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Craniosynostosis v0.110 PHEX Zornitza Stark Classified gene: PHEX as Green List (high evidence)
Craniosynostosis v0.110 PHEX Zornitza Stark Gene: phex has been classified as Green List (High Evidence).
Craniosynostosis v0.109 PHEX Zornitza Stark gene: PHEX was added
gene: PHEX was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: PHEX was set to Other
Publications for gene: PHEX were set to 19242361; 17551721
Phenotypes for gene: PHEX were set to Hypophosphatemic rickets, X-linked dominant, MIM# 307800
Review for gene: PHEX was set to GREEN
Added comment: Craniosynostosis reported in around ~40% of affected individuals.
Sources: Expert list
Gastrointestinal neuromuscular disease v0.14 GDNF Bryony Thompson changed review comment from: Mouse models have a gastrointestinal neuromuscular phenotype, however there is no evidence that variants in GDNF cause Hirschsprung disease or a gastrointestinal neuromuscular disease in humans.
Sources: Expert list; to: Mouse models have a gastrointestinal neuromuscular phenotype, however there is limited evidence that variants in GDNF cause Hirschsprung disease or a gastrointestinal neuromuscular disease in humans.
Sources: Expert list
Gastrointestinal neuromuscular disease v0.14 NRTN Bryony Thompson Marked gene: NRTN as ready
Gastrointestinal neuromuscular disease v0.14 NRTN Bryony Thompson Gene: nrtn has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.14 NRTN Bryony Thompson gene: NRTN was added
gene: NRTN was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: NRTN was set to Unknown
Publications for gene: NRTN were set to 21206993; 10069332; 9700200
Phenotypes for gene: NRTN were set to Hirschsprung disease
Review for gene: NRTN was set to RED
Added comment: A mouse model has a gastrointestinal neuromuscular phenotype, however there is limited evidence that variants in NRTN cause Hirschsprung disease or a gastrointestinal neuromuscular disease in humans.
Sources: Expert list
Gastrointestinal neuromuscular disease v0.13 GDNF Bryony Thompson edited their review of gene: GDNF: Changed publications: 18276829, 8896568, 8657308, 11973622, 21206993
Craniosynostosis v0.108 P4HB Zornitza Stark Marked gene: P4HB as ready
Craniosynostosis v0.108 P4HB Zornitza Stark Gene: p4hb has been classified as Green List (High Evidence).
Craniosynostosis v0.108 P4HB Zornitza Stark Classified gene: P4HB as Green List (high evidence)
Craniosynostosis v0.108 P4HB Zornitza Stark Gene: p4hb has been classified as Green List (High Evidence).
Craniosynostosis v0.107 P4HB Zornitza Stark gene: P4HB was added
gene: P4HB was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: P4HB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: P4HB were set to 25683117; 29384951
Phenotypes for gene: P4HB were set to Cole-Carpenter syndrome 1, MIM# 112240
Review for gene: P4HB was set to GREEN
Added comment: Craniosynostosis is a feature of this syndrome.
Sources: Expert list
Craniosynostosis v0.106 JAG1 Zornitza Stark Marked gene: JAG1 as ready
Craniosynostosis v0.106 JAG1 Zornitza Stark Gene: jag1 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.106 JAG1 Zornitza Stark Classified gene: JAG1 as Amber List (moderate evidence)
Craniosynostosis v0.106 JAG1 Zornitza Stark Gene: jag1 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.105 JAG1 Zornitza Stark gene: JAG1 was added
gene: JAG1 was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: JAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JAG1 were set to 29530693; 12244552
Phenotypes for gene: JAG1 were set to Alagille syndrome 1, MIM# 118450
Review for gene: JAG1 was set to AMBER
Added comment: Craniosynostosis is rarely described in Alagille syndrome, functional data to support role of JAG1 in suture development.
Sources: Expert list
Craniosynostosis v0.104 IHH Zornitza Stark Marked gene: IHH as ready
Craniosynostosis v0.104 IHH Zornitza Stark Gene: ihh has been classified as Green List (High Evidence).
Craniosynostosis v0.104 IHH Zornitza Stark Classified gene: IHH as Green List (high evidence)
Craniosynostosis v0.104 IHH Zornitza Stark Gene: ihh has been classified as Green List (High Evidence).
Craniosynostosis v0.103 IHH Zornitza Stark gene: IHH was added
gene: IHH was added to Craniosynostosis. Sources: Expert list
SV/CNV, 5'UTR tags were added to gene: IHH.
Mode of inheritance for gene: IHH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: IHH were set to Craniosynostosis, Philadelphia type
Mode of pathogenicity for gene: IHH 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: IHH was set to GREEN
Added comment: Green for promoter region 40kb upstream of IHH only. Duplications of 2q35-q36.3 encompassing region 40kb upstream of IHH (within intron of NHEJ1 gene) cause craniosynostosis. Please note SNVs in this gene cause a different phenotype.
Sources: Expert list
Craniosynostosis v0.102 IDUA Zornitza Stark Marked gene: IDUA as ready
Craniosynostosis v0.102 IDUA Zornitza Stark Gene: idua has been classified as Green List (High Evidence).
Craniosynostosis v0.102 IDUA Zornitza Stark Classified gene: IDUA as Green List (high evidence)
Craniosynostosis v0.102 IDUA Zornitza Stark Gene: idua has been classified as Green List (High Evidence).
Craniosynostosis v0.101 IDUA Zornitza Stark gene: IDUA was added
gene: IDUA was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: IDUA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IDUA were set to 23917744
Phenotypes for gene: IDUA were set to Mucopolysaccharidosis Ih/s (Hurler syndrome) 607014; 607016
Review for gene: IDUA was set to GREEN
Added comment: Craniosynostosis of at least one suture was present in 77% of 47 MPS individuals (types I,II,VI, VII). >3 with IDUA, IDS, ARSB variants.
Sources: Expert list
Gastrointestinal neuromuscular disease v0.13 GDNF Bryony Thompson Marked gene: GDNF as ready
Gastrointestinal neuromuscular disease v0.13 GDNF Bryony Thompson Gene: gdnf has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.13 GDNF Bryony Thompson gene: GDNF was added
gene: GDNF was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: GDNF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GDNF were set to 18276829; 8896568; 8657308; 11973622
Phenotypes for gene: GDNF were set to {Hirschsprung disease, susceptibility to, 3} MIM#613711
Review for gene: GDNF was set to RED
Added comment: Mouse models have a gastrointestinal neuromuscular phenotype, however there is no evidence that variants in GDNF cause Hirschsprung disease or a gastrointestinal neuromuscular disease in humans.
Sources: Expert list
Craniosynostosis v0.100 IDS Zornitza Stark Marked gene: IDS as ready
Craniosynostosis v0.100 IDS Zornitza Stark Gene: ids has been classified as Green List (High Evidence).
Craniosynostosis v0.100 IDS Zornitza Stark Classified gene: IDS as Green List (high evidence)
Craniosynostosis v0.100 IDS Zornitza Stark Gene: ids has been classified as Green List (High Evidence).
Craniosynostosis v0.99 IDS Zornitza Stark gene: IDS was added
gene: IDS was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: IDS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IDS were set to 15314824
Phenotypes for gene: IDS were set to Mucopolysaccharidosis II (MPS2, Hunter syndrome) 309900
Review for gene: IDS was set to GREEN
Added comment: Craniosynostosis of at least one suture reported as present in 77% of 47 MPS individuals (types I,II,VI, VII). >3 with IDUA, IDS, ARSB variants.
Sources: Expert list
Craniosynostosis v0.98 GNPTAB Zornitza Stark Marked gene: GNPTAB as ready
Craniosynostosis v0.98 GNPTAB Zornitza Stark Gene: gnptab has been classified as Green List (High Evidence).
Craniosynostosis v0.98 GNPTAB Zornitza Stark Classified gene: GNPTAB as Green List (high evidence)
Craniosynostosis v0.98 GNPTAB Zornitza Stark Gene: gnptab has been classified as Green List (High Evidence).
Craniosynostosis v0.97 GNPTAB Zornitza Stark gene: GNPTAB was added
gene: GNPTAB was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: GNPTAB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNPTAB were set to 24891900; 24060719
Phenotypes for gene: GNPTAB were set to Mucolipidosis II alpha/beta(I cell disease), MIM# 252500
Review for gene: GNPTAB was set to GREEN
Added comment: Recognised complication of I-cell disease.
Sources: Expert list
Craniosynostosis v0.96 GNAS Zornitza Stark Marked gene: GNAS as ready
Craniosynostosis v0.96 GNAS Zornitza Stark Gene: gnas has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.96 GNAS Zornitza Stark Classified gene: GNAS as Amber List (moderate evidence)
Craniosynostosis v0.96 GNAS Zornitza Stark Gene: gnas has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.95 GNAS Zornitza Stark gene: GNAS was added
gene: GNAS was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: GNAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNAS were set to 19530187; 26340332; 26267576
Phenotypes for gene: GNAS were set to Pseudohypoparathyroidism type 1a, MIM# 103580; Craniosynostosis
Review for gene: GNAS was set to AMBER
Added comment: Craniosynostosis is a rare complication of pseudohyoparathyroidism, a small number of published cases.
Sources: Expert list
Craniosynostosis v0.94 FGF10 Zornitza Stark edited their review of gene: FGF10: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.94 FGF10 Zornitza Stark Mode of inheritance for gene: FGF10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.93 FGF10 Zornitza Stark reviewed gene: FGF10: Rating: AMBER; Mode of pathogenicity: None; Publications: 29215649; Phenotypes: ; Mode of inheritance: None
Deafness_IsolatedAndComplex v0.358 DSPP Zornitza Stark Marked gene: DSPP as ready
Deafness_IsolatedAndComplex v0.358 DSPP Zornitza Stark Added comment: Comment when marking as ready: Three families altogether, two with the same variant, V18F. One with isolated deafness, two with dental phenotype as well as deafness. Some functional data to support impact on protein. Mouse model has dental phenotype.
Deafness_IsolatedAndComplex v0.358 DSPP Zornitza Stark Gene: dspp has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v0.358 DSPP Zornitza Stark Publications for gene: DSPP were set to 29741433
Deafness_IsolatedAndComplex v0.357 DSPP Zornitza Stark Phenotypes for gene: DSPP were changed from Deafness, autosomal dominant 39, with dentinogenesis, MIM# 605594 to Deafness, autosomal dominant 39, with dentinogenesis, MIM# 605594
Deafness_IsolatedAndComplex v0.356 DSPP Zornitza Stark Phenotypes for gene: DSPP were changed from to Deafness, autosomal dominant 39, with dentinogenesis, MIM# 605594
Deafness_IsolatedAndComplex v0.356 DSPP Zornitza Stark Publications for gene: DSPP were set to
Deafness_IsolatedAndComplex v0.355 DSPP Zornitza Stark Mode of inheritance for gene: DSPP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.354 DSPP Zornitza Stark Classified gene: DSPP as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v0.354 DSPP Zornitza Stark Gene: dspp has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.12 MPV17 Bryony Thompson Marked gene: MPV17 as ready
Gastrointestinal neuromuscular disease v0.12 MPV17 Bryony Thompson Gene: mpv17 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.12 MPV17 Bryony Thompson Classified gene: MPV17 as Green List (high evidence)
Gastrointestinal neuromuscular disease v0.12 MPV17 Bryony Thompson Gene: mpv17 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.11 MPV17 Bryony Thompson gene: MPV17 was added
gene: MPV17 was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: MPV17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPV17 were set to 22964873; 28673863; 22593919
Phenotypes for gene: MPV17 were set to Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) MIM#256810
Review for gene: MPV17 was set to GREEN
Added comment: Gastrointestinal features including dysmotility have been reported in association biallelic variants in this gene in about 30% of cases with this condition, according to GeneReviews.
Sources: Expert list
Callosome v0.152 FLRT3 Zornitza Stark Marked gene: FLRT3 as ready
Callosome v0.152 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Callosome v0.152 FLRT3 Zornitza Stark Phenotypes for gene: FLRT3 were changed from to Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271)
Callosome v0.151 FLRT3 Zornitza Stark Publications for gene: FLRT3 were set to
Callosome v0.150 FLRT3 Zornitza Stark Mode of inheritance for gene: FLRT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.149 FLRT3 Zornitza Stark Classified gene: FLRT3 as Red List (low evidence)
Callosome v0.149 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Callosome v0.148 FLRT3 Zornitza Stark reviewed gene: FLRT3: Rating: RED; Mode of pathogenicity: None; Publications: 23643382, 31200363; Phenotypes: Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3215 FLRT3 Zornitza Stark Marked gene: FLRT3 as ready
Mendeliome v0.3215 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Mendeliome v0.3215 FLRT3 Zornitza Stark Phenotypes for gene: FLRT3 were changed from to Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271)
Mendeliome v0.3214 FLRT3 Zornitza Stark Publications for gene: FLRT3 were set to
Mendeliome v0.3213 FLRT3 Zornitza Stark Mode of inheritance for gene: FLRT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3212 FLRT3 Zornitza Stark Classified gene: FLRT3 as Red List (low evidence)
Mendeliome v0.3212 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Mendeliome v0.3211 FLRT3 Zornitza Stark reviewed gene: FLRT3: Rating: RED; Mode of pathogenicity: None; Publications: 23643382, 31200363; Phenotypes: Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Marked gene: FLRT3 as ready
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Added comment: Comment when marking as ready: Oligogenic inheritance postulated. I also note one of the variants, Gln69Lys is present in 7 individuals in gnomad.
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Marked gene: FLRT3 as ready
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Phenotypes for gene: FLRT3 were changed from to Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271)
Differences of Sex Development v0.33 FLRT3 Zornitza Stark Publications for gene: FLRT3 were set to
Differences of Sex Development v0.32 FLRT3 Zornitza Stark Classified gene: FLRT3 as Red List (low evidence)
Differences of Sex Development v0.32 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v0.353 DSPP Lilian Downie reviewed gene: DSPP: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 29741433; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.19 HARS2 Lauren Akesson reviewed gene: HARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31827252, 31486067, 31449985, 27650058, 21464306; Phenotypes: Perrault syndrome 2 (MIM# 614926); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.18 GNRH1 Lauren Akesson reviewed gene: GNRH1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32134721, 19567835, 19535795; Phenotypes: ?Hypogonadotropic hypogonadism 12 with or without anosmia (MIM# 614841); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.31 FLRT3 Lauren Akesson reviewed gene: FLRT3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 23643382, 31200363; Phenotypes: Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271); Mode of inheritance: Unknown
Ciliopathies v0.192 CCDC32 Zornitza Stark Marked gene: CCDC32 as ready
Ciliopathies v0.192 CCDC32 Zornitza Stark Gene: ccdc32 has been classified as Green List (High Evidence).
Ciliopathies v0.192 CCDC32 Zornitza Stark Classified gene: CCDC32 as Green List (high evidence)
Ciliopathies v0.192 CCDC32 Zornitza Stark Gene: ccdc32 has been classified as Green List (High Evidence).
Ciliopathies v0.191 CCDC32 Zornitza Stark gene: CCDC32 was added
gene: CCDC32 was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: CCDC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC32 were set to 32307552
Phenotypes for gene: CCDC32 were set to Craniofacial, cardiac, laterality and neurodevelopmental anomalies
Review for gene: CCDC32 was set to GREEN
Added comment: Two unrelated consanguineous families with probands with homozygous frameshift variants reported. Phenotype is a congenital syndrome characterized by craniofacial, cardiac and neurodevelopmental anomalies. Functional studies in zebrafish show that ccdc32 depletion impairs cilia formation and shows a role for ccdc32 in craniofacial, brain and left/right axis development.
Sources: Literature
Mendeliome v0.3211 CCDC32 Zornitza Stark Marked gene: CCDC32 as ready
Mendeliome v0.3211 CCDC32 Zornitza Stark Added comment: Comment when marking as ready: Three affected individuals from two unrelated families, supportive animal model and other functional data consistent with this being a ciliopathy.
Mendeliome v0.3211 CCDC32 Zornitza Stark Gene: ccdc32 has been classified as Green List (High Evidence).
Mendeliome v0.3211 CCDC32 Zornitza Stark Classified gene: CCDC32 as Green List (high evidence)
Mendeliome v0.3211 CCDC32 Zornitza Stark Gene: ccdc32 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2727 CAPZA2 Zornitza Stark Marked gene: CAPZA2 as ready
Intellectual disability syndromic and non-syndromic v0.2727 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2727 CAPZA2 Zornitza Stark Classified gene: CAPZA2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2727 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2726 CAPZA2 Zornitza Stark gene: CAPZA2 was added
gene: CAPZA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CAPZA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAPZA2 were set to 32338762
Phenotypes for gene: CAPZA2 were set to Intellectual disability
Review for gene: CAPZA2 was set to AMBER
Added comment: PMID: 32338762 - Huang et al 2020 - report 2 unrelated families (Chinese and European) in which a de novo heterozygous variant has been identified in CAPZA2 in paediatric probands that present with global motor development delay, speech delay, intellectual disability, hypotonia. One proband had seizures at 7 months but these were controlled with medication and did not repeat. The other proband at age one had an atypical febrile seizure that was controlled without medication. Functional studies in Drosophila suggest that these variants are mild loss of function mutations but that they can act as dominant negative variants in actin polymerization in bristles.
Sources: Literature
Mendeliome v0.3210 CAPZA2 Zornitza Stark Marked gene: CAPZA2 as ready
Mendeliome v0.3210 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3210 CAPZA2 Zornitza Stark Classified gene: CAPZA2 as Amber List (moderate evidence)
Mendeliome v0.3210 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3209 PPP3R1 Zornitza Stark Marked gene: PPP3R1 as ready
Mendeliome v0.3209 PPP3R1 Zornitza Stark Added comment: Comment when marking as ready: Currently just a locus; note multiple mouse models implicating a role for this gene in cardiovascular, renal and brain development.
Mendeliome v0.3209 PPP3R1 Zornitza Stark Gene: ppp3r1 has been classified as Red List (Low Evidence).
Mendeliome v0.3209 PPP3R1 Zornitza Stark Classified gene: PPP3R1 as Red List (low evidence)
Mendeliome v0.3209 PPP3R1 Zornitza Stark Gene: ppp3r1 has been classified as Red List (Low Evidence).
Mendeliome v0.3208 PLEK Zornitza Stark Marked gene: PLEK as ready
Mendeliome v0.3208 PLEK Zornitza Stark Gene: plek has been classified as Red List (Low Evidence).
Mendeliome v0.3208 PLEK Zornitza Stark Classified gene: PLEK as Red List (low evidence)
Mendeliome v0.3208 PLEK Zornitza Stark Gene: plek has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v0.353 CNRIP1 Zornitza Stark Marked gene: CNRIP1 as ready
Deafness_IsolatedAndComplex v0.353 CNRIP1 Zornitza Stark Gene: cnrip1 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v0.353 CNRIP1 Zornitza Stark gene: CNRIP1 was added
gene: CNRIP1 was added to Deafness. Sources: Literature
Mode of inheritance for gene: CNRIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CNRIP1 were set to 32337552; 19159392
Phenotypes for gene: CNRIP1 were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: CNRIP1 was set to RED
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Mendeliome v0.3207 CNRIP1 Zornitza Stark Marked gene: CNRIP1 as ready
Mendeliome v0.3207 CNRIP1 Zornitza Stark Added comment: Comment when marking as ready: Currently just a locus, insufficient evidence for gene-disease association.
Mendeliome v0.3207 CNRIP1 Zornitza Stark Gene: cnrip1 has been classified as Red List (Low Evidence).
Mendeliome v0.3207 CNRIP1 Zornitza Stark Classified gene: CNRIP1 as Red List (low evidence)
Mendeliome v0.3207 CNRIP1 Zornitza Stark Gene: cnrip1 has been classified as Red List (Low Evidence).
Mendeliome v0.3206 RAD21 Zornitza Stark Marked gene: RAD21 as ready
Mendeliome v0.3206 RAD21 Zornitza Stark Gene: rad21 has been classified as Green List (High Evidence).
Mendeliome v0.3206 RAD21 Zornitza Stark Phenotypes for gene: RAD21 were changed from to ?Mungan syndrome, 611376; Cornelia de Lange syndrome 4, 614701; Holoprocencephaly
Mendeliome v0.3205 RAD21 Zornitza Stark Publications for gene: RAD21 were set to 31334757; 25575569; 32193685
Mendeliome v0.3204 RAD21 Zornitza Stark Publications for gene: RAD21 were set to
Mendeliome v0.3203 RAD21 Zornitza Stark Mode of inheritance for gene: RAD21 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3202 CAPZA2 Eleanor Williams gene: CAPZA2 was added
gene: CAPZA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CAPZA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAPZA2 were set to 32338762
Phenotypes for gene: CAPZA2 were set to intellectual disability
Review for gene: CAPZA2 was set to AMBER
Added comment: PMID: 32338762 - Huang et al 2020 - report 2 unrelated families (Chinese and European) in which a de novo heterozygous variant has been identified in CAPZA2 in paediatric probands that present with global motor development delay, speech delay, intellectual disability, hypotonia. One proband had seizures at 7 months but these were controlled with medication and did not repeat. The other proband at age one had an atypical febrile seizure that was controlled without medication. Functional studies in Drosophila suggest that these variants are mild loss of function mutations but that they can act as dominant negative variants in actin polymerization in bristles.
Sources: Literature
Mendeliome v0.3202 PPP3R1 Eleanor Williams gene: PPP3R1 was added
gene: PPP3R1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPP3R1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPP3R1 were set to 32337552; 19159392
Phenotypes for gene: PPP3R1 were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: PPP3R1 was set to RED
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Mendeliome v0.3202 PLEK Eleanor Williams gene: PLEK was added
gene: PLEK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLEK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLEK were set to 32337552; 19159392
Phenotypes for gene: PLEK were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: PLEK was set to RED
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Mendeliome v0.3202 CNRIP1 Eleanor Williams gene: CNRIP1 was added
gene: CNRIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNRIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CNRIP1 were set to 32337552; 19159392
Phenotypes for gene: CNRIP1 were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: CNRIP1 was set to RED
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Mendeliome v0.3202 RAD21 Sarah Leigh reviewed gene: RAD21: Rating: GREEN; Mode of pathogenicity: None; Publications: 31334757, 31704779; Phenotypes: Cornelia de Lange syndrome 4 614701; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Craniosynostosis v0.93 FREM1 Zornitza Stark Marked gene: FREM1 as ready
Craniosynostosis v0.93 FREM1 Zornitza Stark Gene: frem1 has been classified as Red List (Low Evidence).
Craniosynostosis v0.93 FREM1 Zornitza Stark Phenotypes for gene: FREM1 were changed from to Trigonocephaly 2, MIM# 614485
Craniosynostosis v0.92 FREM1 Zornitza Stark Publications for gene: FREM1 were set to
Craniosynostosis v0.91 FREM1 Zornitza Stark Mode of inheritance for gene: FREM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.90 FREM1 Zornitza Stark Classified gene: FREM1 as Red List (low evidence)
Craniosynostosis v0.90 FREM1 Zornitza Stark Gene: frem1 has been classified as Red List (Low Evidence).
Craniosynostosis v0.89 FREM1 Zornitza Stark Tag disputed tag was added to gene: FREM1.
Craniosynostosis v0.89 FREM1 Zornitza Stark reviewed gene: FREM1: Rating: RED; Mode of pathogenicity: None; Publications: 21931569,; Phenotypes: Trigonocephaly 2, MIM# 614485; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.89 FAM20C Zornitza Stark Marked gene: FAM20C as ready
Craniosynostosis v0.89 FAM20C Zornitza Stark Gene: fam20c has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.89 FAM20C Zornitza Stark Classified gene: FAM20C as Amber List (moderate evidence)
Craniosynostosis v0.89 FAM20C Zornitza Stark Gene: fam20c has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.88 FAM20C Zornitza Stark gene: FAM20C was added
gene: FAM20C was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: FAM20C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM20C were set to 19250384
Phenotypes for gene: FAM20C were set to Raine syndrome, MIM# 259775
Review for gene: FAM20C was set to AMBER
Added comment: Osteosclerotic bone dysplasia with increased skull ossification. 2 unrelated cases with missense variants survived beyond infancy and had turribrachycephaly, one also had plagiocephaly.
Sources: Expert list
Craniosynostosis v0.87 CTSK Zornitza Stark Marked gene: CTSK as ready
Craniosynostosis v0.87 CTSK Zornitza Stark Gene: ctsk has been classified as Green List (High Evidence).
Craniosynostosis v0.87 CTSK Zornitza Stark Classified gene: CTSK as Green List (high evidence)
Craniosynostosis v0.87 CTSK Zornitza Stark Gene: ctsk has been classified as Green List (High Evidence).
Craniosynostosis v0.86 CTSK Zornitza Stark gene: CTSK was added
gene: CTSK was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: CTSK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTSK were set to 21968522; 23175007
Phenotypes for gene: CTSK were set to Pycnodysostosis, MIM#265800
Review for gene: CTSK was set to GREEN
Added comment: Craniosynostosis described in some individuals.
Sources: Expert list
Mendeliome v0.3202 CCDC32 Eleanor Williams gene: CCDC32 was added
gene: CCDC32 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC32 were set to 32307552
Phenotypes for gene: CCDC32 were set to craniofacial, cardiac and neurodevelopmental anomalies
Review for gene: CCDC32 was set to AMBER
Added comment: PMID: 32307552 - Harel et al 2020 - reports 2 unrelated consanguineous families with probands with homozygous frameshift variants in CCDC32. Parents are heterozygous. Phenotype is a congenital syndrome characterized by craniofacial, cardiac and neurodevelopmental anomalies. Functional studies in zebrafish show that ccdc32 depletion impairs cilia formation and shows a role for ccdc32 in craniofacial, brain and left/right axis development.
Sources: Literature
Craniosynostosis v0.85 ASXL1 Zornitza Stark Marked gene: ASXL1 as ready
Craniosynostosis v0.85 ASXL1 Zornitza Stark Gene: asxl1 has been classified as Green List (High Evidence).
Craniosynostosis v0.85 ASXL1 Zornitza Stark Classified gene: ASXL1 as Green List (high evidence)
Craniosynostosis v0.85 ASXL1 Zornitza Stark Gene: asxl1 has been classified as Green List (High Evidence).
Craniosynostosis v0.84 ASXL1 Zornitza Stark gene: ASXL1 was added
gene: ASXL1 was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: ASXL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ASXL1 were set to Bohring-Opitz syndrome,MIM# 605039
Review for gene: ASXL1 was set to GREEN
Added comment: Trigonocephaly in 90%, metopic synostosis frequent.
Sources: Expert list
Craniosynostosis v0.83 ARSB Zornitza Stark Marked gene: ARSB as ready
Craniosynostosis v0.83 ARSB Zornitza Stark Gene: arsb has been classified as Green List (High Evidence).
Craniosynostosis v0.83 ARSB Zornitza Stark Classified gene: ARSB as Green List (high evidence)
Craniosynostosis v0.83 ARSB Zornitza Stark Gene: arsb has been classified as Green List (High Evidence).
Craniosynostosis v0.82 ARSB Zornitza Stark gene: ARSB was added
gene: ARSB was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: ARSB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ARSB were set to Mucopolysaccharidosis VI (MPS6, MIM# 253200
Review for gene: ARSB was set to GREEN
Added comment: Synostosis of at least one suture was present in 77% of 47 MPS cases (types I,II,VI, VII). >3 cases with IDUA, IDS, ARSB variants.
Sources: Expert list
Craniosynostosis v0.81 ACTG1 Zornitza Stark reviewed gene: ACTG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Baraitser-Winter syndrome 2, MIM# 614583; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.81 ACTB Zornitza Stark reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Baraitser-Winter syndrome 1, MIM# 243310; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vascular Malformations_Somatic v0.15 ACVRL1 Zornitza Stark Marked gene: ACVRL1 as ready
Vascular Malformations_Somatic v0.15 ACVRL1 Zornitza Stark Gene: acvrl1 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.15 ACVRL1 Zornitza Stark Classified gene: ACVRL1 as Green List (high evidence)
Vascular Malformations_Somatic v0.15 ACVRL1 Zornitza Stark Gene: acvrl1 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.14 AKT3 Zornitza Stark Marked gene: AKT3 as ready
Vascular Malformations_Somatic v0.14 AKT3 Zornitza Stark Gene: akt3 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.14 AKT3 Zornitza Stark Classified gene: AKT3 as Green List (high evidence)
Vascular Malformations_Somatic v0.14 AKT3 Zornitza Stark Gene: akt3 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.10 RRM2B Bryony Thompson Marked gene: RRM2B as ready
Gastrointestinal neuromuscular disease v0.10 RRM2B Bryony Thompson Gene: rrm2b has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.10 RRM2B Bryony Thompson edited their review of gene: RRM2B: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.10 RRM2B Bryony Thompson Mode of inheritance for gene: RRM2B was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.9 RRM2B Bryony Thompson Classified gene: RRM2B as Green List (high evidence)
Gastrointestinal neuromuscular disease v0.9 RRM2B Bryony Thompson Gene: rrm2b has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.8 RRM2B Bryony Thompson gene: RRM2B was added
gene: RRM2B was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: RRM2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RRM2B were set to 19667227; 23107649
Phenotypes for gene: RRM2B were set to Mitochondrial DNA depletion syndrome 8B (MNGIE type) MIM#612075; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5 MIM#613077
Review for gene: RRM2B was set to GREEN
Added comment: Gastrointestinal disturbances have been reported in 6/31 cases with adult onset cases with biallelic and monoallelic variants.
Sources: Expert list
Vascular Malformations_Somatic v0.13 ENG Zornitza Stark Marked gene: ENG as ready
Vascular Malformations_Somatic v0.13 ENG Zornitza Stark Gene: eng has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.13 ENG Zornitza Stark Classified gene: ENG as Green List (high evidence)
Vascular Malformations_Somatic v0.13 ENG Zornitza Stark Gene: eng has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.12 GLMN Zornitza Stark Marked gene: GLMN as ready
Vascular Malformations_Somatic v0.12 GLMN Zornitza Stark Gene: glmn has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.12 GLMN Zornitza Stark Classified gene: GLMN as Green List (high evidence)
Vascular Malformations_Somatic v0.12 GLMN Zornitza Stark Gene: glmn has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.11 RASA1 Zornitza Stark Marked gene: RASA1 as ready
Vascular Malformations_Somatic v0.11 RASA1 Zornitza Stark Gene: rasa1 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.11 RASA1 Zornitza Stark Classified gene: RASA1 as Green List (high evidence)
Vascular Malformations_Somatic v0.11 RASA1 Zornitza Stark Gene: rasa1 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.10 TEK Zornitza Stark Marked gene: TEK as ready
Vascular Malformations_Somatic v0.10 TEK Zornitza Stark Gene: tek has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.10 TEK Zornitza Stark Classified gene: TEK as Green List (high evidence)
Vascular Malformations_Somatic v0.10 TEK Zornitza Stark Gene: tek has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.110 STAMBP Zornitza Stark Marked gene: STAMBP as ready
Vascular Malformations_Germline v0.110 STAMBP Zornitza Stark Gene: stambp has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.110 STAMBP Zornitza Stark Phenotypes for gene: STAMBP were changed from Microcephaly-capillary malformation syndrome to Microcephaly-capillary malformation syndrome, MIM# 614261
Vascular Malformations_Germline v0.109 STAMBP Zornitza Stark Publications for gene: STAMBP were set to
Vascular Malformations_Germline v0.108 STAMBP Zornitza Stark reviewed gene: STAMBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 23542699; Phenotypes: Microcephaly-capillary malformation syndrome, MIM# 614261; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Vascular Malformations_Germline v0.108 SOX18 Zornitza Stark Marked gene: SOX18 as ready
Vascular Malformations_Germline v0.108 SOX18 Zornitza Stark Gene: sox18 has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.108 SOX18 Zornitza Stark Classified gene: SOX18 as Green List (high evidence)
Vascular Malformations_Germline v0.108 SOX18 Zornitza Stark Gene: sox18 has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.107 SOX18 Zornitza Stark gene: SOX18 was added
gene: SOX18 was added to Vascular Malformations_Germline. Sources: Expert list
Mode of inheritance for gene: SOX18 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SOX18 were set to 12740761; 24697860; 2484451; 26148450
Phenotypes for gene: SOX18 were set to Hypotrichosis-lymphedema-telangiectasia syndrome, MIM# 607823; Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome, MIM# 137940
Review for gene: SOX18 was set to GREEN
Added comment: Both mono allelic and bi-allelic variants reported.
Sources: Expert list
Vascular Malformations_Germline v0.106 PDCD10 Zornitza Stark Marked gene: PDCD10 as ready
Vascular Malformations_Germline v0.106 PDCD10 Zornitza Stark Gene: pdcd10 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.106 PDCD10 Zornitza Stark Classified gene: PDCD10 as Amber List (moderate evidence)
Vascular Malformations_Germline v0.106 PDCD10 Zornitza Stark Gene: pdcd10 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.105 PDCD10 Zornitza Stark reviewed gene: PDCD10: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral cavernous malformations 3, MIM# 603285; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v0.4 GDF2 Zornitza Stark Marked gene: GDF2 as ready
Cerebral vascular malformations v0.4 GDF2 Zornitza Stark Gene: gdf2 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.4 GDF2 Zornitza Stark Phenotypes for gene: GDF2 were changed from to Telangiectasia, hereditary hemorrhagic, type 5, MIM# 615506
Cerebral vascular malformations v0.3 GDF2 Zornitza Stark Publications for gene: GDF2 were set to
Cerebral vascular malformations v0.2 GDF2 Zornitza Stark Classified gene: GDF2 as Red List (low evidence)
Cerebral vascular malformations v0.2 GDF2 Zornitza Stark Gene: gdf2 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.1 GDF2 Zornitza Stark reviewed gene: GDF2: Rating: RED; Mode of pathogenicity: None; Publications: 23972370; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 5, MIM# 615506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vascular Malformations_Germline v0.105 GDF2 Zornitza Stark Classified gene: GDF2 as Red List (low evidence)
Vascular Malformations_Germline v0.105 GDF2 Zornitza Stark Gene: gdf2 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.104 GDF2 Zornitza Stark edited their review of gene: GDF2: Changed rating: RED
Vascular Malformations_Germline v0.104 GDF2 Zornitza Stark Marked gene: GDF2 as ready
Vascular Malformations_Germline v0.104 GDF2 Zornitza Stark Gene: gdf2 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.104 GDF2 Zornitza Stark Publications for gene: GDF2 were set to
Vascular Malformations_Germline v0.103 GDF2 Zornitza Stark Classified gene: GDF2 as Amber List (moderate evidence)
Vascular Malformations_Germline v0.103 GDF2 Zornitza Stark Gene: gdf2 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.102 GDF2 Zornitza Stark reviewed gene: GDF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23972370; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 5, MIM# 615506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vascular Malformations_Germline v0.102 CCM2 Zornitza Stark Marked gene: CCM2 as ready
Vascular Malformations_Germline v0.102 CCM2 Zornitza Stark Gene: ccm2 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.102 CCM2 Zornitza Stark Phenotypes for gene: CCM2 were changed from Cerebral cavernous malformations to Cerebral cavernous malformations-2, MIM# 603284
Vascular Malformations_Germline v0.101 CCM2 Zornitza Stark Publications for gene: CCM2 were set to
Vascular Malformations_Germline v0.100 CCM2 Zornitza Stark Classified gene: CCM2 as Amber List (moderate evidence)
Vascular Malformations_Germline v0.100 CCM2 Zornitza Stark Gene: ccm2 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.99 CCM2 Zornitza Stark Tag SV/CNV tag was added to gene: CCM2.
Vascular Malformations_Germline v0.99 CCM2 Zornitza Stark reviewed gene: CCM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 21543988, 14624391; Phenotypes: Cerebral cavernous malformations-2, MIM# 603284; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vascular Malformations_Germline v0.99 ATR Zornitza Stark Marked gene: ATR as ready
Vascular Malformations_Germline v0.99 ATR Zornitza Stark Gene: atr has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.7 OPA1 Bryony Thompson Marked gene: OPA1 as ready
Gastrointestinal neuromuscular disease v0.7 OPA1 Bryony Thompson Gene: opa1 has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.7 OPA1 Bryony Thompson gene: OPA1 was added
gene: OPA1 was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: OPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OPA1 were set to 30395865
Phenotypes for gene: OPA1 were set to gastrointestinal pseudo-obstruction
Review for gene: OPA1 was set to RED
Added comment: Cannot find evidence that gastrointestinal pseudo-obstruction or dysmotility have been reported in association with this gene. There is a single report of an OPA1 heterozygous variant in a case with suggestive MNGIE, but there were no obvious gastrointestinal features identified.
Sources: Expert list
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.18 FGF8 Lauren Akesson reviewed gene: FGF8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20463092,18596921; Phenotypes: Hypogonadotropic hypogonadism 6 with or without anosmia (612702); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gastrointestinal neuromuscular disease v0.6 Bryony Thompson Panel name changed from Visceral Myopathy to Gastrointestinal neuromuscular disease
Vascular Malformations_Germline v0.99 ATR Zornitza Stark gene: ATR was added
gene: ATR was added to Vascular Malformations_Germline. Sources: Expert list
Mode of inheritance for gene: ATR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATR were set to 22341969
Phenotypes for gene: ATR were set to Cutaneous telangiectasia and cancer syndrome, familial, MIM# 614564
Review for gene: ATR was set to RED
Added comment: Single multigenerational family reported.
Sources: Expert list
Vascular Malformations_Germline v0.98 ATM Zornitza Stark Marked gene: ATM as ready
Vascular Malformations_Germline v0.98 ATM Zornitza Stark Gene: atm has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.98 ATM Zornitza Stark Classified gene: ATM as Green List (high evidence)
Vascular Malformations_Germline v0.98 ATM Zornitza Stark Gene: atm has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.97 ATM Zornitza Stark gene: ATM was added
gene: ATM was added to Vascular Malformations_Germline. Sources: Expert list
Mode of inheritance for gene: ATM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATM were set to Ataxia-telangiectasia, MIM# 208900
Review for gene: ATM was set to GREEN
Added comment: Cutaneous telangiectasia are a feature of this disorder.
Sources: Expert list
Vascular Malformations_Somatic v0.9 TEK Chris Richmond gene: TEK was added
gene: TEK was added to Vascular Malformations_Somatic. Sources: Expert Review
Mode of inheritance for gene: TEK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TEK were set to 27519652
Phenotypes for gene: TEK were set to Venous malformations, multiple cutaneous and mucosal (600195); Blue rubber bleb naevus syndrome; Sporadic multifocal vascular malformations
Penetrance for gene: TEK were set to unknown
Mode of pathogenicity for gene: TEK 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: TEK was set to GREEN
Added comment: Gain of function. Germline:

Somatic: Blue Rubber Bleb Naevus Syndrome
PMID 27519652: "Blue Rubber Bleb Nevus (BRBN) Syndrome Is Caused by Somatic TEK (TIE2) Mutations" group studied tissue from 17 individuals with blue rubber bleb nevus and six individuals with sporadic multifocal vascular malformations. They found that most (13 of 15) individuals with blue rubber bleb nevus had tissue double mutations (i.e., two somatic TEK mutations); 10 of these double mutations were in cis, and in the other tissues the allelism could not be determined. Double and cis mutations were present in most sporadic multifocal vascular malformations as well.
Sources: Expert Review
Vascular Malformations_Somatic v0.9 RASA1 Chris Richmond gene: RASA1 was added
gene: RASA1 was added to Vascular Malformations_Somatic. Sources: Expert Review
Mode of inheritance for gene: RASA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RASA1 were set to 31300548; 30635911
Phenotypes for gene: RASA1 were set to Capillary malformation-arteriovenous malformation 1 (608354)
Penetrance for gene: RASA1 were set to Incomplete
Review for gene: RASA1 was set to GREEN
Added comment: PMID: 31300548: "Four distinct mosaic RASA1 mutations, with an allele frequency ranging from 3% to 25%, were identified in four index patients with classical capillary malformation-arteriovenous malformation phenotype. Three mutations were known, one was novel. In one patient, a somatic second hit was also identified. One index case had three affected children, illustrating that the mosaicism was also present in the germline."

PMID 30635911: "Both patients showed different nonsense RASA1 variants in mosaic, ranging from 7% to 21.5%, in blood samples and in the corresponding affected tissue sample from one of the patients. In conclusion, we report for the first time the presence of RASA1 constitutional mosaicism in CM-AVM. "
Sources: Expert Review
Vascular Malformations_Somatic v0.9 GLMN Chris Richmond gene: GLMN was added
gene: GLMN was added to Vascular Malformations_Somatic. Sources: Expert Review
Mode of inheritance for gene: GLMN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLMN were set to 11845407
Phenotypes for gene: GLMN were set to Glomuvenous malformations (138000)
Penetrance for gene: GLMN were set to unknown
Review for gene: GLMN was set to GREEN
Added comment: Loss of function. Likely requires second hit for development of GVM: eg germline with second somatic hit (11845407)
Sources: Expert Review
Vascular Malformations_Somatic v0.9 AKT3 Chris Richmond reviewed gene: AKT3: 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: 22500628, 22729223; Phenotypes: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (615937); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vascular Malformations_Somatic v0.9 AKT3 Chris Richmond Deleted their review
Vascular Malformations_Somatic v0.9 AKT3 Chris Richmond gene: AKT3 was added
gene: AKT3 was added to Vascular Malformations_Somatic. Sources: Expert Review
Mode of inheritance for gene: AKT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AKT3 were set to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2
Phenotypes for gene: AKT3 were set to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (615937)
Penetrance for gene: AKT3 were set to unknown
Mode of pathogenicity for gene: AKT3 was set to Other
Review for gene: AKT3 was set to GREEN
gene: AKT3 was marked as current diagnostic
Added comment: Gain of function. "De Novo Somatic Mutations in Components of the PI3K-AKT3-mTOR Pathway Cause Hemimegalencephaly" (PMID 22729223)
Sources: Expert Review
Vascular Malformations_Somatic v0.9 ACVRL1 Chris Richmond gene: ACVRL1 was added
gene: ACVRL1 was added to Vascular Malformations_Somatic. Sources: Expert Review
Mode of inheritance for gene: ACVRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACVRL1 were set to 21378382
Phenotypes for gene: ACVRL1 were set to Telangiectasia, hereditary hemorrhagic, type 2 (600376)
Penetrance for gene: ACVRL1 were set to unknown
Review for gene: ACVRL1 was set to GREEN
gene: ACVRL1 was marked as current diagnostic
Added comment: Primarily germline, but mosaic cases reported
Sources: Expert Review
Vascular Malformations_Somatic v0.9 ENG Chris Richmond gene: ENG was added
gene: ENG was added to Vascular Malformations_Somatic. Sources: Expert Review
Mode of inheritance for gene: ENG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ENG were set to 21378382
Phenotypes for gene: ENG were set to Telangiectasia, hereditary hemorrhagic, type 2 (600376)
Penetrance for gene: ENG were set to unknown
Review for gene: ENG was set to GREEN
Added comment: Primarily germline, but mosaic cases reported (21378382)
Sources: Expert Review
Vascular Malformations_Somatic v0.9 MTOR Bryony Thompson changed review comment from: Comment on list classification: Vascular malformations are not a prominent feature of the condition caused by germline variants in this gene. Somatic activating mutations are possibly associated with vascular malformations, thus this gene is not suitable for a germline testing panel.; to: Comment on list classification: Vascular malformations are not a prominent feature of the condition caused by germline variants in this gene. Somatic activating mutations are possibly associated with vascular malformations.
Vascular Malformations_Somatic v0.9 NRAS Bryony Thompson Deleted their comment
Vascular Malformations_Somatic v0.9 MAP3K3 Bryony Thompson Deleted their comment
Vascular Malformations_Somatic v0.9 MAP2K1 Bryony Thompson Deleted their comment
Vascular Malformations_Somatic v0.9 KRAS Bryony Thompson Deleted their comment
Vascular Malformations_Somatic v0.9 KRAS Bryony Thompson changed review comment from: Comment on list classification: Somatic activating mutations are the cause of vascular malformations in this gene, thus it is not suitable to include on a germline testing panel.; to: Comment on list classification: Somatic activating mutations are the cause of vascular malformations in this gene.
Vascular Malformations_Somatic v0.9 HRAS Bryony Thompson changed review comment from: Comment on list classification: Somatic activating mutations cause vascular malformations, which is not really appropriate for a germline testing panel; to: Comment on list classification: Somatic activating mutations cause vascular malformations.
Vascular Malformations_Somatic v0.9 GNAQ Bryony Thompson changed review comment from: Comment on list classification: Somatic mutation only causes vascular malformations. Not really suitable for a germline testing panel.; to: Comment on list classification: Somatic mutation only causes vascular malformations.
Vascular Malformations_Somatic v0.9 GNA14 Bryony Thompson changed review comment from: Comment on list classification: Somatic activating mutations have only been reported to cause vascular malformations. This gene is not really suitable for a germline testing panel.; to: Comment on list classification: Somatic activating mutations have only been reported to cause vascular malformations.
Vascular Malformations_Somatic v0.9 GNA11 Bryony Thompson Deleted their comment
Vascular Malformations_Somatic v0.9 BRAF Bryony Thompson changed review comment from: Comment on list classification: Somatic activating mutations only are associated with vascular malformations. Not really suitable for a germline testing panel.; to: Comment on list classification: Somatic activating mutations only are associated with vascular malformations.
Vascular Malformations_Somatic v0.9 AKT1 Bryony Thompson changed review comment from: Comment on list classification: Somatic variants have been reported in association with vascular malformation. This gene is probably not suitable for a germline testing panel.; to: Comment on list classification: Somatic variants have been reported in association with vascular malformation.
Vascular Malformations_Somatic v0.9 KDR Zornitza Stark gene: KDR was added
gene: KDR was added to Vascular Malformations_Somatic. Sources: Expert list
Mode of inheritance for gene: KDR was set to Other
Publications for gene: KDR were set to 11807987; 18931684
Phenotypes for gene: KDR were set to Hemangioma, capillary infantile, somatic, MIM# 602089
Review for gene: KDR was set to RED
Added comment: Limited reports, may be susceptibility factor.
Sources: Expert list
Vascular Malformations_Somatic v0.8 PIK3CA Zornitza Stark Marked gene: PIK3CA as ready
Vascular Malformations_Somatic v0.8 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.8 PIK3CA Zornitza Stark Classified gene: PIK3CA as Green List (high evidence)
Vascular Malformations_Somatic v0.8 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.7 PIK3CA Zornitza Stark gene: PIK3CA was added
gene: PIK3CA was added to Vascular Malformations_Somatic. Sources: Expert list
Mode of inheritance for gene: PIK3CA was set to Other
Publications for gene: PIK3CA were set to 22729224; 23246288
Phenotypes for gene: PIK3CA were set to Megalencephaly-capillary malformation (MCAP) syndrome; Cowden syndrome 5 615108
Mode of pathogenicity for gene: PIK3CA 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: PIK3CA was set to GREEN
Added comment: Somatic activating mutaitons are the main cause of vascular malformations, though note four individuals with germline variants have been reported, hence gene is on both somatic and germline panels.
Sources: Expert list
Vascular Malformations_Germline v0.96 Zornitza Stark Panel name changed from Inherited Vascular Malformations to Vascular Malformations_Germline
Vascular Malformations_Somatic v0.6 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Vascular Malformations_Somatic v0.5 SOS1 Zornitza Stark Marked gene: SOS1 as ready
Vascular Malformations_Somatic v0.5 SOS1 Zornitza Stark Gene: sos1 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Somatic v0.5 SOS1 Zornitza Stark Classified gene: SOS1 as Amber List (moderate evidence)
Vascular Malformations_Somatic v0.5 SOS1 Zornitza Stark Gene: sos1 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Somatic v0.4 PIK3R1 Zornitza Stark Marked gene: PIK3R1 as ready
Vascular Malformations_Somatic v0.4 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Red List (Low Evidence).
Vascular Malformations_Somatic v0.4 PIK3R1 Zornitza Stark Classified gene: PIK3R1 as Red List (low evidence)
Vascular Malformations_Somatic v0.4 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Red List (Low Evidence).
Vascular Malformations_Somatic v0.3 NRAS Zornitza Stark Marked gene: NRAS as ready
Vascular Malformations_Somatic v0.3 NRAS Zornitza Stark Gene: nras has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.3 NRAS Zornitza Stark Tag somatic tag was added to gene: NRAS.
Vascular Malformations_Somatic v0.3 MTOR Zornitza Stark Marked gene: MTOR as ready
Vascular Malformations_Somatic v0.3 MTOR Zornitza Stark Gene: mtor has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Somatic v0.3 MTOR Zornitza Stark Classified gene: MTOR as Amber List (moderate evidence)
Vascular Malformations_Somatic v0.3 MTOR Zornitza Stark Gene: mtor has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Somatic v0.2 MAP3K3 Zornitza Stark Marked gene: MAP3K3 as ready
Vascular Malformations_Somatic v0.2 MAP3K3 Zornitza Stark Gene: map3k3 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.2 MAP3K3 Zornitza Stark Tag somatic tag was added to gene: MAP3K3.
Vascular Malformations_Somatic v0.2 MAP2K1 Zornitza Stark Marked gene: MAP2K1 as ready
Vascular Malformations_Somatic v0.2 MAP2K1 Zornitza Stark Gene: map2k1 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.2 MAP2K1 Zornitza Stark Tag somatic tag was added to gene: MAP2K1.
Vascular Malformations_Somatic v0.2 KRAS Zornitza Stark Marked gene: KRAS as ready
Vascular Malformations_Somatic v0.2 KRAS Zornitza Stark Gene: kras has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.2 KRAS Zornitza Stark Tag somatic tag was added to gene: KRAS.
Vascular Malformations_Somatic v0.2 HRAS Zornitza Stark Marked gene: HRAS as ready
Vascular Malformations_Somatic v0.2 HRAS Zornitza Stark Gene: hras has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.2 HRAS Zornitza Stark Tag somatic tag was added to gene: HRAS.
Vascular Malformations_Somatic v0.2 GNAQ Zornitza Stark Marked gene: GNAQ as ready
Vascular Malformations_Somatic v0.2 GNAQ Zornitza Stark Gene: gnaq has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.2 GNAQ Zornitza Stark Tag somatic tag was added to gene: GNAQ.
Vascular Malformations_Somatic v0.2 GNA14 Zornitza Stark Marked gene: GNA14 as ready
Vascular Malformations_Somatic v0.2 GNA14 Zornitza Stark Gene: gna14 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.2 GNA14 Zornitza Stark Tag somatic tag was added to gene: GNA14.
Vascular Malformations_Somatic v0.2 GNA11 Zornitza Stark Marked gene: GNA11 as ready
Vascular Malformations_Somatic v0.2 GNA11 Zornitza Stark Gene: gna11 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.2 GNA11 Zornitza Stark Phenotypes for gene: GNA11 were changed from Somatic hemangioma to Somatic hemangioma; Phacomatosis pigmentovascularis, somatic
Vascular Malformations_Somatic v0.1 GNA11 Zornitza Stark Tag somatic tag was added to gene: GNA11.
Vascular Malformations_Somatic v0.1 BRAF Zornitza Stark Marked gene: BRAF as ready
Vascular Malformations_Somatic v0.1 BRAF Zornitza Stark Gene: braf has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.1 BRAF Zornitza Stark Tag somatic tag was added to gene: BRAF.
Vascular Malformations_Somatic v0.1 AKT1 Zornitza Stark Marked gene: AKT1 as ready
Vascular Malformations_Somatic v0.1 AKT1 Zornitza Stark Gene: akt1 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.1 AKT1 Zornitza Stark Tag somatic tag was added to gene: AKT1.
Vascular Malformations_Somatic v0.0 SOS1 Zornitza Stark gene: SOS1 was added
gene: SOS1 was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: SOS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SOS1 were set to 29907801
Phenotypes for gene: SOS1 were set to Noonan syndrome 4 610733
Vascular Malformations_Somatic v0.0 PIK3R1 Zornitza Stark gene: PIK3R1 was added
gene: PIK3R1 was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: PIK3R1 was set to Other
Publications for gene: PIK3R1 were set to 29174369
Phenotypes for gene: PIK3R1 were set to capillary and lymphatic malformation
Vascular Malformations_Somatic v0.0 NRAS Zornitza Stark gene: NRAS was added
gene: NRAS was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: NRAS was set to Other
Publications for gene: NRAS were set to 30542204; 29461977
Phenotypes for gene: NRAS were set to Kaposiform lymphangiomatosis; Sporadic vascular malformation
Mode of pathogenicity for gene: NRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Vascular Malformations_Somatic v0.0 MTOR Zornitza Stark gene: MTOR was added
gene: MTOR was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: MTOR was set to Other
Publications for gene: MTOR were set to 29174369; 28892148
Phenotypes for gene: MTOR were set to Smith-Kingsmore syndrome 616638; Focal cortical dysplasia, type II, somatic 607341
Mode of pathogenicity for gene: MTOR was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Vascular Malformations_Somatic v0.0 MAP3K3 Zornitza Stark gene: MAP3K3 was added
gene: MAP3K3 was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: MAP3K3 was set to Other
Publications for gene: MAP3K3 were set to 10700190; 25728774
Phenotypes for gene: MAP3K3 were set to Verrucous venous malformation
Vascular Malformations_Somatic v0.0 MAP2K1 Zornitza Stark gene: MAP2K1 was added
gene: MAP2K1 was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: MAP2K1 was set to Other
Publications for gene: MAP2K1 were set to 31486960; 28190454; 29461977
Phenotypes for gene: MAP2K1 were set to Arteriovenous malformation; Intramuscular fast-flow vascular anomaly
Mode of pathogenicity for gene: MAP2K1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Vascular Malformations_Somatic v0.0 KRAS Zornitza Stark gene: KRAS was added
gene: KRAS was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: KRAS was set to Other
Publications for gene: KRAS were set to 30677207; 30544177; 31160609
Phenotypes for gene: KRAS were set to Arteriovenous malformation of the brain, somatic 108010; Vascular malformation
Mode of pathogenicity for gene: KRAS was set to Other
Vascular Malformations_Somatic v0.0 HRAS Zornitza Stark gene: HRAS was added
gene: HRAS was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: HRAS was set to Other
Publications for gene: HRAS were set to 31160609; 31637524; 30208313
Phenotypes for gene: HRAS were set to Vascular malformation/overgrowth syndromes; Extracranial arteriovenous malformations
Mode of pathogenicity for gene: HRAS was set to Other
Vascular Malformations_Somatic v0.0 GNAQ Zornitza Stark gene: GNAQ was added
gene: GNAQ was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: GNAQ was set to Other
Publications for gene: GNAQ were set to 30920161
Phenotypes for gene: GNAQ were set to Sturge-Weber syndrome, somatic, mosaic 185300; Capillary malformations, congenital, 1, somatic, mosaic 163000; Phacomatosis pigmentovascularis
Vascular Malformations_Somatic v0.0 GNA14 Zornitza Stark gene: GNA14 was added
gene: GNA14 was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: GNA14 was set to Other
Publications for gene: GNA14 were set to 31423605; 31707589; 27476652
Phenotypes for gene: GNA14 were set to Tufted angioma; vascular tumours; Anastomosing hemangioma
Mode of pathogenicity for gene: GNA14 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Vascular Malformations_Somatic v0.0 GNA11 Zornitza Stark gene: GNA11 was added
gene: GNA11 was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: GNA11 was set to Other
Publications for gene: GNA11 were set to 30677207
Phenotypes for gene: GNA11 were set to Somatic hemangioma
Mode of pathogenicity for gene: GNA11 was set to Other
Vascular Malformations_Somatic v0.0 BRAF Zornitza Stark gene: BRAF was added
gene: BRAF was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: BRAF was set to Other
Publications for gene: BRAF were set to 29316280; 30544177; 29461977
Phenotypes for gene: BRAF were set to Sporadic vascular malformations
Mode of pathogenicity for gene: BRAF was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Vascular Malformations_Somatic v0.0 AKT1 Zornitza Stark gene: AKT1 was added
gene: AKT1 was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: AKT1 was set to Other
Publications for gene: AKT1 were set to 23246288
Phenotypes for gene: AKT1 were set to Cowden syndrome 6 615109; Proteus syndrome, somatic 176920
Mode of pathogenicity for gene: AKT1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Vascular Malformations_Somatic v0.0 Zornitza Stark Added panel Vascular Malformations_Somatic
Congenital Heart Defect v0.52 TMEM94 Zornitza Stark Marked gene: TMEM94 as ready
Congenital Heart Defect v0.52 TMEM94 Zornitza Stark Gene: tmem94 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.52 TMEM94 Zornitza Stark Classified gene: TMEM94 as Green List (high evidence)
Congenital Heart Defect v0.52 TMEM94 Zornitza Stark Gene: tmem94 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.51 TMEM94 Zornitza Stark gene: TMEM94 was added
gene: TMEM94 was added to Congenital Heart Defect. Sources: Expert list
Mode of inheritance for gene: TMEM94 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM94 were set to Intellectual developmental disorder with cardiac defects and dysmorphic facies
Phenotypes for gene: TMEM94 were set to 30526868
Review for gene: TMEM94 was set to GREEN
Added comment: Ten individuals from 6 unrelated families reported, variety of congenital heart defects in addition to ID (ASD, VSD, Tetralogy of Fallot).
Sources: Expert list
Mendeliome v0.3202 SKIV2L Zornitza Stark changed review comment from: Multiple families reported with trichohepatoenteric syndrome.; to: Multiple families reported with trichohepatoenteric syndrome, agree unclear if ID is an association.
Mendeliome v0.3202 SKIV2L Zornitza Stark reviewed gene: SKIV2L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Trichohepatoenteric syndrome 2, MIM# 614602; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3202 SKIV2L Zornitza Stark Marked gene: SKIV2L as ready
Mendeliome v0.3202 SKIV2L Zornitza Stark Gene: skiv2l has been classified as Green List (High Evidence).
Mendeliome v0.3202 SKIV2L Zornitza Stark Phenotypes for gene: SKIV2L were changed from to Trichohepatoenteric syndrome 2 614602; Intellectual disability
Mendeliome v0.3201 SKIV2L Zornitza Stark Publications for gene: SKIV2L were set to
Mendeliome v0.3200 SKIV2L Zornitza Stark Mode of inheritance for gene: SKIV2L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3199 NLRP5 Zornitza Stark Marked gene: NLRP5 as ready
Mendeliome v0.3199 NLRP5 Zornitza Stark Gene: nlrp5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3199 NLRP5 Zornitza Stark Classified gene: NLRP5 as Amber List (moderate evidence)
Mendeliome v0.3199 NLRP5 Zornitza Stark Gene: nlrp5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3198 NLRP5 Zornitza Stark gene: NLRP5 was added
gene: NLRP5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NLRP5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NLRP5 were set to 32222962; 31829238; 30877238
Phenotypes for gene: NLRP5 were set to Early embryonic arrest
Review for gene: NLRP5 was set to AMBER
Added comment: At least two families reported.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 Zornitza Stark removed gene:ACVR1 from the panel
Hereditary Neuropathy - complex v0.67 EMILIN1 Zornitza Stark Marked gene: EMILIN1 as ready
Hereditary Neuropathy - complex v0.67 EMILIN1 Zornitza Stark Gene: emilin1 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.67 EMILIN1 Zornitza Stark Classified gene: EMILIN1 as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.67 EMILIN1 Zornitza Stark Gene: emilin1 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.66 EMILIN1 Zornitza Stark gene: EMILIN1 was added
gene: EMILIN1 was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for gene: EMILIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EMILIN1 were set to 31978608; 26462740
Phenotypes for gene: EMILIN1 were set to Peripheral neuropathy; aortic aneurysm
Review for gene: EMILIN1 was set to AMBER
Added comment: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature
Mendeliome v0.3197 EMILIN1 Zornitza Stark Marked gene: EMILIN1 as ready
Mendeliome v0.3197 EMILIN1 Zornitza Stark Gene: emilin1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3197 EMILIN1 Zornitza Stark Classified gene: EMILIN1 as Amber List (moderate evidence)
Mendeliome v0.3197 EMILIN1 Zornitza Stark Gene: emilin1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.137 FOXE3 Zornitza Stark Marked gene: FOXE3 as ready
Aortopathy_Connective Tissue Disorders v0.137 FOXE3 Zornitza Stark Gene: foxe3 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.137 FOXE3 Zornitza Stark Phenotypes for gene: FOXE3 were changed from to {Aortic aneurysm, familial thoracic 11, susceptibility to}, MIM# 617349
Aortopathy_Connective Tissue Disorders v0.136 FOXE3 Zornitza Stark Classified gene: FOXE3 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.136 FOXE3 Zornitza Stark Gene: foxe3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3196 EXOC7 Zornitza Stark gene: EXOC7 was added
gene: EXOC7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC7 were set to 32103185
Phenotypes for gene: EXOC7 were set to brain atrophy; seizures; developmental delay; microcephaly
Review for gene: EXOC7 was set to GREEN
Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families. They showed that EXOC7, a member of the mammalian exocyst complex, is highly expressed in developing human cortex. In addition, a zebrafish model of Exoc7 deficiency recapitulates the human disorder with increased apoptosis and decreased progenitor cells during telencephalon development, suggesting that the brain atrophy in human cases reflects neuronal degeneration.
Sources: Literature
Microcephaly v0.135 EXOC7 Zornitza Stark Marked gene: EXOC7 as ready
Microcephaly v0.135 EXOC7 Zornitza Stark Gene: exoc7 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.736 EXOC7 Zornitza Stark Marked gene: EXOC7 as ready
Genetic Epilepsy v0.736 EXOC7 Zornitza Stark Gene: exoc7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2725 EXOC7 Zornitza Stark Marked gene: EXOC7 as ready
Intellectual disability syndromic and non-syndromic v0.2725 EXOC7 Zornitza Stark Gene: exoc7 has been classified as Green List (High Evidence).
Mendeliome v0.3195 HNRNPH1 Zornitza Stark gene: HNRNPH1 was added
gene: HNRNPH1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HNRNPH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPH1 were set to 32335897; 29938792
Phenotypes for gene: HNRNPH1 were set to HNRNPH1‐related syndromic intellectual disability
Review for gene: HNRNPH1 was set to GREEN
Added comment: 1st patient reported in 2018 with intellectual disability and dysmorphic features and HNRNPH1 heterozygous missense variant. 2020 paper reports additional 7 cases with ID, short stature, microcephaly, distinctive dysmorphic facial features, and congenital anomalies (cranial, brain, genitourinary, palate, ophthalmologic). They all had HNRNPH1 heterozygous pathogenic variants (missense, frameshift, in‐frame deletion, entire gene duplication) and were identified using clinical networks and GeneMatcher. No comments in paper if all de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2725 HNRNPH1 Zornitza Stark Marked gene: HNRNPH1 as ready
Intellectual disability syndromic and non-syndromic v0.2725 HNRNPH1 Zornitza Stark Gene: hnrnph1 has been classified as Green List (High Evidence).
Arthrogryposis v0.69 TPM2 Zornitza Stark Marked gene: TPM2 as ready
Arthrogryposis v0.69 TPM2 Zornitza Stark Gene: tpm2 has been classified as Green List (High Evidence).
Arthrogryposis v0.69 TPM2 Zornitza Stark Phenotypes for gene: TPM2 were changed from to Arthrogryposis, distal, type 1A/2B4 (MIM#108120)
Arthrogryposis v0.68 TPM2 Zornitza Stark Publications for gene: TPM2 were set to
Arthrogryposis v0.67 TPM2 Zornitza Stark Mode of inheritance for gene: TPM2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3194 PDCD6IP Zornitza Stark gene: PDCD6IP was added
gene: PDCD6IP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDCD6IP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCD6IP were set to 32286682
Phenotypes for gene: PDCD6IP were set to Microcephaly; intellectual disability
Review for gene: PDCD6IP was set to AMBER
Added comment: One consanguineous family with 2 affected sibs with primary microcephaly (-4SD), intellectual disability and short stature (-5/6SD), and homozygous frameshift variant in PDCD6IP. The homozygous variant was confirmed in both affected sibs, while the four healthy siblings and parents were heterozygous. The clinical features observed in the patients were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2725 PDCD6IP Zornitza Stark Marked gene: PDCD6IP as ready
Intellectual disability syndromic and non-syndromic v0.2725 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2725 PDCD6IP Zornitza Stark Classified gene: PDCD6IP as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2725 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Microcephaly v0.135 PDCD6IP Zornitza Stark Marked gene: PDCD6IP as ready
Microcephaly v0.135 PDCD6IP Zornitza Stark Added comment: Comment when marking as ready: Single family and animal models, upgrade to Amber.
Microcephaly v0.135 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Microcephaly v0.135 PDCD6IP Zornitza Stark Classified gene: PDCD6IP as Amber List (moderate evidence)
Microcephaly v0.135 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3193 NME5 Zornitza Stark Marked gene: NME5 as ready
Mendeliome v0.3193 NME5 Zornitza Stark Gene: nme5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3193 NME5 Zornitza Stark Classified gene: NME5 as Amber List (moderate evidence)
Mendeliome v0.3193 NME5 Zornitza Stark Gene: nme5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3192 NME5 Zornitza Stark gene: NME5 was added
gene: NME5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NME5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NME5 were set to 32185794
Phenotypes for gene: NME5 were set to Primary ciliary dyskinesia
Review for gene: NME5 was set to AMBER
Added comment: One patient with PCD with situs solitus, with radial spokes (RS) and central pair (CP) defects. Patient had a homozygous nonsense variant in NME5, with parents as carriers. Morpholino knockdown of nme5 in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy.
Sources: Literature
Ciliary Dyskinesia v0.116 NME5 Zornitza Stark Marked gene: NME5 as ready
Ciliary Dyskinesia v0.116 NME5 Zornitza Stark Added comment: Comment when marking as ready: Single family and animal model, upgrade to Amber.
Ciliary Dyskinesia v0.116 NME5 Zornitza Stark Gene: nme5 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.116 NME5 Zornitza Stark Classified gene: NME5 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.116 NME5 Zornitza Stark Gene: nme5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3191 ADAMTS19 Zornitza Stark Publications for gene: ADAMTS19 were set to 31844321
Mendeliome v0.3190 ADAMTS19 Zornitza Stark Classified gene: ADAMTS19 as Green List (high evidence)
Mendeliome v0.3190 ADAMTS19 Zornitza Stark Gene: adamts19 has been classified as Green List (High Evidence).
Mendeliome v0.3189 ADAMTS19 Zornitza Stark reviewed gene: ADAMTS19: Rating: GREEN; Mode of pathogenicity: None; Publications: 32323311, 31844321; Phenotypes: Heart valve disease (HVD); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3189 EMILIN1 Naomi Baker changed review comment from: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature; to: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature
Mendeliome v0.3189 EMILIN1 Naomi Baker gene: EMILIN1 was added
gene: EMILIN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EMILIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EMILIN1 were set to PMID: 31978608; 26462740.
Phenotypes for gene: EMILIN1 were set to peripheral neuropathy
Penetrance for gene: EMILIN1 were set to unknown
Review for gene: EMILIN1 was set to AMBER
Added comment: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature
Vascular Malformations_Germline v0.95 AKT3 Zornitza Stark Marked gene: AKT3 as ready
Vascular Malformations_Germline v0.95 AKT3 Zornitza Stark Gene: akt3 has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.95 AKT3 Zornitza Stark Classified gene: AKT3 as Green List (high evidence)
Vascular Malformations_Germline v0.95 AKT3 Zornitza Stark Gene: akt3 has been classified as Green List (High Evidence).
Lymphoedema_syndromic v0.3 ADAMTS3 Zornitza Stark Marked gene: ADAMTS3 as ready
Lymphoedema_syndromic v0.3 ADAMTS3 Zornitza Stark Gene: adamts3 has been classified as Green List (High Evidence).
Lymphoedema_syndromic v0.3 ADAMTS3 Zornitza Stark Classified gene: ADAMTS3 as Green List (high evidence)
Lymphoedema_syndromic v0.3 ADAMTS3 Zornitza Stark Gene: adamts3 has been classified as Green List (High Evidence).
Lymphoedema_syndromic v0.2 ADAMTS3 Zornitza Stark gene: ADAMTS3 was added
gene: ADAMTS3 was added to Lymphoedema_syndromic. Sources: Expert Review
Mode of inheritance for gene: ADAMTS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS3 were set to 28985353; 30450763
Phenotypes for gene: ADAMTS3 were set to Hennekam lymphangiectasia-lymphedema syndrome 3 (618154)
Review for gene: ADAMTS3 was set to GREEN
Added comment: Two families and functional data. Some dysmorphism described.
Sources: Expert Review
Mendeliome v0.3189 ADAMTS3 Zornitza Stark Marked gene: ADAMTS3 as ready
Mendeliome v0.3189 ADAMTS3 Zornitza Stark Gene: adamts3 has been classified as Green List (High Evidence).
Mendeliome v0.3189 ADAMTS3 Zornitza Stark Classified gene: ADAMTS3 as Green List (high evidence)
Mendeliome v0.3189 ADAMTS3 Zornitza Stark Gene: adamts3 has been classified as Green List (High Evidence).
Mendeliome v0.3188 ADAMTS3 Zornitza Stark gene: ADAMTS3 was added
gene: ADAMTS3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ADAMTS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS3 were set to 28985353; 30450763
Phenotypes for gene: ADAMTS3 were set to Hennekam lymphangiectasia-lymphedema syndrome 3 (618154)
Review for gene: ADAMTS3 was set to GREEN
Added comment: Two families reported, supportive functional data.
Sources: Expert list
Lymphoedema_nonsyndromic v0.7 ADAMTS3 Zornitza Stark Marked gene: ADAMTS3 as ready
Lymphoedema_nonsyndromic v0.7 ADAMTS3 Zornitza Stark Gene: adamts3 has been classified as Green List (High Evidence).
Lymphoedema_nonsyndromic v0.7 ADAMTS3 Zornitza Stark Classified gene: ADAMTS3 as Green List (high evidence)
Lymphoedema_nonsyndromic v0.7 ADAMTS3 Zornitza Stark Gene: adamts3 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.50 GAA Zornitza Stark Marked gene: GAA as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.50 GAA Zornitza Stark Added comment: Comment when marking as ready: Metabolic condition with phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.50 GAA Zornitza Stark Gene: gaa has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.50 GAA Zornitza Stark Classified gene: GAA as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.50 GAA Zornitza Stark Gene: gaa has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.49 GNE Zornitza Stark Marked gene: GNE as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.49 GNE Zornitza Stark Gene: gne has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.49 GNE Zornitza Stark Classified gene: GNE as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.49 GNE Zornitza Stark Gene: gne has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.66 FLNC Zornitza Stark Marked gene: FLNC as ready
Arthrogryposis v0.66 FLNC Zornitza Stark Gene: flnc has been classified as Green List (High Evidence).
Arthrogryposis v0.66 FLNC Zornitza Stark Classified gene: FLNC as Green List (high evidence)
Arthrogryposis v0.66 FLNC Zornitza Stark Gene: flnc has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.135 COL12A1 Bryony Thompson Marked gene: COL12A1 as ready
Aortopathy_Connective Tissue Disorders v0.135 COL12A1 Bryony Thompson Gene: col12a1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.135 COL12A1 Bryony Thompson Classified gene: COL12A1 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.135 COL12A1 Bryony Thompson Gene: col12a1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.48 FLNC Zornitza Stark Marked gene: FLNC as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.48 FLNC Zornitza Stark Added comment: Comment when marking as ready: Causes a range of conditions affecting muscle, phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.48 FLNC Zornitza Stark Gene: flnc has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.134 COL12A1 Bryony Thompson gene: COL12A1 was added
gene: COL12A1 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: COL12A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COL12A1 were set to 28306229; 31273343; 24334604
Phenotypes for gene: COL12A1 were set to Myopathic EDS; Bethlem myopathy 2 MIM#616471; Ullrich congenital muscular dystrophy 2 MIM#616470
Review for gene: COL12A1 was set to GREEN
Added comment: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229).
18 cases from 12 unrelated families have been reported with monoallelic variants (both de novo and inherited), and one family has been reported with a homozygous variant. A null mouse model recapitulates the phenotype.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.48 FLNC Zornitza Stark Classified gene: FLNC as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.48 FLNC Zornitza Stark Gene: flnc has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.47 LAMP2 Zornitza Stark Marked gene: LAMP2 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.47 LAMP2 Zornitza Stark Gene: lamp2 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.47 LAMP2 Zornitza Stark Classified gene: LAMP2 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.47 LAMP2 Zornitza Stark Gene: lamp2 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.46 ETFDH Zornitza Stark Marked gene: ETFDH as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.46 ETFDH Zornitza Stark Added comment: Comment when marking as ready: Metabolic disorder with phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.46 ETFDH Zornitza Stark Gene: etfdh has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.46 ETFDH Zornitza Stark Classified gene: ETFDH as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.46 ETFDH Zornitza Stark Gene: etfdh has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.45 DOK7 Zornitza Stark Classified gene: DOK7 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.45 DOK7 Zornitza Stark Gene: dok7 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.44 LMNA Zornitza Stark Marked gene: LMNA as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.44 LMNA Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.44 LMNA Zornitza Stark Gene: lmna has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.44 LMNA Zornitza Stark Classified gene: LMNA as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.44 LMNA Zornitza Stark Gene: lmna has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.43 LMNA Zornitza Stark Classified gene: LMNA as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.43 LMNA Zornitza Stark Gene: lmna has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.42 CRYAB Zornitza Stark Marked gene: CRYAB as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.42 CRYAB Zornitza Stark Gene: cryab has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.42 CRYAB Zornitza Stark Phenotypes for gene: CRYAB were changed from Myopathy, myofibrillar, 2 608810; Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related 613869 to Myopathy, myofibrillar, 2, MIM# 608810
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.41 CRYAB Zornitza Stark Mode of inheritance for gene: CRYAB was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.40 CRYAB Zornitza Stark Classified gene: CRYAB as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.40 CRYAB Zornitza Stark Gene: cryab has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.39 CRYAB Zornitza Stark reviewed gene: CRYAB: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy, myofibrillar, 2, MIM# 608810; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.39 DES Zornitza Stark Marked gene: DES as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.39 DES Zornitza Stark Added comment: Comment when marking as ready: Variable presentation, some overlap with LGMD.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.39 DES Zornitza Stark Gene: des has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.39 DES Zornitza Stark Classified gene: DES as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.39 DES Zornitza Stark Gene: des has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.57 LPIN1 Zornitza Stark Marked gene: LPIN1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.57 LPIN1 Zornitza Stark Gene: lpin1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.57 LPIN1 Zornitza Stark Publications for gene: LPIN1 were set to
Rhabdomyolysis and Metabolic Myopathy v0.56 LPIN1 Zornitza Stark reviewed gene: LPIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28649549, 18817903, 32410653; Phenotypes: Myoglobinuria, acute recurrent, autosomal recessive (MIM#268200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.38 MYH7 Zornitza Stark Marked gene: MYH7 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.38 MYH7 Zornitza Stark Gene: myh7 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.38 MYH7 Zornitza Stark Classified gene: MYH7 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.38 MYH7 Zornitza Stark Gene: myh7 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.133 COL1A2 Bryony Thompson Marked gene: COL1A2 as ready
Aortopathy_Connective Tissue Disorders v0.133 COL1A2 Bryony Thompson Gene: col1a2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.133 COL1A2 Bryony Thompson Classified gene: COL1A2 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.133 COL1A2 Bryony Thompson Gene: col1a2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.132 COL1A2 Bryony Thompson gene: COL1A2 was added
gene: COL1A2 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: COL1A2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COL1A2 were set to 28306229; 32091183; 2993307; 30821104
Phenotypes for gene: COL1A2 were set to Ehlers-Danlos syndrome, arthrochalasia type, 2 MIM#617821; Ehlers-Danlos syndrome, cardiac valvular type MIM#225320
Review for gene: COL1A2 was set to GREEN
gene: COL1A2 was marked as current diagnostic
Added comment: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229). Monoallelic variants leading to (partial) loss of exon 6 are a well-established cause arthrochalasia type EDS.
Biallelic variant that lead to loss-of-function/absence of pro a2(I) collagen chains cause cardiac-valvular type EDS. 6 cases in 5 unrelated families have been reported with homozygous and compound heterozygous variants (PMID: 30821104).
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.37 MYOT Zornitza Stark Marked gene: MYOT as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.37 MYOT Zornitza Stark Added comment: Comment when marking as ready: Some of the reported variants have high population frequency.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.37 MYOT Zornitza Stark Gene: myot has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.37 MYOT Zornitza Stark Classified gene: MYOT as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.37 MYOT Zornitza Stark Gene: myot has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.36 ORAI1 Zornitza Stark Marked gene: ORAI1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.36 ORAI1 Zornitza Stark Gene: orai1 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.36 ORAI1 Zornitza Stark Classified gene: ORAI1 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.36 ORAI1 Zornitza Stark Gene: orai1 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 ORAI1 Zornitza Stark reviewed gene: ORAI1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy, tubular aggregate, 2 (MIM#615883); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.65 MCM3AP Zornitza Stark Marked gene: MCM3AP as ready
Hereditary Neuropathy - complex v0.65 MCM3AP Zornitza Stark Gene: mcm3ap has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.65 MCM3AP Zornitza Stark Publications for gene: MCM3AP were set to
Hereditary Neuropathy - complex v0.64 MCM3AP Zornitza Stark edited their review of gene: MCM3AP: Added comment: PMID: 32202298 - Woldegebriel et al 2020 - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.; Changed publications: 24123876, 28633435, 28969388, 29982295, 32202298
Intellectual disability syndromic and non-syndromic v0.2724 MCM3AP Zornitza Stark edited their review of gene: MCM3AP: Added comment: PMID: 32202298 - Woldegebriel et al 2020 - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.; Changed publications: 32202298
Intellectual disability syndromic and non-syndromic v0.2724 MCM3AP Zornitza Stark Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295
Intellectual disability syndromic and non-syndromic v0.2723 MCM3AP Zornitza Stark edited their review of gene: MCM3AP: Changed publications: 24123876, 28633435, 28969388, 29982295, 32202298
Mendeliome v0.3187 MCM3AP Zornitza Stark Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295
Mendeliome v0.3186 SP6 Zornitza Stark Marked gene: SP6 as ready
Mendeliome v0.3186 SP6 Zornitza Stark Gene: sp6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3186 SP6 Zornitza Stark Classified gene: SP6 as Amber List (moderate evidence)
Mendeliome v0.3186 SP6 Zornitza Stark Gene: sp6 has been classified as Amber List (Moderate Evidence).
Radial Ray Abnormalities v0.11 TBX5 Zornitza Stark Marked gene: TBX5 as ready
Radial Ray Abnormalities v0.11 TBX5 Zornitza Stark Gene: tbx5 has been classified as Green List (High Evidence).
Radial Ray Abnormalities v0.11 TBX5 Zornitza Stark Phenotypes for gene: TBX5 were changed from to Holt-Oram syndrome, MIM# 142900
Radial Ray Abnormalities v0.10 TBX5 Zornitza Stark Publications for gene: TBX5 were set to
Radial Ray Abnormalities v0.9 TBX5 Zornitza Stark Mode of inheritance for gene: TBX5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Radial Ray Abnormalities v0.8 TBX5 Zornitza Stark reviewed gene: TBX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 10077612, 31373354; Phenotypes: Holt-Oram syndrome, MIM# 142900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3185 TBX5 Zornitza Stark edited their review of gene: TBX5: Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3185 TBX5 Zornitza Stark reviewed gene: TBX5: Rating: ; Mode of pathogenicity: None; Publications: 10077612; Phenotypes: Holt-Oram syndrome, MIM# 142900; Mode of inheritance: None
Aortopathy_Connective Tissue Disorders v0.131 EFEMP2 Zornitza Stark Marked gene: EFEMP2 as ready
Aortopathy_Connective Tissue Disorders v0.131 EFEMP2 Zornitza Stark Gene: efemp2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.131 EFEMP2 Zornitza Stark Phenotypes for gene: EFEMP2 were changed from to Cutis laxa, autosomal recessive, type IB MIM# 614437
Aortopathy_Connective Tissue Disorders v0.130 FOXE3 Ain Roesley gene: FOXE3 was added
gene: FOXE3 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: FOXE3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXE3 were set to 30071989; 26854927
Review for gene: FOXE3 was set to AMBER
Added comment: PMID: 30071989; classification from “moderate” to “limited” after expert review, because the data provided are limited to single supporting publications with few HTAAD families.

Gene validity curation by ClinGen in 2016 was "moderate", citing segregation in the large family and animal models (https://search.clinicalgenome.org/kb/gene-validity/8261, PMID: 26854927)
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.130 EFEMP2 Zornitza Stark Classified gene: EFEMP2 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.130 EFEMP2 Zornitza Stark Gene: efemp2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.129 EFEMP2 Paul De Fazio edited their review of gene: EFEMP2: Changed phenotypes: Cutis laxa, autosomal recessive, type IB MIM# 614437
Aortopathy_Connective Tissue Disorders v0.129 EFEMP2 Paul De Fazio gene: EFEMP2 was added
gene: EFEMP2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: EFEMP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EFEMP2 were set to 20389311; 19664000; 16685658; 17937443; 22943132; 22440127
Review for gene: EFEMP2 was set to GREEN
gene: EFEMP2 was marked as current diagnostic
Added comment: Associated with cutis laxa in at least 6 unrelated individuals (PMID: 20389311; 19664000; 16685658; 17937443).

PMID: 22943132 reports 22 homozygous or compound het infants with: cardiovascular features included aneurysmal dilatation, elongation, tortuosity and narrowing of the aorta, pulmonary artery and their branches. The phenotype included a variable combination of cutis laxa (52%), long philtrum-thin vermillion (90%), micrognathia (43%), hypertelorism (57%), prominent eyes (43%), sagging cheeks (43%), long slender digits (48%), and visible arterial pulsations (38%).

Has also been associated with aortic dissection without presentation of cutis laxa (PMID: 22440127 - reports 9 affected individuals).
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.129 FBLN5 Zornitza Stark Marked gene: FBLN5 as ready
Aortopathy_Connective Tissue Disorders v0.129 FBLN5 Zornitza Stark Gene: fbln5 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.129 FBLN5 Zornitza Stark Classified gene: FBLN5 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.129 FBLN5 Zornitza Stark Gene: fbln5 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.128 FBLN5 Zornitza Stark gene: FBLN5 was added
gene: FBLN5 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: FBLN5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FBLN5 were set to 3232707; 22829427; 11805835
Phenotypes for gene: FBLN5 were set to Cutis laxa, autosomal recessive, type IA, MIM# 219100
Review for gene: FBLN5 was set to GREEN
Added comment: >3 families reported and functional data including mouse model.
Sources: Expert list
Genetic Epilepsy v0.736 EXOC7 Chirag Patel Classified gene: EXOC7 as Green List (high evidence)
Genetic Epilepsy v0.736 EXOC7 Chirag Patel Gene: exoc7 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.736 EXOC7 Chirag Patel Classified gene: EXOC7 as Green List (high evidence)
Genetic Epilepsy v0.736 EXOC7 Chirag Patel Gene: exoc7 has been classified as Green List (High Evidence).
Microcephaly v0.134 EXOC7 Chirag Patel Classified gene: EXOC7 as Green List (high evidence)
Microcephaly v0.134 EXOC7 Chirag Patel Gene: exoc7 has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v0.59 SMCHD1 Crystle Lee reviewed gene: SMCHD1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 28067911, 31243061; Phenotypes: Bosma arhinia microphthalmia syndrome (MIM#603457); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.735 EXOC7 Chirag Patel Classified gene: EXOC7 as Green List (high evidence)
Genetic Epilepsy v0.735 EXOC7 Chirag Patel Gene: exoc7 has been classified as Green List (High Evidence).
Microcephaly v0.133 EXOC7 Chirag Patel gene: EXOC7 was added
gene: EXOC7 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC7 were set to PMID: 32103185
Phenotypes for gene: EXOC7 were set to brain atrophy; seizures; developmental delay; microcephaly
Review for gene: EXOC7 was set to GREEN
Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families. They showed that EXOC7, a member of the mammalian exocyst complex, is highly expressed in developing human cortex. In addition, a zebrafish model of Exoc7 deficiency recapitulates the human disorder with increased apoptosis and decreased progenitor cells during telencephalon development, suggesting that the brain atrophy in human cases reflects neuronal degeneration.
Sources: Literature
Genetic Epilepsy v0.734 EXOC7 Chirag Patel gene: EXOC7 was added
gene: EXOC7 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC7 were set to PMID: 32103185
Phenotypes for gene: EXOC7 were set to brain atrophy; seizures; developmental delay; microcephaly
Review for gene: EXOC7 was set to GREEN
Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families. They showed that EXOC7, a member of the mammalian exocyst complex, is highly expressed in developing human cortex. In addition, a zebrafish model of Exoc7 deficiency recapitulates the human disorder with increased apoptosis and decreased progenitor cells during telencephalon development, suggesting that the brain atrophy in human cases reflects neuronal degeneration.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.126 DSE Bryony Thompson Marked gene: DSE as ready
Aortopathy_Connective Tissue Disorders v0.126 DSE Bryony Thompson Gene: dse has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.126 DSE Bryony Thompson Classified gene: DSE as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.126 DSE Bryony Thompson Gene: dse has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.125 DSE Bryony Thompson gene: DSE was added
gene: DSE was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: DSE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DSE were set to 28306229; 23704329; 25703627; 32130795
Phenotypes for gene: DSE were set to Ehlers-Danlos syndrome, musculocontractural type 2 MIM#615539
Review for gene: DSE was set to GREEN
Added comment: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229).
8 cases from 6 unrelated families have been reported with homozygous variants.
Sources: Expert list
Aortopathy_Connective Tissue Disorders v0.124 MFAP5 Zornitza Stark Marked gene: MFAP5 as ready
Aortopathy_Connective Tissue Disorders v0.124 MFAP5 Zornitza Stark Gene: mfap5 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.124 MFAP5 Zornitza Stark Classified gene: MFAP5 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.124 MFAP5 Zornitza Stark Gene: mfap5 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2723 EXOC7 Chirag Patel Classified gene: EXOC7 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2723 EXOC7 Chirag Patel Gene: exoc7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2722 EXOC7 Chirag Patel gene: EXOC7 was added
gene: EXOC7 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC7 were set to PMID: 32103185
Phenotypes for gene: EXOC7 were set to brain atrophy; seizures; developmental delay; microcephaly
Review for gene: EXOC7 was set to GREEN
Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families. They showed that EXOC7, a member of the mammalian exocyst complex, is highly expressed in developing human cortex. In addition, a zebrafish model of Exoc7 deficiency recapitulates the human disorder with increased apoptosis and decreased progenitor cells during telencephalon development, suggesting that the brain atrophy in human cases reflects neuronal degeneration.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.123 ELN Zornitza Stark Marked gene: ELN as ready
Aortopathy_Connective Tissue Disorders v0.123 ELN Zornitza Stark Gene: eln has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.123 MFAP5 Paul De Fazio gene: MFAP5 was added
gene: MFAP5 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: MFAP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MFAP5 were set to 25434006; 30763214
Phenotypes for gene: MFAP5 were set to Aortic aneurysm, familial thoracic MIM# 616166
Review for gene: MFAP5 was set to AMBER
gene: MFAP5 was marked as current diagnostic
Added comment: 2 families described with thoracic aortic aneurysms and dissections, one with a nonsense variant and one with a missense (PMID:2544006). A recent review doesn't mention any other cases (PMID:30763214).
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.123 CHST14 Zornitza Stark Marked gene: CHST14 as ready
Aortopathy_Connective Tissue Disorders v0.123 CHST14 Zornitza Stark Gene: chst14 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.123 ELN Zornitza Stark Classified gene: ELN as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.123 ELN Zornitza Stark Gene: eln has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.122 FKBP14 Bryony Thompson Classified gene: FKBP14 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.122 FKBP14 Bryony Thompson Gene: fkbp14 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.122 CHST14 Zornitza Stark Classified gene: CHST14 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.122 CHST14 Zornitza Stark Gene: chst14 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.121 FKBP14 Bryony Thompson Classified gene: FKBP14 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.121 FKBP14 Bryony Thompson Gene: fkbp14 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.121 FKBP14 Bryony Thompson Marked gene: FKBP14 as ready
Aortopathy_Connective Tissue Disorders v0.121 FKBP14 Bryony Thompson Gene: fkbp14 has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v0.121 CHST14 Zornitza Stark Classified gene: CHST14 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.121 CHST14 Zornitza Stark Gene: chst14 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.120 FKBP14 Bryony Thompson changed review comment from: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229).
At least 6 unrelated families with homozygous or compound heterozygous variants reported.
Sources: Expert list; to: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229).
At least 6 unrelated families with homozygous or compound heterozygous variants reported with this EDS subtype.
Sources: Expert list
Aortopathy_Connective Tissue Disorders v0.120 FKBP14 Bryony Thompson edited their review of gene: FKBP14: Changed rating: GREEN
Aortopathy_Connective Tissue Disorders v0.120 FKBP14 Bryony Thompson gene: FKBP14 was added
gene: FKBP14 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: FKBP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FKBP14 were set to 22265013; 28306229; 24773188; 27149304
Phenotypes for gene: FKBP14 were set to Ehlers-Danlos syndrome, kyphoscoliotic type, 2 MIM#614557
Added comment: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229).
At least 6 unrelated families with homozygous or compound heterozygous variants reported.
Sources: Expert list
Aortopathy_Connective Tissue Disorders v0.119 ATP6V0A2 Zornitza Stark Marked gene: ATP6V0A2 as ready
Aortopathy_Connective Tissue Disorders v0.119 ATP6V0A2 Zornitza Stark Gene: atp6v0a2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.119 ATP6V0A2 Zornitza Stark Classified gene: ATP6V0A2 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.119 ATP6V0A2 Zornitza Stark Gene: atp6v0a2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.118 NOTCH1 Zornitza Stark Marked gene: NOTCH1 as ready
Aortopathy_Connective Tissue Disorders v0.118 NOTCH1 Zornitza Stark Gene: notch1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.118 NOTCH1 Zornitza Stark Phenotypes for gene: NOTCH1 were changed from Aortic valve disease MIM# 109730 to Aortic valve disease MIM# 109730; Thoracic aortic aneurysm
Aortopathy_Connective Tissue Disorders v0.117 NOTCH1 Zornitza Stark Classified gene: NOTCH1 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.117 NOTCH1 Zornitza Stark Gene: notch1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2721 HNRNPH1 Chirag Patel Classified gene: HNRNPH1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2721 HNRNPH1 Chirag Patel Gene: hnrnph1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.116 ALDH18A1 Zornitza Stark Marked gene: ALDH18A1 as ready
Aortopathy_Connective Tissue Disorders v0.116 ALDH18A1 Zornitza Stark Gene: aldh18a1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.116 ALDH18A1 Zornitza Stark Classified gene: ALDH18A1 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.116 ALDH18A1 Zornitza Stark Gene: aldh18a1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.115 SMAD6 Zornitza Stark Marked gene: SMAD6 as ready
Aortopathy_Connective Tissue Disorders v0.115 SMAD6 Zornitza Stark Added comment: Comment when marking as ready: Primarily associated with aortic valve disease, but increased prevalence of thoracic aneurysm also documented.
Aortopathy_Connective Tissue Disorders v0.115 SMAD6 Zornitza Stark Gene: smad6 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.115 SMAD6 Zornitza Stark Classified gene: SMAD6 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.115 SMAD6 Zornitza Stark Gene: smad6 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.114 PLOD1 Bryony Thompson Marked gene: PLOD1 as ready
Aortopathy_Connective Tissue Disorders v0.114 PLOD1 Bryony Thompson Gene: plod1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.114 PLOD1 Bryony Thompson Classified gene: PLOD1 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.114 PLOD1 Bryony Thompson Gene: plod1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.113 PRDM5 Bryony Thompson Marked gene: PRDM5 as ready
Aortopathy_Connective Tissue Disorders v0.113 PRDM5 Bryony Thompson Gene: prdm5 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.113 PRDM5 Bryony Thompson Classified gene: PRDM5 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.113 PRDM5 Bryony Thompson Gene: prdm5 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.112 PRDM5 Bryony Thompson gene: PRDM5 was added
gene: PRDM5 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: PRDM5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM5 were set to 28306229; 21664999
Phenotypes for gene: PRDM5 were set to Brittle cornea syndrome 2, MIM#614170
Review for gene: PRDM5 was set to GREEN
Added comment: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229). Homozygous variants identified in at least 7 unrelated confirmed/likely consanguineous brittle cornea syndrome families. The mutation spectrum included stopgain, missense, splice site, and a large deletion.
Sources: Expert list
Skeletal dysplasia v0.34 ACVR1 Ain Roesley reviewed gene: ACVR1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30071989, 19085907, 26776312, 18684712, 23572558, 20463014; Phenotypes: Fibrodysplasia ossificans progressiva (MIM# 135100); Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2720 HNRNPH1 Chirag Patel gene: HNRNPH1 was added
gene: HNRNPH1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HNRNPH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPH1 were set to PMID: 32335897; 29938792
Phenotypes for gene: HNRNPH1 were set to HNRNPH1 ‐related syndromic intellectual disability
Review for gene: HNRNPH1 was set to GREEN
Added comment: 1st patient reported in 2018 with intellectual disability and dysmorphic features and HNRNPH1 heterozygous missense variant.

2020 paper reports additional 7 cases with ID, short stature, microcephaly, distinctive dysmorphic facial features, and congenital anomalies (cranial, brain, genitourinary, palate, ophthalmologic). They all had HNRNPH1 heterozygous pathogenic variants (missense, frameshift, in‐frame deletion, entire gene duplication) and were identified using clinical networks and GeneMatcher. No comments in paper if all de novo.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.111 ABCC6 Zornitza Stark Marked gene: ABCC6 as ready
Aortopathy_Connective Tissue Disorders v0.111 ABCC6 Zornitza Stark Gene: abcc6 has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v0.111 ABCC6 Zornitza Stark Classified gene: ABCC6 as Red List (low evidence)
Aortopathy_Connective Tissue Disorders v0.111 ABCC6 Zornitza Stark Gene: abcc6 has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v0.111 SLC39A13 Bryony Thompson Marked gene: SLC39A13 as ready
Aortopathy_Connective Tissue Disorders v0.111 SLC39A13 Bryony Thompson Gene: slc39a13 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.111 SLC39A13 Bryony Thompson Classified gene: SLC39A13 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.111 SLC39A13 Bryony Thompson Gene: slc39a13 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.110 ABCC6 Zornitza Stark reviewed gene: ABCC6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Aortopathy_Connective Tissue Disorders v0.110 TNXB Bryony Thompson Marked gene: TNXB as ready
Aortopathy_Connective Tissue Disorders v0.110 TNXB Bryony Thompson Gene: tnxb has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.110 TNXB Bryony Thompson Classified gene: TNXB as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.110 TNXB Bryony Thompson Added comment: Comment on list classification: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229)
Aortopathy_Connective Tissue Disorders v0.110 TNXB Bryony Thompson Gene: tnxb has been classified as Green List (High Evidence).
Arthrogryposis v0.65 TPM2 Crystle Lee reviewed gene: TPM2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30285720, 27726070, 24692096; Phenotypes: Arthrogryposis, distal, type 1A/2B4 (MIM#108120); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Aortopathy_Connective Tissue Disorders v0.109 ZNF469 Bryony Thompson Marked gene: ZNF469 as ready
Aortopathy_Connective Tissue Disorders v0.109 ZNF469 Bryony Thompson Gene: znf469 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.109 ZNF469 Bryony Thompson Classified gene: ZNF469 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.109 ZNF469 Bryony Thompson Added comment: Comment on list classification: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229)
Aortopathy_Connective Tissue Disorders v0.109 ZNF469 Bryony Thompson Gene: znf469 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2719 PDCD6IP Chirag Patel gene: PDCD6IP was added
gene: PDCD6IP was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PDCD6IP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCD6IP were set to PMID: 32286682
Phenotypes for gene: PDCD6IP were set to Primary microcephaly
Review for gene: PDCD6IP was set to RED
Added comment: One consanguineous family with 2 affected sibs with primary microcephaly (-4SD), intellectual disability and short stature (-5/6SD), and homozygous frameshift variant in PDCD6IP. The homozygous variant was confirmed in both affected sibs, while the four healthy siblings and parents were heterozygous. The clinical features observed in the patients were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.108 C1S Bryony Thompson Publications for gene: C1S were set to 30071989; 27745832; 31921203
Microcephaly v0.132 PDCD6IP Chirag Patel gene: PDCD6IP was added
gene: PDCD6IP was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: PDCD6IP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCD6IP were set to PMID: 32286682
Phenotypes for gene: PDCD6IP were set to Primary microcephaly
Review for gene: PDCD6IP was set to RED
Added comment: One consanguineous family with 2 affected sibs with primary microcephaly (-4SD), intellectual disability and short stature (-5/6SD), and homozygous frameshift variant in PDCD6IP. The homozygous variant was confirmed in both affected sibs, while the four healthy siblings and parents were heterozygous. The clinical features observed in the patients were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.107 C1S Bryony Thompson Classified gene: C1S as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.107 C1S Bryony Thompson Added comment: Comment on list classification: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229)
Aortopathy_Connective Tissue Disorders v0.107 C1S Bryony Thompson Gene: c1s has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.106 ELN Belinda Chong gene: ELN was added
gene: ELN was added to Aortopathy_Connective Tissue Disorders. Sources: Other
Mode of inheritance for gene: ELN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ELN were set to 27866049; 31560829; 19844261; 19844261
Phenotypes for gene: ELN were set to Cutis laxa 123700; Supravalvar aortic stenosis 185500
Review for gene: ELN was set to GREEN
Added comment: >3 families with Cutis laxa or Supravalvar aortic stenosis.

PMID: 30071989
Assertion made by the Aortopathy working group. So far there is no evidence that patients with ELN mutations present with aortic dissection or progressive aortic enlargement. Functional evidence, however, supports a role for ELN in HTAAD. ELN mutations cause AD cutis laxa syndrome, a disease with low risk for thoracic aortic disease and primarily diagnosed based on non-vascular features
Sources: Other
Ciliary Dyskinesia v0.115 NME5 Chirag Patel Mode of inheritance for gene: NME5 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.115 NME5 Chirag Patel Mode of inheritance for gene: NME5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.114 NME5 Chirag Patel Deleted their comment
Ciliary Dyskinesia v0.114 NME5 Chirag Patel edited their review of gene: NME5: Added comment: One patient with PCD with situs solitus, with radial spokes (RS) and central pair (CP) defects. Patient had a homozygous nonsense variant in NME5, with parents as carriers. Morpholino knockdown of nme5 in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy.
Sources: Literature; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.114 NME5 Chirag Patel gene: NME5 was added
gene: NME5 was added to Ciliary Dyskinesia. Sources: Literature
Mode of inheritance for gene: NME5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NME5 were set to PMID: 32185794
Phenotypes for gene: NME5 were set to Primary ciliary dyskinesia
Review for gene: NME5 was set to RED
Added comment: One patient with PCD with situs solitus, with radial spokes (RS) and central pair (CP) defects. Patient had a homozygous nonsense variant in NME5, with parents as carriers. Morpholino knockdown of nme5 in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.106 CHST14 Ain Roesley gene: CHST14 was added
gene: CHST14 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: CHST14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHST14 were set to PMID: 28306229; 25703627; 26373698
Phenotypes for gene: CHST14 were set to Ehlers-Danlos syndrome, musculocontractural type 1 (MIM# 601776)
Review for gene: CHST14 was set to GREEN
Added comment: PMID: 28306229; one of the EDS genes recognised by the International EDS Consortium

PMID: 25703627, 5 individuals from 4 families
PMID: 26373698, 7 individuals from 4 families
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.106 C1R Bryony Thompson Marked gene: C1R as ready
Aortopathy_Connective Tissue Disorders v0.106 C1R Bryony Thompson Gene: c1r has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.106 C1R Bryony Thompson Phenotypes for gene: C1R were changed from to Ehlers-Danlos syndrome, periodontal type, 1 (MIM# 130080)
Aortopathy_Connective Tissue Disorders v0.105 C1R Bryony Thompson Publications for gene: C1R were set to
Aortopathy_Connective Tissue Disorders v0.104 C1R Bryony Thompson Mode of inheritance for gene: C1R was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.104 C1R Bryony Thompson Mode of inheritance for gene: C1R was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.103 C1R Bryony Thompson Classified gene: C1R as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.103 C1R Bryony Thompson Added comment: Comment on list classification: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229)
Aortopathy_Connective Tissue Disorders v0.103 C1R Bryony Thompson Gene: c1r has been classified as Green List (High Evidence).
Congenital Heart Defect v0.50 ADAMTS19 Chirag Patel Classified gene: ADAMTS19 as Green List (high evidence)
Congenital Heart Defect v0.50 ADAMTS19 Chirag Patel Gene: adamts19 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.49 ADAMTS19 Chirag Patel reviewed gene: ADAMTS19: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32323311, 31844321; Phenotypes: Heart valve disease (HVD); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.102 B4GALT7 Bryony Thompson Marked gene: B4GALT7 as ready
Aortopathy_Connective Tissue Disorders v0.102 B4GALT7 Bryony Thompson Gene: b4galt7 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.102 B4GALT7 Bryony Thompson Classified gene: B4GALT7 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.102 B4GALT7 Bryony Thompson Gene: b4galt7 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.101 B4GALT7 Bryony Thompson gene: B4GALT7 was added
gene: B4GALT7 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: B4GALT7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B4GALT7 were set to 28306229; 26940150; 24755949; 23956117
Phenotypes for gene: B4GALT7 were set to Ehlers-Danlos syndrome with short stature and limb anomalies, 130070; Spondylodysplastic EDS
Review for gene: B4GALT7 was set to GREEN
Added comment: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229).
At least 6 families reported with compound heterozygous or homozygous variants, with a spondylodysplastic EDS phenotype.
Sources: Expert list
Aortopathy_Connective Tissue Disorders v0.100 ATP6V0A2 Ain Roesley gene: ATP6V0A2 was added
gene: ATP6V0A2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: ATP6V0A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V0A2 were set to PMID: 23963297
Phenotypes for gene: ATP6V0A2 were set to Cutis laxa, autosomal recessive, type IIA (MIM# 219200), Wrinkly skin syndrome (MIM# 278250)
Penetrance for gene: ATP6V0A2 were set to unknown
Review for gene: ATP6V0A2 was set to GREEN
Added comment: PMID: 23963297; 6 patients from 5 unrelated families with cutis laxa

PMID: 30071989; not a gene for HTAAD by clingen working group
Sources: Literature
Vascular Malformations_Germline v0.94 AKT3 Chris Richmond edited their review of gene: AKT3: Added comment: Established cause of Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (615937). Capillary malformations reported in PMID 23745724 & 22729224, both cases de novo AKT3 variants.; Changed rating: GREEN
Vascular Malformations_Germline v0.94 AKT3 Chris Richmond Deleted their comment
Aortopathy_Connective Tissue Disorders v0.100 B3GALT6 Bryony Thompson Marked gene: B3GALT6 as ready
Aortopathy_Connective Tissue Disorders v0.100 B3GALT6 Bryony Thompson Gene: b3galt6 has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.94 AKT3 Chris Richmond gene: AKT3 was added
gene: AKT3 was added to Inherited Vascular Malformations. Sources: Expert Review
Mode of inheritance for gene: AKT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AKT3 were set to 23745724; 22729224
Phenotypes for gene: AKT3 were set to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (615937)
Penetrance for gene: AKT3 were set to unknown
Mode of pathogenicity for gene: AKT3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Added comment: Established cause of Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (615937). Capillary malformations reported in PMID 23745724 & 22729224, both cases de novo AKT3 variants.
Sources: Expert Review
Aortopathy_Connective Tissue Disorders v0.100 B3GALT6 Bryony Thompson Classified gene: B3GALT6 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.100 B3GALT6 Bryony Thompson Gene: b3galt6 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.99 B3GALT6 Bryony Thompson gene: B3GALT6 was added
gene: B3GALT6 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: B3GALT6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B3GALT6 were set to 29931299; 28306229
Phenotypes for gene: B3GALT6 were set to Ehlers Danlos syndrome, progeroid type, 2, 615349; Spondylodysplastic EDS
Review for gene: B3GALT6 was set to GREEN
Added comment: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229).
In 12 patients from 9 families with EDSSPD2, 8 compound heterozygous mutations and 1 homozygous mutation in B3GALT6 were identified, including 11 missense variants, 2 frameshift variants, a deletion of 19 amino acids, and a start codon alteration (PMID: 29931299).
Sources: Expert list
Aortopathy_Connective Tissue Disorders v0.98 ADAMTS2 Bryony Thompson Marked gene: ADAMTS2 as ready
Aortopathy_Connective Tissue Disorders v0.98 ADAMTS2 Bryony Thompson Gene: adamts2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.98 ADAMTS2 Bryony Thompson Publications for gene: ADAMTS2 were set to PMID: 30071989; 26765342
Aortopathy_Connective Tissue Disorders v0.97 ADAMTS2 Bryony Thompson Classified gene: ADAMTS2 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.97 ADAMTS2 Bryony Thompson Added comment: Comment on list classification: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229)
Aortopathy_Connective Tissue Disorders v0.97 ADAMTS2 Bryony Thompson Gene: adamts2 has been classified as Green List (High Evidence).
Lymphoedema_nonsyndromic v0.6 ADAMTS3 Chris Richmond gene: ADAMTS3 was added
gene: ADAMTS3 was added to Lymphoedema_nonsyndromic. Sources: Expert Review
Mode of inheritance for gene: ADAMTS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS3 were set to 28985353, 30450763
Phenotypes for gene: ADAMTS3 were set to Hennekam lymphangiectasia-lymphedema syndrome 3 (618154)
Review for gene: ADAMTS3 was set to GREEN
Added comment: Note also in UK PanelApp nonsyndromic lymphedema list. Two papers, independent families. 30450763 paper supplies functional evidence.Should potentially add to syndromic lymphedema list also as dysmorphism reported. 28985353: in vitro and murine data that suggest a close functional interaction between ADAMTS3 and CCBE1 (an established lymphedema gene)
Sources: Expert Review
Aortopathy_Connective Tissue Disorders v0.96 NOTCH1 Paul De Fazio gene: NOTCH1 was added
gene: NOTCH1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: NOTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NOTCH1 were set to 16729972; 26820064; 16025100; 25963545
Phenotypes for gene: NOTCH1 were set to Aortic valve disease MIM# 109730
Review for gene: NOTCH1 was set to GREEN
Added comment: NOTCH1 variants are associated with cardiac abnormalities including aortic valve stenosis, a bicuspid aortic valve, coarctation of the aorta, hypoplastic left heart syndrome, and thoracic aortic aneurysms in nonsyndromic individuals (2 families in PMID:16025100; 2 individuals in PMID:16729972; 14 families in PMID:26820064). Penetrance is incomplete and not all individuals display all phenotypes (e.g. only 6/63 individuals from PMID:26820064 had thoracic aortic aneurysms).

Monoallelic NOTCH1 variants are also responsible for Adams-Oliver syndrome, which can have associated cardiac abnormalities (PMID: 25963545).
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.96 TNXB Paul De Fazio gene: TNXB was added
gene: TNXB was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: TNXB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNXB were set to 28306229; 28306225; 23620400
Phenotypes for gene: TNXB were set to Ehlers-Danlos syndrome, classic-like, 1 MIM# 606408
Review for gene: TNXB was set to GREEN
gene: TNXB was marked as current diagnostic
Added comment: Association with classic Ehlers-Danlos syndrome is well-established (PMID:28306229;28306225).

Two families have also been described with Vesicoureteral Reflux caused by a heterozygous missense variant in this gene, some individuals were reported with asymptomatic joint hypermobility (PMID:23620400)
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.96 PLOD1 Paul De Fazio gene: PLOD1 was added
gene: PLOD1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: PLOD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLOD1 were set to 28306225; 28306229
Phenotypes for gene: PLOD1 were set to Ehlers-Danlos syndrome, kyphoscoliotic type, MIM# 225400
Review for gene: PLOD1 was set to GREEN
gene: PLOD1 was marked as current diagnostic
Added comment: Review in PMID: 28306225 states: "A total of 139 mutations in PLOD1 have been identified in the 84 confirmed cases, of these there are 39 different mutations." It is included in The 2017 International Classification of the Ehlers-Danlos Syndromes (PMID: 28306229).

Medium‐sized vessel rupture has been reported in several individual case reports.
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 GAA Elena Savva gene: GAA was added
gene: GAA was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: GAA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAA were set to PMID: 29880332
Phenotypes for gene: GAA were set to Glycogen storage disease II 232300
Review for gene: GAA was set to GREEN
Added comment: PMID: 29880332 - 16 adult patients (9 families) with Pombe disease. Proximal muscle weakness (12/16) and elevated CK were reported. Muscle biopsy showed vacuoles in 4/9 patients. Patients were described as having LGMD.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 GNE Crystle Lee gene: GNE was added
gene: GNE was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: GNE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNE were set to 22883483
Phenotypes for gene: GNE were set to Nonaka myopathy (MIM#605820)
Review for gene: GNE was set to AMBER
Added comment: Primarily a distal myopathy however proximal muscle weakness have also been reported. Limited evidence supporting LGMD phenotype.

PMID: 22883483: Half the patients reported with LGMD type proximal muscle weakness.
Sources: Expert Review
Aortopathy_Connective Tissue Disorders v0.96 SLC39A13 Paul De Fazio gene: SLC39A13 was added
gene: SLC39A13 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: SLC39A13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A13 were set to 18985159; 18513683; 28306229; 28306225
Phenotypes for gene: SLC39A13 were set to Ehlers-Danlos syndrome, spondylodysplastic type, MIM# 612350
Review for gene: SLC39A13 was set to GREEN
gene: SLC39A13 was marked as current diagnostic
Added comment: 3 unrelated families described to date (PMID: 18985159;18513683). Is included in The 2017 International Classification of the Ehlers-Danlos Syndromes (PMID: 28306229). See PMID: 28306225 for a review.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.96 ALDH18A1 Ain Roesley gene: ALDH18A1 was added
gene: ALDH18A1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: ALDH18A1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ALDH18A1 were set to PMID: 30071989; 26320891; 24913064; 18478038; 21739576; 22411858; 28228640
Phenotypes for gene: ALDH18A1 were set to Cutis laxa, autosomal dominant 3 (MIM# 616603); Cutis laxa, autosomal recessive, type IIIA (MIM# 219150)
Review for gene: ALDH18A1 was set to GREEN
Added comment: PMID: 30071989; not a HTAAD gene by clingen working group

Cutis laxa, autosomal dominant 3 (MIM# 616603)

PMID: 28228640;
- Born to consanguineous parents and harbour a de novo missense p.(Arg126His). no functional done

PMID: 26320891;
- 8 unrelated individuals born to non-consanguineous families clinically diagnosed with de-barsy syndrome (DBS) or wrinkly skin syndrome. All variants occur at codon Arg138 and parental DNA from 6 probands confirmed de novo origin. (NOTE: table 1 states paternal origin however this is referring to the allele not variant (Figure S1)).
- Imaging of patients's cells showed increased accumulation of mutant protein at the mitochondrial outer membrane.
- Biochemical studies using patients' fibroblasts demonstrated LoF


Cutis laxa, autosomal recessive, type IIIA (MIM# 219150)

PMID: 24913064;
- 2 patients from consanguineous families, 1x fs (c.2131del)+ 1x 1522bp del (resulting in exon 15 del)
- clinical features like facial dysmorphism, hypotonia, adducted thumbs and cutis laxa, which are frequently found in progeroid cutis laxa syndromes. In addition, they had cardiovascular abnormalities

PMID: 18478038;
- missense c.2350C>T; p.(His784Tyr) found in a a consanguineous New Zealand Maori family with 4 affecteds.
- patients' fibroblasts showed no defect in Proline accumulation

PMID: 21739576;
This severely affected child, born to consanguineous parents of Pakistani origin, presented with lax, wrinkled and thin skin with dilated and tortuous subcutaneous blood vessels, corneal clouding, and hypotonia. The child had severe global developmental delay and feeding difficulties and died in infancy for an unknown reason. The proband was homozygous for a mutation in ALDH18A1 , c.1923 + 1G > A

PMID: 22411858;
pair of siblings chet for p.(Ser742Ile) and p.(Arg425Cys)
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.96 SMAD6 Paul De Fazio gene: SMAD6 was added
gene: SMAD6 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: SMAD6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SMAD6 were set to 22275001; 28659821; 30963242; 30848080; 30796334
Phenotypes for gene: SMAD6 were set to Aortic valve disease 2 MIM# 614823
Review for gene: SMAD6 was set to AMBER
gene: SMAD6 was marked as current diagnostic
Added comment: Missense and LOF SMAD6 variants described as pathogenic or likely pathogenic have been identified in at least 20 individuals from bicuspid aortic valve/nonsyndromic thoracic aortic aneurysm cohorts (PMID:22275001, 30848080, 28659821, 30796334).

Functional studies on two of the missense variants supported abnormal function, but a third variant did not show any functional defect (and was also not well-conserved) (PMID:22275001).

Familial segregation studies in PMID: 30796334 demonstrated reduced penetrance (82%) and variable clinical expressivity, with coarctation of the aorta being a common comorbidity.

Biallelic variants have been decribed in 2 individuals with 'complex cardiac phenotype' (including aortic isthmus stenosis, dysplastic and stenotic pulmonary valve, and dilated cardiomyopathy) (PMID: 30963242).

There appears to be a clear gene-disease relationship but I am not sure if it belongs in this panel.
Sources: Literature
Arthrogryposis v0.65 FLNC Elena Savva gene: FLNC was added
gene: FLNC was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: FLNC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FLNC were set to PMID: 29858533
Phenotypes for gene: FLNC were set to Cardiomyopathy, familial restrictive 5 617047; Myopathy, distal, 4 614065; Myopathy, myofibrillar, 5 609524
Mode of pathogenicity for gene: FLNC was set to Other
Review for gene: FLNC was set to GREEN
Added comment: Myofibrillar myopathy - LOF
Distal myopathy - GOF
Cardiomyopathy, familial hypertrophic - LOF PTCs

PMID: 29858533 - 4 patients with both restrictive cardiomyopathy and congenital myopathy. 4/4 displayed limb girdle muscle weakness, where 1/4 was mild.
3/4 also presented with arthrogryposis
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 FLNC Elena Savva gene: FLNC was added
gene: FLNC was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: FLNC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FLNC were set to PMID: 29858533
Phenotypes for gene: FLNC were set to Cardiomyopathy, familial restrictive 5 617047; Myopathy, distal, 4 614065; Myopathy, myofibrillar, 5 609524
Mode of pathogenicity for gene: FLNC was set to Other
Review for gene: FLNC was set to GREEN
Added comment: Myofibrillar myopathy - LOF
Distal myopathy - GOF
Cardiomyopathy, familial hypertrophic - LOF PTCs

PMID: 29858533 - 4 patients with both restrictive cardiomyopathy and congenital myopathy. 4/4 displayed limb girdle muscle weakness, where 1/4 was mild.
3/4 also presented with arthrogryposis
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 LAMP2 Crystle Lee gene: LAMP2 was added
gene: LAMP2 was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: LAMP2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: LAMP2 were set to 27179547; 22541782
Phenotypes for gene: LAMP2 were set to Danon disease (MIM#300257)
Review for gene: LAMP2 was set to AMBER
Added comment: Primarily presents as a cardiomyopathy condition, skeletal myopathy is less prominent and generally mild. Phenotypic overlap, proximal muscle weakness (85% of patients) (OMIM)

PMID: 27179547: 2 out of 7 affected members of 1 family presented with LGMD.

PMID: 22541782: Reported 2 patients. 1 patient presented with LGMD phenotype. EMG showed myopathic changes.
Sources: Expert Review
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 ETFDH Elena Savva gene: ETFDH was added
gene: ETFDH was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: ETFDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ETFDH were set to PMID: 19592060; 17412732
Phenotypes for gene: ETFDH were set to Glutaric acidemia IIC 231680
Review for gene: ETFDH was set to AMBER
Added comment: PMID: 19592060 - 1 adult patient reported with weakness in pelvic girdle muscles

PMID: 17412732 - 7 patients (5 families) with exercise intolerance and proximal myopathy with elevated CK levels. Onset ranged from childhood to adult-onset. Muscle histology in all five index cases revealed similar findings: moderate to severe myopathy with small vacuoles in most type 1 fibres. Patient also had subacute (3–6 months) exercise intolerance and proximal weakness affecting predominantly hip and shoulder girdle muscles.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 DOK7 Elena Savva gene: DOK7 was added
gene: DOK7 was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: DOK7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOK7 were set to PMID: 31453852; 32360404
Phenotypes for gene: DOK7 were set to Myasthenic syndrome, congenital, 10 254300
Review for gene: DOK7 was set to GREEN
Added comment: PMID: 31453852 - two adult patients with PTC variants and severe proximal muscle weakness with childhood onset. Condition is described as limb girdle myasthenia. Patient 1 had shoulder abduction and severe weakness of the pelvic girdle, patient 2 had muscle biopsy reveal muscle fibre II atrophy.

PMID: 32360404 - one adult patient with late onset atypical limb-girdle pattern of muscle weakness. Biopsy of deltoid muscle shows no features of MD.

PMID: 18626973 - 16 patients report proximal limb weakness, where 10 report neonatal onset.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 LMNA Crystle Lee gene: LMNA was added
gene: LMNA was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: LMNA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LMNA were set to 27220833; 23746545; 17377071
Phenotypes for gene: LMNA were set to Emery-Dreifuss muscular dystrophy 2, autosomal dominant (MIM#181350)
Mode of pathogenicity for gene: LMNA was set to Other
Review for gene: LMNA was set to AMBER
Added comment: Phenotypic overlap, Formerly known as Limb-girdle muscular dystrophy 1B (LGMD1B) but has been reclassified as EDMD (OMIM)

PMID: 27220833: 1 late onset patient with LGMD

PMID: 23746545: Late onset patient with severe LGMD

PMID: 17377071: Later onset phenotypes may be associated with LoF while dominant negative variants result in childhood onset disease
Sources: Expert Review
Aortopathy_Connective Tissue Disorders v0.96 ADAMTS2 Ain Roesley gene: ADAMTS2 was added
gene: ADAMTS2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: ADAMTS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS2 were set to PMID: 30071989; 26765342
Phenotypes for gene: ADAMTS2 were set to Ehlers-Danlos syndrome, dermatosparaxis type (MIM# 225410)
Review for gene: ADAMTS2 was set to GREEN
Added comment: PMID: 30071989; not a gene for HTAAD by Clingen working group

PMID: 26765342;
5 patients form 4 unrelated families (3 PTVs + 1 exon del). qPCR of total RNA demonstrated significantly reduced ADAMTS2 expression and LoF was further supported by functional assays using dermal fibroblasts.
Authors noted that Family 1 and Patient 5 are clinically milder and hypothesised that their C-term variants may lead to some transcripts escaping NMD, producing a truncated yet partially functional protein.
Figure 2 provides an additional 6 previously reported variants (2 PTVs + 4 exon dels.
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 CRYAB Elena Savva gene: CRYAB was added
gene: CRYAB was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: CRYAB was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CRYAB were set to PMID: 21337604; 32420686
Phenotypes for gene: CRYAB were set to Myopathy, myofibrillar, 2 608810; Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related 613869
Review for gene: CRYAB was set to AMBER
Added comment: PMID: 21337604 - 8 children with the same homozygous founder mutation and infantile onset muscular dystrophy. Truncal muscles reported to be more affected than limb muscles, phenotype was recapitulated in mouse models.

PMID: 32420686 - monozygotic twin boys with a heterozygous PTC mutation. Patients showed congenital hypotonia, slightly elevated CK levels. Focal signs of muscle degeneration were observed, no particular mention of the location of muscle weakness.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 DES Elena Savva gene: DES was added
gene: DES was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: DES was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: DES were set to PMID: 20718792
Phenotypes for gene: DES were set to Myopathy, myofibrillar, 1 601419
Review for gene: DES was set to AMBER
Added comment: PMID: 20718792: large review of >100 patients. >70% had myopathy or muscle weakness, 67% presented with both distal and proximal muscle weakness.
Authors note myopathy generally begins with distal limbs, progressing later in life to proximal limb involvement.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 LPIN1 Crystle Lee gene: LPIN1 was added
gene: LPIN1 was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: LPIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LPIN1 were set to 28649549; 18817903; 32410653
Phenotypes for gene: LPIN1 were set to Myoglobinuria, acute recurrent, autosomal recessive (MIM#268200)
Review for gene: LPIN1 was set to AMBER
Added comment: Biallelic variants reported in>5 families. Rhabdomyolysis is a significant feature. Patients present with muscle weakness and elevated CK. Added as a differential diagnosis to LGMD (PanelApp UK)
Sources: Expert Review
Aortopathy_Connective Tissue Disorders v0.96 ACVR1 Ain Roesley gene: ACVR1 was added
gene: ACVR1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: ACVR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACVR1 were set to PMID: 30071989; 19085907; 26776312; 18684712; 23572558; 20463014
Phenotypes for gene: ACVR1 were set to Fibrodysplasia ossificans progressiva (MIM# 135100)
Review for gene: ACVR1 was set to AMBER
Added comment: Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments.

PMID: 19085907; 112 FOP (classic and atypical) cases (104 sporadic and 8 families) with R206H has the recurrent variant and a greater clinical variability seen in non-R206H patients (PMID: 26776312)

PMID: 18684712, 23572558, 20463014; functional studies demonstrating GoF

PMID: 30071989; not a HTAAD gene by Clingen working group
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 MYH7 Crystle Lee gene: MYH7 was added
gene: MYH7 was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: MYH7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MYH7 were set to 27387980; 20733148
Phenotypes for gene: MYH7 were set to Laing distal myopathy (MIM#160500); Scapuloperoneal syndrome, myopathic type (MIM#181430)
Mode of pathogenicity for gene: MYH7 was set to Other
Review for gene: MYH7 was set to AMBER
Added comment: Associated with a spectrum of skeletal myopathies which includes a scapuloperoneal or limb-girdle muscle form.
Sources: Expert Review
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 MYOT Crystle Lee gene: MYOT was added
gene: MYOT was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: MYOT was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MYOT were set to 30055862; 21336781; 15947064
Phenotypes for gene: MYOT were set to Myopathy, myofibrillar, 3 (MIM#609200)
Review for gene: MYOT was set to AMBER
Added comment: Associated phenotype was previously known as LGMD1/LGMD1A (OMIM; PMID: 30055862). Phenotypic overlap.

PMID: 21336781: Reported a severe case of LGMD. Patient presented with late onset progressive proximal muscle weakness. CK was slightly elevated. Authors concluded that gene is a rare cause of adult onset LGMD. Variant present in gnomAD (12 hets).

PMID: 15947064: 5 variants reported in 13 patients (including 3 families). Late onset, EMG showed myopathic changes in most patients. Highest MAF (10 hets in gnomAD; Ser60Phe). 9/13 did not show elevated CK levels.
Sources: Expert Review
Aortopathy_Connective Tissue Disorders v0.96 ZNF469 Paul De Fazio edited their review of gene: ZNF469: Changed phenotypes: Brittle cornea syndrome 1 MIM# 229200
Aortopathy_Connective Tissue Disorders v0.96 ZNF469 Paul De Fazio gene: ZNF469 was added
gene: ZNF469 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: ZNF469 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF469 were set to 28306229; 28306225
Phenotypes for gene: ZNF469 were set to Brittle cornea syndrome 1
Review for gene: ZNF469 was set to GREEN
gene: ZNF469 was marked as current diagnostic
Added comment: Association with brittle cornea syndrome (BCS) is well-established. 32 patients with variants in ZNF469 and BCS are reviewed in PMID: 28306225.

BCS is classified as a form of Ehlers-Danlos syndrome (PMID: 28306229).
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.96 ABCC6 Ain Roesley gene: ABCC6 was added
gene: ABCC6 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: ABCC6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCC6 were set to PMID: 30071989; 11536079
Phenotypes for gene: ABCC6 were set to Pseudoxanthoma elasticum (MIM# 264800)
Review for gene: ABCC6 was set to AMBER
Added comment: PMID: 30071989; not a gene for Heritable Thoracic Aortic Aneurysm and Dissection by Clingen Working Group

PMID: 11536079; a cohort of 122 PXE patients were sequenced and 36 different variants were reported
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 ORAI1 Crystle Lee gene: ORAI1 was added
gene: ORAI1 was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: ORAI1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ORAI1 were set to 31448844
Phenotypes for gene: ORAI1 were set to Myopathy, tubular aggregate, 2 (MIM#615883)
Review for gene: ORAI1 was set to AMBER
Added comment: OMIM notes both proximal and diffuse muscle weakness. There is some phenotypic overlap.

PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence): - Dominant ORAI1 missense variants via a GOF mechanism cause a slowly progressive myopathy (tubular aggregate myopathy/TAM)
Sources: Expert Review
Mendeliome v0.3185 MCM3AP Eleanor Williams changed review comment from: PMID: 32202298 - Woldegebriel et al - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.; to: PMID: 32202298 - Woldegebriel et al 2020 - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.
Mendeliome v0.3185 MCM3AP Eleanor Williams reviewed gene: MCM3AP: Rating: ; Mode of pathogenicity: None; Publications: 32202298; Phenotypes: peripheral neuropathy with or without impaired intellectual development MIM#618124; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3185 SP6 Eleanor Williams gene: SP6 was added
gene: SP6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SP6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SP6 were set to 32167558; 18156176; 18297738; 22676574
Phenotypes for gene: SP6 were set to hypoplastic amelogenesis imperfecta
Review for gene: SP6 was set to AMBER
Added comment: PMID: 32167558 - Smith et al 2020 - report a 2 bp variant c.817_818GC>AA in SP6 in a Caucasian family with autosomal dominant hypoplastic AI which results in a missense change. Report that mice and rat knockouts also show a dental phenotype (PMID: 18156176, 18297738, 22676574 )
Sources: Literature
Mendeliome v0.3185 TBX5 Eleanor Williams reviewed gene: TBX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 31373354; Phenotypes: Holt-Oram syndrome; Mode of inheritance: None
Eye Anterior Segment Abnormalities v0.8 PAX6 Zornitza Stark Marked gene: PAX6 as ready
Eye Anterior Segment Abnormalities v0.8 PAX6 Zornitza Stark Gene: pax6 has been classified as Green List (High Evidence).
Eye Anterior Segment Abnormalities v0.8 PAX6 Zornitza Stark Phenotypes for gene: PAX6 were changed from to Aniridia MIM# 106210; Anterior segment dysgenesis 5, multiple subtypes MIM# 6042293; Cataract with late-onset corneal dystrophy MIM# 106210; Foveal hypoplasia 1 MIM# 136520; Keratitis MIM# 148190; Optic nerve hypoplasia MIM# 165550
Eye Anterior Segment Abnormalities v0.7 PAX6 Zornitza Stark Publications for gene: PAX6 were set to
Eye Anterior Segment Abnormalities v0.6 PAX6 Zornitza Stark Mode of inheritance for gene: PAX6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3185 MYH8 Zornitza Stark Marked gene: MYH8 as ready
Mendeliome v0.3185 MYH8 Zornitza Stark Added comment: Comment when marking as ready: Recurrent variant p.R674Q has occurred de novo in at least some families.
Mendeliome v0.3185 MYH8 Zornitza Stark Gene: myh8 has been classified as Green List (High Evidence).
Mendeliome v0.3185 MYH8 Zornitza Stark Phenotypes for gene: MYH8 were changed from to Trismus-pseudocamptodactyly syndrome MIM# 158300; Carney complex variant MIM# 608837
Mendeliome v0.3184 MYH8 Zornitza Stark Publications for gene: MYH8 were set to
Mendeliome v0.3183 MYH8 Zornitza Stark Mode of inheritance for gene: MYH8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cutis Laxa v0.5 ATP6V1A Bryony Thompson Marked gene: ATP6V1A as ready
Cutis Laxa v0.5 ATP6V1A Bryony Thompson Gene: atp6v1a has been classified as Green List (High Evidence).
Cutis Laxa v0.5 ATP6V1A Bryony Thompson Classified gene: ATP6V1A as Green List (high evidence)
Cutis Laxa v0.5 ATP6V1A Bryony Thompson Gene: atp6v1a has been classified as Green List (High Evidence).
Cutis Laxa v0.4 ATP6V1A Bryony Thompson gene: ATP6V1A was added
gene: ATP6V1A was added to Cutis Laxa. Sources: Literature
Mode of inheritance for gene: ATP6V1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V1A were set to 28065471
Phenotypes for gene: ATP6V1A were set to Cutis laxa, autosomal recessive, type IID MIM#617403
Review for gene: ATP6V1A was set to GREEN
Added comment: 3 unrelated consanguineous families homozygous for 2 different missense variants (G72D, R338C), with supportive molecular analyses of patient cells.
Sources: Literature
Cutis Laxa v0.3 ATP6V1E1 Bryony Thompson Marked gene: ATP6V1E1 as ready
Cutis Laxa v0.3 ATP6V1E1 Bryony Thompson Gene: atp6v1e1 has been classified as Green List (High Evidence).
Cutis Laxa v0.3 ATP6V1E1 Bryony Thompson Classified gene: ATP6V1E1 as Green List (high evidence)
Cutis Laxa v0.3 ATP6V1E1 Bryony Thompson Gene: atp6v1e1 has been classified as Green List (High Evidence).
Cutis Laxa v0.2 ATP6V1E1 Bryony Thompson gene: ATP6V1E1 was added
gene: ATP6V1E1 was added to Cutis Laxa. Sources: Expert list
Mode of inheritance for gene: ATP6V1E1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V1E1 were set to 28065471; 27023906
Phenotypes for gene: ATP6V1E1 were set to Cutis laxa, autosomal recessive, type IIC MIM#617402
Review for gene: ATP6V1E1 was set to GREEN
Added comment: 3 unrelated consanguineous families homozygous for 2 different missense variants (L128P, R212W) with paediatric onset cutis laxa. Molecular anlayses of patient tissues was supportive.
Sources: Expert list
Mendeliome v0.3182 MYH8 Teresa Zhao reviewed gene: MYH8: Rating: GREEN; Mode of pathogenicity: Other; Publications: 28377322, 18049072, 17041932; Phenotypes: Trismus-pseudocamptodactyly syndrome MIM# 158300, Carney complex variant MIM# 608837; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Eye Anterior Segment Abnormalities v0.5 PAX6 Teresa Zhao changed review comment from: Loss of function is a well established mechanism.

This protein consists of paried domain (PD), which consists of N-terminal sub-domain (PAI domain), homeodomain (HD) and C-terminal sub-domain (RED domain) (PMID: 26899008).

Exon 5a of 14 additional aa is inserted into N-terminal sub-domain abolishes the DNA-binding ability of C-terminal sub-domain and functions as a molecular switch that selects and spedifies target genes (PMID: 20132240).

PAX6 has two isoforms, a and b, they cooperatively act in the development of both the posterior and anterior segment of the eye by regulating different gens (PMID: 26899008).
isoform a: induces KRT3 expression.
isoform b: indluced KRT12 expression when combined with KLF4 and OCT4.; to: Loss of function is a well established mechanism.

This protein consists of paried domain (PD), which consists of N-terminal sub-domain (PAI domain), homeodomain (HD) and C-terminal sub-domain (RED domain) (PMID: 26899008).

Exon 5a of 14 additional aa is inserted into N-terminal sub-domain abolishes the DNA-binding ability of C-terminal sub-domain and functions as a molecular switch that selects and spedifies target genes (PMID: 20132240).

PAX6 has two isoforms, a and b, they cooperatively act in the development of both the posterior and anterior segment of the eye by regulating different genes (PMID: 26899008).
isoform a: induces KRT3 expression.
isoform b: indluced KRT12 expression when combined with KLF4 and OCT4.
Eye Anterior Segment Abnormalities v0.5 PAX6 Teresa Zhao reviewed gene: PAX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 27081561, 20132240, 26899008; 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# 6042293, 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, imprinted status unknown
Ataxia - adult onset v0.61 CACNB4 Bryony Thompson Marked gene: CACNB4 as ready
Ataxia - adult onset v0.61 CACNB4 Bryony Thompson Gene: cacnb4 has been classified as Red List (Low Evidence).
Ataxia - adult onset v0.61 CACNB4 Bryony Thompson Mode of inheritance for gene: CACNB4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia - adult onset v0.60 CACNB4 Bryony Thompson Classified gene: CACNB4 as Red List (low evidence)
Ataxia - adult onset v0.60 CACNB4 Bryony Thompson Gene: cacnb4 has been classified as Red List (Low Evidence).
Episodic Ataxia v0.15 Bryony Thompson Panel status changed from internal to public
Episodic Ataxia v0.13 UBR4 Bryony Thompson Classified gene: UBR4 as Amber List (moderate evidence)
Episodic Ataxia v0.13 UBR4 Bryony Thompson Gene: ubr4 has been classified as Amber List (Moderate Evidence).
Ataxia - adult onset v0.58 SLC1A3 Bryony Thompson Classified gene: SLC1A3 as Green List (high evidence)
Ataxia - adult onset v0.58 SLC1A3 Bryony Thompson Gene: slc1a3 has been classified as Green List (High Evidence).
Ataxia - adult onset v0.57 SLC1A3 Bryony Thompson gene: SLC1A3 was added
gene: SLC1A3 was added to Ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: SLC1A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SLC1A3 were set to Episodic ataxia, type 6 MIM#612656
Review for gene: SLC1A3 was set to GREEN
Added comment: Onset mostly in infancy and childhood, but adult onset has been reported
Sources: Literature
Episodic Ataxia v0.12 SLC1A3 Bryony Thompson Marked gene: SLC1A3 as ready
Episodic Ataxia v0.12 SLC1A3 Bryony Thompson Gene: slc1a3 has been classified as Green List (High Evidence).
Episodic Ataxia v0.12 SLC1A3 Bryony Thompson Classified gene: SLC1A3 as Green List (high evidence)
Episodic Ataxia v0.12 SLC1A3 Bryony Thompson Gene: slc1a3 has been classified as Green List (High Evidence).
Episodic Ataxia v0.11 SLC1A3 Bryony Thompson Publications for gene: SLC1A3 were set to
Episodic Ataxia v0.10 SLC1A3 Bryony Thompson reviewed gene: SLC1A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116111, 23107647, 19139306, 29741614, 25497598, 29208948, 29062094; Phenotypes: Episodic ataxia, type 6 MIM#612656; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Episodic Ataxia v0.10 CACNB4 Bryony Thompson Marked gene: CACNB4 as ready
Episodic Ataxia v0.10 CACNB4 Bryony Thompson Gene: cacnb4 has been classified as Red List (Low Evidence).
Episodic Ataxia v0.10 CACNB4 Bryony Thompson reviewed gene: CACNB4: Rating: RED; Mode of pathogenicity: None; Publications: 10762541, 9039265; Phenotypes: Episodic ataxia, type 5 MIM#613855; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Episodic Ataxia v0.10 FGF14 Bryony Thompson Marked gene: FGF14 as ready
Episodic Ataxia v0.10 FGF14 Bryony Thompson Gene: fgf14 has been classified as Green List (High Evidence).
Episodic Ataxia v0.10 FGF14 Bryony Thompson Classified gene: FGF14 as Green List (high evidence)
Episodic Ataxia v0.10 FGF14 Bryony Thompson Gene: fgf14 has been classified as Green List (High Evidence).
Episodic Ataxia v0.9 FGF14 Bryony Thompson reviewed gene: FGF14: Rating: GREEN; Mode of pathogenicity: None; Publications: 32162847; Phenotypes: Episodic ataxia, Paroxysmal dyskinesia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3182 SKIV2L Sarah Leigh reviewed gene: SKIV2L: Rating: AMBER; Mode of pathogenicity: None; Publications: 29334452; Phenotypes: Intellectual disability; Mode of inheritance: None
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 PFKM Zornitza Stark Marked gene: PFKM as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 PFKM Zornitza Stark Added comment: Comment when marking as ready: Some phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 PFKM Zornitza Stark Gene: pfkm has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 PFKM Zornitza Stark Classified gene: PFKM as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 PFKM Zornitza Stark Gene: pfkm has been classified as Amber List (Moderate Evidence).
Glycogen Storage Diseases v0.11 PFKM Zornitza Stark Marked gene: PFKM as ready
Glycogen Storage Diseases v0.11 PFKM Zornitza Stark Gene: pfkm has been classified as Green List (High Evidence).
Glycogen Storage Diseases v0.11 PFKM Zornitza Stark Phenotypes for gene: PFKM were changed from to Glycogen storage disease VII (MIM#232800)
Glycogen Storage Diseases v0.10 PFKM Zornitza Stark Publications for gene: PFKM were set to
Glycogen Storage Diseases v0.9 PFKM Zornitza Stark Mode of inheritance for gene: PFKM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.34 POMK Zornitza Stark Marked gene: POMK as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.34 POMK Zornitza Stark Gene: pomk has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.34 POMK Zornitza Stark Publications for gene: POMK were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.33 POMK Zornitza Stark Classified gene: POMK as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.33 POMK Zornitza Stark Gene: pomk has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.32 CAV3 Zornitza Stark Marked gene: CAV3 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.32 CAV3 Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.32 CAV3 Zornitza Stark Gene: cav3 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.32 CAV3 Zornitza Stark Classified gene: CAV3 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.32 CAV3 Zornitza Stark Gene: cav3 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.31 PYGM Zornitza Stark Marked gene: PYGM as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.31 PYGM Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.31 PYGM Zornitza Stark Gene: pygm has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.31 PYGM Zornitza Stark Classified gene: PYGM as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.31 PYGM Zornitza Stark Gene: pygm has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.30 CASQ1 Zornitza Stark Marked gene: CASQ1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.30 CASQ1 Zornitza Stark Added comment: Comment when marking as ready: Founder variant, but large number of affected individuals reported. Italian, rather than rare, isolated ethnicity.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.30 CASQ1 Zornitza Stark Gene: casq1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.30 CASQ1 Zornitza Stark Classified gene: CASQ1 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.30 CASQ1 Zornitza Stark Gene: casq1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.29 CASQ1 Zornitza Stark Tag founder tag was added to gene: CASQ1.
Mendeliome v0.3182 CACNB1 Zornitza Stark Marked gene: CACNB1 as ready
Mendeliome v0.3182 CACNB1 Zornitza Stark Gene: cacnb1 has been classified as Red List (Low Evidence).
Mendeliome v0.3182 CACNB1 Zornitza Stark gene: CACNB1 was added
gene: CACNB1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CACNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNB1 were set to 27832566; 8943043; 29212769
Phenotypes for gene: CACNB1 were set to Malignant hyperthermia susceptibility
Added comment: A single heterozygous case with a positive IVCT muscle biopsy has been reported with p.Val156Ala. The European non-Finnish allele frequency in gnomAD v2.1 is 0.001146 (148/129,118 alleles), which is higher than the expected population frequency for dominantly inherited malignant hyperthermia (0.1%). Additionally, functional assays of this variant, suggest it would only significantly affect function in the homozygous state (suggesting a recessive condition).
Sources: Expert list
Skeletal Muscle Channelopathies v0.6 CACNB1 Zornitza Stark Marked gene: CACNB1 as ready
Skeletal Muscle Channelopathies v0.6 CACNB1 Zornitza Stark Gene: cacnb1 has been classified as Red List (Low Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.29 PYROXD1 Zornitza Stark Publications for gene: PYROXD1 were set to 30515627
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.28 PYROXD1 Zornitza Stark Marked gene: PYROXD1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.28 PYROXD1 Zornitza Stark Added comment: Comment when marking as ready: Mostly myopathy, some families reported with LGMD phenotype.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.28 PYROXD1 Zornitza Stark Gene: pyroxd1 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.28 PYROXD1 Zornitza Stark Classified gene: PYROXD1 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.28 PYROXD1 Zornitza Stark Gene: pyroxd1 has been classified as Amber List (Moderate Evidence).
Arrhythmogenic Cardiomyopathy v0.9 BVES Zornitza Stark Marked gene: BVES as ready
Arrhythmogenic Cardiomyopathy v0.9 BVES Zornitza Stark Gene: bves has been classified as Amber List (Moderate Evidence).
Arrhythmogenic Cardiomyopathy v0.9 BVES Zornitza Stark Publications for gene: BVES were set to PMID: 26642364; 31119192
Arrhythmogenic Cardiomyopathy v0.8 BVES Zornitza Stark Classified gene: BVES as Amber List (moderate evidence)
Arrhythmogenic Cardiomyopathy v0.8 BVES Zornitza Stark Gene: bves has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.27 BVES Zornitza Stark Marked gene: BVES as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.27 BVES Zornitza Stark Gene: bves has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.27 BVES Zornitza Stark Publications for gene: BVES were set to PMID: 26642364 32528171 31119192
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.26 BVES Zornitza Stark Classified gene: BVES as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.26 BVES Zornitza Stark Gene: bves has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.25 BAG3 Zornitza Stark Marked gene: BAG3 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.25 BAG3 Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.25 BAG3 Zornitza Stark Gene: bag3 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.25 BAG3 Zornitza Stark Classified gene: BAG3 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.25 BAG3 Zornitza Stark Gene: bag3 has been classified as Green List (High Evidence).
Skeletal Muscle Channelopathies v0.6 ATP2A1 Zornitza Stark Marked gene: ATP2A1 as ready
Skeletal Muscle Channelopathies v0.6 ATP2A1 Zornitza Stark Gene: atp2a1 has been classified as Green List (High Evidence).
Skeletal Muscle Channelopathies v0.6 KCNJ5 Zornitza Stark Marked gene: KCNJ5 as ready
Skeletal Muscle Channelopathies v0.6 KCNJ5 Zornitza Stark Gene: kcnj5 has been classified as Red List (Low Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.24 ACTA1 Zornitza Stark Marked gene: ACTA1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.24 ACTA1 Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.24 ACTA1 Zornitza Stark Gene: acta1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.24 ACTA1 Zornitza Stark Publications for gene: ACTA1 were set to PMID: 28606400; 25938801
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.23 ACTA1 Zornitza Stark Phenotypes for gene: ACTA1 were changed from ?Myopathy, scapulohumeroperoneal 616852 to Myopathy, scapulohumeroperoneal 616852
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.22 ACTA1 Zornitza Stark Classified gene: ACTA1 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.22 ACTA1 Zornitza Stark Gene: acta1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.52 SELENON Zornitza Stark Marked gene: SELENON as ready
Muscular dystrophy and myopathy_Paediatric v0.52 SELENON Zornitza Stark Gene: selenon has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.52 SELENON Zornitza Stark Phenotypes for gene: SELENON were changed from to Muscular dystrophy, rigid spine, 1 (MIM#602771)
Muscular dystrophy and myopathy_Paediatric v0.51 SELENON Zornitza Stark Publications for gene: SELENON were set to
Muscular dystrophy and myopathy_Paediatric v0.50 SELENON Zornitza Stark Mode of inheritance for gene: SELENON was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.50 SELENON Zornitza Stark Mode of inheritance for gene: SELENON was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.49 SELENON Zornitza Stark Mode of inheritance for gene: SELENON was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.21 ACADVL Zornitza Stark Marked gene: ACADVL as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.21 ACADVL Zornitza Stark Added comment: Comment when marking as ready: Some phenotypic overlap in view of reports of raised CK, and some individuals having clinical diagnosis of LGMD.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.21 ACADVL Zornitza Stark Gene: acadvl has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.21 ACADVL Zornitza Stark Classified gene: ACADVL as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.21 ACADVL Zornitza Stark Gene: acadvl has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.20 STIM1 Zornitza Stark reviewed gene: STIM1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy, tubular aggregate, 1 (MIM#160565), Stormorken syndrome (MIM#185070); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.20 STIM1 Zornitza Stark Marked gene: STIM1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.20 STIM1 Zornitza Stark Gene: stim1 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.20 STIM1 Zornitza Stark Classified gene: STIM1 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.20 STIM1 Zornitza Stark Gene: stim1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3181 GATA6 Zornitza Stark Marked gene: GATA6 as ready
Mendeliome v0.3181 GATA6 Zornitza Stark Gene: gata6 has been classified as Green List (High Evidence).
Mendeliome v0.3181 GATA6 Zornitza Stark Phenotypes for gene: GATA6 were changed from to Pancreatic agenesis and congenital heart defects, 600001; Atrial septal defect 9, 614475; Atrioventricular septal defect 5, 614474; Tetralogy of Fallot, 187500; Persistent truncus arteriosus, 217095
Mendeliome v0.3180 GATA6 Zornitza Stark Publications for gene: GATA6 were set to
Mendeliome v0.3179 GATA6 Zornitza Stark Mode of pathogenicity for gene: GATA6 was changed from to Other
Mendeliome v0.3178 GATA6 Zornitza Stark Mode of inheritance for gene: GATA6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.19 VMA21 Zornitza Stark Marked gene: VMA21 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.19 VMA21 Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap with LGMD.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.19 VMA21 Zornitza Stark Gene: vma21 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.19 VMA21 Zornitza Stark Classified gene: VMA21 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.19 VMA21 Zornitza Stark Gene: vma21 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 VMA21 Zornitza Stark Tag deep intronic tag was added to gene: VMA21.
Episodic Ataxia v0.9 UBR4 Bryony Thompson gene: UBR4 was added
gene: UBR4 was added to Episodic Ataxia. Sources: Literature
Mode of inheritance for gene: UBR4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: UBR4 were set to Episodic ataxia type 8
Episodic Ataxia v0.8 SLC1A3 Bryony Thompson gene: SLC1A3 was added
gene: SLC1A3 was added to Episodic Ataxia. Sources: Expert list
Mode of inheritance for gene: SLC1A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SLC1A3 were set to Episodic ataxia, type 6 MIM#612656
Episodic Ataxia v0.7 FGF14 Bryony Thompson gene: FGF14 was added
gene: FGF14 was added to Episodic Ataxia. Sources: Literature
Mode of inheritance for gene: FGF14 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGF14 were set to 32162847
Phenotypes for gene: FGF14 were set to Episodic Ataxia type 9
Episodic Ataxia v0.6 CACNB4 Bryony Thompson gene: CACNB4 was added
gene: CACNB4 was added to Episodic Ataxia. Sources: Expert list
Mode of inheritance for gene: CACNB4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CACNB4 were set to Episodic ataxia, type 5 MIM#613855
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 PFKM Crystle Lee gene: PFKM was added
gene: PFKM was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: PFKM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PFKM were set to 24427140; 27066546; 30792690
Phenotypes for gene: PFKM were set to Glycogen storage disease VII (MIM#232800)
Review for gene: PFKM was set to AMBER
Added comment: Metabolic myopathy gene due to accumulation of glycogen in muscle tissue. Unsure if consisten with LGMD phenotype.

PMID: 24427140: Adult patient reported with lifelong muscle weakness.

PMID: 27066546: 2 siblings reported with glycogen storage disease. Juvenile onset exercise intolerance. Muscle biopsy showed myopathic changes in both siblings.

PMID: 30792690: 1 adult patient reported, onset at 33. Presented with mild proximal muscle weakness, mainly in the lower limbs.
Sources: Expert Review
Glycogen Storage Diseases v0.8 PFKM Crystle Lee reviewed gene: PFKM: Rating: GREEN; Mode of pathogenicity: None; Publications: 24427140, 27066546, 30792690; Phenotypes: Glycogen storage disease VII (MIM#232800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 POMK Crystle Lee reviewed gene: POMK: Rating: AMBER; Mode of pathogenicity: None; Publications: 24556084, 24925318, 29910097; Phenotypes: Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 12 (MIM#616094); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Episodic Ataxia v0.5 CACNA1A Bryony Thompson Classified gene: CACNA1A as Green List (high evidence)
Episodic Ataxia v0.5 CACNA1A Bryony Thompson Gene: cacna1a has been classified as Green List (High Evidence).
Episodic Ataxia v0.4 CACNA1A Bryony Thompson gene: CACNA1A was added
gene: CACNA1A was added to Episodic Ataxia. Sources: Expert list
Mode of inheritance for gene: CACNA1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CACNA1A were set to Episodic ataxia, type 2 MIM#108500
Episodic Ataxia v0.3 KCNA1 Bryony Thompson Phenotypes for gene: KCNA1 were changed from Episodic ataxia/myokymia syndrome MIM#160120 to Episodic ataxia/myokymia syndrome MIM#160120; EA1
Episodic Ataxia v0.2 KCNA1 Bryony Thompson Classified gene: KCNA1 as Green List (high evidence)
Episodic Ataxia v0.2 KCNA1 Bryony Thompson Gene: kcna1 has been classified as Green List (High Evidence).
Episodic Ataxia v0.1 KCNA1 Bryony Thompson gene: KCNA1 was added
gene: KCNA1 was added to Episodic Ataxia. Sources: Expert list
Mode of inheritance for gene: KCNA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KCNA1 were set to Episodic ataxia/myokymia syndrome MIM#160120
Episodic Ataxia v0.0 Bryony Thompson Added Panel Episodic Ataxia
Set panel types to: Royal Melbourne Hospital; Rare Disease
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 CAV3 Elena Savva gene: CAV3 was added
gene: CAV3 was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: CAV3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAV3 were set to PMID: 27312022; 26185955; 32090499
Phenotypes for gene: CAV3 were set to Myopathy, distal, Tateyama type 614321; Rippling muscle disease 2 606072
Review for gene: CAV3 was set to AMBER
Added comment: PMID: 27312022 - 8 patients (7 families) with exercise intolerance (7/8), muscle atrophy (2/8) and rhabdomyolysis (2/8). Functional studies show a 50% reduction in protein from patient cells vs controls. Age at onset ranged from 7 years old to 30s, with 3/8 patients presenting <18 years of age.

PMID: 26185955 - 2 patients with muscle hypertrophy
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 PYGM Crystle Lee gene: PYGM was added
gene: PYGM was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: PYGM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYGM were set to 29143597; 25914343
Phenotypes for gene: PYGM were set to McArdle disease (MIM#232600)
Review for gene: PYGM was set to AMBER
Added comment: Well established gene disease association. McArdle disease is "one of the most frequent metabolic myopathies". Included in this panel as a differential diagnosis to LGMD (PanelApp Uk)
Sources: Expert Review
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 CASQ1 Elena Savva gene: CASQ1 was added
gene: CASQ1 was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: CASQ1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CASQ1 were set to PMID: 26136523; 30258016
Phenotypes for gene: CASQ1 were set to Myopathy, vacuolar, with CASQ1 aggregates 616231
Review for gene: CASQ1 was set to GREEN
Added comment: PMID: 26136523 - 3 unrelated families (10 patients) with a founder missense (p.Asp244Gly) with muscle weaknesses. All patients reported adult onset. 1 proband reported lower limb hypertrophy with normal EMG results. 6 patients had muscle biopsy, with minimal fibre size variation, and a few central nuclei.

PMID: 30258016 - 12 families (22 patients), or which 21 had the recurring p.Asp244Gly mutation. Patients all had adult onset, elevated CK, with slowly progressive proximal weakness with quadriceps atrophy and scapular winging. Pelvic girdle weakness was reported in 4/22 patients.
Sources: Expert list
Skeletal Muscle Channelopathies v0.6 CACNB1 Bryony Thompson Classified gene: CACNB1 as Red List (low evidence)
Skeletal Muscle Channelopathies v0.6 CACNB1 Bryony Thompson Gene: cacnb1 has been classified as Red List (Low Evidence).
Skeletal Muscle Channelopathies v0.5 CACNB1 Bryony Thompson reviewed gene: CACNB1: Rating: RED; Mode of pathogenicity: None; Publications: 27832566, 8943043, 29212769; Phenotypes: Malignant hyperthermia; Mode of inheritance: Unknown
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 PYROXD1 Crystle Lee reviewed gene: PYROXD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30345904, 30515627, 27745833; Phenotypes: Myopathy, myofibrillar, 8 (MIM#617258); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arrhythmogenic Cardiomyopathy v0.7 BVES Elena Savva gene: BVES was added
gene: BVES was added to Arrhythmogenic Right Ventricular Cardiomyopathy. Sources: Literature
Mode of inheritance for gene: BVES was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BVES were set to PMID: 26642364; 31119192
Phenotypes for gene: BVES were set to Muscular dystrophy, limb-girdle, autosomal recessive 25 616812
Review for gene: BVES was set to AMBER
Added comment: OMIM: aka POPDC1

PMID: 26642364 - 1 family (3 affecteds) with cardiac arrhythmia and limb-girdle muscular dystrophy. Supported by functional studies. The proband showed lower limb girdle weakness at ~40 years old with muscle biopsy proving dystrophic changes. His 2 affected grandchildren had onset in teenage years.

PMID: 31119192 - 3 families (4 affecteds) with limb-girdle muscular weakness and cardiac abnormalities/arrhythmia. All had onset in adulthood, with exercise intolerance or proximal weakness.

Summary: multiple reports of patients with arrhythmias
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 BVES Elena Savva gene: BVES was added
gene: BVES was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: BVES was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BVES were set to PMID: 26642364 32528171 31119192
Phenotypes for gene: BVES were set to Muscular dystrophy, limb-girdle, autosomal recessive 25 616812
Review for gene: BVES was set to GREEN
Added comment: OMIM: aka POPDC1

PMID: 26642364 - 1 family (3 affecteds) with cardiac arrhythmia and limb-girdle muscular dystrophy. Supported by functional studies. The proband showed lower limb girdle weakness at ~40 years old with muscle biopsy proving dystrophic changes. His 2 affected grandchildren had onset in teenage years.

PMID: 32528171 - 1 patient with limb girdle weakness.

PMID: 31119192 - 3 families (4 affecteds) with limb-girdle muscular weakness and cardiac abnormalities/arrhythmia. All had onset in adulthood, with exercise intolerance or proximal weakness.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 BAG3 Elena Savva gene: BAG3 was added
gene: BAG3 was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: BAG3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BAG3 were set to PMID: 25208129; 22734908; 30061062
Phenotypes for gene: BAG3 were set to Myopathy, myofibrillar, 6 612954
Review for gene: BAG3 was set to GREEN
Added comment: OMIM notes onset is in late childhood to early teens. Mutation p.Pro209Leu is recurring.

PMID: 25208129 - 1 heterozygous patient with lower limb weakness and onset at 34 years.

PMID: 22734908 - 4 patients with heterozygous mutations.
Patient 1 - onset at 13 years old with lumbar spine rigidity, finger flexion constractures and distal wasting in upper/lower limbs.
Patient 2 - onset 8 years old with muscle stiffness in lower limbs and distal wasting at 12 years old.
Patient 3 - lower limb deformity at 7 years old with declining mobility by 11 years of age.
Patient 4 - Unknown onset but wheelchair bound by 14 years old.

PMID: 30061062 - 1 patient with a de novo mutation, and childhood onset proximal muscle weakness and atrophy, with elevated CK.
Sources: Expert list
Skeletal Muscle Channelopathies v0.5 ATP2A1 Bryony Thompson Publications for gene: ATP2A1 were set to
Skeletal Muscle Channelopathies v0.4 KCNJ5 Bryony Thompson gene: KCNJ5 was added
gene: KCNJ5 was added to Skeletal Muscle Channelopathies. Sources: Expert list
Mode of inheritance for gene: KCNJ5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ5 were set to 24574546
Phenotypes for gene: KCNJ5 were set to Andersen-Tawil Syndrome; periodic muscle paralysis
Review for gene: KCNJ5 was set to RED
Added comment: Only a single Japanese case with periodic muscle paralysis with no dysmorphic features, reported with the missense variant p.Gly387Arg. In vitro functional expression studies in Xenopus oocytes showed that coexpression of KCNJ2 with mutant KCNJ5 significantly reduced the inwardly rectifying potassium current compared to that observed with coexpression of KCNJ2 with wildtype KCNJ5. However, the East Asian allele frequency for this variant in gnomAD v2.1 is 0.00251 (50/19,924 alleles). Which is higher than would be expected for a dominantly inherited disorder.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 ACTA1 Elena Savva gene: ACTA1 was added
gene: ACTA1 was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: ACTA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ACTA1 were set to PMID: 28606400; 25938801
Phenotypes for gene: ACTA1 were set to ?Myopathy, scapulohumeroperoneal 616852
Review for gene: ACTA1 was set to GREEN
Added comment: PMID: 28606400 - 1 multigenerational family with dominant ACTA1-scapuloperoneal
myopathy. Proband has progressive limb weakness since childhood, spinal muscular atrophy based on two EMG analyses. Affected carrier children also reported upper limb weakness with onset in chlidhood/teenage years.

PMID: 25938801 - 1 large family (14 affecteds) with dominant ACTA1-scapuloperoneal myopathy. Muscle biopsy specimens demonstrated type I fiber atrophy. Many reported upper and lower body muscle weakness, with age of onset variable between early childhood and adulthood.

PMID: 15832616 - 1 child with a de novo missense mutation, proximal muscle weakness and hypotonia of the shoulder girdle
Sources: Expert list
Muscular dystrophy and myopathy_Paediatric v0.48 SELENON Crystle Lee reviewed gene: SELENON: Rating: GREEN; Mode of pathogenicity: None; Publications: 11528383; Phenotypes: Muscular dystrophy, rigid spine, 1 (MIM#602771); Mode of inheritance: None
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 ACADVL Elena Savva gene: ACADVL was added
gene: ACADVL was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: ACADVL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACADVL were set to PMID: 9546340; 32558070; 22097235; 24305961
Phenotypes for gene: ACADVL were set to VLCAD deficiency 201475
Review for gene: ACADVL was set to AMBER
Added comment: PMID: 9546340 - 4/15 patients developed elevated CK levels and rhabdomyolysis within the first year of life. No mention of myopathy or specific dystrophic features.

PMID: 32558070 - 6 unrelated patients with adult-onset VLCAD deficiency. 4/6 had muscle weakness of the neck flexion, arms abduction and elbow flexion. CK levels varied among the patients, though most were elevated.
Four patients had an EMG showed myopathic changes of the upper and lower limbs, one did not report muscle weakness.
Only 1/6 patients were reported with significant changes on muscle MRI.

PMID: 22097235 - One 18 year old patient with persistent muscle cramps, elevated CK levels. Patient was diagnosed with limb girdle MD, at 21 years old struggled to climb stairs or walk

PMID: 24305961 - 8/12 patients reported either muscle pain and/or exercise intolerance, 9/12 had elevated CK levels. VLCADD patients showed predominantly proximal T1W SI changes.

Summary: dystrophic changes have been reported but does not appear to be a common feature
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 STIM1 Crystle Lee gene: STIM1 was added
gene: STIM1 was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: STIM1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: STIM1 were set to 31448844
Phenotypes for gene: STIM1 were set to Myopathy, tubular aggregate, 1 (MIM#160565); Stormorken syndrome (MIM#185070)
Mode of pathogenicity for gene: STIM1 was set to Other
Review for gene: STIM1 was set to GREEN
Added comment: Dominant STIM1 missense variants via a GOF mechanism cause a spectrum of myopathy covering tubular aggregate myopathy/TAM and Stormorken syndrome/STRMK (slowly progressive muscle weakness with variable multisystemic disease including non-specific dysmorphism, a/hyposplenia, ichthyosis, cytopenias)

PMID: 31448844: Review article. Dominant STIM1 missense variants exert gain of function effect. Variants in EF hand reported in >3 families with childhood and adulthood onset of LGMD.
Sources: Expert Review
Mendeliome v0.3177 GATA6 Elena Savva reviewed gene: GATA6: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:20581743, 19666519; Phenotypes: Pancreatic agenesis and congenital heart defects, 600001, Atrial septal defect 9, 614475, Atrioventricular septal defect 5, 614474, Tetralogy of Fallot, 187500, Persistent truncus arteriosus, 217095; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 VMA21 Crystle Lee gene: VMA21 was added
gene: VMA21 was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: VMA21 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: VMA21 were set to 27916343; 25809233; 23315026
Phenotypes for gene: VMA21 were set to Myopathy, X-linked, with excessive autophagy (MIM#310440)
Review for gene: VMA21 was set to AMBER
Added comment: Childhood onset muscle disease, primarily affecting proximal muscles and elevated CK. No other muscle group involvement. Characterize by progressive muscle weakness with a limb-girdle pattern (PMID: 25809233). Differential diagnosis with LGMD (PanelApp UK)

Intronic variants in multiple families. Onset in childhood

PMID: 25809233: Different splice site variants reported in 2 families, onset in childhood.

PMID: 23315026: 5 splice region and 1 missense reported in 14 families with multiple affected. Quantitative RT-PCR from patient fibroblasts demonstrated reduction in VMA21 mRNA.
Sources: Expert Review
Sources: Expert Review
Callosome v0.148 CDH2 Zornitza Stark Phenotypes for gene: CDH2 were changed from Intellectual disability; corpus callosum abnormalities; congenital abnormalities to Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Callosome v0.147 CDH2 Zornitza Stark edited their review of gene: CDH2: Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Mendeliome v0.3177 CDH2 Zornitza Stark Phenotypes for gene: CDH2 were changed from Intellectual disability; corpus callosum abnormalities; congenital abnormalities to Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Mendeliome v0.3176 CDH2 Zornitza Stark edited their review of gene: CDH2: Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Intellectual disability syndromic and non-syndromic v0.2718 CDH2 Zornitza Stark Phenotypes for gene: CDH2 were changed from Intellectual disability; corpus callosum abnormalities; congenital abnormalities to Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Intellectual disability syndromic and non-syndromic v0.2717 CDH2 Zornitza Stark edited their review of gene: CDH2: Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Arrhythmia_SuperPanel v0.135 Zornitza Stark Changed child panels to: Long QT Syndrome; Brugada syndrome; Catecholaminergic Polymorphic Ventricular Tachycardia; Arrhythmogenic Right Ventricular Cardiomyopathy; Atrial Fibrillation; Ventricular Fibrillation; Sick sinus syndrome; Short QT syndrome
Intellectual disability syndromic and non-syndromic v0.2717 GRIA2 Zornitza Stark Phenotypes for gene: GRIA2 were changed from no OMIM number yet to Neurodevelopmental disorder with language impairment and behavioral abnormalities, MIM# 618917
Intellectual disability syndromic and non-syndromic v0.2716 GRIA2 Zornitza Stark reviewed gene: GRIA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31300657; Phenotypes: Neurodevelopmental disorder with language impairment and behavioral abnormalities, MIM# 618917; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.733 GRIA2 Zornitza Stark edited their review of gene: GRIA2: Changed phenotypes: Intellectual disability, autism, Rett-like features, epileptic encephalopathy, Neurodevelopmental disorder with language impairment and behavioral abnormalities, MIM# 618917
Genetic Epilepsy v0.733 GRIA2 Zornitza Stark Phenotypes for gene: GRIA2 were changed from Intellectual disability; autism; Rett-like features; epileptic encephalopathy to Intellectual disability; autism; Rett-like features; epileptic encephalopathy; Neurodevelopmental disorder with language impairment and behavioral abnormalities, MIM# 618917
Mendeliome v0.3176 GRIA2 Zornitza Stark Phenotypes for gene: GRIA2 were changed from Intellectual disability; autism; Rett-like features; epileptic encephalopathy to Intellectual disability; autism; Rett-like features; epileptic encephalopathy; Neurodevelopmental disorder with language impairment and behavioral abnormalities, MIM# 618917
Mendeliome v0.3175 GRIA2 Zornitza Stark edited their review of gene: GRIA2: Changed phenotypes: Intellectual disability, autism, Rett-like features, epileptic encephalopathy, Neurodevelopmental disorder with language impairment and behavioral abnormalities, MIM# 618917
Intellectual disability syndromic and non-syndromic v0.2716 CDK19 Zornitza Stark Phenotypes for gene: CDK19 were changed from Intellectual disability; epileptic encephalopathy to Intellectual disability; epileptic encephalopathy; Epileptic encephalopathy, early infantile, 87, MIM# 618916
Intellectual disability syndromic and non-syndromic v0.2715 CDK19 Zornitza Stark edited their review of gene: CDK19: Changed phenotypes: Intellectual disability, epileptic encephalopathy, Epileptic encephalopathy, early infantile, 87, MIM# 618916
Genetic Epilepsy v0.732 CDK19 Zornitza Stark Phenotypes for gene: CDK19 were changed from Intellectual disability; epileptic encephalopathy to Intellectual disability; epileptic encephalopathy; Epileptic encephalopathy, early infantile, 87, MIM# 618916
Mendeliome v0.3175 CDK19 Zornitza Stark Phenotypes for gene: CDK19 were changed from Intellectual disability; epileptic encephalopathy to Intellectual disability; epileptic encephalopathy; Epileptic encephalopathy, early infantile, 87, MIM# 618916
Mendeliome v0.3174 CDK19 Zornitza Stark edited their review of gene: CDK19: Changed phenotypes: Intellectual disability, epileptic encephalopathy, Epileptic encephalopathy, early infantile, 87, MIM# 618916
Genetic Epilepsy v0.731 CDK19 Zornitza Stark edited their review of gene: CDK19: Changed phenotypes: Intellectual disability, epileptic encephalopathy, Epileptic encephalopathy, early infantile, 87, MIM# 618916
Mendeliome v0.3174 TSHZ1 Zornitza Stark changed review comment from: Two individuals reported with LoF variants, both with a phenotype of congenital aural atresia and hyposmia (PMID: 22152683). Temporal and spatial expression of Tshz1 mRNA during development of the middle ear is consistent with the phenotype (PMID: 17586487). Tsh2 null mouse model showed a middle ear malformation, and neonatal lethality. A conditional nervous system-specific Tshz1 knock out mouse model demonstrated hyposmia (PMIDs: 24487590; 17586487).; to: Two individuals reported with LoF variants, both with a phenotype of congenital aural atresia and hyposmia (PMID: 22152683). Temporal and spatial expression of Tshz1 mRNA during development of the middle ear is consistent with the phenotype (PMID: 17586487). Tsh2 null mouse model showed a middle ear malformation, and neonatal lethality. A conditional nervous system-specific Tshz1 knock out mouse model demonstrated hyposmia (PMIDs: 24487590; 17586487). Also note original report contains four individuals with deletions of this gene, further supporting gene-disease association.
Mendeliome v0.3174 TSHZ1 Zornitza Stark Mode of inheritance for gene: TSHZ1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3173 TSHZ1 Zornitza Stark Marked gene: TSHZ1 as ready
Mendeliome v0.3173 TSHZ1 Zornitza Stark Gene: tshz1 has been classified as Green List (High Evidence).
Mendeliome v0.3173 TSHZ1 Zornitza Stark Phenotypes for gene: TSHZ1 were changed from to Aural atresia, congenital, MIM# 607842; Hyposmia
Mendeliome v0.3172 TSHZ1 Zornitza Stark Publications for gene: TSHZ1 were set to
Mendeliome v0.3171 TSHZ1 Zornitza Stark Mode of inheritance for gene: TSHZ1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3170 TSHZ1 Zornitza Stark reviewed gene: TSHZ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15834955, 22152683, 17586487, 24487590; Phenotypes: Aural atresia, congenital, MIM# 607842, Hyposmia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3170 ZBTB18 Zornitza Stark Marked gene: ZBTB18 as ready
Mendeliome v0.3170 ZBTB18 Zornitza Stark Gene: zbtb18 has been classified as Green List (High Evidence).
Mendeliome v0.3170 ZBTB18 Zornitza Stark Phenotypes for gene: ZBTB18 were changed from to Mental retardation, autosomal dominant 22, MIM# 612337
Mendeliome v0.3169 ZBTB18 Zornitza Stark Publications for gene: ZBTB18 were set to
Mendeliome v0.3168 ZBTB18 Zornitza Stark Mode of pathogenicity for gene: ZBTB18 was changed from to Other
Mendeliome v0.3167 ZBTB18 Zornitza Stark Mode of inheritance for gene: ZBTB18 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.18 FEZF1 Bryony Thompson Classified gene: FEZF1 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.18 FEZF1 Bryony Thompson Gene: fezf1 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.17 FEZF1 Bryony Thompson reviewed gene: FEZF1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25192046, 32400067, 19479999; Phenotypes: Hypogonadotropic hypogonadism 22, with or without anosmia MIM#616030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.17 FGF17 Bryony Thompson Marked gene: FGF17 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.17 FGF17 Bryony Thompson Gene: fgf17 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.17 FGF17 Bryony Thompson Classified gene: FGF17 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.17 FGF17 Bryony Thompson Gene: fgf17 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.16 FGF17 Bryony Thompson reviewed gene: FGF17: Rating: AMBER; Mode of pathogenicity: None; Publications: 17442747, 23643382; Phenotypes: Hypogonadotropic hypogonadism 20 with or without anosmia MIM#615270; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3166 ESR2 Bryony Thompson Classified gene: ESR2 as Amber List (moderate evidence)
Mendeliome v0.3166 ESR2 Bryony Thompson Gene: esr2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3165 ESR2 Bryony Thompson gene: ESR2 was added
gene: ESR2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ESR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.31 ESR2 Bryony Thompson gene: ESR2 was added
gene: ESR2 was added to Disorders of Sex Differentiation. Sources: Literature
Mode of inheritance for gene: ESR2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ESR2 were set to 29261182; 9861029
Phenotypes for gene: ESR2 were set to 46,XY Disorders of Sex Development
Review for gene: ESR2 was set to AMBER
Added comment: A homozygous indel (Asn181del) was identified in a syndromic case with 46,XY DSD, and 2 heterozygous missense variants were identified in 2 non-syndromic cases with 46,XY DSD. Asn181del and Leu426Arg were found to have significantly increased transcriptional activation in in vitro luciferase assays. Esrb null male mice showed no overt abnormalities and reproduced normally. Older mutant males displayed signs of prostate and bladder hyperplasia.
Sources: Literature
Mendeliome v0.3164 ZBTB18 Elena Savva reviewed gene: ZBTB18: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID 27598823, 29573576; Phenotypes: Mental retardation, autosomal dominant 22 612337; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.16 ESR2 Bryony Thompson Marked gene: ESR2 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.16 ESR2 Bryony Thompson Gene: esr2 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.16 ESR2 Bryony Thompson Classified gene: ESR2 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.16 ESR2 Bryony Thompson Gene: esr2 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.15 ESR2 Bryony Thompson reviewed gene: ESR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30113650, 9861029; Phenotypes: Ovarian dysgenesis 8 MIM#618187; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.15 ERCC6 Bryony Thompson Marked gene: ERCC6 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.15 ERCC6 Bryony Thompson Gene: ercc6 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.15 ERCC6 Bryony Thompson Classified gene: ERCC6 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.15 ERCC6 Bryony Thompson Added comment: Comment on list classification: Strong segregation in one family and supporting functional assays. POI has not been mentioned in carriers for Cockayne syndrome. More evidence is required to determine whether dominant POI associated variants in this gene are specific to the exon expressed in the alternate transcript.
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.15 ERCC6 Bryony Thompson Gene: ercc6 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.14 ERCC6 Bryony Thompson Deleted their comment
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.14 ERCC6 Bryony Thompson Classified gene: ERCC6 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.14 ERCC6 Bryony Thompson Added comment: Comment on list classification: Strong segregation in one family and supporting functional assays.
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.14 ERCC6 Bryony Thompson Gene: ercc6 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.13 ERCC6 Bryony Thompson reviewed gene: ERCC6: Rating: AMBER; Mode of pathogenicity: None; Publications: 26218421; Phenotypes: Premature ovarian failure 11 MIM#616946; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.13 DUSP6 Bryony Thompson Marked gene: DUSP6 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.13 DUSP6 Bryony Thompson Gene: dusp6 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.13 DUSP6 Bryony Thompson Classified gene: DUSP6 as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.13 DUSP6 Bryony Thompson Gene: dusp6 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.12 DUSP6 Bryony Thompson reviewed gene: DUSP6: Rating: RED; Mode of pathogenicity: None; Publications: 23643382, 32389901; Phenotypes: Hypogonadotropic hypogonadism 19 with or without anosmia MIM#615269; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3164 MT-TP Bryony Thompson Marked gene: MT-TP as ready
Mendeliome v0.3164 MT-TP Bryony Thompson Gene: mt-tp has been classified as Red List (Low Evidence).
Mendeliome v0.3164 MT-TP Bryony Thompson Classified gene: MT-TP as Red List (low evidence)
Mendeliome v0.3164 MT-TP Bryony Thompson Added comment: Comment on list classification: This is a mitochondrial gene, which is on the Mitochondrial disease gene panel.
Mendeliome v0.3164 MT-TP Bryony Thompson Gene: mt-tp has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.49 ABL1 Zornitza Stark Marked gene: ABL1 as ready
Congenital Heart Defect v0.49 ABL1 Zornitza Stark Gene: abl1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.49 ABL1 Zornitza Stark Classified gene: ABL1 as Green List (high evidence)
Congenital Heart Defect v0.49 ABL1 Zornitza Stark Gene: abl1 has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.36 SETD2 Zornitza Stark Marked gene: SETD2 as ready
Macrocephaly_Megalencephaly v0.36 SETD2 Zornitza Stark Gene: setd2 has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.36 SETD2 Zornitza Stark Phenotypes for gene: SETD2 were changed from to Luscan-Lumish syndrome, MIM#616831
Macrocephaly_Megalencephaly v0.35 SETD2 Zornitza Stark Publications for gene: SETD2 were set to
Macrocephaly_Megalencephaly v0.34 SETD2 Zornitza Stark Mode of inheritance for gene: SETD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macrocephaly_Megalencephaly v0.33 SETD2 Zornitza Stark reviewed gene: SETD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681085; Phenotypes: Luscan-Lumish syndrome, MIM#616831; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.22 SETD2 Zornitza Stark Marked gene: SETD2 as ready
Overgrowth v0.22 SETD2 Zornitza Stark Gene: setd2 has been classified as Green List (High Evidence).
Overgrowth v0.22 SETD2 Zornitza Stark Phenotypes for gene: SETD2 were changed from to Luscan-Lumish syndrome, MIM#616831
Overgrowth v0.21 SETD2 Zornitza Stark Publications for gene: SETD2 were set to
Overgrowth v0.20 SETD2 Zornitza Stark Mode of inheritance for gene: SETD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.19 SETD2 Zornitza Stark reviewed gene: SETD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681085; Phenotypes: Luscan-Lumish syndrome, MIM#616831; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.34 SETD2 Zornitza Stark Phenotypes for gene: SETD2 were changed from Luscan-Lumish syndrome 616831; Luscan-Lumish syndrome 616831 to Luscan-Lumish syndrome 616831
Intellectual disability syndromic and non-syndromic v0.2715 SETD2 Zornitza Stark Marked gene: SETD2 as ready
Intellectual disability syndromic and non-syndromic v0.2715 SETD2 Zornitza Stark Gene: setd2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2715 SETD2 Zornitza Stark Phenotypes for gene: SETD2 were changed from to Luscan-Lumish syndrome, MIM#616831
Intellectual disability syndromic and non-syndromic v0.2714 SETD2 Zornitza Stark Publications for gene: SETD2 were set to
Intellectual disability syndromic and non-syndromic v0.2713 SETD2 Zornitza Stark Mode of inheritance for gene: SETD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2712 SETD2 Zornitza Stark reviewed gene: SETD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681085; Phenotypes: Luscan-Lumish syndrome, MIM#616831; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3163 SETD2 Zornitza Stark reviewed gene: SETD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681085; Phenotypes: Luscan-Lumish syndrome, MIM#616831; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3163 SETD2 Zornitza Stark Marked gene: SETD2 as ready
Mendeliome v0.3163 SETD2 Zornitza Stark Gene: setd2 has been classified as Green List (High Evidence).
Mendeliome v0.3163 SETD2 Zornitza Stark Phenotypes for gene: SETD2 were changed from to Luscan-Lumish syndrome, MIM#616831
Mendeliome v0.3162 SETD2 Zornitza Stark Publications for gene: SETD2 were set to
Mendeliome v0.3161 SETD2 Zornitza Stark Mode of inheritance for gene: SETD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Haem degradation and bilirubin metabolism defects v0.11 HMBS Zornitza Stark Marked gene: HMBS as ready
Haem degradation and bilirubin metabolism defects v0.11 HMBS Zornitza Stark Gene: hmbs has been classified as Green List (High Evidence).
Haem degradation and bilirubin metabolism defects v0.11 HMBS Zornitza Stark reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Porphyria, acute intermittent, MIM# 176000, Porphyria, acute intermittent, nonerythroid variant, MIM# 176000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Haem degradation and bilirubin metabolism defects v0.11 CPOX Zornitza Stark Marked gene: CPOX as ready
Haem degradation and bilirubin metabolism defects v0.11 CPOX Zornitza Stark Gene: cpox has been classified as Green List (High Evidence).
Haem degradation and bilirubin metabolism defects v0.11 CPOX Zornitza Stark reviewed gene: CPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coproporphyria, MIM# 121300, Harderoporphyria, MIM# 618892; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Haem degradation and bilirubin metabolism defects v0.11 GATA1 Zornitza Stark Marked gene: GATA1 as ready
Haem degradation and bilirubin metabolism defects v0.11 GATA1 Zornitza Stark Gene: gata1 has been classified as Amber List (Moderate Evidence).
Haem degradation and bilirubin metabolism defects v0.11 UROS Zornitza Stark Marked gene: UROS as ready
Haem degradation and bilirubin metabolism defects v0.11 UROS Zornitza Stark Gene: uros has been classified as Green List (High Evidence).
Haem degradation and bilirubin metabolism defects v0.11 UROS Zornitza Stark Publications for gene: UROS were set to
Haem degradation and bilirubin metabolism defects v0.10 UROD Zornitza Stark Marked gene: UROD as ready
Haem degradation and bilirubin metabolism defects v0.10 UROD Zornitza Stark Gene: urod has been classified as Green List (High Evidence).
Haem degradation and bilirubin metabolism defects v0.10 UROD Zornitza Stark Publications for gene: UROD were set to
Haem degradation and bilirubin metabolism defects v0.9 UROD Zornitza Stark Mode of inheritance for gene: UROD was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Haem degradation and bilirubin metabolism defects v0.8 PPOX Zornitza Stark Marked gene: PPOX as ready
Haem degradation and bilirubin metabolism defects v0.8 PPOX Zornitza Stark Gene: ppox has been classified as Green List (High Evidence).
Haem degradation and bilirubin metabolism defects v0.8 PPOX Zornitza Stark Phenotypes for gene: PPOX were changed from Porphyria variegata 176200 to Porphyria variegata, MIM# 176200
Haem degradation and bilirubin metabolism defects v0.7 PPOX Zornitza Stark Publications for gene: PPOX were set to
Haem degradation and bilirubin metabolism defects v0.6 FECH Zornitza Stark Marked gene: FECH as ready
Haem degradation and bilirubin metabolism defects v0.6 FECH Zornitza Stark Gene: fech has been classified as Green List (High Evidence).
Haem degradation and bilirubin metabolism defects v0.6 FECH Zornitza Stark Publications for gene: FECH were set to
Haem degradation and bilirubin metabolism defects v0.5 ALAS2 Zornitza Stark Marked gene: ALAS2 as ready
Haem degradation and bilirubin metabolism defects v0.5 ALAS2 Zornitza Stark Gene: alas2 has been classified as Green List (High Evidence).
Haem degradation and bilirubin metabolism defects v0.5 ALAS2 Zornitza Stark Mode of inheritance for gene: ALAS2 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Haem degradation and bilirubin metabolism defects v0.4 ALAD Zornitza Stark Marked gene: ALAD as ready
Haem degradation and bilirubin metabolism defects v0.4 ALAD Zornitza Stark Gene: alad has been classified as Green List (High Evidence).
Haem degradation and bilirubin metabolism defects v0.4 ALAD Zornitza Stark Publications for gene: ALAD were set to
Haem degradation and bilirubin metabolism defects v0.3 HFE Zornitza Stark Marked gene: HFE as ready
Haem degradation and bilirubin metabolism defects v0.3 HFE Zornitza Stark Gene: hfe has been classified as Red List (Low Evidence).
Haem degradation and bilirubin metabolism defects v0.3 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mendeliome v0.3160 UBE2A Zornitza Stark Marked gene: UBE2A as ready
Mendeliome v0.3160 UBE2A Zornitza Stark Gene: ube2a has been classified as Green List (High Evidence).
Mendeliome v0.3160 UBE2A Zornitza Stark Phenotypes for gene: UBE2A were changed from to Mental retardation, X-linked syndromic, Nascimento-type (MIM#300860)
Mendeliome v0.3159 UBE2A Zornitza Stark Publications for gene: UBE2A were set to
Mendeliome v0.3158 UBE2A Zornitza Stark Mode of inheritance for gene: UBE2A was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3157 UBE2A Zornitza Stark reviewed gene: UBE2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24053514, 16909393; Phenotypes: Mental retardation, X-linked syndromic, Nascimento-type (MIM#300860); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2712 UBE2A Zornitza Stark Marked gene: UBE2A as ready
Intellectual disability syndromic and non-syndromic v0.2712 UBE2A Zornitza Stark Gene: ube2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2712 UBE2A Zornitza Stark Phenotypes for gene: UBE2A were changed from to Mental retardation, X-linked syndromic, Nascimento-type (MIM#300860)
Intellectual disability syndromic and non-syndromic v0.2711 UBE2A Zornitza Stark Publications for gene: UBE2A were set to
Intellectual disability syndromic and non-syndromic v0.2710 UBE2A Zornitza Stark Mode of inheritance for gene: UBE2A was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Aortopathy_Connective Tissue Disorders v0.96 COL5A2 Zornitza Stark Marked gene: COL5A2 as ready
Aortopathy_Connective Tissue Disorders v0.96 COL5A2 Zornitza Stark Gene: col5a2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.96 COL5A2 Zornitza Stark Mode of inheritance for gene: COL5A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.95 COL5A2 Zornitza Stark Classified gene: COL5A2 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.95 COL5A2 Zornitza Stark Gene: col5a2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.94 C1S Zornitza Stark Marked gene: C1S as ready
Aortopathy_Connective Tissue Disorders v0.94 C1S Zornitza Stark Gene: c1s has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.94 C1S Zornitza Stark Phenotypes for gene: C1S were changed from to Ehlers-Danlos syndrome, periodontal type, 1 (MIM# 130080)
Aortopathy_Connective Tissue Disorders v0.93 C1S Zornitza Stark Publications for gene: C1S were set to
Aortopathy_Connective Tissue Disorders v0.92 C1S Zornitza Stark Mode of inheritance for gene: C1S was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.91 TGFBR2 Zornitza Stark Marked gene: TGFBR2 as ready
Aortopathy_Connective Tissue Disorders v0.91 TGFBR2 Zornitza Stark Gene: tgfbr2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.91 TGFBR2 Zornitza Stark Phenotypes for gene: TGFBR2 were changed from to Loeys-Dietz syndrome 2, MIM# 610168
Aortopathy_Connective Tissue Disorders v0.90 TGFBR2 Zornitza Stark Publications for gene: TGFBR2 were set to
Aortopathy_Connective Tissue Disorders v0.89 TGFBR2 Zornitza Stark Mode of inheritance for gene: TGFBR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.88 TGFBR1 Zornitza Stark Marked gene: TGFBR1 as ready
Aortopathy_Connective Tissue Disorders v0.88 TGFBR1 Zornitza Stark Gene: tgfbr1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.88 TGFBR1 Zornitza Stark Phenotypes for gene: TGFBR1 were changed from to Loeys-Dietz syndrome 1, MIM# 609192
Aortopathy_Connective Tissue Disorders v0.87 TGFBR1 Zornitza Stark Publications for gene: TGFBR1 were set to
Aortopathy_Connective Tissue Disorders v0.86 TGFBR1 Zornitza Stark Mode of inheritance for gene: TGFBR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.85 TGFB3 Zornitza Stark Marked gene: TGFB3 as ready
Aortopathy_Connective Tissue Disorders v0.85 TGFB3 Zornitza Stark Gene: tgfb3 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.85 TGFB3 Zornitza Stark Phenotypes for gene: TGFB3 were changed from to Loeys-Dietz syndrome 5, MI# 615582
Aortopathy_Connective Tissue Disorders v0.84 TGFB3 Zornitza Stark Publications for gene: TGFB3 were set to
Aortopathy_Connective Tissue Disorders v0.83 TGFB3 Zornitza Stark Mode of inheritance for gene: TGFB3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.82 TGFB2 Zornitza Stark Marked gene: TGFB2 as ready
Aortopathy_Connective Tissue Disorders v0.82 TGFB2 Zornitza Stark Gene: tgfb2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.82 TGFB2 Zornitza Stark Phenotypes for gene: TGFB2 were changed from to Loeys-Dietz syndrome 4, MIM# 614816
Aortopathy_Connective Tissue Disorders v0.81 TGFB2 Zornitza Stark Publications for gene: TGFB2 were set to
Aortopathy_Connective Tissue Disorders v0.80 TGFB2 Zornitza Stark Mode of inheritance for gene: TGFB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.79 SLC2A10 Zornitza Stark Marked gene: SLC2A10 as ready
Aortopathy_Connective Tissue Disorders v0.79 SLC2A10 Zornitza Stark Gene: slc2a10 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.79 SLC2A10 Zornitza Stark Phenotypes for gene: SLC2A10 were changed from to Arterial tortuosity syndrome MIM#606145
Aortopathy_Connective Tissue Disorders v0.78 SLC2A10 Zornitza Stark Publications for gene: SLC2A10 were set to
Aortopathy_Connective Tissue Disorders v0.77 SLC2A10 Zornitza Stark Mode of inheritance for gene: SLC2A10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.76 SKI Zornitza Stark Marked gene: SKI as ready
Aortopathy_Connective Tissue Disorders v0.76 SKI Zornitza Stark Added comment: Comment when marking as ready: Syndromic connective tissue disorder.
Aortopathy_Connective Tissue Disorders v0.76 SKI Zornitza Stark Gene: ski has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.76 SKI Zornitza Stark Phenotypes for gene: SKI were changed from to Shprintzen-Goldberg syndrome, MIM#164780
Aortopathy_Connective Tissue Disorders v0.75 SKI Zornitza Stark Publications for gene: SKI were set to
Aortopathy_Connective Tissue Disorders v0.74 SKI Zornitza Stark Mode of inheritance for gene: SKI was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.73 PRKG1 Zornitza Stark Marked gene: PRKG1 as ready
Aortopathy_Connective Tissue Disorders v0.73 PRKG1 Zornitza Stark Gene: prkg1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.73 PRKG1 Zornitza Stark Phenotypes for gene: PRKG1 were changed from to Aortic aneurysm, familial thoracic 8, MIM#176894
Aortopathy_Connective Tissue Disorders v0.72 PRKG1 Zornitza Stark Publications for gene: PRKG1 were set to
Aortopathy_Connective Tissue Disorders v0.71 PRKG1 Zornitza Stark Mode of inheritance for gene: PRKG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.70 PCGF2 Zornitza Stark Marked gene: PCGF2 as ready
Aortopathy_Connective Tissue Disorders v0.70 PCGF2 Zornitza Stark Gene: pcgf2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.70 PCGF2 Zornitza Stark Phenotypes for gene: PCGF2 were changed from to Turnpenny-Fry syndrome, MIM#600346
Aortopathy_Connective Tissue Disorders v0.69 PCGF2 Zornitza Stark Publications for gene: PCGF2 were set to
Aortopathy_Connective Tissue Disorders v0.68 PCGF2 Zornitza Stark Mode of inheritance for gene: PCGF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.67 MYLK Zornitza Stark Marked gene: MYLK as ready
Aortopathy_Connective Tissue Disorders v0.67 MYLK Zornitza Stark Gene: mylk has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.67 MYLK Zornitza Stark Phenotypes for gene: MYLK were changed from to Aortic aneurysm, familial thoracic 7, MIM#600922
Aortopathy_Connective Tissue Disorders v0.66 MYLK Zornitza Stark Publications for gene: MYLK were set to
Aortopathy_Connective Tissue Disorders v0.65 MYLK Zornitza Stark Mode of inheritance for gene: MYLK was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.64 MYH11 Zornitza Stark Marked gene: MYH11 as ready
Aortopathy_Connective Tissue Disorders v0.64 MYH11 Zornitza Stark Gene: myh11 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.64 MYH11 Zornitza Stark Phenotypes for gene: MYH11 were changed from to Aortic aneurysm, familial thoracic 4, MIM#160745
Aortopathy_Connective Tissue Disorders v0.63 MYH11 Zornitza Stark Publications for gene: MYH11 were set to
Aortopathy_Connective Tissue Disorders v0.62 MED12 Zornitza Stark Marked gene: MED12 as ready
Aortopathy_Connective Tissue Disorders v0.62 MED12 Zornitza Stark Gene: med12 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.62 MED12 Zornitza Stark Phenotypes for gene: MED12 were changed from to Lujan-Fryns syndrome, MIM# 309520; Ohdo syndrome, X-linked, MIM# 300895; Opitz-Kaveggia syndrome, MIM# 305450
Aortopathy_Connective Tissue Disorders v0.61 MED12 Zornitza Stark Publications for gene: MED12 were set to
Aortopathy_Connective Tissue Disorders v0.60 MED12 Zornitza Stark Mode of inheritance for gene: MED12 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Aortopathy_Connective Tissue Disorders v0.59 LOX Zornitza Stark Marked gene: LOX as ready
Aortopathy_Connective Tissue Disorders v0.59 LOX Zornitza Stark Gene: lox has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.59 LOX Zornitza Stark Phenotypes for gene: LOX were changed from to Aortic aneurysm, familial thoracic 10, MIM#617168
Aortopathy_Connective Tissue Disorders v0.58 LOX Zornitza Stark Publications for gene: LOX were set to
Aortopathy_Connective Tissue Disorders v0.57 LOX Zornitza Stark Mode of inheritance for gene: LOX was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.56 FBN1 Zornitza Stark Marked gene: FBN1 as ready
Aortopathy_Connective Tissue Disorders v0.56 FBN1 Zornitza Stark Gene: fbn1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.56 FBN1 Zornitza Stark Phenotypes for gene: FBN1 were changed from to Marfan syndrome (154700); MASS syndrome (604308)
Aortopathy_Connective Tissue Disorders v0.55 FBN1 Zornitza Stark Publications for gene: FBN1 were set to
Aortopathy_Connective Tissue Disorders v0.54 FBN1 Zornitza Stark Mode of inheritance for gene: FBN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.53 COL5A1 Zornitza Stark Marked gene: COL5A1 as ready
Aortopathy_Connective Tissue Disorders v0.53 COL5A1 Zornitza Stark Gene: col5a1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.53 COL5A1 Zornitza Stark Phenotypes for gene: COL5A1 were changed from to Ehlers-Danlos syndrome, classic type, 1, MIM# 130000
Aortopathy_Connective Tissue Disorders v0.52 COL5A1 Zornitza Stark Publications for gene: COL5A1 were set to
Aortopathy_Connective Tissue Disorders v0.51 COL5A1 Zornitza Stark Mode of inheritance for gene: COL5A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.50 COL3A1 Zornitza Stark Marked gene: COL3A1 as ready
Aortopathy_Connective Tissue Disorders v0.50 COL3A1 Zornitza Stark Gene: col3a1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.50 COL3A1 Zornitza Stark Phenotypes for gene: COL3A1 were changed from to Ehlers-Danlos syndrome, vascular type, MIM# 130050; Polymicrogyria with or without vascular-type EDS, MIM# 618343
Aortopathy_Connective Tissue Disorders v0.49 COL3A1 Zornitza Stark Mode of inheritance for gene: COL3A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.48 COL3A1 Zornitza Stark Publications for gene: COL3A1 were set to
Aortopathy_Connective Tissue Disorders v0.47 COL3A1 Zornitza Stark Mode of inheritance for gene: COL3A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.46 COL1A1 Zornitza Stark Marked gene: COL1A1 as ready
Aortopathy_Connective Tissue Disorders v0.46 COL1A1 Zornitza Stark Gene: col1a1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.46 COL1A1 Zornitza Stark Phenotypes for gene: COL1A1 were changed from to Ehlers-Danlos syndrome, arthrochalasia type, 1, MIM# 130060
Aortopathy_Connective Tissue Disorders v0.45 COL1A1 Zornitza Stark Publications for gene: COL1A1 were set to
Aortopathy_Connective Tissue Disorders v0.44 COL1A1 Zornitza Stark Mode of inheritance for gene: COL1A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.43 CBS Zornitza Stark Marked gene: CBS as ready
Aortopathy_Connective Tissue Disorders v0.43 CBS Zornitza Stark Gene: cbs has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.43 CBS Zornitza Stark Phenotypes for gene: CBS were changed from to Homocystinuria (MIM# 236200)
Aortopathy_Connective Tissue Disorders v0.42 CBS Zornitza Stark Publications for gene: CBS were set to
Aortopathy_Connective Tissue Disorders v0.41 CBS Zornitza Stark Mode of inheritance for gene: CBS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.40 CBS Zornitza Stark reviewed gene: CBS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Aortopathy_Connective Tissue Disorders v0.40 BGN Zornitza Stark Marked gene: BGN as ready
Aortopathy_Connective Tissue Disorders v0.40 BGN Zornitza Stark Added comment: Comment when marking as ready: Females variably affected.
Aortopathy_Connective Tissue Disorders v0.40 BGN Zornitza Stark Gene: bgn has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.40 BGN Zornitza Stark Marked gene: BGN as ready
Aortopathy_Connective Tissue Disorders v0.40 BGN Zornitza Stark Gene: bgn has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.40 BGN Zornitza Stark Mode of inheritance for gene: BGN 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)
Aortopathy_Connective Tissue Disorders v0.39 BGN Zornitza Stark Publications for gene: BGN were set to
Aortopathy_Connective Tissue Disorders v0.38 BGN Zornitza Stark Phenotypes for gene: BGN were changed from to Meester-Loeys syndrome, MIM# 300989
Aortopathy_Connective Tissue Disorders v0.37 ACTA2 Zornitza Stark Marked gene: ACTA2 as ready
Aortopathy_Connective Tissue Disorders v0.37 ACTA2 Zornitza Stark Gene: acta2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.37 ACTA2 Zornitza Stark Phenotypes for gene: ACTA2 were changed from to Aortic aneurysm, familial thoracic 6, MIM# 611788
Aortopathy_Connective Tissue Disorders v0.36 ACTA2 Zornitza Stark Publications for gene: ACTA2 were set to
Aortopathy_Connective Tissue Disorders v0.35 ACTA2 Zornitza Stark Mode of inheritance for gene: ACTA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.34 ABL1 Zornitza Stark Marked gene: ABL1 as ready
Aortopathy_Connective Tissue Disorders v0.34 ABL1 Zornitza Stark Gene: abl1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.34 ABL1 Zornitza Stark Phenotypes for gene: ABL1 were changed from to Congenital heart defects and skeletal malformations syndrome (MIM# 617602)
Haem degradation and bilirubin metabolism defects v0.2 HFE Bryony Thompson Classified gene: HFE as Red List (low evidence)
Haem degradation and bilirubin metabolism defects v0.2 HFE Bryony Thompson Gene: hfe has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v0.33 ABL1 Zornitza Stark Publications for gene: ABL1 were set to
Aortopathy_Connective Tissue Disorders v0.32 ABL1 Zornitza Stark Mode of inheritance for gene: ABL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.12 DIAPH2 Bryony Thompson Marked gene: DIAPH2 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.12 DIAPH2 Bryony Thompson Gene: diaph2 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.12 DIAPH2 Bryony Thompson Tag SV/CNV tag was added to gene: DIAPH2.
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.12 DIAPH2 Bryony Thompson Classified gene: DIAPH2 as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.12 DIAPH2 Bryony Thompson Gene: diaph2 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.11 DIAPH2 Bryony Thompson reviewed gene: DIAPH2: Rating: RED; Mode of pathogenicity: None; Publications: 9497258, 30689869, 26175800, 11129329; Phenotypes: ?Premature ovarian failure 2A MIM#300511; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Aortopathy_Connective Tissue Disorders v0.30 COL5A2 Paul De Fazio changed review comment from: Well-known association with classic Ehlers-Danlos syndrome e.g. PMID 22696272. Reviewed in PMID 20847697 and GeneReviews (Available from: https://www.ncbi.nlm.nih.gov/books/NBK1244/).
Sources: Literature; to: Well-known association with classic Ehlers-Danlos syndrome e.g. PMID 22696272. Variants in this gene make up ~14% of cases. Reviewed in PMID 20847697 and GeneReviews (Available from: https://www.ncbi.nlm.nih.gov/books/NBK1244/).
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.30 COL5A2 Paul De Fazio gene: COL5A2 was added
gene: COL5A2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: COL5A2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COL5A2 were set to 20847697; 22696272
Phenotypes for gene: COL5A2 were set to Ehlers-Danlos syndrome, classic type, 2, MIM#120190
Penetrance for gene: COL5A2 were set to unknown
Review for gene: COL5A2 was set to GREEN
gene: COL5A2 was marked as current diagnostic
Added comment: Well-known association with classic Ehlers-Danlos syndrome e.g. PMID 22696272. Reviewed in PMID 20847697 and GeneReviews (Available from: https://www.ncbi.nlm.nih.gov/books/NBK1244/).
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.30 MED12 Ain Roesley edited their review of gene: MED12: Changed rating: GREEN
Aortopathy_Connective Tissue Disorders v0.30 SMAD4 Paul De Fazio edited their review of gene: SMAD4: Changed rating: GREEN; Changed publications: 30071989, 25931195, 25931195, 30809044
Aortopathy_Connective Tissue Disorders v0.30 SMAD4 Paul De Fazio changed review comment from: "Limited evidence" for association with aortic dilatation/dissection by ClinGen:

"Eight genes scored as moderate (EFEMP2) or limited (ELN, FBN2, FLNA, NOTCH1,
SLC2A10, SMAD4, and SKI) for association with HTAAD. These genes are a heterogeneous group for which the evidence was often difficult to assess...the evidence, therefore, for their association with a presentation of aortic dilatation and/or dissection is often rather lacking. The other common feature of these conditions is that there is no robust evidence of progression to aortic dissection."

The ClinGen review of SMAD4, viewable in the supplementary material, dates to 22/12/2016 and so does not account for the reported individuals in PMID 30809044.

Green in PanelApp UK although with quite a few Amber reviews.

There is an association between people with with SMAD4 variants and aortic dissection (PMID 25931195).; to: "Limited evidence" for association with aortic dilatation/dissection by ClinGen:

"Eight genes scored as moderate (EFEMP2) or limited (ELN, FBN2, FLNA, NOTCH1,
SLC2A10, SMAD4, and SKI) for association with HTAAD. These genes are a heterogeneous group for which the evidence was often difficult to assess...the evidence, therefore, for their association with a presentation of aortic dilatation and/or dissection is often rather lacking. The other common feature of these conditions is that there is no robust evidence of progression to aortic dissection."


Green in PanelApp UK although with quite a few Amber reviews.

There is an association between people with with SMAD4 variants and aortic dissection (PMID 25931195). The ClinGen review of SMAD4, viewable in the supplementary material, dates to 22/12/2016 and so does not account for the reported individuals in PMID 30809044. Given this more recent data Green is appropriate.
Aortopathy_Connective Tissue Disorders v0.30 C1S Zornitza Stark Classified gene: C1S as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.30 C1S Zornitza Stark Gene: c1s has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.29 BGN Belinda Chong changed review comment from: 5 unrelated individuals with TAAD (PMID:27632686) plus mouse model (PMID:17502576)

PMID:27632686
Proband associated with syndromic TAAD: c.5G>A, p.Trp2*, 21 kb del: chrX:152767424-152787984 28 kb del: chrX:152768438-152795976, c.908A>C, p.Gln303Pro, c.238G>A, p.Gly80Ser. Some segregation evidence and mutation-carrying females ranged from unaffected upon repeated echocardiographic evaluation over aortic root dilatation to death due to aortic dissection.
PMID:17502576
Biglycan deficiency in male BALB/cA mice has been shown to lead to sudden death due to aortic rupture.

GEL PanelApp: As per evidence above.

ClinGen assessment uncertain due to focuses on isolated TAAD; however support involvement of BGN in syndromic TAAD: "Strong for syndromic , X-linked TAAD and “limited” for isolated TAAD. The curation shows strong assertion with syndromic TAAD. There was 1 reported proband with isolated TAAD harboring variant in this gene. Given this, the association with isolated TAAD should be limited."; to: 5 unrelated individuals with TAAD (PMID:27632686) plus mouse model (PMID:17502576)

PMID:27632686
Proband associated with syndromic TAAD: c.5G>A, p.Trp2*, 21 kb del: chrX:152767424-152787984 28 kb del: chrX:152768438-152795976, c.908A>C, p.Gln303Pro, c.238G>A, p.Gly80Ser. Some segregation evidence and mutation-carrying females ranged from unaffected upon repeated echocardiographic evaluation over aortic root dilatation to death due to aortic dissection.
PMID:17502576
Biglycan deficiency in male BALB/cA mice has been shown to lead to sudden death due to aortic rupture.

GEL PanelApp: As per evidence above.

ClinGen assessment uncertain due to focus on isolated TAAD; however support involvement of BGN in syndromic TAAD: "Strong for syndromic , X-linked TAAD and “limited” for isolated TAAD. The curation shows strong assertion with syndromic TAAD. There was 1 reported proband with isolated TAAD harboring variant in this gene. Given this, the association with isolated TAAD should be limited."
Aortopathy_Connective Tissue Disorders v0.29 PCGF2 Zornitza Stark reviewed gene: PCGF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30343942; Phenotypes: Turnpenny-Fry syndrome, MIM#600346; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2709 UBE2A Crystle Lee reviewed gene: UBE2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24053514, 16909393; Phenotypes: Mental retardation, X-linked syndromic, Nascimento-type (MIM#300860); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Aortopathy_Connective Tissue Disorders v0.29 TGFB3 Zornitza Stark reviewed gene: TGFB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Aortopathy_Connective Tissue Disorders v0.29 TGFB3 Paul De Fazio changed review comment from: "Uncertain" by ClinGen. 43 patients from 11 families reported in PMID 25835445 but this seemed insufficient for the ClinGen working group.; to: "Uncertain" by ClinGen. 43 patients from 11 families with syndromic presentations of aortic aneurysms reported in PMID 25835445 but this seemed insufficient for the ClinGen working group.
Aortopathy_Connective Tissue Disorders v0.29 TGFB3 Paul De Fazio changed review comment from: "Uncertain" by ClinGen. Quite a few individuals in PMID 25835445 but this seemed insufficient for the ClinGen working group.; to: "Uncertain" by ClinGen. 43 patients from 11 families reported in PMID 25835445 but this seemed insufficient for the ClinGen working group.
Aortopathy_Connective Tissue Disorders v0.29 ABL1 Zornitza Stark reviewed gene: ABL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 28288113; Phenotypes: Congenital heart defects and skeletal malformations syndrome (MIM# 617602); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.29 TGFB3 Paul De Fazio changed review comment from: "Uncertain" by ClinGen. 3 unrelated individuals in PMID 25835445 but this was insufficient for the ClinGen working group.; to: "Uncertain" by ClinGen. Quite a few individuals in PMID 25835445 but this seemed insufficient for the ClinGen working group.
Aortopathy_Connective Tissue Disorders v0.29 FLNA Zornitza Stark Marked gene: FLNA as ready
Aortopathy_Connective Tissue Disorders v0.29 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.29 FLNA Zornitza Stark Phenotypes for gene: FLNA were changed from to Heterotopia, periventricular, 1 MIM# 300049; Cardiac valvular dysplasia, X-linked MIM# 314400.
Haem degradation and bilirubin metabolism defects v0.1 HFE Belinda Chong edited their review of gene: HFE: Changed publications: 30683557
Aortopathy_Connective Tissue Disorders v0.28 FLNA Zornitza Stark Publications for gene: FLNA were set to
Aortopathy_Connective Tissue Disorders v0.27 FLNA Zornitza Stark Mode of inheritance for gene: FLNA 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)
Haem degradation and bilirubin metabolism defects v0.1 HFE Zornitza Stark reviewed gene: HFE: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Porphyria cutanea tarda, susceptibility to} 176100, {Porphyria variegata, susceptibility to} 176200; Mode of inheritance: None
Mendeliome v0.3157 SETD2 Michelle Torres reviewed gene: SETD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681085; Phenotypes: Luscan-Lumish syndrome, 616831 AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3157 AXL Bryony Thompson Marked gene: AXL as ready
Mendeliome v0.3157 AXL Bryony Thompson Gene: axl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3157 AXL Bryony Thompson Classified gene: AXL as Amber List (moderate evidence)
Mendeliome v0.3157 AXL Bryony Thompson Gene: axl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3156 AXL Bryony Thompson gene: AXL was added
gene: AXL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AXL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AXL were set to 18787040; 24476074
Phenotypes for gene: AXL were set to Kallman syndrome; normosmic idiopathic hypogonadotropic hypogonadism
Review for gene: AXL was set to AMBER
Added comment: Axl null mice had delayed first oestrus and persistently abnormal oestrous cyclicality compared with wild-type controls. Only a single study reported screening human cases. In a screen of 104 probands with KS or nIHH, four heterozygous AXL mutations were identified in two KS and two nIHH unrelated subjects (two males and two females). Three of the variants appear to be too common in gnomAD v2.1 given the reported prevalence of KS reported in GeneReviews (1:30,000 in males and 1:125,000 in females): c.587-6C>T (normal splicing in RNA studies, NFE AF 0.0001472), p.Q361P (NFE 0.002560), p.L50F (AJ 0.004405). The other variant p.S202C (4 hets, 1 female in gnomAD v2.1) is rare enough in gnomAD for a dominant disorder. In vitro functional assays were conducted and p.S202C had an significant effect on function, but so did the more common variant p.Q361P.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.11 AXL Bryony Thompson Phenotypes for gene: AXL were changed from to Kallman syndrome; normosmic idiopathic hypogonadotropic hypogonadism
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.10 AXL Bryony Thompson Publications for gene: AXL were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.9 AXL Bryony Thompson Marked gene: AXL as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.9 AXL Bryony Thompson Gene: axl has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.9 AXL Bryony Thompson Classified gene: AXL as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.9 AXL Bryony Thompson Gene: axl has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 AXL Bryony Thompson reviewed gene: AXL: Rating: AMBER; Mode of pathogenicity: None; Publications: 18787040, 24476074; Phenotypes: Kallman syndrome, normosmic idiopathic hypogonadotropic hypogonadism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Haem degradation and bilirubin metabolism defects v0.1 PPOX Paul De Fazio reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 27982422; Phenotypes: Porphyria variegata, MIM#600923; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 MED12 Ain Roesley reviewed gene: MED12: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30071989, 19938245, 17369503; Phenotypes: heritable thoracic aortic aneurysm and dissection, Opitz-Kaveggia syndrome (FS syndrome), X-Linked Ohdo Syndrome (XLOS), Lujan Syndrome (LS); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Aortopathy_Connective Tissue Disorders v0.26 FLNA Naomi Baker reviewed gene: FLNA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30071989, 29334594.; Phenotypes: Heterotopia, periventricular, 1 MIM# 300049, Cardiac valvular dysplasia, X-linked MIM# 314400.; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Haem degradation and bilirubin metabolism defects v0.1 UROD Paul De Fazio reviewed gene: UROD: Rating: GREEN; Mode of pathogenicity: None; Publications: 9792863; Phenotypes: Porphyria cutanea tarda; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 PCGF2 Paul De Fazio changed review comment from: Not reviewed by ClinGen Aortopathy Working Group.

Not on any relevant PanelApp UK panel although green on others.

11 unrelated individuals and a pair of monozygotic twins were reported all with missense variants at proline 65. 5 individuals had aortic dilatation.; to: Not reviewed by ClinGen Aortopathy Working Group.

Not on any relevant PanelApp UK panel although green on others.

11 unrelated individuals and a pair of monozygotic twins were reported all with missense variants at proline 65 in the context of Turnpenny-Fry Syndrome. 5 individuals had aortic dilatation.
Aortopathy_Connective Tissue Disorders v0.26 BGN Belinda Chong reviewed gene: BGN: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 27632686, 17502576; Phenotypes: Heritable Thoracic Aortic Aneurysm and Dissection; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Aortopathy_Connective Tissue Disorders v0.26 SMAD4 Paul De Fazio edited their review of gene: SMAD4: Changed publications: 30071989, 25931195, 25931195
Aortopathy_Connective Tissue Disorders v0.26 SMAD4 Paul De Fazio changed review comment from: "Limited evidence" for association with aortic dilatation/dissection by ClinGen:

"Eight genes scored as moderate (EFEMP2) or limited (ELN, FBN2, FLNA, NOTCH1,
SLC2A10, SMAD4, and SKI) for association with HTAAD. These genes are a heterogeneous group for which the evidence was often difficult to assess...the evidence, therefore, for their association with a presentation of aortic dilatation and/or dissection is often rather lacking. The other common feature of these conditions is that there is no robust evidence of progression to aortic dissection."

The ClinGen review of SMAD4, viewable in the supplementary material, dates to 22/12/2016 and does not account for the reported individuals cited below.; to: "Limited evidence" for association with aortic dilatation/dissection by ClinGen:

"Eight genes scored as moderate (EFEMP2) or limited (ELN, FBN2, FLNA, NOTCH1,
SLC2A10, SMAD4, and SKI) for association with HTAAD. These genes are a heterogeneous group for which the evidence was often difficult to assess...the evidence, therefore, for their association with a presentation of aortic dilatation and/or dissection is often rather lacking. The other common feature of these conditions is that there is no robust evidence of progression to aortic dissection."

The ClinGen review of SMAD4, viewable in the supplementary material, dates to 22/12/2016 and so does not account for the reported individuals in PMID 30809044.

Green in PanelApp UK although with quite a few Amber reviews.

There is an association between people with with SMAD4 variants and aortic dissection (PMID 25931195).
Aortopathy_Connective Tissue Disorders v0.26 TGFBR1 Paul De Fazio changed review comment from: "Definitive" by ClinGen.

Reviewed in PMID 27879313 (176 cases with variants in TGFBR1).; to: "Definitive" by ClinGen Aortopathy working group.

Reviewed in PMID 27879313 (176 cases with variants in TGFBR1).
Aortopathy_Connective Tissue Disorders v0.26 TGFB2 Paul De Fazio changed review comment from: "Definitive" by ClinGen.

ClinGen cite PMID 22772371 which describes 4 families with variants in this gene.; to: "Definitive" by ClinGen Aortopathy Working Group.

The ClinGen Working Group cite PMID 22772371 which describes 4 families with variants in this gene.
Aortopathy_Connective Tissue Disorders v0.26 TGFB3 Paul De Fazio changed review comment from: "Uncertain" by ClinGen. 3 unrelated individuals in PMID 25835445 but insufficient for the ClinGen working group.; to: "Uncertain" by ClinGen. 3 unrelated individuals in PMID 25835445 but this was insufficient for the ClinGen working group.
Aortopathy_Connective Tissue Disorders v0.26 MYH11 Paul De Fazio edited their review of gene: MYH11: Changed rating: GREEN
Aortopathy_Connective Tissue Disorders v0.26 MYH11 Paul De Fazio reviewed gene: MYH11: Rating: ; Mode of pathogenicity: None; Publications: 30071989, 16444274, 17666408, 27081537; Phenotypes: Aortic aneurysm, familial thoracic 4, MIM#160745; Mode of inheritance: None; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 MYLK Paul De Fazio Deleted their comment
Aortopathy_Connective Tissue Disorders v0.26 MYLK Paul De Fazio edited their review of gene: MYLK: Added comment: "Definitive" by Clingen Aortopathy Working Group.

Green on PanelApp UK.

Association between variants in this gene and aortic dissection established in multiple individuals and a 5-generation family (PMID 27586135;21055718;25907466).; Changed rating: GREEN
Aortopathy_Connective Tissue Disorders v0.26 MYLK Paul De Fazio changed review comment from: "Definitive" by Clingen Aortopathy Working Group.

Green on PanelApp UK.

Association between variants in this gene and aortic dissection established in multiple individuals and a 5-generation family (PMID 27586135;21055718;25907466).; to: "Definitive" by Clingen Aortopathy Working Group.

Green on PanelApp UK.

Association between variants in this gene and aortic dissection established in multiple individuals and a 5-generation family (PMID 27586135;21055718;25907466).
Aortopathy_Connective Tissue Disorders v0.26 MYLK Paul De Fazio reviewed gene: MYLK: Rating: ; Mode of pathogenicity: None; Publications: 30071989, 27586135, 21055718, 25907466; Phenotypes: Aortic aneurysm, familial thoracic 7, MIM#600922; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Ataxia - paediatric v0.221 HARS Bryony Thompson Marked gene: HARS as ready
Ataxia - paediatric v0.221 HARS Bryony Thompson Gene: hars has been classified as Amber List (Moderate Evidence).
Ataxia - paediatric v0.221 HARS Bryony Thompson Classified gene: HARS as Amber List (moderate evidence)
Ataxia - paediatric v0.221 HARS Bryony Thompson Gene: hars has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.26 PCGF2 Paul De Fazio changed review comment from: Not reviewed by ClinGen Aortopathy Working Group.

Not on any relevant PanelApp UK panel.

11 unrelated individuals and a pair of monozygotic twins were reported all with missense variants at proline 65. 5 individuals had aortic dilatation.; to: Not reviewed by ClinGen Aortopathy Working Group.

Not on any relevant PanelApp UK panel although green on others.

11 unrelated individuals and a pair of monozygotic twins were reported all with missense variants at proline 65. 5 individuals had aortic dilatation.
Aortopathy_Connective Tissue Disorders v0.26 PCGF2 Paul De Fazio changed review comment from: Not reviewed by ClinGen Aortopathy Working Group.

Not on any relevant PanelApp UK panel.

11 unrelated individuals and a pair of monozygotic twins were reported all with missense variants at proline 65. 5 individuals had aortic dilatation.; to: Not reviewed by ClinGen Aortopathy Working Group.

Not on any relevant PanelApp UK panel.

11 unrelated individuals and a pair of monozygotic twins were reported all with missense variants at proline 65. 5 individuals had aortic dilatation.
Aortopathy_Connective Tissue Disorders v0.26 PCGF2 Paul De Fazio reviewed gene: PCGF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30343942; Phenotypes: Turnpenny-Fry syndrome, MIM#600346; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Ataxia - paediatric v0.220 HARS Bryony Thompson gene: HARS was added
gene: HARS was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: HARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HARS were set to 32296180
Phenotypes for gene: HARS were set to multisystem ataxic syndrome
Review for gene: HARS was set to AMBER
Added comment: 3 cases from 2 unrelated families with biallelic variants and paediatric onset of progressive ataxic gait as a feature of the condition.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2709 HARS Bryony Thompson Marked gene: HARS as ready
Intellectual disability syndromic and non-syndromic v0.2709 HARS Bryony Thompson Gene: hars has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2709 HARS Bryony Thompson Classified gene: HARS as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2709 HARS Bryony Thompson Gene: hars has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2708 HARS Bryony Thompson gene: HARS was added
gene: HARS was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HARS were set to 32296180
Phenotypes for gene: HARS were set to multisystem ataxic syndrome; mild-severe intellectual disability
Review for gene: HARS was set to AMBER
Added comment: 3 cases from 2 unrelated families with biallelic variants and mild to severe intellectual disability as a feature of the condition.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.26 PRKG1 Paul De Fazio reviewed gene: PRKG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 23910461, 30577811; Phenotypes: Aortic aneurysm, familial thoracic 8, MIM#176894; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 SKI Paul De Fazio changed review comment from: "Limited" evidence by ClinGen Aortopathy Working Group but:

"Diagnosis of Loeys-Dietz syndrome versus Shprintzen-Goldberg syndrome is thus important for correct management and risk stratification, and supports the conclusion that the gene for Shprintzen- Goldberg syndrome, SKI, should be included in diagnostic panels for characteristic syndromic presentations, especially in the pediatric setting."

>20 individuals described in the context of Shprintzen-Goldberg syndrome which can involve aortic dilatations (PMID 23023332, 24736733); to: "Limited" evidence by ClinGen Aortopathy Working Group but:

"Diagnosis of Loeys-Dietz syndrome versus Shprintzen-Goldberg syndrome is thus important for correct management and risk stratification, and supports the conclusion that the gene for Shprintzen- Goldberg syndrome, SKI, should be included in diagnostic panels for characteristic syndromic presentations, especially in the pediatric setting."

>20 individuals described in the context of Shprintzen-Goldberg syndrome which can involve aortic dilatations (PMID 23023332, 24736733)

Also Green on PanelApp UK
Aortopathy_Connective Tissue Disorders v0.26 SKI Paul De Fazio reviewed gene: SKI: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 23023332, 24736733; Phenotypes: Shprintzen-Goldberg syndrome, MIM#164780; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 SLC2A10 Paul De Fazio reviewed gene: SLC2A10: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 16550171, 17935213; Phenotypes: Arterial tortuosity syndrome MIM#606145; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 COL5A1 Ain Roesley changed review comment from: PMID: 30071989; Classified as 'No Evidence' by Clingen for heritable thoracic aortic aneurysm and dissection


Gene reviews: 75-78% of classical EDS is caused by pathogenic variants in COL5A1. Haploinsufficiency is the more common disease mechanism whoeever, missense variants in the triple helical domain of the α1(V) or α2(V) chains are likely to have dominant-negative activity.
(https://www.ncbi.nlm.nih.gov/books/NBK1244/); to: PMID: 30071989; Classified as 'No Evidence' by Clingen for heritable thoracic aortic aneurysm and dissection


GeneReviews: 75-78% of classical EDS is caused by pathogenic variants in COL5A1. Haploinsufficiency is the more common disease mechanism whoeever, missense variants in the triple helical domain of the α1(V) or α2(V) chains are likely to have dominant-negative activity.
(https://www.ncbi.nlm.nih.gov/books/NBK1244/)
Aortopathy_Connective Tissue Disorders v0.26 COL5A1 Ain Roesley reviewed gene: COL5A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30071989; Phenotypes: Heritable Thoracic Aortic Aneurysm and Dissection, Classic Ehlers-Danlos Syndrome (MIM# 130000); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.26 SLC2A10 Paul De Fazio Deleted their review
Aortopathy_Connective Tissue Disorders v0.26 SLC2A10 Paul De Fazio reviewed gene: SLC2A10: Rating: RED; Mode of pathogenicity: None; Publications: 30071989; Phenotypes: Hereditary thoracic aortic aneurysm and dissection; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 SLC2A10 Paul De Fazio Deleted their review
Aortopathy_Connective Tissue Disorders v0.26 SLC2A10 Paul De Fazio reviewed gene: SLC2A10: Rating: RED; Mode of pathogenicity: None; Publications: 30071989; Phenotypes: Hereditary thoracic aortic aneurysm and dissection; Mode of inheritance: None
Aortopathy_Connective Tissue Disorders v0.26 COL3A1 Ain Roesley reviewed gene: COL3A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30071989, 25758994; Phenotypes: Ehlers-Danlos syndrome, vascular type, heritable thoracic aortic aneurysm and dissection; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.26 COL1A1 Ain Roesley reviewed gene: COL1A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30071989, 28981071; Phenotypes: Classical Ehlers-Danlos Syndrome, arthrochalasia Ehlers-Danlos Syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.26 LOX Naomi Baker reviewed gene: LOX: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30071989, 26838787, 30675029.; Phenotypes: Aortic aneurysm, familial thoracic 10 MIM#617168; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.26 SMAD3 Paul De Fazio reviewed gene: SMAD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989; Phenotypes: Loeys-Dietz syndrome 3, MIM# 613795; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 SMAD4 Paul De Fazio changed review comment from: "Limited evidence" for association with aortic dilatation/dissection by ClinGen:

"Eight genes scored as moderate (EFEMP2) or limited (ELN, FBN2, FLNA, NOTCH1,
SLC2A10, SMAD4, and SKI) for association with HTAAD. These genes are a heterogeneous group for which the evidence was often difficult to assess...the evidence, therefore, for their association with a presentation of aortic dilatation and/or dissection is often rather lacking. The other common feature of these conditions is that there is no robust evidence of progression to aortic dissection."; to: "Limited evidence" for association with aortic dilatation/dissection by ClinGen:

"Eight genes scored as moderate (EFEMP2) or limited (ELN, FBN2, FLNA, NOTCH1,
SLC2A10, SMAD4, and SKI) for association with HTAAD. These genes are a heterogeneous group for which the evidence was often difficult to assess...the evidence, therefore, for their association with a presentation of aortic dilatation and/or dissection is often rather lacking. The other common feature of these conditions is that there is no robust evidence of progression to aortic dissection."

The ClinGen review of SMAD4, viewable in the supplementary material, dates to 22/12/2016 and does not account for the reported individuals cited below.
Aortopathy_Connective Tissue Disorders v0.26 SMAD4 Paul De Fazio reviewed gene: SMAD4: Rating: AMBER; Mode of pathogenicity: None; Publications: 30071989; Phenotypes: Hereditary thoracic aortic aneurysm and dissection; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 TGFB2 Paul De Fazio reviewed gene: TGFB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 22772371; Phenotypes: Loeys-Dietz syndrome 4; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 TGFB3 Paul De Fazio reviewed gene: TGFB3: Rating: AMBER; Mode of pathogenicity: None; Publications: 30071989, 25835445; Phenotypes: Arrhythmogenic right ventricular dysplasia 1, Loeys-Dietz syndrome 5; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 TGFBR1 Paul De Fazio reviewed gene: TGFBR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 27879313; Phenotypes: Loeys-Dietz syndrome 1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 TGFBR2 Paul De Fazio reviewed gene: TGFBR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 27879313; Phenotypes: Loeys-Dietz syndrome 2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Aortopathy_Connective Tissue Disorders v0.26 CBS Ain Roesley reviewed gene: CBS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30071989, 1301198, 10408774, 7762555, 12815602, 16307898, 25455305, 26667307, 29508359; Phenotypes: Homocystinuria (MIM# 236200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.26 C1S Ain Roesley reviewed gene: C1S: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30071989, 27745832, 31921203; Phenotypes: Ehlers-Danlos syndrome, periodontal type, 1 (MIM# 130080); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.26 C1R Ain Roesley reviewed gene: C1R: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30071989, 27745832; Phenotypes: Ehlers-Danlos syndrome, periodontal type, 1 (MIM# 130080); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.26 ABL1 Ain Roesley reviewed gene: ABL1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30071989, 28288113; Phenotypes: Congenital heart defects and skeletal malformations syndrome (MIM# 617602); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.26 LOX Naomi Baker Deleted their review
Aortopathy_Connective Tissue Disorders v0.26 LOX Naomi Baker reviewed gene: LOX: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Aortic aneurysm, familial thoracic 10 MIM#10617168; Mode of inheritance: None
Aortopathy_Connective Tissue Disorders v0.26 ABL1 Ain Roesley Deleted their review
Aortopathy_Connective Tissue Disorders v0.26 ACTA2 Ain Roesley reviewed gene: ACTA2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30724374; Phenotypes: hereditary thoracic aortic aneurysm and dissection; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.48 ABL1 Ain Roesley gene: ABL1 was added
gene: ABL1 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: ABL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ABL1 were set to PMID: 28288113
Phenotypes for gene: ABL1 were set to Congenital heart defects and skeletal malformations syndrome (MIM# 617602)
Penetrance for gene: ABL1 were set to unknown
Review for gene: ABL1 was set to GREEN
Added comment: PMID: 28288113: six affected individuals from 4 unrelated families who shared similar clinical features including dysmorphic facial features (6/6), congenital heart disease (CHD, 6/6), skeletal abnormalities (6/6), joint problems (5/6), failure to thrive (5/6), gastrointestinal problems (5/6), and male genital/sexual abnormalities (3/4). Missense variants with 3 families sharing the same variant (Tyr245Cys).
Authors also noted similar congenital malformations observed in fetuses exposed to the selective tyrosine kinase inhibitor imatinib, and patients with constitutional ABL1 variants
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.26 ABL1 Ain Roesley reviewed gene: ABL1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30071989, 28288113; Phenotypes: Congenital heart defects and skeletal malformations syndrome (MIM# 617602); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Haem degradation and bilirubin metabolism defects v0.1 GATA1 Belinda Chong reviewed gene: GATA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25251786, 17148589; Phenotypes: Congenital Erythropoietic Porphyria; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arrhythmogenic Cardiomyopathy v0.7 CHD2 Zornitza Stark Marked gene: CHD2 as ready
Arrhythmogenic Cardiomyopathy v0.7 CHD2 Zornitza Stark Gene: chd2 has been classified as Red List (Low Evidence).
Arrhythmogenic Cardiomyopathy v0.7 CHD2 Zornitza Stark gene: CHD2 was added
gene: CHD2 was added to Arrhythmogenic Right Ventricular Cardiomyopathy. Sources: Expert list
Mode of inheritance for gene: CHD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CHD2 were set to Arrhythmogenic right ventricular dysplasia, familial, 14, OMIM#618920
Review for gene: CHD2 was set to RED
Added comment: Several South African families reported, where missense variants segregate with ARVC. Two different variants reported.
Sources: Expert list
Haem degradation and bilirubin metabolism defects v0.1 UROD Paul De Fazio Deleted their review
Haem degradation and bilirubin metabolism defects v0.1 UROD Paul De Fazio reviewed gene: UROD: Rating: GREEN; Mode of pathogenicity: None; Publications: 9792863; Phenotypes: Porphyria cutanea tarda; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Haem degradation and bilirubin metabolism defects v0.1 ALAD Ain Roesley reviewed gene: ALAD: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16343966, 30724374, 31311713; Phenotypes: Porphyria, acute hepatic (MIM# 612740); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Haem degradation and bilirubin metabolism defects v0.1 UROS Paul De Fazio reviewed gene: UROS: Rating: GREEN; Mode of pathogenicity: None; Publications: 8829650; Phenotypes: Congenital erythropoietic porphyria; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Haem degradation and bilirubin metabolism defects v0.1 HFE Belinda Chong reviewed gene: HFE: Rating: RED; Mode of pathogenicity: None; Publications: 235200; Phenotypes: Hemochromatosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.89 MYOM1 Zornitza Stark Classified gene: MYOM1 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.89 MYOM1 Zornitza Stark Gene: myom1 has been classified as Red List (Low Evidence).
Mendeliome v0.3155 GANAB Zornitza Stark Marked gene: GANAB as ready
Mendeliome v0.3155 GANAB Zornitza Stark Gene: ganab has been classified as Green List (High Evidence).
Mendeliome v0.3155 GANAB Zornitza Stark Phenotypes for gene: GANAB were changed from to Polycystic kidney disease 3, MIM# 600666
Mendeliome v0.3154 GANAB Zornitza Stark Publications for gene: GANAB were set to
Mendeliome v0.3153 GANAB Zornitza Stark Mode of inheritance for gene: GANAB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3152 GANAB Zornitza Stark reviewed gene: GANAB: Rating: GREEN; Mode of pathogenicity: None; Publications: 27259053; Phenotypes: Polycystic kidney disease 3, MIM# 600666; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.37 GANAB Zornitza Stark Marked gene: GANAB as ready
Renal Macrocystic Disease v0.37 GANAB Zornitza Stark Gene: ganab has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.37 GANAB Zornitza Stark Phenotypes for gene: GANAB were changed from to Polycystic kidney disease 3, MIM# 600666
Renal Macrocystic Disease v0.36 GANAB Zornitza Stark Publications for gene: GANAB were set to
Renal Macrocystic Disease v0.35 GANAB Zornitza Stark Mode of inheritance for gene: GANAB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.34 GANAB Zornitza Stark reviewed gene: GANAB: Rating: GREEN; Mode of pathogenicity: None; Publications: 27259053; Phenotypes: Polycystic kidney disease 3, MIM# 600666; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.34 PKHD1 Zornitza Stark Marked gene: PKHD1 as ready
Renal Macrocystic Disease v0.34 PKHD1 Zornitza Stark Gene: pkhd1 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.34 PKHD1 Zornitza Stark Phenotypes for gene: PKHD1 were changed from to Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200
Renal Macrocystic Disease v0.33 PKHD1 Zornitza Stark Mode of inheritance for gene: PKHD1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.33 PKHD1 Zornitza Stark Mode of inheritance for gene: PKHD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.32 PKHD1 Zornitza Stark reviewed gene: PKHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.32 LRP5 Zornitza Stark Marked gene: LRP5 as ready
Renal Macrocystic Disease v0.32 LRP5 Zornitza Stark Gene: lrp5 has been classified as Red List (Low Evidence).
Renal Macrocystic Disease v0.32 LRP5 Zornitza Stark gene: LRP5 was added
gene: LRP5 was added to Renal Macrocystic Disease. Sources: Expert list
Mode of inheritance for gene: LRP5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LRP5 were set to 25920554; 24706814
Phenotypes for gene: LRP5 were set to Polycystic liver disease 4 with or without kidney cysts, MIM# 617875
Review for gene: LRP5 was set to RED
Added comment: 5 families reported. However, some non-penetrance reported in family members in original family. In two of the families reported subsequently, PKD1 LP variants were found and LRP5 variant was postulated to be a modifier. Note that one of the variants p.Arg1036Gln is present in 692 individuals in gnomad, p.Trp560Cys is present in 9, and p.Arg1135Cys is present in 70. Overall limited evidence for association with cystic renal phenotype. Note the gene has a well-established association with eye/bone phenotypes.
Sources: Expert list
Muscular dystrophy and myopathy_Paediatric v0.48 DMD Zornitza Stark Marked gene: DMD as ready
Muscular dystrophy and myopathy_Paediatric v0.48 DMD Zornitza Stark Gene: dmd has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.48 DMD Zornitza Stark Tag SV/CNV tag was added to gene: DMD.
Muscular dystrophy and myopathy_Paediatric v0.48 DMD Zornitza Stark Phenotypes for gene: DMD were changed from to Duchenne muscular dystrophy (MIM#310200); Becker muscular dystrophy (MIM#300376)
Muscular dystrophy and myopathy_Paediatric v0.47 DMD Zornitza Stark Mode of inheritance for gene: DMD was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Muscular dystrophy and myopathy_Paediatric v0.46 Zornitza Stark removed gene:SGCG from the panel
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 SGCG Zornitza Stark Marked gene: SGCG as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 SGCG Zornitza Stark Gene: sgcg has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 SGCG Zornitza Stark Publications for gene: SGCG were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.17 SGCG Zornitza Stark reviewed gene: SGCG: Rating: GREEN; Mode of pathogenicity: None; Publications: 30838351, 25802879; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 5, MIM# 253700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.45 CAPN3 Zornitza Stark Marked gene: CAPN3 as ready
Muscular dystrophy and myopathy_Paediatric v0.45 CAPN3 Zornitza Stark Gene: capn3 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.45 CAPN3 Zornitza Stark Classified gene: CAPN3 as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v0.45 CAPN3 Zornitza Stark Gene: capn3 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.44 CAPN3 Zornitza Stark reviewed gene: CAPN3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.17 CAPN3 Zornitza Stark Marked gene: CAPN3 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.17 CAPN3 Zornitza Stark Gene: capn3 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.17 CAPN3 Zornitza Stark Phenotypes for gene: CAPN3 were changed from Muscular dystrophy, limb-girdle, type 2A, 253600 to Muscular dystrophy, limb-girdle, autosomal dominant 4, MIM# 618129; Muscular dystrophy, limb-girdle, autosomal recessive 1, MIM# 253600
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.16 CAPN3 Zornitza Stark Publications for gene: CAPN3 were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.15 CAPN3 Zornitza Stark Mode of inheritance for gene: CAPN3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.14 CAPN3 Zornitza Stark reviewed gene: CAPN3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31937337, 28881388; Phenotypes: Muscular dystrophy, limb-girdle, autosomal dominant 4, MIM# 618129, Muscular dystrophy, limb-girdle, autosomal recessive 1, MIM# 253600; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.44 CAPN3 Zornitza Stark Classified gene: CAPN3 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.44 CAPN3 Zornitza Stark Gene: capn3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.43 GOSR2 Zornitza Stark Marked gene: GOSR2 as ready
Muscular dystrophy and myopathy_Paediatric v0.43 GOSR2 Zornitza Stark Gene: gosr2 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.43 GOSR2 Zornitza Stark Classified gene: GOSR2 as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v0.43 GOSR2 Zornitza Stark Gene: gosr2 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.42 MSTO1 Zornitza Stark Marked gene: MSTO1 as ready
Muscular dystrophy and myopathy_Paediatric v0.42 MSTO1 Zornitza Stark Added comment: Comment when marking as ready: Green for bi-allelic disease.
Muscular dystrophy and myopathy_Paediatric v0.42 MSTO1 Zornitza Stark Gene: msto1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.42 MSTO1 Zornitza Stark Classified gene: MSTO1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.42 MSTO1 Zornitza Stark Gene: msto1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2707 GOLGA2 Zornitza Stark reviewed gene: GOLGA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2707 GOLGA2 Zornitza Stark Marked gene: GOLGA2 as ready
Intellectual disability syndromic and non-syndromic v0.2707 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2707 GOLGA2 Zornitza Stark Classified gene: GOLGA2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2707 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.41 GOLGA2 Zornitza Stark reviewed gene: GOLGA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Muscular dystrophy and myopathy_Paediatric v0.41 GOLGA2 Zornitza Stark Marked gene: GOLGA2 as ready
Muscular dystrophy and myopathy_Paediatric v0.41 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.41 GOLGA2 Zornitza Stark Classified gene: GOLGA2 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.41 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Microcephaly v0.131 GOLGA2 Zornitza Stark Marked gene: GOLGA2 as ready
Microcephaly v0.131 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Microcephaly v0.131 GOLGA2 Zornitza Stark Classified gene: GOLGA2 as Green List (high evidence)
Microcephaly v0.131 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Mendeliome v0.3152 GOLGA2 Zornitza Stark Phenotypes for gene: GOLGA2 were changed from Nueromuscular disorder to Neuromuscular disorder
Mendeliome v0.3151 GOLGA2 Zornitza Stark Marked gene: GOLGA2 as ready
Mendeliome v0.3151 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Mendeliome v0.3151 GOLGA2 Zornitza Stark Classified gene: GOLGA2 as Green List (high evidence)
Mendeliome v0.3151 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.40 FHL1 Zornitza Stark Marked gene: FHL1 as ready
Muscular dystrophy and myopathy_Paediatric v0.40 FHL1 Zornitza Stark Gene: fhl1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.40 FHL1 Zornitza Stark Classified gene: FHL1 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v0.40 FHL1 Zornitza Stark Gene: fhl1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.39 PLEC Zornitza Stark reviewed gene: PLEC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Muscular dystrophy and myopathy_Paediatric v0.39 PLEC Zornitza Stark Marked gene: PLEC as ready
Muscular dystrophy and myopathy_Paediatric v0.39 PLEC Zornitza Stark Gene: plec has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.39 PLEC Zornitza Stark Classified gene: PLEC as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.39 PLEC Zornitza Stark Gene: plec has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.38 EMD Zornitza Stark Marked gene: EMD as ready
Muscular dystrophy and myopathy_Paediatric v0.38 EMD Zornitza Stark Gene: emd has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.38 EMD Zornitza Stark Classified gene: EMD as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.38 EMD Zornitza Stark Gene: emd has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.14 POGLUT1 Zornitza Stark Marked gene: POGLUT1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.14 POGLUT1 Zornitza Stark Gene: poglut1 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.14 POGLUT1 Zornitza Stark Phenotypes for gene: POGLUT1 were changed from Limb-girdle muscular dystrophy to Muscular dystrophy, limb-girdle, autosomal recessive 21 (MIM#617232)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.13 POGLUT1 Zornitza Stark Publications for gene: POGLUT1 were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.12 POGLUT1 Zornitza Stark Classified gene: POGLUT1 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.12 POGLUT1 Zornitza Stark Gene: poglut1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.37 RYR1 Zornitza Stark Marked gene: RYR1 as ready
Muscular dystrophy and myopathy_Paediatric v0.37 RYR1 Zornitza Stark Gene: ryr1 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.37 RYR1 Zornitza Stark Phenotypes for gene: RYR1 were changed from to Central core disease (MIM#117000); Minicore myopathy with external ophthalmoplegia (MIM#255320); Neuromuscular disease, congenital, with uniform type 1 fiber (MIM#117000)
Muscular dystrophy and myopathy_Paediatric v0.36 RYR1 Zornitza Stark Publications for gene: RYR1 were set to
Muscular dystrophy and myopathy_Paediatric v0.35 RYR1 Zornitza Stark Mode of inheritance for gene: RYR1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.34 RYR1 Zornitza Stark Classified gene: RYR1 as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v0.34 RYR1 Zornitza Stark Gene: ryr1 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.33 RYR1 Zornitza Stark reviewed gene: RYR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2706 SIL1 Zornitza Stark Marked gene: SIL1 as ready
Intellectual disability syndromic and non-syndromic v0.2706 SIL1 Zornitza Stark Gene: sil1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2706 SIL1 Zornitza Stark Phenotypes for gene: SIL1 were changed from to Marinesco-Sjogren syndrome (MIM#248800)
Intellectual disability syndromic and non-syndromic v0.2705 SIL1 Zornitza Stark Publications for gene: SIL1 were set to
Intellectual disability syndromic and non-syndromic v0.2704 SIL1 Zornitza Stark Mode of inheritance for gene: SIL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cataract v0.149 SIL1 Zornitza Stark Marked gene: SIL1 as ready
Cataract v0.149 SIL1 Zornitza Stark Gene: sil1 has been classified as Green List (High Evidence).
Cataract v0.149 SIL1 Zornitza Stark Phenotypes for gene: SIL1 were changed from to Marinesco-Sjogren syndrome (MIM#248800)
Cataract v0.148 SIL1 Zornitza Stark Publications for gene: SIL1 were set to
Cataract v0.147 SIL1 Zornitza Stark Mode of inheritance for gene: SIL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.33 SIL1 Zornitza Stark Marked gene: SIL1 as ready
Muscular dystrophy and myopathy_Paediatric v0.33 SIL1 Zornitza Stark Gene: sil1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.33 SIL1 Zornitza Stark Classified gene: SIL1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.33 SIL1 Zornitza Stark Gene: sil1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.32 SIL1 Zornitza Stark reviewed gene: SIL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.11 TCAP Zornitza Stark Marked gene: TCAP as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.11 TCAP Zornitza Stark Gene: tcap has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.11 TCAP Zornitza Stark Publications for gene: TCAP were set to
Muscular dystrophy and myopathy_Paediatric v0.32 TCAP Zornitza Stark Marked gene: TCAP as ready
Muscular dystrophy and myopathy_Paediatric v0.32 TCAP Zornitza Stark Gene: tcap has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.32 TCAP Zornitza Stark Phenotypes for gene: TCAP were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 7 (MIM#601954)
Muscular dystrophy and myopathy_Paediatric v0.31 TCAP Zornitza Stark Publications for gene: TCAP were set to
Muscular dystrophy and myopathy_Paediatric v0.30 TCAP Zornitza Stark Mode of inheritance for gene: TCAP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.29 TCAP Zornitza Stark Classified gene: TCAP as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v0.29 TCAP Zornitza Stark Gene: tcap has been classified as Red List (Low Evidence).
Microcephaly v0.130 DPM1 Zornitza Stark Marked gene: DPM1 as ready
Microcephaly v0.130 DPM1 Zornitza Stark Gene: dpm1 has been classified as Green List (High Evidence).
Microcephaly v0.130 DPM1 Zornitza Stark Classified gene: DPM1 as Green List (high evidence)
Microcephaly v0.130 DPM1 Zornitza Stark Gene: dpm1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.10 TRAPPC11 Zornitza Stark Marked gene: TRAPPC11 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.10 TRAPPC11 Zornitza Stark Gene: trappc11 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.10 TRAPPC11 Zornitza Stark Publications for gene: TRAPPC11 were set to
Muscular dystrophy and myopathy_Paediatric v0.28 TRAPPC11 Zornitza Stark Marked gene: TRAPPC11 as ready
Muscular dystrophy and myopathy_Paediatric v0.28 TRAPPC11 Zornitza Stark Gene: trappc11 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.28 TRAPPC11 Zornitza Stark Classified gene: TRAPPC11 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.28 TRAPPC11 Zornitza Stark Gene: trappc11 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.27 SGCG Elena Savva gene: SGCG was added
gene: SGCG was added to Muscular dystrophy. Sources: Literature
Mode of inheritance for gene: SGCG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGCG were set to PMID: 30838351; 25802879
Phenotypes for gene: SGCG were set to Muscular dystrophy, limb-girdle, autosomal recessive 5 253700
Review for gene: SGCG was set to AMBER
Added comment: PMID: 30838351 - 7 patients with childhood onset limb girdle MD and biallelic variants. Muscle biopsy supported the diagnosis. Mild proximal muscle weakness and increased serum creatine kinase levels

PMID: 25802879 - 2 unrelated patients with a founder missense variant (p.E263K). Patients had childhood onset, with proximal muscle weakness in pelvic girdle muscles and highly elevated CK levels.

Summary: Childhood onset limb girdle rather than muscular dystrophy
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v0.27 CAPN3 Elena Savva gene: CAPN3 was added
gene: CAPN3 was added to Muscular dystrophy. Sources: Literature
Mode of inheritance for gene: CAPN3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAPN3 were set to PMID: 31937337
Phenotypes for gene: CAPN3 were set to Muscular dystrophy, limb-girdle, autosomal recessive 1 253600
Review for gene: CAPN3 was set to GREEN
Added comment: PMID: 31937337 - 15 families with limb girdle muscular dystrophy. 13/15 report childhood onset in multiple affected children, where EMG confirmed a myopathic disorder, with mild-severe dystrophic changes.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v0.27 GOSR2 Elena Savva reviewed gene: GOSR2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30363482, 29855340; Phenotypes: Epilepsy, progressive myoclonic 6 614018; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.27 GOSR2 Elena Savva Deleted their review
Muscular dystrophy and myopathy_Paediatric v0.27 GOSR2 Elena Savva gene: GOSR2 was added
gene: GOSR2 was added to Muscular dystrophy. Sources: Expert list
Mode of inheritance for gene: GOSR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOSR2 were set to PMID: 30363482; 29855340
Phenotypes for gene: GOSR2 were set to Epilepsy, progressive myoclonic 6 614018
Added comment: PMID: 30363482 - 1 chet patient, no mention of myopathy or muscular dystrophy. Patient had a missense and inframe deletion of a single amino acid.

PMID: 29855340 - 1 chet family (2 siblings) with neonatal hypotonia, muscle weaknes and elevated CK levels. One sibling died before genotyping, the other was found to be chet for a missense/start loss variant. Patient had dystrophic muscle biopsy with hypoglycosylation of α-dystroglycan
Paper reviews other patients and notes muscle histology and EMG were normal, no specific abnormalities reported (most carried recurring variant p.Gly144Trp).

Summary: single report of muscular dystrophy but only report of a start loss variant. All others are of an inframe deletion or the recurring missense.
Sources: Expert list
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 IL17RD Bryony Thompson gene: IL17RD was added
gene: IL17RD was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: IL17RD was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: IL17RD were set to Hypogonadotropic hypogonadism 18 with or without anosmia 615267
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 HS6ST1 Bryony Thompson gene: HS6ST1 was added
gene: HS6ST1 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: HS6ST1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: HS6ST1 were set to {Hypogonadotropic hypogonadism 15 with or without anosmia} 614880
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 HNF1B Bryony Thompson gene: HNF1B was added
gene: HNF1B was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: HNF1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: HNF1B were set to Renal cysts and diabetes syndrome 137920 AD
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 HARS2 Bryony Thompson gene: HARS2 was added
gene: HARS2 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: HARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HARS2 were set to ?Perrault syndrome 2 614926
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 GNRHR Bryony Thompson gene: GNRHR was added
gene: GNRHR was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: GNRHR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GNRHR were set to Hypogonadotropic hypogonadism 7 without anosmia 146110
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 GNRH1 Bryony Thompson gene: GNRH1 was added
gene: GNRH1 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: GNRH1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GNRH1 were set to ?Hypogonadotropic hypogonadism 12 with or without anosmia 614841
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 FLRT3 Bryony Thompson gene: FLRT3 was added
gene: FLRT3 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: FLRT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FLRT3 were set to Hypogonadotropic hypogonadism 21 with anosmia 615271
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 FGF8 Bryony Thompson gene: FGF8 was added
gene: FGF8 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: FGF8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FGF8 were set to Hypogonadotropic hypogonadism 6 with or without anosmia 612702
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 FGF17 Bryony Thompson gene: FGF17 was added
gene: FGF17 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: FGF17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FGF17 were set to Hypogonadotropic hypogonadism 20 with or without anosmia 615270
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 FEZF1 Bryony Thompson gene: FEZF1 was added
gene: FEZF1 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: FEZF1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FEZF1 were set to Hypogonadotropic hypogonadism 22, with or without anosmia 616030
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 ESR2 Bryony Thompson gene: ESR2 was added
gene: ESR2 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: ESR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ESR2 were set to ?Ovarian dysgenesis 8 618187
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 ERCC6 Bryony Thompson gene: ERCC6 was added
gene: ERCC6 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: ERCC6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ERCC6 were set to Premature ovarian failure 11 616946
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 DUSP6 Bryony Thompson gene: DUSP6 was added
gene: DUSP6 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: DUSP6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DUSP6 were set to Hypogonadotropic hypogonadism 19 with or without anosmia 615269
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 DIAPH2 Bryony Thompson gene: DIAPH2 was added
gene: DIAPH2 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: DIAPH2 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: DIAPH2 were set to ?Premature ovarian failure 2A 300511
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 CHD7 Bryony Thompson gene: CHD7 was added
gene: CHD7 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: CHD7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CHD7 were set to Hypogonadotropic hypogonadism 5 with or without anosmia 612370; CHARGE syndrome 214800
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 AXL Bryony Thompson gene: AXL was added
gene: AXL was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: AXL was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 ANOS1 Bryony Thompson gene: ANOS1 was added
gene: ANOS1 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: ANOS1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ANOS1 were set to Hypogonadotropic hypogonadism 1 with or without anosmia (Kallmann syndrome 1) 308700
Muscular dystrophy and myopathy_Paediatric v0.27 MSTO1 Crystle Lee gene: MSTO1 was added
gene: MSTO1 was added to Muscular dystrophy. Sources: Expert Review
Mode of inheritance for gene: MSTO1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MSTO1 were set to 28554942; 28544275; 31604776
Phenotypes for gene: MSTO1 were set to Myopathy, mitochondrial, and ataxia (MIM#617675)
Review for gene: MSTO1 was set to GREEN
Added comment: >5 families reported. Early onset, elevated CK levels and myopathic patterns on EMG reported in almost all patients. Primarily a recessive disorder. Limited evidence supporting AD inheritance, which was reported in one family where CK levels were normal and age of onset was later.

PMID: 31604776: One patient reported. Provides review of previously published MSTO1 families.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2703 GOLGA2 Elena Savva gene: GOLGA2 was added
gene: GOLGA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GOLGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOLGA2 were set to PMID: 30237576; 26742501
Phenotypes for gene: GOLGA2 were set to Neuromuscular disorder
Review for gene: GOLGA2 was set to AMBER
Added comment: PMID: 30237576 - One 11 year old patient with a homozygous PTC.
Patient had global dev delay, microcephaly, distal muscle weakness with joint contractures and elevated CK levels. Muscle biopsy showed dystrophin changes. MRI at 2 years old showed brain atrophy with thin corpus callosum and hypomyelination. No seizures or regression.

PMID: 26742501 - One infant with a homozygous PTC.
Patient had dev delay, seizures, microcephaly and muscular dystrophy. Zebrafish null model recapitulates the human phenotype with microcephaly and skeletal muscle disorganization.

Summary: 2 patients
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v0.27 GOLGA2 Elena Savva gene: GOLGA2 was added
gene: GOLGA2 was added to Muscular dystrophy. Sources: Literature
Mode of inheritance for gene: GOLGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOLGA2 were set to PMID: 30237576; 26742501
Phenotypes for gene: GOLGA2 were set to Neuromuscular disorder
Review for gene: GOLGA2 was set to AMBER
Added comment: PMID: 30237576 - One 11 year old patient with a homozygous PTC.
Patient had global dev delay, microcephaly, distal muscle weakness with joint contractures and elevated CK levels. Muscle biopsy showed dystrophin changes. MRI at 2 years old showed brain atrophy with thin corpus callosum and hypomyelination. No seizures or regression.

PMID: 26742501 - One infant with a homozygous PTC.
Patient had dev delay, seizures, microcephaly and muscular dystrophy. Zebrafish null model recapitulates the human phenotype with microcephaly and skeletal muscle disorganization.

Summary: 2 patients + animal model
Sources: Literature
Microcephaly v0.129 GOLGA2 Elena Savva gene: GOLGA2 was added
gene: GOLGA2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: GOLGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOLGA2 were set to PMID: 30237576; 26742501
Phenotypes for gene: GOLGA2 were set to Neuromuscular disorder
Review for gene: GOLGA2 was set to GREEN
Added comment: PMID: 30237576 - One 11 year old patient with a homozygous PTC.
Patient had global dev delay, microcephaly, distal muscle weakness with joint contractures and elevated CK levels. Muscle biopsy showed dystrophin changes. MRI at 2 years old showed brain atrophy with thin corpus callosum and hypomyelination. No seizures or regression.

PMID: 26742501 - One infant with a homozygous PTC.
Patient had dev delay, seizures, microcephaly and muscular dystrophy. Zebrafish null model recapitulates the human phenotype with microcephaly and skeletal muscle disorganization.

Summary: 2 patients + animal model
Sources: Literature
Mendeliome v0.3150 GOLGA2 Elena Savva gene: GOLGA2 was added
gene: GOLGA2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: GOLGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOLGA2 were set to PMID: 30237576; 26742501
Phenotypes for gene: GOLGA2 were set to Nueromuscular disorder
Review for gene: GOLGA2 was set to GREEN
Added comment: PMID: 30237576 - One 11 year old patient with a homozygous PTC.
Patient had global dev delay, microcephaly, distal muscle weakness with joint contractures and elevated CK levels. Muscle biopsy showed dystrophin changes. MRI at 2 years old showed brain atrophy with thin corpus callosum and hypomyelination. No seizures or regression.

PMID: 26742501 - One infant with a homozygous PTC.
Patient had dev delay, seizures, microcephaly and muscular dystrophy. Zebrafish null model recapitulates the human phenotype with microcephaly and skeletal muscle disorganization.

Summary: 2 patients + animal model
Sources: Expert list
Muscular dystrophy and myopathy_Paediatric v0.27 FHL1 Elena Savva gene: FHL1 was added
gene: FHL1 was added to Muscular dystrophy. Sources: Expert list
Mode of inheritance for gene: FHL1 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: FHL1 were set to PMID: 19181672; 19171836
Phenotypes for gene: FHL1 were set to Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset, MIM# 300717
Review for gene: FHL1 was set to AMBER
Added comment: XLD, severe progressive myopathy with onset in infancy.

PMID: 19181672 - 11 patients (9 families) with reducing body myopathy. All patients had progressive muscle weakness with 7/11 having onset <5 years old. Majority had proximal muscle weakness with elevated CK levels. Authors note "we would be hesitant to use the term dystrophic for this myopathy as the mechanisms of cell damage remain to be fully worked out"
p.His123 is a hotspot with recurring de novo missense mutations at this residue.

PMID: 19171836 - 5 patients with reducing body myopathy, 2/5 had fatal infantile forms of disease.

Summary: congenital onset has been found, however unsure if this qualifies as a dystrophy or only myopathy
Sources: Expert list
Muscular dystrophy and myopathy_Paediatric v0.27 PLEC Crystle Lee gene: PLEC was added
gene: PLEC was added to Muscular dystrophy. Sources: Expert Review
Mode of inheritance for gene: PLEC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLEC were set to 20624679; 21109228; 28824526
Phenotypes for gene: PLEC were set to Muscular dystrophy, limb-girdle, autosomal recessive 17 (MIM#613723)
Added comment: Onset in early childhood (OMIM).

PMID: 20624679: Reported 1 patient with congenital muscular dystrophy, hypotonia and elevated CK.

PMID: 21109228: Same homozygous variant affecting isoform 1f reported in 3 families. 2 affected members of one family reported as having early onset LMGD. Authors note that PLEC is usually associated with late-onset progressive muscle dystrophy.

PMID: 28824526: 1 patient reported with early childhood onset. Variant affects isoform 1f.


Rated GREEN in CMD (PanelApp UK)
Sources: Expert Review
Muscular dystrophy and myopathy_Paediatric v0.27 EMD Elena Savva gene: EMD was added
gene: EMD was added to Muscular dystrophy. Sources: Expert list
Mode of inheritance for gene: EMD was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: EMD were set to PMID: 21697856; 31802929
Phenotypes for gene: EMD were set to Emery-Dreifuss muscular dystrophy 1, X-linked 310300
Review for gene: EMD was set to GREEN
Added comment: PMID: 21697856 - 21 male patients with EM muscular dystrophy. Age of onset not well reported, only age at diagnosis. Youngest patient was 5 days old but asymptomatic, eldest was 55 years.
Of those with age of onset reported, 3 had progressive muscle weakness onset from neonatal-5 years.

PMID: 31802929 - 1 family (9 affected males) with elevated CK levels and mild skeletal muscular dystrophy. Youngest affected was 7 years old

PMID: 31645980 - 1 patient with difficulty moving his limb girdle and cervical vertebrae from 5 years old.

Summary: childhood onset reported
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.9 POGLUT1 Crystle Lee reviewed gene: POGLUT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27807076, 29034878; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 21 (MIM#617232); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.27 TCAP Crystle Lee Deleted their comment
Muscular dystrophy and myopathy_Paediatric v0.27 TCAP Crystle Lee edited their review of gene: TCAP: Added comment: >3 variants/families reported. Mean age at onset 12.5 years (OMIM). More suitable for LGMD panel.

PMID: 25055047: 2 different variants reported in 2 Dravidian families with LGMD, with a predominantly proximo - distal form of weakness. Raised CK levels consistent between all patients reported. Age of onset ranged from 4 - 23.

Abstract (https://doi.org/10.1016/j.nmd.2012.06.100): Same frameshift variant reported in (PMID: 25055047) identified in one adult patient who presented with progressive muscle weakness in his late teenage years. Authors notes this is the 9th family reported with variants in this gene.

PMID: 22029105: 1 adult patient with slowly progressive weakness in the upper and lower limbs reported with onset in early twenties. Elevated CK levels.

PMID: 18948002: Reported one patient who presented at the age of 15 with progressive proximal limb weakness.; Changed rating: RED
Muscular dystrophy and myopathy_Paediatric v0.27 RYR1 Crystle Lee reviewed gene: RYR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23553484; Phenotypes: Central core disease (MIM#117000), Minicore myopathy with external ophthalmoplegia (MIM#255320), Neuromuscular disease, congenital, with uniform type 1 fiber (MIM#117000); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2703 SIL1 Crystle Lee reviewed gene: SIL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24176978, 16282977; Phenotypes: Marinesco-Sjogren syndrome (MIM#248800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.146 SIL1 Crystle Lee reviewed gene: SIL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16282977, 24176978; Phenotypes: Marinesco-Sjogren syndrome (MIM#248800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.27 SIL1 Crystle Lee gene: SIL1 was added
gene: SIL1 was added to Muscular dystrophy. Sources: Expert Review
Mode of inheritance for gene: SIL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SIL1 were set to 16282977; 24176978
Phenotypes for gene: SIL1 were set to Marinesco-Sjogren syndrome (MIM#248800)
Added comment: Well reported in patients with the associated phenotype. Onset in infancy. Muscle weakness and elevated CK are consistent features of this phenotype. Myopathic changes observed in muscle biopsy.
Sources: Expert Review
Muscular dystrophy and myopathy_Paediatric v0.27 SYNE1 Zornitza Stark changed review comment from: Congenital onset described in at least two families.; to: Congenital onset described in at least two families with bi-allelic variants.
Muscular dystrophy and myopathy_Paediatric v0.27 SYNE1 Zornitza Stark edited their review of gene: SYNE1: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.27 SYNE1 Zornitza Stark Mode of inheritance for gene: SYNE1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.26 SYNE1 Zornitza Stark Marked gene: SYNE1 as ready
Muscular dystrophy and myopathy_Paediatric v0.26 SYNE1 Zornitza Stark Gene: syne1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.26 SYNE1 Zornitza Stark Phenotypes for gene: SYNE1 were changed from to Emery-Dreifuss muscular dystrophy 4, autosomal dominant 612998
Muscular dystrophy and myopathy_Paediatric v0.25 SYNE1 Zornitza Stark Publications for gene: SYNE1 were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.9 TCAP Crystle Lee reviewed gene: TCAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 25055047, 22029105, 18948002; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 7 (MIM#601954); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.24 SYNE1 Zornitza Stark Mode of inheritance for gene: SYNE1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Muscular dystrophy and myopathy_Paediatric v0.23 SYNE1 Zornitza Stark reviewed gene: SYNE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27782104, 19542096; Phenotypes: Emery-Dreifuss muscular dystrophy 4, autosomal dominant 612998; Mode of inheritance: None
Muscular dystrophy and myopathy_Paediatric v0.23 Zornitza Stark removed gene:ANO5 from the panel
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.9 ANO5 Zornitza Stark Marked gene: ANO5 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.9 ANO5 Zornitza Stark Gene: ano5 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.9 ANO5 Zornitza Stark Phenotypes for gene: ANO5 were changed from Gnathodiaphyseal dysplasia, 166260; Muscular dystrophy, limb-girdle, type 2L, 611307; Miyoshi muscular dystrophy 3, 613319 to Muscular dystrophy, limb-girdle, type 2L, 611307; Miyoshi muscular dystrophy 3, 613319
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.8 ANO5 Zornitza Stark Publications for gene: ANO5 were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.7 ANO5 Zornitza Stark reviewed gene: ANO5: Rating: GREEN; Mode of pathogenicity: None; Publications: 20096397 32399949; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 12 611307; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.22 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Muscular dystrophy and myopathy_Paediatric v0.21 TCAP Crystle Lee reviewed gene: TCAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 25055047, 22029105, 18948002; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 7 (MIM#601954); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.129 DPM1 Elena Savva gene: DPM1 was added
gene: DPM1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: DPM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPM1 were set to PMID:16641202; 10642602; 10642597
Phenotypes for gene: DPM1 were set to Congenital disorder of glycosylation, type Ie 608799
Added comment: PMID: 16641202 - 2 siblings of consanguineous parents. One patient showed retarded motor skills at 1, 2 and 4 years old, with distal myopathy present at 3 years of age. The younger sister presented at 7 weeks of age with generalized hypotonia. Both had normal CK levels. Both siblings were progressively microcephalic.

PMID: 10642602 - 2 chet siblings with hypotonia within the first year of life. Both had elevated CK. Both siblings were progressively microcephalic

PMID: 10642597 - 2 unrelated patients. One had profound hypotonia at 3 years of age. The other patient was markedly hypotonic in infancy. Both were microcephalic and hd elevated CK levels.
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.7 TRAPPC11 Crystle Lee reviewed gene: TRAPPC11: Rating: GREEN; Mode of pathogenicity: None; Publications: 23830518, 26322222, 29855340, 30105108; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 18 (MIM#615356); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.21 TRAPPC11 Crystle Lee gene: TRAPPC11 was added
gene: TRAPPC11 was added to Muscular dystrophy. Sources: Expert list
Mode of inheritance for gene: TRAPPC11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC11 were set to 23830518; 26322222; 29855340; 30105108
Phenotypes for gene: TRAPPC11 were set to Muscular dystrophy, limb-girdle, autosomal recessive 18 (MIM#615356)
Review for gene: TRAPPC11 was set to GREEN
Added comment: >3 patients reported with variable muscle phenotype (primarily LGMD), which is a significant feature of this multisystemic childhood onset condition. Elevated CK consistent feature.

PMID: 23830518: 2 different variants reported. Patients from one family presented with early onset proximal muscle weakness and raised CK levels. The second family presented with muscle weakness and elevated CK suggestive of myopathy.

PMID: 26322222: Reported childhood onset muscular dystrophy in one patient

PMID: 29855340: 1 patient with biallelic variants in TRAPPC11

PMID: 30105108: 2 siblings with promixal muscle weakness reported. Childhood onset.
Sources: Expert list
Mendeliome v0.3150 MUC7 Bryony Thompson Classified gene: MUC7 as Red List (low evidence)
Mendeliome v0.3150 MUC7 Bryony Thompson Gene: muc7 has been classified as Red List (Low Evidence).
Mendeliome v0.3149 MUC7 Bryony Thompson reviewed gene: MUC7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Asthma, protection against} MIM#600807; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3149 HTR3D Bryony Thompson Marked gene: HTR3D as ready
Mendeliome v0.3149 HTR3D Bryony Thompson Gene: htr3d has been classified as Red List (Low Evidence).
Mendeliome v0.3149 HTR3D Bryony Thompson Classified gene: HTR3D as Red List (low evidence)
Mendeliome v0.3149 HTR3D Bryony Thompson Gene: htr3d has been classified as Red List (Low Evidence).
Mendeliome v0.3148 HTR3D Bryony Thompson reviewed gene: HTR3D: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Mendeliome v0.3148 ALOX5AP Bryony Thompson Marked gene: ALOX5AP as ready
Mendeliome v0.3148 ALOX5AP Bryony Thompson Gene: alox5ap has been classified as Red List (Low Evidence).
Mendeliome v0.3148 ALOX5AP Bryony Thompson Classified gene: ALOX5AP as Red List (low evidence)
Mendeliome v0.3148 ALOX5AP Bryony Thompson Gene: alox5ap has been classified as Red List (Low Evidence).
Mendeliome v0.3147 ALOX5AP Bryony Thompson reviewed gene: ALOX5AP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Stroke, susceptibility to} MIM#601367; Mode of inheritance: Unknown
Muscular dystrophy and myopathy_Paediatric v0.21 COL4A2 Zornitza Stark Marked gene: COL4A2 as ready
Muscular dystrophy and myopathy_Paediatric v0.21 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.21 COL4A2 Zornitza Stark Classified gene: COL4A2 as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v0.21 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.20 COL4A1 Zornitza Stark Phenotypes for gene: COL4A1 were changed from ?Retinal arteries, tortuosity of MIM#180000; Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps MIM#611773; Brain small vessel disease with or without ocular anomalies MIM#175780; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant MIM#618564 to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps MIM#611773; Brain small vessel disease with or without ocular anomalies MIM#175780; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant MIM#618564
Muscular dystrophy and myopathy_Paediatric v0.19 COL4A1 Zornitza Stark Publications for gene: COL4A1 were set to 23065703; 20818663
Muscular dystrophy and myopathy_Paediatric v0.18 COL4A1 Zornitza Stark Classified gene: COL4A1 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v0.18 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.17 CAVIN1 Zornitza Stark Publications for gene: CAVIN1 were set to
Muscular dystrophy and myopathy_Paediatric v0.16 CAVIN1 Zornitza Stark edited their review of gene: CAVIN1: Changed publications: 19726876, 12116229
Muscular dystrophy and myopathy_Paediatric v0.16 ANO5 Zornitza Stark Marked gene: ANO5 as ready
Muscular dystrophy and myopathy_Paediatric v0.16 ANO5 Zornitza Stark Gene: ano5 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.16 ANO5 Zornitza Stark Classified gene: ANO5 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.16 ANO5 Zornitza Stark Gene: ano5 has been classified as Green List (High Evidence).
Dystonia - complex v0.69 SQSTM1 Zornitza Stark Marked gene: SQSTM1 as ready
Dystonia - complex v0.69 SQSTM1 Zornitza Stark Gene: sqstm1 has been classified as Green List (High Evidence).
Dystonia - complex v0.69 SQSTM1 Zornitza Stark Classified gene: SQSTM1 as Green List (high evidence)
Dystonia - complex v0.69 SQSTM1 Zornitza Stark Gene: sqstm1 has been classified as Green List (High Evidence).
Arrhythmogenic Cardiomyopathy v0.6 JUP Zornitza Stark Marked gene: JUP as ready
Arrhythmogenic Cardiomyopathy v0.6 JUP Zornitza Stark Gene: jup has been classified as Green List (High Evidence).
Arrhythmogenic Cardiomyopathy v0.6 JUP Zornitza Stark Phenotypes for gene: JUP were changed from to Arrhythmogenic right ventricular dysplasia 12 MIM# 611528; Naxos disease MIM# 601214
Arrhythmogenic Cardiomyopathy v0.5 JUP Zornitza Stark Publications for gene: JUP were set to
Arrhythmogenic Cardiomyopathy v0.4 JUP Zornitza Stark Mode of inheritance for gene: JUP was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.7 PNPLA2 Zornitza Stark Marked gene: PNPLA2 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.7 PNPLA2 Zornitza Stark Gene: pnpla2 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.7 PNPLA2 Zornitza Stark Classified gene: PNPLA2 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.7 PNPLA2 Zornitza Stark Gene: pnpla2 has been classified as Green List (High Evidence).
Mendeliome v0.3147 PHOX2A Zornitza Stark Marked gene: PHOX2A as ready
Mendeliome v0.3147 PHOX2A Zornitza Stark Gene: phox2a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3147 PHOX2A Zornitza Stark Phenotypes for gene: PHOX2A were changed from to Fibrosis of extraocular muscles, congenital, 2 602078
Mendeliome v0.3146 PHOX2A Zornitza Stark Publications for gene: PHOX2A were set to
Mendeliome v0.3145 PHOX2A Zornitza Stark Mode of inheritance for gene: PHOX2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3144 PHOX2A Zornitza Stark Classified gene: PHOX2A as Amber List (moderate evidence)
Mendeliome v0.3144 PHOX2A Zornitza Stark Gene: phox2a has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.64 KLC2 Bryony Thompson edited their review of gene: KLC2: Changed rating: GREEN
Muscular dystrophy and myopathy_Paediatric v0.15 COL4A2 Elena Savva gene: COL4A2 was added
gene: COL4A2 was added to Muscular dystrophy. Sources: Expert list
Mode of inheritance for gene: COL4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COL4A2 were set to PMID: 25719457; 30315939
Phenotypes for gene: COL4A2 were set to Brain small vessel disease 2 614483
Penetrance for gene: COL4A2 were set to Incomplete
Mode of pathogenicity for gene: COL4A2 was set to Other
Review for gene: COL4A2 was set to RED
Added comment: OMIM reports - Variable severity - Incomplete penetrance

PMID: 25719457 - 0/15 heterozygous carriers report any myopathy phenotype. Majority had porencephaly or periventricular leukoencephalopathy.

PMID: 30315939 - two patients with schizencephaly and/or polymicrogyria. Authors specifically noted myopathy was not observed in any patient, one was reported to have normal CK levels.

Both LOF and dominant negative are suggested mechanisms for this gene.
Sources: Expert list
Muscular dystrophy and myopathy_Paediatric v0.15 COL4A1 Elena Savva reviewed gene: COL4A1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 25719457, 21625620, 23225343; Phenotypes: Microangiopathy and leukoencephalopathy, pontine, autosomal dominant 618564, Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps 611773; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Muscular dystrophy and myopathy_Paediatric v0.15 ANO5 Elena Savva gene: ANO5 was added
gene: ANO5 was added to Muscular dystrophy. Sources: Expert list
Mode of inheritance for gene: ANO5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANO5 were set to PMID: 20096397; 32399949
Phenotypes for gene: ANO5 were set to Muscular dystrophy, limb-girdle, autosomal recessive 12 611307
Penetrance for gene: ANO5 were set to unknown
Review for gene: ANO5 was set to GREEN
Added comment: PMID: 20096397 - 5 families (12 patients) with either proximal limb girdle muscular dystrophy (3/5) or distal miyoshi myopathy (2/5). No obvious genotype-phenotype correlation, homozygous PTCs reported to cause both conditions. Age of onset >30 years old.

PMID: 32399949 - 3 patients with biallelic variants. All are carriers of the common c.191dupA variant with a missense in trans. 1/3 has limb girdle muscular dystrophy, all patients have onset >30 years old
Sources: Expert list
Dystonia - complex v0.68 SQSTM1 Elena Savva gene: SQSTM1 was added
gene: SQSTM1 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: SQSTM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SQSTM1 were set to PMID: 27545679
Phenotypes for gene: SQSTM1 were set to Myopathy, distal, with rimmed vacuoles 617158
Review for gene: SQSTM1 was set to GREEN
Added comment: PMID: 27545679 - 9 patients (4 families) with childhood/adolescent onset neurodegeneration syndrome. 7/9 patients presented with dystonia. None noted to have myopathy.
Sources: Literature
Arrhythmogenic Cardiomyopathy v0.3 JUP Teresa Zhao reviewed gene: JUP: Rating: GREEN; Mode of pathogenicity: None; Publications: 16722579, 17924338; Phenotypes: Arrhythmogenic right ventricular dysplasia 12 MIM# 611528, Naxos disease MIM# 601214; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.6 PNPLA2 Elena Savva gene: PNPLA2 was added
gene: PNPLA2 was added to Limb Girdle Muscular Dystrophy. Sources: Literature
Mode of inheritance for gene: PNPLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA2 were set to PMID: 32269696; 21544567
Phenotypes for gene: PNPLA2 were set to Neutral lipid storage disease with myopathy 610717
Review for gene: PNPLA2 was set to GREEN
Added comment: PMID: 32269696 - 1 patient with both upper and lower limb weakness. She had elevated CK levels, with onset >25 years old.

PMID: 21544567 - 6 patients with distal muscle weakness, shoulder girdle weakness and elevated CK levels. Severe dystrophic features of the shoulder girdle noted in 3/3 patients analysed by whole body MRI. Proximal muscle weakness was generalised first, with lower limbs affected in the 3rd/4th decade of life. Earliest age of onset 29 years old, 5/6 patients had homozygous PTCs.
Sources: Literature
Mendeliome v0.3143 PHOX2A Elena Savva reviewed gene: PHOX2A: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 11600883, 18323871; Phenotypes: Fibrosis of extraocular muscles, congenital, 2 602078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.88 TCAP Zornitza Stark Marked gene: TCAP as ready
Hypertrophic cardiomyopathy_HCM v0.88 TCAP Zornitza Stark Gene: tcap has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.88 TCAP Zornitza Stark Publications for gene: TCAP were set to
Hypertrophic cardiomyopathy_HCM v0.87 TCAP Zornitza Stark reviewed gene: TCAP: Rating: RED; Mode of pathogenicity: None; Publications: 16352453, 15582318; Phenotypes: Cardiomyopathy, hypertrophic, 25, MIM# 607487; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.87 TCAP Zornitza Stark Phenotypes for gene: TCAP were changed from to Cardiomyopathy, hypertrophic, 25, MIM# 607487
Hypertrophic cardiomyopathy_HCM v0.86 TCAP Zornitza Stark Mode of inheritance for gene: TCAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.85 TCAP Zornitza Stark Classified gene: TCAP as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.85 TCAP Zornitza Stark Gene: tcap has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.84 VCL Zornitza Stark Marked gene: VCL as ready
Hypertrophic cardiomyopathy_HCM v0.84 VCL Zornitza Stark Gene: vcl has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.84 VCL Zornitza Stark Phenotypes for gene: VCL were changed from to Cardiomyopathy, hypertrophic, 15, MIM# 613255
Hypertrophic cardiomyopathy_HCM v0.83 VCL Zornitza Stark Publications for gene: VCL were set to
Hypertrophic cardiomyopathy_HCM v0.82 VCL Zornitza Stark Mode of inheritance for gene: VCL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.81 VCL Zornitza Stark Classified gene: VCL as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.81 VCL Zornitza Stark Gene: vcl has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.80 VCL Zornitza Stark reviewed gene: VCL: Rating: RED; Mode of pathogenicity: None; Publications: 17097056; Phenotypes: Cardiomyopathy, hypertrophic, 15, MIM# 613255; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.80 NEXN Zornitza Stark Marked gene: NEXN as ready
Hypertrophic cardiomyopathy_HCM v0.80 NEXN Zornitza Stark Gene: nexn has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.80 NEXN Zornitza Stark Phenotypes for gene: NEXN were changed from to Cardiomyopathy, hypertrophic, 20, MIM# 613876
Hypertrophic cardiomyopathy_HCM v0.79 NEXN Zornitza Stark Publications for gene: NEXN were set to
Hypertrophic cardiomyopathy_HCM v0.78 NEXN Zornitza Stark Mode of inheritance for gene: NEXN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.77 NEXN Zornitza Stark reviewed gene: NEXN: Rating: RED; Mode of pathogenicity: None; Publications: 20970104; Phenotypes: Cardiomyopathy, hypertrophic, 20, MIM# 613876; Mode of inheritance: None
Hypertrophic cardiomyopathy_HCM v0.77 NEXN Zornitza Stark Classified gene: NEXN as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.77 NEXN Zornitza Stark Gene: nexn has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.76 MYLK2 Zornitza Stark Publications for gene: MYLK2 were set to 11733062; 24082139; 25825456; 20301725
Hypertrophic cardiomyopathy_HCM v0.75 MYL3 Zornitza Stark Marked gene: MYL3 as ready
Hypertrophic cardiomyopathy_HCM v0.75 MYL3 Zornitza Stark Gene: myl3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.75 MYL3 Zornitza Stark Phenotypes for gene: MYL3 were changed from to Cardiomyopathy, hypertrophic, 8, MIM# 608751
Hypertrophic cardiomyopathy_HCM v0.74 MYL3 Zornitza Stark Publications for gene: MYL3 were set to
Hypertrophic cardiomyopathy_HCM v0.73 MYL3 Zornitza Stark Mode of inheritance for gene: MYL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.72 TNNI3 Zornitza Stark Marked gene: TNNI3 as ready
Hypertrophic cardiomyopathy_HCM v0.72 TNNI3 Zornitza Stark Gene: tnni3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.72 TNNI3 Zornitza Stark Phenotypes for gene: TNNI3 were changed from to Cardiomyopathy, hypertrophic, 7, MIM# 613690
Hypertrophic cardiomyopathy_HCM v0.71 TNNI3 Zornitza Stark Publications for gene: TNNI3 were set to 30681346
Hypertrophic cardiomyopathy_HCM v0.71 TNNI3 Zornitza Stark Publications for gene: TNNI3 were set to
Hypertrophic cardiomyopathy_HCM v0.70 TNNI3 Zornitza Stark Mode of inheritance for gene: TNNI3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.69 TPM1 Zornitza Stark Publications for gene: TPM1 were set to 31270709
Hypertrophic cardiomyopathy_HCM v0.68 MYBPC3 Zornitza Stark Publications for gene: MYBPC3 were set to 20378854
Mendeliome v0.3143 TANC2 Zornitza Stark Phenotypes for gene: TANC2 were changed from Intellectual disability; autism; epilepsy; dysmorphism to Intellectual disability; autism; epilepsy; dysmorphism; Intellectual developmental disorder with autistic features and language delay, with or without seizures, MIM# 618906
Mendeliome v0.3142 TANC2 Zornitza Stark edited their review of gene: TANC2: Changed phenotypes: Intellectual disability, autism, epilepsy, dysmorphism, Intellectual developmental disorder with autistic features and language delay, with or without seizures, MIM# 618906
Intellectual disability syndromic and non-syndromic v0.2703 TANC2 Zornitza Stark Phenotypes for gene: TANC2 were changed from no OMIM number yet; Intellectual disability; autism; epilepsy; dysmorphism to Intellectual disability; autism; epilepsy; dysmorphism; Intellectual developmental disorder with autistic features and language delay, with or without seizures, MIM# 618906
Intellectual disability syndromic and non-syndromic v0.2702 TANC2 Zornitza Stark reviewed gene: TANC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with autistic features and language delay, with or without seizures, MIM# 618906; Mode of inheritance: None
Mendeliome v0.3142 ABCC1 Zornitza Stark Phenotypes for gene: ABCC1 were changed from Nonsyndromic hearing loss to Deafness-77, autosomal dominant (DFNA77), MIM#618915
Mendeliome v0.3141 ABCC1 Zornitza Stark edited their review of gene: ABCC1: Changed phenotypes: Deafness-77, autosomal dominant (DFNA77), MIM#618915
Deafness_IsolatedAndComplex v0.352 ABCC1 Zornitza Stark Phenotypes for gene: ABCC1 were changed from Nonsyndromic hearing loss; Deafness-77, autosomal dominant (DFNA77), MIM#618915 to Nonsyndromic hearing loss; Deafness-77, autosomal dominant (DFNA77), MIM#618915
Deafness_IsolatedAndComplex v0.352 ABCC1 Zornitza Stark Phenotypes for gene: ABCC1 were changed from Nonsyndromic hearing loss (PMID: 31273342) to Nonsyndromic hearing loss; Deafness-77, autosomal dominant (DFNA77), MIM#618915
Deafness_IsolatedAndComplex v0.351 ABCC1 Zornitza Stark edited their review of gene: ABCC1: Changed rating: AMBER; Changed phenotypes: Deafness-77, autosomal dominant (DFNA77), MIM#618915
Mendeliome v0.3141 SORD Zornitza Stark Phenotypes for gene: SORD were changed from isolated hereditary neuropathy to isolated hereditary neuropathy; Sorbitol dehydrogenase deficiency with peripheral neuropathy (SORDDPN), MIM#618912
Mendeliome v0.3140 SORD Zornitza Stark reviewed gene: SORD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sorbitol dehydrogenase deficiency with peripheral neuropathy (SORDDPN), MIM#618912; Mode of inheritance: None
Hereditary Neuropathy_CMT - isolated v0.47 SORD Zornitza Stark Phenotypes for gene: SORD were changed from isolated hereditary neuropathy to isolated hereditary neuropathy; Sorbitol dehydrogenase deficiency with peripheral neuropathy (SORDDPN), MIM#618912
Hereditary Neuropathy_CMT - isolated v0.46 SORD Zornitza Stark edited their review of gene: SORD: Changed rating: GREEN
Hereditary Neuropathy_CMT - isolated v0.46 SORD Zornitza Stark reviewed gene: SORD: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Sorbitol dehydrogenase deficiency with peripheral neuropathy (SORDDPN), MIM#618912; Mode of inheritance: None
Hypertrophic cardiomyopathy_HCM v0.67 MYBPC3 Ivan Macciocca reviewed gene: MYBPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.67 TPM1 Ivan Macciocca reviewed gene: TPM1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.67 TNNI3 Ivan Macciocca reviewed gene: TNNI3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.67 MYL3 Ivan Macciocca reviewed gene: MYL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30681346; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.67 MYLK2 Ivan Macciocca reviewed gene: MYLK2: Rating: RED; Mode of pathogenicity: None; Publications: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.67 NEXN Ivan Macciocca reviewed gene: NEXN: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.67 VCL Ivan Macciocca reviewed gene: VCL: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy - adult onset v0.76 MLC1 Zornitza Stark Classified gene: MLC1 as Amber List (moderate evidence)
Leukodystrophy - adult onset v0.76 MLC1 Zornitza Stark Gene: mlc1 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.75 MLC1 Zornitza Stark edited their review of gene: MLC1: Changed rating: AMBER
Hypertrophic cardiomyopathy_HCM v0.67 TCAP Ivan Macciocca reviewed gene: TCAP: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.67 MYOM1 Ivan Macciocca reviewed gene: MYOM1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.67 MYH6 Ivan Macciocca reviewed gene: MYH6: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy - adult onset v0.75 AARS Zornitza Stark Marked gene: AARS as ready
Leukodystrophy - adult onset v0.75 AARS Zornitza Stark Gene: aars has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.75 AARS Zornitza Stark Classified gene: AARS as Amber List (moderate evidence)
Leukodystrophy - adult onset v0.75 AARS Zornitza Stark Gene: aars has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.74 AARS Zornitza Stark Marked gene: AARS as ready
Leukodystrophy - adult onset v0.74 AARS Zornitza Stark Gene: aars has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.74 AARS Zornitza Stark Classified gene: AARS as Amber List (moderate evidence)
Leukodystrophy - adult onset v0.74 AARS Zornitza Stark Gene: aars has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.73 AARS Zornitza Stark gene: AARS was added
gene: AARS was added to Leukodystrophy - adult onset. Sources: Expert list
Mode of inheritance for gene: AARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AARS were set to 31775912
Phenotypes for gene: AARS were set to Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287
Review for gene: AARS was set to AMBER
Added comment: Limited evidence to link with leukodystrophy.
Sources: Expert list
Leukodystrophy_Superpanel v0.239 Zornitza Stark Panel types changed to Australian Genomics; Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Leukodystrophy - paediatric v0.165 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Leukodystrophy - adult onset v0.72 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Leukodystrophy - paediatric v0.164 RNASEH2A Zornitza Stark Marked gene: RNASEH2A as ready
Leukodystrophy - paediatric v0.164 RNASEH2A Zornitza Stark Gene: rnaseh2a has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.164 RNASEH2A Zornitza Stark Classified gene: RNASEH2A as Green List (high evidence)
Leukodystrophy - paediatric v0.164 RNASEH2A Zornitza Stark Gene: rnaseh2a has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.163 RNASEH2A Zornitza Stark gene: RNASEH2A was added
gene: RNASEH2A was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: RNASEH2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2A were set to 16845400; 23592335; 17846997
Phenotypes for gene: RNASEH2A were set to Aicardi-Goutieres syndrome 4, MIM# 610333
Review for gene: RNASEH2A was set to GREEN
Added comment: Leukodystrophy is a common feature, onset is typically in infancy.
Sources: Expert list
Leukodystrophy - paediatric v0.162 RNASEH2B Zornitza Stark Marked gene: RNASEH2B as ready
Leukodystrophy - paediatric v0.162 RNASEH2B Zornitza Stark Gene: rnaseh2b has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.162 RNASEH2B Zornitza Stark Classified gene: RNASEH2B as Green List (high evidence)
Leukodystrophy - paediatric v0.162 RNASEH2B Zornitza Stark Gene: rnaseh2b has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.161 RNASEH2B Zornitza Stark gene: RNASEH2B was added
gene: RNASEH2B was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: RNASEH2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2B were set to 16845400
Phenotypes for gene: RNASEH2B were set to Aicardi-Goutieres syndrome 2, MIM# 610181
Review for gene: RNASEH2B was set to GREEN
Added comment: Leukodystrophy is common in AGS in general, though basal ganglia calcification seems to predominate here.
Sources: Expert list
Leukodystrophy - paediatric v0.160 RNASEH2C Zornitza Stark Marked gene: RNASEH2C as ready
Leukodystrophy - paediatric v0.160 RNASEH2C Zornitza Stark Gene: rnaseh2c has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.160 RNASEH2C Zornitza Stark Classified gene: RNASEH2C as Green List (high evidence)
Leukodystrophy - paediatric v0.160 RNASEH2C Zornitza Stark Gene: rnaseh2c has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.159 RNASEH2C Zornitza Stark gene: RNASEH2C was added
gene: RNASEH2C was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: RNASEH2C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2C were set to 16845400; 23322642
Phenotypes for gene: RNASEH2C were set to Aicardi-Goutieres syndrome 3, MIM# 610329
Review for gene: RNASEH2C was set to GREEN
Added comment: Leukodystrophy is a prominent feature, onset is typically in infancy.
Sources: Expert list
Leukodystrophy - adult onset v0.71 RNASET2 Zornitza Stark Marked gene: RNASET2 as ready
Leukodystrophy - adult onset v0.71 RNASET2 Zornitza Stark Gene: rnaset2 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.71 RNASET2 Zornitza Stark Publications for gene: RNASET2 were set to
Leukodystrophy - adult onset v0.70 RNASET2 Zornitza Stark Classified gene: RNASET2 as Amber List (moderate evidence)
Leukodystrophy - adult onset v0.70 RNASET2 Zornitza Stark Gene: rnaset2 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.69 RNASET2 Zornitza Stark reviewed gene: RNASET2: Rating: AMBER; Mode of pathogenicity: None; Publications: 19525954; Phenotypes: Leukoencephalopathy, cystic, without megalencephaly, MIM# 612951; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.158 RNASET2 Zornitza Stark changed review comment from: 5 unrelated families in the original publication.
Sources: Expert list; to: 5 unrelated families in the original publication, onset in infancy.
Sources: Expert list
Leukodystrophy - paediatric v0.158 RNASET2 Zornitza Stark Marked gene: RNASET2 as ready
Leukodystrophy - paediatric v0.158 RNASET2 Zornitza Stark Gene: rnaset2 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.158 RNASET2 Zornitza Stark Classified gene: RNASET2 as Green List (high evidence)
Leukodystrophy - paediatric v0.158 RNASET2 Zornitza Stark Gene: rnaset2 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.157 RNASET2 Zornitza Stark gene: RNASET2 was added
gene: RNASET2 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: RNASET2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASET2 were set to 19525954
Phenotypes for gene: RNASET2 were set to Leukoencephalopathy, cystic, without megalencephaly, MIM# 612951
Review for gene: RNASET2 was set to GREEN
Added comment: 5 unrelated families in the original publication.
Sources: Expert list
Leukodystrophy - adult onset v0.69 SAMHD1 Zornitza Stark Marked gene: SAMHD1 as ready
Leukodystrophy - adult onset v0.69 SAMHD1 Zornitza Stark Gene: samhd1 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.69 SAMHD1 Zornitza Stark Publications for gene: SAMHD1 were set to
Leukodystrophy - adult onset v0.68 SAMHD1 Zornitza Stark reviewed gene: SAMHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19525956; Phenotypes: Aicardi-Goutieres syndrome 5, MIM# 612952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.156 SAMHD1 Zornitza Stark Marked gene: SAMHD1 as ready
Leukodystrophy - paediatric v0.156 SAMHD1 Zornitza Stark Gene: samhd1 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.156 SAMHD1 Zornitza Stark Publications for gene: SAMHD1 were set to
Leukodystrophy - paediatric v0.155 SAMHD1 Zornitza Stark Classified gene: SAMHD1 as Green List (high evidence)
Leukodystrophy - paediatric v0.155 SAMHD1 Zornitza Stark Gene: samhd1 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.154 SAMHD1 Zornitza Stark edited their review of gene: SAMHD1: Changed publications: 19525956; Changed phenotypes: Aicardi-Goutieres syndrome 5, MIM# 612952
Leukodystrophy - paediatric v0.154 SAMHD1 Zornitza Stark gene: SAMHD1 was added
gene: SAMHD1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: SAMHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SAMHD1 were set to Aicardi-Goutieres syndrome 5, MIM# 612952
Review for gene: SAMHD1 was set to GREEN
Added comment: Leukodystrophy is a prominent feature, onset is variable but typically in infancy/childhood.
Sources: Expert list
Leukodystrophy - paediatric v0.153 SLC17A5 Zornitza Stark Marked gene: SLC17A5 as ready
Leukodystrophy - paediatric v0.153 SLC17A5 Zornitza Stark Gene: slc17a5 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.153 SLC17A5 Zornitza Stark Classified gene: SLC17A5 as Green List (high evidence)
Leukodystrophy - paediatric v0.153 SLC17A5 Zornitza Stark Gene: slc17a5 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.152 SLC17A5 Zornitza Stark gene: SLC17A5 was added
gene: SLC17A5 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: SLC17A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC17A5 were set to 16417876
Phenotypes for gene: SLC17A5 were set to Salla disease 604369; Sialic acid storage disorder, infantile 269920
Review for gene: SLC17A5 was set to GREEN
Added comment: White matter abnormalities described in this metabolic disorder.
Sources: Expert list
Leukodystrophy - paediatric v0.151 SPG11 Zornitza Stark Publications for gene: SPG11 were set to
Leukodystrophy - adult onset v0.68 SPG11 Zornitza Stark Marked gene: SPG11 as ready
Leukodystrophy - adult onset v0.68 SPG11 Zornitza Stark Gene: spg11 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.68 SPG11 Zornitza Stark Publications for gene: SPG11 were set to
Leukodystrophy - adult onset v0.67 SPG11 Zornitza Stark reviewed gene: SPG11: Rating: GREEN; Mode of pathogenicity: None; Publications: 18067136; Phenotypes: Spastic paraplegia 11, autosomal recessive, MIM# 604360; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.150 SPG11 Zornitza Stark changed review comment from: Complex SPG with central involvement, including white matter changes.
Sources: Expert list; to: Complex SPG with central involvement, including white matter changes. Variable age of onset, including in childhood.
Sources: Expert list
Leukodystrophy - paediatric v0.150 SPG11 Zornitza Stark edited their review of gene: SPG11: Changed publications: 18067136; Changed phenotypes: Spastic paraplegia 11, autosomal recessive, MIM# 604360
Leukodystrophy - paediatric v0.150 SPG11 Zornitza Stark Marked gene: SPG11 as ready
Leukodystrophy - paediatric v0.150 SPG11 Zornitza Stark Gene: spg11 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.150 SPG11 Zornitza Stark Classified gene: SPG11 as Green List (high evidence)
Leukodystrophy - paediatric v0.150 SPG11 Zornitza Stark Gene: spg11 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.149 SPG11 Zornitza Stark gene: SPG11 was added
gene: SPG11 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: SPG11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPG11 were set to Spastic paraplegia 11, autosomal recessive, MIM# 604360
Review for gene: SPG11 was set to GREEN
Added comment: Complex SPG with central involvement, including white matter changes.
Sources: Expert list
Leukodystrophy - adult onset v0.67 TREX1 Zornitza Stark changed review comment from: White matter changes are part of the phenotype. Onset is typically in infancy/early childhood but can be highly variable.; to: AGS: White matter changes are part of the phenotype. Onset is typically in infancy/early childhood but can be highly variable. Vasculopathy, retinal, with cerebral leukodystrophy, MIM# 192315: adult-onset disorder.
Leukodystrophy - adult onset v0.67 TREX1 Zornitza Stark edited their review of gene: TREX1: Changed phenotypes: Aicardi-Goutieres syndrome 1, dominant and recessive, MIM# 225750, Vasculopathy, retinal, with cerebral leukodystrophy 192315
Leukodystrophy - adult onset v0.67 TREX1 Zornitza Stark Marked gene: TREX1 as ready
Leukodystrophy - adult onset v0.67 TREX1 Zornitza Stark Gene: trex1 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.67 TREX1 Zornitza Stark reviewed gene: TREX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 1, dominant and recessive, MIM# 225750; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.148 TREX1 Zornitza Stark Marked gene: TREX1 as ready
Leukodystrophy - paediatric v0.148 TREX1 Zornitza Stark Gene: trex1 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.148 TREX1 Zornitza Stark Classified gene: TREX1 as Green List (high evidence)
Leukodystrophy - paediatric v0.148 TREX1 Zornitza Stark Gene: trex1 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.147 TREX1 Zornitza Stark gene: TREX1 was added
gene: TREX1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: TREX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: TREX1 were set to Aicardi-Goutieres syndrome 1, dominant and recessive, MIM# 225750
Review for gene: TREX1 was set to GREEN
Added comment: White matter changes are part of the phenotype. Onset is typically in infancy/childhood but can be variable.
Sources: Expert list
Leukodystrophy - adult onset v0.67 TUBB4A Zornitza Stark Marked gene: TUBB4A as ready
Leukodystrophy - adult onset v0.67 TUBB4A Zornitza Stark Gene: tubb4a has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.67 TUBB4A Zornitza Stark Phenotypes for gene: TUBB4A were changed from Leukodystrophy, hypomyelinating, 6, 612438 to Leukodystrophy, hypomyelinating, 6, MIM#612438
Leukodystrophy - adult onset v0.66 TUBB4A Zornitza Stark Publications for gene: TUBB4A were set to
Leukodystrophy - adult onset v0.65 TUBB4A Zornitza Stark reviewed gene: TUBB4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 28791129; Phenotypes: Leukodystrophy, hypomyelinating, 6, MIM# 612438; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy - paediatric v0.146 TUBB4A Zornitza Stark Marked gene: TUBB4A as ready
Leukodystrophy - paediatric v0.146 TUBB4A Zornitza Stark Gene: tubb4a has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.146 TUBB4A Zornitza Stark Classified gene: TUBB4A as Green List (high evidence)
Leukodystrophy - paediatric v0.146 TUBB4A Zornitza Stark Gene: tubb4a has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.145 TUBB4A Zornitza Stark gene: TUBB4A was added
gene: TUBB4A was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: TUBB4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB4A were set to 24850488; 23582646
Phenotypes for gene: TUBB4A were set to Leukodystrophy, hypomyelinating, 6, MIM# 612438
Review for gene: TUBB4A was set to GREEN
Added comment: Multiple individuals reported, onset of symptoms is typically in infancy and early childhood.
Sources: Expert list
Leukodystrophy - adult onset v0.65 TYROBP Zornitza Stark Marked gene: TYROBP as ready
Leukodystrophy - adult onset v0.65 TYROBP Zornitza Stark Gene: tyrobp has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.65 TYROBP Zornitza Stark reviewed gene: TYROBP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1, MIM# 221770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.144 ZFYVE26 Zornitza Stark Marked gene: ZFYVE26 as ready
Leukodystrophy - paediatric v0.144 ZFYVE26 Zornitza Stark Gene: zfyve26 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.144 ZFYVE26 Zornitza Stark Classified gene: ZFYVE26 as Green List (high evidence)
Leukodystrophy - paediatric v0.144 ZFYVE26 Zornitza Stark Gene: zfyve26 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.143 ZFYVE26 Zornitza Stark gene: ZFYVE26 was added
gene: ZFYVE26 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: ZFYVE26 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZFYVE26 were set to Spastic paraplegia 15, autosomal recessive, MIM# 270700
Review for gene: ZFYVE26 was set to GREEN
Added comment: Complex spastic paraplegia, including white matter changes. Variable age of onset ranging from paediatric to adult.
Sources: Expert list
Leukodystrophy - adult onset v0.65 ZFYVE26 Zornitza Stark Marked gene: ZFYVE26 as ready
Leukodystrophy - adult onset v0.65 ZFYVE26 Zornitza Stark Gene: zfyve26 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.65 ZFYVE26 Zornitza Stark reviewed gene: ZFYVE26: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 15, autosomal recessive, MIM# 270700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.142 PSAP Zornitza Stark Marked gene: PSAP as ready
Leukodystrophy - paediatric v0.142 PSAP Zornitza Stark Gene: psap has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.142 PSAP Zornitza Stark Classified gene: PSAP as Green List (high evidence)
Leukodystrophy - paediatric v0.142 PSAP Zornitza Stark Gene: psap has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.141 PSAP Zornitza Stark gene: PSAP was added
gene: PSAP was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: PSAP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PSAP were set to Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900
Review for gene: PSAP was set to GREEN
Added comment: Childhood onset.
Sources: Expert list
Leukodystrophy - adult onset v0.65 POLR3B Zornitza Stark Marked gene: POLR3B as ready
Leukodystrophy - adult onset v0.65 POLR3B Zornitza Stark Gene: polr3b has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.65 POLR3B Zornitza Stark Publications for gene: POLR3B were set to
Leukodystrophy - adult onset v0.64 POLR3B Zornitza Stark reviewed gene: POLR3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 25339210; Phenotypes: Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, 614381; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.140 POLR3B Zornitza Stark Marked gene: POLR3B as ready
Leukodystrophy - paediatric v0.140 POLR3B Zornitza Stark Gene: polr3b has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.140 POLR3B Zornitza Stark Classified gene: POLR3B as Green List (high evidence)
Leukodystrophy - paediatric v0.140 POLR3B Zornitza Stark Gene: polr3b has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.139 POLR3B Zornitza Stark gene: POLR3B was added
gene: POLR3B was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: POLR3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3B were set to 27512013; 22036171; 22036172
Phenotypes for gene: POLR3B were set to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 614381
Review for gene: POLR3B was set to GREEN
Added comment: More than 10 families reported. Early childhood onset of cerebellar ataxia and mild intellectual disabilities associated with diffuse hypomyelination apparent on brain MRI. Variable features include oligodontia and/or hypogonadotropic hypogonadism.
Sources: Expert list
Leukodystrophy - adult onset v0.64 POLR3A Zornitza Stark Marked gene: POLR3A as ready
Leukodystrophy - adult onset v0.64 POLR3A Zornitza Stark Gene: polr3a has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.64 POLR3A Zornitza Stark Publications for gene: POLR3A were set to
Leukodystrophy - adult onset v0.63 POLR3A Zornitza Stark reviewed gene: POLR3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31306222; Phenotypes: Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 607694; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.138 POLR3A Zornitza Stark Marked gene: POLR3A as ready
Leukodystrophy - paediatric v0.138 POLR3A Zornitza Stark Gene: polr3a has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.138 POLR3A Zornitza Stark Classified gene: POLR3A as Green List (high evidence)
Leukodystrophy - paediatric v0.138 POLR3A Zornitza Stark Gene: polr3a has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.137 POLR3A Zornitza Stark gene: POLR3A was added
gene: POLR3A was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3A were set to 21855841
Phenotypes for gene: POLR3A were set to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 607694
Review for gene: POLR3A was set to GREEN
Added comment: More than 10 families reported. Neurodegenerative disorder characterised by childhood onset of progressive motor decline manifest as spasticity, ataxia, tremor, and cerebellar signs, as well as mild cognitive regression. Other features may include hypodontia or oligodontia and hypogonadotropic hypogonadism.
Sources: Expert list
Leukodystrophy - adult onset v0.63 POLR1C Zornitza Stark Marked gene: POLR1C as ready
Leukodystrophy - adult onset v0.63 POLR1C Zornitza Stark Gene: polr1c has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.63 POLR1C Zornitza Stark Phenotypes for gene: POLR1C were changed from Leukodystrophy, hypomyelinating, 11 to Leukodystrophy, hypomyelinating, 11, MIM# 616494
Leukodystrophy - adult onset v0.62 POLR1C Zornitza Stark Classified gene: POLR1C as Amber List (moderate evidence)
Leukodystrophy - adult onset v0.62 POLR1C Zornitza Stark Gene: polr1c has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.61 POLR1C Zornitza Stark reviewed gene: POLR1C: Rating: AMBER; Mode of pathogenicity: None; Publications: 26151409, 32042905; Phenotypes: Leukodystrophy, hypomyelinating, 11, MIM# 616494; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.136 POLR1C Zornitza Stark Publications for gene: POLR1C were set to 26151409
Leukodystrophy - paediatric v0.135 POLR1C Zornitza Stark edited their review of gene: POLR1C: Changed publications: 26151409, 32042905; Changed phenotypes: Leukodystrophy, hypomyelinating, 11, MIM# 616494
Leukodystrophy - paediatric v0.135 POLR1C Zornitza Stark Marked gene: POLR1C as ready
Leukodystrophy - paediatric v0.135 POLR1C Zornitza Stark Gene: polr1c has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.135 POLR1C Zornitza Stark Classified gene: POLR1C as Green List (high evidence)
Leukodystrophy - paediatric v0.135 POLR1C Zornitza Stark Gene: polr1c has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.134 POLR1C Zornitza Stark gene: POLR1C was added
gene: POLR1C was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: POLR1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR1C were set to 26151409
Phenotypes for gene: POLR1C were set to Leukodystrophy, hypomyelinating, 11, MIM# 616494
Review for gene: POLR1C was set to GREEN
Added comment: Over 20 individuals reported.
Sources: Expert list
Leukodystrophy - adult onset v0.61 POLG2 Zornitza Stark Marked gene: POLG2 as ready
Leukodystrophy - adult onset v0.61 POLG2 Zornitza Stark Gene: polg2 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.61 POLG2 Zornitza Stark Classified gene: POLG2 as Amber List (moderate evidence)
Leukodystrophy - adult onset v0.61 POLG2 Zornitza Stark Gene: polg2 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.60 POLG2 Zornitza Stark reviewed gene: POLG2: Rating: AMBER; Mode of pathogenicity: None; Publications: 25655951; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.3140 ANKRD1 Zornitza Stark Marked gene: ANKRD1 as ready
Mendeliome v0.3140 ANKRD1 Zornitza Stark Gene: ankrd1 has been classified as Red List (Low Evidence).
Mendeliome v0.3140 ANKRD1 Zornitza Stark Phenotypes for gene: ANKRD1 were changed from to Hypertrophic cardiomyopathy; Dilated cardiomyopathy
Mendeliome v0.3139 ANKRD1 Zornitza Stark Publications for gene: ANKRD1 were set to
Mendeliome v0.3138 ANKRD1 Zornitza Stark Mode of inheritance for gene: ANKRD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3137 ANKRD1 Zornitza Stark Classified gene: ANKRD1 as Red List (low evidence)
Mendeliome v0.3137 ANKRD1 Zornitza Stark Gene: ankrd1 has been classified as Red List (Low Evidence).
Mendeliome v0.3136 ANKRD1 Zornitza Stark reviewed gene: ANKRD1: Rating: RED; Mode of pathogenicity: None; Publications: 19608030, 19525294, 30681346; Phenotypes: Hypertrophic cardiomyopathy, Dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dilated Cardiomyopathy v0.43 ANKRD1 Zornitza Stark Phenotypes for gene: ANKRD1 were changed from to Dilated cardiomyopathy
Dilated Cardiomyopathy v0.42 ANKRD1 Zornitza Stark Publications for gene: ANKRD1 were set to
Dilated Cardiomyopathy v0.41 ANKRD1 Zornitza Stark Mode of inheritance for gene: ANKRD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dilated Cardiomyopathy v0.40 ANKRD1 Zornitza Stark changed review comment from: Three missense variants, P105S, V107L, and M184I reported in 4 individuals in PMID: 19608030. However, note that P105S is present in 45 individuals in gnomad, and V107L in >200. Another 5 missense variants reported in PMID: 19525294. Of these, p.Thr116Met is present in 41 individuals in gnomad, p.Ala276Val in 745 individuals (and 6 homozygotes), p.Glu57Gln is present once, p.Arg66Gln is absent but an alternative change at same residue is present in >300, and p.Leu199Arg is absent. Overall, the population frequency of most of these variants is out of keeping for a Mendelian disorder.; to: DCM: Three missense variants, P105S, V107L, and M184I reported in 4 individuals in PMID: 19608030. However, note that P105S is present in 45 individuals in gnomad, and V107L in >200. Another 5 missense variants reported in PMID: 19525294. Of these, p.Thr116Met is present in 41 individuals in gnomad, p.Ala276Val in 745 individuals (and 6 homozygotes), p.Glu57Gln is present once, p.Arg66Gln is absent but an alternative change at same residue is present in >300, and p.Leu199Arg is absent. Overall, the population frequency of most of these variants is out of keeping for a Mendelian disorder.
Dilated Cardiomyopathy v0.40 ANKRD1 Zornitza Stark edited their review of gene: ANKRD1: Added comment: Three missense variants, P105S, V107L, and M184I reported in 4 individuals in PMID: 19608030. However, note that P105S is present in 45 individuals in gnomad, and V107L in >200. Another 5 missense variants reported in PMID: 19525294. Of these, p.Thr116Met is present in 41 individuals in gnomad, p.Ala276Val in 745 individuals (and 6 homozygotes), p.Glu57Gln is present once, p.Arg66Gln is absent but an alternative change at same residue is present in >300, and p.Leu199Arg is absent. Overall, the population frequency of most of these variants is out of keeping for a Mendelian disorder.; Changed publications: 19608030, 19525294; Changed phenotypes: Dilated cardiomyopathy; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dilated Cardiomyopathy v0.40 ANKRD1 Zornitza Stark Marked gene: ANKRD1 as ready
Dilated Cardiomyopathy v0.40 ANKRD1 Zornitza Stark Gene: ankrd1 has been classified as Red List (Low Evidence).
Dilated Cardiomyopathy v0.40 ANKRD1 Zornitza Stark Classified gene: ANKRD1 as Red List (low evidence)
Dilated Cardiomyopathy v0.40 ANKRD1 Zornitza Stark Gene: ankrd1 has been classified as Red List (Low Evidence).
Dilated Cardiomyopathy v0.39 ANKRD1 Zornitza Stark reviewed gene: ANKRD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hypertrophic cardiomyopathy_HCM v0.67 TNNT2 Zornitza Stark Marked gene: TNNT2 as ready
Hypertrophic cardiomyopathy_HCM v0.67 TNNT2 Zornitza Stark Gene: tnnt2 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.67 TNNT2 Zornitza Stark Publications for gene: TNNT2 were set to
Hypertrophic cardiomyopathy_HCM v0.66 TNNT2 Zornitza Stark Phenotypes for gene: TNNT2 were changed from to Cardiomyopathy, hypertrophic, 2, MIM# 115195
Hypertrophic cardiomyopathy_HCM v0.65 TNNT2 Zornitza Stark Mode of inheritance for gene: TNNT2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.64 MYL2 Zornitza Stark Marked gene: MYL2 as ready
Hypertrophic cardiomyopathy_HCM v0.64 MYL2 Zornitza Stark Gene: myl2 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.64 MYL2 Zornitza Stark Publications for gene: MYL2 were set to
Hypertrophic cardiomyopathy_HCM v0.63 MYL2 Zornitza Stark Phenotypes for gene: MYL2 were changed from to Cardiomyopathy, hypertrophic, 10, MIM# 608758
Hypertrophic cardiomyopathy_HCM v0.62 MYL2 Zornitza Stark Mode of inheritance for gene: MYL2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.61 MYH7 Zornitza Stark Marked gene: MYH7 as ready
Hypertrophic cardiomyopathy_HCM v0.61 MYH7 Zornitza Stark Gene: myh7 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.61 MYH7 Zornitza Stark Phenotypes for gene: MYH7 were changed from to Cardiomyopathy, hypertrophic, 1, MIM# 192600
Hypertrophic cardiomyopathy_HCM v0.60 MYH7 Zornitza Stark Publications for gene: MYH7 were set to
Hypertrophic cardiomyopathy_HCM v0.59 MYH7 Zornitza Stark Mode of inheritance for gene: MYH7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.58 KLHL24 Zornitza Stark Marked gene: KLHL24 as ready
Hypertrophic cardiomyopathy_HCM v0.58 KLHL24 Zornitza Stark Gene: klhl24 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.58 FLNC Zornitza Stark Publications for gene: FLNC were set to 31924696; 28356264
Hypertrophic cardiomyopathy_HCM v0.57 DES Zornitza Stark Marked gene: DES as ready
Hypertrophic cardiomyopathy_HCM v0.57 DES Zornitza Stark Gene: des has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.57 DES Zornitza Stark Phenotypes for gene: DES were changed from to Hypertrophic cardiomyopathy; Dilated cardiomyopathy; Myofibrillar myopathy; ARVC
Hypertrophic cardiomyopathy_HCM v0.56 DES Zornitza Stark Mode of inheritance for gene: DES was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.55 DES Zornitza Stark Mode of inheritance for gene: DES was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.55 DES Zornitza Stark Mode of inheritance for gene: DES was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.54 DES Zornitza Stark Classified gene: DES as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.54 DES Zornitza Stark Gene: des has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.53 CSRP3 Zornitza Stark Marked gene: CSRP3 as ready
Hypertrophic cardiomyopathy_HCM v0.53 CSRP3 Zornitza Stark Added comment: Comment when marking as ready: Sufficient number of families reported with good segregation data but agree caution needed in light of some of these variants being present at low frequency in the population.
Hypertrophic cardiomyopathy_HCM v0.53 CSRP3 Zornitza Stark Gene: csrp3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.53 CSRP3 Zornitza Stark Phenotypes for gene: CSRP3 were changed from to Cardiomyopathy, hypertrophic, 12, MIM# 612124
Hypertrophic cardiomyopathy_HCM v0.52 CSRP3 Zornitza Stark Publications for gene: CSRP3 were set to
Hypertrophic cardiomyopathy_HCM v0.51 CSRP3 Zornitza Stark Mode of inheritance for gene: CSRP3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.50 CAV3 Zornitza Stark Marked gene: CAV3 as ready
Hypertrophic cardiomyopathy_HCM v0.50 CAV3 Zornitza Stark Gene: cav3 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.50 CAV3 Zornitza Stark Phenotypes for gene: CAV3 were changed from to Cardiomyopathy, familial hypertrophic, MIM# 192600
Hypertrophic cardiomyopathy_HCM v0.49 CAV3 Zornitza Stark Publications for gene: CAV3 were set to
Hypertrophic cardiomyopathy_HCM v0.48 CAV3 Zornitza Stark Mode of inheritance for gene: CAV3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.47 CAV3 Zornitza Stark Classified gene: CAV3 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.47 CAV3 Zornitza Stark Gene: cav3 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.46 CALR3 Zornitza Stark Marked gene: CALR3 as ready
Hypertrophic cardiomyopathy_HCM v0.46 CALR3 Zornitza Stark Gene: calr3 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.46 CALR3 Zornitza Stark Tag refuted tag was added to gene: CALR3.
Mendeliome v0.3136 CALR3 Zornitza Stark Marked gene: CALR3 as ready
Mendeliome v0.3136 CALR3 Zornitza Stark Gene: calr3 has been classified as Red List (Low Evidence).
Mendeliome v0.3136 CALR3 Zornitza Stark Phenotypes for gene: CALR3 were changed from to Hypertrophic cardiomyopathy
Mendeliome v0.3135 CALR3 Zornitza Stark Publications for gene: CALR3 were set to
Mendeliome v0.3134 CALR3 Zornitza Stark Mode of inheritance for gene: CALR3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3133 CALR3 Zornitza Stark Classified gene: CALR3 as Red List (low evidence)
Mendeliome v0.3133 CALR3 Zornitza Stark Gene: calr3 has been classified as Red List (Low Evidence).
Mendeliome v0.3132 CALR3 Zornitza Stark Tag refuted tag was added to gene: CALR3.
Mendeliome v0.3132 CALR3 Zornitza Stark reviewed gene: CALR3: Rating: RED; Mode of pathogenicity: None; Publications: 29988065; Phenotypes: Hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.46 CALR3 Zornitza Stark Phenotypes for gene: CALR3 were changed from to Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy_HCM v0.45 CALR3 Zornitza Stark Publications for gene: CALR3 were set to
Hypertrophic cardiomyopathy_HCM v0.44 CALR3 Zornitza Stark Mode of inheritance for gene: CALR3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.43 CALR3 Zornitza Stark Classified gene: CALR3 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.43 CALR3 Zornitza Stark Gene: calr3 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.42 ANKRD1 Zornitza Stark Marked gene: ANKRD1 as ready
Hypertrophic cardiomyopathy_HCM v0.42 ANKRD1 Zornitza Stark Gene: ankrd1 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.42 ANKRD1 Zornitza Stark Phenotypes for gene: ANKRD1 were changed from to hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy_HCM v0.41 ANKRD1 Zornitza Stark Publications for gene: ANKRD1 were set to
Hypertrophic cardiomyopathy_HCM v0.40 ANKRD1 Zornitza Stark Mode of inheritance for gene: ANKRD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.39 ANKRD1 Zornitza Stark Classified gene: ANKRD1 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.39 ANKRD1 Zornitza Stark Gene: ankrd1 has been classified as Red List (Low Evidence).
Dilated Cardiomyopathy v0.39 ALPK3 Zornitza Stark Marked gene: ALPK3 as ready
Dilated Cardiomyopathy v0.39 ALPK3 Zornitza Stark Gene: alpk3 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v0.39 ALPK3 Zornitza Stark Mode of inheritance for gene: ALPK3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Dilated Cardiomyopathy v0.38 ALPK3 Zornitza Stark Phenotypes for gene: ALPK3 were changed from to Cardiomyopathy, familial hypertrophic 27, MIM# 618052
Dilated Cardiomyopathy v0.37 ALPK3 Zornitza Stark Publications for gene: ALPK3 were set to
Dilated Cardiomyopathy v0.36 ALPK3 Zornitza Stark reviewed gene: ALPK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26846950, 27106955, 32480058; Phenotypes: Cardiomyopathy, familial hypertrophic 27, MIM# 618052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3132 ALPK3 Zornitza Stark Marked gene: ALPK3 as ready
Mendeliome v0.3132 ALPK3 Zornitza Stark Gene: alpk3 has been classified as Green List (High Evidence).
Mendeliome v0.3132 ALPK3 Zornitza Stark Phenotypes for gene: ALPK3 were changed from to Cardiomyopathy, familial hypertrophic 27, MIM# 618052
Mendeliome v0.3131 ALPK3 Zornitza Stark Publications for gene: ALPK3 were set to
Mendeliome v0.3130 ALPK3 Zornitza Stark Mode of inheritance for gene: ALPK3 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3129 ALPK3 Zornitza Stark reviewed gene: ALPK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26846950, 27106955, 32480058; Phenotypes: Cardiomyopathy, familial hypertrophic 27, MIM# 618052; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.38 ALPK3 Zornitza Stark Marked gene: ALPK3 as ready
Hypertrophic cardiomyopathy_HCM v0.38 ALPK3 Zornitza Stark Gene: alpk3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.38 ALPK3 Zornitza Stark Phenotypes for gene: ALPK3 were changed from to Cardiomyopathy, familial hypertrophic 27, MIM# 618052
Hypertrophic cardiomyopathy_HCM v0.37 ALPK3 Zornitza Stark Publications for gene: ALPK3 were set to
Hypertrophic cardiomyopathy_HCM v0.36 ALPK3 Zornitza Stark Mode of inheritance for gene: ALPK3 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.35 ACTN2 Zornitza Stark Marked gene: ACTN2 as ready
Hypertrophic cardiomyopathy_HCM v0.35 ACTN2 Zornitza Stark Gene: actn2 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.35 ACTN2 Zornitza Stark Phenotypes for gene: ACTN2 were changed from to Cardiomyopathy, hypertrophic, 23, with or without LVNC, MIM# 612158
Hypertrophic cardiomyopathy_HCM v0.34 ACTN2 Zornitza Stark Publications for gene: ACTN2 were set to
Hypertrophic cardiomyopathy_HCM v0.33 ACTN2 Zornitza Stark Mode of inheritance for gene: ACTN2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.32 ACTN2 Zornitza Stark Classified gene: ACTN2 as Amber List (moderate evidence)
Hypertrophic cardiomyopathy_HCM v0.32 ACTN2 Zornitza Stark Gene: actn2 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.31 ACTC1 Zornitza Stark Marked gene: ACTC1 as ready
Hypertrophic cardiomyopathy_HCM v0.31 ACTC1 Zornitza Stark Gene: actc1 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.31 ACTC1 Zornitza Stark Mode of inheritance for gene: ACTC1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.30 ACTC1 Zornitza Stark Phenotypes for gene: ACTC1 were changed from to Cardiomyopathy, hypertrophic, 11 612098
Hypertrophic cardiomyopathy_HCM v0.29 ACTC1 Zornitza Stark Mode of inheritance for gene: ACTC1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.29 ACTC1 Zornitza Stark Mode of inheritance for gene: ACTC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 MYL2 Ivan Macciocca reviewed gene: MYL2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 TNNT2 Ivan Macciocca reviewed gene: TNNT2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM, LVNC, RCM, DCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 MYH7 Ivan Macciocca reviewed gene: MYH7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: hypertrophic cardiomyopathy, LVNC, DCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 FLNC Ivan Macciocca reviewed gene: FLNC: Rating: GREEN; Mode of pathogenicity: None; Publications: 30411535; Phenotypes: hypertrophic cardiomyopathy, distal myopathy, restrictive cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 DES Ivan Macciocca reviewed gene: DES: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: arrhythmogenic right ventricular cardiomyopathy, myofibrillar myopathy 1, dilated cardiomyopathy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.28 CSRP3 Ivan Macciocca changed review comment from: Assessed as MODERATE by ClinGen HCM working group PMID: 30681346
Associated with HCM in 4 families reported by a German group with some functional evidence and including 2 large multi-generational families with 6 and 8 affected relatives segregating the variants.
3 of the 4 variants reported in these families have a low frequency (up to 4 alleles) in Gnomad.; to: Assessed as MODERATE by ClinGen HCM working group PMID: 30681346
Associated with HCM in 4 families reported by a German group with some functional evidence and including 2 large multi-generational families with 6 and 8 affected relatives segregating the variants.
3 of the 4 variants reported in these families have a low frequency (up to 4 alleles) in Gnomad.
Assess variants in this gene with caution due to the limited number of families currently reported with pathogenic/likely[pathogenic variants in this gene.
Hypertrophic cardiomyopathy_HCM v0.28 CSRP3 Ivan Macciocca reviewed gene: CSRP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18505755, 30681346; Phenotypes: hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 CAV3 Ivan Macciocca reviewed gene: CAV3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 14672715,27483260,12138167; Phenotypes: hypertrophic cardiomyopathy, long QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 C1QBP Ivan Macciocca reviewed gene: C1QBP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:28942965; Phenotypes: COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 33, hypertrophic cardiomyopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.28 ANKRD1 Ivan Macciocca reviewed gene: ANKRD1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 ALPK3 Ivan Macciocca reviewed gene: ALPK3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26846950, 27106955, 32480058; Phenotypes: hypertrophic cardiomyopathy, dilated cardiomyopathy; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.28 ACTN2 Ivan Macciocca reviewed gene: ACTN2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: hypertrophic cardiomyopathy, left ventricular non compaction, dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 ACTC1 Ivan Macciocca reviewed gene: ACTC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: hypertrophic cardiomyopathy, left ventricular non compaction, dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.48 SPG7 Bryony Thompson Marked gene: SPG7 as ready
Motor Neurone Disease v0.48 SPG7 Bryony Thompson Gene: spg7 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.48 SPG7 Bryony Thompson Classified gene: SPG7 as Green List (high evidence)
Motor Neurone Disease v0.48 SPG7 Bryony Thompson Gene: spg7 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.47 SPG7 Bryony Thompson gene: SPG7 was added
gene: SPG7 was added to Motor Neuron Disease. Sources: Literature
Mode of inheritance for gene: SPG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPG7 were set to 16765570; 19364936
Phenotypes for gene: SPG7 were set to Spastic paraplegia 7, autosomal recessive MIM#607259
Review for gene: SPG7 was set to GREEN
Added comment: The HSP caused by this gene can be classified as a non-ALS MND, affecting the upper motor neurons. There are multiple reports of the condition mimicking MND.
Sources: Literature
Motor Neurone Disease v0.46 SPAST Bryony Thompson Marked gene: SPAST as ready
Motor Neurone Disease v0.46 SPAST Bryony Thompson Gene: spast has been classified as Green List (High Evidence).
Motor Neurone Disease v0.46 SPAST Bryony Thompson Classified gene: SPAST as Green List (high evidence)
Motor Neurone Disease v0.46 SPAST Bryony Thompson Gene: spast has been classified as Green List (High Evidence).
Motor Neurone Disease v0.45 SPAST Bryony Thompson gene: SPAST was added
gene: SPAST was added to Motor Neuron Disease. Sources: Expert list
Mode of inheritance for gene: SPAST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPAST were set to 16765570; 19364936
Review for gene: SPAST was set to GREEN
Added comment: The HSP caused by this gene can be classified as a non-ALS MND, affecting the upper motor neurons. There are multiple reports of the condition mimicking MND.
Sources: Expert list
Motor Neurone Disease v0.44 REEP1 Bryony Thompson Marked gene: REEP1 as ready
Motor Neurone Disease v0.44 REEP1 Bryony Thompson Gene: reep1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.44 REEP1 Bryony Thompson Classified gene: REEP1 as Green List (high evidence)
Motor Neurone Disease v0.44 REEP1 Bryony Thompson Gene: reep1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.43 REEP1 Bryony Thompson gene: REEP1 was added
gene: REEP1 was added to Motor Neuron Disease. Sources: Expert list
Mode of inheritance for gene: REEP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: REEP1 were set to 23108492; 22703882
Phenotypes for gene: REEP1 were set to Spastic paraplegia 31, autosomal dominant MIM#610250
Review for gene: REEP1 was set to GREEN
Added comment: The HSP caused by this gene can be classified as a non-ALS MND, affecting the upper and lower motor neurons.
Sources: Expert list
Motor Neurone Disease v0.42 GBE1 Bryony Thompson Classified gene: GBE1 as Green List (high evidence)
Motor Neurone Disease v0.42 GBE1 Bryony Thompson Gene: gbe1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.41 GBE1 Bryony Thompson gene: GBE1 was added
gene: GBE1 was added to Motor Neuron Disease. Sources: Expert list
Mode of inheritance for gene: GBE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBE1 were set to 20301758; 26194201
Phenotypes for gene: GBE1 were set to Polyglucosan body disease, adult form MIM#263570
Review for gene: GBE1 was set to GREEN
Added comment: APBD can have upper and lower motor neuron involvement, and at least 5 cases in a cohort of 30 were misdiagnosed with ALS.
Sources: Expert list
Mendeliome v0.3129 HSF4 Zornitza Stark Marked gene: HSF4 as ready
Mendeliome v0.3129 HSF4 Zornitza Stark Gene: hsf4 has been classified as Green List (High Evidence).
Mendeliome v0.3129 HSF4 Zornitza Stark Phenotypes for gene: HSF4 were changed from to Cataract 5, multiple types, 116800
Mendeliome v0.3128 HSF4 Zornitza Stark Publications for gene: HSF4 were set to
Mendeliome v0.3127 HSF4 Zornitza Stark Mode of inheritance for gene: HSF4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3126 HSF4 Zornitza Stark reviewed gene: HSF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31815953, 29243736, 26490182; Phenotypes: Cataract 5, multiple types, 116800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cataract v0.146 HSF4 Zornitza Stark Marked gene: HSF4 as ready
Cataract v0.146 HSF4 Zornitza Stark Gene: hsf4 has been classified as Green List (High Evidence).
Cataract v0.146 HSF4 Zornitza Stark Phenotypes for gene: HSF4 were changed from to Cataract 5, multiple types, 116800
Cataract v0.145 HSF4 Zornitza Stark Publications for gene: HSF4 were set to
Cataract v0.144 HSF4 Zornitza Stark Mode of inheritance for gene: HSF4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Motor Neurone Disease v0.40 BSCL2 Bryony Thompson Classified gene: BSCL2 as Green List (high evidence)
Motor Neurone Disease v0.40 BSCL2 Bryony Thompson Gene: bscl2 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.39 BSCL2 Bryony Thompson gene: BSCL2 was added
gene: BSCL2 was added to Motor Neuron Disease. Sources: Expert list
Mode of inheritance for gene: BSCL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BSCL2 were set to 16765570
Phenotypes for gene: BSCL2 were set to Silver spastic paraplegia syndrome MIM#270685; Neuropathy, distal hereditary motor, type VA MIM#600794
Review for gene: BSCL2 was set to GREEN
Added comment: The HSP and distal HMN caused by this gene can be classified as a non-ALS MND, affecting both upper and lower motor neurons.
Sources: Expert list
Motor Neurone Disease v0.38 ATL1 Bryony Thompson Classified gene: ATL1 as Green List (high evidence)
Motor Neurone Disease v0.38 ATL1 Bryony Thompson Gene: atl1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.37 ATL1 Bryony Thompson gene: ATL1 was added
gene: ATL1 was added to Motor Neuron Disease. Sources: Expert list
Mode of inheritance for gene: ATL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATL1 were set to 16765570
Phenotypes for gene: ATL1 were set to Spastic paraplegia 3A, autosomal dominant MIM#182600
Review for gene: ATL1 was set to GREEN
Added comment: The HSP caused by this gene can be classified as a non-ALS MND, affecting the upper motor neurons.
Sources: Expert list
Dystonia - complex v0.68 UBTF Bryony Thompson Marked gene: UBTF as ready
Dystonia - complex v0.68 UBTF Bryony Thompson Gene: ubtf has been classified as Green List (High Evidence).
Dystonia - complex v0.68 UBTF Bryony Thompson Classified gene: UBTF as Green List (high evidence)
Dystonia - complex v0.68 UBTF Bryony Thompson Gene: ubtf has been classified as Green List (High Evidence).
Dystonia - complex v0.67 UBTF Bryony Thompson gene: UBTF was added
gene: UBTF was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: UBTF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBTF were set to 28777933; 29300972
Phenotypes for gene: UBTF were set to Neurodegeneration, childhood-onset, with brain atrophy MIM#617672
Mode of pathogenicity for gene: UBTF 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: UBTF was set to GREEN
Added comment: 7 out of 11 unrelated cases with a recurrent de novo gain of function missense variant (p.Glu210Lys) have dystonia as a feature of the condition.
Sources: Expert list
Mendeliome v0.3126 FITM2 Bryony Thompson Marked gene: FITM2 as ready
Mendeliome v0.3126 FITM2 Bryony Thompson Gene: fitm2 has been classified as Green List (High Evidence).
Mendeliome v0.3126 FITM2 Bryony Thompson Classified gene: FITM2 as Green List (high evidence)
Mendeliome v0.3126 FITM2 Bryony Thompson Gene: fitm2 has been classified as Green List (High Evidence).
Mendeliome v0.3125 FITM2 Bryony Thompson gene: FITM2 was added
gene: FITM2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FITM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FITM2 were set to 28067622; 30214770; 30288795
Phenotypes for gene: FITM2 were set to Siddiqi syndrome MIM#618635; dystonia; deafness
Review for gene: FITM2 was set to GREEN
Added comment: 7 cases from 3 unrelated families (2 consanguineous) with a dystonia-deafness syndrome and a supporting Drosophila model.
Sources: Expert list
Deafness_IsolatedAndComplex v0.351 FITM2 Bryony Thompson Marked gene: FITM2 as ready
Deafness_IsolatedAndComplex v0.351 FITM2 Bryony Thompson Gene: fitm2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.351 FITM2 Bryony Thompson Classified gene: FITM2 as Green List (high evidence)
Deafness_IsolatedAndComplex v0.351 FITM2 Bryony Thompson Gene: fitm2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.350 FITM2 Bryony Thompson gene: FITM2 was added
gene: FITM2 was added to Deafness. Sources: Literature
Mode of inheritance for gene: FITM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FITM2 were set to 28067622; 30214770; 30288795
Phenotypes for gene: FITM2 were set to Siddiqi syndrome MIM#618635; dystonia; deafness
Review for gene: FITM2 was set to GREEN
Added comment: 7 cases from 3 unrelated families (2 consanguineous) with a dystonia-deafness syndrome and a supporting Drosophila model.
Sources: Literature
Dystonia - complex v0.66 FITM2 Bryony Thompson changed review comment from: Three unrelated cases with a dystonia-deafness syndrome and a supporting Drosophila model.
Sources: Expert list; to: 7 cases from 3 unrelated families (2 consanguineous) with a dystonia-deafness syndrome and a supporting Drosophila model.
Sources: Expert list
Dystonia - complex v0.66 FITM2 Bryony Thompson Marked gene: FITM2 as ready
Dystonia - complex v0.66 FITM2 Bryony Thompson Gene: fitm2 has been classified as Green List (High Evidence).
Dystonia - complex v0.66 FITM2 Bryony Thompson Classified gene: FITM2 as Green List (high evidence)
Dystonia - complex v0.66 FITM2 Bryony Thompson Gene: fitm2 has been classified as Green List (High Evidence).
Dystonia - complex v0.65 FITM2 Bryony Thompson gene: FITM2 was added
gene: FITM2 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: FITM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FITM2 were set to 28067622; 30214770; 30288795
Phenotypes for gene: FITM2 were set to Siddiqi syndrome MIM#618635; dystonia; deafness
Review for gene: FITM2 was set to GREEN
Added comment: Three unrelated cases with a dystonia-deafness syndrome and a supporting Drosophila model.
Sources: Expert list
Cataract v0.143 HSF4 Chern Lim reviewed gene: HSF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31815953, 29243736, 26490182; Phenotypes: Cataract 5, multiple types, 116800.; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3124 DALRD3 Zornitza Stark Phenotypes for gene: DALRD3 were changed from Epileptic encephalopathy to Epileptic encephalopathy; Epileptic encephalopathy, early infantile, 86 618910
Mendeliome v0.3123 DALRD3 Zornitza Stark edited their review of gene: DALRD3: Changed phenotypes: Epileptic encephalopathy, Epileptic encephalopathy, early infantile, 86 618910
Genetic Epilepsy v0.731 DALRD3 Zornitza Stark Phenotypes for gene: DALRD3 were changed from Epileptic encephalopathy to Epileptic encephalopathy; Epileptic encephalopathy, early infantile, 86 618910
Genetic Epilepsy v0.730 DALRD3 Zornitza Stark edited their review of gene: DALRD3: Changed phenotypes: Epileptic encephalopathy, Epileptic encephalopathy, early infantile, 86 618910
Mendeliome v0.3123 CHD1L Zornitza Stark Marked gene: CHD1L as ready
Mendeliome v0.3123 CHD1L Zornitza Stark Gene: chd1l has been classified as Red List (Low Evidence).
Mendeliome v0.3123 CHD1L Zornitza Stark Phenotypes for gene: CHD1L were changed from to CAKUT
Mendeliome v0.3122 CHD1L Zornitza Stark Publications for gene: CHD1L were set to
Mendeliome v0.3121 CHD1L Zornitza Stark Mode of inheritance for gene: CHD1L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3120 CHD1L Zornitza Stark Classified gene: CHD1L as Red List (low evidence)
Mendeliome v0.3120 CHD1L Zornitza Stark Gene: chd1l has been classified as Red List (Low Evidence).
Mendeliome v0.3119 CHD1L Zornitza Stark Tag disputed tag was added to gene: CHD1L.
Mendeliome v0.3119 CHD1L Zornitza Stark reviewed gene: CHD1L: Rating: RED; Mode of pathogenicity: None; Publications: 22146311, 24429398; Phenotypes: CAKUT; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.72 CHD1L Zornitza Stark Marked gene: CHD1L as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.72 CHD1L Zornitza Stark Added comment: Comment when marking as ready: The population variant frequencies are out of keeping for a Mendelian disorder.
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.72 CHD1L Zornitza Stark Gene: chd1l has been classified as Red List (Low Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.72 CHD1L Zornitza Stark Classified gene: CHD1L as Red List (low evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.72 CHD1L Zornitza Stark Gene: chd1l has been classified as Red List (Low Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.71 CHD1L Zornitza Stark Tag disputed tag was added to gene: CHD1L.
Genetic Epilepsy v0.730 NEXMIF Zornitza Stark Marked gene: NEXMIF as ready
Genetic Epilepsy v0.730 NEXMIF Zornitza Stark Gene: nexmif has been classified as Green List (High Evidence).
Genetic Epilepsy v0.730 NEXMIF Zornitza Stark Phenotypes for gene: NEXMIF were changed from to Mental retardation, X-linked 98, MIM# 300912
Genetic Epilepsy v0.729 NEXMIF Zornitza Stark Publications for gene: NEXMIF were set to
Genetic Epilepsy v0.728 NEXMIF Zornitza Stark Mode of inheritance for gene: NEXMIF 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)
Genetic Epilepsy v0.727 NEXMIF Zornitza Stark reviewed gene: NEXMIF: Rating: GREEN; Mode of pathogenicity: None; Publications: 27358180; Phenotypes: Mental retardation, X-linked 98, MIM# 300912; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.2702 NEXMIF Zornitza Stark Marked gene: NEXMIF as ready
Intellectual disability syndromic and non-syndromic v0.2702 NEXMIF Zornitza Stark Gene: nexmif has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2702 NEXMIF Zornitza Stark Phenotypes for gene: NEXMIF were changed from to Mental retardation, X-linked 98, MIM# 300912
Intellectual disability syndromic and non-syndromic v0.2701 NEXMIF Zornitza Stark Publications for gene: NEXMIF were set to
Intellectual disability syndromic and non-syndromic v0.2700 NEXMIF Zornitza Stark Mode of inheritance for gene: NEXMIF 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)
Intellectual disability syndromic and non-syndromic v0.2699 NEXMIF Zornitza Stark reviewed gene: NEXMIF: Rating: GREEN; Mode of pathogenicity: None; Publications: 27358180; Phenotypes: Mental retardation, X-linked 98 300912; 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 v0.3119 NEXMIF Zornitza Stark Marked gene: NEXMIF as ready
Mendeliome v0.3119 NEXMIF Zornitza Stark Gene: nexmif has been classified as Green List (High Evidence).
Mendeliome v0.3119 NEXMIF Zornitza Stark Phenotypes for gene: NEXMIF were changed from to Mental retardation, X-linked 98 300912
Mendeliome v0.3118 NEXMIF Zornitza Stark Publications for gene: NEXMIF were set to
Mendeliome v0.3117 NEXMIF Zornitza Stark Mode of inheritance for gene: NEXMIF 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)
Mendeliome v0.3116 MEF2C Zornitza Stark Marked gene: MEF2C as ready
Mendeliome v0.3116 MEF2C Zornitza Stark Gene: mef2c has been classified as Green List (High Evidence).
Mendeliome v0.3116 MEF2C Zornitza Stark Phenotypes for gene: MEF2C were changed from to Chromosome 5q14.3 deletion syndrome, 613443; Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, 613443
Mendeliome v0.3115 MEF2C Zornitza Stark Mode of inheritance for gene: MEF2C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3114 KDM6A Zornitza Stark Marked gene: KDM6A as ready
Mendeliome v0.3114 KDM6A Zornitza Stark Gene: kdm6a has been classified as Green List (High Evidence).
Mendeliome v0.3114 KDM6A Zornitza Stark Phenotypes for gene: KDM6A were changed from to Kabuki syndrome 2, 300867
Mendeliome v0.3113 KDM6A Zornitza Stark Publications for gene: KDM6A were set to
Mendeliome v0.3112 KDM6A Zornitza Stark Mode of inheritance for gene: KDM6A 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 v0.81 SPECC1L Bryony Thompson Marked gene: SPECC1L as ready
Craniosynostosis v0.81 SPECC1L Bryony Thompson Gene: specc1l has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.81 SPECC1L Bryony Thompson Classified gene: SPECC1L as Amber List (moderate evidence)
Craniosynostosis v0.81 SPECC1L Bryony Thompson Gene: specc1l has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.80 SPECC1L Bryony Thompson gene: SPECC1L was added
gene: SPECC1L was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: SPECC1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPECC1L were set to 26111080; 30472488
Phenotypes for gene: SPECC1L were set to Hypertelorism, Teebi type MIM#145420
Review for gene: SPECC1L was set to AMBER
Added comment: Three unrelated cases reported with craniosynostosis as a feature of the condition.
Sources: Expert list
Craniosynostosis v0.79 IFT122 Bryony Thompson Marked gene: IFT122 as ready
Craniosynostosis v0.79 IFT122 Bryony Thompson Gene: ift122 has been classified as Green List (High Evidence).
Craniosynostosis v0.79 IFT122 Bryony Thompson Classified gene: IFT122 as Green List (high evidence)
Craniosynostosis v0.79 IFT122 Bryony Thompson Gene: ift122 has been classified as Green List (High Evidence).
Craniosynostosis v0.78 IFT122 Bryony Thompson gene: IFT122 was added
gene: IFT122 was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: IFT122 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT122 were set to 26792575; 28370949; 29037998
Phenotypes for gene: IFT122 were set to Cranioectodermal dysplasia 1 MIM#218330
Review for gene: IFT122 was set to GREEN
Added comment: Craniosynostosis has been reported as a prominent feature of the condition in greater than 10 cases.
Sources: Expert list
Craniosynostosis v0.77 GLI3 Bryony Thompson Marked gene: GLI3 as ready
Craniosynostosis v0.77 GLI3 Bryony Thompson Gene: gli3 has been classified as Green List (High Evidence).
Craniosynostosis v0.77 GLI3 Bryony Thompson Classified gene: GLI3 as Green List (high evidence)
Craniosynostosis v0.77 GLI3 Bryony Thompson Gene: gli3 has been classified as Green List (High Evidence).
Craniosynostosis v0.76 GLI3 Bryony Thompson gene: GLI3 was added
gene: GLI3 was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: GLI3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLI3 were set to 20583172; 20570969; 21326280
Phenotypes for gene: GLI3 were set to Metopic craniosynostosis; Greig cephalopolysyndactyly syndrome MIM#175700
Review for gene: GLI3 was set to GREEN
Added comment: Metopic or sagittal synostosis has been reported as a feature of Greig cephalopolysyndactyly syndrome in at least 7 unrelated cases, and there is a supporting mouse model with craniosynostosis.
Sources: Expert list
Craniosynostosis v0.75 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Maturity-onset Diabetes of the Young v0.9 Bryony Thompson Panel types changed to Royal Melbourne Hospital; Rare Disease
Maturity-onset Diabetes of the Young v0.8 CEL Bryony Thompson Marked gene: CEL as ready
Maturity-onset Diabetes of the Young v0.8 CEL Bryony Thompson Gene: cel has been classified as Amber List (Moderate Evidence).
Maturity-onset Diabetes of the Young v0.8 CEL Bryony Thompson Classified gene: CEL as Amber List (moderate evidence)
Maturity-onset Diabetes of the Young v0.8 CEL Bryony Thompson Gene: cel has been classified as Amber List (Moderate Evidence).
Maturity-onset Diabetes of the Young v0.7 RFX6 Bryony Thompson Marked gene: RFX6 as ready
Maturity-onset Diabetes of the Young v0.7 RFX6 Bryony Thompson Gene: rfx6 has been classified as Green List (High Evidence).
Maturity-onset Diabetes of the Young v0.7 RFX6 Bryony Thompson Classified gene: RFX6 as Green List (high evidence)
Maturity-onset Diabetes of the Young v0.7 RFX6 Bryony Thompson Gene: rfx6 has been classified as Green List (High Evidence).
Maturity-onset Diabetes of the Young v0.6 RFX6 Bryony Thompson gene: RFX6 was added
gene: RFX6 was added to Maturity-onset Diabetes of the Young. Sources: Expert list
Mode of inheritance for gene: RFX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RFX6 were set to 20148032; 25048417; 27185633; 29026101; 31001871
Phenotypes for gene: RFX6 were set to Maturity-onset diabetes of the young
Review for gene: RFX6 was set to GREEN
Added comment: At least 3 unrelated cases with heterozygous variants and a suspected diagnosis of MODY. Null mouse model demonstrates abnormal pancreatic islet cells.
Sources: Expert list
Mendeliome v0.3111 KDM6A Elena Savva reviewed gene: KDM6A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:27302555, 24664873; Phenotypes: Kabuki syndrome 2, 300867; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Mendeliome v0.3111 MEF2C Elena Savva reviewed gene: MEF2C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Chromosome 5q14.3 deletion syndrome, 613443, Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, 613443; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3111 NEXMIF Elena Savva reviewed gene: NEXMIF: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27358180; Phenotypes: Mental retardation, X-linked 98 300912; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.71 CHD1L Melanie Marty reviewed gene: CHD1L: Rating: AMBER; Mode of pathogenicity: None; Publications: 22146311, 24429398; Phenotypes: CAKUT; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3111 STAG3 Bryony Thompson Marked gene: STAG3 as ready
Mendeliome v0.3111 STAG3 Bryony Thompson Gene: stag3 has been classified as Green List (High Evidence).
Mendeliome v0.3111 STAG3 Bryony Thompson Classified gene: STAG3 as Green List (high evidence)
Mendeliome v0.3111 STAG3 Bryony Thompson Gene: stag3 has been classified as Green List (High Evidence).
Mendeliome v0.3110 STAG3 Bryony Thompson gene: STAG3 was added
gene: STAG3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: STAG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAG3 were set to 24597867; 26059840; 31803224; 31363903
Phenotypes for gene: STAG3 were set to Premature ovarian failure 8 MIM#615723
Review for gene: STAG3 was set to GREEN
Added comment: At least four unrelated families with ovarian failure and a supporting null mouse model.
Sources: Expert list
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.6 STAG3 Bryony Thompson Marked gene: STAG3 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.6 STAG3 Bryony Thompson Gene: stag3 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.6 STAG3 Bryony Thompson Phenotypes for gene: STAG3 were changed from to Premature ovarian failure 8 MIM#615723
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.5 STAG3 Bryony Thompson Publications for gene: STAG3 were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.4 STAG3 Bryony Thompson reviewed gene: STAG3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24597867, 26059840, 31803224, 31363903; Phenotypes: Premature ovarian failure 8 MIM#615723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3109 SOHLH1 Bryony Thompson Marked gene: SOHLH1 as ready
Mendeliome v0.3109 SOHLH1 Bryony Thompson Gene: sohlh1 has been classified as Green List (High Evidence).
Mendeliome v0.3109 SOHLH1 Bryony Thompson Classified gene: SOHLH1 as Green List (high evidence)
Mendeliome v0.3109 SOHLH1 Bryony Thompson Gene: sohlh1 has been classified as Green List (High Evidence).
Mendeliome v0.3108 SOHLH1 Bryony Thompson gene: SOHLH1 was added
gene: SOHLH1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SOHLH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SOHLH1 were set to 25774885; 16690745; 31042289; 20506135; 28718531
Phenotypes for gene: SOHLH1 were set to Ovarian dysgenesis 5 MIM#617690; Spermatogenic failure 32 MIM#618115
Review for gene: SOHLH1 was set to GREEN
Added comment: Women in 3 unrelated families with ovarian dysgenesis and homozygous variants, and a supporting null mouse model.
At least 4 males with heterozygous variants and spermatogenic failure.
Sources: Expert list
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.4 SOHLH1 Bryony Thompson Marked gene: SOHLH1 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.4 SOHLH1 Bryony Thompson Gene: sohlh1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.4 SOHLH1 Bryony Thompson Phenotypes for gene: SOHLH1 were changed from to Ovarian dysgenesis 5 MIM#617690
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.3 SOHLH1 Bryony Thompson Publications for gene: SOHLH1 were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.2 SOHLH1 Bryony Thompson reviewed gene: SOHLH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25774885, 16690745, 31042289; Phenotypes: Ovarian dysgenesis 5 MIM#617690; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3107 HFM1 Bryony Thompson Marked gene: HFM1 as ready
Mendeliome v0.3107 HFM1 Bryony Thompson Gene: hfm1 has been classified as Green List (High Evidence).
Mendeliome v0.3107 HFM1 Bryony Thompson Classified gene: HFM1 as Green List (high evidence)
Mendeliome v0.3107 HFM1 Bryony Thompson Gene: hfm1 has been classified as Green List (High Evidence).
Mendeliome v0.3106 HFM1 Bryony Thompson gene: HFM1 was added
gene: HFM1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: HFM1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: HFM1 were set to 23555294; 24597873; 31279343
Phenotypes for gene: HFM1 were set to Premature ovarian failure 9 MIM#615724
Review for gene: HFM1 was set to GREEN
Added comment: Three cases from 2 unrelated families with compound heterozygous variants, and a single family with a heterozygous variant have been reported with ovarian failure. There is also a supporting null mouse model.
Sources: Expert list
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.2 HFM1 Bryony Thompson reviewed gene: HFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23555294, 24597873, 31279343; Phenotypes: Premature ovarian failure 9 MIM#615724; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.2 GDF9 Bryony Thompson Classified gene: GDF9 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.2 GDF9 Bryony Thompson Gene: gdf9 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.1 GDF9 Bryony Thompson reviewed gene: GDF9: Rating: AMBER; Mode of pathogenicity: None; Publications: 29044499, 8849725; Phenotypes: Premature ovarian failure 14 MIM#618014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.1 FMR1 Bryony Thompson Tag STR tag was added to gene: FMR1.
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.1 Bryony Thompson Panel status changed from internal to public
Panel types changed to Royal Melbourne Hospital; Rare Disease
Craniosynostosis v0.74 ZNF462 Tiong Tan Marked gene: ZNF462 as ready
Craniosynostosis v0.74 ZNF462 Tiong Tan Gene: znf462 has been classified as Green List (High Evidence).
Craniosynostosis v0.74 ZNF462 Tiong Tan Classified gene: ZNF462 as Green List (high evidence)
Craniosynostosis v0.74 ZNF462 Tiong Tan Gene: znf462 has been classified as Green List (High Evidence).
Craniosynostosis v0.73 ZNF462 Tiong Tan gene: ZNF462 was added
gene: ZNF462 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: ZNF462 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF462 were set to 28513610
Phenotypes for gene: ZNF462 were set to WEISS-KRUSZKA SYNDROME
Penetrance for gene: ZNF462 were set to Complete
Review for gene: ZNF462 was set to GREEN
Added comment: Craniosynostosis observed in 38% of affected individuals
Sources: Literature
Craniosynostosis v0.72 WDR35 Tiong Tan Marked gene: WDR35 as ready
Craniosynostosis v0.72 WDR35 Tiong Tan Gene: wdr35 has been classified as Green List (High Evidence).
Craniosynostosis v0.72 WDR35 Tiong Tan Classified gene: WDR35 as Green List (high evidence)
Craniosynostosis v0.72 WDR35 Tiong Tan Gene: wdr35 has been classified as Green List (High Evidence).
Craniosynostosis v0.71 WDR35 Tiong Tan gene: WDR35 was added
gene: WDR35 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: WDR35 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR35 were set to 20817137; 24123776
Phenotypes for gene: WDR35 were set to CRANIOECTODERMAL DYSPLASIA
Penetrance for gene: WDR35 were set to Complete
Review for gene: WDR35 was set to GREEN
Added comment: Craniosynostosis is a well-established feature of Sensenbrenner/Cranioectodermal dysplasia
Sources: Literature
Craniosynostosis v0.70 SMAD3 Tiong Tan Marked gene: SMAD3 as ready
Craniosynostosis v0.70 SMAD3 Tiong Tan Gene: smad3 has been classified as Green List (High Evidence).
Craniosynostosis v0.70 SMAD3 Tiong Tan Classified gene: SMAD3 as Green List (high evidence)
Craniosynostosis v0.70 SMAD3 Tiong Tan Gene: smad3 has been classified as Green List (High Evidence).
Craniosynostosis v0.69 SMAD3 Tiong Tan gene: SMAD3 was added
gene: SMAD3 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: SMAD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD3 were set to 20301312
Phenotypes for gene: SMAD3 were set to LOEYS-DIETZ SYNDROME
Penetrance for gene: SMAD3 were set to Complete
Added comment: Craniosynostosis is a well-established feature of LDS - TGFBR1, TGFBR2 and SMAD3
Sources: Literature
Craniosynostosis v0.68 TGFBR2 Tiong Tan Classified gene: TGFBR2 as Green List (high evidence)
Craniosynostosis v0.68 TGFBR2 Tiong Tan Gene: tgfbr2 has been classified as Green List (High Evidence).
Craniosynostosis v0.67 TGFBR2 Tiong Tan Classified gene: TGFBR2 as Green List (high evidence)
Craniosynostosis v0.67 TGFBR2 Tiong Tan Gene: tgfbr2 has been classified as Green List (High Evidence).
Craniosynostosis v0.66 TGFBR2 Tiong Tan Marked gene: TGFBR2 as ready
Craniosynostosis v0.66 TGFBR2 Tiong Tan Gene: tgfbr2 has been classified as Red List (Low Evidence).
Craniosynostosis v0.66 TGFBR2 Tiong Tan gene: TGFBR2 was added
gene: TGFBR2 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: TGFBR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TGFBR2 were set to 15731757
Phenotypes for gene: TGFBR2 were set to LOEYS-DIETZ SYNDROME
Penetrance for gene: TGFBR2 were set to Complete
Review for gene: TGFBR2 was set to GREEN
Added comment: Craniosynostosis is a well-established feature of LDS - TGFBR1, TGFBR2 and SMAD3
Sources: Literature
Craniosynostosis v0.65 TGFBR1 Tiong Tan Marked gene: TGFBR1 as ready
Craniosynostosis v0.65 TGFBR1 Tiong Tan Gene: tgfbr1 has been classified as Green List (High Evidence).
Craniosynostosis v0.65 TGFBR1 Tiong Tan Classified gene: TGFBR1 as Green List (high evidence)
Craniosynostosis v0.65 TGFBR1 Tiong Tan Gene: tgfbr1 has been classified as Green List (High Evidence).
Craniosynostosis v0.64 TGFBR1 Tiong Tan gene: TGFBR1 was added
gene: TGFBR1 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: TGFBR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TGFBR1 were set to 15731757
Phenotypes for gene: TGFBR1 were set to Loeys-Dietz syndrome
Penetrance for gene: TGFBR1 were set to Complete
Review for gene: TGFBR1 was set to GREEN
Added comment: Craniosynostosis is a well-established feature of LDS - TGFBR1, TGFBR2 and SMAD3
Sources: Literature
Craniosynostosis v0.63 SMO Tiong Tan Marked gene: SMO as ready
Craniosynostosis v0.63 SMO Tiong Tan Gene: smo has been classified as Green List (High Evidence).
Craniosynostosis v0.63 SMO Tiong Tan Classified gene: SMO as Green List (high evidence)
Craniosynostosis v0.63 SMO Tiong Tan Gene: smo has been classified as Green List (High Evidence).
Craniosynostosis v0.62 SMO Tiong Tan gene: SMO was added
gene: SMO was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: SMO was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMO were set to 27236920
Phenotypes for gene: SMO were set to Curry-Jones syndrome
Penetrance for gene: SMO were set to Complete
Mode of pathogenicity for gene: SMO 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: SMO was set to GREEN
Added comment: Mosaic activating variants in SMO associated with Curry-Jones syndrome - craniosynostosis is a key feature.
Sources: Literature
Craniosynostosis v0.61 SMAD6 Tiong Tan Marked gene: SMAD6 as ready
Craniosynostosis v0.61 SMAD6 Tiong Tan Gene: smad6 has been classified as Green List (High Evidence).
Craniosynostosis v0.61 SMAD6 Tiong Tan Classified gene: SMAD6 as Green List (high evidence)
Craniosynostosis v0.61 SMAD6 Tiong Tan Gene: smad6 has been classified as Green List (High Evidence).
Craniosynostosis v0.60 SMAD6 Tiong Tan gene: SMAD6 was added
gene: SMAD6 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: SMAD6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD6 were set to 32499606; 27606499
Phenotypes for gene: SMAD6 were set to non-syndromic craniosynostosis
Penetrance for gene: SMAD6 were set to Incomplete
Review for gene: SMAD6 was set to GREEN
Added comment: Penetrance is 57%. A common polymorphism near BMP2 (rs1884302) was initially proposed to influence penetrance, but follow-up study did not corroborate this. In vitro luciferase assays suggest loss of SMAD6 inhibitory function.
Sources: Literature
Craniosynostosis v0.59 SKI Tiong Tan Classified gene: SKI as Green List (high evidence)
Craniosynostosis v0.59 SKI Tiong Tan Gene: ski has been classified as Green List (High Evidence).
Craniosynostosis v0.58 SKI Tiong Tan gene: SKI was added
gene: SKI was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: SKI was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SKI were set to 23023332; 23103230; 24736733
Phenotypes for gene: SKI were set to SHPRINTZEN-GOLDBERG CRANIOSYNOSTOSIS SYNDROME
Penetrance for gene: SKI were set to Complete
Mode of pathogenicity for gene: SKI was set to Other
Review for gene: SKI was set to GREEN
Added comment: Mutational hotspot suggests a mechanism that is not LOF
Sources: Literature
Craniosynostosis v0.57 SHOC2 Tiong Tan Marked gene: SHOC2 as ready
Craniosynostosis v0.57 SHOC2 Tiong Tan Gene: shoc2 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.57 SHOC2 Tiong Tan Classified gene: SHOC2 as Amber List (moderate evidence)
Craniosynostosis v0.57 SHOC2 Tiong Tan Gene: shoc2 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.56 SHOC2 Tiong Tan gene: SHOC2 was added
gene: SHOC2 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: SHOC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SHOC2 were set to 28650561; 25123707
Phenotypes for gene: SHOC2 were set to Noonan syndrome with loose anagen hair
Penetrance for gene: SHOC2 were set to Complete
Mode of pathogenicity for gene: SHOC2 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: SHOC2 was set to AMBER
Added comment: Two unrelated individuals with SHOC2-related Noonan syndrome and craniosynostosis; other Noonan syndrome genotypes have higher incidence of craniosynostosis.
Sources: Literature
Craniosynostosis v0.55 MEGF8 Tiong Tan Marked gene: MEGF8 as ready
Craniosynostosis v0.55 MEGF8 Tiong Tan Gene: megf8 has been classified as Green List (High Evidence).
Craniosynostosis v0.55 MEGF8 Tiong Tan Classified gene: MEGF8 as Green List (high evidence)
Craniosynostosis v0.55 MEGF8 Tiong Tan Gene: megf8 has been classified as Green List (High Evidence).
Craniosynostosis v0.54 MEGF8 Tiong Tan gene: MEGF8 was added
gene: MEGF8 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: MEGF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MEGF8 were set to 23063620
Phenotypes for gene: MEGF8 were set to Carpenter syndrome
Penetrance for gene: MEGF8 were set to Complete
Review for gene: MEGF8 was set to GREEN
Added comment: Craniosynostosis is a key feature of Carpenter syndrome - identified in 4/4 unrelated individuals with MEGF8 biallelic variants
Sources: Literature
Craniosynostosis v0.53 MASP1 Tiong Tan Classified gene: MASP1 as Green List (high evidence)
Craniosynostosis v0.53 MASP1 Tiong Tan Gene: masp1 has been classified as Green List (High Evidence).
Craniosynostosis v0.52 MASP1 Tiong Tan gene: MASP1 was added
gene: MASP1 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: MASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MASP1 were set to 7677137; 21258343
Phenotypes for gene: MASP1 were set to 3MC syndrome
Penetrance for gene: MASP1 were set to Complete
Review for gene: MASP1 was set to GREEN
Added comment: Craniosynostosis occurs in 20-30% of individuals with 3MC syndrome
Sources: Literature
Mendeliome v0.3105 NEK9 Zornitza Stark Marked gene: NEK9 as ready
Mendeliome v0.3105 NEK9 Zornitza Stark Gene: nek9 has been classified as Red List (Low Evidence).
Mendeliome v0.3105 NEK9 Zornitza Stark Phenotypes for gene: NEK9 were changed from to Lethal congenital contracture syndrome 10, MIM# 617022; Skeletal dysplasia
Mendeliome v0.3104 NEK9 Zornitza Stark Publications for gene: NEK9 were set to
Mendeliome v0.3103 NEK9 Zornitza Stark Mode of inheritance for gene: NEK9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3102 NEK9 Zornitza Stark Classified gene: NEK9 as Red List (low evidence)
Mendeliome v0.3102 NEK9 Zornitza Stark Gene: nek9 has been classified as Red List (Low Evidence).
Mendeliome v0.3101 NEK9 Zornitza Stark reviewed gene: NEK9: Rating: RED; Mode of pathogenicity: None; Publications: 26908619; Phenotypes: Lethal congenital contracture syndrome 10, MIM# 617022, Skeletal dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.22 NEK9 Zornitza Stark Marked gene: NEK9 as ready
Skeletal Dysplasia_Fetal v0.22 NEK9 Zornitza Stark Gene: nek9 has been classified as Red List (Low Evidence).
Skeletal Dysplasia_Fetal v0.22 NEK9 Zornitza Stark Tag founder tag was added to gene: NEK9.
Skeletal Dysplasia_Fetal v0.22 NEK9 Zornitza Stark gene: NEK9 was added
gene: NEK9 was added to Skeletal Dysplasia_Fetal. Sources: Expert list
Mode of inheritance for gene: NEK9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEK9 were set to 26908619
Phenotypes for gene: NEK9 were set to Lethal congenital contracture syndrome 10, MIM# 617022; Skeletal dysplasia
Review for gene: NEK9 was set to RED
Added comment: Two Irish traveller families, 5 affected individuals, same homozygous variant identified (founder effect). Limited functional data.
Sources: Expert list
Skeletal dysplasia v0.33 NEK9 Zornitza Stark Tag founder tag was added to gene: NEK9.
Skeletal dysplasia v0.33 NEK9 Zornitza Stark Marked gene: NEK9 as ready
Skeletal dysplasia v0.33 NEK9 Zornitza Stark Gene: nek9 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.33 NEK9 Zornitza Stark gene: NEK9 was added
gene: NEK9 was added to Skeletal dysplasia. Sources: Expert list
Mode of inheritance for gene: NEK9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEK9 were set to 26908619
Phenotypes for gene: NEK9 were set to Lethal congenital contracture syndrome 10, MIM# 617022; Skeletal dysplasia
Review for gene: NEK9 was set to RED
Added comment: Two Irish traveller families, 5 affected individuals, same homozygous variant identified (founder effect). Limited functional data.
Sources: Expert list
Mendeliome v0.3101 MSTN Zornitza Stark Marked gene: MSTN as ready
Mendeliome v0.3101 MSTN Zornitza Stark Gene: mstn has been classified as Red List (Low Evidence).
Mendeliome v0.3101 MSTN Zornitza Stark Phenotypes for gene: MSTN were changed from to Muscle hypertrophy, MIM# 614160
Mendeliome v0.3100 MSTN Zornitza Stark Publications for gene: MSTN were set to
Mendeliome v0.3099 MSTN Zornitza Stark Mode of inheritance for gene: MSTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3098 MSTN Zornitza Stark Classified gene: MSTN as Red List (low evidence)
Mendeliome v0.3098 MSTN Zornitza Stark Gene: mstn has been classified as Red List (Low Evidence).
Mendeliome v0.3097 MSTN Zornitza Stark reviewed gene: MSTN: Rating: RED; Mode of pathogenicity: None; Publications: 15215484; Phenotypes: Muscle hypertrophy, MIM# 614160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3097 HSPB8 Zornitza Stark Marked gene: HSPB8 as ready
Mendeliome v0.3097 HSPB8 Zornitza Stark Gene: hspb8 has been classified as Green List (High Evidence).
Mendeliome v0.3097 HSPB8 Zornitza Stark Phenotypes for gene: HSPB8 were changed from to Distal myopathy; Vacuolar myopathy; Neuropathy, distal hereditary motor type IIA, 158590; Charcot-Marie-Tooth disease, axonal, type 2L, MIM# 608673
Mendeliome v0.3096 HSPB8 Zornitza Stark Publications for gene: HSPB8 were set to
Mendeliome v0.3095 HSPB8 Zornitza Stark Mode of inheritance for gene: HSPB8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3094 HSPB8 Zornitza Stark reviewed gene: HSPB8: Rating: GREEN; Mode of pathogenicity: None; Publications: 32165108, 31403083, 28780615, 15122253, 26718575; Phenotypes: Distal myopathy, Vacuolar myopathy, Neuropathy, distal hereditary motor type IIA, 158590, Charcot-Marie-Tooth disease, axonal, type 2L, MIM# 608673; Mode of inheritance: None
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.6 DYSF Zornitza Stark Marked gene: DYSF as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.6 DYSF Zornitza Stark Gene: dysf has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.6 DYSF Zornitza Stark Publications for gene: DYSF were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.5 DNAJB6 Zornitza Stark Marked gene: DNAJB6 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.5 DNAJB6 Zornitza Stark Gene: dnajb6 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.5 DNAJB6 Zornitza Stark Publications for gene: DNAJB6 were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 STAG3 Bryony Thompson gene: STAG3 was added
gene: STAG3 was added to Amenorrhoea. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: STAG3 was set to BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 SOHLH1 Bryony Thompson gene: SOHLH1 was added
gene: SOHLH1 was added to Amenorrhoea. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: SOHLH1 was set to BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 PMM2 Bryony Thompson gene: PMM2 was added
gene: PMM2 was added to Amenorrhoea. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: PMM2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PMM2 were set to Congenital disorder of glycosylation, type Ia 212065
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 HFM1 Bryony Thompson gene: HFM1 was added
gene: HFM1 was added to Amenorrhoea. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: HFM1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HFM1 were set to Premature ovarian failure 9,615724
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 FSHB Bryony Thompson gene: FSHB was added
gene: FSHB was added to Amenorrhoea. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: FSHB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FSHB were set to Hypogonadotropic hypogonadism 24 without anosmia 229070
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 AARS2 Bryony Thompson gene: AARS2 was added
gene: AARS2 was added to Amenorrhoea. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: AARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AARS2 were set to Leukoencephalopathy, progressive, with ovarian failure 615889
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 WT1 Bryony Thompson gene: WT1 was added
gene: WT1 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: WT1 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 WDR11 Bryony Thompson gene: WDR11 was added
gene: WDR11 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: WDR11 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 TACR3 Bryony Thompson gene: TACR3 was added
gene: TACR3 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: TACR3 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 TAC3 Bryony Thompson gene: TAC3 was added
gene: TAC3 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: TAC3 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 STAR Bryony Thompson gene: STAR was added
gene: STAR was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: STAR was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 SEMA3A Bryony Thompson gene: SEMA3A was added
gene: SEMA3A was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: SEMA3A was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 PSMC3IP Bryony Thompson gene: PSMC3IP was added
gene: PSMC3IP was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PSMC3IP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PSMC3IP were set to Ovarian dysgenesis 3,614324
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 PROKR2 Bryony Thompson gene: PROKR2 was added
gene: PROKR2 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PROKR2 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 PROK2 Bryony Thompson gene: PROK2 was added
gene: PROK2 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PROK2 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 POR Bryony Thompson gene: POR was added
gene: POR was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: POR was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 POLG Bryony Thompson gene: POLG was added
gene: POLG was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: POLG was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: POLG were set to Progressive external ophthalmoplegia, autosomal recessive 1 258450; Progressive external ophthalmoplegia, autosomal dominant 1 157640
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 NUP107 Bryony Thompson gene: NUP107 was added
gene: NUP107 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: NUP107 was set to BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 NR5A1 Bryony Thompson gene: NR5A1 was added
gene: NR5A1 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: NR5A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NR5A1 were set to Spermatogenic failure 8,613957; 46XY sex reversal 3,612965; Premature ovarian failure 7,612964
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 NOBOX Bryony Thompson gene: NOBOX was added
gene: NOBOX was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: NOBOX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NOBOX were set to Premature ovarian failure 5,611548
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 MCM9 Bryony Thompson gene: MCM9 was added
gene: MCM9 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: MCM9 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MCM9 were set to Ovarian dysgenesis 4, 616185
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 MCM8 Bryony Thompson gene: MCM8 was added
gene: MCM8 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: MCM8 was set to BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 LMNA Bryony Thompson gene: LMNA was added
gene: LMNA was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: LMNA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 LHCGR Bryony Thompson gene: LHCGR was added
gene: LHCGR was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: LHCGR was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 LHB Bryony Thompson gene: LHB was added
gene: LHB was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: LHB was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 LARS2 Bryony Thompson gene: LARS2 was added
gene: LARS2 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: LARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LARS2 were set to Perrault syndrome 4 615300
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 KISS1R Bryony Thompson gene: KISS1R was added
gene: KISS1R was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: KISS1R was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 KISS1 Bryony Thompson gene: KISS1 was added
gene: KISS1 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: KISS1 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 HSD17B4 Bryony Thompson gene: HSD17B4 was added
gene: HSD17B4 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: HSD17B4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HSD17B4 were set to Perrault syndrome 1 233400
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 GNAS Bryony Thompson gene: GNAS was added
gene: GNAS was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: GNAS was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 GDF9 Bryony Thompson gene: GDF9 was added
gene: GDF9 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: GDF9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 GALT Bryony Thompson gene: GALT was added
gene: GALT was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: GALT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GALT were set to Galactosemia, 230400
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 FSHR Bryony Thompson gene: FSHR was added
gene: FSHR was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: FSHR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FSHR were set to Ovarian dysgenesis 1 233300; Ovarian response to FSH stimulation 276400
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 FOXL2 Bryony Thompson gene: FOXL2 was added
gene: FOXL2 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: FOXL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FOXL2 were set to Blepharophimosis,epicanthus inversus and ptosis,type 1 and 2,110100; Premature ovarian failure 3,608996
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 FMR1 Bryony Thompson gene: FMR1 was added
gene: FMR1 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: FMR1 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: FMR1 were set to Fragile X tremor ataxia syndrome, 300623; Fragile X syndrome, 300624; Premature ovarian failure 1, 311360
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 FIGLA Bryony Thompson gene: FIGLA was added
gene: FIGLA was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: FIGLA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FIGLA were set to Premature ovarian failure,612310
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 FGFR1 Bryony Thompson gene: FGFR1 was added
gene: FGFR1 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: FGFR1 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 ESR1 Bryony Thompson gene: ESR1 was added
gene: ESR1 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: ESR1 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 EIF2B5 Bryony Thompson gene: EIF2B5 was added
gene: EIF2B5 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: EIF2B5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2B5 were set to Ovarioleukodystrophy 603896
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 EIF2B4 Bryony Thompson gene: EIF2B4 was added
gene: EIF2B4 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: EIF2B4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2B4 were set to Ovarioleukodystrophy 603896
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 EIF2B2 Bryony Thompson gene: EIF2B2 was added
gene: EIF2B2 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: EIF2B2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2B2 were set to Ovarioleukodystrophy 603896
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 CYP19A1 Bryony Thompson gene: CYP19A1 was added
gene: CYP19A1 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CYP19A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYP19A1 were set to Aromatase deficiency 613546
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 CYP17A1 Bryony Thompson gene: CYP17A1 was added
gene: CYP17A1 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CYP17A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYP17A1 were set to 17-alpha-hydroxylase, 17,20-lyase deficiency 202110
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 CLPP Bryony Thompson gene: CLPP was added
gene: CLPP was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CLPP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CLPP were set to Perrault syndrome 3 614129
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 TWNK Bryony Thompson gene: TWNK was added
gene: TWNK was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: TWNK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TWNK were set to Perrault syndrome 5, 616138
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 BMP15 Bryony Thompson gene: BMP15 was added
gene: BMP15 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: BMP15 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: BMP15 were set to Ovarian dysgenesis 2,300510; Premature ovarian failure 4300510
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 AMHR2 Bryony Thompson gene: AMHR2 was added
gene: AMHR2 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: AMHR2 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 AMH Bryony Thompson gene: AMH was added
gene: AMH was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: AMH was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 AIRE Bryony Thompson gene: AIRE was added
gene: AIRE was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: AIRE was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 Bryony Thompson Added panel Amenorrhoea
Glycogen Storage Diseases v0.8 GAA Crystle Lee reviewed gene: GAA: Rating: GREEN; Mode of pathogenicity: None; Publications: 25103075, 27365701; Phenotypes: Glycogen storage disease II (MIM#232300); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.65 CHST14 Zornitza Stark Marked gene: CHST14 as ready
Arthrogryposis v0.65 CHST14 Zornitza Stark Gene: chst14 has been classified as Green List (High Evidence).
Arthrogryposis v0.65 CHST14 Zornitza Stark Phenotypes for gene: CHST14 were changed from to Ehlers-Danlos syndrome, musculocontractural type 1 (MIM#601776)
Arthrogryposis v0.64 CHST14 Zornitza Stark Publications for gene: CHST14 were set to
Arthrogryposis v0.63 CHST14 Zornitza Stark Mode of inheritance for gene: CHST14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.15 CAVIN1 Zornitza Stark Marked gene: CAVIN1 as ready
Muscular dystrophy and myopathy_Paediatric v0.15 CAVIN1 Zornitza Stark Gene: cavin1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.15 CAVIN1 Zornitza Stark Classified gene: CAVIN1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.15 CAVIN1 Zornitza Stark Gene: cavin1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.14 CAVIN1 Zornitza Stark gene: CAVIN1 was added
gene: CAVIN1 was added to Muscular dystrophy. Sources: Expert list
Mode of inheritance for gene: CAVIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CAVIN1 were set to Lipodystrophy, congenital generalized, type 4 (MIM#613327)
Review for gene: CAVIN1 was set to GREEN
Added comment: Gene also known as PTRF. Multiple families reported with onset of disease in childhood, muscular dystrophy is a feature.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.56 AMPD1 Zornitza Stark Marked gene: AMPD1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.56 AMPD1 Zornitza Stark Gene: ampd1 has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.56 AMPD1 Zornitza Stark Classified gene: AMPD1 as Red List (low evidence)
Rhabdomyolysis and Metabolic Myopathy v0.56 AMPD1 Zornitza Stark Gene: ampd1 has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.55 AMPD1 Zornitza Stark Tag disputed tag was added to gene: AMPD1.
Rhabdomyolysis and Metabolic Myopathy v0.55 AMPD1 Zornitza Stark reviewed gene: AMPD1: Rating: RED; Mode of pathogenicity: None; Publications: 21343608, 27296017; Phenotypes: Myopathy due to myoadenylate deaminase deficiency (MIM#615511); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3094 AMPD1 Zornitza Stark Marked gene: AMPD1 as ready
Mendeliome v0.3094 AMPD1 Zornitza Stark Gene: ampd1 has been classified as Red List (Low Evidence).
Mendeliome v0.3094 AMPD1 Zornitza Stark Phenotypes for gene: AMPD1 were changed from to Myopathy due to myoadenylate deaminase deficiency (MIM#615511)
Mendeliome v0.3093 AMPD1 Zornitza Stark Publications for gene: AMPD1 were set to
Mendeliome v0.3092 AMPD1 Zornitza Stark Mode of inheritance for gene: AMPD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3091 AMPD1 Zornitza Stark Classified gene: AMPD1 as Red List (low evidence)
Mendeliome v0.3091 AMPD1 Zornitza Stark Gene: ampd1 has been classified as Red List (Low Evidence).
Mendeliome v0.3090 AMPD1 Zornitza Stark Tag disputed tag was added to gene: AMPD1.
Mendeliome v0.3090 AMPD1 Zornitza Stark reviewed gene: AMPD1: Rating: RED; Mode of pathogenicity: None; Publications: 21343608, 27296017; Phenotypes: Myopathy due to myoadenylate deaminase deficiency (MIM#615511); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia - adult onset v0.21 SLC25A15 Bryony Thompson Marked gene: SLC25A15 as ready
Hereditary Spastic Paraplegia - adult onset v0.21 SLC25A15 Bryony Thompson Gene: slc25a15 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - adult onset v0.21 SLC25A15 Bryony Thompson Classified gene: SLC25A15 as Green List (high evidence)
Hereditary Spastic Paraplegia - adult onset v0.21 SLC25A15 Bryony Thompson Gene: slc25a15 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - adult onset v0.20 SLC25A15 Bryony Thompson gene: SLC25A15 was added
gene: SLC25A15 was added to Hereditary Spastic Paraplegia - adult onset. Sources: Expert list
Mode of inheritance for gene: SLC25A15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A15 were set to 16376511; 22465082; 28592010
Phenotypes for gene: SLC25A15 were set to Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome MIM#238970
Review for gene: SLC25A15 was set to GREEN
Added comment: At least four unrelated cases reported with an adult onset spastic paraparesis as a feature of the condition.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.4 DYSF Crystle Lee reviewed gene: DYSF: Rating: GREEN; Mode of pathogenicity: None; Publications: 23243261; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 2 (MIM#253601); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia - paediatric v0.105 GPT2 Bryony Thompson Marked gene: GPT2 as ready
Hereditary Spastic Paraplegia - paediatric v0.105 GPT2 Bryony Thompson Gene: gpt2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.105 GPT2 Bryony Thompson Classified gene: GPT2 as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v0.105 GPT2 Bryony Thompson Gene: gpt2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.104 GPT2 Bryony Thompson gene: GPT2 was added
gene: GPT2 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: GPT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPT2 were set to 29882329; 31471722; 27601654
Phenotypes for gene: GPT2 were set to Mental retardation, autosomal recessive 49 MIM#616281
Review for gene: GPT2 was set to GREEN
Added comment: Paediatric onset spastic paraglegia is a prominent feature of the condition, >3 unrelated families reported.
Sources: Expert list
Hereditary Spastic Paraplegia - adult onset v0.19 GBE1 Bryony Thompson Marked gene: GBE1 as ready
Hereditary Spastic Paraplegia - adult onset v0.19 GBE1 Bryony Thompson Gene: gbe1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - adult onset v0.19 GBE1 Bryony Thompson Classified gene: GBE1 as Green List (high evidence)
Hereditary Spastic Paraplegia - adult onset v0.19 GBE1 Bryony Thompson Gene: gbe1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - adult onset v0.18 GBE1 Bryony Thompson gene: GBE1 was added
gene: GBE1 was added to Hereditary Spastic Paraplegia - adult onset. Sources: Expert list
Mode of inheritance for gene: GBE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBE1 were set to 23034915
Phenotypes for gene: GBE1 were set to Polyglucosan body disease, adult form MIM#263570
Review for gene: GBE1 was set to GREEN
Added comment: Spastic paraplegia is a reported as a prominent feature of the condition in 45/50 cases diagnosed with adult polyglucosan body disease.
Sources: Expert list
Hereditary Spastic Paraplegia - adult onset v0.17 GALC Bryony Thompson Marked gene: GALC as ready
Hereditary Spastic Paraplegia - adult onset v0.17 GALC Bryony Thompson Gene: galc has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - adult onset v0.17 GALC Bryony Thompson Classified gene: GALC as Green List (high evidence)
Hereditary Spastic Paraplegia - adult onset v0.17 GALC Bryony Thompson Gene: galc has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - adult onset v0.16 GALC Bryony Thompson gene: GALC was added
gene: GALC was added to Hereditary Spastic Paraplegia - adult onset. Sources: Expert list
Mode of inheritance for gene: GALC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALC were set to 9272171; 11971051; 22959700; 26396125; 26915362; 28547031; 31185936; 32064984
Phenotypes for gene: GALC were set to Krabbe disease MIM#245200
Review for gene: GALC was set to GREEN
Added comment: Adult onset spastic paraplegia is reported as a feature of the condition in greater than 3 cases.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.4 DNAJB6 Crystle Lee reviewed gene: DNAJB6: Rating: GREEN; Mode of pathogenicity: None; Publications: 26847086, 26338452, 24170373; Phenotypes: Muscular dystrophy, limb-girdle, autosomal dominant 1 (MIM#603511); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Arthrogryposis v0.62 CHST14 Crystle Lee reviewed gene: CHST14: Rating: GREEN; Mode of pathogenicity: None; Publications: 26373698; Phenotypes: Ehlers-Danlos syndrome, musculocontractural type 1 (MIM#601776); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia - paediatric v0.219 UBTF Bryony Thompson changed review comment from: Ataxia reported as a feature of the condition in 4 unrelated cases with de novo missense variants.
Sources: Expert list; to: Paediatric ataxia reported as a feature of the condition in 4 unrelated cases with de novo missense variants.
Sources: Expert list
Ataxia - paediatric v0.219 UBTF Bryony Thompson Marked gene: UBTF as ready
Ataxia - paediatric v0.219 UBTF Bryony Thompson Gene: ubtf has been classified as Green List (High Evidence).
Ataxia - paediatric v0.219 UBTF Bryony Thompson Classified gene: UBTF as Green List (high evidence)
Ataxia - paediatric v0.219 UBTF Bryony Thompson Gene: ubtf has been classified as Green List (High Evidence).
Ataxia - paediatric v0.218 UBTF Bryony Thompson gene: UBTF was added
gene: UBTF was added to Ataxia - paediatric. Sources: Expert list
Mode of inheritance for gene: UBTF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBTF were set to 29300972
Phenotypes for gene: UBTF were set to Neurodegeneration, childhood-onset, with brain atrophy MIM#617672
Review for gene: UBTF was set to GREEN
Added comment: Ataxia reported as a feature of the condition in 4 unrelated cases with de novo missense variants.
Sources: Expert list
Mendeliome v0.3090 FBXW11 Zornitza Stark Phenotypes for gene: FBXW11 were changed from Intellectual disability; developmental eye anomalies; digital anomalies to Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Intellectual disability; developmental eye anomalies; digital anomalies
Mendeliome v0.3089 FBXW11 Zornitza Stark reviewed gene: FBXW11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Anophthalmia_Microphthalmia_Coloboma v0.59 FBXW11 Zornitza Stark Phenotypes for gene: FBXW11 were changed from Intellectual disability; developmental eye anomalies; digital anomalies to Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Intellectual disability; developmental eye anomalies; digital anomalies
Anophthalmia_Microphthalmia_Coloboma v0.58 FBXW11 Zornitza Stark reviewed gene: FBXW11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2699 FBXW11 Zornitza Stark Phenotypes for gene: FBXW11 were changed from Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Intellectual disability; developmental eye anomalies; digital anomalies to Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Intellectual disability; developmental eye anomalies; digital anomalies
Intellectual disability syndromic and non-syndromic v0.2699 FBXW11 Zornitza Stark Phenotypes for gene: FBXW11 were changed from Intellectual disability; developmental eye anomalies; digital anomalies to Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Intellectual disability; developmental eye anomalies; digital anomalies
Intellectual disability syndromic and non-syndromic v0.2698 FBXW11 Zornitza Stark reviewed gene: FBXW11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia - paediatric v0.217 MTFMT Bryony Thompson Marked gene: MTFMT as ready
Ataxia - paediatric v0.217 MTFMT Bryony Thompson Gene: mtfmt has been classified as Green List (High Evidence).
Ataxia - paediatric v0.217 MTFMT Bryony Thompson Classified gene: MTFMT as Green List (high evidence)
Ataxia - paediatric v0.217 MTFMT Bryony Thompson Gene: mtfmt has been classified as Green List (High Evidence).
Ataxia - paediatric v0.216 MTFMT Bryony Thompson gene: MTFMT was added
gene: MTFMT was added to Ataxia - paediatric. Sources: Expert list
Mode of inheritance for gene: MTFMT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTFMT were set to 26060307; 24461907
Phenotypes for gene: MTFMT were set to Combined oxidative phosphorylation deficiency 15 MIM#614947; Mitochondrial complex I deficiency, nuclear type 27 MIM#618248
Review for gene: MTFMT was set to GREEN
Added comment: Five unrelated cases reported with paediatric onset ataxia as a prominent feature of the condition.
Sources: Expert list
Ataxia - adult onset v0.56 LMNB1 Bryony Thompson changed review comment from: Four unrelated families reported with cerebellar ataxia as a feature of the condition.
Sources: Expert list; to: Four unrelated families reported with adult onset cerebellar ataxia as a feature of the condition.
Sources: Expert list
Ataxia - adult onset v0.56 LMNB1 Bryony Thompson Marked gene: LMNB1 as ready
Ataxia - adult onset v0.56 LMNB1 Bryony Thompson Gene: lmnb1 has been classified as Green List (High Evidence).
Ataxia - adult onset v0.56 LMNB1 Bryony Thompson Classified gene: LMNB1 as Green List (high evidence)
Ataxia - adult onset v0.56 LMNB1 Bryony Thompson Gene: lmnb1 has been classified as Green List (High Evidence).
Ataxia - adult onset v0.55 LMNB1 Bryony Thompson gene: LMNB1 was added
gene: LMNB1 was added to Ataxia - adult onset. Sources: Expert list
Mode of inheritance for gene: LMNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LMNB1 were set to 31695592
Phenotypes for gene: LMNB1 were set to Leukodystrophy, adult-onset, autosomal dominant MIM#169500
Review for gene: LMNB1 was set to GREEN
Added comment: Four unrelated families reported with cerebellar ataxia as a feature of the condition.
Sources: Expert list
Ataxia - paediatric v0.215 FA2H Bryony Thompson Marked gene: FA2H as ready
Ataxia - paediatric v0.215 FA2H Bryony Thompson Gene: fa2h has been classified as Green List (High Evidence).
Ataxia - paediatric v0.215 FA2H Bryony Thompson Classified gene: FA2H as Green List (high evidence)
Ataxia - paediatric v0.215 FA2H Bryony Thompson Gene: fa2h has been classified as Green List (High Evidence).
Ataxia - paediatric v0.214 FA2H Bryony Thompson gene: FA2H was added
gene: FA2H was added to Ataxia - paediatric. Sources: Expert list
Mode of inheritance for gene: FA2H was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FA2H were set to 31135052
Phenotypes for gene: FA2H were set to Spastic paraplegia 35, autosomal recessive MIM#612319
Review for gene: FA2H was set to GREEN
Added comment: Limb ataxia is reported as a feature of the condition in at least 13 cases with mainly paediatric onset.
Sources: Expert list
Leukodystrophy - paediatric v0.133 FDX2 Bryony Thompson Marked gene: FDX2 as ready
Leukodystrophy - paediatric v0.133 FDX2 Bryony Thompson Gene: fdx2 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.133 FDX2 Bryony Thompson Classified gene: FDX2 as Amber List (moderate evidence)
Leukodystrophy - paediatric v0.133 FDX2 Bryony Thompson Gene: fdx2 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.132 FDX2 Bryony Thompson gene: FDX2 was added
gene: FDX2 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: FDX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDX2 were set to 30010796
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 AMBER
Added comment: Two apparently unrelated consanguineous Brazilian families reported with reversible leukoencephalopathy with a paediatric onset as a feature of the condition.
Sources: Expert list
Leukodystrophy - paediatric v0.131 COA7 Bryony Thompson Marked gene: COA7 as ready
Leukodystrophy - paediatric v0.131 COA7 Bryony Thompson Gene: coa7 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.131 COA7 Bryony Thompson Classified gene: COA7 as Green List (high evidence)
Leukodystrophy - paediatric v0.131 COA7 Bryony Thompson Gene: coa7 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.130 COA7 Bryony Thompson changed review comment from: At least 3 unrelated cases reported with leukoencephalopathy as a feature of the condition.
Sources: Expert list; to: At least 3 unrelated cases reported with leukoencephalopathy as a feature of the condition. Paediatric age of onset.
Sources: Expert list
Leukodystrophy - paediatric v0.130 COA7 Bryony Thompson gene: COA7 was added
gene: COA7 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: COA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COA7 were set to 27683825; 29718187
Phenotypes for gene: COA7 were set to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MIM#618387
Review for gene: COA7 was set to GREEN
Added comment: At least 3 unrelated cases reported with leukoencephalopathy as a feature of the condition.
Sources: Expert list
Leukodystrophy - paediatric v0.129 AP4B1 Bryony Thompson Marked gene: AP4B1 as ready
Leukodystrophy - paediatric v0.129 AP4B1 Bryony Thompson Gene: ap4b1 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.129 AP4B1 Bryony Thompson Classified gene: AP4B1 as Green List (high evidence)
Leukodystrophy - paediatric v0.129 AP4B1 Bryony Thompson Gene: ap4b1 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.128 AP4B1 Bryony Thompson gene: AP4B1 was added
gene: AP4B1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: AP4B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP4B1 were set to 29193663
Phenotypes for gene: AP4B1 were set to Spastic paraplegia 47, autosomal recessive MIM#614066
Review for gene: AP4B1 was set to GREEN
Added comment: White matter changes have been reported as a feature of the condition in at least ten unrelated cases with biallelic variants. The onset of the condition is paediatric.
Sources: Expert list
Craniosynostosis v0.51 PTPN11 Tiong Tan Marked gene: PTPN11 as ready
Craniosynostosis v0.51 PTPN11 Tiong Tan Gene: ptpn11 has been classified as Green List (High Evidence).
Craniosynostosis v0.51 PTPN11 Tiong Tan Classified gene: PTPN11 as Green List (high evidence)
Craniosynostosis v0.51 PTPN11 Tiong Tan Gene: ptpn11 has been classified as Green List (High Evidence).
Craniosynostosis v0.50 PTPN11 Tiong Tan gene: PTPN11 was added
gene: PTPN11 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: PTPN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN11 were set to 28650561
Phenotypes for gene: PTPN11 were set to Noonan syndrome
Penetrance for gene: PTPN11 were set to Complete
Mode of pathogenicity for gene: PTPN11 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: PTPN11 was set to GREEN
Added comment: Three unrelated individuals with PTPN11-related Noonan syndrome and craniosynostosis
Sources: Literature
Craniosynostosis v0.49 BRAF Tiong Tan Marked gene: BRAF as ready
Craniosynostosis v0.49 BRAF Tiong Tan Gene: braf has been classified as Green List (High Evidence).
Craniosynostosis v0.49 BRAF Tiong Tan Classified gene: BRAF as Green List (high evidence)
Craniosynostosis v0.49 BRAF Tiong Tan Gene: braf has been classified as Green List (High Evidence).
Craniosynostosis v0.48 BRAF Tiong Tan gene: BRAF was added
gene: BRAF was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRAF were set to 28650561
Phenotypes for gene: BRAF were set to CFC
Penetrance for gene: BRAF were set to Complete
Mode of pathogenicity for gene: BRAF 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: BRAF was set to GREEN
Added comment: Four unrelated individuals with CFC and craniosynostosis
Sources: Literature
Craniosynostosis v0.47 KRAS Tiong Tan Marked gene: KRAS as ready
Craniosynostosis v0.47 KRAS Tiong Tan Gene: kras has been classified as Green List (High Evidence).
Craniosynostosis v0.47 KRAS Tiong Tan Classified gene: KRAS as Green List (high evidence)
Craniosynostosis v0.47 KRAS Tiong Tan Gene: kras has been classified as Green List (High Evidence).
Craniosynostosis v0.46 KRAS Tiong Tan gene: KRAS was added
gene: KRAS was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: KRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRAS were set to 26249544; 28650561
Phenotypes for gene: KRAS were set to Noonan syndrome
Penetrance for gene: KRAS were set to Complete
Mode of pathogenicity for gene: KRAS 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: KRAS was set to GREEN
Added comment: 10% of all individuals with KRAS-related Noonan syndrome have craniosynostosis
Sources: Literature
Craniosynostosis v0.45 KAT6A Tiong Tan Classified gene: KAT6A as Green List (high evidence)
Craniosynostosis v0.45 KAT6A Tiong Tan Gene: kat6a has been classified as Green List (High Evidence).
Craniosynostosis v0.44 KAT6A Tiong Tan Classified gene: KAT6A as Green List (high evidence)
Craniosynostosis v0.44 KAT6A Tiong Tan Gene: kat6a has been classified as Green List (High Evidence).
Craniosynostosis v0.43 KAT6A Tiong Tan Marked gene: KAT6A as ready
Craniosynostosis v0.43 KAT6A Tiong Tan Gene: kat6a has been classified as Red List (Low Evidence).
Craniosynostosis v0.43 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Craniosynostosis v0.42 KAT6A Tiong Tan gene: KAT6A was added
gene: KAT6A was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: KAT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KAT6A were set to 30245513; 25728777
Phenotypes for gene: KAT6A were set to Arboleda-Tham syndrome
Penetrance for gene: KAT6A were set to Complete
Review for gene: KAT6A was set to GREEN
Added comment: Low frequency association of craniosynostosis in Arboleda-Tham syndrome. Six individuals reported in two publications.
Sources: Literature
Craniosynostosis v0.41 FLNA Tiong Tan Marked gene: FLNA as ready
Craniosynostosis v0.41 FLNA Tiong Tan Gene: flna has been classified as Green List (High Evidence).
Craniosynostosis v0.41 FLNA Tiong Tan Classified gene: FLNA as Green List (high evidence)
Craniosynostosis v0.41 FLNA Tiong Tan Gene: flna has been classified as Green List (High Evidence).
Craniosynostosis v0.40 FLNA Tiong Tan gene: FLNA was added
gene: FLNA was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: FLNA 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: FLNA were set to 25873011; 16835913; 21031081
Phenotypes for gene: FLNA were set to otopalatodigital spectrum
Penetrance for gene: FLNA were set to Complete
Mode of pathogenicity for gene: FLNA 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: FLNA was set to GREEN
Added comment: LOF variants cause PVNH; GOF variants cause OPD spectrum. Craniosynostosis is a low frequency association with FLNA-related OPD spectrum. Six unrelated probands reported in three publications.
Sources: Literature
Hereditary Spastic Paraplegia - paediatric v0.103 ARL6IP1 Zornitza Stark Publications for gene: ARL6IP1 were set to 30980493; 24482476; 28471035
Hereditary Spastic Paraplegia - paediatric v0.102 ARL6IP1 Zornitza Stark Phenotypes for gene: ARL6IP1 were changed from ?Spastic paraplegia 61, autosomal recessive, MIM#615685 to Spastic paraplegia 61, autosomal recessive, MIM#615685
Hereditary Spastic Paraplegia - paediatric v0.101 ARL6IP1 Zornitza Stark Marked gene: ARL6IP1 as ready
Hereditary Spastic Paraplegia - paediatric v0.101 ARL6IP1 Zornitza Stark Gene: arl6ip1 has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.10 NOTCH3 Bryony Thompson Classified gene: NOTCH3 as Amber List (moderate evidence)
Alternating Hemiplegia and Hemiplegic Migraine v0.10 NOTCH3 Bryony Thompson Gene: notch3 has been classified as Amber List (Moderate Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.9 NOTCH3 Bryony Thompson gene: NOTCH3 was added
gene: NOTCH3 was added to Alternating Hemiplegia and Hemiplegic Migraine. Sources: Expert list
Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH3 were set to 22250206; 10356105; 27881154; 28271496
Phenotypes for gene: NOTCH3 were set to Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 MIM#125310
Review for gene: NOTCH3 was set to AMBER
Added comment: Migraine with aura is a common feature of CADASIL and the condition can be misdiagnosed as familial hemiplegic migraine. However, can only find one family reported with a confirmed NOTCH3 variant and a diagnosis of hemiplegic migraine (PMID: 22250206).
Sources: Expert list
Alternating Hemiplegia and Hemiplegic Migraine v0.8 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mendeliome v0.3089 DCAF8 Bryony Thompson Classified gene: DCAF8 as Amber List (moderate evidence)
Mendeliome v0.3089 DCAF8 Bryony Thompson Gene: dcaf8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3088 DCAF8 Bryony Thompson gene: DCAF8 was added
gene: DCAF8 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DCAF8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DCAF8 were set to 24500646
Phenotypes for gene: DCAF8 were set to Giant axonal neuropathy 2, autosomal dominant MIM#610100
Review for gene: DCAF8 was set to AMBER
Added comment: A single large family segregating a missense variant and in vitro functional assays demonstrating the variant reduces the association of DCAF8 and DDB1, which is important in Cul4-ubiquitin E3 function
Sources: Expert list
Hereditary Neuropathy - complex v0.64 DCAF8 Bryony Thompson Classified gene: DCAF8 as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.64 DCAF8 Bryony Thompson Gene: dcaf8 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.63 DCAF8 Bryony Thompson edited their review of gene: DCAF8: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.63 DCAF8 Bryony Thompson reviewed gene: DCAF8: Rating: AMBER; Mode of pathogenicity: None; Publications: 24500646; Phenotypes: Giant axonal neuropathy 2, autosomal dominant MIM#610100; Mode of inheritance: None
Mendeliome v0.3087 ARL6IP1 Bryony Thompson Marked gene: ARL6IP1 as ready
Mendeliome v0.3087 ARL6IP1 Bryony Thompson Gene: arl6ip1 has been classified as Green List (High Evidence).
Mendeliome v0.3087 ARL6IP1 Bryony Thompson Classified gene: ARL6IP1 as Green List (high evidence)
Mendeliome v0.3087 ARL6IP1 Bryony Thompson Gene: arl6ip1 has been classified as Green List (High Evidence).
Mendeliome v0.3086 ARL6IP1 Bryony Thompson gene: ARL6IP1 was added
gene: ARL6IP1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARL6IP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL6IP1 were set to 24482476; 31272422; 30980493; 28471035
Phenotypes for gene: ARL6IP1 were set to Spastic paraplegia 61, autosomal recessive MIM#615685
Review for gene: ARL6IP1 was set to GREEN
gene: ARL6IP1 was marked as current diagnostic
Added comment: At least 4 families reported with paediatric onset complicated spastic paraplegia and neuropathy. Supporting zebrafish model.
Sources: Expert list
Hereditary Neuropathy - complex v0.63 ARL6IP1 Bryony Thompson Marked gene: ARL6IP1 as ready
Hereditary Neuropathy - complex v0.63 ARL6IP1 Bryony Thompson Gene: arl6ip1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.63 ARL6IP1 Bryony Thompson reviewed gene: ARL6IP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24482476, 31272422, 30980493, 28471035; Phenotypes: Spastic paraplegia 61, autosomal recessive MIM#615685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3085 RFC1 Bryony Thompson Tag STR tag was added to gene: RFC1.
Mendeliome v0.3085 PMP2 Bryony Thompson Marked gene: PMP2 as ready
Mendeliome v0.3085 PMP2 Bryony Thompson Gene: pmp2 has been classified as Green List (High Evidence).
Mendeliome v0.3085 PMP2 Bryony Thompson Classified gene: PMP2 as Green List (high evidence)
Mendeliome v0.3085 PMP2 Bryony Thompson Gene: pmp2 has been classified as Green List (High Evidence).
Mendeliome v0.3084 PMP2 Bryony Thompson gene: PMP2 was added
gene: PMP2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PMP2 were set to 26257172; 26828946; 27009151
Phenotypes for gene: PMP2 were set to Charcot-Marie-Tooth disease, demyelinating, type 1G MIM#618279
Review for gene: PMP2 was set to GREEN
Added comment: 4 unrelated families reported with missense variants, with supporting transgenic mouse and null zebrafish models.
Sources: Expert list
Hereditary Neuropathy_CMT - isolated v0.46 PMP2 Bryony Thompson reviewed gene: PMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26257172, 26828946, 27009151; Phenotypes: Charcot-Marie-Tooth disease, demyelinating, type 1G MIM#618279; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy_CMT - isolated v0.46 PMP22 Bryony Thompson Classified gene: PMP22 as Green List (high evidence)
Hereditary Neuropathy_CMT - isolated v0.46 PMP22 Bryony Thompson Added comment: Comment on list classification: Both SNVs and CNVs cause disease
Hereditary Neuropathy_CMT - isolated v0.46 PMP22 Bryony Thompson Gene: pmp22 has been classified as Green List (High Evidence).
Hereditary Neuropathy_CMT - isolated v0.45 PMP22 Bryony Thompson Tag SV/CNV tag was added to gene: PMP22.
Mendeliome v0.3083 HPRT1 Zornitza Stark Publications for gene: HPRT1 were set to
Mendeliome v0.3082 HPRT1 Zornitza Stark Mode of inheritance for gene: HPRT1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3081 HPRT1 Ain Roesley reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20176575; Phenotypes: HPRT-related gout (MIM# 300323), Lesch-Nyhan syndrome (MIM# 300322); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3081 ASTN2 Zornitza Stark Phenotypes for gene: ASTN2 were changed from to Intellectual disability
Mendeliome v0.3080 ASTN2 Zornitza Stark Publications for gene: ASTN2 were set to
Mendeliome v0.3079 ASTN2 Zornitza Stark Mode of inheritance for gene: ASTN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3078 ASTN2 Zornitza Stark edited their review of gene: ASTN2: Changed phenotypes: Intellectual disability
Mendeliome v0.3078 ASTN2 Zornitza Stark edited their review of gene: ASTN2: Changed phenotypes: Intellectual disability, microcephaly
Arthrogryposis v0.62 ASCC1 Zornitza Stark Marked gene: ASCC1 as ready
Arthrogryposis v0.62 ASCC1 Zornitza Stark Gene: ascc1 has been classified as Green List (High Evidence).
Arthrogryposis v0.62 ASCC1 Zornitza Stark Classified gene: ASCC1 as Green List (high evidence)
Arthrogryposis v0.62 ASCC1 Zornitza Stark Gene: ascc1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.55 ATP2A1 Zornitza Stark Marked gene: ATP2A1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.55 ATP2A1 Zornitza Stark Gene: atp2a1 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.55 ATP2A1 Zornitza Stark Classified gene: ATP2A1 as Amber List (moderate evidence)
Rhabdomyolysis and Metabolic Myopathy v0.55 ATP2A1 Zornitza Stark Gene: atp2a1 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.54 ATP2A1 Zornitza Stark gene: ATP2A1 was added
gene: ATP2A1 was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: ATP2A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP2A1 were set to 32040565
Phenotypes for gene: ATP2A1 were set to Brody myopathy, MIM# 601003
Review for gene: ATP2A1 was set to AMBER
Added comment: Two patients reported with rhabdomyolysis
Sources: Expert list
Mendeliome v0.3078 SI Zornitza Stark Marked gene: SI as ready
Mendeliome v0.3078 SI Zornitza Stark Gene: si has been classified as Green List (High Evidence).
Mendeliome v0.3078 SI Zornitza Stark Phenotypes for gene: SI were changed from to Sucrase-isomaltase deficiency, congenital #222900
Mendeliome v0.3077 SI Zornitza Stark Publications for gene: SI were set to
Mendeliome v0.3076 SI Zornitza Stark Mode of inheritance for gene: SI was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hydrocephalus_Ventriculomegaly v0.18 B4GAT1 Zornitza Stark Marked gene: B4GAT1 as ready
Hydrocephalus_Ventriculomegaly v0.18 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Hydrocephalus_Ventriculomegaly v0.18 B4GAT1 Zornitza Stark Classified gene: B4GAT1 as Amber List (moderate evidence)
Hydrocephalus_Ventriculomegaly v0.18 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Familial hypercholesterolaemia v0.11 CAV3 Zornitza Stark Marked gene: CAV3 as ready
Familial hypercholesterolaemia v0.11 CAV3 Zornitza Stark Gene: cav3 has been classified as Amber List (Moderate Evidence).
Familial hypercholesterolaemia v0.11 CAV3 Zornitza Stark Publications for gene: CAV3 were set to PMID: 32004987; 28807458
Familial hypercholesterolaemia v0.10 CAV3 Zornitza Stark Classified gene: CAV3 as Amber List (moderate evidence)
Familial hypercholesterolaemia v0.10 CAV3 Zornitza Stark Gene: cav3 has been classified as Amber List (Moderate Evidence).
Familial hypercholesterolaemia v0.9 CAV3 Elena Savva gene: CAV3 was added
gene: CAV3 was added to Familial hypercholesterolaemia. Sources: Literature
Mode of inheritance for gene: CAV3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAV3 were set to PMID: 32004987; 28807458
Phenotypes for gene: CAV3 were set to Myopathy, distal, Tateyama type 614321; Rippling muscle disease 2 606072
Review for gene: CAV3 was set to AMBER
Added comment: PMID: 32004987 - 1 family (2 siblings) with elevated creatine kinase, myalgia and hypercholesterolemia. Onset was ~30 years old.

PMID: 28807458 - 1 patient with rippling muscle disease, who remains asymptomatic at 45 years old. Patient also had high LDL and CK levels and therefore hyperlipidemia.

Summary: 2 patients reported
Sources: Literature
Mendeliome v0.3075 SV2B Seb Lunke Marked gene: SV2B as ready
Mendeliome v0.3075 SV2B Seb Lunke Gene: sv2b has been classified as Red List (Low Evidence).
Mendeliome v0.3075 SV2B Seb Lunke gene: SV2B was added
gene: SV2B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SV2B was set to Unknown
Publications for gene: SV2B were set to 23617838; 23937191
Phenotypes for gene: SV2B were set to seizures
Review for gene: SV2B was set to RED
Added comment: Multiply described in Epilepsy studies investigating role of SV2 gene family, however no patients directly attributed to variants in this gene and mouse models indicate viability without seizures. Sources: Literature
Sources: Literature
Genetic Epilepsy v0.727 SV2B Seb Lunke Marked gene: SV2B as ready
Genetic Epilepsy v0.727 SV2B Seb Lunke Gene: sv2b has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.727 SV2B Seb Lunke gene: SV2B was added
gene: SV2B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SV2B was set to Unknown
Publications for gene: SV2B were set to 23617838; 23937191
Phenotypes for gene: SV2B were set to seizures
Review for gene: SV2B was set to RED
Added comment: Multiply described in Epilepsy studies investigating role of SV2 gene family, however no patients directly attributed to variants in this gene and mouse models indicate viability without seizures.
Sources: Literature
Hydrocephalus_Ventriculomegaly v0.17 B4GAT1 Elena Savva gene: B4GAT1 was added
gene: B4GAT1 was added to Hydrocephalus_Ventriculomegaly. Sources: Expert list
Mode of inheritance for gene: B4GAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B4GAT1 were set to PMID: 23359570; 23877401
Phenotypes for gene: B4GAT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 615287
Review for gene: B4GAT1 was set to AMBER
Added comment: aka B3GNT1 (OMIM)

PMID: 23359570 - One family with congenital muscular dystrophy. Index patient had hydrocephalus, seizures, severe hypotonia and retinal dysplasia. Patients were homozygous for TWO missense

PMID: 23877401 - One family with congenital onset Walker-warburg syndrome and hydrocephalus, seizure and cognitive impairment.

Summary: 2 families with hydrocephalus
Sources: Expert list
Mendeliome v0.3074 ADGRG1 Elena Savva reviewed gene: ADGRG1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24531968; Phenotypes: Polymicrogyria, bilateral frontoparietal 606854, Polymicrogyria, bilateral perisylvian 615752; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3074 SI Elena Savva reviewed gene: SI: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 3149304, 31557950; Phenotypes: Sucrase-isomaltase deficiency, congenital #222900; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3074 RYR3 Zornitza Stark Marked gene: RYR3 as ready
Mendeliome v0.3074 RYR3 Zornitza Stark Gene: ryr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3074 RYR3 Zornitza Stark Classified gene: RYR3 as Amber List (moderate evidence)
Mendeliome v0.3074 RYR3 Zornitza Stark Gene: ryr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3073 RYR3 Zornitza Stark gene: RYR3 was added
gene: RYR3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RYR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RYR3 were set to 29498452; 32451403; 31230720
Phenotypes for gene: RYR3 were set to Nemaline myopathy; fetal akinesia; arthrogryposis
Review for gene: RYR3 was set to AMBER
Added comment: One family reported with nemaline myopathy and other cases reported as part of large fetal akinesia/arthrogryposis discovery cohorts reporting multiple novel gene candidates.
Sources: Expert list
Arthrogryposis v0.61 ASCC1 Elena Savva gene: ASCC1 was added
gene: ASCC1 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: ASCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASCC1 were set to PMID: 28218388; 30327447; 26924529
Phenotypes for gene: ASCC1 were set to Spinal muscular atrophy with congenital bone fractures 2 MIM#616867
Review for gene: ASCC1 was set to GREEN
Added comment: PMID: 28218388 - 1 Portuguese child with a homozygous PTC and mild arthrogryposis, and ongenital generalized hypotonia, lack of spontaneous movements and atrophic muscle fibres. Papers reviews another report (PMID: 26924529) where the Turkish patient also had arthrogryposis and the same homozygous PTC

PMID: 30327447 - 3 unrelated families with severe prenatal onset muscle weakness, neonatal hypotonia and arthrogryposis. All families had biallelic PTCs, where one family was homozygous and another compound heterozygous for the recurring p.Glu53fs*19 mutation.
Sources: Literature
Long QT Syndrome v0.59 KCNE2 Zornitza Stark Mode of inheritance for gene: KCNE2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3072 SCN3A Zornitza Stark Marked gene: SCN3A as ready
Mendeliome v0.3072 SCN3A Zornitza Stark Gene: scn3a has been classified as Green List (High Evidence).
Mendeliome v0.3072 SCN3A Zornitza Stark Phenotypes for gene: SCN3A were changed from to Epilepsy, familial focal, with variable foci 4, MIM# 617935; Epileptic encephalopathy, early infantile, 62, MIM# 617938; Intellectual disability; Malformations of cortical development
Mendeliome v0.3071 SCN3A Zornitza Stark Publications for gene: SCN3A were set to
Mendeliome v0.3070 SCN3A Zornitza Stark Mode of pathogenicity for gene: SCN3A was changed from to Other
Mendeliome v0.3069 SCN3A Zornitza Stark Mode of inheritance for gene: SCN3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3068 SCN3A Zornitza Stark reviewed gene: SCN3A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 32515017; Phenotypes: Epilepsy, familial focal, with variable foci 4, MIM# 617935, Epileptic encephalopathy, early infantile, 62, MIM# 617938, Intellectual disability, Malformations of cortical development; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2698 SCN3A Zornitza Stark Marked gene: SCN3A as ready
Intellectual disability syndromic and non-syndromic v0.2698 SCN3A Zornitza Stark Gene: scn3a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2698 SCN3A Zornitza Stark Phenotypes for gene: SCN3A were changed from to Epilepsy, familial focal, with variable foci 4, MIM# 617935; Epileptic encephalopathy, early infantile, 62, MIM# 617938; Intellectual disability; Malformations of cortical development
Intellectual disability syndromic and non-syndromic v0.2697 SCN3A Zornitza Stark Publications for gene: SCN3A were set to
Intellectual disability syndromic and non-syndromic v0.2696 SCN3A Zornitza Stark Mode of pathogenicity for gene: SCN3A was changed from to Other
Intellectual disability syndromic and non-syndromic v0.2695 SCN3A Zornitza Stark Mode of inheritance for gene: SCN3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2694 SCN3A Zornitza Stark reviewed gene: SCN3A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 32515017; Phenotypes: Epilepsy, familial focal, with variable foci 4, MIM# 617935, Epileptic encephalopathy, early infantile, 62, MIM# 617938, Intellectual disability, Malformations of cortical development; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.726 SCN3A Zornitza Stark Marked gene: SCN3A as ready
Genetic Epilepsy v0.726 SCN3A Zornitza Stark Gene: scn3a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.726 SCN3A Zornitza Stark Phenotypes for gene: SCN3A were changed from to Epilepsy, familial focal, with variable foci 4, MIM# 617935; Epileptic encephalopathy, early infantile, 62, MIM# 617938; Intellectual disability; Malformations of cortical development
Genetic Epilepsy v0.725 SCN3A Zornitza Stark Publications for gene: SCN3A were set to
Genetic Epilepsy v0.724 SCN3A Zornitza Stark Mode of pathogenicity for gene: SCN3A was changed from to Other
Genetic Epilepsy v0.723 SCN3A Zornitza Stark Mode of inheritance for gene: SCN3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.722 SCN3A Zornitza Stark reviewed gene: SCN3A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 32515017; Phenotypes: Epilepsy, familial focal, with variable foci 4, MIM# 617935, Epileptic encephalopathy, early infantile, 62, MIM# 617938, Intellectual disability, Malformations of cortical development; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3068 HMGA2 Zornitza Stark Phenotypes for gene: HMGA2 were changed from Silver-Russel syndrome to Silver-Russel syndrome, MIM#618908
Mendeliome v0.3067 HMGA2 Zornitza Stark Publications for gene: HMGA2 were set to 29655892; 25809938
Mendeliome v0.3066 HMGA2 Zornitza Stark Classified gene: HMGA2 as Green List (high evidence)
Mendeliome v0.3066 HMGA2 Zornitza Stark Gene: hmga2 has been classified as Green List (High Evidence).
Mendeliome v0.3065 HMGA2 Zornitza Stark edited their review of gene: HMGA2: Added comment: At least four families reported with SNVs.; Changed rating: GREEN; Changed publications: 29655892, 25809938, 29453418, 29655892, 28796236; Changed phenotypes: Silver-Russel syndrome, MIM#618908
Mendeliome v0.3065 PLAG1 Zornitza Stark Marked gene: PLAG1 as ready
Mendeliome v0.3065 PLAG1 Zornitza Stark Gene: plag1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3065 PLAG1 Zornitza Stark Phenotypes for gene: PLAG1 were changed from to Silver-Russell syndrome, MIM#618907
Mendeliome v0.3064 PLAG1 Zornitza Stark Publications for gene: PLAG1 were set to
Mendeliome v0.3063 PLAG1 Zornitza Stark Mode of inheritance for gene: PLAG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3062 PLAG1 Zornitza Stark Classified gene: PLAG1 as Amber List (moderate evidence)
Mendeliome v0.3062 PLAG1 Zornitza Stark Gene: plag1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3061 PLAG1 Zornitza Stark reviewed gene: PLAG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28796236, 29913240; Phenotypes: Silver-Russell syndrome, MIM#618907; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoinflammatory Disorders v0.83 MEFV Zornitza Stark Marked gene: MEFV as ready
Autoinflammatory Disorders v0.83 MEFV Zornitza Stark Gene: mefv has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.83 MEFV Zornitza Stark Phenotypes for gene: MEFV were changed from to Familial Mediterranean fever, AD, MIM# 134610; Familial Mediterranean fever, AR, MIM# 249100; Neutrophilic dermatosis, MIM#608068
Autoinflammatory Disorders v0.82 MEFV Zornitza Stark Publications for gene: MEFV were set to
Autoinflammatory Disorders v0.81 MEFV Zornitza Stark Mode of inheritance for gene: MEFV was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Autoinflammatory Disorders v0.80 MEFV Zornitza Stark reviewed gene: MEFV: Rating: GREEN; Mode of pathogenicity: None; Publications: 27030597, 28835462; Phenotypes: Familial Mediterranean fever, AD, MIM# 134610, Familial Mediterranean fever, AR, MIM# 249100, Neutrophilic dermatosis, MIM#608068; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2694 KIF1BP Zornitza Stark Marked gene: KIF1BP as ready
Intellectual disability syndromic and non-syndromic v0.2694 KIF1BP Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name KIFBP.
Intellectual disability syndromic and non-syndromic v0.2694 KIF1BP Zornitza Stark Gene: kif1bp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2694 KIF1BP Zornitza Stark Tag new gene name tag was added to gene: KIF1BP.
Polymicrogyria and Schizencephaly v0.88 KIF1BP Zornitza Stark Marked gene: KIF1BP as ready
Polymicrogyria and Schizencephaly v0.88 KIF1BP Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name is KIFBP.
Polymicrogyria and Schizencephaly v0.88 KIF1BP Zornitza Stark Gene: kif1bp has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.88 KIF1BP Zornitza Stark Phenotypes for gene: KIF1BP were changed from Goldberg-Shprintzen megacolon syndrome MIM#609460 to Goldberg-Shprintzen megacolon syndrome MIM#609460
Polymicrogyria and Schizencephaly v0.87 KIF1BP Zornitza Stark Phenotypes for gene: KIF1BP were changed from to Goldberg-Shprintzen megacolon syndrome MIM#609460
Polymicrogyria and Schizencephaly v0.86 KIF1BP Zornitza Stark Mode of inheritance for gene: KIF1BP was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.86 KIF1BP Zornitza Stark Mode of inheritance for gene: KIF1BP was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.85 KIF1BP Zornitza Stark Publications for gene: KIF1BP were set to
Polymicrogyria and Schizencephaly v0.84 KIF1BP Zornitza Stark Tag new gene name tag was added to gene: KIF1BP.
Polymicrogyria and Schizencephaly v0.84 KIF1BP Zornitza Stark Mode of inheritance for gene: KIF1BP was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.84 KIF1BP Zornitza Stark Mode of inheritance for gene: KIF1BP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy_CMT - isolated v0.45 NEFH Zornitza Stark Marked gene: NEFH as ready
Hereditary Neuropathy_CMT - isolated v0.45 NEFH Zornitza Stark Gene: nefh has been classified as Green List (High Evidence).
Hereditary Neuropathy_CMT - isolated v0.45 NEFH Zornitza Stark Publications for gene: NEFH were set to
Mendeliome v0.3061 NEFH Zornitza Stark Marked gene: NEFH as ready
Mendeliome v0.3061 NEFH Zornitza Stark Gene: nefh has been classified as Green List (High Evidence).
Hereditary Neuropathy_CMT - isolated v0.44 NEFH Zornitza Stark reviewed gene: NEFH: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30992180, 27040688, 28709447; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2CC, MIM#616924; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3061 NEFH Zornitza Stark Phenotypes for gene: NEFH were changed from to Charcot-Marie-Tooth disease, axonal, type 2CC, MIM#616924
Mendeliome v0.3060 NEFH Zornitza Stark Publications for gene: NEFH were set to
Mendeliome v0.3059 NEFH Zornitza Stark Mode of pathogenicity for gene: NEFH was changed from to Other
Mendeliome v0.3058 NEFH Zornitza Stark Mode of inheritance for gene: NEFH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2694 SLC6A1 Zornitza Stark Marked gene: SLC6A1 as ready
Intellectual disability syndromic and non-syndromic v0.2694 SLC6A1 Zornitza Stark Gene: slc6a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2694 SLC6A1 Zornitza Stark Phenotypes for gene: SLC6A1 were changed from to Myoclonic-atonic epilepsy, MIM#616421
Intellectual disability syndromic and non-syndromic v0.2693 SLC6A1 Zornitza Stark Publications for gene: SLC6A1 were set to
Autism v0.100 SLC6A1 Zornitza Stark Marked gene: SLC6A1 as ready
Autism v0.100 SLC6A1 Zornitza Stark Gene: slc6a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2692 SLC6A1 Zornitza Stark Mode of inheritance for gene: SLC6A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.100 SLC6A1 Zornitza Stark Phenotypes for gene: SLC6A1 were changed from to Myoclonic-atonic epilepsy, MIM#616421
Intellectual disability syndromic and non-syndromic v0.2691 SLC6A1 Zornitza Stark reviewed gene: SLC6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29315614; Phenotypes: Myoclonic-atonic epilepsy, MIM#616421; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.99 SLC6A1 Zornitza Stark Publications for gene: SLC6A1 were set to
Autism v0.98 SLC6A1 Zornitza Stark Mode of inheritance for gene: SLC6A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.97 SLC6A1 Zornitza Stark reviewed gene: SLC6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29315614; Phenotypes: Myoclonic-atonic epilepsy, MIM#616421; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.722 SLC6A1 Zornitza Stark Marked gene: SLC6A1 as ready
Genetic Epilepsy v0.722 SLC6A1 Zornitza Stark Gene: slc6a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.722 SLC6A1 Zornitza Stark Phenotypes for gene: SLC6A1 were changed from to Myoclonic-atonic epilepsy, MIM#616421
Genetic Epilepsy v0.721 SLC6A1 Zornitza Stark Publications for gene: SLC6A1 were set to
Genetic Epilepsy v0.720 SLC6A1 Zornitza Stark Mode of inheritance for gene: SLC6A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.719 SLC6A1 Zornitza Stark reviewed gene: SLC6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29315614; Phenotypes: Myoclonic-atonic epilepsy, MIM#616421; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3057 SLC6A1 Zornitza Stark Marked gene: SLC6A1 as ready
Mendeliome v0.3057 SLC6A1 Zornitza Stark Gene: slc6a1 has been classified as Green List (High Evidence).
Mendeliome v0.3057 SLC6A1 Zornitza Stark Phenotypes for gene: SLC6A1 were changed from to Myoclonic-atonic epilepsy, MIM#616421
Mendeliome v0.3056 SLC6A1 Zornitza Stark Publications for gene: SLC6A1 were set to
Mendeliome v0.3055 SLC6A1 Zornitza Stark Mode of inheritance for gene: SLC6A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3054 GATM Zornitza Stark Marked gene: GATM as ready
Mendeliome v0.3054 GATM Zornitza Stark Gene: gatm has been classified as Green List (High Evidence).
Mendeliome v0.3054 GATM Zornitza Stark Phenotypes for gene: GATM were changed from to Cerebral creatine deficiency syndrome 3, MIM# 612718; Fanconi renotubular syndrome 1, MIM# 134600
Mendeliome v0.3053 GATM Zornitza Stark Publications for gene: GATM were set to
Mendeliome v0.3052 GATM Zornitza Stark Mode of inheritance for gene: GATM was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3051 GATM Zornitza Stark reviewed gene: GATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 12468279, 20682460, 22386973, 29654216; Phenotypes: Cerebral creatine deficiency syndrome 3, MIM# 612718, Fanconi renotubular syndrome 1, MIM# 134600; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Regression v0.121 GATM Zornitza Stark Marked gene: GATM as ready
Regression v0.121 GATM Zornitza Stark Gene: gatm has been classified as Green List (High Evidence).
Regression v0.121 GATM Zornitza Stark Phenotypes for gene: GATM were changed from to Cerebral creatine deficiency syndrome 3, MIM# 612718
Regression v0.120 GATM Zornitza Stark Publications for gene: GATM were set to
Regression v0.119 GATM Zornitza Stark Mode of inheritance for gene: GATM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.118 GATM Zornitza Stark reviewed gene: GATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 12468279, 20682460, 22386973; Phenotypes: Cerebral creatine deficiency syndrome 3, MIM# 612718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2691 GATM Zornitza Stark Marked gene: GATM as ready
Intellectual disability syndromic and non-syndromic v0.2691 GATM Zornitza Stark Gene: gatm has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2691 GATM Zornitza Stark Phenotypes for gene: GATM were changed from to Cerebral creatine deficiency syndrome 3, MIM# 612718
Intellectual disability syndromic and non-syndromic v0.2690 GATM Zornitza Stark Publications for gene: GATM were set to
Intellectual disability syndromic and non-syndromic v0.2689 GATM Zornitza Stark Mode of inheritance for gene: GATM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2688 GATM Zornitza Stark reviewed gene: GATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 12468279, 20682460, 22386973; Phenotypes: Cerebral creatine deficiency syndrome 3, MIM# 612718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Susceptibility to Viral Infections v0.61 FUT2 Zornitza Stark Marked gene: FUT2 as ready
Susceptibility to Viral Infections v0.61 FUT2 Zornitza Stark Gene: fut2 has been classified as Red List (Low Evidence).
Susceptibility to Viral Infections v0.61 FUT2 Zornitza Stark gene: FUT2 was added
gene: FUT2 was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: FUT2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FUT2 were set to Norwalk virus infection, resistance to
Review for gene: FUT2 was set to RED
Added comment: Not a monogenic condition, but individuals homozygous for p.(Trp143Ter) are resistant to norovirus infection.
Sources: Expert list
Susceptibility to Viral Infections v0.60 CCR5 Zornitza Stark Marked gene: CCR5 as ready
Susceptibility to Viral Infections v0.60 CCR5 Zornitza Stark Gene: ccr5 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.60 CCR5 Zornitza Stark Classified gene: CCR5 as Green List (high evidence)
Susceptibility to Viral Infections v0.60 CCR5 Zornitza Stark Gene: ccr5 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.59 CCR5 Zornitza Stark gene: CCR5 was added
gene: CCR5 was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: CCR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CCR5 were set to {Hepatitis C virus, resistance to} 609532; {HIV infection, susceptibility/resistance to}; {West nile virus, susceptibility to}MIM# 610379
Review for gene: CCR5 was set to GREEN
Added comment: Particular SNVs in this gene are well established as conferring resistance to certain viral infections, notably HIV.
Sources: Expert list
Susceptibility to Viral Infections v0.58 TNFRSF4 Zornitza Stark Marked gene: TNFRSF4 as ready
Susceptibility to Viral Infections v0.58 TNFRSF4 Zornitza Stark Gene: tnfrsf4 has been classified as Red List (Low Evidence).
Susceptibility to Viral Infections v0.58 TNFRSF4 Zornitza Stark gene: TNFRSF4 was added
gene: TNFRSF4 was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: TNFRSF4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNFRSF4 were set to 23897980
Phenotypes for gene: TNFRSF4 were set to Immunodeficiency 16, MIM# 615593
Review for gene: TNFRSF4 was set to RED
Added comment: Single case report in an individual with childhood-onset Kaposi's sarcoma (susceptibility to HHV8), homozygous missense variant, plausible biological candidate but direct evidence of causality limited.
Sources: Expert list
Susceptibility to Viral Infections v0.57 MAGT1 Zornitza Stark Marked gene: MAGT1 as ready
Susceptibility to Viral Infections v0.57 MAGT1 Zornitza Stark Gene: magt1 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.57 MAGT1 Zornitza Stark Classified gene: MAGT1 as Green List (high evidence)
Susceptibility to Viral Infections v0.57 MAGT1 Zornitza Stark Gene: magt1 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.56 MAGT1 Zornitza Stark gene: MAGT1 was added
gene: MAGT1 was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: MAGT1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MAGT1 were set to 21796205; 24550228; 25504528
Phenotypes for gene: MAGT1 were set to Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia, MIM# 300853
Review for gene: MAGT1 was set to GREEN
Added comment: Multiple unrelated families reported.
Sources: Expert list
Mendeliome v0.3051 TRIM69 Zornitza Stark Marked gene: TRIM69 as ready
Mendeliome v0.3051 TRIM69 Zornitza Stark Gene: trim69 has been classified as Red List (Low Evidence).
Mendeliome v0.3051 TRIM69 Zornitza Stark gene: TRIM69 was added
gene: TRIM69 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TRIM69 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TRIM69 were set to 22105173
Phenotypes for gene: TRIM69 were set to Susceptibility to herpes simplex encephalitis
Review for gene: TRIM69 was set to RED
Added comment: One individual with bi-allelic and one individual with mono-allelic variants in this gene described.
Sources: Expert list
Susceptibility to Viral Infections v0.55 TRIM69 Zornitza Stark Marked gene: TRIM69 as ready
Susceptibility to Viral Infections v0.55 TRIM69 Zornitza Stark Gene: trim69 has been classified as Red List (Low Evidence).
Susceptibility to Viral Infections v0.55 TRIM69 Zornitza Stark gene: TRIM69 was added
gene: TRIM69 was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: TRIM69 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TRIM69 were set to 22105173
Phenotypes for gene: TRIM69 were set to Susceptibility to herpes simplex encephalitis
Review for gene: TRIM69 was set to RED
Added comment: One individual with bi-allelic and one individual with mono-allelic variants in this gene described.
Sources: Expert list
Mendeliome v0.3050 SLC6A1 Chern Lim reviewed gene: SLC6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29315614; Phenotypes: Myoclonic-atonic epilepsy, MIM#616421; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.3050 NEFH Chern Lim reviewed gene: NEFH: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30992180, 27040688, 28709447; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2CC, MIM#616924; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Polymicrogyria and Schizencephaly v0.83 KIF1BP Chloe Stutterd reviewed gene: KIF1BP: Rating: GREEN; Mode of pathogenicity: None; Publications: 23427148, 15883926; Phenotypes: Polymicrogryia in Goldberg-Shprintzen megacolon syndrome MIM#609460; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia Superpanel v0.110 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Hereditary Spastic Paraplegia - paediatric v0.101 TUBB4A Zornitza Stark Marked gene: TUBB4A as ready
Hereditary Spastic Paraplegia - paediatric v0.101 TUBB4A Zornitza Stark Gene: tubb4a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.101 TUBB4A Zornitza Stark Classified gene: TUBB4A as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v0.101 TUBB4A Zornitza Stark Gene: tubb4a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.100 TUBB4A Zornitza Stark gene: TUBB4A was added
gene: TUBB4A was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: TUBB4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB4A were set to 23582646; 24850488
Phenotypes for gene: TUBB4A were set to Leukodystrophy, hypomyelinating, 6, MIM# 612438
Review for gene: TUBB4A was set to GREEN
Added comment: Complex neurological disorder with childhood onset, spasticity is a feature.
Sources: Expert list
Hereditary Spastic Paraplegia - paediatric v0.99 RTN2 Zornitza Stark Marked gene: RTN2 as ready
Hereditary Spastic Paraplegia - paediatric v0.99 RTN2 Zornitza Stark Gene: rtn2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.99 RTN2 Zornitza Stark Classified gene: RTN2 as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v0.99 RTN2 Zornitza Stark Gene: rtn2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.98 RTN2 Zornitza Stark gene: RTN2 was added
gene: RTN2 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: RTN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RTN2 were set to 22232211; 27165006
Phenotypes for gene: RTN2 were set to Spastic paraplegia 12, autosomal dominant, MIM# 604805
Review for gene: RTN2 was set to GREEN
Added comment: At least 5 unrelated families reported. Variable age of onset from childhood to early adulthood.
Sources: Expert list
Hereditary Spastic Paraplegia - paediatric v0.97 PNPLA6 Zornitza Stark Marked gene: PNPLA6 as ready
Hereditary Spastic Paraplegia - paediatric v0.97 PNPLA6 Zornitza Stark Gene: pnpla6 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia - paediatric v0.97 PNPLA6 Zornitza Stark Classified gene: PNPLA6 as Amber List (moderate evidence)
Hereditary Spastic Paraplegia - paediatric v0.97 PNPLA6 Zornitza Stark Gene: pnpla6 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia - paediatric v0.96 PNPLA6 Zornitza Stark gene: PNPLA6 was added
gene: PNPLA6 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: PNPLA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA6 were set to 18313024
Phenotypes for gene: PNPLA6 were set to Spastic paraplegia 39, autosomal recessive, MIM# 612020
Review for gene: PNPLA6 was set to AMBER
Added comment: Bi-allelic variants cause a range of complex phenotypes, including ataxia, retinal dystrophy, spasticity and hypogonadotrophic hypogonadism. Symptom onset is generally in adulthood, although at least one family with onset of spasticity in childhood reported.
Sources: Expert list
Hereditary Spastic Paraplegia - paediatric v0.95 OPA3 Zornitza Stark Marked gene: OPA3 as ready
Hereditary Spastic Paraplegia - paediatric v0.95 OPA3 Zornitza Stark Gene: opa3 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.95 OPA3 Zornitza Stark Classified gene: OPA3 as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v0.95 OPA3 Zornitza Stark Gene: opa3 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.94 OPA3 Zornitza Stark gene: OPA3 was added
gene: OPA3 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: OPA3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: OPA3 were set to 3-methylglutaconic aciduria, type III, MIM# 258501
Review for gene: OPA3 was set to GREEN
Added comment: Onset of optic atrophy generally precedes other features including spasticity, which generally begins in the second decade.
Sources: Expert list
Hereditary Spastic Paraplegia - paediatric v0.93 AP5Z1 Zornitza Stark Marked gene: AP5Z1 as ready
Hereditary Spastic Paraplegia - paediatric v0.93 AP5Z1 Zornitza Stark Gene: ap5z1 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia - paediatric v0.93 AP5Z1 Zornitza Stark Classified gene: AP5Z1 as Amber List (moderate evidence)
Hereditary Spastic Paraplegia - paediatric v0.93 AP5Z1 Zornitza Stark Gene: ap5z1 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia - paediatric v0.92 AP5Z1 Zornitza Stark gene: AP5Z1 was added
gene: AP5Z1 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: AP5Z1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP5Z1 were set to 26085577
Phenotypes for gene: AP5Z1 were set to Spastic paraplegia 48, autosomal recessive, MIM# 613647
Review for gene: AP5Z1 was set to AMBER
Added comment: Onset is generally in adulthood though at least one individual with childhood onset reported.
Sources: Expert list
Hereditary Spastic Paraplegia - paediatric v0.91 ALDH18A1 Zornitza Stark Marked gene: ALDH18A1 as ready
Hereditary Spastic Paraplegia - paediatric v0.91 ALDH18A1 Zornitza Stark Gene: aldh18a1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.91 ALDH18A1 Zornitza Stark Phenotypes for gene: ALDH18A1 were changed from Spastic paraplegia 9B, autosomal recessive, MIM# 616586 to Spastic paraplegia 9B, autosomal recessive, MIM# 616586; Spastic paraplegia 9A, autosomal dominant, MIM# 601162
Hereditary Spastic Paraplegia - paediatric v0.90 ALDH18A1 Zornitza Stark Classified gene: ALDH18A1 as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v0.90 ALDH18A1 Zornitza Stark Gene: aldh18a1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v0.89 ALDH18A1 Zornitza Stark edited their review of gene: ALDH18A1: Changed phenotypes: Spastic paraplegia 9B, autosomal recessive, MIM# 616586, Spastic paraplegia 9A, autosomal dominant, MIM# 601162
Hereditary Spastic Paraplegia - paediatric v0.89 ALDH18A1 Zornitza Stark gene: ALDH18A1 was added
gene: ALDH18A1 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: ALDH18A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ALDH18A1 were set to 26026163; 29915212
Phenotypes for gene: ALDH18A1 were set to Spastic paraplegia 9B, autosomal recessive, MIM# 616586
Review for gene: ALDH18A1 was set to GREEN
Added comment: At least four unrelated families reported with bi-allelic complex HSP, including microcephaly and ID. Mono-allelic variants are also associated with HSP (at least 15 patients from 3 families) but this tends to be with adult onset, although some childhood onset also reported.
Sources: Expert list
Early-onset Parkinson disease v0.31 PSEN2 Bryony Thompson changed review comment from: Parkinson disease and parkinsonism is not a prominent feature of Alzheimer disease caused by PSEN2. A couple of isolated cases with parkinsonism as a feature of the condition and a single family have been reported with established pathogenic variants and a VUS (PMID: 22118943, 26422362, 18427071). VUS or now likely benign/benign missense variants have been identified in a Parkinson Disease cases used in case-control studies (PMID: 29692703, 26522186).
Sources: Other; to: Parkinson disease and parkinsonism is not a prominent feature of Alzheimer disease caused by PSEN2. A couple of isolated cases with VUS and parkinsonism as a feature of the condition and a single family with multiple members with parkinsonism with pathogenic missense variant have been reported (PMID: 22118943, 26422362, 18427071). VUS or now likely benign/benign missense variants have been identified in Parkinson Disease cases used in case-control studies (PMID: 29692703, 26522186).
Sources: Other
Early-onset Parkinson disease v0.31 PSEN2 Bryony Thompson changed review comment from: Parkinson disease and parkinsonism is not a prominent feature of Alzheimer disease caused by PSEN2. A couple of isolated cases with parkinsonism as a feature of the condition and a single family have been reported with established pathogenic or probable pathogenic variants (PMID: 22118943, 26422362, 18427071). VUS or now likely benign/benign missense variants have been identified in a Parkinson Disease cases used in case-control studies (PMID: 29692703, 26522186).
Sources: Other; to: Parkinson disease and parkinsonism is not a prominent feature of Alzheimer disease caused by PSEN2. A couple of isolated cases with parkinsonism as a feature of the condition and a single family have been reported with established pathogenic variants and a VUS (PMID: 22118943, 26422362, 18427071). VUS or now likely benign/benign missense variants have been identified in a Parkinson Disease cases used in case-control studies (PMID: 29692703, 26522186).
Sources: Other
Early-onset Parkinson disease v0.31 PSEN2 Bryony Thompson Marked gene: PSEN2 as ready
Early-onset Parkinson disease v0.31 PSEN2 Bryony Thompson Gene: psen2 has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.31 PSEN2 Bryony Thompson gene: PSEN2 was added
gene: PSEN2 was added to Early-onset Parkinson disease. Sources: Other
Mode of inheritance for gene: PSEN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSEN2 were set to 22118943; 26422362; 18427071; 29692703
Phenotypes for gene: PSEN2 were set to Parkinsonism; Alzheimer disease-4 MIM#606889
Review for gene: PSEN2 was set to RED
Added comment: Parkinson disease and parkinsonism is not a prominent feature of Alzheimer disease caused by PSEN2. A couple of isolated cases with parkinsonism as a feature of the condition and a single family have been reported with established pathogenic or probable pathogenic variants (PMID: 22118943, 26422362, 18427071). VUS or now likely benign/benign missense variants have been identified in a Parkinson Disease cases used in case-control studies (PMID: 29692703, 26522186).
Sources: Other
Mendeliome v0.3050 LIMS2 Zornitza Stark Marked gene: LIMS2 as ready
Mendeliome v0.3050 LIMS2 Zornitza Stark Gene: lims2 has been classified as Red List (Low Evidence).
Mendeliome v0.3050 LIMS2 Zornitza Stark gene: LIMS2 was added
gene: LIMS2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: LIMS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIMS2 were set to 25589244; 16317048
Phenotypes for gene: LIMS2 were set to Muscular dystrophy, autosomal recessive, with cardiomyopathy and triangular tongue MIM#616827
Review for gene: LIMS2 was set to RED
Added comment: Only one family reported and Pinch2 -/- mice were viable and fertile with no apparent phenotype.
Sources: Expert list
Mendeliome v0.3049 FAN1 Elena Savva reviewed gene: FAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22772369; Phenotypes: Interstitial nephritis, karyomegalic 614817; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3049 RAD21 Elena Savva reviewed gene: RAD21: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31334757, 25575569, 32193685; Phenotypes: ?Mungan syndrome, 611376, Cornelia de Lange syndrome 4, 614701, Holoprocencephaly; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Holoprosencephaly and septo-optic dysplasia v0.23 RAD21 Zornitza Stark Marked gene: RAD21 as ready
Holoprosencephaly and septo-optic dysplasia v0.23 RAD21 Zornitza Stark Gene: rad21 has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v0.23 RAD21 Zornitza Stark Classified gene: RAD21 as Green List (high evidence)
Holoprosencephaly and septo-optic dysplasia v0.23 RAD21 Zornitza Stark Gene: rad21 has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v0.22 RAD21 Zornitza Stark gene: RAD21 was added
gene: RAD21 was added to Holoprosencephaly and septo-optic dysplasia. Sources: Literature
Mode of inheritance for gene: RAD21 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAD21 were set to 31334757
Phenotypes for gene: RAD21 were set to Holoprosencephaly; Septo-optic dysplasia
Review for gene: RAD21 was set to GREEN
Added comment: Three individuals reported with variants in this gene and HPE phenotype. Note paper reports variants in other cohesinopathy genes also.
Sources: Literature
Mendeliome v0.3049 PSMB1 Zornitza Stark Marked gene: PSMB1 as ready
Mendeliome v0.3049 PSMB1 Zornitza Stark Gene: psmb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3049 PSMB1 Zornitza Stark Classified gene: PSMB1 as Amber List (moderate evidence)
Mendeliome v0.3049 PSMB1 Zornitza Stark Gene: psmb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3048 PSMB1 Zornitza Stark gene: PSMB1 was added
gene: PSMB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB1 were set to 32129449
Phenotypes for gene: PSMB1 were set to Intellectual disability; microcephaly
Review for gene: PSMB1 was set to AMBER
Added comment: Two siblings reported with a homozygous missense variant in this gene; supportive experimental evidence including zebrafish model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2688 PSMB1 Zornitza Stark Marked gene: PSMB1 as ready
Intellectual disability syndromic and non-syndromic v0.2688 PSMB1 Zornitza Stark Gene: psmb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2688 PSMB1 Zornitza Stark Classified gene: PSMB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2688 PSMB1 Zornitza Stark Gene: psmb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2687 PSMB1 Zornitza Stark gene: PSMB1 was added
gene: PSMB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PSMB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB1 were set to 32129449
Phenotypes for gene: PSMB1 were set to Intellectual disability; microcephaly
Review for gene: PSMB1 was set to AMBER
Added comment: Two siblings reported with a homozygous missense variant in this gene; supportive experimental evidence including zebrafish model.
Sources: Literature
Mendeliome v0.3047 SLC12A6 Zornitza Stark Marked gene: SLC12A6 as ready
Mendeliome v0.3047 SLC12A6 Zornitza Stark Gene: slc12a6 has been classified as Green List (High Evidence).
Mendeliome v0.3047 SLC12A6 Zornitza Stark Phenotypes for gene: SLC12A6 were changed from to Andermann syndrome; Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum; Intermediate CMT
Mendeliome v0.3046 SLC12A6 Zornitza Stark Publications for gene: SLC12A6 were set to
Mendeliome v0.3045 SLC12A6 Zornitza Stark Mode of inheritance for gene: SLC12A6 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3044 SLC12A6 Zornitza Stark reviewed gene: SLC12A6: Rating: GREEN; Mode of pathogenicity: None; Publications: 31439721; Phenotypes: Andermann syndrome, Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum, Intermediate CMT; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.63 SLC12A6 Zornitza Stark Marked gene: SLC12A6 as ready
Hereditary Neuropathy - complex v0.63 SLC12A6 Zornitza Stark Gene: slc12a6 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.63 SLC12A6 Zornitza Stark Phenotypes for gene: SLC12A6 were changed from Andermann syndrome; Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum; HMSN to Andermann syndrome; Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum; Intermediate CMT
Hereditary Neuropathy - complex v0.62 SLC12A6 Zornitza Stark Publications for gene: SLC12A6 were set to
Hereditary Neuropathy - complex v0.61 SLC12A6 Zornitza Stark Mode of inheritance for gene: SLC12A6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.60 SLC12A6 Zornitza Stark reviewed gene: SLC12A6: Rating: GREEN; Mode of pathogenicity: None; Publications: 31439721; Phenotypes: Agenesis of the corpus callosum with peripheral neuropathy, MM# 218000, Intermediate CMT; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Anophthalmia_Microphthalmia_Coloboma v0.58 C16orf62 Zornitza Stark Marked gene: C16orf62 as ready
Anophthalmia_Microphthalmia_Coloboma v0.58 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Anophthalmia_Microphthalmia_Coloboma v0.58 C16orf62 Zornitza Stark Classified gene: C16orf62 as Amber List (moderate evidence)
Anophthalmia_Microphthalmia_Coloboma v0.58 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2686 C16orf62 Zornitza Stark changed review comment from: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475).
Sources: Expert list; to: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475;31712251).
Sources: Expert list
Anophthalmia_Microphthalmia_Coloboma v0.57 C16orf62 Zornitza Stark gene: C16orf62 was added
gene: C16orf62 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Literature
Mode of inheritance for gene: C16orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C16orf62 were set to 25434475; 31712251
Phenotypes for gene: C16orf62 were set to 3C/Ritscher-Schinzel-like syndrome
Review for gene: C16orf62 was set to AMBER
Added comment: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475;31712251).
Sources: Literature
Mendeliome v0.3044 C16orf62 Zornitza Stark changed review comment from: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475).
Sources: Expert list; to: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475;31712251).
Sources: Expert list
Mendeliome v0.3044 C16orf62 Zornitza Stark edited their review of gene: C16orf62: Changed publications: 25434475, 31712251
Intellectual disability syndromic and non-syndromic v0.2686 C16orf62 Zornitza Stark Publications for gene: C16orf62 were set to 25434475; 31712251
Intellectual disability syndromic and non-syndromic v0.2685 C16orf62 Zornitza Stark Publications for gene: C16orf62 were set to 25434475
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark edited their review of gene: C16orf62: Changed publications: 25434475, 31712251
Mendeliome v0.3044 EWSR1 Seb Lunke Marked gene: EWSR1 as ready
Mendeliome v0.3044 EWSR1 Seb Lunke Gene: ewsr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3044 EWSR1 Seb Lunke Phenotypes for gene: EWSR1 were changed from to Amyotrophic lateral sclerosis
Mendeliome v0.3043 EWSR1 Seb Lunke Publications for gene: EWSR1 were set to
Mendeliome v0.3042 EWSR1 Seb Lunke Mode of inheritance for gene: EWSR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3041 EWSR1 Seb Lunke Classified gene: EWSR1 as Amber List (moderate evidence)
Mendeliome v0.3041 EWSR1 Seb Lunke Gene: ewsr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3040 EWSR1 Seb Lunke reviewed gene: EWSR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 29731676, 22454397; Phenotypes: Amyotrophic lateral sclerosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.39 FGF10 Tiong Tan Publications for gene: FGF10 were set to
Craniosynostosis v0.38 FGF10 Tiong Tan Marked gene: FGF10 as ready
Craniosynostosis v0.38 FGF10 Tiong Tan Gene: fgf10 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.38 FGF10 Tiong Tan Classified gene: FGF10 as Amber List (moderate evidence)
Craniosynostosis v0.38 FGF10 Tiong Tan Added comment: Comment on list classification: Two unrelated individuals in large craniosynostosis cohort with pathogenic variants in FGF10.
Craniosynostosis v0.38 FGF10 Tiong Tan Gene: fgf10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3040 TRPM7 Zornitza Stark Marked gene: TRPM7 as ready
Mendeliome v0.3040 TRPM7 Zornitza Stark Gene: trpm7 has been classified as Red List (Low Evidence).
Mendeliome v0.3040 TRPM7 Zornitza Stark Phenotypes for gene: TRPM7 were changed from to {Amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to}, MIM# 105500
Mendeliome v0.3039 TRPM7 Zornitza Stark Classified gene: TRPM7 as Red List (low evidence)
Mendeliome v0.3039 TRPM7 Zornitza Stark Gene: trpm7 has been classified as Red List (Low Evidence).
Mendeliome v0.3038 TRPM7 Zornitza Stark reviewed gene: TRPM7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to}, MIM# 105500; Mode of inheritance: None
Mendeliome v0.3038 C16orf62 Zornitza Stark Tag new gene name tag was added to gene: C16orf62.
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark Tag new gene name tag was added to gene: C16orf62.
Genetic Epilepsy v0.719 SMC1A Zornitza Stark Marked gene: SMC1A as ready
Genetic Epilepsy v0.719 SMC1A Zornitza Stark Gene: smc1a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.719 SMC1A Zornitza Stark Phenotypes for gene: SMC1A were changed from to Epileptic encephalopathy, early infantile, 85, with or without midline brain defects, MIM# 301044
Genetic Epilepsy v0.718 SMC1A Zornitza Stark Publications for gene: SMC1A were set to
Genetic Epilepsy v0.717 SMC1A Zornitza Stark Mode of inheritance for gene: SMC1A was changed from Unknown to Other
Genetic Epilepsy v0.716 SMC1A Zornitza Stark reviewed gene: SMC1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31334757, 28166369; Phenotypes: Epileptic encephalopathy, early infantile, 85, with or without midline brain defects, MIM# 301044; Mode of inheritance: Other
Holoprosencephaly and septo-optic dysplasia v0.21 SMC1A Zornitza Stark Marked gene: SMC1A as ready
Holoprosencephaly and septo-optic dysplasia v0.21 SMC1A Zornitza Stark Gene: smc1a has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v0.21 SMC1A Zornitza Stark Classified gene: SMC1A as Green List (high evidence)
Holoprosencephaly and septo-optic dysplasia v0.21 SMC1A Zornitza Stark Gene: smc1a has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v0.20 SMC1A Zornitza Stark gene: SMC1A was added
gene: SMC1A was added to Holoprosencephaly and septo-optic dysplasia. Sources: Literature
Mode of inheritance for gene: SMC1A was set to Other
Publications for gene: SMC1A were set to 31334757; 28166369
Phenotypes for gene: SMC1A were set to Epileptic encephalopathy, early infantile, 85, with or without midline brain defects, MIM# 301044
Review for gene: SMC1A was set to GREEN
Added comment: Multiple females reported with EE/HPE and LOF variants in this gene. Note gene also causes CdL.
Sources: Literature
Holoprosencephaly and septo-optic dysplasia v0.19 STAG2 Zornitza Stark Marked gene: STAG2 as ready
Holoprosencephaly and septo-optic dysplasia v0.19 STAG2 Zornitza Stark Gene: stag2 has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v0.19 STAG2 Zornitza Stark Phenotypes for gene: STAG2 were changed from Holoprosencephaly to Holoprosencephaly 13, X-linked, MIM# 301043
Holoprosencephaly and septo-optic dysplasia v0.18 STAG2 Zornitza Stark Classified gene: STAG2 as Green List (high evidence)
Holoprosencephaly and septo-optic dysplasia v0.18 STAG2 Zornitza Stark Gene: stag2 has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v0.17 STAG2 Zornitza Stark gene: STAG2 was added
gene: STAG2 was added to Holoprosencephaly and septo-optic dysplasia. Sources: Literature
Mode of inheritance for gene: STAG2 was set to Other
Publications for gene: STAG2 were set to 31334757
Phenotypes for gene: STAG2 were set to Holoprosencephaly
Review for gene: STAG2 was set to GREEN
Added comment: Six females reported with LoF variants in this gene and HPE spectrum disorders.
Sources: Literature
Mendeliome v0.3038 C16orf62 Zornitza Stark Marked gene: C16orf62 as ready
Mendeliome v0.3038 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3038 C16orf62 Zornitza Stark Classified gene: C16orf62 as Amber List (moderate evidence)
Mendeliome v0.3038 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3037 C16orf62 Zornitza Stark gene: C16orf62 was added
gene: C16orf62 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: C16orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C16orf62 were set to 25434475
Phenotypes for gene: C16orf62 were set to 3C/Ritscher-Schinzel-like syndrome
Review for gene: C16orf62 was set to AMBER
Added comment: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475).
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark Marked gene: C16orf62 as ready
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark Classified gene: C16orf62 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2683 C16orf62 Zornitza Stark gene: C16orf62 was added
gene: C16orf62 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: C16orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C16orf62 were set to 25434475
Phenotypes for gene: C16orf62 were set to 3C/Ritscher-Schinzel-like syndrome
Review for gene: C16orf62 was set to AMBER
Added comment: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475).
Sources: Expert list
Mendeliome v0.3036 RHOBTB2 Zornitza Stark Marked gene: RHOBTB2 as ready
Mendeliome v0.3036 RHOBTB2 Zornitza Stark Gene: rhobtb2 has been classified as Green List (High Evidence).
Mendeliome v0.3036 RHOBTB2 Zornitza Stark Phenotypes for gene: RHOBTB2 were changed from to Epileptic encephalopathy, early infantile, 64, MIM#618004
Mendeliome v0.3035 RHOBTB2 Zornitza Stark Publications for gene: RHOBTB2 were set to
Mendeliome v0.3034 RHOBTB2 Zornitza Stark Mode of pathogenicity for gene: RHOBTB2 was changed from to Other
Mendeliome v0.3033 RHOBTB2 Zornitza Stark Mode of inheritance for gene: RHOBTB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3032 RHOBTB2 Elena Savva reviewed gene: RHOBTB2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:29276004, 29768694; Phenotypes: Epileptic encephalopathy, early infantile, 64, 618004; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.2682 PPP1CB Zornitza Stark Marked gene: PPP1CB as ready
Intellectual disability syndromic and non-syndromic v0.2682 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2682 PPP1CB Zornitza Stark Phenotypes for gene: PPP1CB were changed from to Noonan syndrome-like disorder with loose anlagen hair 2, OMIM # 617506
Intellectual disability syndromic and non-syndromic v0.2681 PPP1CB Zornitza Stark Publications for gene: PPP1CB were set to
Intellectual disability syndromic and non-syndromic v0.2680 PPP1CB Zornitza Stark Mode of inheritance for gene: PPP1CB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2679 PPP1CB Zornitza Stark reviewed gene: PPP1CB: Rating: GREEN; Mode of pathogenicity: None; Publications: 32476286, 28211982, 27264673, 27681385, 27868344; Phenotypes: Noonan syndrome-like disorder with loose anlagen hair 2, OMIM # 617506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3032 PPP1CB Zornitza Stark Marked gene: PPP1CB as ready
Mendeliome v0.3032 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Green List (High Evidence).
Mendeliome v0.3032 PPP1CB Zornitza Stark Phenotypes for gene: PPP1CB were changed from to Noonan syndrome-like disorder with loose anagen hair 2, OMIM # 617506
Mendeliome v0.3031 PPP1CB Zornitza Stark Publications for gene: PPP1CB were set to
Mendeliome v0.3030 PPP1CB Zornitza Stark Mode of inheritance for gene: PPP1CB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3029 PPP1CB Zornitza Stark reviewed gene: PPP1CB: Rating: GREEN; Mode of pathogenicity: None; Publications: 32476286, 28211982, 27264673, 27681385, 27868344; Phenotypes: Noonan syndrome-like disorder with loose anagen hair 2, OMIM # 617506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rasopathy v0.17 PPP1CB Zornitza Stark Marked gene: PPP1CB as ready
Rasopathy v0.17 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Green List (High Evidence).
Rasopathy v0.17 PPP1CB Chirag Patel Classified gene: PPP1CB as Green List (high evidence)
Rasopathy v0.17 PPP1CB Chirag Patel Gene: ppp1cb has been classified as Green List (High Evidence).
Rasopathy v0.16 PPP1CB Chirag Patel gene: PPP1CB was added
gene: PPP1CB was added to Rasopathy. Sources: Literature
Mode of inheritance for gene: PPP1CB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP1CB were set to PMID: 32476286; 28211982; 27264673; 27681385; 27868344
Phenotypes for gene: PPP1CB were set to Noonan syndrome-like disorder with loose anagen hair 2; OMIM # 617506
Review for gene: PPP1CB was set to GREEN
Added comment: > 20 patients reported from different families and different ethnicities with Noonan syndrome-like features and hair abnormalities. All patients so far with missense variants.
Sources: Literature
Mendeliome v0.3029 NUP88 Zornitza Stark Marked gene: NUP88 as ready
Mendeliome v0.3029 NUP88 Zornitza Stark Gene: nup88 has been classified as Green List (High Evidence).
Mendeliome v0.3029 NUP88 Zornitza Stark Classified gene: NUP88 as Green List (high evidence)
Mendeliome v0.3029 NUP88 Zornitza Stark Gene: nup88 has been classified as Green List (High Evidence).
Mendeliome v0.3028 NUP88 Zornitza Stark gene: NUP88 was added
gene: NUP88 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUP88 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP88 were set to 30543681
Phenotypes for gene: NUP88 were set to Fetal akinesia deformation sequence 4, MIM# 618393
Review for gene: NUP88 was set to GREEN
Added comment: Two unrelated families, functional data on the variants support pathogenicity as does a zebrafish model.
Sources: Literature
Arthrogryposis v0.61 NUP88 Zornitza Stark Marked gene: NUP88 as ready
Arthrogryposis v0.61 NUP88 Zornitza Stark Gene: nup88 has been classified as Green List (High Evidence).
Arthrogryposis v0.61 NUP88 Zornitza Stark Classified gene: NUP88 as Green List (high evidence)
Arthrogryposis v0.61 NUP88 Zornitza Stark Gene: nup88 has been classified as Green List (High Evidence).
Arthrogryposis v0.60 NUP88 Zornitza Stark changed review comment from: Two unrelated families and a zebrafish model reported.
Sources: Literature; to: Two unrelated families, functional data on the variants support pathogenicity as does a zebrafish model.
Sources: Literature
Arthrogryposis v0.60 NUP88 Zornitza Stark edited their review of gene: NUP88: Changed rating: GREEN; Changed phenotypes: Fetal akinesia deformation sequence 4, MIM# 618393
Arthrogryposis v0.60 NUP88 Zornitza Stark gene: NUP88 was added
gene: NUP88 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: NUP88 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP88 were set to 30543681
Phenotypes for gene: NUP88 were set to Fetal akinesia deformation sequence 4, MIM# 618393
Review for gene: NUP88 was set to AMBER
Added comment: Two unrelated families and a zebrafish model reported.
Sources: Literature
Microcephaly v0.129 SMO Zornitza Stark Marked gene: SMO as ready
Microcephaly v0.129 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Microcephaly v0.129 SMO Zornitza Stark Classified gene: SMO as Green List (high evidence)
Microcephaly v0.129 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Microcephaly v0.128 SMO Zornitza Stark gene: SMO was added
gene: SMO was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SMO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMO were set to 32413283
Phenotypes for gene: SMO were set to Microcephaly, congenital heart disease, polydactyly, aganglionosis
Review for gene: SMO was set to GREEN
Added comment: Bi-allelic loss-of-function variations in SMO reported in seven individuals from five independent families. Wide phenotypic spectrum of developmental anomalies affecting the brain (hypothalamic hamartoma and microcephaly), heart (atrioventricular septal defect), skeleton (postaxial polydactyly, narrow chest, and shortening of long bones), and enteric nervous system (aganglionosis).
Sources: Literature
Callosome v0.147 SMO Zornitza Stark Tag somatic tag was added to gene: SMO.
Hirschsprung disease v0.3 SMO Zornitza Stark Marked gene: SMO as ready
Hirschsprung disease v0.3 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Hirschsprung disease v0.3 SMO Zornitza Stark Classified gene: SMO as Green List (high evidence)
Hirschsprung disease v0.3 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Hirschsprung disease v0.2 SMO Zornitza Stark gene: SMO was added
gene: SMO was added to Hirschsprung disease. Sources: Literature
Mode of inheritance for gene: SMO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMO were set to 32413283
Phenotypes for gene: SMO were set to Microcephaly, congenital heart disease, polydactyly, aganglionosis
Review for gene: SMO was set to GREEN
Added comment: Bi-allelic loss-of-function variations in SMO reported in seven individuals from five independent families. Wide phenotypic spectrum of developmental anomalies affecting the brain (hypothalamic hamartoma and microcephaly), heart (atrioventricular septal defect), skeleton (postaxial polydactyly, narrow chest, and shortening of long bones), and enteric nervous system (aganglionosis).
Sources: Literature
Congenital Heart Defect v0.48 SMO Zornitza Stark Marked gene: SMO as ready
Congenital Heart Defect v0.48 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Congenital Heart Defect v0.48 SMO Zornitza Stark Classified gene: SMO as Green List (high evidence)
Congenital Heart Defect v0.48 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Congenital Heart Defect v0.47 SMO Zornitza Stark gene: SMO was added
gene: SMO was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: SMO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMO were set to 32413283
Phenotypes for gene: SMO were set to Microcephaly, congenital heart disease, polydactyly, aganglionosis
Review for gene: SMO was set to GREEN
Added comment: Bi-allelic loss-of-function variations in SMO reported in seven individuals from five independent families. Wide phenotypic spectrum of developmental anomalies affecting the brain (hypothalamic hamartoma and microcephaly), heart (atrioventricular septal defect), skeleton (postaxial polydactyly, narrow chest, and shortening of long bones), and enteric nervous system (aganglionosis).
Sources: Literature
Congenital Heart Defect v0.46 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Callosome v0.147 SMO Zornitza Stark Marked gene: SMO as ready
Callosome v0.147 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Callosome v0.147 SMO Zornitza Stark Phenotypes for gene: SMO were changed from to Curry-Jones syndrome, somatic mosaic 601707
Callosome v0.146 SMO Zornitza Stark Publications for gene: SMO were set to
Callosome v0.145 SMO Zornitza Stark Mode of inheritance for gene: SMO was changed from Unknown to Other
Callosome v0.144 SMO Zornitza Stark reviewed gene: SMO: Rating: GREEN; Mode of pathogenicity: None; Publications: 27236920; Phenotypes: Curry-Jones syndrome, somatic mosaic 601707; Mode of inheritance: Other
Anophthalmia_Microphthalmia_Coloboma v0.56 SMO Zornitza Stark Tag somatic tag was added to gene: SMO.
Polydactyly v0.36 SMO Zornitza Stark Marked gene: SMO as ready
Polydactyly v0.36 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Polydactyly v0.36 SMO Zornitza Stark Phenotypes for gene: SMO were changed from to Microcephaly, congenital heart disease, polydactyly, aganglionosis; Curry-Jones syndrome, somatic mosaic 601707
Polydactyly v0.35 SMO Zornitza Stark Publications for gene: SMO were set to
Polydactyly v0.34 SMO Zornitza Stark Mode of inheritance for gene: SMO was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.33 SMO Zornitza Stark reviewed gene: SMO: Rating: GREEN; Mode of pathogenicity: None; Publications: 32413283, 27236920; Phenotypes: Microcephaly, congenital heart disease, polydactyly, aganglionosis, Curry-Jones syndrome, somatic mosaic 601707; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3027 SMO Zornitza Stark Marked gene: SMO as ready
Mendeliome v0.3027 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Mendeliome v0.3027 SMO Zornitza Stark Phenotypes for gene: SMO were changed from to Microcephaly, congenital heart disease, polydactyly, aganglionosis; Curry-Jones syndrome, somatic mosaic 601707
Mendeliome v0.3026 SMO Zornitza Stark Publications for gene: SMO were set to
Mendeliome v0.3025 SMO Zornitza Stark Mode of inheritance for gene: SMO was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3024 SMO Zornitza Stark reviewed gene: SMO: Rating: GREEN; Mode of pathogenicity: None; Publications: 32413283, 27236920; Phenotypes: Microcephaly, congenital heart disease, polydactyly, aganglionosis, Curry-Jones syndrome, somatic mosaic 601707; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3024 RBL2 Zornitza Stark Marked gene: RBL2 as ready
Mendeliome v0.3024 RBL2 Zornitza Stark Gene: rbl2 has been classified as Red List (Low Evidence).
Mendeliome v0.3024 RBL2 Zornitza Stark gene: RBL2 was added
gene: RBL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RBL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBL2 were set to 32105419; 9806916
Phenotypes for gene: RBL2 were set to Intellectual disability
Review for gene: RBL2 was set to RED
Added comment: Single family reported with pair of affected siblings. Supportive mouse model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2679 RBL2 Zornitza Stark Marked gene: RBL2 as ready
Intellectual disability syndromic and non-syndromic v0.2679 RBL2 Zornitza Stark Gene: rbl2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2679 RBL2 Zornitza Stark gene: RBL2 was added
gene: RBL2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RBL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBL2 were set to 32105419; 9806916
Phenotypes for gene: RBL2 were set to Intellectual disability
Review for gene: RBL2 was set to RED
Added comment: Single family reported with pair of affected siblings. Supportive mouse model.
Sources: Literature
Microcephaly v0.127 GRM7 Zornitza Stark Marked gene: GRM7 as ready
Microcephaly v0.127 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Microcephaly v0.127 GRM7 Zornitza Stark Classified gene: GRM7 as Green List (high evidence)
Microcephaly v0.127 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Microcephaly v0.126 GRM7 Zornitza Stark gene: GRM7 was added
gene: GRM7 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 32286009; 32248644
Phenotypes for gene: GRM7 were set to Epilepsy, microcephaly, developmental delay
Review for gene: GRM7 was set to GREEN
Added comment: Eleven individuals from six families reported, three different homozygous variants (two missense, one LoF). Developmental delay, neonatal‐ or infantile‐onset epilepsy, and microcephaly were universal. Supportive mouse model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2678 GRM7 Zornitza Stark Marked gene: GRM7 as ready
Intellectual disability syndromic and non-syndromic v0.2678 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2678 GRM7 Zornitza Stark Classified gene: GRM7 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2678 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2677 GRM7 Zornitza Stark gene: GRM7 was added
gene: GRM7 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 32286009; 32248644
Phenotypes for gene: GRM7 were set to Epilepsy, microcephaly, developmental delay
Review for gene: GRM7 was set to GREEN
Added comment: Eleven individuals from six families reported, three different homozygous variants (two missense, one LoF). Developmental delay, neonatal‐ or infantile‐onset epilepsy, and microcephaly were universal. Supportive mouse model.
Sources: Literature
Genetic Epilepsy v0.716 GRM7 Zornitza Stark Marked gene: GRM7 as ready
Genetic Epilepsy v0.716 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Mendeliome v0.3023 GRM7 Zornitza Stark Marked gene: GRM7 as ready
Mendeliome v0.3023 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Mendeliome v0.3023 GRM7 Zornitza Stark Classified gene: GRM7 as Green List (high evidence)
Mendeliome v0.3023 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Mendeliome v0.3022 GRM7 Zornitza Stark gene: GRM7 was added
gene: GRM7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 32286009; 32248644
Phenotypes for gene: GRM7 were set to Epilepsy, microcephaly, developmental delay
Review for gene: GRM7 was set to GREEN
Added comment: Eleven individuals from six families reported, three different homozygous variants (two missense, one LoF). Developmental delay, neonatal‐ or infantile‐onset epilepsy, and microcephaly were universal. Supportive mouse model.
Sources: Literature
Genetic Epilepsy v0.716 GRM7 Zornitza Stark Classified gene: GRM7 as Green List (high evidence)
Genetic Epilepsy v0.716 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.715 GRM7 Zornitza Stark gene: GRM7 was added
gene: GRM7 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 32286009; 32248644
Phenotypes for gene: GRM7 were set to Epilepsy, microcephaly, developmental delay
Review for gene: GRM7 was set to GREEN
Added comment: Eleven individuals from six families reported, three different homozygous variants (two missense, one LoF). Developmental delay, neonatal‐ or infantile‐onset epilepsy, and microcephaly were universal.
Sources: Literature
Glycogen Storage Diseases v0.8 PYGM Zornitza Stark Marked gene: PYGM as ready
Glycogen Storage Diseases v0.8 PYGM Zornitza Stark Gene: pygm has been classified as Green List (High Evidence).
Glycogen Storage Diseases v0.8 PYGM Zornitza Stark Publications for gene: PYGM were set to 32386344
Mendeliome v0.3021 PYGM Zornitza Stark Marked gene: PYGM as ready
Mendeliome v0.3021 PYGM Zornitza Stark Gene: pygm has been classified as Green List (High Evidence).
Mendeliome v0.3021 PYGM Zornitza Stark Phenotypes for gene: PYGM were changed from to McArdle disease, MIM# 232600; Glycogen storage disease, autosomal dominant
Mendeliome v0.3020 PYGM Zornitza Stark Publications for gene: PYGM were set to
Mendeliome v0.3019 PYGM Zornitza Stark Mode of inheritance for gene: PYGM was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Glycogen Storage Diseases v0.7 PYGM Zornitza Stark Phenotypes for gene: PYGM were changed from to McArdle disease, MIM# 232600; Glycogen storage disease, autosomal dominant
Mendeliome v0.3018 PYGM Zornitza Stark reviewed gene: PYGM: Rating: GREEN; Mode of pathogenicity: None; Publications: 32386344; Phenotypes: McArdle disease, MIM# 232600, Glycogen storage disease, autosomal dominant; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Glycogen Storage Diseases v0.6 PYGM Zornitza Stark Publications for gene: PYGM were set to 32386344
Glycogen Storage Diseases v0.6 PYGM Zornitza Stark Publications for gene: PYGM were set to
Glycogen Storage Diseases v0.5 PYGM Zornitza Stark Mode of inheritance for gene: PYGM was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Glycogen Storage Diseases v0.4 PYGM Zornitza Stark reviewed gene: PYGM: Rating: GREEN; Mode of pathogenicity: None; Publications: 32386344; Phenotypes: McArdle disease, MIM# 232600, Glycogen storage disease, autosomal dominant; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3018 PERP Zornitza Stark Marked gene: PERP as ready
Mendeliome v0.3018 PERP Zornitza Stark Gene: perp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3018 PERP Zornitza Stark Classified gene: PERP as Amber List (moderate evidence)
Mendeliome v0.3018 PERP Zornitza Stark Gene: perp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3017 PERP Zornitza Stark gene: PERP was added
gene: PERP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PERP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PERP were set to 31898316
Phenotypes for gene: PERP were set to Erythrokeratoderma, no OMIM # yet
Review for gene: PERP was set to AMBER
Added comment: One extended multiplex consanguineous family with Erythrokeratoderma (striking similarity to that observed in Perp −/− mice), and a novel homozygous variant (c.466G>A; p.Gly156Arg) in PERP that fully segregated with the phenotype. Functional analysis of patient‐ and control‐derived keratinocytes revealed a deleterious effect of the identified variant on the intracellular localization of PERP. A previous report showed that PERP mutation causes a dominant form of keratoderma but a single patient in that report with a homozygous variant in PERP suggests that recessive inheritance is also possible.
Sources: Literature
Palmoplantar Keratoderma and Erythrokeratoderma v0.7 PERP Zornitza Stark Marked gene: PERP as ready
Palmoplantar Keratoderma and Erythrokeratoderma v0.7 PERP Zornitza Stark Added comment: Comment when marking as ready: One family and a mouse model, upgrade to Amber.
Palmoplantar Keratoderma and Erythrokeratoderma v0.7 PERP Zornitza Stark Gene: perp has been classified as Amber List (Moderate Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.7 PERP Zornitza Stark Classified gene: PERP as Amber List (moderate evidence)
Palmoplantar Keratoderma and Erythrokeratoderma v0.7 PERP Zornitza Stark Gene: perp has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.52 GBA Zornitza Stark Marked gene: GBA as ready
Early-onset Dementia v0.52 GBA Zornitza Stark Gene: gba has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.52 GBA Zornitza Stark Phenotypes for gene: GBA were changed from to {Lewy body dementia, susceptibility to} (MIM# 127750)
Early-onset Dementia v0.51 GBA Zornitza Stark Publications for gene: GBA were set to
Early-onset Dementia v0.50 GBA Zornitza Stark Mode of inheritance for gene: GBA was changed from Unknown to Other
Early-onset Dementia v0.49 GBA Zornitza Stark Classified gene: GBA as Amber List (moderate evidence)
Early-onset Dementia v0.49 GBA Zornitza Stark Gene: gba has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3016 ADCY6 Zornitza Stark Marked gene: ADCY6 as ready
Mendeliome v0.3016 ADCY6 Zornitza Stark Gene: adcy6 has been classified as Green List (High Evidence).
Mendeliome v0.3016 ADCY6 Zornitza Stark Classified gene: ADCY6 as Green List (high evidence)
Mendeliome v0.3016 ADCY6 Zornitza Stark Gene: adcy6 has been classified as Green List (High Evidence).
Mendeliome v0.3015 ADCY6 Zornitza Stark gene: ADCY6 was added
gene: ADCY6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADCY6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADCY6 were set to 24319099; 26257172; 31846058
Phenotypes for gene: ADCY6 were set to Lethal congenital contracture syndrome 8, OMIM # 616287
Review for gene: ADCY6 was set to GREEN
Added comment: Laquerriere et al. (2014): 2 sibs from a consanguineous family with an axoglial form of lethal congenital contracture syndrome, and homozygous missense ADCY6 mutation (R1116C). The parents were heterozygous for the mutation. Knocked down ADCY6 orthologs in zebrafish showed a loss of myelin basic protein expression in the peripheral nervous system but no defects in Schwann cell migration and axonal growth. Gonzaga‐Jauregui et al. (2015): 1 patient with congenital hypotonia, distal joint contractures, hypomyelinating neuropathy, and vocal cord paralysis, and a homozygous missense ADCY6 variant. No functional studies. Deceased sister with a similar phenotype with hypotonia, areflexia, and hypomyelinating neuropathy who died at 18 months of respiratory insufficiency. Agolini et al. (2020): 1 patient with severe form of AMC, with two novel compound heterozygous variants in ADCY6 (parents confirmed carriers), but no functional studies.
Sources: Literature
Arthrogryposis v0.59 ADCY6 Zornitza Stark Marked gene: ADCY6 as ready
Arthrogryposis v0.59 ADCY6 Zornitza Stark Gene: adcy6 has been classified as Green List (High Evidence).
Early-onset Dementia v0.48 GBA Ain Roesley reviewed gene: GBA: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 23588557, 32439597, 31010158; Phenotypes: {Lewy body dementia, susceptibility to} (MIM# 127750); Mode of inheritance: Other
Arthrogryposis v0.59 ADCY6 Zornitza Stark Phenotypes for gene: ADCY6 were changed from ?Lethal congenital contracture syndrome 8, OMIM # 616287 to Lethal congenital contracture syndrome 8, OMIM # 616287
Mendeliome v0.3014 DSCR3 Zornitza Stark Marked gene: DSCR3 as ready
Mendeliome v0.3014 DSCR3 Zornitza Stark Gene: dscr3 has been classified as Red List (Low Evidence).
Mendeliome v0.3014 DSCR3 Zornitza Stark gene: DSCR3 was added
gene: DSCR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DSCR3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DSCR3 were set to 31845315
Phenotypes for gene: DSCR3 were set to Intellectual disability, no OMIM # yet
Review for gene: DSCR3 was set to RED
Added comment: 1 family/2 cousins with cognitive impairment, growth failure, skeletal abnormalities, and distinctive facial features. Both shared the homozygous nonsense variant c.178G>T (p.Glu60*) in the VPS26C gene. This gene encodes VPS26C, a member of the retriever integral membrane protein recycling pathway. The nature of the variant which is predicted to result in loss‐of‐function, expression studies revealing significant reduction in the mutant transcript, and the co‐segregation of the homozygous variant with the phenotype in two affected individuals.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2676 DSCR3 Zornitza Stark Marked gene: DSCR3 as ready
Intellectual disability syndromic and non-syndromic v0.2676 DSCR3 Zornitza Stark Gene: dscr3 has been classified as Red List (Low Evidence).
Mendeliome v0.3013 LEF1 Zornitza Stark Marked gene: LEF1 as ready
Mendeliome v0.3013 LEF1 Zornitza Stark Gene: lef1 has been classified as Red List (Low Evidence).
Mendeliome v0.3013 LEF1 Zornitza Stark gene: LEF1 was added
gene: LEF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LEF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LEF1 were set to 32022899
Phenotypes for gene: LEF1 were set to Ectodermal dysplasia, no OMIM# yet
Review for gene: LEF1 was set to RED
Added comment: In mice, targeted inactivation of the LEF1 gene results in a complete block of development of multiple ectodermal appendages. One report of two unrelated patients with 4q25 de novo deletion encompassing LEF1 , associated with severe oligodontia of primary and permanent dentition, hypotrichosis and hypohidrosis compatible with hypohidrotic ectodermal dysplasia. So far, no pathogenic variants or variations involving the LEF1 gene have been reported in human.
Sources: Literature
Oligodontia v0.5 LEF1 Zornitza Stark Marked gene: LEF1 as ready
Oligodontia v0.5 LEF1 Zornitza Stark Gene: lef1 has been classified as Red List (Low Evidence).
Ectodermal Dysplasia v0.24 LEF1 Zornitza Stark Marked gene: LEF1 as ready
Ectodermal Dysplasia v0.24 LEF1 Zornitza Stark Gene: lef1 has been classified as Red List (Low Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.6 PERP Chirag Patel gene: PERP was added
gene: PERP was added to Palmoplantar Keratoderma and Erythrokeratoderma. Sources: Literature
Mode of inheritance for gene: PERP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PERP were set to PMID: 31898316
Phenotypes for gene: PERP were set to Erythrokeratoderma, no OMIM # yet
Review for gene: PERP was set to RED
Added comment: One extended multiplex consanguineous family with Erythrokeratoderma (striking similarity to that observed in Perp −/− mice), and a novel homozygous variant (c.466G>A; p.Gly156Arg) in PERP that fully segregated with the phenotype. Functional analysis of patient‐ and control‐derived keratinocytes revealed a deleterious effect of the identified variant on the intracellular localization of PERP.

A previous report showed that PERP mutation causes a dominant form of keratoderma but a single patient in that report with a homozygous variant in PERP suggests that recessive inheritance is also possible.
Sources: Literature
Mendeliome v0.3012 OTUD7A Zornitza Stark Marked gene: OTUD7A as ready
Mendeliome v0.3012 OTUD7A Zornitza Stark Gene: otud7a has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2676 OTUD7A Zornitza Stark Phenotypes for gene: OTUD7A were changed from Epileptic encephalopathy, no OMIM# yet to Epileptic encephalopathy, intellectual disability, no OMIM# yet
Intellectual disability syndromic and non-syndromic v0.2675 OTUD7A Zornitza Stark Publications for gene: OTUD7A were set to PMID: 31997314
Intellectual disability syndromic and non-syndromic v0.2674 OTUD7A Zornitza Stark reviewed gene: OTUD7A: Rating: RED; Mode of pathogenicity: None; Publications: 29395075, 29395074; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.3012 OTUD7A Zornitza Stark Phenotypes for gene: OTUD7A were changed from Epileptic encephalopathy, no OMIM# yet to Epileptic encephalopathy, intellectual disability, no OMIM# yet
Mendeliome v0.3011 OTUD7A Zornitza Stark Publications for gene: OTUD7A were set to 31997314
Mendeliome v0.3010 OTUD7A Zornitza Stark edited their review of gene: OTUD7A: Changed publications: 31997314, 29395075, 29395074
Mendeliome v0.3010 OTUD7A Zornitza Stark gene: OTUD7A was added
gene: OTUD7A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: OTUD7A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OTUD7A were set to 31997314
Phenotypes for gene: OTUD7A were set to Epileptic encephalopathy, no OMIM# yet
Review for gene: OTUD7A was set to RED
Added comment: One patient with severe global developmental delay, language impairment and epileptic encephalopathy. Homozygous OTUD7A missense variant (c.697C>T, p.Leu233Phe), predicted to alter an ultraconserved amino acid, lying within the OTU catalytic domain. Its subsequent segregation analysis revealed that the parents, presenting with learning disability, and brother were heterozygous carriers. Biochemical assays demonstrated that proteasome complex formation and function were significantly reduced in patient‐derived fibroblasts and in OTUD7A knockout HAP1 cell line. Gene lies in the chromosome 15q13.3 region. Heterozygous microdeletions of chromosome 15q13.3 show incomplete penetrance and are associated with a highly variable phenotype that may include intellectual disability, epilepsy, facial dysmorphism and digit anomalies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2674 OTUD7A Zornitza Stark Marked gene: OTUD7A as ready
Intellectual disability syndromic and non-syndromic v0.2674 OTUD7A Zornitza Stark Gene: otud7a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.714 OTUD7A Zornitza Stark Marked gene: OTUD7A as ready
Genetic Epilepsy v0.714 OTUD7A Zornitza Stark Gene: otud7a has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2674 GATAD2B Zornitza Stark Marked gene: GATAD2B as ready
Intellectual disability syndromic and non-syndromic v0.2674 GATAD2B Zornitza Stark Gene: gatad2b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2674 GATAD2B Zornitza Stark Phenotypes for gene: GATAD2B were changed from to Mental retardation, autosomal dominant 18, OMIM # 615074
Intellectual disability syndromic and non-syndromic v0.2673 GATAD2B Zornitza Stark Publications for gene: GATAD2B were set to
Intellectual disability syndromic and non-syndromic v0.2672 GATAD2B Zornitza Stark Mode of inheritance for gene: GATAD2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3009 GATAD2B Zornitza Stark Marked gene: GATAD2B as ready
Mendeliome v0.3009 GATAD2B Zornitza Stark Gene: gatad2b has been classified as Green List (High Evidence).
Mendeliome v0.3009 GATAD2B Zornitza Stark Phenotypes for gene: GATAD2B were changed from to Mental retardation, autosomal dominant 18, OMIM # 615074
Mendeliome v0.3008 GATAD2B Zornitza Stark Publications for gene: GATAD2B were set to
Mendeliome v0.3007 GATAD2B Zornitza Stark Mode of inheritance for gene: GATAD2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3006 GATAD2B Zornitza Stark reviewed gene: GATAD2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31949314; Phenotypes: Mental retardation, autosomal dominant 18, OMIM # 615074; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macrocephaly_Megalencephaly v0.33 GATAD2B Zornitza Stark Marked gene: GATAD2B as ready
Macrocephaly_Megalencephaly v0.33 GATAD2B Zornitza Stark Gene: gatad2b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2671 KMT2D Zornitza Stark Marked gene: KMT2D as ready
Intellectual disability syndromic and non-syndromic v0.2671 KMT2D Zornitza Stark Gene: kmt2d has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2671 KMT2D Zornitza Stark Phