias v0.2 SRP54 Tiong Tan Gene: srp54 has been classified as Amber List (Moderate Evidence).
Metaphyseal dysplasias v0.1 Tiong Tan Panel status changed from internal to public
Metaphyseal dysplasias v0.0 SRP54 Tiong Tan Marked gene: SRP54 as ready
Metaphyseal dysplasias v0.0 SRP54 Tiong Tan Gene: srp54 has been classified as Green List (High Evidence).
Metaphyseal dysplasias v0.0 SRP54 Tiong Tan reviewed gene: SRP54: Rating: AMBER; Mode of pathogenicity: None; Publications: 29914977; Phenotypes: SBDS-like, severe congenital neutropenia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.24 RUNX2 Tiong Tan Added phenotypes Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly 156510; Cleidocranial dysplasia, forme fruste, dental anomalies only 119600; Cleidocranial dysplasia, forme fruste, with brachydactyly 119600; Cleidocranial dysplasia 119600 for gene: RUNX2
Skeletal dysplasia v0.24 MMP9 Tiong Tan Added phenotypes 613073METAPHYSEAL ANADYSPLASIA 2 for gene: MMP9
Publications for gene MMP9 were updated from 28342220; 19615667 to 28342220; 19615667
Skeletal dysplasia v0.24 MMP13 Tiong Tan Added phenotypes Metaphyseal anadysplasia 1 602111; Spondyloepimetaphyseal dysplasia, Missouri type 602111; Metaphyseal dysplasia, Spahr type - 250400 for gene: MMP13
Skeletal dysplasia v0.24 SRP54 Tiong Tan Added phenotypes 618752 NEUTROPENIA, SEVERE CONGENITAL, 8, AUTOSOMAL DOMINANT; SCN8 for gene: SRP54
Skeletal dysplasia v0.24 DNAJC21 Tiong Tan Added phenotypes BMFS3; 617052 BONE MARROW FAILURE SYNDROME 3 for gene: DNAJC21
Skeletal dysplasia v0.24 EFL1 Tiong Tan Added phenotypes 617941 SHWACHMAN-DIAMOND SYNDROME 2; SDS2 for gene: EFL1
Skeletal dysplasia v0.24 SBDS Tiong Tan Added phenotypes Shwachman-Diamond syndrome 260400; Shwachman-Diamond syndrome 260400 for gene: SBDS
Skeletal dysplasia v0.24 PTH1R Tiong Tan Added phenotypes Failure of tooth eruption, primary 125350; Eiken syndrome 600002; Metaphyseal chondrodysplasia, Murk Jansen type 156400; Chondrodysplasia, Blomstrand type 215045 for gene: PTH1R
Skeletal dysplasia v0.24 RMRP Tiong Tan Added phenotypes Cartilage-hair hypoplasia 250250; Metaphyseal dysplasia without hypotrichosis 250460; Anauxetic dysplasia 607095 for gene: RMRP
Skeletal dysplasia v0.24 POLR1D Tiong Tan Added phenotypes Treacher Collins syndrome 2 613717 for gene: POLR1D
Skeletal dysplasia v0.24 COL10A1 Tiong Tan Added phenotypes Metaphyseal chondrodysplasia, Schmid type 156500 for gene: COL10A1
Metaphyseal dysplasias v0.0 RUNX2 Tiong Tan gene: RUNX2 was added
gene: RUNX2 was added to Metaphyseal dysplasias. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: RUNX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RUNX2 were set to Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly 156510; Cleidocranial dysplasia 119600; Cleidocranial dysplasia, forme fruste, dental anomalies only 119600; Cleidocranial dysplasia, forme fruste, with brachydactyly 119600
Metaphyseal dysplasias v0.0 MMP9 Tiong Tan gene: MMP9 was added
gene: MMP9 was added to Metaphyseal dysplasias. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: MMP9 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MMP9 were set to 19615667
Phenotypes for gene: MMP9 were set to 613073METAPHYSEAL ANADYSPLASIA 2
Metaphyseal dysplasias v0.0 MMP13 Tiong Tan gene: MMP13 was added
gene: MMP13 was added to Metaphyseal dysplasias. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: MMP13 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MMP13 were set to 24648384
Phenotypes for gene: MMP13 were set to Metaphyseal anadysplasia 1 602111; Spondyloepimetaphyseal dysplasia, Missouri type 602111; Metaphyseal dysplasia, Spahr type - 250400
Metaphyseal dysplasias v0.0 SRP54 Tiong Tan gene: SRP54 was added
gene: SRP54 was added to Metaphyseal dysplasias. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SRP54 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SRP54 were set to SCN8; 618752 NEUTROPENIA, SEVERE CONGENITAL, 8, AUTOSOMAL DOMINANT
Metaphyseal dysplasias v0.0 DNAJC21 Tiong Tan gene: DNAJC21 was added
gene: DNAJC21 was added to Metaphyseal dysplasias. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: DNAJC21 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DNAJC21 were set to 617052 BONE MARROW FAILURE SYNDROME 3; BMFS3
Metaphyseal dysplasias v0.0 EFL1 Tiong Tan gene: EFL1 was added
gene: EFL1 was added to Metaphyseal dysplasias. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: EFL1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EFL1 were set to SDS2; 617941 SHWACHMAN-DIAMOND SYNDROME 2
Metaphyseal dysplasias v0.0 SBDS Tiong Tan gene: SBDS was added
gene: SBDS was added to Metaphyseal dysplasias. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SBDS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SBDS were set to Shwachman-Diamond syndrome 260400; Shwachman-Diamond syndrome 260400
Metaphyseal dysplasias v0.0 PTH1R Tiong Tan gene: PTH1R was added
gene: PTH1R was added to Metaphyseal dysplasias. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: PTH1R was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: PTH1R were set to Failure of tooth eruption, primary 125350; Eiken syndrome 600002; Chondrodysplasia, Blomstrand type 215045; Metaphyseal chondrodysplasia, Murk Jansen type 156400
Metaphyseal dysplasias v0.0 RMRP Tiong Tan gene: RMRP was added
gene: RMRP was added to Metaphyseal dysplasias. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: RMRP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RMRP were set to Metaphyseal dysplasia without hypotrichosis 250460; Cartilage-hair hypoplasia 250250; Anauxetic dysplasia 607095
Metaphyseal dysplasias v0.0 POLR1D Tiong Tan gene: POLR1D was added
gene: POLR1D was added to Metaphyseal dysplasias. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: POLR1D was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: POLR1D were set to Treacher Collins syndrome 2 613717
Metaphyseal dysplasias v0.0 COL10A1 Tiong Tan gene: COL10A1 was added
gene: COL10A1 was added to Metaphyseal dysplasias. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: COL10A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: COL10A1 were set to Metaphyseal chondrodysplasia, Schmid type 156500
Metaphyseal dysplasias v0.0 Tiong Tan Added panel Metaphyseal dysplasias
Skeletal dysplasia v0.24 RUNX2 Tiong Tan Added phenotypes Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly 156510; Cleidocranial dysplasia, forme fruste, dental anomalies only 119600; Cleidocranial dysplasia, forme fruste, with brachydactyly 119600; Cleidocranial dysplasia 119600 for gene: RUNX2
Skeletal dysplasia v0.24 MMP9 Tiong Tan Added phenotypes 613073METAPHYSEAL ANADYSPLASIA 2 for gene: MMP9
Publications for gene MMP9 were updated from 19615667; 28342220 to 28342220; 19615667
Skeletal dysplasia v0.24 MMP13 Tiong Tan Added phenotypes Metaphyseal anadysplasia 1 602111; Spondyloepimetaphyseal dysplasia, Missouri type 602111; Metaphyseal dysplasia, Spahr type - 250400 for gene: MMP13
Skeletal dysplasia v0.24 SRP54 Tiong Tan Added phenotypes 618752 NEUTROPENIA, SEVERE CONGENITAL, 8, AUTOSOMAL DOMINANT; SCN8 for gene: SRP54
Skeletal dysplasia v0.24 DNAJC21 Tiong Tan Added phenotypes BMFS3; 617052 BONE MARROW FAILURE SYNDROME 3 for gene: DNAJC21
Skeletal dysplasia v0.24 EFL1 Tiong Tan Added phenotypes 617941 SHWACHMAN-DIAMOND SYNDROME 2; SDS2 for gene: EFL1
Skeletal dysplasia v0.24 SBDS Tiong Tan Added phenotypes Shwachman-Diamond syndrome 260400; Shwachman-Diamond syndrome 260400 for gene: SBDS
Skeletal dysplasia v0.24 PTH1R Tiong Tan Added phenotypes Failure of tooth eruption, primary 125350; Eiken syndrome 600002; Metaphyseal chondrodysplasia, Murk Jansen type 156400; Chondrodysplasia, Blomstrand type 215045 for gene: PTH1R
Skeletal dysplasia v0.24 RMRP Tiong Tan Added phenotypes Cartilage-hair hypoplasia 250250; Metaphyseal dysplasia without hypotrichosis 250460; Anauxetic dysplasia 607095 for gene: RMRP
Skeletal dysplasia v0.24 POLR1D Tiong Tan Added phenotypes Treacher Collins syndrome 2 613717 for gene: POLR1D
Skeletal dysplasia v0.24 COL10A1 Tiong Tan Added phenotypes Metaphyseal chondrodysplasia, Schmid type 156500 for gene: COL10A1
Skeletal dysplasia v0.23 RUNX2 Tiong Tan Source Victorian Clinical Genetics Services was added to RUNX2.
Added phenotypes Cleidocranial dysplasia, forme fruste, dental anomalies only 119600; Cleidocranial dysplasia, forme fruste, with brachydactyly 119600; Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly 156510; Cleidocranial dysplasia 119600 for gene: RUNX2
Skeletal dysplasia v0.23 MMP9 Tiong Tan Source Victorian Clinical Genetics Services was added to MMP9.
Source Expert Review Green was added to MMP9.
Mode of inheritance for gene MMP9 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Added phenotypes 613073METAPHYSEAL ANADYSPLASIA 2 for gene: MMP9
Publications for gene MMP9 were updated from 28342220; 19615667 to 19615667; 28342220
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v0.23 MMP13 Tiong Tan Source Victorian Clinical Genetics Services was added to MMP13.
Added phenotypes Metaphyseal anadysplasia 1 602111; Spondyloepimetaphyseal dysplasia, Missouri type 602111; Metaphyseal dysplasia, Spahr type - 250400 for gene: MMP13
Skeletal dysplasia v0.23 SRP54 Tiong Tan gene: SRP54 was added
gene: SRP54 was added to Skeletal dysplasia. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SRP54 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SRP54 were set to 618752 NEUTROPENIA, SEVERE CONGENITAL, 8, AUTOSOMAL DOMINANT; SCN8
Skeletal dysplasia v0.23 DNAJC21 Tiong Tan gene: DNAJC21 was added
gene: DNAJC21 was added to Skeletal dysplasia. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: DNAJC21 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DNAJC21 were set to 617052 BONE MARROW FAILURE SYNDROME 3; BMFS3
Skeletal dysplasia v0.23 EFL1 Tiong Tan gene: EFL1 was added
gene: EFL1 was added to Skeletal dysplasia. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: EFL1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EFL1 were set to 617941 SHWACHMAN-DIAMOND SYNDROME 2; SDS2
Skeletal dysplasia v0.23 SBDS Tiong Tan Source Victorian Clinical Genetics Services was added to SBDS.
Added phenotypes Shwachman-Diamond syndrome 260400; Shwachman-Diamond syndrome 260400 for gene: SBDS
Skeletal dysplasia v0.23 PTH1R Tiong Tan Source Victorian Clinical Genetics Services was added to PTH1R.
Added phenotypes Metaphyseal chondrodysplasia, Murk Jansen type 156400; Eiken syndrome 600002; Failure of tooth eruption, primary 125350; Chondrodysplasia, Blomstrand type 215045 for gene: PTH1R
Skeletal dysplasia v0.23 RMRP Tiong Tan Source Victorian Clinical Genetics Services was added to RMRP.
Added phenotypes Metaphyseal dysplasia without hypotrichosis 250460; Cartilage-hair hypoplasia 250250; Anauxetic dysplasia 607095 for gene: RMRP
Skeletal dysplasia v0.23 POLR1D Tiong Tan Source Victorian Clinical Genetics Services was added to POLR1D.
Added phenotypes Treacher Collins syndrome 2 613717 for gene: POLR1D
Skeletal dysplasia v0.23 COL10A1 Tiong Tan Source Victorian Clinical Genetics Services was added to COL10A1.
Mode of inheritance for gene COL10A1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Metaphyseal chondrodysplasia, Schmid type 156500 for gene: COL10A1
Multiple epiphyseal dysplasia and pseudoachondroplasia v0.2 CANT1 Tiong Tan Marked gene: CANT1 as ready
Multiple epiphyseal dysplasia and pseudoachondroplasia v0.2 CANT1 Tiong Tan Gene: cant1 has been classified as Green List (High Evidence).
Multiple epiphyseal dysplasia and pseudoachondroplasia v0.2 CANT1 Tiong Tan reviewed gene: CANT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28742282; Phenotypes: Multiple epiphyseal dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2652 MADD Zornitza Stark Marked gene: MADD as ready
Intellectual disability syndromic and non-syndromic v0.2652 MADD Zornitza Stark Gene: madd has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2652 MADD Zornitza Stark Phenotypes for gene: MADD were changed from to intellectual disability
Intellectual disability syndromic and non-syndromic v0.2651 MADD Zornitza Stark Publications for gene: MADD were set to
Intellectual disability syndromic and non-syndromic v0.2650 MADD Zornitza Stark Mode of inheritance for gene: MADD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ichthyosis v0.79 ALOXE3 Zornitza Stark Marked gene: ALOXE3 as ready
Ichthyosis v0.79 ALOXE3 Zornitza Stark Gene: aloxe3 has been classified as Green List (High Evidence).
Ichthyosis v0.79 ALOXE3 Zornitza Stark Phenotypes for gene: ALOXE3 were changed from to Ichthyosis, congenital, autosomal recessive 3, MIM#606545
Ichthyosis v0.78 ALOXE3 Zornitza Stark Publications for gene: ALOXE3 were set to
Ichthyosis v0.77 ALOXE3 Zornitza Stark Mode of inheritance for gene: ALOXE3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ichthyosis v0.76 ALOXE3 Zornitza Stark reviewed gene: ALOXE3: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116617, 31046801, 26370990; Phenotypes: Ichthyosis, congenital, autosomal recessive 3, MIM#606545; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2906 ALOXE3 Zornitza Stark Marked gene: ALOXE3 as ready
Mendeliome v0.2906 ALOXE3 Zornitza Stark Gene: aloxe3 has been classified as Green List (High Evidence).
Mendeliome v0.2906 ALOXE3 Zornitza Stark Phenotypes for gene: ALOXE3 were changed from to Ichthyosis, congenital, autosomal recessive 3, MIM#606545
Mendeliome v0.2905 ALOXE3 Zornitza Stark Publications for gene: ALOXE3 were set to
Mendeliome v0.2904 ALOXE3 Zornitza Stark Mode of inheritance for gene: ALOXE3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2903 ARMC1 Zornitza Stark Marked gene: ARMC1 as ready
Mendeliome v0.2903 ARMC1 Zornitza Stark Gene: armc1 has been classified as Red List (Low Evidence).
Mendeliome v0.2903 ARMC1 Zornitza Stark Classified gene: ARMC1 as Red List (low evidence)
Mendeliome v0.2903 ARMC1 Zornitza Stark Gene: armc1 has been classified as Red List (Low Evidence).
Mendeliome v0.2902 ARMC1 Zornitza Stark reviewed gene: ARMC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Callosome v0.144 ARMC1 Zornitza Stark Marked gene: ARMC1 as ready
Callosome v0.144 ARMC1 Zornitza Stark Gene: armc1 has been classified as Red List (Low Evidence).
Callosome v0.144 ARMC1 Zornitza Stark Classified gene: ARMC1 as Red List (low evidence)
Callosome v0.144 ARMC1 Zornitza Stark Gene: armc1 has been classified as Red List (Low Evidence).
Callosome v0.143 ARMC1 Zornitza Stark reviewed gene: ARMC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.2902 ALOXE3 Chern Lim reviewed gene: ALOXE3: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116617, 31046801, 26370990; Phenotypes: Ichthyosis, congenital, autosomal recessive 3, MIM#606545; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Optic Atrophy v0.108 YME1L1 Zornitza Stark Marked gene: YME1L1 as ready
Optic Atrophy v0.108 YME1L1 Zornitza Stark Gene: yme1l1 has been classified as Red List (Low Evidence).
Achromatopsia v0.17 PDE6H Bryony Thompson Classified gene: PDE6H as Green List (high evidence)
Achromatopsia v0.17 PDE6H Bryony Thompson Gene: pde6h has been classified as Green List (High Evidence).
Achromatopsia v0.16 PDE6H Bryony Thompson gene: PDE6H was added
gene: PDE6H was added to Achromatopsia. Sources: Expert list
Mode of inheritance for gene: PDE6H was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: PDE6H were set to Achromatopsia 6 MIM#610024
Achromatopsia v0.15 PDE6C Bryony Thompson Classified gene: PDE6C as Green List (high evidence)
Achromatopsia v0.15 PDE6C Bryony Thompson Gene: pde6c has been classified as Green List (High Evidence).
Achromatopsia v0.14 PDE6C Bryony Thompson gene: PDE6C was added
gene: PDE6C was added to Achromatopsia. Sources: Expert list
Mode of inheritance for gene: PDE6C was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PDE6C were set to Achromatopsia-5
Achromatopsia v0.13 CNGB3 Bryony Thompson Classified gene: CNGB3 as Green List (high evidence)
Achromatopsia v0.13 CNGB3 Bryony Thompson Gene: cngb3 has been classified as Green List (High Evidence).
Achromatopsia v0.12 CNGB3 Bryony Thompson gene: CNGB3 was added
gene: CNGB3 was added to Achromatopsia. Sources: Expert list
Mode of inheritance for gene: CNGB3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CNGB3 were set to Achromatopsia 3 MIM#262300
Achromatopsia v0.11 CNGA3 Bryony Thompson Classified gene: CNGA3 as Green List (high evidence)
Achromatopsia v0.11 CNGA3 Bryony Thompson Gene: cnga3 has been classified as Green List (High Evidence).
Achromatopsia v0.10 CNGA3 Bryony Thompson gene: CNGA3 was added
gene: CNGA3 was added to Achromatopsia. Sources: Expert list
Mode of inheritance for gene: CNGA3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CNGA3 were set to Achromatopsia 2 MIM#216900
Macular Dystrophy/Stargardt Disease v0.13 Bryony Thompson removed gene:ZFYVE26 from the panel
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.54 Bryony Thompson removed gene:ZFYVE26 from the panel
Syndromic Retinopathy v0.68 ZFYVE26 Bryony Thompson Classified gene: ZFYVE26 as Green List (high evidence)
Syndromic Retinopathy v0.68 ZFYVE26 Bryony Thompson Gene: zfyve26 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.67 ZFYVE26 Bryony Thompson gene: ZFYVE26 was added
gene: ZFYVE26 was added to Syndromic Retinopathy. Sources: Expert Review
Mode of inheritance for gene: ZFYVE26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZFYVE26 were set to 31385551; 18394578; 14409555
Phenotypes for gene: ZFYVE26 were set to Spastic paraplegia 15, autosomal recessive MIM#270700
Optic Atrophy v0.108 YME1L1 Bryony Thompson gene: YME1L1 was added
gene: YME1L1 was added to Optic Atrophy. Sources: Expert list
Mode of inheritance for gene: YME1L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YME1L1 were set to 27495975
Phenotypes for gene: YME1L1 were set to Optic atrophy 11 MIM#617302
Review for gene: YME1L1 was set to RED
Added comment: Single family reported with optic atrophy
Sources: Expert list
Mendeliome v0.2902 STK36 Zornitza Stark Marked gene: STK36 as ready
Mendeliome v0.2902 STK36 Zornitza Stark Gene: stk36 has been classified as Red List (Low Evidence).
Mendeliome v0.2902 STK36 Zornitza Stark Phenotypes for gene: STK36 were changed from to Primary ciliary dyskinesia
Mendeliome v0.2901 STK36 Zornitza Stark Publications for gene: STK36 were set to
Mendeliome v0.2900 STK36 Zornitza Stark Mode of inheritance for gene: STK36 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2899 STK36 Zornitza Stark Classified gene: STK36 as Red List (low evidence)
Mendeliome v0.2899 STK36 Zornitza Stark Gene: stk36 has been classified as Red List (Low Evidence).
Mendeliome v0.2898 STK36 Zornitza Stark reviewed gene: STK36: Rating: RED; Mode of pathogenicity: None; Publications: 28543983; Phenotypes: Primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.51 STK36 Zornitza Stark Marked gene: STK36 as ready
Heterotaxy v0.51 STK36 Zornitza Stark Gene: stk36 has been classified as Red List (Low Evidence).
Heterotaxy v0.51 STK36 Zornitza Stark Phenotypes for gene: STK36 were changed from to Primary ciliary dyskinesia
Heterotaxy v0.50 STK36 Zornitza Stark Publications for gene: STK36 were set to
Heterotaxy v0.49 STK36 Zornitza Stark Mode of inheritance for gene: STK36 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.48 STK36 Zornitza Stark Classified gene: STK36 as Red List (low evidence)
Heterotaxy v0.48 STK36 Zornitza Stark Gene: stk36 has been classified as Red List (Low Evidence).
Heterotaxy v0.47 STK36 Zornitza Stark reviewed gene: STK36: Rating: RED; Mode of pathogenicity: None; Publications: 28543983; Phenotypes: Primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.99 STK36 Zornitza Stark Marked gene: STK36 as ready
Ciliary Dyskinesia v0.99 STK36 Zornitza Stark Gene: stk36 has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.99 STK36 Zornitza Stark gene: STK36 was added
gene: STK36 was added to Ciliary Dyskinesia. Sources: Expert list
Mode of inheritance for gene: STK36 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STK36 were set to 28543983
Phenotypes for gene: STK36 were set to Primary ciliary dyskinesia
Review for gene: STK36 was set to RED
Added comment: Single individual reported with homozygous LoF variant, PCD and situs solitus. Some functional data.
Sources: Expert list
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.53 Bryony Thompson removed gene:USH1C from the panel
Ciliary Dyskinesia v0.98 RPGR Zornitza Stark Marked gene: RPGR as ready
Ciliary Dyskinesia v0.98 RPGR Zornitza Stark Gene: rpgr has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.98 RPGR Zornitza Stark Phenotypes for gene: RPGR were changed from to Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness, MIM# 300455
Ciliary Dyskinesia v0.97 RPGR Zornitza Stark Publications for gene: RPGR were set to
Ciliary Dyskinesia v0.96 RPGR Zornitza Stark Mode of inheritance for gene: RPGR was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ciliary Dyskinesia v0.95 RPGR Zornitza Stark reviewed gene: RPGR: Rating: GREEN; Mode of pathogenicity: None; Publications: 10094550, 12920075, 16055928; Phenotypes: Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness, MIM# 300455; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ciliary Dyskinesia v0.95 GAS2L2 Zornitza Stark Classified gene: GAS2L2 as Green List (high evidence)
Ciliary Dyskinesia v0.95 GAS2L2 Zornitza Stark Gene: gas2l2 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.94 GAS2L2 Zornitza Stark Deleted their comment
Ciliary Dyskinesia v0.94 GAS2L2 Zornitza Stark edited their review of gene: GAS2L2: Added comment: Two families and functional evidence.; Changed rating: GREEN; Changed publications: 30665704; Changed phenotypes: Ciliary dyskinesia, primary, 41 (MIM # 618449); Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.94 DNAH8 Zornitza Stark Classified gene: DNAH8 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.94 DNAH8 Zornitza Stark Gene: dnah8 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.93 DNAH8 Zornitza Stark Marked gene: DNAH8 as ready
Ciliary Dyskinesia v0.93 DNAH8 Zornitza Stark Gene: dnah8 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.93 DNAH8 Zornitza Stark Phenotypes for gene: DNAH8 were changed from to Asthenozoospermia; primary ciliary dyskinesia
Ciliary Dyskinesia v0.92 DNAH8 Zornitza Stark Publications for gene: DNAH8 were set to
Ciliary Dyskinesia v0.91 DNAH8 Zornitza Stark Mode of inheritance for gene: DNAH8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.47 FOXJ1 Zornitza Stark Marked gene: FOXJ1 as ready
Heterotaxy v0.47 FOXJ1 Zornitza Stark Gene: foxj1 has been classified as Green List (High Evidence).
Heterotaxy v0.47 FOXJ1 Zornitza Stark Classified gene: FOXJ1 as Green List (high evidence)
Heterotaxy v0.47 FOXJ1 Zornitza Stark Gene: foxj1 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.90 NFKB1 Zornitza Stark Marked gene: NFKB1 as ready
Ciliary Dyskinesia v0.90 NFKB1 Zornitza Stark Added comment: Comment when marking as ready: Not a PCD, but overlapping clinical features.
Ciliary Dyskinesia v0.90 NFKB1 Zornitza Stark Gene: nfkb1 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.90 NFKB1 Zornitza Stark Classified gene: NFKB1 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.90 NFKB1 Zornitza Stark Gene: nfkb1 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.89 NFKB2 Zornitza Stark Marked gene: NFKB2 as ready
Ciliary Dyskinesia v0.89 NFKB2 Zornitza Stark Added comment: Comment when marking as ready: Not a PCD, but can have overlapping presenting features.
Ciliary Dyskinesia v0.89 NFKB2 Zornitza Stark Gene: nfkb2 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.89 NFKB2 Zornitza Stark Classified gene: NFKB2 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.89 NFKB2 Zornitza Stark Gene: nfkb2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2898 NME8 Zornitza Stark Marked gene: NME8 as ready
Mendeliome v0.2898 NME8 Zornitza Stark Gene: nme8 has been classified as Red List (Low Evidence).
Mendeliome v0.2898 NME8 Zornitza Stark Phenotypes for gene: NME8 were changed from to Ciliary dyskinesia, primary, 6, MIM# 610852
Mendeliome v0.2897 NME8 Zornitza Stark Publications for gene: NME8 were set to
Mendeliome v0.2896 NME8 Zornitza Stark Mode of inheritance for gene: NME8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2895 NME8 Zornitza Stark Classified gene: NME8 as Red List (low evidence)
Mendeliome v0.2895 NME8 Zornitza Stark Gene: nme8 has been classified as Red List (Low Evidence).
Heterotaxy v0.46 NME8 Zornitza Stark Marked gene: NME8 as ready
Heterotaxy v0.46 NME8 Zornitza Stark Gene: nme8 has been classified as Red List (Low Evidence).
Heterotaxy v0.46 NME8 Zornitza Stark Phenotypes for gene: NME8 were changed from to Ciliary dyskinesia, primary, 6, MIM# 610852
Heterotaxy v0.45 NME8 Zornitza Stark Publications for gene: NME8 were set to
Heterotaxy v0.44 NME8 Zornitza Stark Mode of inheritance for gene: NME8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.43 NME8 Zornitza Stark Classified gene: NME8 as Red List (low evidence)
Heterotaxy v0.43 NME8 Zornitza Stark Gene: nme8 has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.88 NME8 Zornitza Stark Marked gene: NME8 as ready
Ciliary Dyskinesia v0.88 NME8 Zornitza Stark Gene: nme8 has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.88 NME8 Zornitza Stark Phenotypes for gene: NME8 were changed from to Ciliary dyskinesia, primary, 6, MIM# 610852
Ciliary Dyskinesia v0.87 NME8 Zornitza Stark Publications for gene: NME8 were set to
Ciliary Dyskinesia v0.86 NME8 Zornitza Stark Mode of inheritance for gene: NME8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.85 NME8 Zornitza Stark Classified gene: NME8 as Red List (low evidence)
Ciliary Dyskinesia v0.85 NME8 Zornitza Stark Gene: nme8 has been classified as Red List (Low Evidence).
Syndromic Retinopathy v0.66 TMEM231 Bryony Thompson Marked gene: TMEM231 as ready
Syndromic Retinopathy v0.66 TMEM231 Bryony Thompson Gene: tmem231 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.66 TMEM231 Bryony Thompson Classified gene: TMEM231 as Green List (high evidence)
Syndromic Retinopathy v0.66 TMEM231 Bryony Thompson Gene: tmem231 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.65 TMEM231 Bryony Thompson gene: TMEM231 was added
gene: TMEM231 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: TMEM231 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM231 were set to 23012439; 27449316
Phenotypes for gene: TMEM231 were set to Joubert syndrome 20 MIM#614970
Review for gene: TMEM231 was set to GREEN
Added comment: Three unrelated families reported with retinopathy as a feature of the condition.
Sources: Expert list
Mendeliome v0.2894 TFAP2A Zornitza Stark Marked gene: TFAP2A as ready
Mendeliome v0.2894 TFAP2A Zornitza Stark Gene: tfap2a has been classified as Green List (High Evidence).
Mendeliome v0.2894 TFAP2A Zornitza Stark Phenotypes for gene: TFAP2A were changed from to Branchiooculofacial syndrome, MIM 113620
Mendeliome v0.2893 TFAP2A Zornitza Stark Publications for gene: TFAP2A were set to
Mendeliome v0.2892 TFAP2A Zornitza Stark Mode of pathogenicity for gene: TFAP2A was changed from to Other
Mendeliome v0.2891 TFAP2A Zornitza Stark Mode of inheritance for gene: TFAP2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliary Dyskinesia v0.84 PIK3CD Zornitza Stark Marked gene: PIK3CD as ready
Ciliary Dyskinesia v0.84 PIK3CD Zornitza Stark Added comment: Comment when marking as ready: Include as overlapping phenotype.
Ciliary Dyskinesia v0.84 PIK3CD Zornitza Stark Gene: pik3cd has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.84 PIK3CD Zornitza Stark Classified gene: PIK3CD as Amber List (moderate evidence)
Ciliary Dyskinesia v0.84 PIK3CD Zornitza Stark Gene: pik3cd has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.83 PIK3R1 Zornitza Stark Marked gene: PIK3R1 as ready
Ciliary Dyskinesia v0.83 PIK3R1 Zornitza Stark Added comment: Comment when marking as ready: Can cause bronchiectasis with limited immunological findings, include as an overlapping phenotype on this panel.
Ciliary Dyskinesia v0.83 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.83 PIK3R1 Zornitza Stark Classified gene: PIK3R1 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.83 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.82 PIK3R1 Zornitza Stark Classified gene: PIK3R1 as Red List (low evidence)
Ciliary Dyskinesia v0.82 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Red List (Low Evidence).
Cholestasis v0.24 VIPAS39 Zornitza Stark Marked gene: VIPAS39 as ready
Cholestasis v0.24 VIPAS39 Zornitza Stark Gene: vipas39 has been classified as Green List (High Evidence).
Cholestasis v0.24 VIPAS39 Zornitza Stark Phenotypes for gene: VIPAS39 were changed from to Arthrogryposis, renal dysfunction, and cholestasis 2, MIM#613404
Cholestasis v0.23 VIPAS39 Zornitza Stark Publications for gene: VIPAS39 were set to
Cholestasis v0.22 VIPAS39 Zornitza Stark Mode of inheritance for gene: VIPAS39 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.42 DNAH6 Zornitza Stark Marked gene: DNAH6 as ready
Heterotaxy v0.42 DNAH6 Zornitza Stark Gene: dnah6 has been classified as Amber List (Moderate Evidence).
Heterotaxy v0.42 DNAH6 Zornitza Stark Classified gene: DNAH6 as Amber List (moderate evidence)
Heterotaxy v0.42 DNAH6 Zornitza Stark Gene: dnah6 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.81 DNAH6 Zornitza Stark Marked gene: DNAH6 as ready
Ciliary Dyskinesia v0.81 DNAH6 Zornitza Stark Gene: dnah6 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.81 DNAH6 Zornitza Stark Mode of inheritance for gene: DNAH6 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.80 DNAH6 Zornitza Stark Classified gene: DNAH6 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.80 DNAH6 Zornitza Stark Gene: dnah6 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.79 DNAH6 Zornitza Stark reviewed gene: DNAH6: Rating: AMBER; Mode of pathogenicity: None; Publications: 26918822; Phenotypes: Heterotaxy, male infertility; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Syndromic Retinopathy v0.64 TMEM107 Bryony Thompson Marked gene: TMEM107 as ready
Syndromic Retinopathy v0.64 TMEM107 Bryony Thompson Gene: tmem107 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.64 TMEM107 Bryony Thompson Classified gene: TMEM107 as Amber List (moderate evidence)
Syndromic Retinopathy v0.64 TMEM107 Bryony Thompson Gene: tmem107 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.63 TMEM107 Bryony Thompson gene: TMEM107 was added
gene: TMEM107 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: TMEM107 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM107 were set to 26595381
Phenotypes for gene: TMEM107 were set to Joubert syndrome 29 MIM#617562; Orofaciodigital syndrome XVI MIM#617563
Review for gene: TMEM107 was set to AMBER
Added comment: A set of twins and an unrelated case reported with retinopathy as a feature of the condition.
Sources: Expert list
Pierre Robin Sequence v0.8 BMPR1B Zornitza Stark Classified gene: BMPR1B as Amber List (moderate evidence)
Pierre Robin Sequence v0.8 BMPR1B Zornitza Stark Gene: bmpr1b has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.79 CFTR Zornitza Stark Marked gene: CFTR as ready
Ciliary Dyskinesia v0.79 CFTR Zornitza Stark Gene: cftr has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.79 CFTR Zornitza Stark Phenotypes for gene: CFTR were changed from Disseminated bronchiectasis to Cystic fibrosis; bronchiectasis
Ciliary Dyskinesia v0.78 CFTR Zornitza Stark Classified gene: CFTR as Green List (high evidence)
Ciliary Dyskinesia v0.78 CFTR Zornitza Stark Gene: cftr has been classified as Green List (High Evidence).
Cholestasis v0.21 VIPAS39 Chern Lim changed review comment from: PMID:20190753: 7 unrelated ARC patients hom/chet with protein-truncating variants. Knockdown of gene in zebrafish resulted in biliary excretion and E-cadherin defects similar to those in individuals with ARC.; to: PMID:20190753: 7 unrelated ARC patients hom/chet with protein-truncating variants or start-loss variant. Knockdown of gene in zebrafish resulted in biliary excretion and E-cadherin defects similar to those in individuals with ARC.
Ciliary Dyskinesia v0.77 CFAP54 Zornitza Stark Marked gene: CFAP54 as ready
Ciliary Dyskinesia v0.77 CFAP54 Zornitza Stark Gene: cfap54 has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.77 CFAP54 Zornitza Stark Classified gene: CFAP54 as Red List (low evidence)
Ciliary Dyskinesia v0.77 CFAP54 Zornitza Stark Gene: cfap54 has been classified as Red List (Low Evidence).
Cholestasis v0.21 VIPAS39 Chern Lim reviewed gene: VIPAS39: Rating: GREEN; Mode of pathogenicity: None; Publications: 20190753; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 2, MIM#613404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Heterotaxy v0.41 CFAP53 Zornitza Stark Marked gene: CFAP53 as ready
Heterotaxy v0.41 CFAP53 Zornitza Stark Gene: cfap53 has been classified as Green List (High Evidence).
Heterotaxy v0.41 CFAP53 Zornitza Stark Classified gene: CFAP53 as Green List (high evidence)
Heterotaxy v0.41 CFAP53 Zornitza Stark Gene: cfap53 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.73 ADGRG1 Zornitza Stark Marked gene: ADGRG1 as ready
Polymicrogyria and Schizencephaly v0.73 ADGRG1 Zornitza Stark Gene: adgrg1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.73 ADGRG1 Zornitza Stark Phenotypes for gene: ADGRG1 were changed from to Polymicrogyria, bilateral frontoparietal, MIM#606854
Polymicrogyria and Schizencephaly v0.72 ADGRG1 Zornitza Stark Publications for gene: ADGRG1 were set to
Polymicrogyria and Schizencephaly v0.71 ADGRG1 Zornitza Stark Mode of inheritance for gene: ADGRG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.62 SRD5A3 Bryony Thompson Marked gene: SRD5A3 as ready
Syndromic Retinopathy v0.62 SRD5A3 Bryony Thompson Gene: srd5a3 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.62 SRD5A3 Bryony Thompson Classified gene: SRD5A3 as Green List (high evidence)
Syndromic Retinopathy v0.62 SRD5A3 Bryony Thompson Gene: srd5a3 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.61 SRD5A3 Bryony Thompson gene: SRD5A3 was added
gene: SRD5A3 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: SRD5A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SRD5A3 were set to 31638560
Phenotypes for gene: SRD5A3 were set to Congenital disorder of glycosylation, type Iq MIM#612379
Review for gene: SRD5A3 was set to GREEN
Added comment: Retinopathy is a reported feature of the condition in >3 cases.
Sources: Expert list
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.52 SCLT1 Bryony Thompson gene: SCLT1 was added
gene: SCLT1 was added to Autosomal Recessive/X-Linked Retinitis Pigmentosa. Sources: Literature
Mode of inheritance for gene: SCLT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCLT1 were set to 30425282
Phenotypes for gene: SCLT1 were set to Nonsyndromic retinitis pigmentosa
Review for gene: SCLT1 was set to RED
Added comment: One family reported with nonsyndromic RP.
Sources: Literature
Syndromic Retinopathy v0.60 SCLT1 Bryony Thompson Marked gene: SCLT1 as ready
Syndromic Retinopathy v0.60 SCLT1 Bryony Thompson Gene: sclt1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.60 SCLT1 Bryony Thompson Classified gene: SCLT1 as Green List (high evidence)
Syndromic Retinopathy v0.60 SCLT1 Bryony Thompson Gene: sclt1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.70 ADGRG1 Zornitza Stark reviewed gene: ADGRG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16240336; Phenotypes: Polymicrogyria, bilateral frontoparietal, MIM#606854; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.59 SCLT1 Bryony Thompson gene: SCLT1 was added
gene: SCLT1 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: SCLT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCLT1 were set to 32253632; 30425282
Phenotypes for gene: SCLT1 were set to Bardet Biedl syndrome; Senior-Loken syndrome
Review for gene: SCLT1 was set to GREEN
Added comment: Three unrelated cases reported with retinal dystrophy as a feature of the condition (2 with BBS and 1 with SLS).
Sources: Expert list
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.51 SCAPER Bryony Thompson Classified gene: SCAPER as Red List (low evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.51 SCAPER Bryony Thompson Added comment: Comment on list classification: Gene is on the syndromic retinopathy panel
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.51 SCAPER Bryony Thompson Gene: scaper has been classified as Red List (Low Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.50 SCAPER Bryony Thompson Classified gene: SCAPER as Red List (low evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.50 SCAPER Bryony Thompson Gene: scaper has been classified as Red List (Low Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.49 SCAPER Bryony Thompson reviewed gene: SCAPER: Rating: RED; Mode of pathogenicity: None; Publications: 30561111; Phenotypes: Nonsyndromic retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.58 SCAPER Bryony Thompson Deleted their review
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.49 SCAPER Bryony Thompson Deleted their review
Syndromic Retinopathy v0.57 SCAPER Bryony Thompson Marked gene: SCAPER as ready
Syndromic Retinopathy v0.57 SCAPER Bryony Thompson Gene: scaper has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.57 SCAPER Bryony Thompson Classified gene: SCAPER as Green List (high evidence)
Syndromic Retinopathy v0.57 SCAPER Bryony Thompson Gene: scaper has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.56 SCAPER Bryony Thompson gene: SCAPER was added
gene: SCAPER was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: SCAPER was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCAPER were set to 28794130
Phenotypes for gene: SCAPER were set to Intellectual developmental disorder and retinitis pigmentosa MIM#618195
Syndromic Retinopathy v0.55 PISD Bryony Thompson gene: PISD was added
gene: PISD was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: PISD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PISD were set to 31263216
Phenotypes for gene: PISD were set to Liberfarb syndrome MIM#618889
Review for gene: PISD was set to RED
Added comment: Retinal degeneration is reported in two families with the same homozygous variant and an apparently common ancestor, based on haplotype analysis.
Sources: Expert list
Ciliary Dyskinesia v0.76 PIK3R1 Elena Savva gene: PIK3R1 was added
gene: PIK3R1 was added to Ciliary Dyskinesia. Sources: Expert list
Mode of inheritance for gene: PIK3R1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PIK3R1 were set to PMID: 30018075; 31111319
Phenotypes for gene: PIK3R1 were set to ?Agammaglobulinemia 7, autosomal recessive 615214; Immunodeficiency 36 616005; SHORT syndrome 269880
Mode of pathogenicity for gene: PIK3R1 was set to Other
Review for gene: PIK3R1 was set to AMBER
Added comment: PMID: 30018075/OMIM reports gain of function as a proven mechanism, where variants cause increased phosphorylation of a target protein AKT and hyperactivation of PI3K-dependent signaling pathway

PMID: 31111319 - Review of >170 patients found where respiratory tract infections are a common feature

No other phenotypes reports reminiscent of PCD
Sources: Expert list
Ciliary Dyskinesia v0.76 PIK3CD Elena Savva gene: PIK3CD was added
gene: PIK3CD was added to Ciliary Dyskinesia. Sources: Expert list
Mode of inheritance for gene: PIK3CD was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PIK3CD were set to PMID: 30018075; 31111319
Phenotypes for gene: PIK3CD were set to Immunodeficiency 14 615513
Mode of pathogenicity for gene: PIK3CD was set to Other
Review for gene: PIK3CD was set to AMBER
Added comment: PMID: 30018075/OMIM reports gain of function as a proven mechanism, where variants cause increased phosphorylation of a target protein AKT and hyperactivation of PI3K-dependent signaling pathway

PMID: 31111319 - Review of >170 patients found where respiratory tract infections are a common feature

No other phenotypes reports reminiscent of PCD
Sources: Expert list
Mendeliome v0.2890 TFAP2A Teresa Zhao reviewed gene: TFAP2A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 23578821, 21204207, 21728810, 21539471; Phenotypes: Branchiooculofacial syndrome, MIM 113620; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2890 NME8 Elena Savva reviewed gene: NME8: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 17360648; Phenotypes: Ciliary dyskinesia, primary, 6 610852; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.40 NME8 Elena Savva reviewed gene: NME8: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 17360648, 31966386; Phenotypes: Ciliary dyskinesia, primary, 6 610852; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.76 NME8 Elena Savva reviewed gene: NME8: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 17360648; Phenotypes: Ciliary dyskinesia, primary, 6 610852; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal Disorders Superpanel v0.127 Bryony Thompson Changed child panels to: Optic Atrophy; Syndromic Retinopathy; Autosomal Recessive/X-Linked Retinitis Pigmentosa; Bardet Biedl syndrome; Cone-rod Dystrophy; Macular Dystrophy/Stargardt Disease; Autosomal Dominant Retinitis Pigmentosa; Vitreoretinopathy; Achromatopsia; Usher Syndrome; Foveal Hypoplasia; Stickler Syndrome; Congenital Stationary Night Blindness
Ciliary Dyskinesia v0.76 NFKB2 Elena Savva gene: NFKB2 was added
gene: NFKB2 was added to Ciliary Dyskinesia. Sources: Expert list
Mode of inheritance for gene: NFKB2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NFKB2 were set to PMID: 30941118
Phenotypes for gene: NFKB2 were set to Immunodeficiency, common variable, 10 615577
Review for gene: NFKB2 was set to AMBER
Added comment: PMID: 30941118 - reports 11 unrelated families (15 patients), four families carry the recurring nonsense p.Arg853* mutation. Many patients report recurrent upper and lower respiratory infections (>80%), less commonly bronchiectasis (57%)

Summary: really doesnt seem like a PCD gene but some features are shared.
Sources: Expert list
Ciliary Dyskinesia v0.76 NFKB1 Elena Savva gene: NFKB1 was added
gene: NFKB1 was added to Ciliary Dyskinesia. Sources: Expert list
Mode of inheritance for gene: NFKB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NFKB1 were set to PMID: 32278790
Phenotypes for gene: NFKB1 were set to Immunodeficiency, common variable, 12 616576
Review for gene: NFKB1 was set to AMBER
Added comment: PMID: 32278790 - review of >150 patients with heterozygous mutations found ~25% had bronchiectasis, and 83% had upper respiratory infections. Incomplete penetrance (70%) with age dependent severity well reported.

OMIM describes haploinsufficiency

Summary: really doesnt seem like a PCD gene but some features are shared.
Sources: Expert list
Heterotaxy v0.40 FOXJ1 Elena Savva Deleted their comment
Heterotaxy v0.40 FOXJ1 Elena Savva edited their review of gene: FOXJ1: Added comment: PMID 31630787 - Six unrelated individuals with de novo variants in this gene. Patients have hydrocephaly, bronchiectasis and respiratory disease. Situs inversus was shown in 3/6 patients.
Electron microscopy of demonstrated cilia were unable to general fluid flow and were less frequent on cells. All reported variants were truncating mutations affecting the last exon in the protein, therefore loss of function is less likely the mechanism of pathogenicity; Changed mode of pathogenicity: Other
Heterotaxy v0.40 FOXJ1 Elena Savva gene: FOXJ1 was added
gene: FOXJ1 was added to Heterotaxy. Sources: Literature
Mode of inheritance for gene: FOXJ1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXJ1 were set to PMID 31630787
Phenotypes for gene: FOXJ1 were set to Hydrocephalus; chronic destructive airway disease; randomization of left/right body asymmetry
Review for gene: FOXJ1 was set to GREEN
Added comment: PMID 31630787 - Six unrelated individuals with de novo variants in this gene. Patients have hydrocephaly, bronchiectasis and respiratory disease. Situs inversus was shown in 3/6 patients.
Electron microscopy of demonstrated cilia were unable to general fluid flow and were less frequent on cells. All reported variants were truncating mutations affecting the last exon in the protein, therefore loss of function is less likely the mechanism of pathogenicity
Sources: Literature
Ciliary Dyskinesia v0.76 DNAH8 Elena Savva reviewed gene: DNAH8: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 31178125, 24307375; Phenotypes: Asthenozoospermia, primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.54 PEX26 Bryony Thompson Marked gene: PEX26 as ready
Syndromic Retinopathy v0.54 PEX26 Bryony Thompson Gene: pex26 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.54 PEX26 Bryony Thompson Classified gene: PEX26 as Amber List (moderate evidence)
Syndromic Retinopathy v0.54 PEX26 Bryony Thompson Gene: pex26 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.53 PEX26 Bryony Thompson gene: PEX26 was added
gene: PEX26 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: PEX26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX26 were set to 28944237
Phenotypes for gene: PEX26 were set to Peroxisome biogenesis disorder 7A (Zellweger) MIM#614872; Peroxisome biogenesis disorder 7B MIM#614873
Review for gene: PEX26 was set to AMBER
Added comment: Two cases reported with retinitis pigmentosa as a feature of the condition.
Sources: Expert list
Joubert syndrome and other neurological ciliopathies v0.79 ARL3 Zornitza Stark Marked gene: ARL3 as ready
Joubert syndrome and other neurological ciliopathies v0.79 ARL3 Zornitza Stark Gene: arl3 has been classified as Green List (High Evidence).
Heterotaxy v0.40 DNAH6 Elena Savva gene: DNAH6 was added
gene: DNAH6 was added to Heterotaxy. Sources: Literature
Mode of inheritance for gene: DNAH6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH6 were set to PMID: 26918822
Phenotypes for gene: DNAH6 were set to Heterotaxy, Azoospermia
Review for gene: DNAH6 was set to AMBER
Added comment: PMID: 26918822 - zebrafish model has disrupted motile cilia and cilia length, with some body axis defects within embryos. Transfected human cells also had defective motile cilia and cilia width.
Two patients with heterotaxy, one homozygous (missense), the other heterozygous (missense), but the heterozygous carrier has an additional known PCD mutation in DNA1.

Summary: 1 convincing patient with animal model
Sources: Literature
Ciliary Dyskinesia v0.76 DNAH6 Elena Savva gene: DNAH6 was added
gene: DNAH6 was added to Ciliary Dyskinesia. Sources: Expert list
Mode of inheritance for gene: DNAH6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DNAH6 were set to PMID: 26918822; 28206990; 31676830; 29356036
Phenotypes for gene: DNAH6 were set to Heterotaxy, Azoospermia
Review for gene: DNAH6 was set to AMBER
Added comment: PMID: 26918822 - zebrafish model has disrupted motile cilia and cilia length, with some body axis defects within embryos. Transfected human cells also had defective motile cilia and cilia width.
Two patients with heterotaxy, one homozygous (missense), the other heterozygous (missense), but the heterozygous carrier has an additional known PCD mutation in DNA1.

PMID: 28206990 - 1 homozygous family (2 siblings) with azoospermia. Authors note no recurrent respiratory infections

PMID: 31676830 - 2 chet unrelated families with spermatogenesis defects, and specifically noted to have no PCD manifestations. Phenotypes included sperm flagella defects. Patients carried missense and frameshift mutations.

PMID: 29356036 - 1 chet patient (missense) with globozoospermia and acephalic spermatozoa. Functional analysis showed near null gene expression.

Summary: Multiple patients + animal model with some features of PCD but nothing convincing
Sources: Expert list
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.49 Bryony Thompson removed gene:PHYH from the panel
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.47 Bryony Thompson removed gene:PEX7 from the panel
Pierre Robin Sequence v0.7 BMPR1B Tiong Tan Marked gene: BMPR1B as ready
Pierre Robin Sequence v0.7 BMPR1B Tiong Tan Gene: bmpr1b has been classified as Red List (Low Evidence).
Pierre Robin Sequence v0.7 BMPR1B Tiong Tan gene: BMPR1B was added
gene: BMPR1B was added to Pierre Robin Sequence. Sources: Literature
Mode of inheritance for gene: BMPR1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMPR1B were set to 28418932
Phenotypes for gene: BMPR1B were set to PRS; pectus excavatum; radioulnar synostosis
Penetrance for gene: BMPR1B were set to unknown
Review for gene: BMPR1B was set to AMBER
Added comment: Two unrelated families reported with lesions predicted to affect BMPR1B: translocation with deletion of two genes one of which was BMPR1B and a canonical splice site variant. Both genomic lesions segregated with the PRS phenotype in both families.
Sources: Literature
Ciliary Dyskinesia v0.76 CFTR Elena Savva gene: CFTR was added
gene: CFTR was added to Ciliary Dyskinesia. Sources: Expert list
Mode of inheritance for gene: CFTR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CFTR were set to Disseminated bronchiectasis
Review for gene: CFTR was set to GREEN
Added comment: CFTR-related disease features recurrent bronchial infection.

GREEN
Sources: Expert list
Vitreoretinopathy v0.9 P3H2 Bryony Thompson Classified gene: P3H2 as Green List (high evidence)
Vitreoretinopathy v0.9 P3H2 Bryony Thompson Gene: p3h2 has been classified as Green List (High Evidence).
Vitreoretinopathy v0.8 P3H2 Bryony Thompson gene: P3H2 was added
gene: P3H2 was added to Vitreoretinopathy. Sources: Expert list
Mode of inheritance for gene: P3H2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: P3H2 were set to 21885030; 24172257; 25469533
Phenotypes for gene: P3H2 were set to Myopia, high, with cataract and vitreoretinal degeneration MIM#614292
Review for gene: P3H2 was set to GREEN
Added comment: At least 3 unrelated consanguineous families reported with vitreoretinal degeneration as a feature of the condition.
Sources: Expert list
Ciliary Dyskinesia v0.76 CFAP57 Elena Savva reviewed gene: CFAP57: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 21574244; Phenotypes: Van der Woude Syndrome, Primary ciliary dyskinesia; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Syndromic Retinopathy v0.52 MMACHC Bryony Thompson Marked gene: MMACHC as ready
Syndromic Retinopathy v0.52 MMACHC Bryony Thompson Gene: mmachc has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.52 MMACHC Bryony Thompson Classified gene: MMACHC as Green List (high evidence)
Syndromic Retinopathy v0.52 MMACHC Bryony Thompson Gene: mmachc has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.51 MMACHC Bryony Thompson gene: MMACHC was added
gene: MMACHC was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: MMACHC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMACHC were set to 28481040
Phenotypes for gene: MMACHC were set to Methylmalonic aciduria and homocystinuria, cblC type MIM#277400
Review for gene: MMACHC was set to GREEN
Added comment: Maculopathy/pigmentary retinopathy reported as a feature of the condition in at least 9 cases.
Sources: Expert list
Ciliary Dyskinesia v0.76 CFAP54 Elena Savva gene: CFAP54 was added
gene: CFAP54 was added to Ciliary Dyskinesia. Sources: Literature
Mode of inheritance for gene: CFAP54 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP54 were set to PMID: 26224312
Phenotypes for gene: CFAP54 were set to Hydrocephalus, male infertility, mucus accumulation
Review for gene: CFAP54 was set to RED
Added comment: PMID: 26224312: Homozygous mice have PCD characterized by hydrocephalus, male infertility (spermatogenesis defects in flagella maturation), and mucus accumulation. Brain analysis showed mild dilatation of the lateral ventricles. Tracheal cilia beat frequency was significantly reduced. The gene was highest expressed in the testis and lungs

No patients reported as of yet
Sources: Literature
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.46 MVK Bryony Thompson Classified gene: MVK as Amber List (moderate evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.46 MVK Bryony Thompson Gene: mvk has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.45 MVK Bryony Thompson reviewed gene: MVK: Rating: AMBER; Mode of pathogenicity: None; Publications: 24084495; Phenotypes: nonsyndromic retinitis pigmentosa; Mode of inheritance: None
Syndromic Retinopathy v0.50 LRP2 Bryony Thompson Marked gene: LRP2 as ready
Syndromic Retinopathy v0.50 LRP2 Bryony Thompson Gene: lrp2 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.50 LRP2 Bryony Thompson Classified gene: LRP2 as Green List (high evidence)
Syndromic Retinopathy v0.50 LRP2 Bryony Thompson Gene: lrp2 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.49 LRP2 Bryony Thompson gene: LRP2 was added
gene: LRP2 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: LRP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRP2 were set to 17632512
Phenotypes for gene: LRP2 were set to Donnai-Barrow syndrome MIM#222448
Review for gene: LRP2 was set to GREEN
Added comment: At least 3 families reported with retinopathy as a feature of the condition.
Sources: Expert list
Heterotaxy v0.40 CFAP53 Elena Savva gene: CFAP53 was added
gene: CFAP53 was added to Heterotaxy. Sources: Literature
Mode of inheritance for gene: CFAP53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP53 were set to PMID:28621423; 22577226; 26531781
Phenotypes for gene: CFAP53 were set to Heterotaxy, visceral, 6, autosomal recessive 614779
Review for gene: CFAP53 was set to GREEN
Added comment: aka CCDC11

PMID: 22577226 - 2 siblings with a homozygous splice variant. One sibling had situs invertus syndrome and the other heterotaxy. One sibling far less severely affected. Patients had normal beating cilia, no respiratory issues

PMID: 28621423 - no new patients, performs functional studies on patient cells from ^, and frog animal models. Assays demonstrate mislocalized protein, increased cilia length in patient samples, while animal models showed CFAP53/CCDC11 is important for left-right patterning.

PMID: 26531781 - 1 patient with a homozygous PTC with situs inversus. Respiratory function was described as normal. Zebrafish model recapitulates the human phenotype.

Summary: 2 patients described with situs invertus/heterotaxy + animal models
Sources: Literature
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.45 KCNJ13 Bryony Thompson Marked gene: KCNJ13 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.45 KCNJ13 Bryony Thompson Gene: kcnj13 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.45 KCNJ13 Bryony Thompson Classified gene: KCNJ13 as Green List (high evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.45 KCNJ13 Bryony Thompson Gene: kcnj13 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.44 KCNJ13 Bryony Thompson gene: KCNJ13 was added
gene: KCNJ13 was added to Autosomal Recessive/X-Linked Retinitis Pigmentosa. Sources: Expert list
Mode of inheritance for gene: KCNJ13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KCNJ13 were set to 25921210; 21763485
Phenotypes for gene: KCNJ13 were set to Leber congenital amaurosis 16 MIM#614186
Review for gene: KCNJ13 was set to GREEN
Added comment: At least 3 families reported with homozygous variants and shRNA lentiviral mouse assays that recapitulate LCA phenotype.
Sources: Expert list
Syndromic Retinopathy v0.48 Bryony Thompson removed gene:KCNJ13 from the panel
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.43 Bryony Thompson removed gene:EXOSC2 from the panel
Syndromic Retinopathy v0.46 Bryony Thompson removed gene:COL9A1 from the panel
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.42 CLN3 Bryony Thompson reviewed gene: CLN3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32441891, 30446867, 24154662; Phenotypes: nonsyndromic retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cone-rod Dystrophy v0.13 Bryony Thompson removed gene:CEP78 from the panel
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.42 ARL6 Bryony Thompson Classified gene: ARL6 as Amber List (moderate evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.42 ARL6 Bryony Thompson Gene: arl6 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.41 ARL6 Bryony Thompson reviewed gene: ARL6: Rating: AMBER; Mode of pathogenicity: None; Publications: 28130426, 19956407; Phenotypes: Retinitis pigmentosa 55 MIM#613575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.185 ARL3 Bryony Thompson Classified gene: ARL3 as Green List (high evidence)
Ciliopathies v0.185 ARL3 Bryony Thompson Gene: arl3 has been classified as Green List (High Evidence).
Ciliopathies v0.184 ARL3 Bryony Thompson gene: ARL3 was added
gene: ARL3 was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: ARL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL3 were set to 30269812; 16565502
Phenotypes for gene: ARL3 were set to Joubert syndrome 35 MIM#618161
Review for gene: ARL3 was set to GREEN
Added comment: 4 patients from 2 unrelated consanguineous families with a phenotype resembling Joubert syndrome with homozygous missense mutations affecting the same residue (R149C, R149H), and supporting in vitro functional assays. All reported cases had rod-cone dystrophy. An Arl3 null mouse model has a ciliary disease phenotype affecting the kidney, biliary tract, pancreas, and retina.
Sources: Literature
Joubert syndrome and other neurological ciliopathies v0.79 ARL3 Bryony Thompson Classified gene: ARL3 as Green List (high evidence)
Joubert syndrome and other neurological ciliopathies v0.79 ARL3 Bryony Thompson Gene: arl3 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.78 ARL3 Bryony Thompson gene: ARL3 was added
gene: ARL3 was added to Joubert syndrome and other neurological ciliopathies. Sources: Literature
Mode of inheritance for gene: ARL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL3 were set to 30269812; 16565502
Phenotypes for gene: ARL3 were set to Joubert syndrome 35 MIM#618161
Review for gene: ARL3 was set to GREEN
Added comment: 4 patients from 2 unrelated consanguineous families with a phenotype resembling Joubert syndrome with homozygous missense mutations affecting the same residue (R149C, R149H), and supporting in vitro functional assays. An Arl3 null mouse model has a ciliary disease phenotype affecting the kidney, biliary tract, pancreas, and retina.
Sources: Literature
Mendeliome v0.2890 ARL3 Bryony Thompson Marked gene: ARL3 as ready
Mendeliome v0.2890 ARL3 Bryony Thompson Gene: arl3 has been classified as Green List (High Evidence).
Mendeliome v0.2890 ARL3 Bryony Thompson Classified gene: ARL3 as Green List (high evidence)
Mendeliome v0.2890 ARL3 Bryony Thompson Gene: arl3 has been classified as Green List (High Evidence).
Mendeliome v0.2889 ARL3 Bryony Thompson gene: ARL3 was added
gene: ARL3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARL3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ARL3 were set to 30269812; 16565502; 26964041; 30932721
Phenotypes for gene: ARL3 were set to Joubert syndrome 35 MIM#618161; Retinitis pigmentosa 83 MIM#618173
Review for gene: ARL3 was set to GREEN
Added comment: 4 patients from 2 unrelated consanguineous families with a phenotype resembling Joubert syndrome with homozygous missense mutations affecting the same residue (R149C, R149H), and supporting in vitro functional assays. All reported cases had rod-cone dystrophy. An Arl3 null mouse model has a ciliary disease phenotype affecting the kidney, biliary tract, pancreas, and retina.
Two unrelated families with retinitis pigmentosa segregating the same heterozygous missense variant (Y90C).
Sources: Expert list
Syndromic Retinopathy v0.45 ARL3 Bryony Thompson Marked gene: ARL3 as ready
Syndromic Retinopathy v0.45 ARL3 Bryony Thompson Gene: arl3 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.45 ARL3 Bryony Thompson Classified gene: ARL3 as Green List (high evidence)
Syndromic Retinopathy v0.45 ARL3 Bryony Thompson Gene: arl3 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.44 ARL3 Bryony Thompson gene: ARL3 was added
gene: ARL3 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: ARL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL3 were set to 30269812; 16565502
Phenotypes for gene: ARL3 were set to Joubert syndrome 35 MIM#618161
Review for gene: ARL3 was set to GREEN
Added comment: 4 patients from 2 unrelated consanguineous families with a phenotype resembling Joubert syndrome with homozygous missense mutations affecting the same residue (R149C, R149H), and supporting in vitro functional assays. All reported cases had rod-cone dystrophy. An Arl3 null mouse model has a ciliary disease phenotype affecting the kidney, biliary tract, pancreas, and retina.
Sources: Expert list
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.41 Bryony Thompson removed gene:ARL3 from the panel
Retinitis pigmentosa_Autosomal Dominant v0.9 ARL3 Bryony Thompson Classified gene: ARL3 as Amber List (moderate evidence)
Retinitis pigmentosa_Autosomal Dominant v0.9 ARL3 Bryony Thompson Gene: arl3 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa_Autosomal Dominant v0.8 ARL3 Bryony Thompson reviewed gene: ARL3: Rating: AMBER; Mode of pathogenicity: None; Publications: 26964041, 30932721; Phenotypes: Retinitis pigmentosa 83 MIM#618173; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.40 AHI1 Bryony Thompson Phenotypes for gene: AHI1 were changed from Joubert syndrome 17 to nonsyndromic retinitis pigmentosa; Joubert syndrome 17
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.39 AHI1 Bryony Thompson Publications for gene: AHI1 were set to
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.38 ABHD12 Bryony Thompson Phenotypes for gene: ABHD12 were changed from Polyneuropathy, Hearing Loss, Ataxia, Retinitis Pigmentosa andCataract (PHARC); Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract, 614857 to nonsyndromic retinitis pigmentosa; Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract, 614857
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.37 ABHD12 Bryony Thompson Publications for gene: ABHD12 were set to
Syndromic Retinopathy v0.43 DTHD1 Bryony Thompson gene: DTHD1 was added
gene: DTHD1 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: DTHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DTHD1 were set to 23105016
Phenotypes for gene: DTHD1 were set to Leber congenital amaurosis with muscle dystrophy
Review for gene: DTHD1 was set to RED
Added comment: Single family reported with homozygous initiation codon variant. Reduced protein expression demonstrated by Western blot.
Sources: Expert list
Syndromic Retinopathy v0.41 CTC1 Bryony Thompson Marked gene: CTC1 as ready
Syndromic Retinopathy v0.41 CTC1 Bryony Thompson Gene: ctc1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.41 CTC1 Bryony Thompson Classified gene: CTC1 as Green List (high evidence)
Syndromic Retinopathy v0.41 CTC1 Bryony Thompson Gene: ctc1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.40 CTC1 Bryony Thompson gene: CTC1 was added
gene: CTC1 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: CTC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTC1 were set to 22267198
Phenotypes for gene: CTC1 were set to Cerebroretinal microangiopathy with calcifications and cysts MIM#612199
Review for gene: CTC1 was set to GREEN
Added comment: Retinopathy is a feature of the condition. At least 10 families reported.
Sources: Expert list
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.50 EVC2 Zornitza Stark reviewed gene: EVC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ellis-van Creveld syndrome (MIM#225500); Mode of inheritance: None
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.50 EVC2 Zornitza Stark Marked gene: EVC2 as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.50 EVC2 Zornitza Stark Gene: evc2 has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.50 EVC2 Zornitza Stark Phenotypes for gene: EVC2 were changed from to Ellis-van Creveld syndrome (MIM#225500)
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.49 EVC2 Zornitza Stark Publications for gene: EVC2 were set to
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.48 EVC2 Zornitza Stark Mode of inheritance for gene: EVC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.47 ICK Zornitza Stark Marked gene: ICK as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.47 ICK Zornitza Stark Gene: ick has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.47 ICK Zornitza Stark Phenotypes for gene: ICK were changed from to Endocrine-cerebroosteodysplasia (MIM#612651)
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.46 ICK Zornitza Stark Publications for gene: ICK were set to
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.45 ICK Zornitza Stark Mode of inheritance for gene: ICK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.44 Zornitza Stark Panel name changed from Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy to Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.43 PIK3C2A Zornitza Stark Marked gene: PIK3C2A as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.43 PIK3C2A Zornitza Stark Gene: pik3c2a has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.43 PIK3C2A Zornitza Stark Classified gene: PIK3C2A as Green List (high evidence)
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.43 PIK3C2A Zornitza Stark Gene: pik3c2a has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.42 PIK3C2A Zornitza Stark gene: PIK3C2A was added
gene: PIK3C2A was added to Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy. Sources: Expert list
Mode of inheritance for gene: PIK3C2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIK3C2A were set to 31034465
Phenotypes for gene: PIK3C2A were set to Oculoskeletodental syndrome, MIM# 618440
Review for gene: PIK3C2A was set to GREEN
Added comment: Ciliary dysfunction associated with prominent skeletal abnormalities in three unrelated families.
Sources: Expert list
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.41 OFD1 Zornitza Stark Marked gene: OFD1 as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.41 OFD1 Zornitza Stark Gene: ofd1 has been classified as Amber List (Moderate Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.41 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from to Orofaciodigital syndrome I, MIM# 311200
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.40 OFD1 Zornitza Stark Mode of inheritance for gene: OFD1 was changed from Unknown to Other
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.39 OFD1 Zornitza Stark Classified gene: OFD1 as Amber List (moderate evidence)
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.39 OFD1 Zornitza Stark Gene: ofd1 has been classified as Amber List (Moderate Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.38 OFD1 Zornitza Stark reviewed gene: OFD1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Orofaciodigital syndrome I, MIM# 311200; Mode of inheritance: Other
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.38 LBR Zornitza Stark Marked gene: LBR as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.38 LBR Zornitza Stark Gene: lbr has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.38 LBR Zornitza Stark Classified gene: LBR as Green List (high evidence)
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.38 LBR Zornitza Stark Gene: lbr has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.37 LBR Zornitza Stark gene: LBR was added
gene: LBR was added to Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy. Sources: Expert list
Mode of inheritance for gene: LBR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LBR were set to 29068549
Phenotypes for gene: LBR were set to Greenberg skeletal dysplasia, MIM#215140
Review for gene: LBR was set to GREEN
Added comment: Overlap with ATD in particular.
Sources: Expert list
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.36 KIF7 Zornitza Stark Marked gene: KIF7 as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.36 KIF7 Zornitza Stark Gene: kif7 has been classified as Amber List (Moderate Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.36 KIF7 Zornitza Stark Phenotypes for gene: KIF7 were changed from to Acrocallosal syndrome, MIM# 200990; Joubert syndrome 12, MIM# 200990
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.35 KIF7 Zornitza Stark Mode of inheritance for gene: KIF7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.34 KIF7 Zornitza Stark Classified gene: KIF7 as Amber List (moderate evidence)
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.34 KIF7 Zornitza Stark Gene: kif7 has been classified as Amber List (Moderate Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.33 KIF7 Zornitza Stark reviewed gene: KIF7: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Acrocallosal syndrome, MIM# 200990, Joubert syndrome 12, MIM# 200990; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.33 KIAA0753 Zornitza Stark Marked gene: KIAA0753 as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.33 KIAA0753 Zornitza Stark Gene: kiaa0753 has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.33 KIAA0753 Zornitza Stark Classified gene: KIAA0753 as Green List (high evidence)
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.33 KIAA0753 Zornitza Stark Gene: kiaa0753 has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.32 KIAA0753 Zornitza Stark gene: KIAA0753 was added
gene: KIAA0753 was added to Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy. Sources: Expert list
Mode of inheritance for gene: KIAA0753 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0753 were set to 29138412
Phenotypes for gene: KIAA0753 were set to Short-rib skeletal dysplasia
Review for gene: KIAA0753 was set to GREEN
Added comment: Four individuals from three unrelated families reported with a predominantly skeletal ciliopathy phenotype.
Sources: Expert list
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.31 KIAA0586 Zornitza Stark Marked gene: KIAA0586 as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.31 KIAA0586 Zornitza Stark Gene: kiaa0586 has been classified as Amber List (Moderate Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.31 KIAA0586 Zornitza Stark Phenotypes for gene: KIAA0586 were changed from to Short-rib thoracic dysplasia 14 with polydactyly, MIM# 616546
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.30 KIAA0586 Zornitza Stark Publications for gene: KIAA0586 were set to
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.29 KIAA0586 Zornitza Stark Mode of inheritance for gene: KIAA0586 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.28 KIAA0586 Zornitza Stark Classified gene: KIAA0586 as Amber List (moderate evidence)
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.28 KIAA0586 Zornitza Stark Gene: kiaa0586 has been classified as Amber List (Moderate Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.27 KIAA0586 Zornitza Stark reviewed gene: KIAA0586: Rating: AMBER; Mode of pathogenicity: None; Publications: 26166481; Phenotypes: Short-rib thoracic dysplasia 14 with polydactyly, MIM# 616546; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.27 HYLS1 Zornitza Stark Marked gene: HYLS1 as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.27 HYLS1 Zornitza Stark Gene: hyls1 has been classified as Amber List (Moderate Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.27 HYLS1 Zornitza Stark Phenotypes for gene: HYLS1 were changed from to Hydrolethalus syndrome, MIM# 236680
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.26 HYLS1 Zornitza Stark Mode of inheritance for gene: HYLS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.25 HYLS1 Zornitza Stark Classified gene: HYLS1 as Amber List (moderate evidence)
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.25 HYLS1 Zornitza Stark Gene: hyls1 has been classified as Amber List (Moderate Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.24 HYLS1 Zornitza Stark reviewed gene: HYLS1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Hydrolethalus syndrome, MIM# 236680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.24 GLI3 Zornitza Stark Marked gene: GLI3 as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.24 GLI3 Zornitza Stark Gene: gli3 has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.24 GLI3 Zornitza Stark Classified gene: GLI3 as Green List (high evidence)
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.24 GLI3 Zornitza Stark Gene: gli3 has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.23 GLI3 Zornitza Stark gene: GLI3 was added
gene: GLI3 was added to Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy. Sources: Expert list
Mode of inheritance for gene: GLI3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GLI3 were set to Greig cephalopolysyndactyly syndrome, MIM# 175700; Polydactyly
Review for gene: GLI3 was set to GREEN
Added comment: Not a ciliopathy, but relatively common condition with phenotypic overlap.
Sources: Expert list
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.22 DHCR7 Zornitza Stark Marked gene: DHCR7 as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.22 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.22 DHCR7 Zornitza Stark Classified gene: DHCR7 as Green List (high evidence)
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.22 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.21 DHCR7 Zornitza Stark gene: DHCR7 was added
gene: DHCR7 was added to Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy. Sources: Expert list
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DHCR7 were set to Smith-Lemli-Opitz syndrome, MIM# 270400
Review for gene: DHCR7 was set to GREEN
Added comment: Not a ciliopathy, but relatively common condition with phenotypic overlap.
Sources: Expert list
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.20 CSPP1 Zornitza Stark Marked gene: CSPP1 as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.20 CSPP1 Zornitza Stark Gene: cspp1 has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.20 CSPP1 Zornitza Stark Phenotypes for gene: CSPP1 were changed from to Joubert syndrome 21, MIM# 615636
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.19 CSPP1 Zornitza Stark Publications for gene: CSPP1 were set to
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.18 CSPP1 Zornitza Stark Mode of inheritance for gene: CSPP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.17 CSPP1 Zornitza Stark reviewed gene: CSPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24360808; Phenotypes: Joubert syndrome 21, MIM# 615636; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2888 RARA Zornitza Stark Marked gene: RARA as ready
Mendeliome v0.2888 RARA Zornitza Stark Gene: rara has been classified as Red List (Low Evidence).
Mendeliome v0.2888 RARA Zornitza Stark Classified gene: RARA as Red List (low evidence)
Mendeliome v0.2888 RARA Zornitza Stark Gene: rara has been classified as Red List (Low Evidence).
Mendeliome v0.2887 RARA Zornitza Stark reviewed gene: RARA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.2887 ERBB2 Zornitza Stark Marked gene: ERBB2 as ready
Mendeliome v0.2887 ERBB2 Zornitza Stark Gene: erbb2 has been classified as Red List (Low Evidence).
Mendeliome v0.2887 ERBB2 Zornitza Stark Classified gene: ERBB2 as Red List (low evidence)
Mendeliome v0.2887 ERBB2 Zornitza Stark Gene: erbb2 has been classified as Red List (Low Evidence).
Mendeliome v0.2886 ERBB2 Zornitza Stark Classified gene: ERBB2 as Red List (low evidence)
Mendeliome v0.2886 ERBB2 Zornitza Stark Gene: erbb2 has been classified as Red List (Low Evidence).
Mendeliome v0.2885 ERBB2 Zornitza Stark reviewed gene: ERBB2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Callosome v0.143 ERBB2 Zornitza Stark Marked gene: ERBB2 as ready
Callosome v0.143 ERBB2 Zornitza Stark Gene: erbb2 has been classified as Red List (Low Evidence).
Callosome v0.143 ERBB2 Zornitza Stark Classified gene: ERBB2 as Red List (low evidence)
Callosome v0.143 ERBB2 Zornitza Stark Gene: erbb2 has been classified as Red List (Low Evidence).
Callosome v0.142 ERBB2 Zornitza Stark reviewed gene: ERBB2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.2885 BCR Zornitza Stark Marked gene: BCR as ready
Mendeliome v0.2885 BCR Zornitza Stark Gene: bcr has been classified as Red List (Low Evidence).
Mendeliome v0.2885 BCR Zornitza Stark Phenotypes for gene: BCR were changed from to Leukemia, acute lymphocytic, Philadelphia chromosome positive, somatic 613065; Leukemia, chronic myeloid, Philadelphia chromosome positive, somatic 608232
Mendeliome v0.2884 BCR Zornitza Stark Classified gene: BCR as Red List (low evidence)
Mendeliome v0.2884 BCR Zornitza Stark Gene: bcr has been classified as Red List (Low Evidence).
Mendeliome v0.2883 BCR Zornitza Stark reviewed gene: BCR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukemia, acute lymphocytic, Philadelphia chromosome positive, somatic 613065, Leukemia, chronic myeloid, Philadelphia chromosome positive, somatic 608232; Mode of inheritance: None
Ciliopathies v0.183 CEP19 Zornitza Stark Marked gene: CEP19 as ready
Ciliopathies v0.183 CEP19 Zornitza Stark Gene: cep19 has been classified as Red List (Low Evidence).
Ciliopathies v0.183 CEP19 Zornitza Stark gene: CEP19 was added
gene: CEP19 was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: CEP19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP19 were set to 29127258; 24268657
Phenotypes for gene: CEP19 were set to Bardet-Biedl syndorme
Review for gene: CEP19 was set to RED
Added comment: Single family with BBS phenotype reported with a homozygous predicted loss of function variant. Has been reported in another family with a morbid obesity syndrome.
Sources: Literature
Bardet Biedl syndrome v0.28 CEP19 Zornitza Stark Marked gene: CEP19 as ready
Bardet Biedl syndrome v0.28 CEP19 Zornitza Stark Gene: cep19 has been classified as Red List (Low Evidence).
Mendeliome v0.2883 CEP19 Bryony Thompson Classified gene: CEP19 as Amber List (moderate evidence)
Mendeliome v0.2883 CEP19 Bryony Thompson Gene: cep19 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2882 CEP19 Bryony Thompson gene: CEP19 was added
gene: CEP19 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CEP19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP19 were set to 29127258; 24268657
Phenotypes for gene: CEP19 were set to Morbid obesity and spermatogenic failure MIM#615703
Review for gene: CEP19 was set to AMBER
Added comment: A consanguineous Arab family with morbid obesity and infertility with a homozygous predicted null variant, and a mouse model that recapitulates the phenotype. Another homozygous variant has been identified in a consanguineous Bardet Beidl syndrome.
Sources: Literature
Bardet Biedl syndrome v0.28 CEP19 Bryony Thompson gene: CEP19 was added
gene: CEP19 was added to Bardet Biedl syndrome. Sources: Expert list
Mode of inheritance for gene: CEP19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP19 were set to 29127258; 24268657
Phenotypes for gene: CEP19 were set to Bardet Biedl syndrome
Review for gene: CEP19 was set to RED
Added comment: Single family with BBS phenotype reported with a homozygous predicted loss of function variant. Has been reported in another family with a morbid obesity syndrome.
Sources: Expert list
Mendeliome v0.2881 DALRD3 Zornitza Stark Marked gene: DALRD3 as ready
Mendeliome v0.2881 DALRD3 Zornitza Stark Gene: dalrd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2881 DALRD3 Zornitza Stark Classified gene: DALRD3 as Amber List (moderate evidence)
Mendeliome v0.2881 DALRD3 Zornitza Stark Gene: dalrd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2880 DALRD3 Zornitza Stark gene: DALRD3 was added
gene: DALRD3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DALRD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DALRD3 were set to 32427860
Phenotypes for gene: DALRD3 were set to Epileptic encephalopathy
Review for gene: DALRD3 was set to AMBER
Added comment: Two individuals reported with same homozygous nonsense variant, functional data.
Sources: Literature
Genetic Epilepsy v0.713 DALRD3 Zornitza Stark Marked gene: DALRD3 as ready
Genetic Epilepsy v0.713 DALRD3 Zornitza Stark Gene: dalrd3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.713 DALRD3 Zornitza Stark Classified gene: DALRD3 as Amber List (moderate evidence)
Genetic Epilepsy v0.713 DALRD3 Zornitza Stark Gene: dalrd3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.712 DALRD3 Zornitza Stark gene: DALRD3 was added
gene: DALRD3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: DALRD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DALRD3 were set to 32427860
Phenotypes for gene: DALRD3 were set to Epileptic encephalopathy
Review for gene: DALRD3 was set to AMBER
Added comment: Two individuals reported with same homozygous nonsense variant, functional data.
Sources: Literature
Mendeliome v0.2879 GDF3 Zornitza Stark Marked gene: GDF3 as ready
Mendeliome v0.2879 GDF3 Zornitza Stark Gene: gdf3 has been classified as Red List (Low Evidence).
Mendeliome v0.2879 GDF3 Zornitza Stark Phenotypes for gene: GDF3 were changed from to Microphthalmia with coloboma 6, MIM# 613703; Microphthalmia, isolated 7, MIM# 613704
Mendeliome v0.2878 GDF3 Zornitza Stark Publications for gene: GDF3 were set to
Mendeliome v0.2877 GDF3 Zornitza Stark Classified gene: GDF3 as Red List (low evidence)
Mendeliome v0.2877 GDF3 Zornitza Stark Gene: gdf3 has been classified as Red List (Low Evidence).
Mendeliome v0.2876 GDF3 Zornitza Stark reviewed gene: GDF3: Rating: RED; Mode of pathogenicity: None; Publications: 19864492; Phenotypes: Microphthalmia with coloboma 6 613703, Microphthalmia, isolated 7 613704; Mode of inheritance: None
Polymicrogyria and Schizencephaly v0.70 PAX6 Zornitza Stark Marked gene: PAX6 as ready
Polymicrogyria and Schizencephaly v0.70 PAX6 Zornitza Stark Gene: pax6 has been classified as Amber List (Moderate Evidence).
Polymicrogyria and Schizencephaly v0.70 PAX6 Zornitza Stark Phenotypes for gene: PAX6 were changed from to ?Coloboma of optic nerve MIM# 120430; ?Coloboma, ocular MIM# 120200; ?Morning glory disc anomaly MIM# 120430; Aniridia MIM# 106210; Anterior segment dysgenesis 5, multiple subtypes MIM# 604229; Cataract with late-onset corneal dystrophy MIM# 106210; Foveal hypoplasia 1 MIM# 136520; Keratitis MIM# 148190; Optic nerve hypoplasia MIM# 165550
Polymicrogyria and Schizencephaly v0.69 PAX6 Zornitza Stark Publications for gene: PAX6 were set to
Polymicrogyria and Schizencephaly v0.68 PAX6 Zornitza Stark Mode of inheritance for gene: PAX6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polymicrogyria and Schizencephaly v0.67 PAX6 Zornitza Stark Classified gene: PAX6 as Amber List (moderate evidence)
Polymicrogyria and Schizencephaly v0.67 PAX6 Zornitza Stark Gene: pax6 has been classified as Amber List (Moderate Evidence).
Cone-rod Dystrophy v0.11 VSX2 Zornitza Stark Marked gene: VSX2 as ready
Cone-rod Dystrophy v0.11 VSX2 Zornitza Stark Gene: vsx2 has been classified as Red List (Low Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.36 USP45 Zornitza Stark Marked gene: USP45 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.36 USP45 Zornitza Stark Gene: usp45 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.66 NHEJ1 Zornitza Stark Marked gene: NHEJ1 as ready
Polymicrogyria and Schizencephaly v0.66 NHEJ1 Zornitza Stark Gene: nhej1 has been classified as Amber List (Moderate Evidence).
Polymicrogyria and Schizencephaly v0.66 NHEJ1 Zornitza Stark Phenotypes for gene: NHEJ1 were changed from to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation (MIM# 611291)
Polymicrogyria and Schizencephaly v0.65 NHEJ1 Zornitza Stark Publications for gene: NHEJ1 were set to
Polymicrogyria and Schizencephaly v0.64 NHEJ1 Zornitza Stark Classified gene: NHEJ1 as Amber List (moderate evidence)
Polymicrogyria and Schizencephaly v0.64 NHEJ1 Zornitza Stark Gene: nhej1 has been classified as Amber List (Moderate Evidence).
Macular Dystrophy/Stargardt Disease v0.12 TEAD1 Zornitza Stark Marked gene: TEAD1 as ready
Macular Dystrophy/Stargardt Disease v0.12 TEAD1 Zornitza Stark Gene: tead1 has been classified as Amber List (Moderate Evidence).
Lissencephaly and Band Heterotopia v0.42 LAMA2 Zornitza Stark Marked gene: LAMA2 as ready
Lissencephaly and Band Heterotopia v0.42 LAMA2 Zornitza Stark Gene: lama2 has been classified as Green List (High Evidence).
Lissencephaly and Band Heterotopia v0.42 LAMA2 Zornitza Stark Phenotypes for gene: LAMA2 were changed from to LAMA2-related muscular dystrophy
Lissencephaly and Band Heterotopia v0.41 LAMA2 Zornitza Stark Publications for gene: LAMA2 were set to
Lissencephaly and Band Heterotopia v0.40 LAMA2 Zornitza Stark Mode of inheritance for gene: LAMA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2876 KRAS Zornitza Stark Marked gene: KRAS as ready
Mendeliome v0.2876 KRAS Zornitza Stark Gene: kras has been classified as Green List (High Evidence).
Mendeliome v0.2876 KRAS Zornitza Stark Phenotypes for gene: KRAS were changed from to Cardiofaciocutaneous syndrome 2 615278; Noonan syndrome 3 609942; RAS-associated autoimmune leukoproliferative disorder 614470; Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic 163200
Mendeliome v0.2875 KRAS Zornitza Stark Publications for gene: KRAS were set to
Mendeliome v0.2874 KRAS Zornitza Stark Mode of pathogenicity for gene: KRAS was changed from to Other
Mendeliome v0.2873 KRAS Zornitza Stark Mode of inheritance for gene: KRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cone-rod Dystrophy v0.11 SLC6A6 Zornitza Stark Marked gene: SLC6A6 as ready
Cone-rod Dystrophy v0.11 SLC6A6 Zornitza Stark Gene: slc6a6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2872 GAA Zornitza Stark Marked gene: GAA as ready
Mendeliome v0.2872 GAA Zornitza Stark Gene: gaa has been classified as Green List (High Evidence).
Mendeliome v0.2872 GAA Zornitza Stark Phenotypes for gene: GAA were changed from to Glycogen storage disease II, MIM# 232300
Mendeliome v0.2871 GAA Zornitza Stark Mode of inheritance for gene: GAA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2870 HEXA Zornitza Stark Marked gene: HEXA as ready
Mendeliome v0.2870 HEXA Zornitza Stark Gene: hexa has been classified as Green List (High Evidence).
Mendeliome v0.2870 HEXA Zornitza Stark Phenotypes for gene: HEXA were changed from to GM2-gangliosidosis, several forms 272800; Tay-Sachs disease 272800
Mendeliome v0.2869 HEXA Zornitza Stark Publications for gene: HEXA were set to
Mendeliome v0.2868 HEXA Zornitza Stark Mode of inheritance for gene: HEXA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.711 DHX30 Zornitza Stark Marked gene: DHX30 as ready
Genetic Epilepsy v0.711 DHX30 Zornitza Stark Gene: dhx30 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.711 DHX30 Zornitza Stark Phenotypes for gene: DHX30 were changed from to Neurodevelopmental disorder with severe motor impairment and absent language, MIM#617804
Genetic Epilepsy v0.710 DHX30 Zornitza Stark Publications for gene: DHX30 were set to
Genetic Epilepsy v0.709 DHX30 Zornitza Stark Mode of inheritance for gene: DHX30 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.708 DHX30 Zornitza Stark reviewed gene: DHX30: Rating: GREEN; Mode of pathogenicity: None; Publications: 29100085; Phenotypes: Neurodevelopmental disorder with severe motor impairment and absent language, MIM#617804; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2649 DHX30 Zornitza Stark Marked gene: DHX30 as ready
Intellectual disability syndromic and non-syndromic v0.2649 DHX30 Zornitza Stark Gene: dhx30 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2649 DHX30 Zornitza Stark Phenotypes for gene: DHX30 were changed from to Neurodevelopmental disorder with severe motor impairment and absent language, MIM#617804
Intellectual disability syndromic and non-syndromic v0.2648 DHX30 Zornitza Stark Publications for gene: DHX30 were set to
Intellectual disability syndromic and non-syndromic v0.2647 DHX30 Zornitza Stark Mode of inheritance for gene: DHX30 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2646 DHX30 Zornitza Stark reviewed gene: DHX30: Rating: GREEN; Mode of pathogenicity: None; Publications: 29100085; Phenotypes: Neurodevelopmental disorder with severe motor impairment and absent language, MIM#617804; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2867 DHX30 Zornitza Stark Marked gene: DHX30 as ready
Mendeliome v0.2867 DHX30 Zornitza Stark Added comment: Comment when marking as ready: Twelve unrelated individuals reported with de novo missense variants, some recurrent.
Mendeliome v0.2867 DHX30 Zornitza Stark Gene: dhx30 has been classified as Green List (High Evidence).
Mendeliome v0.2867 DHX30 Zornitza Stark Phenotypes for gene: DHX30 were changed from to Neurodevelopmental disorder with severe motor impairment and absent language, 617804
Mendeliome v0.2866 DHX30 Zornitza Stark Publications for gene: DHX30 were set to
Mendeliome v0.2865 DHX30 Zornitza Stark Mode of inheritance for gene: DHX30 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Foveal Hypoplasia v0.4 PAX6 Zornitza Stark Marked gene: PAX6 as ready
Foveal Hypoplasia v0.4 PAX6 Zornitza Stark Gene: pax6 has been classified as Green List (High Evidence).
Foveal Hypoplasia v0.4 SLC38A8 Zornitza Stark Marked gene: SLC38A8 as ready
Foveal Hypoplasia v0.4 SLC38A8 Zornitza Stark Gene: slc38a8 has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v0.56 FAT1 Zornitza Stark Marked gene: FAT1 as ready
Anophthalmia_Microphthalmia_Coloboma v0.56 FAT1 Zornitza Stark Gene: fat1 has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v0.56 FAT1 Zornitza Stark Classified gene: FAT1 as Green List (high evidence)
Anophthalmia_Microphthalmia_Coloboma v0.56 FAT1 Zornitza Stark Gene: fat1 has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v0.55 FAT1 Zornitza Stark gene: FAT1 was added
gene: FAT1 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Expert Review
Mode of inheritance for gene: FAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAT1 were set to 30862798; 26905694
Phenotypes for gene: FAT1 were set to facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy
Review for gene: FAT1 was set to GREEN
Added comment: 5 families reported with eye abnormalities in addition to the renal phenotype.
Sources: Expert Review
Proteinuria v0.112 FAT1 Zornitza Stark Deleted their comment
Proteinuria v0.112 FAT1 Zornitza Stark edited their review of gene: FAT1: Added comment: Another 5 families reported.; Changed rating: GREEN; Changed publications: 30862798; Changed phenotypes: facial dysmorphism, colobomatous microphthalmia, ptosis, syndactyly with or without nephropathy; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuria v0.112 FAT1 Zornitza Stark Marked gene: FAT1 as ready
Proteinuria v0.112 FAT1 Zornitza Stark Added comment: Comment when marking as ready: Five families reported.
Proteinuria v0.112 FAT1 Zornitza Stark Gene: fat1 has been classified as Green List (High Evidence).
Proteinuria v0.112 FAT1 Zornitza Stark Phenotypes for gene: FAT1 were changed from to facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy
Proteinuria v0.111 FAT1 Zornitza Stark Publications for gene: FAT1 were set to
Proteinuria v0.110 FAT1 Zornitza Stark Mode of inheritance for gene: FAT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2864 FAT1 Zornitza Stark Marked gene: FAT1 as ready
Mendeliome v0.2864 FAT1 Zornitza Stark Gene: fat1 has been classified as Green List (High Evidence).
Mendeliome v0.2864 FAT1 Zornitza Stark Phenotypes for gene: FAT1 were changed from to facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy
Mendeliome v0.2863 FAT1 Zornitza Stark Publications for gene: FAT1 were set to
Mendeliome v0.2862 FAT1 Zornitza Stark Mode of inheritance for gene: FAT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cone-rod Dystrophy v0.11 OPN1SW Zornitza Stark Marked gene: OPN1SW as ready
Cone-rod Dystrophy v0.11 OPN1SW Zornitza Stark Gene: opn1sw has been classified as Green List (High Evidence).
Retinal Disorders Superpanel v0.92 Bryony Thompson Changed child panels to: Syndromic Retinopathy; Autosomal Recessive/X-Linked Retinitis Pigmentosa; Bardet Biedl syndrome; Macular Dystrophy/Stargardt Disease; Cone-rod Dystrophy; Achromatopsia; Autosomal Dominant Retinitis Pigmentosa; Usher Syndrome; Vitreoretinopathy; Foveal Hypoplasia; Stickler Syndrome; Congenital Stationary Night Blindness
Syndromic Retinopathy v0.38 Bryony Thompson removed gene:BBIP1 from the panel
Polymicrogyria and Schizencephaly v0.63 PAX6 Lauren Akesson reviewed gene: PAX6: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 12731001; Phenotypes: ?Coloboma of optic nerve MIM# 120430, ?Coloboma, ocular MIM# 120200, ?Morning glory disc anomaly MIM# 120430, Aniridia MIM# 106210, Anterior segment dysgenesis 5, multiple subtypes MIM# 604229, Cataract with late-onset corneal dystrophy MIM# 106210, Foveal hypoplasia 1 MIM# 136520, Keratitis MIM# 148190, Optic nerve hypoplasia MIM# 165550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cone-rod Dystrophy v0.11 VSX2 Bryony Thompson gene: VSX2 was added
gene: VSX2 was added to Cone-rod Dystrophy. Sources: Expert list
Mode of inheritance for gene: VSX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VSX2 were set to 24001013
Phenotypes for gene: VSX2 were set to smooth irides; lens subluxation; cone-rod dysfunction; high myopia
Review for gene: VSX2 was set to RED
Added comment: Single consanguineous case reported with cone-rod dysfunction as a feature of a retinal phenotype.
Sources: Expert list
Syndromic Retinopathy v0.37 VPS13B Bryony Thompson Marked gene: VPS13B as ready
Syndromic Retinopathy v0.37 VPS13B Bryony Thompson Gene: vps13b has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.37 VPS13B Bryony Thompson Classified gene: VPS13B as Green List (high evidence)
Syndromic Retinopathy v0.37 VPS13B Bryony Thompson Gene: vps13b has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.36 VPS13B Bryony Thompson gene: VPS13B was added
gene: VPS13B was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: VPS13B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS13B were set to 31580008; 24334764
Phenotypes for gene: VPS13B were set to Cohen syndrome MIM#216550
Review for gene: VPS13B was set to GREEN
Added comment: Retinopathy is a common feature of the condition. >10 cases reported.
Sources: Expert list
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.35 USP45 Bryony Thompson Classified gene: USP45 as Green List (high evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.35 USP45 Bryony Thompson Gene: usp45 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.34 USP45 Bryony Thompson gene: USP45 was added
gene: USP45 was added to Autosomal Recessive/X-Linked Retinitis Pigmentosa. Sources: Literature
Mode of inheritance for gene: USP45 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP45 were set to 30573563
Phenotypes for gene: USP45 were set to Lebers congenital amaurosis
Syndromic Retinopathy v0.34 TUBB4B Bryony Thompson Marked gene: TUBB4B as ready
Syndromic Retinopathy v0.34 TUBB4B Bryony Thompson Gene: tubb4b has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.34 TUBB4B Bryony Thompson Classified gene: TUBB4B as Green List (high evidence)
Syndromic Retinopathy v0.34 TUBB4B Bryony Thompson Gene: tubb4b has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.33 TUBB4B Bryony Thompson gene: TUBB4B was added
gene: TUBB4B was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: TUBB4B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB4B were set to 29198720
Phenotypes for gene: TUBB4B were set to Leber congenital amaurosis with early-onset deafness MIM#617879
Review for gene: TUBB4B was set to GREEN
Added comment: At least 5 affected individuals from 4 families with Leber congenital amaurosis and early-onset deafness with heterozygosity for 2 missense (R391H, R391C). Functional analysis demonstrated that the mutations have a significant dampening impact on microtubular growth.
Sources: Expert list
Polymicrogyria and Schizencephaly v0.63 NHEJ1 Lauren Akesson reviewed gene: NHEJ1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 17191205; Phenotypes: Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation (MIM# 611291); Mode of inheritance: Unknown
Syndromic Retinopathy v0.32 TRAF3IP1 Bryony Thompson Marked gene: TRAF3IP1 as ready
Syndromic Retinopathy v0.32 TRAF3IP1 Bryony Thompson Gene: traf3ip1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.32 TRAF3IP1 Bryony Thompson Classified gene: TRAF3IP1 as Green List (high evidence)
Syndromic Retinopathy v0.32 TRAF3IP1 Bryony Thompson Gene: traf3ip1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.31 TRAF3IP1 Bryony Thompson gene: TRAF3IP1 was added
gene: TRAF3IP1 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: TRAF3IP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAF3IP1 were set to 26487268
Phenotypes for gene: TRAF3IP1 were set to Senior-Loken syndrome 9 MIM#616629
Review for gene: TRAF3IP1 was set to GREEN
Added comment: At least 5 families reported with retinal degeneration as a feature of the condition and a zebrafish model with retinal degeneration.
Sources: Expert list
Anophthalmia_Microphthalmia_Coloboma v0.54 TMEM98 Bryony Thompson Marked gene: TMEM98 as ready
Anophthalmia_Microphthalmia_Coloboma v0.54 TMEM98 Bryony Thompson Gene: tmem98 has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v0.54 TMEM98 Bryony Thompson Classified gene: TMEM98 as Green List (high evidence)
Anophthalmia_Microphthalmia_Coloboma v0.54 TMEM98 Bryony Thompson Gene: tmem98 has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v0.53 TMEM98 Bryony Thompson gene: TMEM98 was added
gene: TMEM98 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Expert list
Mode of inheritance for gene: TMEM98 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM98 were set to 24852644; 26392740
Phenotypes for gene: TMEM98 were set to Nanophthalmos 4 MIM#615972
Review for gene: TMEM98 was set to GREEN
Added comment: At least three large multi-generational unrelated families reported to segregate heterozygous variants. Nanophthalmos is a rare form of microphthalmia.
Sources: Expert list
Macular Dystrophy/Stargardt Disease v0.12 TEAD1 Bryony Thompson Classified gene: TEAD1 as Amber List (moderate evidence)
Macular Dystrophy/Stargardt Disease v0.12 TEAD1 Bryony Thompson Gene: tead1 has been classified as Amber List (Moderate Evidence).
Macular Dystrophy/Stargardt Disease v0.11 TEAD1 Bryony Thompson gene: TEAD1 was added
gene: TEAD1 was added to Macular Dystrophy/Stargardt Disease. Sources: Expert list
Mode of inheritance for gene: TEAD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TEAD1 were set to 15016762; 17689488; 30903741; 26091538
Phenotypes for gene: TEAD1 were set to Sveinsson chorioretinal atrophy MIM#108985
Review for gene: TEAD1 was set to AMBER
Added comment: Heterozygous missense variant identified in a large Icelandic pedigree and some supporting functional assays. Same missense reported in another family with a clinical diagnosis of circumpapillary dysgenesis of the pigment epithelium (described as a form of macular degeneration). A de novo nonsense variant has also been reported in a case with Aicardi syndrome with infantile spasms, agenesis of the corpus callosum, and chorioretinal lacunae.
Sources: Expert list
Lissencephaly and Band Heterotopia v0.39 LAMA2 Lauren Akesson reviewed gene: LAMA2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20207543, 18406646; Phenotypes: LAMA2-related muscular dystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2861 KRAS Elena Savva reviewed gene: KRAS: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 23059812, 17056636; Phenotypes: Arteriovenous malformation of the brain, somatic 108010, Bladder cancer, somatic 109800, Breast cancer, somatic 114480, Cardiofaciocutaneous syndrome 2 615278, Gastric cancer, somatic 137215, Leukemia, acute myeloid 601626, . Lung cancer, somatic 211980, Noonan syndrome 3 609942, Pancreatic carcinoma, somatic 260350, RAS-associated autoimmune leukoproliferative disorder 614470, Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic 163200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Cone-rod Dystrophy v0.9 SLC6A6 Bryony Thompson Classified gene: SLC6A6 as Amber List (moderate evidence)
Cone-rod Dystrophy v0.9 SLC6A6 Bryony Thompson Gene: slc6a6 has been classified as Amber List (Moderate Evidence).
Cone-rod Dystrophy v0.8 SLC6A6 Bryony Thompson gene: SLC6A6 was added
gene: SLC6A6 was added to Cone-rod Dystrophy. Sources: Literature
Mode of inheritance for gene: SLC6A6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC6A6 were set to 31345061; 31903486; 29886034
Phenotypes for gene: SLC6A6 were set to Cone-rod retinopathy; cardiomyopathy
Mendeliome v0.2861 GAA Elena Savva reviewed gene: GAA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glycogen storage disease II 232300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Foveal Hypoplasia v0.4 PAX6 Bryony Thompson reviewed gene: PAX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 15629294, 9931324, 31861090; Phenotypes: Foveal hypoplasia 1 MIM#136520; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2861 HEXA Elena Savva reviewed gene: HEXA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31388111; Phenotypes: [Hex A pseudodeficiency] 272800, GM2-gangliosidosis, several forms 272800, Tay-Sachs disease 272800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2861 DHX30 Elena Savva reviewed gene: DHX30: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29100085; Phenotypes: Neurodevelopmental disorder with severe motor impairment and absent language, 617804; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Foveal Hypoplasia v0.4 PAX6 Bryony Thompson Classified gene: PAX6 as Green List (high evidence)
Foveal Hypoplasia v0.4 PAX6 Bryony Thompson Gene: pax6 has been classified as Green List (High Evidence).
Foveal Hypoplasia v0.3 PAX6 Bryony Thompson gene: PAX6 was added
gene: PAX6 was added to Foveal Hypoplasia. Sources: Expert list
Mode of inheritance for gene: PAX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PAX6 were set to Foveal hypoplasia 1 MIM#136520
Foveal Hypoplasia v0.2 SLC38A8 Bryony Thompson Classified gene: SLC38A8 as Green List (high evidence)
Foveal Hypoplasia v0.2 SLC38A8 Bryony Thompson Gene: slc38a8 has been classified as Green List (High Evidence).
Retinal Disorders Superpanel v0.70 Bryony Thompson Changed child panels to: Autosomal Recessive/X-Linked Retinitis Pigmentosa; Syndromic Retinopathy; Macular Dystrophy/Stargardt Disease; Achromatopsia; Autosomal Dominant Retinitis Pigmentosa; Cone-rod Dystrophy; Usher Syndrome; Vitreoretinopathy; Stickler Syndrome; Congenital Stationary Night Blindness; Foveal Hypoplasia
Foveal Hypoplasia v0.1 SLC38A8 Bryony Thompson gene: SLC38A8 was added
gene: SLC38A8 was added to Foveal Hypoplasia. Sources: Expert list
Mode of inheritance for gene: SLC38A8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC38A8 were set to 24045842; 24290379
Phenotypes for gene: SLC38A8 were set to Foveal hypoplasia 2, with or without optic nerve misrouting and/or anterior segment dysgenesis MIM#609218
Review for gene: SLC38A8 was set to GREEN
Added comment: At least 10 families reported with foveal hypoplasia as the main feature of the condition.
Sources: Expert list
Foveal Hypoplasia v0.0 Bryony Thompson Added Panel Foveal Hypoplasia
Set panel types to: Royal Melbourne Hospital; Rare Disease
Mendeliome v0.2861 FAT1 Ee Ming Wong changed review comment from: - 5 consanguineous families with homozygous frameshift mutations in FAN1
- FAN1 KO mice had microphthalmia, with fully penetrant coloboma which was not observed in heterozygous mice
- in human retinal pigment epithelium (RPE) cells, FAN1 knockdown resulted in compromised early cell-cell junction integrity and filament organisation; to: - 5 consanguineous families with homozygous frameshift mutations in FAN1
- FAN1 KO mice had microphthalmia, with fully penetrant coloboma which was not observed in heterozygous mice
- in human retinal pigment epithelium (RPE) cells, FAN1 knockdown resulted in compromised early cell-cell junction integrity and filament organisation
Proteinuria v0.109 FAT1 Ee Ming Wong reviewed gene: FAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26905694; Phenotypes: SRNS, tubular ectasia, haematuria, facultative neurological involvement; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Cone-rod Dystrophy v0.7 RIMS1 Bryony Thompson Marked gene: RIMS1 as ready
Cone-rod Dystrophy v0.7 RIMS1 Bryony Thompson Gene: rims1 has been classified as Red List (Low Evidence).
Cone-rod Dystrophy v0.7 RIMS1 Bryony Thompson Classified gene: RIMS1 as Red List (low evidence)
Cone-rod Dystrophy v0.7 RIMS1 Bryony Thompson Gene: rims1 has been classified as Red List (Low Evidence).
Mendeliome v0.2861 PITPNM3 Bryony Thompson Marked gene: PITPNM3 as ready
Mendeliome v0.2861 PITPNM3 Bryony Thompson Gene: pitpnm3 has been classified as Red List (Low Evidence).
Mendeliome v0.2861 PITPNM3 Bryony Thompson Classified gene: PITPNM3 as Red List (low evidence)
Mendeliome v0.2861 PITPNM3 Bryony Thompson Gene: pitpnm3 has been classified as Red List (Low Evidence).
Mendeliome v0.2860 PITPNM3 Bryony Thompson reviewed gene: PITPNM3: Rating: RED; Mode of pathogenicity: None; Publications: 17377520, 22405330, 20590364; Phenotypes: Cone-rod dystrophy 5 MIM#600977; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cone-rod Dystrophy v0.5 PITPNM3 Bryony Thompson Classified gene: PITPNM3 as Red List (low evidence)
Cone-rod Dystrophy v0.5 PITPNM3 Bryony Thompson Added comment: Comment on list classification: No convincing evidence and no recent reports
Cone-rod Dystrophy v0.5 PITPNM3 Bryony Thompson Gene: pitpnm3 has been classified as Red List (Low Evidence).
Cone-rod Dystrophy v0.4 PITPNM3 Bryony Thompson edited their review of gene: PITPNM3: Changed publications: 17377520, 22405330, 20590364
Cone-rod Dystrophy v0.4 PITPNM3 Bryony Thompson changed review comment from: Only a single missense (p.Gln626His) identified in 2 Swedish families. Macular atrophy is feature of the cone-rod dystrophy in these families. The allele frequency of this variant in the European (non-finnish) population is 0.3%, which is common for a dominant rare disease. No functional assays have been conducted.; to: Single missense (p.Gln626His) identified in 2 Swedish families and two British macular dystrophy cases. The allele frequency of this variant in the European (non-finnish) population is 0.3%, which is common for a dominant rare disease. Three other variants reported in isolated cases. No functional assays have been conducted.
Achromatopsia v0.9 RGS9BP Bryony Thompson Marked gene: RGS9BP as ready
Achromatopsia v0.9 RGS9BP Bryony Thompson Gene: rgs9bp has been classified as Green List (High Evidence).
Achromatopsia v0.9 RGS9BP Bryony Thompson Classified gene: RGS9BP as Green List (high evidence)
Achromatopsia v0.9 RGS9BP Bryony Thompson Gene: rgs9bp has been classified as Green List (High Evidence).
Achromatopsia v0.8 RGS9BP Bryony Thompson gene: RGS9BP was added
gene: RGS9BP was added to Achromatopsia. Sources: Expert list
Mode of inheritance for gene: RGS9BP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS9BP were set to 14702087; 19818506
Phenotypes for gene: RGS9BP were set to Bradyopsia MIM#608415
Review for gene: RGS9BP was set to GREEN
Added comment: At least 3 families reported with homozygous variants
Sources: Expert list
Mendeliome v0.2860 FAT1 Ee Ming Wong reviewed gene: FAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30862798; Phenotypes: facial dysmorphism, colobomatous microphthalmia, ptosis, syndactyly with or without nephropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Achromatopsia v0.7 RGS9 Bryony Thompson Marked gene: RGS9 as ready
Achromatopsia v0.7 RGS9 Bryony Thompson Gene: rgs9 has been classified as Green List (High Evidence).
Achromatopsia v0.7 RGS9 Bryony Thompson Classified gene: RGS9 as Green List (high evidence)
Achromatopsia v0.7 RGS9 Bryony Thompson Gene: rgs9 has been classified as Green List (High Evidence).
Achromatopsia v0.6 RGS9 Bryony Thompson gene: RGS9 was added
gene: RGS9 was added to Achromatopsia. Sources: Expert list
Mode of inheritance for gene: RGS9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS9 were set to 14702087; 10676965; 29107794
Phenotypes for gene: RGS9 were set to Bradyopsia MIM#608415
Review for gene: RGS9 was set to GREEN
Added comment: At least 7 families reported with homozygous variants and a supporting null mouse model.
Sources: Expert list
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.33 RCBTB1 Bryony Thompson Marked gene: RCBTB1 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.33 RCBTB1 Bryony Thompson Gene: rcbtb1 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.33 RCBTB1 Bryony Thompson Classified gene: RCBTB1 as Green List (high evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.33 RCBTB1 Bryony Thompson Gene: rcbtb1 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.32 RCBTB1 Bryony Thompson gene: RCBTB1 was added
gene: RCBTB1 was added to Autosomal Recessive/X-Linked Retinitis Pigmentosa. Sources: Expert list
Mode of inheritance for gene: RCBTB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RCBTB1 were set to 27486781
Phenotypes for gene: RCBTB1 were set to Retinal dystrophy with or without extraocular anomalies MIM#617175
Review for gene: RCBTB1 was set to GREEN
Added comment: Six families with retinal dystrophy with or without extraocular anomalies with homozygous missense variants. Ocular phenotypes ranged from typical RP starting in the second decade to chorioretinal dystrophy with a later age of onset.
Sources: Expert list
Anophthalmia_Microphthalmia_Coloboma v0.52 RBP4 Bryony Thompson Classified gene: RBP4 as Green List (high evidence)
Anophthalmia_Microphthalmia_Coloboma v0.52 RBP4 Bryony Thompson Gene: rbp4 has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v0.51 RBP4 Bryony Thompson gene: RBP4 was added
gene: RBP4 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Literature
Mode of inheritance for gene: RBP4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RBP4 were set to 25910211; 29178648
Phenotypes for gene: RBP4 were set to Microphthalmia, isolated, with coloboma 10 MIM#616428
Review for gene: RBP4 was set to GREEN
Added comment: At least 3 unrelated microphthalmia, anophthalmia and coloboma families and supporting functional assays. Study established an uncharacterized mode of maternal inheritance, distinct from imprinting and oocyte-derived mRNA.
Sources: Literature
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.31 RBP4 Bryony Thompson Marked gene: RBP4 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.31 RBP4 Bryony Thompson Gene: rbp4 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.31 RBP4 Bryony Thompson Classified gene: RBP4 as Green List (high evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.31 RBP4 Bryony Thompson Gene: rbp4 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.30 RBP4 Bryony Thompson gene: RBP4 was added
gene: RBP4 was added to Autosomal Recessive/X-Linked Retinitis Pigmentosa. Sources: Expert list
Mode of inheritance for gene: RBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBP4 were set to 23189188; 9888420; 32323592
Phenotypes for gene: RBP4 were set to Retinal dystrophy, iris coloboma, and comedogenic acne syndrome MIM#615147
Review for gene: RBP4 was set to GREEN
Added comment: At least three families reported with arRP
Sources: Expert list
Cone-rod Dystrophy v0.3 OPN1SW Bryony Thompson Classified gene: OPN1SW as Green List (high evidence)
Cone-rod Dystrophy v0.3 OPN1SW Bryony Thompson Gene: opn1sw has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.2 OPN1SW Bryony Thompson gene: OPN1SW was added
gene: OPN1SW was added to Cone-rod Dystrophy. Sources: Expert list
Mode of inheritance for gene: OPN1SW was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OPN1SW were set to 22065927; 1531728
Phenotypes for gene: OPN1SW were set to Colorblindness, tritan MIM#190900
Review for gene: OPN1SW was set to GREEN
Added comment: Has been included on this panel, so that it is with the other cone-specific colour blindness genes. At least 6 missense variants associated with tritanopia.
Sources: Expert list
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.29 NMNAT1 Bryony Thompson Marked gene: NMNAT1 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.29 NMNAT1 Bryony Thompson Gene: nmnat1 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.29 NMNAT1 Bryony Thompson Classified gene: NMNAT1 as Green List (high evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.29 NMNAT1 Bryony Thompson Gene: nmnat1 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.28 NMNAT1 Bryony Thompson gene: NMNAT1 was added
gene: NMNAT1 was added to Autosomal Recessive/X-Linked Retinitis Pigmentosa. Sources: Expert list
Mode of inheritance for gene: NMNAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NMNAT1 were set to 22842230; 17132048
Phenotypes for gene: NMNAT1 were set to Leber congenital amaurosis 9 MIM#608553
Review for gene: NMNAT1 was set to GREEN
Added comment: At least 8 families with biallelic variants and a supporting drosophila model with retinal degeneration.
Sources: Expert list
Mendeliome v0.2860 JARID2 Zornitza Stark Marked gene: JARID2 as ready
Mendeliome v0.2860 JARID2 Zornitza Stark Gene: jarid2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2860 JARID2 Zornitza Stark Classified gene: JARID2 as Amber List (moderate evidence)
Mendeliome v0.2860 JARID2 Zornitza Stark Gene: jarid2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2859 JARID2 Zornitza Stark gene: JARID2 was added
gene: JARID2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: JARID2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JARID2 were set to 23294540
Phenotypes for gene: JARID2 were set to Intellectual disability
Review for gene: JARID2 was set to AMBER
Added comment: Emerging evidence that haploinsufficiency causes neurodevelopmental phenotypes, mostly based on CNV data to date.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2646 JARID2 Zornitza Stark Marked gene: JARID2 as ready
Intellectual disability syndromic and non-syndromic v0.2646 JARID2 Zornitza Stark Gene: jarid2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2646 JARID2 Zornitza Stark Classified gene: JARID2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2646 JARID2 Zornitza Stark Gene: jarid2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2645 JARID2 Zornitza Stark gene: JARID2 was added
gene: JARID2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: JARID2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JARID2 were set to 23294540
Phenotypes for gene: JARID2 were set to Intellectual disability
Review for gene: JARID2 was set to AMBER
Added comment: Emerging evidence, mostly based on CNV data to date.
Sources: Expert Review
Incidentalome v0.26 ITM2B Bryony Thompson Classified gene: ITM2B as Green List (high evidence)
Incidentalome v0.26 ITM2B Bryony Thompson Gene: itm2b has been classified as Green List (High Evidence).
Incidentalome v0.25 ITM2B Bryony Thompson gene: ITM2B was added
gene: ITM2B was added to Incidentalome. Sources: Expert list
Mode of inheritance for gene: ITM2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ITM2B were set to Dementia, familial British MIM#176500; Dementia, familial Danish MIM#117300
Mendeliome v0.2858 Bryony Thompson removed gene:ITM2B from the panel
Syndromic Retinopathy v0.30 MSTO1 Bryony Thompson Marked gene: MSTO1 as ready
Syndromic Retinopathy v0.30 MSTO1 Bryony Thompson Gene: msto1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.30 MSTO1 Bryony Thompson Classified gene: MSTO1 as Green List (high evidence)
Syndromic Retinopathy v0.30 MSTO1 Bryony Thompson Gene: msto1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.29 MSTO1 Bryony Thompson gene: MSTO1 was added
gene: MSTO1 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: MSTO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MSTO1 were set to 29339779; 28544275
Phenotypes for gene: MSTO1 were set to Myopathy, mitochondrial, and ataxia MIM#617675
Review for gene: MSTO1 was set to GREEN
Added comment: Pigmentary retinopathy reported as a feature of the condition in at least 3 unrelated cases with biallelic variants.
Sources: Expert list
Congenital Stationary Night Blindness v0.2 ITM2B Bryony Thompson Marked gene: ITM2B as ready
Congenital Stationary Night Blindness v0.2 ITM2B Bryony Thompson Gene: itm2b has been classified as Red List (Low Evidence).
Congenital Stationary Night Blindness v0.2 ITM2B Bryony Thompson gene: ITM2B was added
gene: ITM2B was added to Congenital Stationary Night Blindness. Sources: Expert list
Mode of inheritance for gene: ITM2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ITM2B were set to 24026677
Phenotypes for gene: ITM2B were set to ?Retinal dystrophy with inner retinal dysfunction and ganglion cell abnormalities MIM#616079
Review for gene: ITM2B was set to RED
Added comment: Single family reported with an unusual retinal dystrophy phenotype (most similar to CSNB), segregating a heterozygous missense variant. Minimal functional evidence assessing protein expression and localisation in different tissues.
Sources: Expert list
Syndromic Retinopathy v0.28 HACE1 Bryony Thompson Marked gene: HACE1 as ready
Syndromic Retinopathy v0.28 HACE1 Bryony Thompson Gene: hace1 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.28 HACE1 Bryony Thompson Classified gene: HACE1 as Amber List (moderate evidence)
Syndromic Retinopathy v0.28 HACE1 Bryony Thompson Gene: hace1 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.27 HACE1 Bryony Thompson gene: HACE1 was added
gene: HACE1 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: HACE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HACE1 were set to 26424145
Phenotypes for gene: HACE1 were set to Spastic paraplegia and psychomotor retardation with or without seizures MIM#616756
Review for gene: HACE1 was set to AMBER
Added comment: Retinal dystrophy reported as a feature of the condition in two families.
Sources: Expert list
Achromatopsia v0.4 GNAT2 Bryony Thompson Marked gene: GNAT2 as ready
Achromatopsia v0.4 GNAT2 Bryony Thompson Gene: gnat2 has been classified as Green List (High Evidence).
Achromatopsia v0.4 GNAT2 Bryony Thompson Classified gene: GNAT2 as Green List (high evidence)
Achromatopsia v0.4 GNAT2 Bryony Thompson Gene: gnat2 has been classified as Green List (High Evidence).
Achromatopsia v0.3 GNAT2 Bryony Thompson gene: GNAT2 was added
gene: GNAT2 was added to Achromatopsia. Sources: Expert list
Mode of inheritance for gene: GNAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNAT2 were set to 32203983; 17251445
Phenotypes for gene: GNAT2 were set to Achromatopsia 4 MIM#613856
Review for gene: GNAT2 was set to GREEN
Added comment: Nine cases from four unrelated consanguineous families and a supporting zebrafish model.
Sources: Expert list
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.26 GDF6 Bryony Thompson Marked gene: GDF6 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.26 GDF6 Bryony Thompson Gene: gdf6 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.26 GDF6 Bryony Thompson Classified gene: GDF6 as Amber List (moderate evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.26 GDF6 Bryony Thompson Gene: gdf6 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.25 GDF6 Bryony Thompson gene: GDF6 was added
gene: GDF6 was added to Autosomal Recessive/X-Linked Retinitis Pigmentosa. Sources: Expert list
Mode of inheritance for gene: GDF6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GDF6 were set to 23307924
Phenotypes for gene: GDF6 were set to Leber congenital amaurosis 17 MIM#615360
Review for gene: GDF6 was set to AMBER
Added comment: One compound heterozygote and three cases with a single heterozygous variant where unaffected parent carrier status and allele frequency of variants in gnomAD suggest presence of a second unidentified allele. Supporting in vitro functional assays and retinal apoptosis is observed in both murine and zebrafish mutant models, a characteristic feature of human retinal dystrophies.
Sources: Expert list
Syndromic Retinopathy v0.26 ADIPOR1 Zornitza Stark Marked gene: ADIPOR1 as ready
Syndromic Retinopathy v0.26 ADIPOR1 Zornitza Stark Gene: adipor1 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.26 ADIPOR1 Zornitza Stark Publications for gene: ADIPOR1 were set to
Syndromic Retinopathy v0.25 ADIPOR1 Zornitza Stark Classified gene: ADIPOR1 as Amber List (moderate evidence)
Syndromic Retinopathy v0.25 ADIPOR1 Zornitza Stark Gene: adipor1 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.24 ADIPOR1 Zornitza Stark changed review comment from: Not syndromic.; to: ID and obesity in addition to RP reported with bi-allelic disease.
Syndromic Retinopathy v0.24 ADIPOR1 Zornitza Stark edited their review of gene: ADIPOR1: Changed rating: AMBER
Syndromic Retinopathy v0.24 ADIPOR1 Zornitza Stark reviewed gene: ADIPOR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.2857 ADIPOR1 Zornitza Stark Marked gene: ADIPOR1 as ready
Mendeliome v0.2857 ADIPOR1 Zornitza Stark Gene: adipor1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2857 ADIPOR1 Zornitza Stark Phenotypes for gene: ADIPOR1 were changed from to Retinitis pigmentosa
Mendeliome v0.2856 ADIPOR1 Zornitza Stark Publications for gene: ADIPOR1 were set to
Mendeliome v0.2855 ADIPOR1 Zornitza Stark Mode of inheritance for gene: ADIPOR1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2854 ADIPOR1 Zornitza Stark Classified gene: ADIPOR1 as Amber List (moderate evidence)
Mendeliome v0.2854 ADIPOR1 Zornitza Stark Gene: adipor1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2853 ADIPOR1 Zornitza Stark reviewed gene: ADIPOR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27655171, 26662040; Phenotypes: Retinitis pigmentosa; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2853 TRIP12 Zornitza Stark commented on gene: TRIP12: At least 10 unrelated patients reported with ID with or without autism (PMIDs: 27848077, 28251352).
Autism v0.96 TRIP12 Zornitza Stark Marked gene: TRIP12 as ready
Autism v0.96 TRIP12 Zornitza Stark Gene: trip12 has been classified as Green List (High Evidence).
Autism v0.96 TRIP12 Zornitza Stark Phenotypes for gene: TRIP12 were changed from to Mental retardation autosomal dominant 49, Clark-Baraitser Syndrome, MIM#617752
Autism v0.95 TRIP12 Zornitza Stark Mode of inheritance for gene: TRIP12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.94 TRIP12 Zornitza Stark reviewed gene: TRIP12: Rating: GREEN; Mode of pathogenicity: None; Publications: 27848077, 28251352; Phenotypes: Mental retardation autosomal dominant 49, Clark-Baraitser Syndrome, MIM#617752; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2853 TRIP12 Zornitza Stark Marked gene: TRIP12 as ready
Mendeliome v0.2853 TRIP12 Zornitza Stark Gene: trip12 has been classified as Green List (High Evidence).
Mendeliome v0.2853 TRIP12 Zornitza Stark Phenotypes for gene: TRIP12 were changed from to Mental retardation autosomal dominant 49, Clark-Baraitser Syndrome, MIM#617752
Mendeliome v0.2852 TRIP12 Zornitza Stark Publications for gene: TRIP12 were set to
Mendeliome v0.2851 TRIP12 Zornitza Stark Mode of inheritance for gene: TRIP12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2850 TRIP12 Zornitza Stark reviewed gene: TRIP12: Rating: GREEN; Mode of pathogenicity: None; Publications: 27848077, 28251352; Phenotypes: Mental retardation autosomal dominant 49, Clark-Baraitser Syndrome, MIM#617752; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2644 TRIP12 Zornitza Stark Marked gene: TRIP12 as ready
Intellectual disability syndromic and non-syndromic v0.2644 TRIP12 Zornitza Stark Gene: trip12 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2644 TRIP12 Zornitza Stark Phenotypes for gene: TRIP12 were changed from to Mental retardation autosomal dominant 49, Clark-Baraitser Syndrome, MIM#617752
Intellectual disability syndromic and non-syndromic v0.2643 TRIP12 Zornitza Stark Publications for gene: TRIP12 were set to 27848077; 28251352
Intellectual disability syndromic and non-syndromic v0.2643 TRIP12 Zornitza Stark Publications for gene: TRIP12 were set to
Intellectual disability syndromic and non-syndromic v0.2642 TRIP12 Zornitza Stark Mode of inheritance for gene: TRIP12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2641 TRIP12 Chern Lim reviewed gene: TRIP12: Rating: GREEN; Mode of pathogenicity: None; Publications: 27848077, 28251352; Phenotypes: Mental retardation autosomal dominant 49, Clark-Baraitser Syndrome, MIM#617752; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Syndromic Retinopathy v0.24 ERCC8 Bryony Thompson Marked gene: ERCC8 as ready
Syndromic Retinopathy v0.24 ERCC8 Bryony Thompson Gene: ercc8 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.24 ERCC8 Bryony Thompson Classified gene: ERCC8 as Green List (high evidence)
Syndromic Retinopathy v0.24 ERCC8 Bryony Thompson Gene: ercc8 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.23 ERCC8 Bryony Thompson gene: ERCC8 was added
gene: ERCC8 was added to Syndromic Retinopathy. Sources: Literature
Mode of inheritance for gene: ERCC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC8 were set to 26204423
Phenotypes for gene: ERCC8 were set to Cockayne syndrome, type A MIM#216400
Review for gene: ERCC8 was set to GREEN
Added comment: Retinal dystrophy was reported as a feature of the condition in 43% of cases in a cohort of 108 individuals in 81 families. Genetic confirmation of CS was available in 40 pedigrees: ERCC6 mutations were found in 28 (70%), ERCC8 mutations in 11 (27.5%).
Sources: Literature
Syndromic Retinopathy v0.22 ERCC6 Bryony Thompson Classified gene: ERCC6 as Green List (high evidence)
Syndromic Retinopathy v0.22 ERCC6 Bryony Thompson Gene: ercc6 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.21 ERCC6 Bryony Thompson gene: ERCC6 was added
gene: ERCC6 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: ERCC6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC6 were set to 26204423
Phenotypes for gene: ERCC6 were set to Cockayne syndrome, type B MIM#133540
Review for gene: ERCC6 was set to GREEN
Added comment: Retinal dystrophy was reported as a feature of the condition in 43% of cases in a cohort of 108 individuals in 81 families. Genetic confirmation of CS was available in 40 pedigrees: ERCC6 mutations were found in 28 (70%), ERCC8 mutations in 11 (27.5%).
Sources: Expert list
Mendeliome v0.2850 CX3CR1 Zornitza Stark Marked gene: CX3CR1 as ready
Mendeliome v0.2850 CX3CR1 Zornitza Stark Gene: cx3cr1 has been classified as Red List (Low Evidence).
Mendeliome v0.2850 CX3CR1 Zornitza Stark Phenotypes for gene: CX3CR1 were changed from to Coronary artery disease, resistance to}, MIM# 607339; {Macular degeneration, age-related, 12} 613784; {Rapid progression to AIDS from HIV1 infection} 609423
Mendeliome v0.2849 CX3CR1 Zornitza Stark Classified gene: CX3CR1 as Red List (low evidence)
Mendeliome v0.2849 CX3CR1 Zornitza Stark Gene: cx3cr1 has been classified as Red List (Low Evidence).
Mendeliome v0.2849 CX3CR1 Bryony Thompson Classified gene: CX3CR1 as Red List (low evidence)
Mendeliome v0.2849 CX3CR1 Bryony Thompson Gene: cx3cr1 has been classified as Red List (Low Evidence).
Mendeliome v0.2848 CX3CR1 Zornitza Stark reviewed gene: CX3CR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Coronary artery disease, resistance to}, MIM# 607339, {Macular degeneration, age-related, 12} 613784, {Rapid progression to AIDS from HIV1 infection} 609423; Mode of inheritance: None
Mendeliome v0.2848 CX3CR1 Bryony Thompson reviewed gene: CX3CR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.24 CLCC1 Zornitza Stark Marked gene: CLCC1 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.24 CLCC1 Zornitza Stark Gene: clcc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2848 CLCC1 Zornitza Stark Marked gene: CLCC1 as ready
Mendeliome v0.2848 CLCC1 Zornitza Stark Gene: clcc1 has been classified as Amber List (Moderate Evidence).
Polymicrogyria and Schizencephaly v0.63 GRIN2B Zornitza Stark Marked gene: GRIN2B as ready
Polymicrogyria and Schizencephaly v0.63 GRIN2B Zornitza Stark Gene: grin2b has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.63 GRIN2B Zornitza Stark Phenotypes for gene: GRIN2B were changed from to GRIN2B-related neurodevelopmental disorder
Polymicrogyria and Schizencephaly v0.62 GRIN2B Zornitza Stark Publications for gene: GRIN2B were set to
Polymicrogyria and Schizencephaly v0.61 GRIN2B Zornitza Stark Mode of inheritance for gene: GRIN2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cholestasis v0.21 ABCB11 Zornitza Stark Marked gene: ABCB11 as ready
Cholestasis v0.21 ABCB11 Zornitza Stark Gene: abcb11 has been classified as Green List (High Evidence).
Cholestasis v0.21 ABCB11 Zornitza Stark Phenotypes for gene: ABCB11 were changed from to Cholestasis, benign recurrent intrahepatic, 2, MIM# 605479 AR; Cholestasis, progressive familial intrahepatic 2, MIM# 601847 AR
Cholestasis v0.20 ABCB11 Zornitza Stark Publications for gene: ABCB11 were set to 23141890
Cholestasis v0.20 ABCB11 Zornitza Stark Publications for gene: ABCB11 were set to
Syndromic Retinopathy v0.19 CNNM4 Bryony Thompson Marked gene: CNNM4 as ready
Syndromic Retinopathy v0.19 CNNM4 Bryony Thompson Gene: cnnm4 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.19 CNNM4 Bryony Thompson Classified gene: CNNM4 as Green List (high evidence)
Syndromic Retinopathy v0.19 CNNM4 Bryony Thompson Gene: cnnm4 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.18 CNNM4 Bryony Thompson gene: CNNM4 was added
gene: CNNM4 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: CNNM4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNNM4 were set to 30705057
Phenotypes for gene: CNNM4 were set to Jalili syndrome MIM#217080
Mendeliome v0.2848 CLCC1 Bryony Thompson Classified gene: CLCC1 as Amber List (moderate evidence)
Mendeliome v0.2848 CLCC1 Bryony Thompson Gene: clcc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2847 CLCC1 Bryony Thompson gene: CLCC1 was added
gene: CLCC1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CLCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLCC1 were set to 30157172
Phenotypes for gene: CLCC1 were set to Retinitis pigmentosa 32
Review for gene: CLCC1 was set to AMBER
Added comment: A presumptive Pakastani founder mutation (c.75C>A, p.D25E) was identified in 8 consanguineous arRP families. A knockout zebrafish model and a Clcc1 +/- mouse model had a supporting retinal phenotype.
Sources: Expert list
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.24 CLCC1 Bryony Thompson Classified gene: CLCC1 as Amber List (moderate evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.24 CLCC1 Bryony Thompson Gene: clcc1 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.23 CLCC1 Bryony Thompson reviewed gene: CLCC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30157172; Phenotypes: retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.17 BBIP1 Bryony Thompson Marked gene: BBIP1 as ready
Syndromic Retinopathy v0.17 BBIP1 Bryony Thompson Gene: bbip1 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.17 BBIP1 Bryony Thompson Classified gene: BBIP1 as Amber List (moderate evidence)
Syndromic Retinopathy v0.17 BBIP1 Bryony Thompson Gene: bbip1 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.16 BBIP1 Bryony Thompson gene: BBIP1 was added
gene: BBIP1 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: BBIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBIP1 were set to 24026985
Phenotypes for gene: BBIP1 were set to Bardet-Biedl syndrome 18 MIM#615995
Review for gene: BBIP1 was set to AMBER
Added comment: Single case with homozygous stopgain that has retinitis pigmentosa has a feature of the syndromic phenotype. A null zebrafish model also has a retinal phenotype.
Sources: Expert list
Cholestasis v0.19 ABCB11 Zornitza Stark Mode of inheritance for gene: ABCB11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.60 GRIN1 Zornitza Stark Marked gene: GRIN1 as ready
Polymicrogyria and Schizencephaly v0.60 GRIN1 Zornitza Stark Gene: grin1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.60 GRIN1 Zornitza Stark Phenotypes for gene: GRIN1 were changed from to GRIN1-related neurodevelopmental disorder
Polymicrogyria and Schizencephaly v0.59 GRIN1 Zornitza Stark Publications for gene: GRIN1 were set to
Polymicrogyria and Schizencephaly v0.58 GRIN1 Zornitza Stark Mode of inheritance for gene: GRIN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliopathies v0.182 RPGRIP1 Zornitza Stark Marked gene: RPGRIP1 as ready
Ciliopathies v0.182 RPGRIP1 Zornitza Stark Gene: rpgrip1 has been classified as Green List (High Evidence).
Ciliopathies v0.182 RPGRIP1 Zornitza Stark Classified gene: RPGRIP1 as Green List (high evidence)
Ciliopathies v0.182 RPGRIP1 Zornitza Stark Gene: rpgrip1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.15 ATXN7 Bryony Thompson Tag STR tag was added to gene: ATXN7.
Retinal Disorders Superpanel v0.30 Bryony Thompson Changed child panels to: Autosomal Recessive/X-Linked Retinitis Pigmentosa; Syndromic Retinopathy; Macular Dystrophy/Stargardt Disease; Autosomal Dominant Retinitis Pigmentosa; Usher Syndrome; Vitreoretinopathy; Stickler Syndrome; Achromatopsia; Congenital Stationary Night Blindness; Cone-rod Dystrophy
Achromatopsia v0.2 ATF6 Bryony Thompson Marked gene: ATF6 as ready
Achromatopsia v0.2 ATF6 Bryony Thompson Gene: atf6 has been classified as Green List (High Evidence).
Achromatopsia v0.2 ATF6 Bryony Thompson Classified gene: ATF6 as Green List (high evidence)
Achromatopsia v0.2 ATF6 Bryony Thompson Gene: atf6 has been classified as Green List (High Evidence).
Achromatopsia v0.1 ATF6 Bryony Thompson gene: ATF6 was added
gene: ATF6 was added to Achromatopsia. Sources: Expert list
Mode of inheritance for gene: ATF6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATF6 were set to 26063662; 26029869
Phenotypes for gene: ATF6 were set to Achromatopsia 7 MIM#616517
Review for gene: ATF6 was set to GREEN
Added comment: At least 11 families reported with the biallelic variants and a null mouse model with retinal degeneration.
Sources: Expert list
Achromatopsia v0.0 Bryony Thompson Added Panel Achromatopsia
Set panel types to: Royal Melbourne Hospital; Rare Disease
Ciliopathies v0.181 DHCR7 Zornitza Stark Marked gene: DHCR7 as ready
Ciliopathies v0.181 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Green List (High Evidence).
Ciliopathies v0.181 DHCR7 Zornitza Stark Classified gene: DHCR7 as Green List (high evidence)
Ciliopathies v0.181 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Green List (High Evidence).
Ciliopathies v0.180 DHCR7 Zornitza Stark reviewed gene: DHCR7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Smith-Lemli-Opitz syndrome (MIM#270400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.103 DCDC2 Zornitza Stark Publications for gene: DCDC2 were set to 25557784
Ciliopathies v0.180 DCDC2 Zornitza Stark Publications for gene: DCDC2 were set to 25557784
Syndromic Retinopathy v0.15 ARMC9 Bryony Thompson Marked gene: ARMC9 as ready
Syndromic Retinopathy v0.15 ARMC9 Bryony Thompson Gene: armc9 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.15 ARMC9 Bryony Thompson Classified gene: ARMC9 as Amber List (moderate evidence)
Syndromic Retinopathy v0.15 ARMC9 Bryony Thompson Gene: armc9 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.14 ARMC9 Bryony Thompson gene: ARMC9 was added
gene: ARMC9 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: ARMC9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARMC9 were set to 28625504
Phenotypes for gene: ARMC9 were set to Joubert syndrome 30 MIM#617622
Review for gene: ARMC9 was set to AMBER
Added comment: Retinal dystrophy has been reported in two out of nine cases. Knockout of Armc9 in zebrafish resulted in curved body shape, retinal dystrophy, coloboma, reduced cilia number in ventricles, and shortened cilia in photoreceptor outer segments.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2641 B9D1 Zornitza Stark Classified gene: B9D1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2641 B9D1 Zornitza Stark Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2640 B9D1 Zornitza Stark changed review comment from: Two unrelated individuals with JS and bi-allelic variants in this gene, plus one individual with a more severe Meckel phenotype described. Intellectual disability is part of the phenotype.; to: Two unrelated individuals with JS and bi-allelic variants in this gene, plus one individual with a more severe Meckel phenotype described. Intellectual disability is part of the phenotype. However note that in Meckel individual one of the variants identified is a multi-gene deletion and in addition a likely path CEP290 variant also reported.
Intellectual disability syndromic and non-syndromic v0.2640 B9D1 Zornitza Stark edited their review of gene: B9D1: Changed rating: AMBER
Polydactyly v0.33 B9D1 Zornitza Stark Marked gene: B9D1 as ready
Polydactyly v0.33 B9D1 Zornitza Stark Gene: b9d1 has been classified as Red List (Low Evidence).
Polydactyly v0.33 B9D1 Zornitza Stark Phenotypes for gene: B9D1 were changed from to Joubert syndrome 27, MIM#617120; Meckel syndrome 9, MIM#614209
Polydactyly v0.32 B9D1 Zornitza Stark Publications for gene: B9D1 were set to
Syndromic Retinopathy v0.13 ARL13B Bryony Thompson Marked gene: ARL13B as ready
Syndromic Retinopathy v0.13 ARL13B Bryony Thompson Gene: arl13b has been classified as Green List (High Evidence).
Polydactyly v0.31 B9D1 Zornitza Stark Mode of inheritance for gene: B9D1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.13 ARL13B Bryony Thompson Classified gene: ARL13B as Green List (high evidence)
Syndromic Retinopathy v0.13 ARL13B Bryony Thompson Gene: arl13b has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.12 ARL13B Bryony Thompson gene: ARL13B was added
gene: ARL13B was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: ARL13B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL13B were set to 18674751; 30573647; 25138100; 29255182
Phenotypes for gene: ARL13B were set to Joubert syndrome 8 MIM#612291
Review for gene: ARL13B was set to GREEN
Added comment: At least three families reported with retinopathy as a feature of the syndrome. An Arl13b null mouse has defects in retinal development with reduced cell proliferation.
Sources: Expert list
Polydactyly v0.30 B9D1 Zornitza Stark Classified gene: B9D1 as Red List (low evidence)
Polydactyly v0.30 B9D1 Zornitza Stark Gene: b9d1 has been classified as Red List (Low Evidence).
Polydactyly v0.29 B9D1 Zornitza Stark changed review comment from: Two unrelated individuals with JS and bi-allelic variants in this gene, plus one individual with a more severe Meckel phenotype described. Intellectual disability is part of the phenotype.; to: Two unrelated individuals with JS and bi-allelic variants in this gene, plus one individual with a more severe Meckel phenotype described: however note one of the variants was a multi-gene deletion, and in addition the individual had a CEP290 likely path variant. None had polydactyly.
Polydactyly v0.29 B9D1 Zornitza Stark edited their review of gene: B9D1: Changed rating: RED
Syndromic Retinopathy v0.10 ALPK1 Bryony Thompson Classified gene: ALPK1 as Green List (high evidence)
Syndromic Retinopathy v0.10 ALPK1 Bryony Thompson Gene: alpk1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.9 ALPK1 Bryony Thompson gene: ALPK1 was added
gene: ALPK1 was added to Syndromic Retinopathy. Sources: Literature
Mode of inheritance for gene: ALPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALPK1 were set to 30967659; 31939038
Phenotypes for gene: ALPK1 were set to ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache
Mendeliome v0.2846 B9D1 Zornitza Stark Marked gene: B9D1 as ready
Mendeliome v0.2846 B9D1 Zornitza Stark Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2846 B9D1 Zornitza Stark Phenotypes for gene: B9D1 were changed from to Joubert syndrome 27, MIM#617120; Meckel syndrome 9, MIM#614209
Mendeliome v0.2845 B9D1 Zornitza Stark Publications for gene: B9D1 were set to
Mendeliome v0.2844 B9D1 Zornitza Stark Mode of inheritance for gene: B9D1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2843 B9D1 Zornitza Stark Classified gene: B9D1 as Amber List (moderate evidence)
Mendeliome v0.2843 B9D1 Zornitza Stark Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2842 B9D1 Zornitza Stark changed review comment from: Two unrelated individuals with JS and bi-allelic variants in this gene, plus one individual with a more severe Meckel phenotype described. Intellectual disability is part of the phenotype.
Sources: Expert list; to: Two unrelated individuals with JS and bi-allelic variants in this gene, plus one individual with a more severe Meckel phenotype described. This latter individual had a splice site variant and a deletion. Splice variant proven to result in exon skipping -> PTC, but the deletion spans a large region including 18 other genes. Patient also had an additional variant in CEP290 called LP. Authors perform functional studies on patient cells but given the large deletion/CEP290 variant i dont see the results are usable PMID: 25920555 - another report of digenic inheritance - not usable, patient was only heterozygous for a single B9D1 variant.
Mendeliome v0.2842 B9D1 Zornitza Stark edited their review of gene: B9D1: Changed publications: 24886560, 21493627, 25920555
Mendeliome v0.2842 B9D1 Zornitza Stark edited their review of gene: B9D1: Changed rating: AMBER
Joubert syndrome and other neurological ciliopathies v0.77 B9D1 Zornitza Stark Marked gene: B9D1 as ready
Joubert syndrome and other neurological ciliopathies v0.77 B9D1 Zornitza Stark Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.77 B9D1 Zornitza Stark Phenotypes for gene: B9D1 were changed from to Meckel syndrome 9, MIM# 614209; Joubert syndrome 27, MIM# 617120
Joubert syndrome and other neurological ciliopathies v0.76 B9D1 Zornitza Stark Publications for gene: B9D1 were set to
Joubert syndrome and other neurological ciliopathies v0.75 B9D1 Zornitza Stark Mode of inheritance for gene: B9D1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Anophthalmia_Microphthalmia_Coloboma v0.50 ABCB6 Bryony Thompson gene: ABCB6 was added
gene: ABCB6 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Literature
Mode of inheritance for gene: ABCB6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ABCB6 were set to 22226084; 24281366
Phenotypes for gene: ABCB6 were set to Microphthalmia, isolated, with coloboma 7 MIM#614497
Review for gene: ABCB6 was set to RED
Added comment: Segregation of a missense variant reported in a single Chinese family. Morpholino knockdown of abcb6 in zebrafish produces a phenotype characteristic of coloboma. The missenses p.Ala57Thr and p.Arg192Gln reported in cases with coloboma are too common in gnomAD for a dominant condition. No convincing evidence reported since the 2012 publication.
Sources: Literature
Joubert syndrome and other neurological ciliopathies v0.74 B9D1 Zornitza Stark Classified gene: B9D1 as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.74 B9D1 Zornitza Stark Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.73 B9D1 Zornitza Stark reviewed gene: B9D1: Rating: AMBER; Mode of pathogenicity: None; Publications: 24886560, 21493627, 25920555; Phenotypes: Meckel syndrome 9, MIM# 614209, Joubert syndrome 27, MIM# 617120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.179 B9D1 Zornitza Stark Marked gene: B9D1 as ready
Ciliopathies v0.179 B9D1 Zornitza Stark Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.179 B9D1 Zornitza Stark Phenotypes for gene: B9D1 were changed from to Meckel syndrome 9, MIM# 614209; Joubert syndrome 27, MIM# 617120
Ciliopathies v0.178 B9D1 Zornitza Stark Publications for gene: B9D1 were set to
Ciliopathies v0.177 B9D1 Zornitza Stark Mode of inheritance for gene: B9D1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.176 B9D1 Zornitza Stark Classified gene: B9D1 as Amber List (moderate evidence)
Ciliopathies v0.176 B9D1 Zornitza Stark Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Polymicrogyria and Schizencephaly v0.57 L1CAM Lauren Akesson reviewed gene: L1CAM: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 9926316, 27066571; Phenotypes: L1CAM-related disease; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ciliopathies v0.175 TOPORS Zornitza Stark Marked gene: TOPORS as ready
Ciliopathies v0.175 TOPORS Zornitza Stark Gene: topors has been classified as Green List (High Evidence).
Ciliopathies v0.175 TOPORS Zornitza Stark Classified gene: TOPORS as Green List (high evidence)
Ciliopathies v0.175 TOPORS Zornitza Stark Gene: topors has been classified as Green List (High Evidence).
Ciliopathies v0.174 BBIP1 Zornitza Stark edited their review of gene: BBIP1: Changed publications: 24026985, 32055034
Renal Ciliopathies and Nephronophthisis v0.102 BBIP1 Zornitza Stark Publications for gene: BBIP1 were set to 24026985
Renal Ciliopathies and Nephronophthisis v0.101 BBIP1 Zornitza Stark edited their review of gene: BBIP1: Added comment: Additional family reported.; Changed publications: 24026985, 32055034V
Mendeliome v0.2842 BBIP1 Zornitza Stark Phenotypes for gene: BBIP1 were changed from to Bardet-Biedl syndrome 18, MIM#615995
Mendeliome v0.2841 BBIP1 Zornitza Stark Publications for gene: BBIP1 were set to
Mendeliome v0.2840 BBIP1 Zornitza Stark Mode of inheritance for gene: BBIP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2839 BBIP1 Zornitza Stark edited their review of gene: BBIP1: Added comment: Additional family reported.; Changed publications: 24026985, 32055034
Bardet Biedl syndrome v0.27 BBIP1 Zornitza Stark Publications for gene: BBIP1 were set to 24026985
Ciliopathies v0.174 BBIP1 Zornitza Stark Publications for gene: BBIP1 were set to 24026985
Polymicrogyria and Schizencephaly v0.57 GRIN2B Lauren Akesson reviewed gene: GRIN2B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28377535; Phenotypes: GRIN2B-related neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cholestasis v0.18 ABCB11 Michelle Torres reviewed gene: ABCB11: Rating: GREEN; Mode of pathogenicity: None; Publications: 23141890; Phenotypes: Cholestasis, benign recurrent intrahepatic, 2 605479 AR, Cholestasis, progressive familial intrahepatic 2 601847 AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Polymicrogyria and Schizencephaly v0.57 GRIN1 Lauren Akesson reviewed gene: GRIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29365063; Phenotypes: GRIN1-related neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliopathies v0.173 TULP1 Zornitza Stark Marked gene: TULP1 as ready
Ciliopathies v0.173 TULP1 Zornitza Stark Gene: tulp1 has been classified as Green List (High Evidence).
Ciliopathies v0.173 TULP1 Zornitza Stark Classified gene: TULP1 as Green List (high evidence)
Ciliopathies v0.173 TULP1 Zornitza Stark Gene: tulp1 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.101 ZNF423 Zornitza Stark Classified gene: ZNF423 as Amber List (moderate evidence)
Renal Ciliopathies and Nephronophthisis v0.101 ZNF423 Zornitza Stark Gene: znf423 has been classified as Amber List (Moderate Evidence).
Renal Ciliopathies and Nephronophthisis v0.100 ZNF423 Zornitza Stark edited their review of gene: ZNF423: Changed rating: AMBER
Mendeliome v0.2839 ZNF423 Zornitza Stark Classified gene: ZNF423 as Amber List (moderate evidence)
Mendeliome v0.2839 ZNF423 Zornitza Stark Gene: znf423 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2838 ZNF423 Zornitza Stark edited their review of gene: ZNF423: Changed rating: AMBER
Joubert syndrome and other neurological ciliopathies v0.73 ZNF423 Zornitza Stark Marked gene: ZNF423 as ready
Joubert syndrome and other neurological ciliopathies v0.73 ZNF423 Zornitza Stark Gene: znf423 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.73 ZNF423 Zornitza Stark Classified gene: ZNF423 as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.73 ZNF423 Zornitza Stark Gene: znf423 has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.172 ZNF423 Zornitza Stark Classified gene: ZNF423 as Amber List (moderate evidence)
Ciliopathies v0.172 ZNF423 Zornitza Stark Gene: znf423 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.24 GPD1L Zornitza Stark Marked gene: GPD1L as ready
Incidentalome v0.24 GPD1L Zornitza Stark Gene: gpd1l has been classified as Amber List (Moderate Evidence).
Incidentalome v0.24 GPD1L Zornitza Stark Phenotypes for gene: GPD1L were changed from to Brugada syndrome 2, MIM# 611777
Incidentalome v0.23 GPD1L Zornitza Stark Publications for gene: GPD1L were set to
Incidentalome v0.22 GPD1L Zornitza Stark Mode of inheritance for gene: GPD1L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.21 GPD1L Zornitza Stark Classified gene: GPD1L as Amber List (moderate evidence)
Incidentalome v0.21 GPD1L Zornitza Stark Gene: gpd1l has been classified as Amber List (Moderate Evidence).
Incidentalome v0.20 GPD1L Zornitza Stark Tag disputed tag was added to gene: GPD1L.
Incidentalome v0.20 GPD1L Zornitza Stark reviewed gene: GPD1L: Rating: AMBER; Mode of pathogenicity: None; Publications: 17967977, 19666841; Phenotypes: Brugada syndrome 2, MIM# 611777; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brugada syndrome v0.10 GPD1L Zornitza Stark Marked gene: GPD1L as ready
Brugada syndrome v0.10 GPD1L Zornitza Stark Added comment: Comment when marking as ready: Rated as DISPUTED by ClinGen.
Brugada syndrome v0.10 GPD1L Zornitza Stark Gene: gpd1l has been classified as Amber List (Moderate Evidence).
Brugada syndrome v0.10 GPD1L Zornitza Stark Phenotypes for gene: GPD1L were changed from to Brugada syndrome 2, MIM# 611777
Brugada syndrome v0.9 GPD1L Zornitza Stark Publications for gene: GPD1L were set to
Brugada syndrome v0.8 GPD1L Zornitza Stark Mode of inheritance for gene: GPD1L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brugada syndrome v0.7 GPD1L Zornitza Stark Tag disputed tag was added to gene: GPD1L.
Brugada syndrome v0.7 GPD1L Zornitza Stark Classified gene: GPD1L as Amber List (moderate evidence)
Brugada syndrome v0.7 GPD1L Zornitza Stark Gene: gpd1l has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.171 POC1B Zornitza Stark Marked gene: POC1B as ready
Ciliopathies v0.171 POC1B Zornitza Stark Gene: poc1b has been classified as Green List (High Evidence).
Ciliopathies v0.171 POC1B Zornitza Stark Phenotypes for gene: POC1B were changed from to Cone-rod dystrophy 20 (MIM#615973)
Ciliopathies v0.170 POC1B Zornitza Stark Publications for gene: POC1B were set to
Ciliopathies v0.169 POC1B Zornitza Stark Mode of inheritance for gene: POC1B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.168 RPGR Zornitza Stark Marked gene: RPGR as ready
Ciliopathies v0.168 RPGR Zornitza Stark Gene: rpgr has been classified as Green List (High Evidence).
Ciliopathies v0.168 RPGR Zornitza Stark Phenotypes for gene: RPGR were changed from to Retinitis pigmentosa 3 (MIM#300029)
Ciliopathies v0.167 RPGR Zornitza Stark Publications for gene: RPGR were set to
Ciliopathies v0.166 RPGR Zornitza Stark Mode of inheritance for gene: RPGR was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Autism v0.94 PACS1 Zornitza Stark Marked gene: PACS1 as ready
Autism v0.94 PACS1 Zornitza Stark Gene: pacs1 has been classified as Green List (High Evidence).
Autism v0.94 PACS1 Zornitza Stark Phenotypes for gene: PACS1 were changed from to Schuurs-Hoeijmakers syndrome (MIM# 615009)
Autism v0.93 PACS1 Zornitza Stark Publications for gene: PACS1 were set to
Autism v0.92 PACS1 Zornitza Stark Mode of inheritance for gene: PACS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.91 PACS1 Zornitza Stark reviewed gene: PACS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26842493, 23159249; Phenotypes: Schuurs-Hoeijmakers syndrome (MIM# 615009); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.708 PACS1 Zornitza Stark Marked gene: PACS1 as ready
Genetic Epilepsy v0.708 PACS1 Zornitza Stark Gene: pacs1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.708 PACS1 Zornitza Stark Phenotypes for gene: PACS1 were changed from to Schuurs-Hoeijmakers syndrome (MIM# 615009)
Genetic Epilepsy v0.707 PACS1 Zornitza Stark Publications for gene: PACS1 were set to
Genetic Epilepsy v0.706 PACS1 Zornitza Stark Mode of inheritance for gene: PACS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.705 PACS1 Zornitza Stark reviewed gene: PACS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26842493, 23159249; Phenotypes: Schuurs-Hoeijmakers syndrome (MIM# 615009); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2640 PACS1 Zornitza Stark Marked gene: PACS1 as ready
Intellectual disability syndromic and non-syndromic v0.2640 PACS1 Zornitza Stark Gene: pacs1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2640 PACS1 Zornitza Stark Phenotypes for gene: PACS1 were changed from to Schuurs-Hoeijmakers syndrome (MIM# 615009)
Intellectual disability syndromic and non-syndromic v0.2639 PACS1 Zornitza Stark Publications for gene: PACS1 were set to
Intellectual disability syndromic and non-syndromic v0.2638 PACS1 Zornitza Stark Mode of inheritance for gene: PACS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2637 PACS1 Zornitza Stark reviewed gene: PACS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26842493, 23159249; Phenotypes: Schuurs-Hoeijmakers syndrome (MIM# 615009); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2838 PACS1 Zornitza Stark Marked gene: PACS1 as ready
Mendeliome v0.2838 PACS1 Zornitza Stark Gene: pacs1 has been classified as Green List (High Evidence).
Mendeliome v0.2838 PACS1 Zornitza Stark Phenotypes for gene: PACS1 were changed from to Schuurs-Hoeijmakers syndrome (MIM# 615009)
Mendeliome v0.2837 PACS1 Zornitza Stark Publications for gene: PACS1 were set to
Mendeliome v0.2836 PACS1 Zornitza Stark Mode of inheritance for gene: PACS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2835 SLC15A4 Zornitza Stark Marked gene: SLC15A4 as ready
Mendeliome v0.2835 SLC15A4 Zornitza Stark Gene: slc15a4 has been classified as Red List (Low Evidence).
Mendeliome v0.2835 SLC15A4 Zornitza Stark Publications for gene: SLC15A4 were set to
Mendeliome v0.2834 SLC15A4 Zornitza Stark Classified gene: SLC15A4 as Red List (low evidence)
Mendeliome v0.2834 SLC15A4 Zornitza Stark Gene: slc15a4 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.72 ZSWIM6 Zornitza Stark Marked gene: ZSWIM6 as ready
Joubert syndrome and other neurological ciliopathies v0.72 ZSWIM6 Zornitza Stark Added comment: Comment when marking as ready: Not entirely clear at this stage whether this is a ciliopathy.
Joubert syndrome and other neurological ciliopathies v0.72 ZSWIM6 Zornitza Stark Gene: zswim6 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.72 ZSWIM6 Zornitza Stark Phenotypes for gene: ZSWIM6 were changed from Acromelic frontonasal dysostosis (MIM#603671) to Acromelic frontonasal dysostosis (MIM#603671); Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features, MIM#617865
Joubert syndrome and other neurological ciliopathies v0.71 ZSWIM6 Zornitza Stark Classified gene: ZSWIM6 as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.71 ZSWIM6 Zornitza Stark Gene: zswim6 has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.165 RPGRIP1 Crystle Lee gene: RPGRIP1 was added
gene: RPGRIP1 was added to Ciliopathies. Sources: Expert Review
Mode of inheritance for gene: RPGRIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPGRIP1 were set to 25414380; 28456785; 24997176; 28559085
Phenotypes for gene: RPGRIP1 were set to Leber congenital amaurosis 6 (MIM#613826)
Review for gene: RPGRIP1 was set to GREEN
Added comment: Plays an essential role in the photoreceptor connecting cilia (PMID: 25414380). Multiple families reported.

PMID: 28456785; Huang 2017: 3 families reported. 1 of which harboured intragenic (exon 1-22) deletion.

PMID: 24997176; Khan 2014: Reported 11 consang families with variants in RPGRIP1 but 9 of 11 harboured the same p.(Glu370Asnfs*5) variant.

PMID: 28559085; Stone 2017: 2 additional LCA patients reported.

Hameed 2003: Reported 2 different hom missense in 2 families. One of which, Ala547Ser, is present in gnomad (6704 homozygotes)

Green in Retinal disorders panel - PanelApp UK
Sources: Expert Review
Ciliopathies v0.165 DHCR7 Elena Savva gene: DHCR7 was added
gene: DHCR7 was added to Ciliopathies. Sources: Expert list
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHCR7 were set to PMID 23059950
Phenotypes for gene: DHCR7 were set to Smith-Lemli-Opitz syndrome (MIM#270400)
Added comment: Not a ciliopathy however presents with many overlapping JS features including central nervous system anomalies, cleft palate, postaxial polydactyly

PanelApp UK: Important differential diagnosis of ciliopathy
Sources: Expert Review
Sources: Expert list
Renal Ciliopathies and Nephronophthisis v0.100 DCDC2 Elena Savva reviewed gene: DCDC2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 25557784, 31821705; Phenotypes: Nephronophthisis 19 616217; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.165 DCDC2 Elena Savva reviewed gene: DCDC2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 25557784, 31821705; Phenotypes: Nephronophthisis 19 616217; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.165 B9D1 Elena Savva reviewed gene: B9D1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 24886560, 21493627, 25920555; Phenotypes: ?Meckel syndrome 9 614209, Joubert syndrome 27 617120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.165 TOPORS Crystle Lee gene: TOPORS was added
gene: TOPORS was added to Ciliopathies. Sources: Expert Review
Mode of inheritance for gene: TOPORS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TOPORS were set to 21159800; 17924349; 28453362; 18509552
Phenotypes for gene: TOPORS were set to Retinitis pigmentosa 31 (MIM#609923)
Review for gene: TOPORS was set to GREEN
Added comment: TOPORS is a ciliopathy protein localized to the base of the primary cilium (OMIM). No inheritance pattern noted in OMIM however AD appears to be consistent between 5 families currently reported.

PMID: 17924349; Chakarova 2007: Reported different het variants in 2 families. Haploinsufficiency suggested meechanism. Variants not present in gnomAD.

PMID: 28453362; Latasiewicz 2017: Het variant reported in one family.

PMID: 18509552; Bowne 2008: 2 additional adRP families reported.

Green in 'Retinal disorders' panel - PanelApp UK
Sources: Expert Review
Ciliopathies v0.165 UMOD Zornitza Stark Marked gene: UMOD as ready
Ciliopathies v0.165 UMOD Zornitza Stark Gene: umod has been classified as Green List (High Evidence).
Ciliopathies v0.165 UMOD Zornitza Stark Phenotypes for gene: UMOD were changed from to Glomerulocystic kidney disease with hyperuricemia and isosthenuria (MIM#609886); Hyperuricemic nephropathy, familial juvenile 1 (MIM#162000); Medullary cystic kidney disease 2 (MIM#603860)
Ciliopathies v0.164 UMOD Zornitza Stark Publications for gene: UMOD were set to
Ciliopathies v0.163 UMOD Zornitza Stark Mode of inheritance for gene: UMOD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ichthyosis v0.76 FLG Zornitza Stark Marked gene: FLG as ready
Ichthyosis v0.76 FLG Zornitza Stark Gene: flg has been classified as Green List (High Evidence).
Ichthyosis v0.76 FLG Zornitza Stark Phenotypes for gene: FLG were changed from to Ichthyosis vulgaris 146700; {Dermatitis, atopic, susceptibility to, 2} 605803
Ichthyosis v0.75 FLG Zornitza Stark Publications for gene: FLG were set to
Ichthyosis v0.74 FLG Zornitza Stark Mode of inheritance for gene: FLG was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Bardet Biedl syndrome v0.26 BBIP1 Elena Savva reviewed gene: BBIP1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 24026985, 32055034; Phenotypes: Bardet-Biedl Syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.162 BBIP1 Elena Savva edited their review of gene: BBIP1: Added comment: PMID: 24026985 - Single patient with BBS described with bi-allelic variants in this gene.

PMID: 32055034 - An additional patient with classic BBS with a homozygous splice variant confirmed by RT-PCR to result in NMD

Only one other 'pathogenic' variant in ClinVar but homozygous missense and no evidence provided.; Changed phenotypes: Bardet-Biedl Syndrome
Ciliopathies v0.162 BBIP1 Elena Savva reviewed gene: BBIP1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 24026985; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.17 EVC Zornitza Stark Marked gene: EVC as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.17 EVC Zornitza Stark Gene: evc has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.17 EVC Zornitza Stark Phenotypes for gene: EVC were changed from to Ellis-van Creveld syndrome, MIM# 225500
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.16 EVC Zornitza Stark Publications for gene: EVC were set to
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.15 EVC Zornitza Stark Mode of inheritance for gene: EVC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.14 EVC Zornitza Stark reviewed gene: EVC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ellis-van Creveld syndrome, MIM# 225500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.162 TULP1 Crystle Lee gene: TULP1 was added
gene: TULP1 was added to Ciliopathies. Sources: Expert Review
Mode of inheritance for gene: TULP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TULP1 were set to 17620573; 27440997; 21987678; 15557452
Phenotypes for gene: TULP1 were set to Retinitis pigmentosa 14 M(MIM#600132)
Review for gene: TULP1 was set to GREEN
Added comment: Reported in multiple RP families.
TULP1 expressed in the retina and localizes to the inner segments and connecting cilium of photoreceptors (PMID: 17620573)

Green in 'Retinal disorders' - PanelApp UK
Sources: Expert Review
Joubert syndrome and other neurological ciliopathies v0.70 ZNF423 Crystle Lee gene: ZNF423 was added
gene: ZNF423 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: ZNF423 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ZNF423 were set to 22863007
Phenotypes for gene: ZNF423 were set to Joubert syndrome 19 (MIM#614844)
Mode of pathogenicity for gene: ZNF423 was set to Other
Review for gene: ZNF423 was set to AMBER
Added comment: Limited reports, single publication in 2012 reported AD and AR inheritance. Mechanism not well established. Pending additional reports.

2 Turkish sibs with Joubert syndrome with homozygous mutation in the ZNF423 gene.
Two additional patients with Joubert syndrome were found to carry heterozygous ZNF423 mutations , which caused a dominant-negative effect on protein function in cellular studies. Published variants not present in gnomAD at unexpected frequencies and minimal LoF variants in gnomAD
Sources: Expert Review
Ciliopathies v0.162 ZNF423 Crystle Lee reviewed gene: ZNF423: Rating: AMBER; Mode of pathogenicity: Other; Publications: 22863007; Phenotypes: Joubert syndrome 19 (MIM#614844); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Brugada syndrome v0.6 GPD1L Elena Savva reviewed gene: GPD1L: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 17967977, 19666841; Phenotypes: Brugada syndrome 2 611777; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ciliopathies v0.162 POC1B Crystle Lee reviewed gene: POC1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 25018096, 24945461, 25044745, 29220607, 29377742; Phenotypes: Cone-rod dystrophy 20 (MIM#615973); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.162 PIK3C2A Zornitza Stark Marked gene: PIK3C2A as ready
Ciliopathies v0.162 PIK3C2A Zornitza Stark Gene: pik3c2a has been classified as Green List (High Evidence).
Ciliopathies v0.162 PIK3C2A Zornitza Stark Classified gene: PIK3C2A as Green List (high evidence)
Ciliopathies v0.162 PIK3C2A Zornitza Stark Gene: pik3c2a has been classified as Green List (High Evidence).
Ciliopathies v0.161 RPGR Crystle Lee reviewed gene: RPGR: Rating: GREEN; Mode of pathogenicity: None; Publications: 19815619, 31775781, 26093275, 30105367; Phenotypes: Retinitis pigmentosa 3 (MIM#300029); 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 v0.2833 PACS1 Ain Roesley reviewed gene: PACS1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 26842493, 23159249; Phenotypes: Schuurs-Hoeijmakers syndrome (MIM# 615009); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2833 SLC15A4 Naomi Baker reviewed gene: SLC15A4: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 25238095; Phenotypes: ; Mode of inheritance: None
Joubert syndrome and other neurological ciliopathies v0.70 ZSWIM6 Crystle Lee gene: ZSWIM6 was added
gene: ZSWIM6 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: ZSWIM6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZSWIM6 were set to 25105228; 28213462; 29198722
Phenotypes for gene: ZSWIM6 were set to Acromelic frontonasal dysostosis (MIM#603671)
Review for gene: ZSWIM6 was set to AMBER
Added comment: There are some phenotypic overlap, primarily skeletal abnormalities.

PMID: 25105228: 4 pts with AFND (Arg1163Trp)

PMID: 28213462; AFND caused by this gene was classified as "Likely ciliopathy"

PMID: 29198722; Reported 7 unrelated individuals with a recurrent truncating variant. This patients were "Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features". No functional studies performed but postulated to be dominant-negative.
Sources: Expert Review
Hereditary Haemorrhagic Telangiectasia v0.8 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Ciliopathies v0.161 UMOD Crystle Lee reviewed gene: UMOD: Rating: GREEN; Mode of pathogenicity: None; Publications: 20172860, 31068150; Phenotypes: Glomerulocystic kidney disease with hyperuricemia and isosthenuria (MIM#609886), Hyperuricemic nephropathy, familial juvenile 1 (MIM#162000), Medullary cystic kidney disease 2 (MIM#603860); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ichthyosis v0.73 FLG Elena Savva reviewed gene: FLG: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17291859, 30681730; Phenotypes: Ichthyosis vulgaris 146700, {Dermatitis, atopic, susceptibility to, 2} 605803; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Ciliopathies v0.161 PIK3C2A Elena Savva gene: PIK3C2A was added
gene: PIK3C2A was added to Ciliopathies. Sources: Expert list
Mode of inheritance for gene: PIK3C2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIK3C2A were set to PMID: 31034465
Phenotypes for gene: PIK3C2A were set to Oculoskeletodental syndrome 618440
Review for gene: PIK3C2A was set to GREEN
Added comment: Function: catalyzes the phosphorylation of the lipids that are essential for a variety of cellular processes including cilia formation and vesicle trafficking.

PMID: 31034465 - 3 unrelated families (5 patients) with cataracts, skeletal abnormalities, hearing loss, nephrocalcinosis, visual defects etc. Variants included a nonsense, canonical splice causing a large inframe deletion-insertion and intragenic CNV.
MRIs revealed multiple forntal and periventricular lacunar infarcts, lesions of white matter. No mention of MTS or cerebellar atrophy.
Functional assays on patents fibroblasts showed reduced accumulation of PI(3)P (a downstream target of this gene) at the base of cilia and reduced cilia length.
Sources: Expert list
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.14 EVC Elena Savva reviewed gene: EVC: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 23220543; Phenotypes: Ellis-van Creveld syndrome 225500, ?Weyers acrofacial dysostosis 193530; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Haemorrhagic Telangiectasia v0.7 GDF2 Bryony Thompson Classified gene: GDF2 as Red List (low evidence)
Hereditary Haemorrhagic Telangiectasia v0.7 GDF2 Bryony Thompson Added comment: Comment on list classification: No adequate replication studies exist for this gene, since the initial publication in 2013.
Hereditary Haemorrhagic Telangiectasia v0.7 GDF2 Bryony Thompson Gene: gdf2 has been classified as Red List (Low Evidence).
Mendeliome v0.2833 STARD7 Zornitza Stark Marked gene: STARD7 as ready
Mendeliome v0.2833 STARD7 Zornitza Stark Gene: stard7 has been classified as Green List (High Evidence).
Mendeliome v0.2833 STARD7 Zornitza Stark Classified gene: STARD7 as Green List (high evidence)
Mendeliome v0.2833 STARD7 Zornitza Stark Gene: stard7 has been classified as Green List (High Evidence).
Mendeliome v0.2832 STARD7 Zornitza Stark gene: STARD7 was added
gene: STARD7 was added to Mendeliome. Sources: Expert list
STR tags were added to gene: STARD7.
Mode of inheritance for gene: STARD7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STARD7 were set to 11701600; 24114805; 31664034
Phenotypes for gene: STARD7 were set to Epilepsy, familial adult myoclonic, 2, 607876
Mode of pathogenicity for gene: STARD7 was set to Other
Review for gene: STARD7 was set to GREEN
Added comment: 158 individuals from 22 families reported with heterozygous 5-bp repeat expansion (ATTTC)n in intron 1 of the STARD7 gene.
Sources: Expert list
Genetic Epilepsy v0.705 STARD7 Zornitza Stark Marked gene: STARD7 as ready
Genetic Epilepsy v0.705 STARD7 Zornitza Stark Gene: stard7 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.705 STARD7 Zornitza Stark Classified gene: STARD7 as Green List (high evidence)
Genetic Epilepsy v0.705 STARD7 Zornitza Stark Gene: stard7 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.704 STARD7 Zornitza Stark gene: STARD7 was added
gene: STARD7 was added to Genetic Epilepsy. Sources: Literature
STR tags were added to gene: STARD7.
Mode of inheritance for gene: STARD7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STARD7 were set to 11701600; 24114805; 31664034
Phenotypes for gene: STARD7 were set to Epilepsy, familial adult myoclonic, 2, 607876
Mode of pathogenicity for gene: STARD7 was set to Other
Review for gene: STARD7 was set to GREEN
Added comment: 158 individuals from 22 families reported with heterozygous 5-bp repeat expansion (ATTTC)n in intron 1 of the STARD7 gene.
Sources: Literature
Hereditary Haemorrhagic Telangiectasia v0.6 RASA1 Naomi Baker reviewed gene: RASA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27081547, 29891884, 30507091; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Lissencephaly and Band Heterotopia v0.39 GMPPB Zornitza Stark Marked gene: GMPPB as ready
Lissencephaly and Band Heterotopia v0.39 GMPPB Zornitza Stark Gene: gmppb has been classified as Amber List (Moderate Evidence).
Lissencephaly and Band Heterotopia v0.39 GMPPB Zornitza Stark Phenotypes for gene: GMPPB were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350); Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 (MIM# 615351); Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (MIM# 615352)
Lissencephaly and Band Heterotopia v0.38 GMPPB Zornitza Stark Publications for gene: GMPPB were set to
Lissencephaly and Band Heterotopia v0.37 GMPPB Zornitza Stark Mode of inheritance for gene: GMPPB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Lissencephaly and Band Heterotopia v0.36 GMPPB Zornitza Stark Classified gene: GMPPB as Amber List (moderate evidence)
Lissencephaly and Band Heterotopia v0.36 GMPPB Zornitza Stark Gene: gmppb has been classified as Amber List (Moderate Evidence).
Hereditary Haemorrhagic Telangiectasia v0.6 GDF2 Zornitza Stark reviewed gene: GDF2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 5, MIM# 615506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Lissencephaly and Band Heterotopia v0.35 GMPPB Lauren Akesson reviewed gene: GMPPB: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 23768512, 30257713, 26310427, 24780531; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350), Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 (MIM# 615351), Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (MIM# 615352); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Haemorrhagic Telangiectasia v0.6 GDF2 Naomi Baker reviewed gene: GDF2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 23972370, 27081547, 25674101.; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal Disorders Superpanel v0.22 Bryony Thompson Changed child panels to: Autosomal Recessive/X-Linked Retinitis Pigmentosa; Macular Dystrophy/Stargardt Disease; Syndromic Retinopathy; Autosomal Dominant Retinitis Pigmentosa; Vitreoretinopathy; Usher Syndrome; Stickler Syndrome; Cone-rod Dystrophy; Congenital Stationary Night Blindness
Syndromic Retinopathy v0.8 ACBD5 Bryony Thompson Publications for gene: ACBD5 were set to
Cone-rod Dystrophy v0.1 UNC119 Bryony Thompson reviewed gene: UNC119: Rating: GREEN; Mode of pathogenicity: None; Publications: 11006213, 23563732, 27079236; Phenotypes: Cone-rod dystrophy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cone-rod Dystrophy v0.1 Bryony Thompson Panel name changed from Cone-rod Dystrophies to Cone-rod Dystrophy
Panel status changed from internal to public
Panel types changed to Royal Melbourne Hospital; Rare Disease
Cone-rod Dystrophy v0.0 UNC119 Bryony Thompson gene: UNC119 was added
gene: UNC119 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: UNC119 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: UNC119 were set to 30679166
Phenotypes for gene: UNC119 were set to ?Cone-rod dystrophy
Cone-rod Dystrophy v0.0 TTLL5 Bryony Thompson gene: TTLL5 was added
gene: TTLL5 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: TTLL5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTLL5 were set to 30679166
Phenotypes for gene: TTLL5 were set to Cone-rod dystrophy 19,615860
Cone-rod Dystrophy v0.0 SEMA4A Bryony Thompson gene: SEMA4A was added
gene: SEMA4A was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: SEMA4A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SEMA4A were set to 30679166
Phenotypes for gene: SEMA4A were set to Cone-rod dystrophy 10, 610283
Cone-rod Dystrophy v0.0 RPGRIP1 Bryony Thompson gene: RPGRIP1 was added
gene: RPGRIP1 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: RPGRIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPGRIP1 were set to 30679166
Phenotypes for gene: RPGRIP1 were set to Cone-rod dystrophy 13, 608194
Cone-rod Dystrophy v0.0 RPGR Bryony Thompson gene: RPGR was added
gene: RPGR was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: RPGR 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: RPGR were set to 30679166
Phenotypes for gene: RPGR were set to Cone-rod dystrophy, X-linked, 1, 304020
Cone-rod Dystrophy v0.0 RIMS1 Bryony Thompson gene: RIMS1 was added
gene: RIMS1 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: RIMS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RIMS1 were set to 30679166
Phenotypes for gene: RIMS1 were set to Cone-rod dystrophy 7, 603649
Cone-rod Dystrophy v0.0 RAX2 Bryony Thompson gene: RAX2 was added
gene: RAX2 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: RAX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RAX2 were set to 30679166
Phenotypes for gene: RAX2 were set to Cone-rod dystrophy 11
Cone-rod Dystrophy v0.0 RAB28 Bryony Thompson gene: RAB28 was added
gene: RAB28 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: RAB28 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB28 were set to 30679166
Phenotypes for gene: RAB28 were set to Cone-rod dystrophy 18, 615374
Cone-rod Dystrophy v0.0 PRPH2 Bryony Thompson gene: PRPH2 was added
gene: PRPH2 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PRPH2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRPH2 were set to 30679166
Phenotypes for gene: PRPH2 were set to Choroidal dystrophy, central areolar 2 MIM#613105
Cone-rod Dystrophy v0.0 PROM1 Bryony Thompson gene: PROM1 was added
gene: PROM1 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PROM1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PROM1 were set to 30679166
Phenotypes for gene: PROM1 were set to Cone-rod dystrophy 12, 612657
Cone-rod Dystrophy v0.0 POC1B Bryony Thompson gene: POC1B was added
gene: POC1B was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: POC1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POC1B were set to 30679166
Phenotypes for gene: POC1B were set to Cone-rod dystrophy 20, 615973
Cone-rod Dystrophy v0.0 PITPNM3 Bryony Thompson gene: PITPNM3 was added
gene: PITPNM3 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PITPNM3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PITPNM3 were set to 30679166; 17377520; 22405330
Phenotypes for gene: PITPNM3 were set to Cone-rod dystrophy 5, 600977
Cone-rod Dystrophy v0.0 PDE6H Bryony Thompson gene: PDE6H was added
gene: PDE6H was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PDE6H was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE6H were set to 30679166
Phenotypes for gene: PDE6H were set to Retinal Cone Dystrophy 3, 610024; Achromatopsia 6, 610024
Cone-rod Dystrophy v0.0 PDE6C Bryony Thompson gene: PDE6C was added
gene: PDE6C was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PDE6C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE6C were set to 30679166
Phenotypes for gene: PDE6C were set to Cone dystrophy 4 MIM#613093
Cone-rod Dystrophy v0.0 OPN1MW Bryony Thompson gene: OPN1MW was added
gene: OPN1MW was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: OPN1MW was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: OPN1MW were set to 30679166
Phenotypes for gene: OPN1MW were set to Blue cone monochromacy MIM#303700; Colorblindness, deutan MIM#303800
Cone-rod Dystrophy v0.0 OPN1LW Bryony Thompson gene: OPN1LW was added
gene: OPN1LW was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: OPN1LW was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: OPN1LW were set to 30679166
Phenotypes for gene: OPN1LW were set to Blue cone monochromacy MIM#303700; Colorblindness, protan MIM#303900
Cone-rod Dystrophy v0.0 KCNV2 Bryony Thompson gene: KCNV2 was added
gene: KCNV2 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: KCNV2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KCNV2 were set to 30679166
Phenotypes for gene: KCNV2 were set to Retinal cone dystrophy 3B MIM#610356
Cone-rod Dystrophy v0.0 GUCY2D Bryony Thompson gene: GUCY2D was added
gene: GUCY2D was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: GUCY2D was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GUCY2D were set to 30679166
Phenotypes for gene: GUCY2D were set to Cone-rod dystrophy 6 MIM#601777
Cone-rod Dystrophy v0.0 GUCA1A Bryony Thompson gene: GUCA1A was added
gene: GUCA1A was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: GUCA1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GUCA1A were set to 30679166
Phenotypes for gene: GUCA1A were set to Cone dystrophy-3, 602093
Cone-rod Dystrophy v0.0 CRX Bryony Thompson gene: CRX was added
gene: CRX was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CRX was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CRX were set to 30679166
Phenotypes for gene: CRX were set to Cone-rod retinal dystrophy-2, 120970
Cone-rod Dystrophy v0.0 CNGB3 Bryony Thompson gene: CNGB3 was added
gene: CNGB3 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CNGB3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNGB3 were set to 30679166
Phenotypes for gene: CNGB3 were set to Achromatopsia-3, 262300
Cone-rod Dystrophy v0.0 CNGA3 Bryony Thompson gene: CNGA3 was added
gene: CNGA3 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CNGA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNGA3 were set to 30679166
Phenotypes for gene: CNGA3 were set to Achromatopsia 2MIM#216900
Cone-rod Dystrophy v0.0 CERKL Bryony Thompson gene: CERKL was added
gene: CERKL was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CERKL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CERKL were set to 30679166
Phenotypes for gene: CERKL were set to Cone-rod dystrophy
Cone-rod Dystrophy v0.0 CEP78 Bryony Thompson gene: CEP78 was added
gene: CEP78 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CEP78 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP78 were set to 30679166
Phenotypes for gene: CEP78 were set to Cone-Rod Dystrophy and Hearing Loss; CRDHL; OMIM: 617236
Cone-rod Dystrophy v0.0 CDHR1 Bryony Thompson gene: CDHR1 was added
gene: CDHR1 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CDHR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDHR1 were set to 30679166
Phenotypes for gene: CDHR1 were set to Cone-rod dystrophy 15, 613660
Cone-rod Dystrophy v0.0 CACNA2D4 Bryony Thompson gene: CACNA2D4 was added
gene: CACNA2D4 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CACNA2D4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACNA2D4 were set to 30679166
Phenotypes for gene: CACNA2D4 were set to Retinal cone dystrophy 4, 610478
Cone-rod Dystrophy v0.0 CACNA1F Bryony Thompson gene: CACNA1F was added
gene: CACNA1F was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CACNA1F 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: CACNA1F were set to 30679166
Phenotypes for gene: CACNA1F were set to Cone-rod dystropy, X-linked, 3, 300476
Cone-rod Dystrophy v0.0 C8orf37 Bryony Thompson gene: C8orf37 was added
gene: C8orf37 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: C8orf37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C8orf37 were set to 30679166
Phenotypes for gene: C8orf37 were set to Cone-rod dystrophy 16, 614500; Retinitis pigmentosa 64, 614500
Cone-rod Dystrophy v0.0 C21orf2 Bryony Thompson gene: C21orf2 was added
gene: C21orf2 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: C21orf2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C21orf2 were set to 30679166
Phenotypes for gene: C21orf2 were set to Retinal dystrophy with macular staphyloma, 617547
Cone-rod Dystrophy v0.0 AIPL1 Bryony Thompson gene: AIPL1 was added
gene: AIPL1 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: AIPL1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: AIPL1 were set to 30679166
Phenotypes for gene: AIPL1 were set to Leber congenital amaurosis 4, 604393; Cone-rod dystrophy, 604393; Retinitis pigmentosa, juvenile, 604393
Cone-rod Dystrophy v0.0 ADAM9 Bryony Thompson gene: ADAM9 was added
gene: ADAM9 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: ADAM9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAM9 were set to 30679166
Phenotypes for gene: ADAM9 were set to Cone-rod dystrophy 9, 612775
Cone-rod Dystrophy v0.0 ABCA4 Bryony Thompson gene: ABCA4 was added
gene: ABCA4 was added to Cone-rod Dystrophies. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: ABCA4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA4 were set to 30679166
Phenotypes for gene: ABCA4 were set to Cone-rod dystrophy 3, 604116
Cone-rod Dystrophy v0.0 Bryony Thompson Added panel Cone-rod Dystrophies
Retinitis pigmentosa_Autosomal Dominant v0.7 PRKCG Bryony Thompson gene: PRKCG was added
gene: PRKCG was added to Autosomal Dominant Retinitis Pigmentosa. Sources: Expert list
Mode of inheritance for gene: PRKCG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRKCG were set to 9545390; 16828200
Phenotypes for gene: PRKCG were set to Retinitis pigmentosa 11 MIM#600138
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.22 IDH3A Bryony Thompson Classified gene: IDH3A as Green List (high evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.22 IDH3A Bryony Thompson Gene: idh3a has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.21 IDH3A Bryony Thompson gene: IDH3A was added
gene: IDH3A was added to Autosomal Recessive/X-Linked Retinitis Pigmentosa. Sources: NHS GMS
Mode of inheritance for gene: IDH3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IDH3A were set to 31012789; 30478029; 30058936; 28412069
Phenotypes for gene: IDH3A were set to Retinitis pigmentosa; Leber congenital amaurosis
Mendeliome v0.2831 ERC1 Zornitza Stark Marked gene: ERC1 as ready
Mendeliome v0.2831 ERC1 Zornitza Stark Gene: erc1 has been classified as Red List (Low Evidence).
Mendeliome v0.2831 ERC1 Zornitza Stark Classified gene: ERC1 as Red List (low evidence)
Mendeliome v0.2831 ERC1 Zornitza Stark Gene: erc1 has been classified as Red List (Low Evidence).
Mendeliome v0.2830 ERC1 Chloe Stutterd reviewed gene: ERC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cerebral vascular malformations v0.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Cerebral vascular malformations v0.0 WDR62 Zornitza Stark gene: WDR62 was added
gene: WDR62 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: WDR62 was set to
Phenotypes for gene: WDR62 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 VLDLR Zornitza Stark gene: VLDLR was added
gene: VLDLR was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: VLDLR was set to
Phenotypes for gene: VLDLR were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TUBG1 Zornitza Stark gene: TUBG1 was added
gene: TUBG1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TUBG1 was set to
Phenotypes for gene: TUBG1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TUBB3 Zornitza Stark gene: TUBB3 was added
gene: TUBB3 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TUBB3 was set to
Phenotypes for gene: TUBB3 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TUBB2B Zornitza Stark gene: TUBB2B was added
gene: TUBB2B was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TUBB2B was set to
Phenotypes for gene: TUBB2B were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TUBB2A Zornitza Stark gene: TUBB2A was added
gene: TUBB2A was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TUBB2A was set to
Phenotypes for gene: TUBB2A were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TUBB Zornitza Stark gene: TUBB was added
gene: TUBB was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TUBB was set to
Phenotypes for gene: TUBB were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TUBA8 Zornitza Stark gene: TUBA8 was added
gene: TUBA8 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TUBA8 was set to
Phenotypes for gene: TUBA8 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TUBA1A Zornitza Stark gene: TUBA1A was added
gene: TUBA1A was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TUBA1A was set to
Phenotypes for gene: TUBA1A were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TRAIP Zornitza Stark gene: TRAIP was added
gene: TRAIP was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TRAIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAIP were set to 26595769
Phenotypes for gene: TRAIP were set to Seckel syndrome 9 616777
Cerebral vascular malformations v0.0 TMEM5 Zornitza Stark gene: TMEM5 was added
gene: TMEM5 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TMEM5 was set to
Phenotypes for gene: TMEM5 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 TGFBR2 Zornitza Stark gene: TGFBR2 was added
gene: TGFBR2 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
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 610168
Cerebral vascular malformations v0.0 TGFBR1 Zornitza Stark gene: TGFBR1 was added
gene: TGFBR1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
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 609192
Cerebral vascular malformations v0.0 TGFB2 Zornitza Stark gene: TGFB2 was added
gene: TGFB2 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
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 614816
Cerebral vascular malformations v0.0 TEK Zornitza Stark gene: TEK was added
gene: TEK was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TEK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TEK were set to Venous malformations, multiple cutaneous and mucosal, 600195; Multiple Cutaneous and Mucosal Venous Malformations
Cerebral vascular malformations v0.0 STAMBP Zornitza Stark gene: STAMBP was added
gene: STAMBP was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: STAMBP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STAMBP were set to Microcephaly-capillary malformation syndrome, 614261; Microcephaly-capillary malformation syndrome
Cerebral vascular malformations v0.0 SRPX2 Zornitza Stark gene: SRPX2 was added
gene: SRPX2 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: SRPX2 was set to
Phenotypes for gene: SRPX2 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 SMARCAL1 Zornitza Stark gene: SMARCAL1 was added
gene: SMARCAL1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: SMARCAL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMARCAL1 were set to 9674900
Phenotypes for gene: SMARCAL1 were set to Schimke immunoosseous dysplasia 242900
Cerebral vascular malformations v0.0 SMAD3 Zornitza Stark gene: SMAD3 was added
gene: SMAD3 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
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 613795
Cerebral vascular malformations v0.0 RTTN Zornitza Stark gene: RTTN was added
gene: RTTN was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: RTTN was set to
Phenotypes for gene: RTTN were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 RELN Zornitza Stark gene: RELN was added
gene: RELN was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: RELN was set to
Phenotypes for gene: RELN were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 RBBP8 Zornitza Stark gene: RBBP8 was added
gene: RBBP8 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: RBBP8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBBP8 were set to 21998596
Phenotypes for gene: RBBP8 were set to Seckel syndrome 2 606744
Cerebral vascular malformations v0.0 PTEN Zornitza Stark gene: PTEN was added
gene: PTEN was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: PTEN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PTEN were set to Bannayan-Riley-Ruvalcaba Syndrome
Cerebral vascular malformations v0.0 POMT2 Zornitza Stark gene: POMT2 was added
gene: POMT2 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: POMT2 was set to
Phenotypes for gene: POMT2 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 POMT1 Zornitza Stark gene: POMT1 was added
gene: POMT1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: POMT1 was set to
Phenotypes for gene: POMT1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 POMGNT1 Zornitza Stark gene: POMGNT1 was added
gene: POMGNT1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: POMGNT1 was set to
Phenotypes for gene: POMGNT1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 PIK3R2 Zornitza Stark gene: PIK3R2 was added
gene: PIK3R2 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: PIK3R2 was set to
Phenotypes for gene: PIK3R2 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 PIK3CA Zornitza Stark gene: PIK3CA was added
gene: PIK3CA was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: PIK3CA was set to
Phenotypes for gene: PIK3CA were set to Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome; Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic; Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic, 602501; Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi; Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 PAFAH1B1 Zornitza Stark gene: PAFAH1B1 was added
gene: PAFAH1B1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: PAFAH1B1 was set to
Phenotypes for gene: PAFAH1B1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 OPHN1 Zornitza Stark gene: OPHN1 was added
gene: OPHN1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: OPHN1 was set to
Phenotypes for gene: OPHN1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 OCLN Zornitza Stark gene: OCLN was added
gene: OCLN was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: OCLN was set to
Phenotypes for gene: OCLN were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 NOTCH3 Zornitza Stark gene: NOTCH3 was added
gene: NOTCH3 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NOTCH3 were set to 20301673; 8878478
Phenotypes for gene: NOTCH3 were set to Cerebral Arteriopathy, Autosomal Dominant, With Subcortical Infarcts And Leukoencephalopathy (CADASIL); Moyamoya disease; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, 125310; Cerebral Arteriopathy, Autosomal Dominant, With Subcortical Infarcts And Leukoencephalopathy; Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
Mode of pathogenicity for gene: NOTCH3 was set to Other - please provide details in the comments
Cerebral vascular malformations v0.0 NIN Zornitza Stark gene: NIN was added
gene: NIN was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: NIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NIN were set to 22933543
Phenotypes for gene: NIN were set to Seckel syndrome 7 614851
Cerebral vascular malformations v0.0 NDE1 Zornitza Stark gene: NDE1 was added
gene: NDE1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: NDE1 was set to
Phenotypes for gene: NDE1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 MEF2C Zornitza Stark gene: MEF2C was added
gene: MEF2C was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: MEF2C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MEF2C were set to Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations; Intellectual Disability, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations; Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, 613443
Cerebral vascular malformations v0.0 LARGE1 Zornitza Stark gene: LARGE1 was added
gene: LARGE1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: LARGE1 was set to
Phenotypes for gene: LARGE1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 LAMC3 Zornitza Stark gene: LAMC3 was added
gene: LAMC3 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: LAMC3 was set to
Phenotypes for gene: LAMC3 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 LAMB1 Zornitza Stark gene: LAMB1 was added
gene: LAMB1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: LAMB1 was set to
Phenotypes for gene: LAMB1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 KDR Zornitza Stark gene: KDR was added
gene: KDR was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: KDR was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: KDR were set to Hemangioma, capillary infantile, somatic; Hemangioma, capillary infantile, somatic, 602089; {Hemangioma, capillary infantile, susceptibility to}, 602089; {Hemangioma, capillary infantile, susceptibility to}
Cerebral vascular malformations v0.0 JAG1 Zornitza Stark gene: JAG1 was added
gene: JAG1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: JAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JAG1 were set to 22759690
Phenotypes for gene: JAG1 were set to Alagille syndrome 1, 118450; Moyamoya disease
Cerebral vascular malformations v0.0 IL6 Zornitza Stark gene: IL6 was added
gene: IL6 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: IL6 was set to
Phenotypes for gene: IL6 were set to {Intracranial hemorrhage in brain cerebrovascular malformations, susceptibility to}
Cerebral vascular malformations v0.0 HTRA1 Zornitza Stark gene: HTRA1 was added
gene: HTRA1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: HTRA1 was set to Unknown
Phenotypes for gene: HTRA1 were set to Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2, 616779; Moyamoya disease
Cerebral vascular malformations v0.0 HLA-DRB1 Zornitza Stark gene: HLA-DRB1 was added
gene: HLA-DRB1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: HLA-DRB1 was set to Unknown
Publications for gene: HLA-DRB1 were set to PMID: 7886716; 21349441
Phenotypes for gene: HLA-DRB1 were set to Moyamoya disease
Cerebral vascular malformations v0.0 HLA-DQB1 Zornitza Stark gene: HLA-DQB1 was added
gene: HLA-DQB1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: HLA-DQB1 was set to Unknown
Publications for gene: HLA-DQB1 were set to PMID: 21349441; 9409445
Phenotypes for gene: HLA-DQB1 were set to Moyamoya disease
Cerebral vascular malformations v0.0 HLA-B Zornitza Stark gene: HLA-B was added
gene: HLA-B was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: HLA-B was set to Unknown
Publications for gene: HLA-B were set to 14676447; PMID: 21349441
Phenotypes for gene: HLA-B were set to Moyamoya disease
Cerebral vascular malformations v0.0 GNAQ Zornitza Stark gene: GNAQ was added
gene: GNAQ was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: GNAQ was set to
Phenotypes for gene: GNAQ were set to Cerebral diseases of vascular origin with epilepsy; Capillary malformations, congenital, 1, somatic, mosaic, 163000
Cerebral vascular malformations v0.0 GLMN Zornitza Stark gene: GLMN was added
gene: GLMN was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: GLMN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: GLMN were set to Glomuvenous Malformation; Glomuvenous malformations
Cerebral vascular malformations v0.0 GLA Zornitza Stark gene: GLA was added
gene: GLA was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: GLA was set to Unknown
Phenotypes for gene: GLA were set to Moyamoya disease
Cerebral vascular malformations v0.0 FOXF1 Zornitza Stark gene: FOXF1 was added
gene: FOXF1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: FOXF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: FOXF1 were set to Alveolar capillary dysplasia with misalignment of pulmonary veins, 265380; Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins
Cerebral vascular malformations v0.0 FLT4 Zornitza Stark gene: FLT4 was added
gene: FLT4 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: FLT4 was set to
Phenotypes for gene: FLT4 were set to Hemangioma, capillary infantile, somatic; Hemangioma, capillary infantile, somatic, 602089
Cerebral vascular malformations v0.0 FBN1 Zornitza Stark gene: FBN1 was added
gene: FBN1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: FBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FBN1 were set to Marfan syndrome 154700
Cerebral vascular malformations v0.0 ELN Zornitza Stark gene: ELN was added
gene: ELN was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: ELN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELN were set to 8460548
Phenotypes for gene: ELN were set to Moyamoya disease; Aneurysm, intracranial berry, 1 105800
Cerebral vascular malformations v0.0 DNA2 Zornitza Stark gene: DNA2 was added
gene: DNA2 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: DNA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNA2 were set to 24389050
Phenotypes for gene: DNA2 were set to Seckel syndrome 8 615807
Cerebral vascular malformations v0.0 DCX Zornitza Stark gene: DCX was added
gene: DCX was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: DCX was set to
Phenotypes for gene: DCX were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 CTSA Zornitza Stark gene: CTSA was added
gene: CTSA was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: CTSA was set to Unknown
Cerebral vascular malformations v0.0 CRB1 Zornitza Stark gene: CRB1 was added
gene: CRB1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: CRB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CRB1 were set to Pigmented Paravenous Chorioretinal Atrophy
Cerebral vascular malformations v0.0 COL4A2 Zornitza Stark gene: COL4A2 was added
gene: COL4A2 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: COL4A2 was set to
Phenotypes for gene: COL4A2 were set to {Hemorrhage, intracerebral, susceptibility to}, 614519; {Hemorrhage, intracerebral, susceptibility to}
Cerebral vascular malformations v0.0 COL4A1 Zornitza Stark gene: COL4A1 was added
gene: COL4A1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: COL4A1 were set to {Hemorrhage, intracerebral, susceptibility to}, 614519; Brain small vessel disease with or without ocular anomalies; Brain Small Vessel Disease with Hemorrhage; {Hemorrhage, intracerebral, susceptibility to}
Cerebral vascular malformations v0.0 CEP63 Zornitza Stark gene: CEP63 was added
gene: CEP63 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: CEP63 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP63 were set to 21983783
Phenotypes for gene: CEP63 were set to Seckel syndrome 6 614728
Cerebral vascular malformations v0.0 CENPJ Zornitza Stark gene: CENPJ was added
gene: CENPJ was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: CENPJ was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CENPJ were set to Seckel syndrome 4 613676
Cerebral vascular malformations v0.0 BRCC3 Zornitza Stark gene: BRCC3 was added
gene: BRCC3 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: BRCC3 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: BRCC3 were set to 21596366
Phenotypes for gene: BRCC3 were set to Moyamoya disease
Cerebral vascular malformations v0.0 ATP7A Zornitza Stark gene: ATP7A was added
gene: ATP7A was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: ATP7A 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: ATP7A were set to Moyamoya disease
Cerebral vascular malformations v0.0 ARX Zornitza Stark gene: ARX was added
gene: ARX was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: ARX was set to
Phenotypes for gene: ARX were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 ANTXR1 Zornitza Stark gene: ANTXR1 was added
gene: ANTXR1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: ANTXR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ANTXR1 were set to {Hemangioma, capillary infantile, susceptibility to}, 602089; {Hemangioma, capillary infantile, susceptibility to}
Cerebral vascular malformations v0.0 ADGRG1 Zornitza Stark gene: ADGRG1 was added
gene: ADGRG1 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: ADGRG1 was set to
Phenotypes for gene: ADGRG1 were set to Cerebral Malformation Disorders
Cerebral vascular malformations v0.0 ACE Zornitza Stark gene: ACE was added
gene: ACE was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: ACE was set to
Phenotypes for gene: ACE were set to {Stroke, hemorrhagic}
Cerebral vascular malformations v0.0 ABCC6 Zornitza Stark gene: ABCC6 was added
gene: ABCC6 was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: ABCC6 was set to Unknown
Phenotypes for gene: ABCC6 were set to Moyamoya disease
Cerebral vascular malformations v0.0 THSD1 Zornitza Stark gene: THSD1 was added
gene: THSD1 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: THSD1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: THSD1 were set to 27895300
Phenotypes for gene: THSD1 were set to subarachnoid hemorrhage
Cerebral vascular malformations v0.0 SMAD9 Zornitza Stark gene: SMAD9 was added
gene: SMAD9 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: SMAD9 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cerebral vascular malformations v0.0 PKD2 Zornitza Stark gene: PKD2 was added
gene: PKD2 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: PKD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PKD2 were set to Polycystic kidney disease 2 613095
Cerebral vascular malformations v0.0 PKD1 Zornitza Stark gene: PKD1 was added
gene: PKD1 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: PKD1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: PKD1 were set to Polycystic kidney disease, adult type I 173900
Cerebral vascular malformations v0.0 PCNT Zornitza Stark gene: PCNT was added
gene: PCNT was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: PCNT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCNT were set to 15368497
Phenotypes for gene: PCNT were set to Microcephalic osteodysplastic primordial dwarfism, type II 210720; Moyamoya disease
Cerebral vascular malformations v0.0 NF1 Zornitza Stark gene: NF1 was added
gene: NF1 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NF1 were set to 10754001
Phenotypes for gene: NF1 were set to Moyamoya disease; Neurofibromatosis, type 1 162200
Cerebral vascular malformations v0.0 MYH11 Zornitza Stark gene: MYH11 was added
gene: MYH11 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: MYH11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MYH11 were set to 16444274; 29263223
Phenotypes for gene: MYH11 were set to Aortic aneurysm, familial thoracic 4, 132900; moyamoya-like angiopath
Cerebral vascular malformations v0.0 MRVI1 Zornitza Stark gene: MRVI1 was added
gene: MRVI1 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: MRVI1 was set to Unknown
Cerebral vascular malformations v0.0 HBB Zornitza Stark gene: HBB was added
gene: HBB was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: HBB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HBB were set to 20301551
Phenotypes for gene: HBB were set to Sickle cell anemia 603903
Cerebral vascular malformations v0.0 GDF2 Zornitza Stark gene: GDF2 was added
gene: GDF2 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: GDF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v0.0 FLVCR2 Zornitza Stark gene: FLVCR2 was added
gene: FLVCR2 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: FLVCR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLVCR2 were set to 20206334
Phenotypes for gene: FLVCR2 were set to Proliferative Vasculopathy And Hydranencephaly-Hydrocephaly Syndrome
Cerebral vascular malformations v0.0 EPHB4 Zornitza Stark gene: EPHB4 was added
gene: EPHB4 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: EPHB4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: EPHB4 were set to Capillary malformation-arteriovenous malformation 2, 618196
Cerebral vascular malformations v0.0 CEP152 Zornitza Stark gene: CEP152 was added
gene: CEP152 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: CEP152 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP152 were set to 21131973
Phenotypes for gene: CEP152 were set to Seckel syndrome 5 613823
Cerebral vascular malformations v0.0 CBL Zornitza Stark gene: CBL was added
gene: CBL was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: CBL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CBL were set to 25283271; 28343148
Phenotypes for gene: CBL were set to early-onset moyamoya angiopathy; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, 613563
Mode of pathogenicity for gene: CBL was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Cerebral vascular malformations v0.0 ATR Zornitza Stark gene: ATR was added
gene: ATR was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: ATR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATR were set to 12640452
Phenotypes for gene: ATR were set to Seckel syndrome 1 210600
Cerebral vascular malformations v0.0 ADA2 Zornitza Stark gene: ADA2 was added
gene: ADA2 was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: ADA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADA2 were set to 3471198, 25528372
Phenotypes for gene: ADA2 were set to Sneddon syndrome 182410; Polyarteritis nodosa
Cerebral vascular malformations v0.0 YY1AP1 Zornitza Stark gene: YY1AP1 was added
gene: YY1AP1 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: YY1AP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: YY1AP1 were set to Grange syndrome, 602531
Cerebral vascular malformations v0.0 SMAD4 Zornitza Stark gene: SMAD4 was added
gene: SMAD4 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: SMAD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMAD4 were set to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome 175050
Cerebral vascular malformations v0.0 SLC2A10 Zornitza Stark gene: SLC2A10 was added
gene: SLC2A10 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: SLC2A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC2A10 were set to 16550171
Phenotypes for gene: SLC2A10 were set to 208050; Moyamoya disease; Arterial tortuosity syndrome
Cerebral vascular malformations v0.0 SAMHD1 Zornitza Stark gene: SAMHD1 was added
gene: SAMHD1 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: SAMHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SAMHD1 were set to 20653736; 21402907
Phenotypes for gene: SAMHD1 were set to Moyamoya disease
Cerebral vascular malformations v0.0 RNF213 Zornitza Stark gene: RNF213 was added
gene: RNF213 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: RNF213 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RNF213 were set to 21048783
Phenotypes for gene: RNF213 were set to {Moyamoya disease 2, susceptibility to}
Cerebral vascular malformations v0.0 RASA1 Zornitza Stark gene: RASA1 was added
gene: RASA1 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: RASA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RASA1 were set to 14639529
Phenotypes for gene: RASA1 were set to Parkes Weber syndrome; Capillary malformation-arteriovenous malformation, 608354; Parkes Weber Syndrome; Parkes Weber syndrome (PKWS); Parkes Weber syndrome, 608355; Capillary Malformation-Arteriovenous Malformation Syndrome
Cerebral vascular malformations v0.0 PDCD10 Zornitza Stark gene: PDCD10 was added
gene: PDCD10 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: PDCD10 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PDCD10 were set to 15543491; 20301470
Phenotypes for gene: PDCD10 were set to Cerebral Cavernous Malformations; Cerebral cavernous malformations 3; Cerebral cavernous malformations 3, 603285; Cerebral Cavernous Malformation; Familial Cerebral Cavernous Malformation
Mode of pathogenicity for gene: PDCD10 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Cerebral vascular malformations v0.0 KRIT1 Zornitza Stark gene: KRIT1 was added
gene: KRIT1 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: KRIT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KRIT1 were set to 10508515; 20301470
Phenotypes for gene: KRIT1 were set to Cerebral cavernous malformations 1; Cerebral cavernous malformations-1, 116860; Cerebral Cavernous Malformations; Cerebral Cavernous Malformation; Angiokeratoma Corporis Diffusum with Arteriovenous Fistulas; Familial Cerebral Cavernous Malformation; Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations, 116860
Cerebral vascular malformations v0.0 GUCY1A3 Zornitza Stark gene: GUCY1A3 was added
gene: GUCY1A3 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: GUCY1A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GUCY1A3 were set to 24581742; 26777256
Phenotypes for gene: GUCY1A3 were set to Moyamoya 6 with achalasia; Moyamoya 6 with achalasia, 615750
Cerebral vascular malformations v0.0 ENG Zornitza Stark gene: ENG was added
gene: ENG was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: ENG was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ENG were set to 15024723; 20301525
Phenotypes for gene: ENG were set to Telangiectasia, hereditary hemorrhagic, type 1 187300
Cerebral vascular malformations v0.0 COL3A1 Zornitza Stark gene: COL3A1 was added
gene: COL3A1 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
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, type IV 130050
Cerebral vascular malformations v0.0 CCM2 Zornitza Stark gene: CCM2 was added
gene: CCM2 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: CCM2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CCM2 were set to 14624391; 20301470
Phenotypes for gene: CCM2 were set to Cerebral cavernous malformations 2; Cerebral Cavernous Malformation; Capillary malformation-arteriovenous malformation 608354; Cerebral Cavernous Malformations
Cerebral vascular malformations v0.0 ACVRL1 Zornitza Stark gene: ACVRL1 was added
gene: ACVRL1 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: ACVRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ACVRL1 were set to Telangiectasia, hereditary hemorrhagic, type 2 600376
Cerebral vascular malformations v0.0 ACTA2 Zornitza Stark gene: ACTA2 was added
gene: ACTA2 was added to Cerebral vascular malformations. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: ACTA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ACTA2 were set to Multisystemic smooth muscle dysfunction syndrome,613834; Aortic aneurysm familial thoracic 6,611788; Moyamoya Disease; Moyamoya disease 5; Moyamoya disease 5,614042
Cerebral vascular malformations v0.0 Zornitza Stark Added panel Cerebral vascular malformations
Osteogenesis Imperfecta and Osteoporosis v0.21 P3H1 Zornitza Stark Marked gene: P3H1 as ready
Osteogenesis Imperfecta and Osteoporosis v0.21 P3H1 Zornitza Stark Gene: p3h1 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.21 P3H1 Zornitza Stark Phenotypes for gene: P3H1 were changed from to Osteogenesis imperfecta, type VIII, (MIM# 610915)
Osteogenesis Imperfecta and Osteoporosis v0.20 P3H1 Zornitza Stark Publications for gene: P3H1 were set to
Osteogenesis Imperfecta and Osteoporosis v0.19 P3H1 Zornitza Stark Mode of inheritance for gene: P3H1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.161 CENPF Zornitza Stark Marked gene: CENPF as ready
Ciliopathies v0.161 CENPF Zornitza Stark Gene: cenpf has been classified as Green List (High Evidence).
Ciliopathies v0.161 CENPF Zornitza Stark Phenotypes for gene: CENPF were changed from to Stromme syndrome (MIM#243605)
Ciliopathies v0.160 CENPF Zornitza Stark Publications for gene: CENPF were set to
Ciliopathies v0.159 CENPF Zornitza Stark Mode of inheritance for gene: CENPF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.70 DDX59 Zornitza Stark Marked gene: DDX59 as ready
Joubert syndrome and other neurological ciliopathies v0.70 DDX59 Zornitza Stark Gene: ddx59 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.70 DDX59 Zornitza Stark Classified gene: DDX59 as Green List (high evidence)
Joubert syndrome and other neurological ciliopathies v0.70 DDX59 Zornitza Stark Gene: ddx59 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.69 ICK Zornitza Stark Marked gene: ICK as ready
Joubert syndrome and other neurological ciliopathies v0.69 ICK Zornitza Stark Gene: ick has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.69 ICK Zornitza Stark Classified gene: ICK as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.69 ICK Zornitza Stark Gene: ick has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2830 DHCR7 Zornitza Stark Marked gene: DHCR7 as ready
Mendeliome v0.2830 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Green List (High Evidence).
Mendeliome v0.2830 DHCR7 Zornitza Stark Phenotypes for gene: DHCR7 were changed from to Smith-Lemli-Opitz syndrome (MIM#270400)
Mendeliome v0.2829 DHCR7 Zornitza Stark Publications for gene: DHCR7 were set to
Mendeliome v0.2828 DHCR7 Zornitza Stark Mode of inheritance for gene: DHCR7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.68 DHCR7 Zornitza Stark Marked gene: DHCR7 as ready
Joubert syndrome and other neurological ciliopathies v0.68 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.68 DHCR7 Zornitza Stark Classified gene: DHCR7 as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.68 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.158 EVC2 Zornitza Stark Marked gene: EVC2 as ready
Ciliopathies v0.158 EVC2 Zornitza Stark Gene: evc2 has been classified as Green List (High Evidence).
Ciliopathies v0.158 EVC2 Zornitza Stark Phenotypes for gene: EVC2 were changed from to Ellis-van Creveld syndrome (MIM#225500)
Ciliopathies v0.157 EVC2 Zornitza Stark Publications for gene: EVC2 were set to
Ciliopathies v0.156 EVC2 Zornitza Stark Mode of inheritance for gene: EVC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.67 EVC Zornitza Stark Marked gene: EVC as ready
Joubert syndrome and other neurological ciliopathies v0.67 EVC Zornitza Stark Gene: evc has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.67 EVC Zornitza Stark Classified gene: EVC as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.67 EVC Zornitza Stark Gene: evc has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.66 GLI3 Zornitza Stark Marked gene: GLI3 as ready
Joubert syndrome and other neurological ciliopathies v0.66 GLI3 Zornitza Stark Gene: gli3 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.66 GLI3 Zornitza Stark Mode of inheritance for gene: GLI3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Joubert syndrome and other neurological ciliopathies v0.65 GLI3 Zornitza Stark Classified gene: GLI3 as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.65 GLI3 Zornitza Stark Gene: gli3 has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.155 GLI3 Zornitza Stark Marked gene: GLI3 as ready
Ciliopathies v0.155 GLI3 Zornitza Stark Gene: gli3 has been classified as Green List (High Evidence).
Ciliopathies v0.155 GLI3 Zornitza Stark Phenotypes for gene: GLI3 were changed from to Greig cephalopolysyndactyly syndrome (MIM#175700); Pallister-Hall syndrome (MIM#146510)
Ciliopathies v0.154 GLI3 Zornitza Stark Publications for gene: GLI3 were set to
Ciliopathies v0.153 GLI3 Zornitza Stark Mode of inheritance for gene: GLI3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.14 TTC21B Zornitza Stark Marked gene: TTC21B as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.14 TTC21B Zornitza Stark Gene: ttc21b has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.14 TTC21B Zornitza Stark Phenotypes for gene: TTC21B were changed from to Short-rib thoracic dysplasia 4 with or without polydactyly (MIM#613819)
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.13 TTC21B Zornitza Stark Publications for gene: TTC21B were set to
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.12 TTC21B Zornitza Stark Mode of inheritance for gene: TTC21B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Optic Atrophy v0.107 PDXK Zornitza Stark Marked gene: PDXK as ready
Optic Atrophy v0.107 PDXK Zornitza Stark Gene: pdxk has been classified as Amber List (Moderate Evidence).
Optic Atrophy v0.107 PDXK Zornitza Stark Classified gene: PDXK as Amber List (moderate evidence)
Optic Atrophy v0.107 PDXK Zornitza Stark Gene: pdxk has been classified as Amber List (Moderate Evidence).
Optic Atrophy v0.106 PDXK Zornitza Stark gene: PDXK was added
gene: PDXK was added to Optic Atrophy. Sources: Literature
Mode of inheritance for gene: PDXK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDXK were set to 31187503
Phenotypes for gene: PDXK were set to Axonal polyneuropathy; optic atrophy
Review for gene: PDXK was set to AMBER
Added comment: 5 individuals from two unrelated families, cell-based functional assays. Response to pyridoxal 5'-phosphate supplementation.
Sources: Literature
Hereditary Neuropathy - complex v0.60 PDXK Zornitza Stark Marked gene: PDXK as ready
Hereditary Neuropathy - complex v0.60 PDXK Zornitza Stark Gene: pdxk has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.60 PDXK Zornitza Stark Classified gene: PDXK as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.60 PDXK Zornitza Stark Gene: pdxk has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.59 PDXK Zornitza Stark gene: PDXK was added
gene: PDXK was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for gene: PDXK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDXK were set to 31187503
Phenotypes for gene: PDXK were set to Axonal polyneuropathy; optic atrophy
Review for gene: PDXK was set to AMBER
Added comment: 5 individuals from two unrelated families, cell-based functional assays. Response to pyridoxal 5'-phosphate supplementation.
Sources: Literature
Mendeliome v0.2827 PDXK Zornitza Stark Marked gene: PDXK as ready
Mendeliome v0.2827 PDXK Zornitza Stark Gene: pdxk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2827 PDXK Zornitza Stark Publications for gene: PDXK were set to (PMID: 31187503)
Mendeliome v0.2826 PDXK Zornitza Stark Classified gene: PDXK as Amber List (moderate evidence)
Mendeliome v0.2826 PDXK Zornitza Stark Gene: pdxk has been classified as Amber List (Moderate Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.18 P3H1 Ain Roesley reviewed gene: P3H1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17277775, 18566967; Phenotypes: Osteogenesis imperfecta, type VIII, (MIM# 610915); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2825 PDXK Zornitza Stark reviewed gene: PDXK: Rating: AMBER; Mode of pathogenicity: None; Publications: 31187503; Phenotypes: Axonal polyneuropathy, optic atrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.64 TTC21B Zornitza Stark Marked gene: TTC21B as ready
Joubert syndrome and other neurological ciliopathies v0.64 TTC21B Zornitza Stark Gene: ttc21b has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.64 TTC21B Zornitza Stark Publications for gene: TTC21B were set to
Joubert syndrome and other neurological ciliopathies v0.63 TTC21B Zornitza Stark Classified gene: TTC21B as Red List (low evidence)
Joubert syndrome and other neurological ciliopathies v0.63 TTC21B Zornitza Stark Gene: ttc21b has been classified as Red List (Low Evidence).
Bone Marrow Failure v0.61 MECOM Zornitza Stark Mode of pathogenicity for gene: MECOM was changed from None to Other
Joubert syndrome and other neurological ciliopathies v0.62 CENPF Crystle Lee gene: CENPF was added
gene: CENPF was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: CENPF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPF were set to 25564561; 28407396; 26820108
Phenotypes for gene: CENPF were set to Stromme syndrome (MIM#243605)
Review for gene: CENPF was set to AMBER
Added comment: Stromme syndrome is well reported as a ciliopathy phenotype with some overlapping JS features although does not seem to be consistent between patients. Amber for this panel

PMID: 25564561; Waters 2015; 2 families reported. Ciliopathy features such as cerebellar vermis hypoplasia and cleft palate reported in one family. Functional studies performed.
PMID: 28407396; Ozkinay 2017; 1 family reported. Brain MRI showed lissecephaly.
PMID: 26820108; Filges 2016; 2 families reported.
Sources: Expert Review
Ciliopathies v0.152 CENPF Crystle Lee reviewed gene: CENPF: Rating: GREEN; Mode of pathogenicity: None; Publications: 25564561, 28407396, 26820108; Phenotypes: Stromme syndrome (MIM#243605); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.62 DDX59 Crystle Lee gene: DDX59 was added
gene: DDX59 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: DDX59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX59 were set to 29127725; 23972372; 28711741
Phenotypes for gene: DDX59 were set to Orofaciodigital syndrome V (MIM#174300)
Review for gene: DDX59 was set to GREEN
Added comment: Overlapping JS features including cerebellar vermis hypoplasia, cleft palate and postaxial polydactyly. 4 or 5 families reported to date and functional studies performed.

PMID: 29127725; 1 family with OFD
PMID: 23972372; 2 different hom variants reported in 2 families. Functional studies showed impaired ciliary signaling
PMID: 28711741; Same hom variant reported in 2 apparently unrelated consang families. Cerebellar vermis hypoplasia reported in 1 patient
Sources: Expert Review
Joubert syndrome and other neurological ciliopathies v0.62 ICK Crystle Lee gene: ICK was added
gene: ICK was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: ICK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ICK were set to 19185282; 27069622; 27466187; 24797473; 24853502
Phenotypes for gene: ICK were set to Endocrine-cerebroosteodysplasia (MIM#612651)
Review for gene: ICK was set to AMBER
Added comment: 3 families reported, functional studies and animal models. Primarily a skeletal ciliopathy and rare reports of brain and cerebellar malformations. Amber for this panel.

PMID: 19185282; 6 affected from 2 Amish families with endocrine-cerebro-osteodysplasia (ECO)

PMID: 27069622; A different variant reported in a Turkish fetus presenting with ECO and overlapping features of ciliopathies. Functional studies showed abnormal ciliary localization.

PMID: 27466187; Additional variant identified in a patient with short rib polydactyly syndromes (SRPS). Functional studies showed that the variant caused ciliary defects

PMID: 24797473; Ick deficient mice showed ciliary defects. Authors concluded that ICK is required for normal ciliogenesis

PMID: 24853502; Ick knockout mice recapitulates clinical symptoms of ECO. Defects in ICK caused aberrant ciliogenesis
Sources: Expert Review
Mendeliome v0.2825 DHCR7 Crystle Lee reviewed gene: DHCR7: Rating: GREEN; Mode of pathogenicity: None; Publications: 23059950; Phenotypes: Smith-Lemli-Opitz syndrome (MIM#270400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.62 DHCR7 Crystle Lee gene: DHCR7 was added
gene: DHCR7 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHCR7 were set to 23059950
Phenotypes for gene: DHCR7 were set to Smith-Lemli-Opitz syndrome (MIM#270400)
Review for gene: DHCR7 was set to AMBER
Added comment: Not a ciliopathy however presents with many overlapping JS features including central nervous system anomalies, cleft palate, postaxial polydactyly

PanelApp UK: Important differential diagnosis of ciliopathy
Sources: Expert Review
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.11 EVC2 Crystle Lee reviewed gene: EVC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23220543; Phenotypes: Ellis-van Creveld syndrome (MIM#225500); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.152 EVC2 Crystle Lee reviewed gene: EVC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23220543; Phenotypes: Ellis-van Creveld syndrome (MIM#225500); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.62 EVC Crystle Lee gene: EVC was added
gene: EVC was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: EVC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EVC were set to 23220543
Phenotypes for gene: EVC were set to Ellis-van Creveld syndrome (MIM#225500)
Review for gene: EVC was set to AMBER
Added comment: Well established ciliopathy gene, primarily with skeletal manifestations and rare reports of cerebellar malformations (Dandy-Walker malformation)
Sources: Expert Review
Joubert syndrome and other neurological ciliopathies v0.62 GLI3 Crystle Lee gene: GLI3 was added
gene: GLI3 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: GLI3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: GLI3 were set to Greig cephalopolysyndactyly syndrome (MIM#175700); Pallister-Hall syndrome (MIM#146510)
Review for gene: GLI3 was set to AMBER
Added comment: Ciliopathy with some overlapping features of JS, primarily skeletal manifestation.

PMID: 24736735; In a cohort of 55 families, hypoplastic cerebellum was found in 2 patients but without the characteristic molar tooth sign. There appears to be overlapping JS features including limb and craniofacial abnormalities
Sources: Expert Review
Ciliopathies v0.152 GLI3 Crystle Lee reviewed gene: GLI3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24736735; Phenotypes: Greig cephalopolysyndactyly syndrome (MIM#175700), Pallister-Hall syndrome (MIM#146510); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v0.11 TTC21B Crystle Lee reviewed gene: TTC21B: Rating: GREEN; Mode of pathogenicity: None; Publications: 29068549, 25492405, 21258341; Phenotypes: Short-rib thoracic dysplasia 4 with or without polydactyly (MIM#613819); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2825 PDXK Russell Gear gene: PDXK was added
gene: PDXK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDXK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDXK were set to (PMID: 31187503)
Phenotypes for gene: PDXK were set to Axonal polyneuropathy; optic atrophy
Review for gene: PDXK was set to RED
Added comment: Currently two unrelated families with axonal polyneuropathy and optic atrophy described in the same paper, with bi-allelic PDXK pathogenic variants. Functional work in the same paper includes work on patient derived fibroblasts, measurement of an axonal damage biomarker (NFL protein), and response to PLP supplementation treatment.

Need one further unrelated family to upgrade to green?
Sources: Literature
Joubert syndrome and other neurological ciliopathies v0.62 TTC21B Crystle Lee changed review comment from: Weak evidence supporting gene as causative of JS.


PMID: 21258341; Davis 2011; Reported het variants in 3 JBTS patients however one of the missense variants, M1186V, present in gnomAD (10 hets) and multiple MKS patients. T231S in one MKS patient present in gnomAD 280 hets and 2 hom.; to: Weak evidence supporting gene as causative of JS.

PMID: 21258341; Davis 2011; Reported het variants in 3 JBTS patients however one of the missense variants, M1186V, present in gnomAD (10 hets) and multiple MKS patients. T231S in one MKS patient present in gnomAD 280 hets and 2 hom.
Joubert syndrome and other neurological ciliopathies v0.62 TTC21B Crystle Lee reviewed gene: TTC21B: Rating: RED; Mode of pathogenicity: None; Publications: 21258341; Phenotypes: ; Mode of inheritance: None
Joubert syndrome and other neurological ciliopathies v0.62 TTC21B Crystle Lee Deleted their review
Joubert syndrome and other neurological ciliopathies v0.62 TTC21B Crystle Lee reviewed gene: TTC21B: Rating: RED; Mode of pathogenicity: None; Publications: 25492405, 21258341; Phenotypes: Short-rib thoracic dysplasia 4 with or without polydactyly (MIM#613819); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bone Marrow Failure v0.60 MECOM Ain Roesley changed review comment from: PMID: 29146883; 6 unrelated individuals with heamatological defects without RUS. de novo variants cause severe aplastic anemia (AA) occuring within the first months of life that requries hematopoietic stem cel transplatation (HSCT).
Mutational spectrum: 2 missense, 2 frameshifts, 1 nonsense and 1 splice; to: PMID: 29146883; 5 unrelated individuals with heamatological defects without RUS. de novo variants cause severe aplastic anemia (AA) occuring within the first months of life that requries hematopoietic stem cel transplatation (HSCT).
Mutational spectrum: 1 missense, 2 frameshifts, 1 nonsense and 1 splice
Bone Marrow Failure v0.60 MECOM Zornitza Stark Phenotypes for gene: MECOM were changed from Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, MIM#616738 to Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, MIM#616738; Bone marrow failure without radioulnar synostosis (RUS)
Bone Marrow Failure v0.59 MECOM Zornitza Stark Publications for gene: MECOM were set to 26581901; 29519864
Proteinuria v0.109 ANLN Michelle Torres reviewed gene: ANLN: Rating: AMBER; Mode of pathogenicity: None; Publications: 24676636, 30002222; Phenotypes: Focal segmental glomerulosclerosis 8 616032; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Proteinuria v0.109 ANLN Michelle Torres Deleted their review
Proteinuria v0.109 ANLN Michelle Torres reviewed gene: ANLN: Rating: GREEN; Mode of pathogenicity: None; Publications: 24676636, 30002222; Phenotypes: Focal segmental glomerulosclerosis 8 616032; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bone Marrow Failure v0.58 MECOM Ain Roesley reviewed gene: MECOM: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29146883; Phenotypes: bone marrow failure without radioulnar synostosis (RUS); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliopathies v0.152 IQCE Zornitza Stark Marked gene: IQCE as ready
Ciliopathies v0.152 IQCE Zornitza Stark Gene: iqce has been classified as Green List (High Evidence).
Ciliopathies v0.152 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Ciliopathies v0.150 IQCE Bryony Thompson Classified gene: IQCE as Green List (high evidence)
Ciliopathies v0.150 IQCE Bryony Thompson Gene: iqce has been classified as Green List (High Evidence).
Ciliopathies v0.149 IQCE Bryony Thompson gene: IQCE was added
gene: IQCE was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: IQCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IQCE were set to 31549751; 28488682
Phenotypes for gene: IQCE were set to Postaxial polydactyly
Joubert syndrome and other neurological ciliopathies v0.61 PDE6D Zornitza Stark Classified gene: PDE6D as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.61 PDE6D Zornitza Stark Gene: pde6d has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.60 PDE6D Zornitza Stark edited their review of gene: PDE6D: Changed rating: AMBER
Joubert syndrome and other neurological ciliopathies v0.60 PDE6D Zornitza Stark commented on gene: PDE6D: Second family reported.
Joubert syndrome and other neurological ciliopathies v0.60 PDE6D Zornitza Stark edited their review of gene: PDE6D: Changed publications: 24166846, 30423442
Ciliopathies v0.147 PDE6D Zornitza Stark edited their review of gene: PDE6D: Changed rating: AMBER; Changed publications: 24166846, 30423442
Joubert syndrome and other neurological ciliopathies v0.60 PDE6D Zornitza Stark Marked gene: PDE6D as ready
Joubert syndrome and other neurological ciliopathies v0.60 PDE6D Zornitza Stark Gene: pde6d has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.60 PDE6D Zornitza Stark Classified gene: PDE6D as Red List (low evidence)
Joubert syndrome and other neurological ciliopathies v0.60 PDE6D Zornitza Stark Gene: pde6d has been classified as Red List (Low Evidence).
Mendeliome v0.2825 NDP Zornitza Stark Marked gene: NDP as ready
Mendeliome v0.2825 NDP Zornitza Stark Gene: ndp has been classified as Green List (High Evidence).
Mendeliome v0.2825 NDP Zornitza Stark Phenotypes for gene: NDP were changed from to Exudative vitreoretinopathy 2, X-linked, MIM 305390; Norrie disease, MIM 310600
Mendeliome v0.2824 NDP Zornitza Stark Publications for gene: NDP were set to
Mendeliome v0.2823 NDP Zornitza Stark Mode of inheritance for gene: NDP was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Joubert syndrome and other neurological ciliopathies v0.59 SCLT1 Zornitza Stark Marked gene: SCLT1 as ready
Joubert syndrome and other neurological ciliopathies v0.59 SCLT1 Zornitza Stark Gene: sclt1 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.59 SCLT1 Zornitza Stark Phenotypes for gene: SCLT1 were changed from Orofaciodigital syndrome type IX; Senior-Loken syndrome to Orofaciodigital syndrome type IX; Senior-Loken syndrome; Bardet-Biedl syndrome
Joubert syndrome and other neurological ciliopathies v0.58 SCLT1 Zornitza Stark Classified gene: SCLT1 as Red List (low evidence)
Joubert syndrome and other neurological ciliopathies v0.58 SCLT1 Zornitza Stark Gene: sclt1 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.57 SCLT1 Zornitza Stark reviewed gene: SCLT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Orofaciodigital syndrome type IX, Senior-Loken syndrome, Bardet-Biedl syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.57 POC1B Zornitza Stark Marked gene: POC1B as ready
Joubert syndrome and other neurological ciliopathies v0.57 POC1B Zornitza Stark Added comment: Comment when marking as ready: Mostly ocular phenotype consistent with ciliopathy, insufficient reports to support association with JS/brain phenotypes.
Joubert syndrome and other neurological ciliopathies v0.57 POC1B Zornitza Stark Gene: poc1b has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.57 POC1B Zornitza Stark Classified gene: POC1B as Red List (low evidence)
Joubert syndrome and other neurological ciliopathies v0.57 POC1B Zornitza Stark Gene: poc1b has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.56 KIAA0753 Zornitza Stark Marked gene: KIAA0753 as ready
Joubert syndrome and other neurological ciliopathies v0.56 KIAA0753 Zornitza Stark Added comment: Comment when marking as ready: Sufficient number of families with neurological features consistent with ciliopathy/JS.
Joubert syndrome and other neurological ciliopathies v0.56 KIAA0753 Zornitza Stark Gene: kiaa0753 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.56 KIAA0753 Zornitza Stark Classified gene: KIAA0753 as Green List (high evidence)
Joubert syndrome and other neurological ciliopathies v0.56 KIAA0753 Zornitza Stark Gene: kiaa0753 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.55 VPS13B Zornitza Stark Marked gene: VPS13B as ready
Joubert syndrome and other neurological ciliopathies v0.55 VPS13B Zornitza Stark Gene: vps13b has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.55 VPS13B Zornitza Stark Classified gene: VPS13B as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.55 VPS13B Zornitza Stark Gene: vps13b has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.54 TMEM107 Zornitza Stark Phenotypes for gene: TMEM107 were changed from Meckel syndrome 13 (MIM#617562); Orofaciodigital syndrome XVI (MIM#617563) to Meckel syndrome 13 (MIM#617562); Orofaciodigital syndrome XVI (MIM#617563); Joubert syndrome 29, MIM# 617562
Mendeliome v0.2822 TMEM107 Zornitza Stark Marked gene: TMEM107 as ready
Mendeliome v0.2822 TMEM107 Zornitza Stark Gene: tmem107 has been classified as Green List (High Evidence).
Mendeliome v0.2822 TMEM107 Zornitza Stark Phenotypes for gene: TMEM107 were changed from to Meckel syndrome 13 (MIM#617562); Orofaciodigital syndrome XVI (MIM#617563); Joubert syndrome 29, MIM# 617562
Mendeliome v0.2821 TMEM107 Zornitza Stark Publications for gene: TMEM107 were set to
Mendeliome v0.2820 TMEM107 Zornitza Stark Mode of inheritance for gene: TMEM107 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2819 TMEM107 Zornitza Stark reviewed gene: TMEM107: Rating: GREEN; Mode of pathogenicity: None; Publications: 26518474, 26595381, 26123494; Phenotypes: Meckel syndrome 13 (MIM#617562), Orofaciodigital syndrome XVI (MIM#617563), Joubert syndrome 29 617562; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.146 TMEM107 Zornitza Stark Marked gene: TMEM107 as ready
Ciliopathies v0.146 TMEM107 Zornitza Stark Gene: tmem107 has been classified as Green List (High Evidence).
Ciliopathies v0.146 TMEM107 Zornitza Stark Phenotypes for gene: TMEM107 were changed from to Meckel syndrome 13 (MIM#617562); Orofaciodigital syndrome XVI (MIM#617563); Joubert syndrome 29 617562
Ciliopathies v0.145 TMEM107 Zornitza Stark Publications for gene: TMEM107 were set to
Ciliopathies v0.144 TMEM107 Zornitza Stark Mode of inheritance for gene: TMEM107 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.143 TMEM107 Zornitza Stark reviewed gene: TMEM107: Rating: GREEN; Mode of pathogenicity: None; Publications: 26518474, 26595381, 26123494; Phenotypes: Meckel syndrome 13 (MIM#617562), Orofaciodigital syndrome XVI (MIM#617563), Joubert syndrome 29 617562; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.100 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; KidGen; Royal Melbourne Hospital; Rare Disease
Joubert syndrome and other neurological ciliopathies v0.53 TMEM107 Zornitza Stark Marked gene: TMEM107 as ready
Joubert syndrome and other neurological ciliopathies v0.53 TMEM107 Zornitza Stark Gene: tmem107 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.53 TMEM107 Zornitza Stark Classified gene: TMEM107 as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.53 TMEM107 Zornitza Stark Gene: tmem107 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.52 HYLS1 Zornitza Stark Marked gene: HYLS1 as ready
Joubert syndrome and other neurological ciliopathies v0.52 HYLS1 Zornitza Stark Gene: hyls1 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.52 HYLS1 Zornitza Stark Classified gene: HYLS1 as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.52 HYLS1 Zornitza Stark Gene: hyls1 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.51 TXNDC15 Zornitza Stark Marked gene: TXNDC15 as ready
Joubert syndrome and other neurological ciliopathies v0.51 TXNDC15 Zornitza Stark Gene: txndc15 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.51 TXNDC15 Zornitza Stark Classified gene: TXNDC15 as Green List (high evidence)
Joubert syndrome and other neurological ciliopathies v0.51 TXNDC15 Zornitza Stark Gene: txndc15 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.21 ALPL Zornitza Stark Marked gene: ALPL as ready
Skeletal Dysplasia_Fetal v0.21 ALPL Zornitza Stark Gene: alpl has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.21 ALPL Zornitza Stark Phenotypes for gene: ALPL were changed from to Hypophosphatasia, infantile MIM# 241500
Skeletal Dysplasia_Fetal v0.20 ALPL Zornitza Stark Publications for gene: ALPL were set to
Skeletal Dysplasia_Fetal v0.19 ALPL Zornitza Stark Mode of inheritance for gene: ALPL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.18 ALPL Zornitza Stark reviewed gene: ALPL: Rating: GREEN; Mode of pathogenicity: None; Publications: 19500388, 23688511; Phenotypes: Hypophosphatasia, infantile MIM# 241500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2819 ALPL Zornitza Stark Marked gene: ALPL as ready
Mendeliome v0.2819 ALPL Zornitza Stark Gene: alpl has been classified as Green List (High Evidence).
Mendeliome v0.2819 ALPL Zornitza Stark Phenotypes for gene: ALPL were changed from to Hypophosphatasia, adult 146300 (AD, AR); Hypophosphatasia, childhood 241510 AR; Hypophosphatasia, infantile 241500 AR; Odontohypophosphatasia 146300 AD, AR
Mendeliome v0.2818 ALPL Zornitza Stark Publications for gene: ALPL were set to
Mendeliome v0.2817 ALPL Zornitza Stark Mode of pathogenicity for gene: ALPL was changed from to Other
Mendeliome v0.2816 ALPL Zornitza Stark Mode of inheritance for gene: ALPL was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Ciliopathies v0.143 MUC1 Zornitza Stark Marked gene: MUC1 as ready
Ciliopathies v0.143 MUC1 Zornitza Stark Added comment: Comment when marking as ready: Agree, some phenotypic overlap but not a ciliopathy and main variant type not currently readily tractable by NGS.
Ciliopathies v0.143 MUC1 Zornitza Stark Gene: muc1 has been classified as Red List (Low Evidence).
Ciliopathies v0.143 MUC1 Zornitza Stark Phenotypes for gene: MUC1 were changed from to Medullary cystic kidney disease 1 (MIM#174000)
Ciliopathies v0.142 MUC1 Zornitza Stark Publications for gene: MUC1 were set to
Ciliopathies v0.141 MUC1 Zornitza Stark Mode of inheritance for gene: MUC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliopathies v0.140 MUC1 Zornitza Stark Classified gene: MUC1 as Red List (low evidence)
Ciliopathies v0.140 MUC1 Zornitza Stark Gene: muc1 has been classified as Red List (Low Evidence).
Joubert syndrome and other neurological ciliopathies v0.50 C2CD3 Zornitza Stark Marked gene: C2CD3 as ready
Joubert syndrome and other neurological ciliopathies v0.50 C2CD3 Zornitza Stark Gene: c2cd3 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.50 C2CD3 Zornitza Stark Classified gene: C2CD3 as Green List (high evidence)
Joubert syndrome and other neurological ciliopathies v0.50 C2CD3 Zornitza Stark Gene: c2cd3 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.76 LRRC56 Zornitza Stark Marked gene: LRRC56 as ready
Ciliary Dyskinesia v0.76 LRRC56 Zornitza Stark Gene: lrrc56 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.76 LRRC56 Zornitza Stark Classified gene: LRRC56 as Green List (high evidence)
Ciliary Dyskinesia v0.76 LRRC56 Zornitza Stark Gene: lrrc56 has been classified as Green List (High Evidence).
Mendeliome v0.2815 LRRC56 Zornitza Stark Marked gene: LRRC56 as ready
Mendeliome v0.2815 LRRC56 Zornitza Stark Gene: lrrc56 has been classified as Green List (High Evidence).
Mendeliome v0.2815 LRRC56 Zornitza Stark Classified gene: LRRC56 as Green List (high evidence)
Mendeliome v0.2815 LRRC56 Zornitza Stark Gene: lrrc56 has been classified as Green List (High Evidence).
Mendeliome v0.2814 LRRC56 Zornitza Stark reviewed gene: LRRC56: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 39, MIM# 618254; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2637 IQSEC3 Zornitza Stark Phenotypes for gene: IQSEC3 were changed from Intellectual disability to Intellectual disability; Fetal akinesia
Intellectual disability syndromic and non-syndromic v0.2636 IQSEC3 Zornitza Stark Publications for gene: IQSEC3 were set to 31130284
Joubert syndrome and other neurological ciliopathies v0.49 KIAA0586 Zornitza Stark Marked gene: KIAA0586 as ready
Joubert syndrome and other neurological ciliopathies v0.49 KIAA0586 Zornitza Stark Gene: kiaa0586 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.49 KIAA0586 Zornitza Stark Classified gene: KIAA0586 as Green List (high evidence)
Joubert syndrome and other neurological ciliopathies v0.49 KIAA0586 Zornitza Stark Gene: kiaa0586 has been classified as Green List (High Evidence).
Mendeliome v0.2814 NDP Teresa Zhao reviewed gene: NDP: Rating: GREEN; Mode of pathogenicity: None; Publications: 23444378, 8268931, 17325173, 27217716, 29181528, 31827910; Phenotypes: Exudative vitreoretinopathy 2, X-linked, MIM 305390, Norrie disease, MIM 310600; Mode of inheritance: Other
Joubert syndrome and other neurological ciliopathies v0.48 SCLT1 Elena Savva gene: SCLT1 was added
gene: SCLT1 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert list
Mode of inheritance for gene: SCLT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCLT1 were set to PMID: 24285566; 32253632; 30425282
Phenotypes for gene: SCLT1 were set to Orofaciodigital syndrome type IX; Senior-Loken syndrome
Review for gene: SCLT1 was set to AMBER
Added comment: PMID: 24285566 - 1 patient with a homozygous splice variant, proven to result in a fs and NMD protein. MRI results show agenesis of corpus callosum and pachygyria - no mention of cerebellar hypoplasia or MTS. Additional features include coloboma and cleft lip/palate

PMID: 32253632 - 2 unrelated patients with Bardet-Biedl syndrome. Both patients were chet for the same variants (missense), one found to have splice consequences. Neither patient had polydactyly, but both had ID and renal dysfunction.

PMID: 30425282 - 1 patient (chet splice/splice) with Senior Løken syndrome. Patient had renal dysfunction, mild ID but no MRI performed. Authors suggest biallelic null LOF variants are more severe.

Summary: no JS patients but a clear relationship to similar ciliopathies. Potentially needs adding to the BBS gene list.
Sources: Expert list
Joubert syndrome and other neurological ciliopathies v0.48 POC1B Elena Savva gene: POC1B was added
gene: POC1B was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert list
Mode of inheritance for gene: POC1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POC1B were set to PMID: 25044745; 31390656; 25018096
Phenotypes for gene: POC1B were set to Cone-rod dystrophy 20 615973
Review for gene: POC1B was set to RED
Added comment: PMID: 25044745 - 1 homozygous family (missense) with leber congenital amaurosis, JS and polycystic kidney disease. 13 healthy relatives were wildtype or heterozygous carriers only.
MRI shows MTS, cerebellar vermis hypoplasia and malorientated cerebellar peduncles.
Null zebrafish model had cystic kidney and retinal degeneration - no mention of JS features.

PMID: 31390656 - 7 families (8 patients) either chet (PTC/missense) or homozygous (missense) with retinopathies. No mention of JS-related phenotypes eg. polydactyly, brain malformation, intellectual disability

PMID: 25018096 - 1 homozygous family (missense) with cone rod dystrophy. No mention of JS-related phenotypes eg. polydactyly, brain malformation, intellectual disability

Summary: single example of JS, doesnt seem to correlate with a particular genotype
Sources: Expert list
Joubert syndrome and other neurological ciliopathies v0.48 KIAA0753 Elena Savva gene: KIAA0753 was added
gene: KIAA0753 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert list
Mode of inheritance for gene: KIAA0753 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0753 were set to PMID: 31816441; 28220259; 29138412; 26643951
Phenotypes for gene: KIAA0753 were set to ?Orofaciodigital syndrome XV 617127; Joubert syndrome
Review for gene: KIAA0753 was set to GREEN
Added comment: PMID: 31816441 - 1 patient with a homozygous PTC. No MTS on MRI at 8 months old, clearly stated by authors. Patient had a skeletal dysplasia. Authors summerize reports, no obvious genotype-phenotype correlation.

PMID: 28220259 - 2 chet (missense/inframe del) siblings with JS. Both siblings showed the MTS on MRI, one also had additional hypoplasia of cerebellar vermis. Functional studies on patient cells demonstrated significantly less cilia.

PMID: 29138412 - All patients had brachydactyly.
Patient 1 and 2 (cousins) - showed MTS on MRI, inferior vermis dysplasia. Patients had a homozygous PTC.
Patient 3 - no MTS, but described as having brain features consistent with JS.
Patient 4 - vermis dysplasia, no mention of MTS. Not regarded as having JS, diagnosed with short-rib thoracic dyplasia. Patient was chet for two PTCs.
Zebrafish null models have skeletal abnormalities, no mention of brain analysis/abnormalities

PMID: 26643951 - 1 chet patient (PTC/splice causing fs) with OFD syndrome. MRI shows MTS and vermis hypoplasia
Sources: Expert list
Joubert syndrome and other neurological ciliopathies v0.48 VPS13B Crystle Lee gene: VPS13B was added
gene: VPS13B was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: VPS13B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS13B were set to Cohen syndrome (MIM# 216550)
Review for gene: VPS13B was set to AMBER
Added comment: Well reported to cause Cohen syndrome. Amber for this gene panel due to phenotypic overlap although not strictly a cilipoathy.
Sources: Expert Review
Joubert syndrome and other neurological ciliopathies v0.48 TMEM107 Crystle Lee gene: TMEM107 was added
gene: TMEM107 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: TMEM107 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM107 were set to 26595381; 26123494
Phenotypes for gene: TMEM107 were set to Meckel syndrome 13 (MIM#617562); Orofaciodigital syndrome XVI (MIM#617563)
Review for gene: TMEM107 was set to AMBER
Added comment: Minimal reports to date. Left as amber for now pending additional reports. Bordeline amber/green

PMID: 26595381; Lambacher 2016: Reported hom (OFDVI female twins) and chet variants (JBTS male) in 2 families. All possesed JBTS-associated molar tooth sign

PMID: 26123494; Shaheen 2015: Same hom splice variant reported in 2 apparently unrelated families (counted as 1). Anaylsis of patient fibroblasts shows ciliogenesis defect.
Sources: Expert Review
Joubert syndrome and other neurological ciliopathies v0.48 HYLS1 Elena Savva gene: HYLS1 was added
gene: HYLS1 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert list
Mode of inheritance for gene: HYLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HYLS1 were set to PMID: 26830932
Phenotypes for gene: HYLS1 were set to Hydrolethalus syndrome 236680
Review for gene: HYLS1 was set to AMBER
Added comment: OMIM notes Dandy Walker anomaly as a neurological feature. All patients results in either stillbirths or neonatal death, so limited information available. Almost all patients have the same recurring missense (p.Asp211Gly)

PMID: 18648327 - describes many patients with the recurring missense mutation. Summary table describes brain features of 19 patients, none appear to be consistent with JS

PMID: 26830932 - 2 homozygous living siblings (stop-loss, extension) both diagnosed with JS. Patients had molar tooth signs and dysplasia of cerebellar vermis

Single reported family, but likely due to a unique mutational spectrum separate from the recurring missense
Sources: Expert list
Joubert syndrome and other neurological ciliopathies v0.48 TXNDC15 Crystle Lee gene: TXNDC15 was added
gene: TXNDC15 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
Mode of inheritance for gene: TXNDC15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TXNDC15 were set to 30851085; 27894351
Phenotypes for gene: TXNDC15 were set to Meckel-Gruber syndrome
Review for gene: TXNDC15 was set to GREEN
Added comment: No OMIM number. Total of 4 families reported with supporting functional studies in ciliogenesis defects. Emerging MKS gene.

PMID: 30851085; Ridnoi 2019: Chet variants identified in a prenatally diagnosed case of Meckel-Gruber syndrome.

PMID: 27894351; Shaheen 2016: Reported 3 diff hom variants in 3 consang families with Meckel-Gruber syndrome.Functional studies performed showing defects in ciliogenesis
Sources: Expert Review
Mendeliome v0.2814 ALPL Melanie Marty reviewed gene: ALPL: Rating: GREEN; Mode of pathogenicity: Other; Publications: 19500388, 23688511; Phenotypes: Hypophosphatasia, adult 146300 (AD, AR), Hypophosphatasia, childhood 241510 AR, Hypophosphatasia, infantile 241500 AR, Odontohypophosphatasia 146300 AD, AR; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Ciliopathies v0.139 MUC1 Crystle Lee reviewed gene: MUC1: Rating: RED; Mode of pathogenicity: None; Publications: 29186029, 29156055, 29520014; Phenotypes: Medullary cystic kidney disease 1 (MIM#174000); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Joubert syndrome and other neurological ciliopathies v0.48 C2CD3 Elena Savva gene: C2CD3 was added
gene: C2CD3 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert list
Mode of inheritance for gene: C2CD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2CD3 were set to PMID: 24997988
Phenotypes for gene: C2CD3 were set to Orofaciodigital syndrome XIV 615948
Review for gene: C2CD3 was set to GREEN
Added comment: Molar tooth sign (MTS) a listed phenotype in OMIM

PMID: 24997988 - 1 patient with a homozygous PTC. MRI showed MTS

PMID: 30097616 -
1 chet (two splice) patient with MTS, polydactyly. Sibling also had polydactyly, mild cerebellar hypoplasia and grey matter heterotopia.
1 chet (two missense) patient with MTS, was noted to have a diagnosis of Joubert syndrome
Summary Table 3 reviews previous reports, and notes 6/12 cases also had MTS.
Sources: Expert list
Ciliary Dyskinesia v0.75 LRRC56 Elena Savva gene: LRRC56 was added
gene: LRRC56 was added to Ciliary Dyskinesia. Sources: Expert list
Mode of inheritance for gene: LRRC56 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC56 were set to PMID: 30388400
Phenotypes for gene: LRRC56 were set to Ciliary dyskinesia, primary, 39 618254
Review for gene: LRRC56 was set to GREEN
Added comment: PMID: 30388400 - PMID: 30388400 - used protist null model to show abnormal ciliary beatings, replicated the phenotype when the protist was transfected with mutant allele observed in a patient.
3 unrelated families reported with either homozygous splice, missense or chet (nonsense/splice). Patients exhibited phenotypes including chronic respiratory/ear infections, situs inversus
Sources: Expert list
Mendeliome v0.2814 LRRC56 Elena Savva gene: LRRC56 was added
gene: LRRC56 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: LRRC56 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC56 were set to PMID: 30388400
Phenotypes for gene: LRRC56 were set to Ciliary dyskinesia, primary, 39 618254
Added comment: PMID: 30388400 - used protist null model to show abnormal ciliary beatings, replicated the phenotype when the protist was transfected with mutant allele observed in a patient.
3 unrelated families reported with either homozygous splice, missense or chet (nonsense/splice). Patients exhibited phenotypes including chronic respiratory/ear infections, situs inversus
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2635 IQSEC3 Elena Savva reviewed gene: IQSEC3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32049026, 31130284, 31680123; Phenotypes: Intellectual disability, Fetal akinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.48 KIAA0586 Elena Savva gene: KIAA0586 was added
gene: KIAA0586 was added to Joubert syndrome and other neurological ciliopathies. Sources: Literature
Mode of inheritance for gene: KIAA0586 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0586 were set to PMID: 26096313
Phenotypes for gene: KIAA0586 were set to Joubert syndrome 23 616490; Short-rib thoracic dysplasia 14 with polydactyly 616546
Review for gene: KIAA0586 was set to GREEN
Added comment: PMID: 26096313 - 9 unrelated families with Joubert syndrome. MRI shows the molar tooth sign in 3/3 scanned patients. Patients tended to have biallelic PTCs, though missense also reported. p.Arg143Lysfs*4 appears to be a recurring mutation, seen in patients either as a homozygote or in chet with another unique mutation in 7/9 families. Interestingly these 7 families were of different ethnicity
Sources: Literature
Stroke v0.54 YY1AP1 Bryony Thompson Classified gene: YY1AP1 as Green List (high evidence)
Stroke v0.54 YY1AP1 Bryony Thompson Gene: yy1ap1 has been classified as Green List (High Evidence).
Stroke v0.53 YY1AP1 Bryony Thompson gene: YY1AP1 was added
gene: YY1AP1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: YY1AP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YY1AP1 were set to 31633303; 30356112; 31270375; 22987684; 16691574
Phenotypes for gene: YY1AP1 were set to Grange syndrome MIM#602531
Review for gene: YY1AP1 was set to GREEN
Added comment: At least 3 cases reported with early-onset stroke
Sources: Literature
Osteogenesis Imperfecta and Osteoporosis v0.18 IFITM5 Zornitza Stark Marked gene: IFITM5 as ready
Osteogenesis Imperfecta and Osteoporosis v0.18 IFITM5 Zornitza Stark Gene: ifitm5 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.18 IFITM5 Zornitza Stark Phenotypes for gene: IFITM5 were changed from to Osteogenesis imperfecta type V, MIM#610967
Osteogenesis Imperfecta and Osteoporosis v0.17 IFITM5 Zornitza Stark Publications for gene: IFITM5 were set to
Osteogenesis Imperfecta and Osteoporosis v0.16 IFITM5 Zornitza Stark Mode of pathogenicity for gene: IFITM5 was changed from to Other
Osteogenesis Imperfecta and Osteoporosis v0.15 IFITM5 Zornitza Stark Mode of inheritance for gene: IFITM5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Disorders of Glycosylation v0.50 MOGS Zornitza Stark Marked gene: MOGS as ready
Congenital Disorders of Glycosylation v0.50 MOGS Zornitza Stark Gene: mogs has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.50 MOGS Zornitza Stark Phenotypes for gene: MOGS were changed from to Congenital disorder of glycosylation, type IIb, MIM# 606056
Congenital Disorders of Glycosylation v0.49 MOGS Zornitza Stark Publications for gene: MOGS were set to
Congenital Disorders of Glycosylation v0.48 MOGS Zornitza Stark Mode of inheritance for gene: MOGS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.47 MOGS Zornitza Stark reviewed gene: MOGS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31925597; Phenotypes: Congenital disorder of glycosylation, type IIb, MIM# 606056; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.14 IFITM5 Chern Lim reviewed gene: IFITM5: Rating: GREEN; Mode of pathogenicity: Other; Publications: 22863190, 22863195, 32383316, 24519609; Phenotypes: Osteogenesis imperfecta type V, MIM#610967; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.2814 MOGS Zornitza Stark Marked gene: MOGS as ready
Mendeliome v0.2814 MOGS Zornitza Stark Gene: mogs has been classified as Green List (High Evidence).
Mendeliome v0.2814 MOGS Zornitza Stark Phenotypes for gene: MOGS were changed from to Congenital disorder of glycosylation, type IIb 606056
Mendeliome v0.2813 MOGS Zornitza Stark Publications for gene: MOGS were set to
Mendeliome v0.2812 MOGS Zornitza Stark Mode of inheritance for gene: MOGS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2811 TCF7L1 Zornitza Stark Marked gene: TCF7L1 as ready
Mendeliome v0.2811 TCF7L1 Zornitza Stark Gene: tcf7l1 has been classified as Red List (Low Evidence).
Mendeliome v0.2811 TCF7L1 Zornitza Stark Phenotypes for gene: TCF7L1 were changed from to Congenital hypopituitarism
Mendeliome v0.2810 TCF7L1 Zornitza Stark Publications for gene: TCF7L1 were set to
Mendeliome v0.2809 TCF7L1 Zornitza Stark Mode of inheritance for gene: TCF7L1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2808 TCF7L1 Zornitza Stark Classified gene: TCF7L1 as Red List (low evidence)
Mendeliome v0.2808 TCF7L1 Zornitza Stark Gene: tcf7l1 has been classified as Red List (Low Evidence).
Stroke v0.52 SMARCAL1 Bryony Thompson Classified gene: SMARCAL1 as Green List (high evidence)
Stroke v0.52 SMARCAL1 Bryony Thompson Gene: smarcal1 has been classified as Green List (High Evidence).
Stroke v0.51 SMARCAL1 Bryony Thompson gene: SMARCAL1 was added
gene: SMARCAL1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: SMARCAL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMARCAL1 were set to 16840568; 9674900; 30356112; 30026777; 20301550
Phenotypes for gene: SMARCAL1 were set to Schimke immunoosseous dysplasia MIM#242900
Review for gene: SMARCAL1 was set to GREEN
Added comment: Moyamoya type strokes or cerebral ischaemic attacks have been reported as features of the condition.
Sources: Literature
Stroke v0.50 SERPINC1 Bryony Thompson Marked gene: SERPINC1 as ready
Stroke v0.50 SERPINC1 Bryony Thompson Gene: serpinc1 has been classified as Green List (High Evidence).
Stroke v0.50 SERPINC1 Bryony Thompson Classified gene: SERPINC1 as Green List (high evidence)
Stroke v0.50 SERPINC1 Bryony Thompson Gene: serpinc1 has been classified as Green List (High Evidence).
Stroke v0.49 SERPINC1 Bryony Thompson gene: SERPINC1 was added
gene: SERPINC1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: SERPINC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERPINC1 were set to 31359133; 30356112; 23910795
Phenotypes for gene: SERPINC1 were set to Thrombophilia due to antithrombin III deficiency MIM#613118
Review for gene: SERPINC1 was set to GREEN
Added comment: There is a high incidence of stroke in the condition.
Sources: Literature
Mendeliome v0.2807 TCF7L1 Naomi Baker reviewed gene: TCF7L1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 26764381; Phenotypes: Congenital hypopituitarism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Stroke v0.48 SCN5A Bryony Thompson Classified gene: SCN5A as Green List (high evidence)
Stroke v0.48 SCN5A Bryony Thompson Gene: scn5a has been classified as Green List (High Evidence).
Stroke v0.47 SCN5A Bryony Thompson gene: SCN5A was added
gene: SCN5A was added to Stroke. Sources: Literature
Mode of inheritance for gene: SCN5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN5A were set to 30356112; 29579189; 28294644; 16684018
Phenotypes for gene: SCN5A were set to Atrial fibrillation, familial, 10 MIM#614022
Review for gene: SCN5A was set to GREEN
Added comment: Early onset stroke has been reported in at least 4 families.
Sources: Literature
Brugada syndrome v0.6 SCN3B Bryony Thompson reviewed gene: SCN3B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Brugada syndrome 7 MIM#613120; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Stroke v0.46 SAMHD1 Bryony Thompson Marked gene: SAMHD1 as ready
Stroke v0.46 SAMHD1 Bryony Thompson Gene: samhd1 has been classified as Green List (High Evidence).
Stroke v0.46 SAMHD1 Bryony Thompson Classified gene: SAMHD1 as Green List (high evidence)
Stroke v0.46 SAMHD1 Bryony Thompson Gene: samhd1 has been classified as Green List (High Evidence).
Stroke v0.45 SAMHD1 Bryony Thompson gene: SAMHD1 was added
gene: SAMHD1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: SAMHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SAMHD1 were set to 20842748; 21402907; 27051737; 25672750; 28289923
Phenotypes for gene: SAMHD1 were set to Aicardi-Goutieres syndrome 5 MIM#612952
Review for gene: SAMHD1 was set to GREEN
Added comment: At least 4 families where early onset stroke has been reported and a zebrafish model.
Sources: Literature
Stroke v0.44 PROS1 Bryony Thompson Marked gene: PROS1 as ready
Stroke v0.44 PROS1 Bryony Thompson Gene: pros1 has been classified as Green List (High Evidence).
Stroke v0.44 PROS1 Bryony Thompson Classified gene: PROS1 as Green List (high evidence)
Stroke v0.44 PROS1 Bryony Thompson Gene: pros1 has been classified as Green List (High Evidence).
Stroke v0.43 PROS1 Bryony Thompson gene: PROS1 was added
gene: PROS1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: PROS1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: PROS1 were set to 20484936; 25997409; 21172841; 19729839
Phenotypes for gene: PROS1 were set to Thrombophilia due to protein S deficiency
Review for gene: PROS1 was set to GREEN
Added comment: At least 3 families reported with stroke and a supporting null mouse model.
Sources: Literature
Stroke v0.42 PROC Bryony Thompson Classified gene: PROC as Green List (high evidence)
Stroke v0.42 PROC Bryony Thompson Gene: proc has been classified as Green List (High Evidence).
Stroke v0.41 PROC Bryony Thompson gene: PROC was added
gene: PROC was added to Stroke. Sources: Literature
Mode of inheritance for gene: PROC was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: PROC were set to 1511989; 20187890; 30356112; 32351850
Phenotypes for gene: PROC were set to Thrombophilia due to protein C deficiency
Review for gene: PROC was set to GREEN
Added comment: PC deficiency is a cause for the development of stroke, particularly in young adults.
Sources: Literature
Stroke v0.40 PDE3A Bryony Thompson Marked gene: PDE3A as ready
Stroke v0.40 PDE3A Bryony Thompson Gene: pde3a has been classified as Green List (High Evidence).
Stroke v0.40 PDE3A Bryony Thompson Classified gene: PDE3A as Green List (high evidence)
Stroke v0.40 PDE3A Bryony Thompson Gene: pde3a has been classified as Green List (High Evidence).
Stroke v0.39 PDE3A Bryony Thompson gene: PDE3A was added
gene: PDE3A was added to Stroke. Sources: Literature
Mode of inheritance for gene: PDE3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDE3A were set to 31589936; 25961942; 30356112
Phenotypes for gene: PDE3A were set to Hypertension and brachydactyly syndrome MIM#112410
Review for gene: PDE3A was set to GREEN
Added comment: Stroke is a prominent feature of the condition if left untreated.
Sources: Literature
Stroke v0.38 PDCD10 Bryony Thompson Classified gene: PDCD10 as Green List (high evidence)
Stroke v0.38 PDCD10 Bryony Thompson Gene: pdcd10 has been classified as Green List (High Evidence).
Stroke v0.37 PDCD10 Bryony Thompson gene: PDCD10 was added
gene: PDCD10 was added to Stroke. Sources: Literature
Mode of inheritance for gene: PDCD10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDCD10 were set to 30356112; 15543491
Phenotypes for gene: PDCD10 were set to Cerebral cavernous malformations 3 MIM#603285
Review for gene: PDCD10 was set to GREEN
Added comment: At least 7 families reported and stroke can be a feature of the condition.
Sources: Literature
Stroke v0.36 PCCB Bryony Thompson Classified gene: PCCB as Green List (high evidence)
Stroke v0.36 PCCB Bryony Thompson Gene: pccb has been classified as Green List (High Evidence).
Stroke v0.35 PCCB Bryony Thompson gene: PCCB was added
gene: PCCB was added to Stroke. Sources: Literature
Mode of inheritance for gene: PCCB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCCB were set to 30356112; 7769171; 6497733; 30037889; 18986243
Review for gene: PCCB was set to GREEN
Added comment: Metabolic stroke can be a feature of the condition.
Sources: Literature
Stroke v0.34 PCCA Bryony Thompson Classified gene: PCCA as Green List (high evidence)
Stroke v0.34 PCCA Bryony Thompson Gene: pcca has been classified as Green List (High Evidence).
Stroke v0.33 PCCA Bryony Thompson gene: PCCA was added
gene: PCCA was added to Stroke. Sources: Literature
Mode of inheritance for gene: PCCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCCA were set to 21986446; 18986243; 20142522
Review for gene: PCCA was set to GREEN
Added comment: Metabolic stroke can be a feature of the condition.
Sources: Literature
Stroke v0.32 NF1 Bryony Thompson Classified gene: NF1 as Green List (high evidence)
Stroke v0.32 NF1 Bryony Thompson Gene: nf1 has been classified as Green List (High Evidence).
Stroke v0.31 NF1 Bryony Thompson gene: NF1 was added
gene: NF1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NF1 were set to 31080139; 30356112; 8157015; 31279841
Phenotypes for gene: NF1 were set to Neurofibromatosis, type 1 MIM#162200
Review for gene: NF1 was set to GREEN
Added comment: Stroke can be a feature of the condition, with diolicoectasia, occlusion, and MoyaMoya-like subtypes reported.
Sources: Literature
Polydactyly v0.29 ALX3 Zornitza Stark Classified gene: ALX3 as Red List (low evidence)
Polydactyly v0.29 ALX3 Zornitza Stark Gene: alx3 has been classified as Red List (Low Evidence).
Polydactyly v0.28 ALX3 Zornitza Stark edited their review of gene: ALX3: Added comment: Polydactyly not specifically associated with FND1. One family reported in 8362915, but polydactyly considered to be a separate feature.; Changed rating: RED; Changed publications: 19409524, 8362915
Polydactyly v0.28 ALX3 Zornitza Stark Marked gene: ALX3 as ready
Polydactyly v0.28 ALX3 Zornitza Stark Gene: alx3 has been classified as Green List (High Evidence).
Polydactyly v0.28 ALX3 Zornitza Stark Phenotypes for gene: ALX3 were changed from to Frontonasal dysplasia 1, MIM#136760
Polydactyly v0.27 ALX3 Zornitza Stark Publications for gene: ALX3 were set to
Polydactyly v0.26 ALX3 Zornitza Stark Mode of inheritance for gene: ALX3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.25 B9D2 Zornitza Stark Marked gene: B9D2 as ready
Polydactyly v0.25 B9D2 Zornitza Stark Gene: b9d2 has been classified as Green List (High Evidence).
Polydactyly v0.25 B9D2 Zornitza Stark Phenotypes for gene: B9D2 were changed from to Joubert syndrome 34, MIM#614175; Meckel syndrome 10, MIM#614175
Polydactyly v0.24 B9D2 Zornitza Stark Publications for gene: B9D2 were set to
Polydactyly v0.23 B9D2 Zornitza Stark Mode of inheritance for gene: B9D2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Stroke v0.30 HBB Bryony Thompson Classified gene: HBB as Green List (high evidence)
Stroke v0.30 HBB Bryony Thompson Gene: hbb has been classified as Green List (High Evidence).
Stroke v0.29 HBB Bryony Thompson gene: HBB was added
gene: HBB was added to Stroke. Sources: Literature
Mode of inheritance for gene: HBB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HBB were set to 30356112; 19589461; 7782612; 20301551
Phenotypes for gene: HBB were set to Sickle cell anemia MIM#603903
Review for gene: HBB was set to GREEN
Added comment: Stroke can be a feature of sickle cell anemia, with the following subtypes reported: large artery non-atherosclerosis aneurysms, venous thrombosis, and arterial thrombosis.
Sources: Literature
Stroke v0.28 GUCY1A3 Bryony Thompson Marked gene: GUCY1A3 as ready
Stroke v0.28 GUCY1A3 Bryony Thompson Gene: gucy1a3 has been classified as Green List (High Evidence).
Stroke v0.28 GUCY1A3 Bryony Thompson Classified gene: GUCY1A3 as Green List (high evidence)
Stroke v0.28 GUCY1A3 Bryony Thompson Gene: gucy1a3 has been classified as Green List (High Evidence).
Stroke v0.27 GUCY1A3 Bryony Thompson gene: GUCY1A3 was added
gene: GUCY1A3 was added to Stroke. Sources: Literature
Mode of inheritance for gene: GUCY1A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GUCY1A3 were set to 24581742; 26777256
Phenotypes for gene: GUCY1A3 were set to Moyamoya 6 with achalasia MIM#615750
Review for gene: GUCY1A3 was set to GREEN
Added comment: Ischaemic stroke has been reported in at least one individual from five families.
Sources: Literature
Bleeding and Platelet Disorders v0.21 GFI1B Bryony Thompson Marked gene: GFI1B as ready
Bleeding and Platelet Disorders v0.21 GFI1B Bryony Thompson Gene: gfi1b has been classified as Green List (High Evidence).
Mendeliome v0.2807 GFI1B Bryony Thompson Marked gene: GFI1B as ready
Mendeliome v0.2807 GFI1B Bryony Thompson Gene: gfi1b has been classified as Green List (High Evidence).
Mendeliome v0.2807 GFI1B Bryony Thompson Classified gene: GFI1B as Green List (high evidence)
Mendeliome v0.2807 GFI1B Bryony Thompson Gene: gfi1b has been classified as Green List (High Evidence).
Mendeliome v0.2806 GFI1B Bryony Thompson gene: GFI1B was added
gene: GFI1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GFI1B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GFI1B were set to 24325358; 23927492; 28041820; 11825872
Phenotypes for gene: GFI1B were set to Bleeding disorder, platelet-type, 17 MIM#187900
Review for gene: GFI1B was set to GREEN
Added comment: Three families with a heterozygous variant and one case with a homozygous variant, with supporting in vitro functional assays. A null mouse model contained erythroid and megakaryocytic precursors arrested in their development.
Sources: Literature
Bleeding and Platelet Disorders v0.21 GFI1B Bryony Thompson Classified gene: GFI1B as Green List (high evidence)
Bleeding and Platelet Disorders v0.21 GFI1B Bryony Thompson Gene: gfi1b has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v0.20 GFI1B Bryony Thompson gene: GFI1B was added
gene: GFI1B was added to Bleeding Disorders. Sources: Literature
Mode of inheritance for gene: GFI1B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GFI1B were set to 24325358; 23927492; 28041820; 11825872
Phenotypes for gene: GFI1B were set to Bleeding disorder, platelet-type, 17 MIM#187900
Review for gene: GFI1B was set to GREEN
Added comment: Three families with a heterozygous variant and one case with a homozygous variant, with supporting in vitro functional assays. A null mouse model contained erythroid and megakaryocytic precursors arrested in their development.
Sources: Literature
Mendeliome v0.2805 MOGS Elena Savva reviewed gene: MOGS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31925597; Phenotypes: Congenital disorder of glycosylation, type IIb 606056; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia - paediatric v0.87 ATL1 Zornitza Stark Phenotypes for gene: ATL1 were changed from Spastic paraplegia 3A, autosomal dominant MIM#182600 to Hereditary sensory neuropathy type ID, MIM 613708; Spastic paraplegia 3A, MIM 182600; Hereditary spastic paraplegia, AR
Hereditary Spastic Paraplegia - paediatric v0.86 ATL1 Zornitza Stark Publications for gene: ATL1 were set to
Hereditary Spastic Paraplegia - paediatric v0.85 ATL1 Zornitza Stark Mode of inheritance for gene: ATL1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia - paediatric v0.84 ATL1 Zornitza Stark reviewed gene: ATL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16401858, 16537571, 17657515, 28396731, 24473461, 26888483; Phenotypes: Hereditary sensory neuropathy type ID, MIM 613708, Spastic paraplegia 3A, MIM 182600, Hereditary spastic paraplegia, AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2635 PRKD1 Zornitza Stark Marked gene: PRKD1 as ready
Intellectual disability syndromic and non-syndromic v0.2635 PRKD1 Zornitza Stark Gene: prkd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2635 PRKD1 Zornitza Stark Phenotypes for gene: PRKD1 were changed from to Congenital heart defects and ectodermal dysplasia, 617364
Intellectual disability syndromic and non-syndromic v0.2634 PRKD1 Zornitza Stark Publications for gene: PRKD1 were set to
Intellectual disability syndromic and non-syndromic v0.2633 PRKD1 Zornitza Stark Mode of inheritance for gene: PRKD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2632 PRKD1 Zornitza Stark reviewed gene: PRKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27479907; Phenotypes: Congenital heart defects and ectodermal dysplasia, 617364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.40 PRKD1 Zornitza Stark Marked gene: PRKD1 as ready
Congenital Heart Defect v0.40 PRKD1 Zornitza Stark Gene: prkd1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.40 PRKD1 Zornitza Stark Phenotypes for gene: PRKD1 were changed from to Congenital heart defects and ectodermal dysplasia, 617364
Congenital Heart Defect v0.39 PRKD1 Zornitza Stark Publications for gene: PRKD1 were set to
Congenital Heart Defect v0.38 PRKD1 Zornitza Stark Mode of inheritance for gene: PRKD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.37 PRKD1 Zornitza Stark reviewed gene: PRKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27479907; Phenotypes: Congenital heart defects and ectodermal dysplasia, 617364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2805 PRKD1 Zornitza Stark Marked gene: PRKD1 as ready
Mendeliome v0.2805 PRKD1 Zornitza Stark Gene: prkd1 has been classified as Green List (High Evidence).
Mendeliome v0.2805 PRKD1 Zornitza Stark Phenotypes for gene: PRKD1 were changed from to Congenital heart defects and ectodermal dysplasia, 617364
Mendeliome v0.2804 PRKD1 Zornitza Stark Publications for gene: PRKD1 were set to
Mendeliome v0.2803 PRKD1 Zornitza Stark Mode of inheritance for gene: PRKD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dilated Cardiomyopathy v0.36 JPH2 Zornitza Stark Tag founder tag was added to gene: JPH2.
Holoprosencephaly and septo-optic dysplasia v0.16 NODAL Zornitza Stark Tag disputed tag was added to gene: NODAL.
Ciliopathies v0.139 NODAL Zornitza Stark Tag disputed tag was added to gene: NODAL.
Congenital Heart Defect v0.37 NODAL Zornitza Stark Tag disputed tag was added to gene: NODAL.
Dilated Cardiomyopathy v0.36 JPH2 Zornitza Stark Marked gene: JPH2 as ready
Dilated Cardiomyopathy v0.36 JPH2 Zornitza Stark Added comment: Comment when marking as ready: Likely founder effect.
Dilated Cardiomyopathy v0.36 JPH2 Zornitza Stark Gene: jph2 has been classified as Red List (Low Evidence).
Dilated Cardiomyopathy v0.36 JPH2 Zornitza Stark Classified gene: JPH2 as Red List (low evidence)
Dilated Cardiomyopathy v0.36 JPH2 Zornitza Stark Gene: jph2 has been classified as Red List (Low Evidence).
Mendeliome v0.2802 NODAL Zornitza Stark Marked gene: NODAL as ready
Mendeliome v0.2802 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Mendeliome v0.2802 NODAL Zornitza Stark Phenotypes for gene: NODAL were changed from to Heterotaxy, visceral, 5 (MIM#270100)
Mendeliome v0.2801 NODAL Zornitza Stark Publications for gene: NODAL were set to
Mendeliome v0.2800 NODAL Zornitza Stark Mode of inheritance for gene: NODAL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2799 NODAL Zornitza Stark Classified gene: NODAL as Red List (low evidence)
Mendeliome v0.2799 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Mendeliome v0.2798 NODAL Zornitza Stark Tag disputed tag was added to gene: NODAL.
Mendeliome v0.2798 NODAL Zornitza Stark reviewed gene: NODAL: Rating: RED; Mode of pathogenicity: None; Publications: 9354794, 19064609; Phenotypes: Heterotaxy, visceral, 5 (MIM#270100); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.37 NODAL Zornitza Stark Marked gene: NODAL as ready
Congenital Heart Defect v0.37 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.37 NODAL Zornitza Stark Phenotypes for gene: NODAL were changed from to Heterotaxy, visceral, 5 (MIM#270100)
Congenital Heart Defect v0.36 NODAL Zornitza Stark Publications for gene: NODAL were set to
Congenital Heart Defect v0.35 NODAL Zornitza Stark Mode of inheritance for gene: NODAL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.34 NODAL Zornitza Stark Classified gene: NODAL as Red List (low evidence)
Congenital Heart Defect v0.34 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.33 NODAL Zornitza Stark reviewed gene: NODAL: Rating: RED; Mode of pathogenicity: None; Publications: 9354794, 19064609; Phenotypes: Heterotaxy, visceral, 5 (MIM#270100); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Holoprosencephaly and septo-optic dysplasia v0.16 NODAL Zornitza Stark Marked gene: NODAL as ready
Holoprosencephaly and septo-optic dysplasia v0.16 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Holoprosencephaly and septo-optic dysplasia v0.16 NODAL Zornitza Stark Phenotypes for gene: NODAL were changed from to Heterotaxy, visceral, 5 (MIM#270100)
Holoprosencephaly and septo-optic dysplasia v0.15 NODAL Zornitza Stark Publications for gene: NODAL were set to
Holoprosencephaly and septo-optic dysplasia v0.14 NODAL Zornitza Stark Mode of inheritance for gene: NODAL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Holoprosencephaly and septo-optic dysplasia v0.13 NODAL Zornitza Stark Classified gene: NODAL as Red List (low evidence)
Holoprosencephaly and septo-optic dysplasia v0.13 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Holoprosencephaly and septo-optic dysplasia v0.12 NODAL Zornitza Stark reviewed gene: NODAL: Rating: RED; Mode of pathogenicity: None; Publications: 9354794, 19064609; Phenotypes: Heterotaxy, visceral, 5 (MIM#270100); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliopathies v0.139 NODAL Zornitza Stark Mode of inheritance for gene: NODAL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Heterotaxy v0.40 NODAL Zornitza Stark Marked gene: NODAL as ready
Heterotaxy v0.40 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Heterotaxy v0.40 NODAL Zornitza Stark Classified gene: NODAL as Red List (low evidence)
Heterotaxy v0.40 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Heterotaxy v0.39 NODAL Zornitza Stark Tag disputed tag was added to gene: NODAL.
Ciliopathies v0.138 NODAL Zornitza Stark Marked gene: NODAL as ready
Ciliopathies v0.138 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Ciliopathies v0.138 NODAL Zornitza Stark Phenotypes for gene: NODAL were changed from to Heterotaxy, visceral, 5 (MIM#270100)
Ciliopathies v0.137 NODAL Zornitza Stark Classified gene: NODAL as Red List (low evidence)
Ciliopathies v0.137 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Mendeliome v0.2798 PIH1D3 Zornitza Stark Marked gene: PIH1D3 as ready
Mendeliome v0.2798 PIH1D3 Zornitza Stark Gene: pih1d3 has been classified as Green List (High Evidence).
Mendeliome v0.2798 PIH1D3 Zornitza Stark Phenotypes for gene: PIH1D3 were changed from to Ciliary dyskinesia, primary, 36, X-linked (MIM#300991)
Mendeliome v0.2797 PIH1D3 Zornitza Stark Publications for gene: PIH1D3 were set to
Mendeliome v0.2796 PIH1D3 Zornitza Stark Mode of inheritance for gene: PIH1D3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2795 PIH1D3 Zornitza Stark reviewed gene: PIH1D3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28041644, 24421334, 28176794; Phenotypes: Ciliary dyskinesia, primary, 36, X-linked (MIM#300991); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Heterotaxy v0.39 PIH1D3 Zornitza Stark Marked gene: PIH1D3 as ready
Heterotaxy v0.39 PIH1D3 Zornitza Stark Gene: pih1d3 has been classified as Green List (High Evidence).
Heterotaxy v0.39 PIH1D3 Zornitza Stark Phenotypes for gene: PIH1D3 were changed from to Ciliary dyskinesia, primary, 36, X-linked (MIM#300991)
Heterotaxy v0.38 PIH1D3 Zornitza Stark Publications for gene: PIH1D3 were set to
Heterotaxy v0.37 PIH1D3 Zornitza Stark Mode of inheritance for gene: PIH1D3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Heterotaxy v0.36 PIH1D3 Zornitza Stark reviewed gene: PIH1D3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28041644, 24421334, 28176794; Phenotypes: Ciliary dyskinesia, primary, 36, X-linked (MIM#300991); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ciliary Dyskinesia v0.75 PIH1D3 Zornitza Stark Marked gene: PIH1D3 as ready
Ciliary Dyskinesia v0.75 PIH1D3 Zornitza Stark Gene: pih1d3 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.75 PIH1D3 Zornitza Stark Phenotypes for gene: PIH1D3 were changed from to Ciliary dyskinesia, primary, 36, X-linked (MIM#300991)
Ciliary Dyskinesia v0.74 PIH1D3 Zornitza Stark Publications for gene: PIH1D3 were set to
Ciliary Dyskinesia v0.73 PIH1D3 Zornitza Stark Mode of inheritance for gene: PIH1D3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2795 COL10A1 Zornitza Stark Marked gene: COL10A1 as ready
Mendeliome v0.2795 COL10A1 Zornitza Stark Gene: col10a1 has been classified as Green List (High Evidence).
Mendeliome v0.2795 COL10A1 Zornitza Stark Phenotypes for gene: COL10A1 were changed from to Metaphyseal chondrodysplasia, Schmid type, MIM#156500
Mendeliome v0.2794 COL10A1 Zornitza Stark Publications for gene: COL10A1 were set to
Mendeliome v0.2793 COL10A1 Zornitza Stark Mode of inheritance for gene: COL10A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2792 COL10A1 Zornitza Stark reviewed gene: COL10A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15880705, 31633898; Phenotypes: Metaphyseal chondrodysplasia, Schmid type, MIM#156500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v0.22 COL10A1 Zornitza Stark Marked gene: COL10A1 as ready
Skeletal dysplasia v0.22 COL10A1 Zornitza Stark Gene: col10a1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.22 COL10A1 Zornitza Stark Publications for gene: COL10A1 were set to
Skeletal dysplasia v0.21 COL10A1 Zornitza Stark Mode of inheritance for gene: COL10A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Severe Combined Immunodeficiency (absent T absent B cells) v0.13 RAG2 Zornitza Stark Marked gene: RAG2 as ready
Severe Combined Immunodeficiency (absent T absent B cells) v0.13 RAG2 Zornitza Stark Gene: rag2 has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency (absent T absent B cells) v0.13 RAG2 Zornitza Stark Phenotypes for gene: RAG2 were changed from to Severe combined immunodeficiency, B cell-negative (MIM#601457)
Severe Combined Immunodeficiency (absent T absent B cells) v0.12 RAG2 Zornitza Stark Publications for gene: RAG2 were set to
Severe Combined Immunodeficiency (absent T absent B cells) v0.11 RAG2 Zornitza Stark Mode of inheritance for gene: RAG2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency (absent T absent B cells) v0.10 RAG1 Zornitza Stark Marked gene: RAG1 as ready
Severe Combined Immunodeficiency (absent T absent B cells) v0.10 RAG1 Zornitza Stark Added comment: Comment when marking as ready: Well established SCID gene.
Severe Combined Immunodeficiency (absent T absent B cells) v0.10 RAG1 Zornitza Stark Gene: rag1 has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency (absent T absent B cells) v0.10 RAG1 Zornitza Stark Phenotypes for gene: RAG1 were changed from to Severe combined immunodeficiency, B cell-negative (MIM#601457)
Severe Combined Immunodeficiency (absent T absent B cells) v0.9 RAG1 Zornitza Stark Publications for gene: RAG1 were set to
Severe Combined Immunodeficiency (absent T absent B cells) v0.8 RAG1 Zornitza Stark Mode of inheritance for gene: RAG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2792 CEP112 Bryony Thompson Classified gene: CEP112 as Amber List (moderate evidence)
Mendeliome v0.2792 CEP112 Bryony Thompson Gene: cep112 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2791 CEP112 Bryony Thompson gene: CEP112 was added
gene: CEP112 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CEP112 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP112 were set to 31654588
Phenotypes for gene: CEP112 were set to Acephalic spermatozoa; infertility
Review for gene: CEP112 was set to AMBER
Added comment: Two unrelated cases reported with acephalic spermatozoa, one case with a homozygous nonsense variant and the other case with biallelic missense variants. CEP112 expression was significantly reduced in one of the cases, suggesting loss of function as a mechanism of disease.
Sources: Literature
Mendeliome v0.2790 PRKD1 Kristin Rigbye changed review comment from: Only 3 pathogenic missense reported to date, although two of these are recurring in unrelated individuals (ClinVar, Decipher, PMID: 27479907). No functional studies performed.; to: Only 3 pathogenic missense reported to date in unrelated individuals (ClinVar, Decipher, PMID: 27479907). No functional studies performed.
Mendeliome v0.2790 PRKD1 Kristin Rigbye reviewed gene: PRKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27479907; Phenotypes: Congenital heart defects and ectodermal dysplasia, 617364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Stroke v0.26 FOXC1 Bryony Thompson Marked gene: FOXC1 as ready
Stroke v0.26 FOXC1 Bryony Thompson Gene: foxc1 has been classified as Green List (High Evidence).
Stroke v0.26 FOXC1 Bryony Thompson Classified gene: FOXC1 as Green List (high evidence)
Stroke v0.26 FOXC1 Bryony Thompson Gene: foxc1 has been classified as Green List (High Evidence).
Stroke v0.25 FOXC1 Bryony Thompson gene: FOXC1 was added
gene: FOXC1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: FOXC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXC1 were set to 29751260; 31719132; 25250569
Phenotypes for gene: FOXC1 were set to Stroke; cerebral small-vessel disease
Review for gene: FOXC1 was set to GREEN
Added comment: >3 cases reported with stroke and a zebrafish model.
Sources: Literature
Dilated Cardiomyopathy v0.35 JPH2 Ain Roesley gene: JPH2 was added
gene: JPH2 was added to Dilated Cardiomyopathy. Sources: Literature
Mode of inheritance for gene: JPH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JPH2 were set to PMID: 31227780
Phenotypes for gene: JPH2 were set to dilated cardiomyopathy
Review for gene: JPH2 was set to AMBER
Added comment: 2 consanguineous Iranian families with DCM, harbouring homozygous p.(E641*) with healthy carriers reported.
Sources: Literature
Leukodystrophy - paediatric v0.126 POLG Zornitza Stark Marked gene: POLG as ready
Leukodystrophy - paediatric v0.126 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.126 POLG Zornitza Stark Classified gene: POLG as Green List (high evidence)
Leukodystrophy - paediatric v0.126 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.125 POLG Zornitza Stark gene: POLG was added
gene: POLG was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: POLG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POLG were set to Mitochondrial DNA depletion syndrome 4B (MNGIE type), MIM# 613662
Review for gene: POLG was set to GREEN
Added comment: Variable age of onset, including in infancy. White matter changes in some.
Sources: Expert list
Leukodystrophy - adult onset v0.59 POLG Zornitza Stark reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 4B (MNGIE type), MIM# 613662; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - adult onset v0.59 PLP1 Zornitza Stark Marked gene: PLP1 as ready
Leukodystrophy - adult onset v0.59 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.59 PLP1 Zornitza Stark Publications for gene: PLP1 were set to
Leukodystrophy - adult onset v0.58 PLP1 Zornitza Stark reviewed gene: PLP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16130097; Phenotypes: Pelizaeus-Merzbacher disease, MIM# 312080; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Leukodystrophy - paediatric v0.124 PLP1 Zornitza Stark Marked gene: PLP1 as ready
Leukodystrophy - paediatric v0.124 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.124 PLP1 Zornitza Stark Classified gene: PLP1 as Green List (high evidence)
Leukodystrophy - paediatric v0.124 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.123 PLP1 Zornitza Stark gene: PLP1 was added
gene: PLP1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: PLP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: PLP1 were set to Pelizaeus-Merzbacher disease, MIM# 312080
Review for gene: PLP1 was set to GREEN
Added comment: Hypomyelinative leukodystrophy, typical onset in infancy.
Sources: Expert list
Stroke v0.24 CTSA Bryony Thompson Classified gene: CTSA as Amber List (moderate evidence)
Stroke v0.24 CTSA Bryony Thompson Gene: ctsa has been classified as Amber List (Moderate Evidence).
Stroke v0.23 CTSA Bryony Thompson gene: CTSA was added
gene: CTSA was added to Stroke. Sources: Literature
Mode of inheritance for gene: CTSA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTSA were set to 27664989; 31177426; 23175731
Phenotypes for gene: CTSA were set to Cathepsin A-related Arteriopathy With Strokes and Leukoencephalopathy (CARASAL)
Review for gene: CTSA was set to AMBER
Added comment: Three families reported with the same variant (c.973C > T), and a study mapping the condition to 20q13, where CTSA is located, but no sequencing conducted.
Sources: Literature
Ciliopathies v0.136 OFD1 Zornitza Stark Marked gene: OFD1 as ready
Ciliopathies v0.136 OFD1 Zornitza Stark Gene: ofd1 has been classified as Green List (High Evidence).
Heterotaxy v0.36 NODAL Crystle Lee gene: NODAL was added
gene: NODAL was added to Heterotaxy. Sources: Expert Review
Mode of inheritance for gene: NODAL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NODAL were set to 9354794; 19064609
Phenotypes for gene: NODAL were set to Heterotaxy, visceral, 5 (MIM#270100)
Review for gene: NODAL was set to RED
Added comment: Minimal reports and variants in original publications present in gnomAD at a higher than expected frequency, originally concluded to be due to incomplete penetrance.

PMID: 9354794 (1997): R183Q reported in affected daughter and unaffected mother. (26 hets; 1 hom in gnomAD)

PMID: 19064609 (2009): Reported 4 missense, 1 indel and 2 splice site variants. G260R also found in unaffected individual, concluded to have incomplete penetrance (80 hets in gnomAD); R275C (13 hets in gnomAD); E203K (113 hets and 1 hom)
Sources: Expert Review
Ciliopathies v0.136 NODAL Crystle Lee reviewed gene: NODAL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Heterotaxy, visceral, 5 (MIM#270100); Mode of inheritance: None
Ciliopathies v0.136 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from Retinitis pigmentosa 23, MIM# 300424; Joubert syndrome 10, MIM# 300804; Orofaciodigital syndrome I, MIM# 311200 to Retinitis pigmentosa 23, MIM# 300424; Joubert syndrome 10, MIM# 300804; Orofaciodigital syndrome I, MIM# 311200
Ciliopathies v0.136 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from to Retinitis pigmentosa 23, MIM# 300424; Joubert syndrome 10, MIM# 300804; Orofaciodigital syndrome I, MIM# 311200
Ciliopathies v0.135 OFD1 Zornitza Stark Publications for gene: OFD1 were set to
Ciliopathies v0.134 OFD1 Zornitza Stark Mode of inheritance for gene: OFD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ciliopathies v0.133 OFD1 Zornitza Stark reviewed gene: OFD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32276433, 31373179; Phenotypes: Retinitis pigmentosa 23, MIM# 300424, Joubert syndrome 10, MIM# 300804, Orofaciodigital syndrome I, MIM# 311200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ciliary Dyskinesia v0.72 OFD1 Zornitza Stark Classified gene: OFD1 as Red List (low evidence)
Ciliary Dyskinesia v0.72 OFD1 Zornitza Stark Gene: ofd1 has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.71 OFD1 Zornitza Stark reviewed gene: OFD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa 23, MIM# 300424, Joubert syndrome 10, MIM# 300804, Orofaciodigital syndrome I, MIM# 311200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ciliary Dyskinesia v0.71 Zornitza Stark removed gene:RAG1 from the panel
Ciliary Dyskinesia v0.70 SCNN1A Zornitza Stark Marked gene: SCNN1A as ready
Ciliary Dyskinesia v0.70 SCNN1A Zornitza Stark Gene: scnn1a has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.70 SCNN1A Zornitza Stark Classified gene: SCNN1A as Green List (high evidence)
Ciliary Dyskinesia v0.70 SCNN1A Zornitza Stark Gene: scnn1a has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.69 SCNN1B Zornitza Stark Marked gene: SCNN1B as ready
Ciliary Dyskinesia v0.69 SCNN1B Zornitza Stark Gene: scnn1b has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.69 SCNN1B Zornitza Stark Classified gene: SCNN1B as Green List (high evidence)
Ciliary Dyskinesia v0.69 SCNN1B Zornitza Stark Gene: scnn1b has been classified as Green List (High Evidence).
Stroke v0.22 COL4A2 Bryony Thompson Marked gene: COL4A2 as ready
Stroke v0.22 COL4A2 Bryony Thompson Gene: col4a2 has been classified as Green List (High Evidence).
Stroke v0.22 COL4A2 Bryony Thompson Classified gene: COL4A2 as Green List (high evidence)
Stroke v0.22 COL4A2 Bryony Thompson Gene: col4a2 has been classified as Green List (High Evidence).
Stroke v0.21 COL4A2 Bryony Thompson gene: COL4A2 was added
gene: COL4A2 was added to Stroke. Sources: Literature
Mode of inheritance for gene: COL4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A2 were set to 22209247; 30356112; 27794444
Review for gene: COL4A2 was set to GREEN
Added comment: At least 6 cases reported with intracerebral bleeding/stroke, and a mouse model with stroke.
Sources: Literature
Ciliary Dyskinesia v0.68 PIH1D3 Crystle Lee Deleted their comment
Ciliary Dyskinesia v0.68 PIH1D3 Crystle Lee edited their review of gene: PIH1D3: Added comment: >5 families reported with PCD

PMID: 28176794; 6 families reported

PMID: 28041644; Reported 4 affected males from 2 families. Functional studies showed cilia and flagella immotility. (2016)

PMID: 24421334: Mouse model (2014); Changed publications: 28041644, 24421334, 28176794
Ciliary Dyskinesia v0.68 PIH1D3 Crystle Lee reviewed gene: PIH1D3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28041644, 24421334; Phenotypes: Ciliary dyskinesia, primary, 36, X-linked (MIM#300991); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal dysplasia v0.20 COL10A1 Kristin Rigbye reviewed gene: COL10A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15880705, 31633898; Phenotypes: Metaphyseal chondrodysplasia, Schmid type, 156500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe Combined Immunodeficiency (absent T absent B cells) v0.7 RAG2 Crystle Lee reviewed gene: RAG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26996199; Phenotypes: Severe combined immunodeficiency, B cell-negative (MIM#601457); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.68 RAG1 Crystle Lee Deleted their review
Severe Combined Immunodeficiency (absent T absent B cells) v0.7 RAG1 Crystle Lee reviewed gene: RAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26689875, 26186701; Phenotypes: Severe combined immunodeficiency, B cell-negative (MIM#601457); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.68 RAG1 Crystle Lee gene: RAG1 was added
gene: RAG1 was added to Ciliary Dyskinesia. Sources: Expert Review
Mode of inheritance for gene: RAG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAG1 were set to 26689875; 26186701
Phenotypes for gene: RAG1 were set to Severe combined immunodeficiency, B cell-negative (MIM#601457)
Added comment: Phenotypic over with PCD (recurrent respiratory problems).

PMID: 26689875; Reported 2 patients with classic SCID, 1 atypical SCID and one with Omen syndrome

PMID: 26186701: 1 patient with compound het variants in RAG1

Green in PanelApp UK - Respiratory ciliopathies list
Sources: Expert Review
Ciliary Dyskinesia v0.68 SCNN1A Crystle Lee gene: SCNN1A was added
gene: SCNN1A was added to Ciliary Dyskinesia. Sources: Expert Review
Mode of inheritance for gene: SCNN1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SCNN1A were set to 22207244; 19017867; 19462466
Phenotypes for gene: SCNN1A were set to Bronchiectasis with or without elevated sweat chloride 2 (MIM#613021)
Review for gene: SCNN1A was set to GREEN
Added comment: Phenotypic overlap with PCD
Encodes for the alpha subunit of the epithelial sodium channel, which is distributed along the motile cilia. (PMID: 22207244)
Sources: Expert Review
Ciliary Dyskinesia v0.68 SCNN1B Crystle Lee gene: SCNN1B was added
gene: SCNN1B was added to Ciliary Dyskinesia. Sources: Expert Review
Mode of inheritance for gene: SCNN1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SCNN1B were set to 22207244; 16207733; 18507830
Phenotypes for gene: SCNN1B were set to Bronchiectasis with or without elevated sweat chloride 1 (MIM#211400)
Review for gene: SCNN1B was set to GREEN
Added comment: Phenotypic overlap with PCD
Encodes for the beta subunit of the epithelial sodium channel, which is distributed along the motile cilia. (PMID: 22207244)

PMID: 16207733: 2 patients reported
PMID: 18507830: 2 patients with bronchiectasis
Sources: Expert Review
Mendeliome v0.2790 KPNA7 Alison Yeung Marked gene: KPNA7 as ready
Mendeliome v0.2790 KPNA7 Alison Yeung Gene: kpna7 has been classified as Red List (Low Evidence).
Mendeliome v0.2790 KPNA7 Alison Yeung gene: KPNA7 was added
gene: KPNA7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KPNA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KPNA7 were set to 24045845; 32179771
Phenotypes for gene: KPNA7 were set to Epilepsy; intellectual disability
Review for gene: KPNA7 was set to RED
Added comment: Single family with two siblings
Sources: Literature
Stroke v0.20 COL3A1 Bryony Thompson Marked gene: COL3A1 as ready
Stroke v0.20 COL3A1 Bryony Thompson Gene: col3a1 has been classified as Green List (High Evidence).
Stroke v0.20 COL3A1 Bryony Thompson Classified gene: COL3A1 as Green List (high evidence)
Stroke v0.20 COL3A1 Bryony Thompson Gene: col3a1 has been classified as Green List (High Evidence).
Stroke v0.19 COL3A1 Bryony Thompson gene: COL3A1 was added
gene: COL3A1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: COL3A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL3A1 were set to 30356112; 12786757; 31903434; 25355833
Phenotypes for gene: COL3A1 were set to Ehlers-Danlos syndrome, vascular type MIM#130050
Review for gene: COL3A1 was set to GREEN
Added comment: At least 4 cervical artery dissection cases with a heterozygous COL3A1 variant, which is a major cause of ischaemic stroke.
Sources: Literature
Stroke v0.18 CD59 Bryony Thompson Marked gene: CD59 as ready
Stroke v0.18 CD59 Bryony Thompson Gene: cd59 has been classified as Green List (High Evidence).
Stroke v0.18 CD59 Bryony Thompson Classified gene: CD59 as Green List (high evidence)
Stroke v0.18 CD59 Bryony Thompson Gene: cd59 has been classified as Green List (High Evidence).
Stroke v0.17 CD59 Bryony Thompson gene: CD59 was added
gene: CD59 was added to Stroke. Sources: Literature
Mode of inheritance for gene: CD59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD59 were set to 30356112; 28622911; 1699124; 25716358
Phenotypes for gene: CD59 were set to Hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathy MIM#612300
Review for gene: CD59 was set to GREEN
Added comment: Recurrent strokes have been reported in at least 6 cases, with an arterial thrombosis stroke subtype. Condition is paediatric onset.
Sources: Literature
Stroke v0.16 KRIT1 Bryony Thompson Marked gene: KRIT1 as ready
Stroke v0.16 KRIT1 Bryony Thompson Gene: krit1 has been classified as Green List (High Evidence).
Stroke v0.16 KRIT1 Bryony Thompson Classified gene: KRIT1 as Green List (high evidence)
Stroke v0.16 KRIT1 Bryony Thompson Gene: krit1 has been classified as Green List (High Evidence).
Stroke v0.15 KRIT1 Bryony Thompson gene: KRIT1 was added
gene: KRIT1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: KRIT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRIT1 were set to 30356112; 14755725; 11310633; 9811928
Phenotypes for gene: KRIT1 were set to Cavernous malformations of CNS and retina MIM#116860; Cerebral cavernous malformations-1 MIM#116860; Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations MIM#116860
Review for gene: KRIT1 was set to GREEN
Added comment: Cases reported with intracerebral bleeding and cavernoma stroke subtypes.
Sources: Literature
Mendeliome v0.2789 NR4A2 Zornitza Stark Marked gene: NR4A2 as ready
Mendeliome v0.2789 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Green List (High Evidence).
Mendeliome v0.2789 NR4A2 Zornitza Stark Classified gene: NR4A2 as Green List (high evidence)
Mendeliome v0.2789 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Green List (High Evidence).
Mendeliome v0.2788 NR4A2 Zornitza Stark gene: NR4A2 was added
gene: NR4A2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NR4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NR4A2 were set to 31428396; 30504930; 29770430; 12756136; 9092472
Phenotypes for gene: NR4A2 were set to Intellectual disability; epilepsy
Review for gene: NR4A2 was set to GREEN
Added comment: Over ten individuals reported with mono-allelic variants in this gene and neurodevelopmental phenotypes. Link with dementia/Parkinson's disease disputed.
Sources: Literature
Incidentalome v0.20 NR4A2 Zornitza Stark Marked gene: NR4A2 as ready
Incidentalome v0.20 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Red List (Low Evidence).
Incidentalome v0.20 NR4A2 Zornitza Stark Classified gene: NR4A2 as Red List (low evidence)
Incidentalome v0.20 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Red List (Low Evidence).
Incidentalome v0.19 NR4A2 Zornitza Stark reviewed gene: NR4A2: Rating: RED; Mode of pathogenicity: None; Publications: 12756136, 9092472; Phenotypes: ; Mode of inheritance: None
Genetic Epilepsy v0.703 NR4A2 Zornitza Stark Marked gene: NR4A2 as ready
Genetic Epilepsy v0.703 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.703 NR4A2 Zornitza Stark Publications for gene: NR4A2 were set to 31428396
Genetic Epilepsy v0.702 NR4A2 Zornitza Stark reviewed gene: NR4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32366965; Phenotypes: Intellectual disability, epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.702 NR4A2 Zornitza Stark Publications for gene: NR4A2 were set to https://doi.org/10.1038/s41436-020-0815-4; 31428396
Genetic Epilepsy v0.701 NR4A2 Zornitza Stark Classified gene: NR4A2 as Green List (high evidence)
Genetic Epilepsy v0.701 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2632 NR4A2 Zornitza Stark Marked gene: NR4A2 as ready
Intellectual disability syndromic and non-syndromic v0.2632 NR4A2 Zornitza Stark Added comment: Comment when marking as ready: Upgrade to Green in view of new publication reporting 9 additional individuals.
Intellectual disability syndromic and non-syndromic v0.2632 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2632 NR4A2 Zornitza Stark Classified gene: NR4A2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2632 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.700 NR4A2 Konstantinos Varvagiannis gene: NR4A2 was added
gene: NR4A2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: NR4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NR4A2 were set to https://doi.org/10.1038/s41436-020-0815-4; 31428396
Phenotypes for gene: NR4A2 were set to Generalized hypotonia, Global developmental delay, Intellectual disability, Seizures, Behavioral abnormality, Abnormality of movement, Joint hypermobility
Penetrance for gene: NR4A2 were set to unknown
Review for gene: NR4A2 was set to GREEN
Added comment: Seizures have been reported in at least 6 unrelated individuals with NR4A2 variants (not including cases with contiguous gene deletions spanning also this gene). Please consider inclusion with amber or green rating.
---
Singh et al (2020 - https://doi.org/10.1038/s41436-020-0815-4) provide details on the phenotype of 9 unrelated individuals with NR4A2 pathogenic variants (in almost all cases de novo).

Features included hypotonia (in 6/9), DD (9/9), varying levels of ID (mild to severe in 8/8 for whom this information was available), seizures (6/9 - variable epilepsy phenotypes), behavioral problems (5/9 - with autism reported for one). Less frequent features incl. hypermobility (in 3), ataxia/movement disorder (in 3).

8 total pLoF and missense variants were identified as de novo events following trio exome sequencing with Sanger validation (7/8 variants). For 1(/8) individual with a stopgain variant, a single parental sample was available. A 9th individual was found to harbor a ~3.7 Mb 2q deletion spanning also other genes (which might also contribute to his phenotype of epilepsy).

Only the effect of a variant affecting the splice-acceptor site was studied (c.865-1_865delGCinsAAAAAGGAGT - NM_006186.3) with RT-PCR demonstrating an out-of-frame skipping of exon 4. Another variant (NM_006186.3:c.325dup) found in a subject with DD, ID and epilepsy had also previously been reported in another individual with similar phenotype of epilepsy and ID (Ramos et al - PMID: 31428396 - the variant was de novo with other causes for his phenotype excluded).

As discussed by Singh et al, NR4A2 encodes a steroid-thyroid-retinoid receptor which acts as a nuclear receptor transcription factor. The authors summarize previous reports on NR4A2 haploinsufficiency (NR4A2 has a pLI of 1 and HI score of 1.28% - Z-score is 2.24).

The authors comment on mouse models suggesting a role of NR4A2 for dopaminergic neurons, and provide plausible explanations for the phenotype of ID/seizures.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2631 NR4A2 Konstantinos Varvagiannis reviewed gene: NR4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: https://doi.org/10.1038/s41436-020-0815-4, 31428396, 29770430, 30504930, 28544326, 27569545, 23554088, 28135719, 27479843, 25363768; Phenotypes: Generalized hypotonia, Global developmental delay, Intellectual disability, Seizures, Behavioral abnormality, Abnormality of movement, Joint hypermobility; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Leukodystrophy - adult onset v0.58 NOTCH3 Zornitza Stark Marked gene: NOTCH3 as ready
Leukodystrophy - adult onset v0.58 NOTCH3 Zornitza Stark Gene: notch3 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.58 NOTCH3 Zornitza Stark Mode of inheritance for gene: NOTCH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy - adult onset v0.57 NOTCH3 Zornitza Stark reviewed gene: NOTCH3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM# 125310; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy - adult onset v0.57 MLC1 Zornitza Stark Marked gene: MLC1 as ready
Leukodystrophy - adult onset v0.57 MLC1 Zornitza Stark Gene: mlc1 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.57 MLC1 Zornitza Stark Publications for gene: MLC1 were set to
Leukodystrophy - adult onset v0.56 MLC1 Zornitza Stark reviewed gene: MLC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11254442, 21419380, 21624973; Phenotypes: Megalencephalic leukoencephalopathy with subcortical cysts, MIM# 604004; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.122 MLC1 Zornitza Stark Marked gene: MLC1 as ready
Leukodystrophy - paediatric v0.122 MLC1 Zornitza Stark Gene: mlc1 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.122 MLC1 Zornitza Stark Classified gene: MLC1 as Green List (high evidence)
Leukodystrophy - paediatric v0.122 MLC1 Zornitza Stark Gene: mlc1 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.121 MLC1 Zornitza Stark gene: MLC1 was added
gene: MLC1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: MLC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MLC1 were set to 11254442; 21419380; 21624973
Phenotypes for gene: MLC1 were set to Megalencephalic leukoencephalopathy with subcortical cysts, MIM# 604004
Review for gene: MLC1 was set to GREEN
Added comment: Childhood onset, progressive MRI changes.
Sources: Expert list
Leukodystrophy - adult onset v0.56 MCOLN1 Zornitza Stark Marked gene: MCOLN1 as ready
Leukodystrophy - adult onset v0.56 MCOLN1 Zornitza Stark Gene: mcoln1 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.56 MCOLN1 Zornitza Stark Classified gene: MCOLN1 as Amber List (moderate evidence)
Leukodystrophy - adult onset v0.56 MCOLN1 Zornitza Stark Gene: mcoln1 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.55 MCOLN1 Zornitza Stark reviewed gene: MCOLN1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucolipidosis IV, MIM# 252650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.120 MCOLN1 Zornitza Stark Marked gene: MCOLN1 as ready
Leukodystrophy - paediatric v0.120 MCOLN1 Zornitza Stark Gene: mcoln1 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.120 MCOLN1 Zornitza Stark Classified gene: MCOLN1 as Green List (high evidence)
Leukodystrophy - paediatric v0.120 MCOLN1 Zornitza Stark Gene: mcoln1 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.119 MCOLN1 Zornitza Stark gene: MCOLN1 was added
gene: MCOLN1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: MCOLN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCOLN1 were set to 10973263; 11030752
Phenotypes for gene: MCOLN1 were set to Mucolipidosis IV, MIM# 252650
Review for gene: MCOLN1 was set to GREEN
Added comment: Sources: Expert list
Mendeliome v0.2787 TET2 Zornitza Stark edited their review of gene: TET2: Added comment: Association study (PMID 32330418) found enrichment of non-coding and LoF TET2 variants in cohort of individuals with early onset dementia, unclear if this is monogenic or polygenic contribution.; Changed publications: 30890702, 31827242, 32330418
Mendeliome v0.2787 TOMM70 Zornitza Stark Marked gene: TOMM70 as ready
Mendeliome v0.2787 TOMM70 Zornitza Stark Gene: tomm70 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2787 TOMM70 Zornitza Stark Classified gene: TOMM70 as Amber List (moderate evidence)
Mendeliome v0.2787 TOMM70 Zornitza Stark Gene: tomm70 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2786 TOMM70 Zornitza Stark gene: TOMM70 was added
gene: TOMM70 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TOMM70 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TOMM70 were set to 31907385; 32356556
Phenotypes for gene: TOMM70 were set to Severe anaemia, lactic acidosis, developmental delay; White matter abnormalities, developmental delay, regression, movement disorder
Review for gene: TOMM70 was set to AMBER
Added comment: TOM70 is a member of the TOM complex that transports cytosolic proteins into mitochondria.
Bi-allelic disease: one individual reported with compound heterozygous variants in TOMM70 [c.794C>T (p.T265M) and c.1745C>T (p.A582V)]. Clinical features included severe anaemia, lactic acidosis, and developmental delay. Some functional data: in vitro cell model compensatory experiments.
Monoallelic disease: de novo mono allelic variants in the C-terminal region of TOMM70 reported in two individuals. While both individuals exhibited shared symptoms including hypotonia, hyperreflexia, ataxia, dystonia, and significant white matter abnormalities, there were differences between the two individuals, most prominently the age of symptom onset, with one experiencing episodes of regression. Some functional data.
Sources: Expert list
Mitochondrial disease v0.448 TOMM70 Zornitza Stark Publications for gene: TOMM70 were set to
Mitochondrial disease v0.447 TOMM70 Zornitza Stark edited their review of gene: TOMM70: Changed publications: 31907385
Leukodystrophy - paediatric v0.118 TOMM70 Zornitza Stark Marked gene: TOMM70 as ready
Leukodystrophy - paediatric v0.118 TOMM70 Zornitza Stark Gene: tomm70 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.118 TOMM70 Zornitza Stark Classified gene: TOMM70 as Amber List (moderate evidence)
Leukodystrophy - paediatric v0.118 TOMM70 Zornitza Stark Gene: tomm70 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.117 TOMM70 Zornitza Stark gene: TOMM70 was added
gene: TOMM70 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: TOMM70 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TOMM70 were set to 32356556
Phenotypes for gene: TOMM70 were set to White matter abnormalities; Developmental delay; Regression; Movement disorder
Review for gene: TOMM70 was set to AMBER
Added comment: De novo mono allelic variants in the C-terminal region of TOMM70 reported in two individuals. While both individuals exhibited shared symptoms including hypotonia, hyperreflexia, ataxia, dystonia, and significant white matter abnormalities, there were differences between the two individuals, most prominently the age of symptom onset, with one experiencing episodes of regression. Some functional data. Note bi-allelic disease also reported in one individual, with features of a mitochondrial disorder.
Sources: Literature
Mitochondrial disease v0.447 TOMM70 Zornitza Stark Marked gene: TOMM70 as ready
Mitochondrial disease v0.447 TOMM70 Zornitza Stark Gene: tomm70 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.447 TOMM70 Zornitza Stark Classified gene: TOMM70 as Amber List (moderate evidence)
Mitochondrial disease v0.447 TOMM70 Zornitza Stark Gene: tomm70 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.446 TOMM70 Zornitza Stark gene: TOMM70 was added
gene: TOMM70 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: TOMM70 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TOMM70 were set to Severe anaemia; Lactic acidosis; Developmental delay
Review for gene: TOMM70 was set to AMBER
Added comment: TOM70 is a member of the TOM complex that transports cytosolic proteins into mitochondria. One individual reported with compound heterozygous variants in TOMM70 [c.794C>T (p.T265M) and c.1745C>T (p.A582V)]. Clinical features included severe anaemia, lactic acidosis, and developmental delay. Some functional data: in vitro cell model compensatory experiments.
Sources: Literature
Hypertension and Aldosterone disorders v0.15 CUL3 Zornitza Stark Marked gene: CUL3 as ready
Hypertension and Aldosterone disorders v0.15 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Mendeliome v0.2785 CUL3 Zornitza Stark Publications for gene: CUL3 were set to 22495309; 22914163; 25363760; 27824329; 32341456
Hypertension and Aldosterone disorders v0.15 CUL3 Zornitza Stark Phenotypes for gene: CUL3 were changed from Pseudohypoaldosteronism, type IIE, MIM# 614496 to Pseudohypoaldosteronism, type IIE, MIM# 614496
Mendeliome v0.2784 CUL3 Zornitza Stark edited their review of gene: CUL3: Changed publications: 22495309, 22914163, 25363760, 27824329, 32341456, 22266938
Hypertension and Aldosterone disorders v0.15 CUL3 Zornitza Stark Phenotypes for gene: CUL3 were changed from to Pseudohypoaldosteronism, type IIE, MIM# 614496
Hypertension and Aldosterone disorders v0.14 CUL3 Zornitza Stark Publications for gene: CUL3 were set to
Hypertension and Aldosterone disorders v0.13 CUL3 Zornitza Stark Mode of inheritance for gene: CUL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertension and Aldosterone disorders v0.12 CUL3 Zornitza Stark reviewed gene: CUL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22266938; Phenotypes: Pseudohypoaldosteronism, type IIE, MIM# 614496; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2784 CUL3 Zornitza Stark Marked gene: CUL3 as ready
Mendeliome v0.2784 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Mendeliome v0.2784 CUL3 Zornitza Stark Phenotypes for gene: CUL3 were changed from to Pseudohypoaldosteronism, type IIE 614496; Intellectual disability; Autism; Seizures
Mendeliome v0.2783 CUL3 Zornitza Stark Publications for gene: CUL3 were set to
Mendeliome v0.2782 CUL3 Zornitza Stark Mode of inheritance for gene: CUL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2781 CUL3 Zornitza Stark reviewed gene: CUL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22495309, 22914163, 25363760, 27824329, 32341456; Phenotypes: Pseudohypoaldosteronism, type IIE 614496, Intellectual disability, Autism, Seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.91 CUL3 Zornitza Stark Phenotypes for gene: CUL3 were changed from Autism to Autism; Intellectual disability; Epilepsy
Autism v0.90 CUL3 Zornitza Stark edited their review of gene: CUL3: Added comment: Further publication (PMID 32341456) reporting three unrelated individuals with neurodevelopmental phenotype.; Changed publications: 22495309, 22914163, 25363760, 27824329, 32341456; Changed phenotypes: Autism, Intellectual disability, Epilepsy
Genetic Epilepsy v0.700 CUL3 Zornitza Stark Marked gene: CUL3 as ready
Genetic Epilepsy v0.700 CUL3 Zornitza Stark Gene: cul3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.700 CUL3 Zornitza Stark Phenotypes for gene: CUL3 were changed from Global developmental delay; Intellectual disability; Seizures; Abnormality of cardiovascular system morphology; Abnormality of the palate; Pseudohypoaldosteronism, type IIE - MIM #614496 to Global developmental delay; Intellectual disability; Seizures; Abnormality of cardiovascular system morphology; Abnormality of the palate
Genetic Epilepsy v0.699 CUL3 Zornitza Stark Classified gene: CUL3 as Amber List (moderate evidence)
Genetic Epilepsy v0.699 CUL3 Zornitza Stark Gene: cul3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2631 CUL3 Zornitza Stark Marked gene: CUL3 as ready
Intellectual disability syndromic and non-syndromic v0.2631 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2631 CUL3 Zornitza Stark Phenotypes for gene: CUL3 were changed from Global developmental delay; Intellectual disability; Seizures; Abnormality of cardiovascular system morphology; Abnormality of the palate; Pseudohypoaldosteronism, type IIE - MIM #614496 to Global developmental delay; Intellectual disability; Seizures; Abnormality of cardiovascular system morphology; Abnormality of the palate
Intellectual disability syndromic and non-syndromic v0.2630 CUL3 Zornitza Stark Classified gene: CUL3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2630 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.698 CUL3 Konstantinos Varvagiannis gene: CUL3 was added
gene: CUL3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CUL3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CUL3 were set to 32341456
Phenotypes for gene: CUL3 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of cardiovascular system morphology; Abnormality of the palate; Pseudohypoaldosteronism, type IIE - MIM #614496
Penetrance for gene: CUL3 were set to unknown
Review for gene: CUL3 was set to AMBER
Added comment: Nakashima et al (2020 - PMID:32341456) provide clinical details on 3 unrelated individuals with de novo CUL3 variants.

Features included DD, variable degrees of ID (P1: severe, P3: mild, P2: NA although he displayed motor and severe speech and language delay and had severe learning difficulties). Two out of three had intractable seizures (onset 2 - 6 months). One presented with congenital heart defects (ASD, PV stenosis) and another submucosal palatoschisis/bifid uvula. There were no facial dysmorphisms reported.

CUL3 encodes Cullin-3, a core piece of the E3 ubiquitin ligase complex, thus playing a role in the ubiquitin-proteasome system. [ https://ghr.nlm.nih.gov/gene/CUL3 ]. Germline variants in some other Cullin family genes (eg. CUL4B, CUL7) cause disorders with ID as a feature.

The 3 individuals reported by Nakashima had variable previous investigations (karyotype, CMA, metabolic testing) which were non-diagnostic. Singleton or trio exome sequencing identified 2 frameshift and 1 missense variant (NM_003590.4:c.854T>C / p.Val285Ala), further confirmed with Sanger sequencing. De novo occurrence was confirmed by analysis of microsatellite markers in an individual with singleton ES.

While the frameshift variants were presumed to lead to NMD (not studied), studies in HEK293T cells suggested that the Val285Ala reduced binding ability with KEAP1, possibly leading to instability of the Cullin-RING ligase (CRL) complex and impairment of the ubiquitin-proteasome system.

In OMIM, the phenotype associated with heterozygous CUL3 mutations is Pseudohypoaldosteronism type IIE (PHA2E - # 614496). As OMIM and Nakashima et al comment, PHA2E-associated variants are clustered around exon 9, most lead to skipping of exon 9 and produce an in-frame deletion of 57 aa in the cullin homology domain. Few (probably 3) missense variants in exon 9 have also been reported. Individuals with PHA2E do not display DD/ID and conversely individuals with NDD did not display features of PHA2E.

Nakashima et al summarize the phenotypes associated with 12 further de novo CUL3 variants in the literature with most pLOF ones detected in individuals with autism and/or developmental disorders and in few cases with congenital heart disease. Few additional missense variants and a stoploss one have been reported in individuals with NDD and one in SCZ.

Heterozygous Cul3 (/tissue-specific) deletion in mice resulted in autism-like behavior. Cul3 deficient mice also demonstrated NMDAR hypofunction and decreased spine density. [PMIDs cited : 31455858, 31780330]

Overall haploinsufficiency is favored as the underlying mechanism of variants associated with NDD. Nakashima et al comment that the pathogenesis of missense variants remains unknown and/or that a dominant-negative effect on CRL may be possible.

Studies on larger cohorts reporting on individuals with relevant phenotypes due to de novo CUL3 variants (eg. DDD study - PMID: 28135719, Lelieveld et al - PMID: 27479843), are better summarized in denovo-db (after filtering for coding variants):

http://denovo-db.gs.washington.edu/denovo-db/QueryVariantServlet?searchBy=Gene&target=cul3

Overall, this gene can be considered for inclusion in the ID (amber/green), epilepsy (amber) and/or ASD panels.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2629 CUL3 Konstantinos Varvagiannis gene: CUL3 was added
gene: CUL3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CUL3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CUL3 were set to 32341456
Phenotypes for gene: CUL3 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of cardiovascular system morphology; Abnormality of the palate; Pseudohypoaldosteronism, type IIE - MIM #614496
Penetrance for gene: CUL3 were set to unknown
Review for gene: CUL3 was set to GREEN
Added comment: Please consider inclusion with amber / green rating.
--
Nakashima et al (2020 - PMID:32341456) provide clinical details on 3 unrelated individuals with de novo CUL3 variants.

Features included DD, variable degrees of ID (P1: severe, P3: mild, P2: NA although he displayed motor and severe speech and language delay and had severe learning difficulties). Two out of three had intractable seizures (onset 2 - 6 months). One presented with congenital heart defects (ASD, PV stenosis) and another submucosal palatoschisis/bifid uvula. There were no facial dysmorphisms reported.

CUL3 encodes Cullin-3, a core piece of the E3 ubiquitin ligase complex, thus playing a role in the ubiquitin-proteasome system. [ https://ghr.nlm.nih.gov/gene/CUL3 ]. Germline variants in some other Cullin family genes (eg. CUL4B, CUL7) cause disorders with ID as a feature.

The 3 individuals reported by Nakashima had variable previous investigations (karyotype, CMA, metabolic testing) which were non-diagnostic. Singleton or trio exome sequencing identified 2 frameshift and 1 missense variant (NM_003590.4:c.854T>C / p.Val285Ala), further confirmed with Sanger sequencing. De novo occurrence was confirmed by analysis of microsatellite markers in an individual with singleton ES.

While the frameshift variants were presumed to lead to NMD (not studied), studies in HEK293T cells suggested that the Val285Ala reduced binding ability with KEAP1, possibly leading to instability of the Cullin-RING ligase (CRL) complex and impairment of the ubiquitin-proteasome system.

In OMIM, the phenotype associated with heterozygous CUL3 mutations is Pseudohypoaldosteronism type IIE (PHA2E - # 614496). As OMIM and Nakashima et al comment, PHA2E-associated variants are clustered around exon 9, most lead to skipping of exon 9 and produce an in-frame deletion of 57 aa in the cullin homology domain. Few (probably 3) missense variants in exon 9 have also been reported. Individuals with PHA2E do not display DD/ID and conversely individuals with NDD did not display features of PHA2E.

Nakashima et al summarize the phenotypes associated with 12 further de novo CUL3 variants in the literature with most pLOF ones detected in individuals with autism and/or developmental disorders and in few cases with congenital heart disease. Few additional missense variants and a stoploss one have been reported in individuals with NDD and one in SCZ.

Heterozygous Cul3 (/tissue-specific) deletion in mice resulted in autism-like behavior. Cul3 deficient mice also demonstrated NMDAR hypofunction and decreased spine density. [PMIDs cited : 31455858, 31780330]

Overall haploinsufficiency is favored as the underlying mechanism of variants associated with NDD. Nakashima et al comment that the pathogenesis of missense variants remains unknown and/or that a dominant-negative effect on CRL may be possible.

Studies on larger cohorts reporting on individuals with relevant phenotypes due to de novo CUL3 variants (eg. DDD study - PMID: 28135719, Lelieveld et al - PMID: 27479843), are summarized in denovo-db (after filtering for coding variants):

http://denovo-db.gs.washington.edu/denovo-db/QueryVariantServlet?searchBy=Gene&target=cul3

Overall, this gene can be considered for inclusion in the ID (amber/green), epilepsy (amber) and/or ASD panels.
Sources: Literature
Stroke v0.14 CBS Bryony Thompson Marked gene: CBS as ready
Stroke v0.14 CBS Bryony Thompson Gene: cbs has been classified as Green List (High Evidence).
Stroke v0.14 CBS Bryony Thompson Classified gene: CBS as Green List (high evidence)
Stroke v0.14 CBS Bryony Thompson Gene: cbs has been classified as Green List (High Evidence).
Stroke v0.13 CBS Bryony Thompson gene: CBS was added
gene: CBS was added to Stroke. Sources: Literature
Mode of inheritance for gene: CBS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CBS were set to 30356112; 20142522; 12552044
Phenotypes for gene: CBS were set to Homocystinuria, B6-responsive and nonresponsive types MIM#236200; Thrombosis, hyperhomocysteinemic MIM#236200
Review for gene: CBS was set to GREEN
Added comment: Large artery atherosclerosis/non-atherosclerosis, small-vessel disease, venous thrombosis, and arterial thrombosis stroke subtypes have been reported in the condition.
Sources: Literature
Genetic Epilepsy v0.698 KCNT1 Zornitza Stark Marked gene: KCNT1 as ready
Genetic Epilepsy v0.698 KCNT1 Zornitza Stark Gene: kcnt1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.698 KCNT1 Zornitza Stark Phenotypes for gene: KCNT1 were changed from to Epilepsy, nocturnal frontal lobe, 5, MIM# 615005; Epileptic encephalopathy, early infantile, 14, MIM# 614959
Genetic Epilepsy v0.697 KCNT1 Zornitza Stark Publications for gene: KCNT1 were set to
Genetic Epilepsy v0.696 KCNT1 Zornitza Stark Mode of inheritance for gene: KCNT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.695 KCNT1 Zornitza Stark reviewed gene: KCNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23086397, 23086396, 31872048, 31532509; Phenotypes: Epilepsy, nocturnal frontal lobe, 5, MIM# 615005, Epileptic encephalopathy, early infantile, 14, MIM# 614959; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Oligodontia v0.4 WNT10A Zornitza Stark Marked gene: WNT10A as ready
Oligodontia v0.4 WNT10A Zornitza Stark Gene: wnt10a has been classified as Green List (High Evidence).
Oligodontia v0.4 WNT10A Zornitza Stark Phenotypes for gene: WNT10A were changed from to Odontoonychodermal dysplasia 257980 AR; Schopf-Schulz-Passarge syndrome 224750 AR; Tooth agenesis, selective, 4 150400 AR, AD
Oligodontia v0.3 WNT10A Zornitza Stark Publications for gene: WNT10A were set to
Oligodontia v0.2 WNT10A Zornitza Stark Mode of inheritance for gene: WNT10A was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.2781 EGR2 Zornitza Stark Marked gene: EGR2 as ready
Mendeliome v0.2781 EGR2 Zornitza Stark Gene: egr2 has been classified as Green List (High Evidence).
Mendeliome v0.2781 EGR2 Zornitza Stark Phenotypes for gene: EGR2 were changed from to Charcot-Marie-Tooth disease, type 1D 607678 AD; Dejerine-Sottas disease 145900 AD, AR; Hypomyelinating neuropathy, congenital, 1 605253 AD, AR
Mendeliome v0.2780 EGR2 Zornitza Stark Publications for gene: EGR2 were set to
Mendeliome v0.2779 EGR2 Zornitza Stark Mode of pathogenicity for gene: EGR2 was changed from to Other
Mendeliome v0.2778 EGR2 Zornitza Stark Mode of inheritance for gene: EGR2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2777 EGR2 Zornitza Stark reviewed gene: EGR2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 11523566, 31852952; Phenotypes: Charcot-Marie-Tooth disease, type 1D 607678 AD, Dejerine-Sottas disease 145900 AD, AR, Hypomyelinating neuropathy, congenital, 1 605253 AD, AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy_CMT - isolated v0.41 EGR2 Zornitza Stark Marked gene: EGR2 as ready
Hereditary Neuropathy_CMT - isolated v0.41 EGR2 Zornitza Stark Gene: egr2 has been classified as Green List (High Evidence).
Hereditary Neuropathy_CMT - isolated v0.41 EGR2 Zornitza Stark Phenotypes for gene: EGR2 were changed from HMSN; Charcot Marie Tooth disease, type 1D, 607678 to Charcot-Marie-Tooth disease, type 1D 607678 AD; Dejerine-Sottas disease 145900 AD, AR; Hypomyelinating neuropathy, congenital, 1 605253 AD, AR
Hereditary Neuropathy_CMT - isolated v0.40 EGR2 Zornitza Stark Publications for gene: EGR2 were set to
Hereditary Neuropathy_CMT - isolated v0.39 EGR2 Zornitza Stark Mode of pathogenicity for gene: EGR2 was changed from to Other
Hereditary Neuropathy_CMT - isolated v0.38 EGR2 Zornitza Stark Mode of inheritance for gene: EGR2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Oligodontia v0.1 WNT10A Michelle Torres reviewed gene: WNT10A: Rating: GREEN; Mode of pathogenicity: None; Publications: 19559398, 30426266; Phenotypes: Odontoonychodermal dysplasia 257980 AR, Schopf-Schulz-Passarge syndrome 224750 AR, Tooth agenesis, selective, 4 150400 AR, AD; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary Neuropathy_CMT - isolated v0.37 EGR2 Michelle Torres reviewed gene: EGR2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 11523566, 31852952; Phenotypes: Charcot-Marie-Tooth disease, type 1D 607678 AD, Dejerine-Sottas disease 145900 AD, AR, Hypomyelinating neuropathy, congenital, 1 605253 AD, AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2777 GAS2L2 Zornitza Stark Marked gene: GAS2L2 as ready
Mendeliome v0.2777 GAS2L2 Zornitza Stark Gene: gas2l2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2777 GAS2L2 Zornitza Stark Phenotypes for gene: GAS2L2 were changed from to Ciliary dyskinesia, primary, 41 (MIM # 618449)
Mendeliome v0.2776 GAS2L2 Zornitza Stark Publications for gene: GAS2L2 were set to
Mendeliome v0.2775 GAS2L2 Zornitza Stark Mode of inheritance for gene: GAS2L2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2774 GAS2L2 Zornitza Stark Classified gene: GAS2L2 as Amber List (moderate evidence)
Mendeliome v0.2774 GAS2L2 Zornitza Stark Gene: gas2l2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2773 GAS2L2 Zornitza Stark reviewed gene: GAS2L2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30665704; Phenotypes: Ciliary dyskinesia, primary, 41 (MIM # 618449); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2629 ADAM22 Zornitza Stark gene: ADAM22 was added
gene: ADAM22 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: ADAM22 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAM22 were set to 27066583; 30237576
Phenotypes for gene: ADAM22 were set to Epileptic encephalopathy, early infantile, 61, MIM# 617933
Review for gene: ADAM22 was set to AMBER
Added comment: Two families reported; the second one as part of a large consanguineous cohort.
Sources: Expert Review
Differences of Sex Development v0.28 KLB Zornitza Stark Marked gene: KLB as ready
Differences of Sex Development v0.28 KLB Zornitza Stark Gene: klb has been classified as Green List (High Evidence).
Differences of Sex Development v0.28 KLB Zornitza Stark Classified gene: KLB as Green List (high evidence)
Differences of Sex Development v0.28 KLB Zornitza Stark Gene: klb has been classified as Green List (High Evidence).
Differences of Sex Development v0.27 KLB Zornitza Stark gene: KLB was added
gene: KLB was added to Disorders of Sex Differentiation. Sources: Literature
Mode of inheritance for gene: KLB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLB were set to 28754744
Phenotypes for gene: KLB were set to Hypogonadotropic hypogonadism
Review for gene: KLB was set to GREEN
Added comment: Seven heterozygous loss‐of‐function KLB mutations in 13 individuals reported. In mice, lack of Klb led to delayed puberty, altered estrous cyclicity, and subfertility due to a hypothalamic defect associated with inability of GnRH neurons to release GnRH in response to FGF21. Functional analysis showed decreased activity in response to FGF21 and FGF8. KLB is an obligate coreceptor for FGF21 alongside FGFR1.
Sources: Literature
Mendeliome v0.2773 KLB Zornitza Stark Marked gene: KLB as ready
Mendeliome v0.2773 KLB Zornitza Stark Gene: klb has been classified as Green List (High Evidence).
Mendeliome v0.2773 KLB Zornitza Stark Phenotypes for gene: KLB were changed from to Hypogonadotropic hypogonadism
Mendeliome v0.2772 KLB Zornitza Stark Classified gene: KLB as Green List (high evidence)
Mendeliome v0.2772 KLB Zornitza Stark Gene: klb has been classified as Green List (High Evidence).
Mendeliome v0.2771 KLB Zornitza Stark gene: KLB was added
gene: KLB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KLB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLB were set to 28754744
Review for gene: KLB was set to GREEN
Added comment: Seven heterozygous loss‐of‐function KLB mutations in 13 individuals reported. In mice, lack of Klb led to delayed puberty, altered estrous cyclicity, and subfertility due to a hypothalamic defect associated with inability of GnRH neurons to release GnRH in response to FGF21.
Functional analysis showed decreased activity in response to FGF21 and FGF8.
KLB is an obligate coreceptor for FGF21 alongside FGFR1.
Sources: Literature
Differences of Sex Development v0.26 NDNF Zornitza Stark Marked gene: NDNF as ready
Differences of Sex Development v0.26 NDNF Zornitza Stark Gene: ndnf has been classified as Green List (High Evidence).
Differences of Sex Development v0.26 NDNF Zornitza Stark Classified gene: NDNF as Green List (high evidence)
Differences of Sex Development v0.26 NDNF Zornitza Stark Gene: ndnf has been classified as Green List (High Evidence).
Differences of Sex Development v0.25 NDNF Zornitza Stark gene: NDNF was added
gene: NDNF was added to Disorders of Sex Differentiation. Sources: Literature
Mode of inheritance for gene: NDNF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NDNF were set to 31883645
Phenotypes for gene: NDNF were set to Congenital hypogonadotropic hypogonadism (CHH)
Review for gene: NDNF was set to GREEN
Added comment: Three heterozygous protein-truncating variants and one heterozygous missense variant identified in a cohort of 240 unrelated IHH patients. The authors also provided supporting evidence from animal models.
Sources: Literature
Mendeliome v0.2770 NDNF Zornitza Stark Marked gene: NDNF as ready
Mendeliome v0.2770 NDNF Zornitza Stark Gene: ndnf has been classified as Green List (High Evidence).
Mendeliome v0.2770 NDNF Zornitza Stark Classified gene: NDNF as Green List (high evidence)
Mendeliome v0.2770 NDNF Zornitza Stark Gene: ndnf has been classified as Green List (High Evidence).
Mendeliome v0.2769 NDNF Zornitza Stark gene: NDNF was added
gene: NDNF was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NDNF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NDNF were set to 31883645
Phenotypes for gene: NDNF were set to Congenital hypogonadotropic hypogonadism (CHH)
Review for gene: NDNF was set to GREEN
Added comment: Three heterozygous protein-truncating variants and one heterozygous missense variant identified in a cohort of 240 unrelated IHH patients. The authors also provided supporting evidence from animal models.
Sources: Literature
Mendeliome v0.2768 UGDH Zornitza Stark Marked gene: UGDH as ready
Mendeliome v0.2768 UGDH Zornitza Stark Gene: ugdh has been classified as Green List (High Evidence).
Mendeliome v0.2768 UGDH Zornitza Stark Classified gene: UGDH as Green List (high evidence)
Mendeliome v0.2768 UGDH Zornitza Stark Gene: ugdh has been classified as Green List (High Evidence).
Mendeliome v0.2767 UGDH Zornitza Stark gene: UGDH was added
gene: UGDH was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGDH were set to 32001716
Phenotypes for gene: UGDH were set to Epileptic encephalopathy, early infantile, 84 - MIM #618792
Review for gene: UGDH was set to GREEN
Added comment: 36 individuals with biallelic UGDH pathogenic variants reported. The phenotype corresponded overall to a developmental epileptic encephalopathy with hypotonia, feeding difficulties, severe global DD, moderate or commonly severe ID in all. Hypotonia and motor disorder (incl. spasticity, dystonia, ataxia, chorea, etc) often occurred prior to the onset of seizures. A single individual did not present seizures and 2 sibs had only seizures in the setting of fever. There were no individuals with biallelic pLoF variants identified. Parental/sib studies were all compatible with AR inheritance mode.

UGDH encodes the enzyme UDP-glucose dehydrogenase which converts UDP-glucose to UDP-glucuronate, the latter being a critical component of the glycosaminoglycans, hyaluronan, chondroitin sulfate, and heparan sulfate. Patient fibroblast and biochemical assays suggested a LoF effect of variants leading to impairment of UGDH stability, oligomerization or enzymatic activity (decreased UGDH-catalyzed reduction of NAD+ to NADH / hyaluronic acid production which requires UDP-glucuronate).

Attempts to model the disorder using an already developped zebrafish model (for a hypomorphic LoF allele) were unsuccessful as fish did not exhibit seizures spontaneously or upon induction with PTZ. Modelling of the disorder in vitro using patient-derived cerebral organoids demonstrated smaller organoids due to reduced number of proliferating neural progenitors
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2628 UGDH Zornitza Stark Marked gene: UGDH as ready
Intellectual disability syndromic and non-syndromic v0.2628 UGDH Zornitza Stark Gene: ugdh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2628 UGDH Zornitza Stark Classified gene: UGDH as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2628 UGDH Zornitza Stark Gene: ugdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.695 UGDH Zornitza Stark Marked gene: UGDH as ready
Genetic Epilepsy v0.695 UGDH Zornitza Stark Gene: ugdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.695 UGDH Zornitza Stark Classified gene: UGDH as Green List (high evidence)
Genetic Epilepsy v0.695 UGDH Zornitza Stark Gene: ugdh has been classified as Green List (High Evidence).
Mendeliome v0.2766 TRIM33 Zornitza Stark Marked gene: TRIM33 as ready
Mendeliome v0.2766 TRIM33 Zornitza Stark Gene: trim33 has been classified as Red List (Low Evidence).
Mendeliome v0.2766 TRIM33 Zornitza Stark Classified gene: TRIM33 as Red List (low evidence)
Mendeliome v0.2766 TRIM33 Zornitza Stark Gene: trim33 has been classified as Red List (Low Evidence).
Mendeliome v0.2765 TRIM33 Zornitza Stark reviewed gene: TRIM33: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ciliopathies v0.133 ADAMTS9 Zornitza Stark Marked gene: ADAMTS9 as ready
Ciliopathies v0.133 ADAMTS9 Zornitza Stark Gene: adamts9 has been classified as Green List (High Evidence).
Ciliopathies v0.133 ADAMTS9 Zornitza Stark Classified gene: ADAMTS9 as Green List (high evidence)
Ciliopathies v0.133 ADAMTS9 Zornitza Stark Gene: adamts9 has been classified as Green List (High Evidence).
Ciliopathies v0.132 ADAMTS9 Zornitza Stark gene: ADAMTS9 was added
gene: ADAMTS9 was added to Ciliopathies. Sources: Expert list
Mode of inheritance for gene: ADAMTS9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS9 were set to 30609407
Phenotypes for gene: ADAMTS9 were set to Nephronophthisis-Related Ciliopathy
Review for gene: ADAMTS9 was set to GREEN
Added comment: Two families reported with functional evidence.
Sources: Expert list
Genetic Epilepsy v0.694 UGDH Konstantinos Varvagiannis gene: UGDH was added
gene: UGDH was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: UGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGDH were set to 32001716
Phenotypes for gene: UGDH were set to Epileptic encephalopathy, early infantile, 84 - MIM #618792
Penetrance for gene: UGDH were set to Complete
Review for gene: UGDH was set to GREEN
Added comment: Hengel et al (2020 - PMID: 32001716) report on 36 individuals with biallelic UGDH pathogenic variants.

The phenotype corresponded overall to a developmental epileptic encephalopathy with hypotonia, feeding difficulties, severe global DD, moderate or commonly severe ID in all. Hypotonia and motor disorder (incl. spasticity, dystonia, ataxia, chorea, etc) often occurred prior to the onset of seizures. A single individual did not present seizures and 2 sibs had only seizures in the setting of fever.

Affected subjects were tested by exome sequencing and UGDH variants were the only/best candidates for the phenotype following also segregation studies. Many were compound heterozygous or homozygous (~6 families were consanguineous) for missense variants and few were compound heterozygous for missense and pLoF variants. There were no individuals with biallelic pLoF variants identified. Parental/sib studies were all compatible with AR inheritance mode.

UGDH encodes the enzyme UDP-glucose dehydrogenase which converts UDP-glucose to UDP-glucuronate, the latter being a critical component of the glycosaminoglycans, hyaluronan, chondroitin sulfate, and heparan sulfate [OMIM].

Patient fibroblast and biochemical assays suggested a LoF effect of variants leading to impairment of UGDH stability, oligomerization or enzymatic activity (decreased UGDH-catalyzed reduction of NAD+ to NADH / hyaluronic acid production which requires UDP-glucuronate).

Attempts to model the disorder using an already developped zebrafish model (for a hypomorphic LoF allele) were unsuccessful as fish did not exhibit seizures spontaneously or upon induction with PTZ.

Modelling of the disorder in vitro using patient-derived cerebral organoids demonstrated smaller organoids due to reduced number of proliferating neural progenitors.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2627 UGDH Konstantinos Varvagiannis gene: UGDH was added
gene: UGDH was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: UGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGDH were set to 32001716
Phenotypes for gene: UGDH were set to Epileptic encephalopathy, early infantile, 84 - MIM #618792
Penetrance for gene: UGDH were set to Complete
Review for gene: UGDH was set to GREEN
Added comment: Hengel et al (2020 - PMID: 32001716) report on 36 individuals with biallelic UGDH pathogenic variants.

The phenotype corresponded overall to a developmental epileptic encephalopathy with hypotonia, feeding difficulties, severe global DD, moderate or commonly severe ID in all. Hypotonia and motor disorder (incl. spasticity, dystonia, ataxia, chorea, etc) often occurred prior to the onset of seizures. A single individual did not present seizures and 2 sibs had only seizures in the setting of fever.

Affected subjects were tested by exome sequencing and UGDH variants were the only/best candidates for the phenotype following also segregation studies. Many were compound heterozygous or homozygous (~6 families were consanguineous) for missense variants and few were compound heterozygous for missense and pLoF variants. There were no individuals with biallelic pLoF variants identified. Parental/sib studies were all compatible with AR inheritance mode.

UGDH encodes the enzyme UDP-glucose dehydrogenase which converts UDP-glucose to UDP-glucuronate, the latter being a critical component of the glycosaminoglycans, hyaluronan, chondroitin sulfate, and heparan sulfate [OMIM].

Patient fibroblast and biochemical assays suggested a LoF effect of variants leading to impairment of UGDH stability, oligomerization or enzymatic activity (decreased UGDH-catalyzed reduction of NAD+ to NADH / hyaluronic acid production which requires UDP-glucuronate).

Attempts to model the disorder using an already developped zebrafish model (for a hypomorphic LoF allele) were unsuccessful as fish did not exhibit seizures spontaneously or upon induction with PTZ.

Modelling of the disorder in vitro using patient-derived cerebral organoids demonstrated smaller organoids due to reduced number of proliferating neural progenitors.
Sources: Literature
Leukodystrophy - adult onset v0.55 L2HGDH Zornitza Stark Marked gene: L2HGDH as ready
Leukodystrophy - adult onset v0.55 L2HGDH Zornitza Stark Gene: l2hgdh has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.55 L2HGDH Zornitza Stark Publications for gene: L2HGDH were set to
Leukodystrophy - adult onset v0.54 L2HGDH Zornitza Stark reviewed gene: L2HGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 10399870; Phenotypes: L-2-hydroxyglutaric aciduria, MIM# 236792; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.116 L2HGDH Zornitza Stark Marked gene: L2HGDH as ready
Leukodystrophy - paediatric v0.116 L2HGDH Zornitza Stark Gene: l2hgdh has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.116 L2HGDH Zornitza Stark Classified gene: L2HGDH as Green List (high evidence)
Leukodystrophy - paediatric v0.116 L2HGDH Zornitza Stark Gene: l2hgdh has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.115 L2HGDH Zornitza Stark gene: L2HGDH was added
gene: L2HGDH was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: L2HGDH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: L2HGDH were set to L-2-hydroxyglutaric aciduria, MIM# 236792
Review for gene: L2HGDH was set to GREEN
Added comment: Age of onset is variable, but typically in infancy/childhood.
Sources: Expert list
Leukodystrophy - adult onset v0.54 HTRA1 Zornitza Stark Marked gene: HTRA1 as ready
Leukodystrophy - adult onset v0.54 HTRA1 Zornitza Stark Gene: htra1 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.54 HTRA1 Zornitza Stark reviewed gene: HTRA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: CARASIL syndrome, MIM# 600142, Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2, MIM# 616779; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Leukodystrophy - adult onset v0.54 HEXA Zornitza Stark Marked gene: HEXA as ready
Leukodystrophy - adult onset v0.54 HEXA Zornitza Stark Gene: hexa has been classified as Green List (High Evidence).
Genetic Epilepsy v0.694 SPTBN4 Zornitza Stark Marked gene: SPTBN4 as ready
Genetic Epilepsy v0.694 SPTBN4 Zornitza Stark Gene: sptbn4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.694 SPTBN4 Zornitza Stark Classified gene: SPTBN4 as Green List (high evidence)
Genetic Epilepsy v0.694 SPTBN4 Zornitza Stark Gene: sptbn4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2627 SPTBN4 Zornitza Stark Marked gene: SPTBN4 as ready
Intellectual disability syndromic and non-syndromic v0.2627 SPTBN4 Zornitza Stark Gene: sptbn4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2627 SPTBN4 Zornitza Stark Classified gene: SPTBN4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2627 SPTBN4 Zornitza Stark Gene: sptbn4 has been classified as Green List (High Evidence).
Mendeliome v0.2765 YIF1B Zornitza Stark Marked gene: YIF1B as ready
Mendeliome v0.2765 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Mendeliome v0.2765 YIF1B Zornitza Stark Classified gene: YIF1B as Green List (high evidence)
Mendeliome v0.2765 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Mendeliome v0.2764 YIF1B Zornitza Stark gene: YIF1B was added
gene: YIF1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to 32006098; 26077767
Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Review for gene: YIF1B was set to GREEN
Added comment: 6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.
Sources: Literature
Microcephaly v0.123 YIF1B Zornitza Stark Marked gene: YIF1B as ready
Microcephaly v0.123 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Microcephaly v0.123 YIF1B Zornitza Stark Classified gene: YIF1B as Green List (high evidence)
Microcephaly v0.123 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Microcephaly v0.122 YIF1B Zornitza Stark gene: YIF1B was added
gene: YIF1B was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to 32006098; 26077767
Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Review for gene: YIF1B was set to GREEN
Added comment: 6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.
Sources: Literature
Genetic Epilepsy v0.693 YIF1B Zornitza Stark Marked gene: YIF1B as ready
Genetic Epilepsy v0.693 YIF1B Zornitza Stark Gene: yif1b has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.693 YIF1B Zornitza Stark Classified gene: YIF1B as Amber List (moderate evidence)
Genetic Epilepsy v0.693 YIF1B Zornitza Stark Gene: yif1b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2626 YIF1B Zornitza Stark Marked gene: YIF1B as ready
Intellectual disability syndromic and non-syndromic v0.2626 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2626 YIF1B Zornitza Stark Classified gene: YIF1B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2626 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.54 HEXA Zornitza Stark reviewed gene: HEXA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tay-Sachs disease, MIM# 272800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.114 HEXA Zornitza Stark Marked gene: HEXA as ready
Leukodystrophy - paediatric v0.114 HEXA Zornitza Stark Gene: hexa has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.114 HEXA Zornitza Stark Classified gene: HEXA as Green List (high evidence)
Leukodystrophy - paediatric v0.114 HEXA Zornitza Stark Gene: hexa has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.113 HEXA Zornitza Stark gene: HEXA was added
gene: HEXA was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: HEXA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HEXA were set to Tay-Sachs disease, MIM# 272800
Review for gene: HEXA was set to GREEN
Added comment: Sources: Expert list
Genetic Epilepsy v0.692 YIF1B Konstantinos Varvagiannis changed review comment from: Abnormality of movement
AlMuhaizea et al (2020 - PMID: 32006098) report on the phenotype of 6 individuals (from 5 families) with biallelic YIF1B truncating variants.

Affected subjects presented hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID (as evident from best motor/language milestones achieved - Table S1) as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3.

Variable initial investigations were performed including SNP CMA, MECP2, microcephaly / neurotransmitter disorders gene panel testing did not reveal P/LP variants.

YIF1B variants were identified in 3 families within ROH. Following exome sequencing, affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*.

YIF1B encodes an intracellular transmembrane protein.

It has been previously demonstrated that - similarly to other proteins of the Yip family being implicated in intracellular traffic between the Golgi - Yif1B is involved in the anterograde traffic pathway. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). The rat ortholog interacts with serotonin receptor 1 (5-HT1AR) with colocalization of Yif1BB and 5-HT1AR in intermediate compartment vesicles and involvement of the former in intracellular trafficing/modulation of 5-HT1AR transport to dendrites (PMID cited: 18685031).

Available mRNA and protein expression data (Protein Atlas) suggest that the gene is widely expressed in all tissues incl. neuronal cells. Immunochemistry data from the Human Brain Atlas also suggest that YIF1B is found in vesicles and localized to the Golgi apparatus. Immunohistochemistry in normal human brain tissue (cerebral cortex) demonstrated labeling of neuronal cells (Human Protein Atlas).

Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.

Please consider inclusion in other panels that may be relevant (e.g. microcephaly, etc).
Sources: Literature; to: AlMuhaizea et al (2020 - PMID: 32006098) report on the phenotype of 6 individuals (from 5 families) with biallelic YIF1B truncating variants.

Affected subjects presented hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID (as evident from best motor/language milestones achieved - Table S1) as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3.

Variable initial investigations were performed including SNP CMA, MECP2, microcephaly / neurotransmitter disorders gene panel testing did not reveal P/LP variants.

YIF1B variants were identified in 3 families within ROH. Following exome sequencing, affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*.

YIF1B encodes an intracellular transmembrane protein.

It has been previously demonstrated that - similarly to other proteins of the Yip family being implicated in intracellular traffic between the Golgi - Yif1B is involved in the anterograde traffic pathway. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). The rat ortholog interacts with serotonin receptor 1 (5-HT1AR) with colocalization of Yif1BB and 5-HT1AR in intermediate compartment vesicles and involvement of the former in intracellular trafficing/modulation of 5-HT1AR transport to dendrites (PMID cited: 18685031).

Available mRNA and protein expression data (Protein Atlas) suggest that the gene is widely expressed in all tissues incl. neuronal cells. Immunochemistry data from the Human Brain Atlas also suggest that YIF1B is found in vesicles and localized to the Golgi apparatus. Immunohistochemistry in normal human brain tissue (cerebral cortex) demonstrated labeling of neuronal cells (Human Protein Atlas).

Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.

Please consider inclusion in other panels that may be relevant (e.g. microcephaly, etc).
Sources: Literature
Genetic Epilepsy v0.692 YIF1B Konstantinos Varvagiannis gene: YIF1B was added
gene: YIF1B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to 32006098
Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Penetrance for gene: YIF1B were set to Complete
Review for gene: YIF1B was set to AMBER
Added comment: Abnormality of movement
AlMuhaizea et al (2020 - PMID: 32006098) report on the phenotype of 6 individuals (from 5 families) with biallelic YIF1B truncating variants.

Affected subjects presented hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID (as evident from best motor/language milestones achieved - Table S1) as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3.

Variable initial investigations were performed including SNP CMA, MECP2, microcephaly / neurotransmitter disorders gene panel testing did not reveal P/LP variants.

YIF1B variants were identified in 3 families within ROH. Following exome sequencing, affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*.

YIF1B encodes an intracellular transmembrane protein.

It has been previously demonstrated that - similarly to other proteins of the Yip family being implicated in intracellular traffic between the Golgi - Yif1B is involved in the anterograde traffic pathway. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). The rat ortholog interacts with serotonin receptor 1 (5-HT1AR) with colocalization of Yif1BB and 5-HT1AR in intermediate compartment vesicles and involvement of the former in intracellular trafficing/modulation of 5-HT1AR transport to dendrites (PMID cited: 18685031).

Available mRNA and protein expression data (Protein Atlas) suggest that the gene is widely expressed in all tissues incl. neuronal cells. Immunochemistry data from the Human Brain Atlas also suggest that YIF1B is found in vesicles and localized to the Golgi apparatus. Immunohistochemistry in normal human brain tissue (cerebral cortex) demonstrated labeling of neuronal cells (Human Protein Atlas).

Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.

Please consider inclusion in other panels that may be relevant (e.g. microcephaly, etc).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2625 YIF1B Konstantinos Varvagiannis gene: YIF1B was added
gene: YIF1B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to 32006098
Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Penetrance for gene: YIF1B were set to Complete
Review for gene: YIF1B was set to GREEN
Added comment: AlMuhaizea et al (2020 - PMID: 32006098) report on the phenotype of 6 individuals (from 5 families) with biallelic YIF1B truncating variants.

Affected subjects presented hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID (as evident from best motor/language milestones achieved - Table S1) as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3.

Variable initial investigations were performed including SNP CMA, MECP2, microcephaly / neurotransmitter disorders gene panel testing did not reveal P/LP variants.

YIF1B variants were identified in 3 families within ROH. Following exome sequencing, affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*.

YIF1B encodes an intracellular transmembrane protein.

It has been previously demonstrated that - similarly to other proteins of the Yip family being implicated in intracellular traffic between the Golgi - Yif1B is involved in the anterograde traffic pathway. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). The rat ortholog interacts with serotonin receptor 1 (5-HT1AR) with colocalization of Yif1BB and 5-HT1AR in intermediate compartment vesicles and involvement of the former in intracellular trafficing/modulation of 5-HT1AR transport to dendrites (PMID cited: 18685031).

Available mRNA and protein expression data (Protein Atlas) suggest that the gene is widely expressed in all tissues incl. neuronal cells. Immunochemistry data from the Human Brain Atlas also suggest that YIF1B is found in vesicles and localized to the Golgi apparatus. Immunohistochemistry in normal human brain tissue (cerebral cortex) demonstrated labeling of neuronal cells (Human Protein Atlas).

Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.

Please consider inclusion in other panels that may be relevant (e.g. microcephaly, etc).
Sources: Literature
Genetic Epilepsy v0.692 SPTBN4 Konstantinos Varvagiannis gene: SPTBN4 was added
gene: SPTBN4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SPTBN4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPTBN4 were set to 28540413; 28940097; 29861105; 31230720; 31857255
Phenotypes for gene: SPTBN4 were set to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness MIM#617519
Penetrance for gene: SPTBN4 were set to Complete
Review for gene: SPTBN4 was set to GREEN
Added comment: Biallelic pathogenic SPTBN4 variants cause Neurodevelopmental disorder with hypotonia, neuropathy, and deafness (MIM #617519).

There are several reports on the phenotype of relevant affected individuals with severe/profound DD/ID in at least 9 individuals :

- Knierim et al (2017 - PMID: 28540413) [1 affected individual]
- Anazi et al (2017 - PMID: 28940097) [1]
- Wang et al (2018 - PMID: 29861105) [6]
- Pehlivan et al (2019 - PMID: 31230720) [1]

A recent article by Häusler et al (2019 - PMID: 31857255) describes the phenotype of 2 sibs, both presenting with motor and speech delay, although the older one had reportedly 'normal' cognitive performance allowing attendance of regular school at the age of 6 years.

Features include congenital hypotonia, severe DD and ID (in most as outlined above, ID was the primary indication for testing on several occasions), poor or absent reflexes and weakness secondary to axonal motor neuropathy, feeding and respiratory difficulties, hearing and visual impairment. Seizures have been reported in at least 4 unrelated individuals (3 by Wang et al / 1 by Pehlivan et al).

Variants in most cases were nonsense/frameshift although biallelic missense variants have also been reported. Sibs in the report by Häusler et al harbored a homozygous splicing variant.

SPTBN4 encodes a member of the beta-spectrin protein family that is expressed in the brain, peripheral nervous system, pancreas, and skeletal muscle.

βIV spectrin links ankyrinG and clustered ion channels (at axon initial segments and nodes of Ranvier) to the axonal cytoskeleton. Pathogenic variants are proposed to disrupt the cytoskeletal machinery controlling proper localization of ion channels and function of axonal domains where ion channels are normally clustered in high density. Among the evidence provided : nerve biopsies from an affected individual displayed reduced nodal Na+ channels and no nodal KCNQ2 K+ channels / Loss of AnkyrinG and βIV spectrin in animal model resulted in loss of KCNQ2- and KCNQ3- subunit containing K+ channels.

Apart from the ID / epilepsy panels please consider inclusion in other relevant ones.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2625 SPTBN4 Konstantinos Varvagiannis reviewed gene: SPTBN4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28540413, 28940097, 29861105, 31230720, 31857255; Phenotypes: Neurodevelopmental disorder with hypotonia, neuropathy, and deafness MIM#617519; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2763 TNRC6B Zornitza Stark Phenotypes for gene: TNRC6B were changed from to Global developmental delay; Intellectual disability; Autistic behavior
Mendeliome v0.2762 TNRC6B Zornitza Stark Publications for gene: TNRC6B were set to
Mendeliome v0.2761 TNRC6B Zornitza Stark Mode of inheritance for gene: TNRC6B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2760 TNRC6B Zornitza Stark Classified gene: TNRC6B as Green List (high evidence)
Mendeliome v0.2760 TNRC6B Zornitza Stark Gene: tnrc6b has been classified as Green List (High Evidence).
Mendeliome v0.2759 TNRC6B Zornitza Stark edited their review of gene: TNRC6B: Added comment: 17 unrelated individuals with heterozygous TNRC6B variants reported. Features included hypotonia (10/17), DD/ID (17/17 - ID was not universal: average IQ of 12 individuals was 73 (range : 50-113) with 4 having below 70), ADHD (11/17), ASD or autistic traits (8/17 and 5/17). Some/few presented with abnormal OFC (micro- / macrocephaly in 3/17 and 2/17), abnormal vision or hearing, variable other congenital anomalies, echocardiographic, GI or renal abnormalities, etc. Epilepsy was reported in 1/17. There was no recognisable gestalt.Detected variants included 14 pLoF, 1 missense SNV and 2 intragenic deletions. Variants had occurred as de novo events in 10/13 subjects for whom testing of both parents was possible. 3/13 subjects had inherited the variant from a parent with milder phenotype. Based on the type of variants identified, the pLI score of 1 in gnomAD and the HI index of 5.61%, the authors suggest haploinsufficiency as the most likely mechanism. Individuals with de novo TNRC6B variants have also been reported in larger cohorts (e.g. DDD study - PMID: 28135719, Iossifov et al - PMID: 25363768, Lelieveld et al - PMID: 27479843, Jónsson et al - PMID: 28959963). A previous study provided details on 2 sibs harboring a translocation which disrupted both TNRC6B and TCF20 (also associated with ID)(Babbs et al - PMID: 25228304).; Changed rating: GREEN; Changed publications: 32152250, 28135719, 25363768, 27479843, 28959963, 25228304; Changed phenotypes: Global developmental delay, Intellectual disability, Autistic behavior; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.90 TNRC6B Zornitza Stark Phenotypes for gene: TNRC6B were changed from to Global developmental delay; Intellectual disability; Autistic behavior
Autism v0.89 TNRC6B Zornitza Stark Publications for gene: TNRC6B were set to
Autism v0.88 TNRC6B Zornitza Stark Mode of inheritance for gene: TNRC6B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.87 TNRC6B Zornitza Stark Classified gene: TNRC6B as Green List (high evidence)
Autism v0.87 TNRC6B Zornitza Stark Gene: tnrc6b has been classified as Green List (High Evidence).
Autism v0.86 TNRC6B Zornitza Stark edited their review of gene: TNRC6B: Added comment: 17 unrelated individuals with heterozygous TNRC6B variants reported. Features included hypotonia (10/17), DD/ID (17/17 - ID was not universal: average IQ of 12 individuals was 73 (range : 50-113) with 4 having below 70), ADHD (11/17), ASD or autistic traits (8/17 and 5/17). Some/few presented with abnormal OFC (micro- / macrocephaly in 3/17 and 2/17), abnormal vision or hearing, variable other congenital anomalies, echocardiographic, GI or renal abnormalities, etc. Epilepsy was reported in 1/17. There was no recognisable gestalt.Detected variants included 14 pLoF, 1 missense SNV and 2 intragenic deletions. Variants had occurred as de novo events in 10/13 subjects for whom testing of both parents was possible. 3/13 subjects had inherited the variant from a parent with milder phenotype. Based on the type of variants identified, the pLI score of 1 in gnomAD and the HI index of 5.61%, the authors suggest haploinsufficiency as the most likely mechanism. Individuals with de novo TNRC6B variants have also been reported in larger cohorts (e.g. DDD study - PMID: 28135719, Iossifov et al - PMID: 25363768, Lelieveld et al - PMID: 27479843, Jónsson et al - PMID: 28959963). A previous study provided details on 2 sibs harboring a translocation which disrupted both TNRC6B and TCF20 (also associated with ID)(Babbs et al - PMID: 25228304).; Changed rating: GREEN; Changed publications: 32152250, 28135719, 25363768, 27479843, 28959963, 25228304; Changed phenotypes: Global developmental delay, Intellectual disability, Autistic behavior; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2625 TNRC6B Zornitza Stark Phenotypes for gene: TNRC6B were changed from to Global developmental delay; Intellectual disability; Autistic behavior
Intellectual disability syndromic and non-syndromic v0.2624 TNRC6B Zornitza Stark Publications for gene: TNRC6B were set to
Intellectual disability syndromic and non-syndromic v0.2623 TNRC6B Zornitza Stark Mode of inheritance for gene: TNRC6B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2622 TNRC6B Zornitza Stark Classified gene: TNRC6B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2622 TNRC6B Zornitza Stark Gene: tnrc6b has been classified as Green List (High Evidence).
Mendeliome v0.2759 CDC42BPB Zornitza Stark Marked gene: CDC42BPB as ready
Mendeliome v0.2759 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Green List (High Evidence).
Mendeliome v0.2759 CDC42BPB Zornitza Stark Classified gene: CDC42BPB as Green List (high evidence)
Mendeliome v0.2759 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Green List (High Evidence).
Mendeliome v0.2758 CDC42BPB Zornitza Stark gene: CDC42BPB was added
gene: CDC42BPB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDC42BPB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDC42BPB were set to 32031333
Phenotypes for gene: CDC42BPB were set to Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality
Review for gene: CDC42BPB was set to GREEN
Added comment: 14 individuals with missense and loss-of-function CDC42BPB variants reported. Features included hypotonia (8/11), DD (12/13 - the 14th was a fetus), ID (7/13), ASD (8/12), clinical seizures (in 3 - a 4th had abnormal EEG without seizures), behavioral abnormalities. Variable non-specific dysmorphic features were reported in some (sparse hair being the most frequent - 4/8). Additional features were observed in few (=<4) incl. cryptorchidism, ophthalmological issues, constipation, kidney abnormalities, micropenis, etc. Most variants occurred as de novo events (11/14) while inheritance was not available for few (3/14).
Sources: Literature
Genetic Epilepsy v0.692 CDC42BPB Zornitza Stark Marked gene: CDC42BPB as ready
Genetic Epilepsy v0.692 CDC42BPB Zornitza Stark Added comment: Comment when marking as ready: Primarily an ID gene, remains to be seen whether seizures are a prominent part of the phenotype.
Genetic Epilepsy v0.692 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.692 CDC42BPB Zornitza Stark Mode of inheritance for gene: CDC42BPB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.691 CDC42BPB Zornitza Stark Classified gene: CDC42BPB as Amber List (moderate evidence)
Genetic Epilepsy v0.691 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.691 CDC42BPB Zornitza Stark Classified gene: CDC42BPB as Green List (high evidence)
Genetic Epilepsy v0.691 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2621 CDC42BPB Zornitza Stark Marked gene: CDC42BPB as ready
Intellectual disability syndromic and non-syndromic v0.2621 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2621 CDC42BPB Zornitza Stark Mode of inheritance for gene: CDC42BPB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2620 CDC42BPB Zornitza Stark Classified gene: CDC42BPB as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2620 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2619 TNRC6B Konstantinos Varvagiannis reviewed gene: TNRC6B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32152250, 28135719, 25363768, 27479843, 28959963, 25228304; Phenotypes: Global developmental delay, Intellectual disability, Autistic behavior; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.690 CDC42BPB Konstantinos Varvagiannis gene: CDC42BPB was added
gene: CDC42BPB was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CDC42BPB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CDC42BPB were set to 32031333
Phenotypes for gene: CDC42BPB were set to Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality
Penetrance for gene: CDC42BPB were set to unknown
Review for gene: CDC42BPB was set to AMBER
Added comment: Chilton et al (2020 - PMID: 32031333) report on 14 individuals with missense and loss-of-function CDC42BPB variants.

Features included hypotonia (8/11), DD (12/13 - the 14th was a fetus), ID (7/13), ASD (8/12), clinical seizures (in 3 - a 4th had abnormal EEG without seizures), behavioral abnormalities. Variable non-specific dysmorphic features were reported in some (sparse hair being the most frequent - 4/8). Additional features were observed in few (=<4) incl. cryptorchidism, ophthalmological issues, constipation, kidney abnormalities, micropenis, etc.

All individuals had non-diagnostic prior genetic testing (incl. CMA, FMR1, MECP2, Angelman/Prader-Willi methylation studies, autism gene panel - suggesting relevance to the current panel) or metabolic testing.

Variants were identified following clinical exome sequencing with Sanger confirmation. Most occurred as de novo events (11/14) while inheritance was not available for few (3/14). Missense variants did not display (particular) clustering.

Almost all variants were absent from gnomAD and were predicted to be deleterious in silico (among others almost all had CADD scores >25).

As the authors comment, CDC42BPB encodes myotonic dystrophy-related Cdc42-binding kinase β (MRCKβ) a serine/threonine protein kinase playing a role in regulation of cytoskeletal reorganization and cell migration in nonmuscle cells (through phosporylation of MLC2).

Previous studies have demonstrated that it is ubiquitously expressed with prenatal brain expression.

The gene appears to be intolerant to pLoF (pLI of 1) as well as to missense variants (Z-score of 3.66).

CDC42BPB is a downstream effector of CDC42. Mutations of the latter cause Takenouchi-Kosaki syndrome with DD/ID and some further overlapping features (with CDC42BPB-associated phenotypes).

Homozygous Cdc42bpb KO in mouse appears to be nonviable (MGI:2136459). Loss of gek in the eyes of Drosophila results in disrupted growth cone targeting to the lamina (gek is the fly CDC42BPB ortholog).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2619 CDC42BPB Konstantinos Varvagiannis gene: CDC42BPB was added
gene: CDC42BPB was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CDC42BPB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CDC42BPB were set to 32031333
Phenotypes for gene: CDC42BPB were set to Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality
Penetrance for gene: CDC42BPB were set to unknown
Review for gene: CDC42BPB was set to GREEN
Added comment: Chilton et al (2020 - PMID: 32031333) report on 14 individuals with missense and loss-of-function CDC42BPB variants.

Features included hypotonia (8/11), DD (12/13 - the 14th was a fetus), ID (7/13), ASD (8/12), clinical seizures (in 3 - a 4th had abnormal EEG without seizures), behavioral abnormalities. Variable non-specific dysmorphic features were reported in some (sparse hair being the most frequent - 4/8). Additional features were observed in few (=<4) incl. cryptorchidism, ophthalmological issues, constipation, kidney abnormalities, micropenis, etc.

All individuals had non-diagnostic prior genetic testing (incl. CMA, FMR1, MECP2, Angelman/Prader-Willi methylation studies, autism gene panel - suggesting relevance to the current panel) or metabolic testing.

Variants were identified following clinical exome sequencing with Sanger confirmation. Most occurred as de novo events (11/14) while inheritance was not available for few (3/14). Missense variants did not display (particular) clustering.

Almost all variants were absent from gnomAD and were predicted to be deleterious in silico (among others almost all had CADD scores >25).

As the authors comment, CDC42BPB encodes myotonic dystrophy-related Cdc42-binding kinase β (MRCKβ) a serine/threonine protein kinase playing a role in regulation of cytoskeletal reorganization and cell migration in nonmuscle cells (through phosporylation of MLC2).

Previous studies have demonstrated that it is ubiquitously expressed with prenatal brain expression.

The gene appears to be intolerant to pLoF (pLI of 1) as well as to missense variants (Z-score of 3.66).

CDC42BPB is a downstream effector of CDC42. Mutations of the latter cause Takenouchi-Kosaki syndrome with DD/ID and some further overlapping features (with CDC42BPB-associated phenotypes).

Homozygous Cdc42bpb KO in mouse appears to be nonviable (MGI:2136459). Loss of gek in the eyes of Drosophila results in disrupted growth cone targeting to the lamina (gek is the fly CDC42BPB ortholog).

Please consider inclusion with amber / green rating in the ID panel (>=4 relevant individuals / variants) and other panels (e.g. for epilepsy, ASD).
Sources: Literature
Ciliopathies v0.131 ACVR2B Zornitza Stark Marked gene: ACVR2B as ready
Ciliopathies v0.131 ACVR2B Zornitza Stark Gene: acvr2b has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.68 ARMC4 Zornitza Stark Marked gene: ARMC4 as ready
Ciliary Dyskinesia v0.68 ARMC4 Zornitza Stark Gene: armc4 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.68 RSPH3 Zornitza Stark Marked gene: RSPH3 as ready
Ciliary Dyskinesia v0.68 RSPH3 Zornitza Stark Gene: rsph3 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.68 RSPH3 Zornitza Stark Phenotypes for gene: RSPH3 were changed from Ciliary dyskinesia, primary, 32 (MIM#616481) to Ciliary dyskinesia, primary, 32 (MIM#616481)
Heterotaxy v0.36 GDF1 Zornitza Stark Marked gene: GDF1 as ready
Heterotaxy v0.36 GDF1 Zornitza Stark Gene: gdf1 has been classified as Green List (High Evidence).
Heterotaxy v0.36 GDF1 Zornitza Stark Classified gene: GDF1 as Green List (high evidence)
Heterotaxy v0.36 GDF1 Zornitza Stark Gene: gdf1 has been classified as Green List (High Evidence).
Heterotaxy v0.35 GDF1 Zornitza Stark gene: GDF1 was added
gene: GDF1 was added to Heterotaxy. Sources: Expert list
Mode of inheritance for gene: GDF1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: GDF1 were set to 32144877
Phenotypes for gene: GDF1 were set to Congenital heart defects, multiple types, 6 613854; Right atrial isomerism (Ivemark) 208530
Review for gene: GDF1 was set to GREEN
Added comment: PMID: 32144877 - founder PTC in Arab population causing congenital heart detects AND right isomerism in 3 (unrelated?) families. Reviews other publications and reports additional chet (two PTC) or homozygous (missense) families with situs inversus and/or heart defects. No apparent genotype-phenotype correlation btw dominant and recessive disease.
Sources: Expert list
Ciliopathies v0.131 GDF1 Zornitza Stark Marked gene: GDF1 as ready
Ciliopathies v0.131 GDF1 Zornitza Stark Added comment: Comment when marking as ready: Agree, this gene belongs on the Heterotaxy panel.
Ciliopathies v0.131 GDF1 Zornitza Stark Gene: gdf1 has been classified as Red List (Low Evidence).
Ciliopathies v0.131 GDF1 Zornitza Stark Phenotypes for gene: GDF1 were changed from Congenital heart defects, multiple types, 6 613854; Right atrial isomerism (Ivemark) 208530 to Congenital heart defects, multiple types, 6 613854; Right atrial isomerism (Ivemark) 208530
Ciliopathies v0.131 GDF1 Zornitza Stark Phenotypes for gene: GDF1 were changed from to Congenital heart defects, multiple types, 6 613854; Right atrial isomerism (Ivemark) 208530
Ciliary Dyskinesia v0.67 RSPH3 Zornitza Stark Phenotypes for gene: RSPH3 were changed from to Ciliary dyskinesia, primary, 32 (MIM#616481)
Ciliary Dyskinesia v0.66 RSPH3 Zornitza Stark Publications for gene: RSPH3 were set to
Ciliopathies v0.130 GDF1 Zornitza Stark Publications for gene: GDF1 were set to
Ciliopathies v0.129 GDF1 Zornitza Stark Mode of inheritance for gene: GDF1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Ciliary Dyskinesia v0.65 RSPH3 Zornitza Stark Mode of inheritance for gene: RSPH3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.128 GDF1 Zornitza Stark Classified gene: GDF1 as Red List (low evidence)
Ciliopathies v0.128 GDF1 Zornitza Stark Gene: gdf1 has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.64 RSPH4A Zornitza Stark Marked gene: RSPH4A as ready
Ciliary Dyskinesia v0.64 RSPH4A Zornitza Stark Gene: rsph4a has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.64 RSPH4A Zornitza Stark Phenotypes for gene: RSPH4A were changed from to Ciliary dyskinesia, primary, 11 (MIM#612649)
Ciliary Dyskinesia v0.63 RSPH4A Zornitza Stark Publications for gene: RSPH4A were set to 25789548; 22448264
Ciliary Dyskinesia v0.63 RSPH4A Zornitza Stark Publications for gene: RSPH4A were set to
Ciliary Dyskinesia v0.62 RSPH4A Zornitza Stark Mode of inheritance for gene: RSPH4A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2757 DNAJB13 Zornitza Stark Marked gene: DNAJB13 as ready
Mendeliome v0.2757 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2757 DNAJB13 Zornitza Stark Phenotypes for gene: DNAJB13 were changed from to Ciliary dyskinesia, primary, 34, MIM# 617091
Mendeliome v0.2756 DNAJB13 Zornitza Stark Publications for gene: DNAJB13 were set to
Mendeliome v0.2755 DNAJB13 Zornitza Stark Mode of inheritance for gene: DNAJB13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2754 DNAJB13 Zornitza Stark Classified gene: DNAJB13 as Amber List (moderate evidence)
Mendeliome v0.2754 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2753 DNAJB13 Zornitza Stark reviewed gene: DNAJB13: Rating: AMBER; Mode of pathogenicity: None; Publications: 27486783; Phenotypes: Ciliary dyskinesia, primary, 34, MIM# 617091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.34 DNAJB13 Zornitza Stark Marked gene: DNAJB13 as ready
Heterotaxy v0.34 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Red List (Low Evidence).
Heterotaxy v0.34 DNAJB13 Zornitza Stark Phenotypes for gene: DNAJB13 were changed from to Ciliary dyskinesia, primary, 34, MIM# 617091
Heterotaxy v0.33 DNAJB13 Zornitza Stark Publications for gene: DNAJB13 were set to
Heterotaxy v0.32 DNAJB13 Zornitza Stark Mode of inheritance for gene: DNAJB13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.31 DNAJB13 Zornitza Stark Classified gene: DNAJB13 as Red List (low evidence)
Heterotaxy v0.31 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Red List (Low Evidence).
Heterotaxy v0.30 DNAJB13 Zornitza Stark reviewed gene: DNAJB13: Rating: RED; Mode of pathogenicity: None; Publications: 27486783; Phenotypes: Ciliary dyskinesia, primary, 34 617091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.61 DNAJB13 Zornitza Stark Marked gene: DNAJB13 as ready
Ciliary Dyskinesia v0.61 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.61 DNAJB13 Zornitza Stark Classified gene: DNAJB13 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.61 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.60 DNAH1 Zornitza Stark Marked gene: DNAH1 as ready
Ciliary Dyskinesia v0.60 DNAH1 Zornitza Stark Gene: dnah1 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.60 DNAH1 Zornitza Stark Phenotypes for gene: DNAH1 were changed from to ?Ciliary dyskinesia, primary, 37 617577; Spermatogenic failure 18 617576
Ciliary Dyskinesia v0.59 DNAH1 Zornitza Stark Publications for gene: DNAH1 were set to
Ciliary Dyskinesia v0.58 DNAH1 Zornitza Stark Mode of inheritance for gene: DNAH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal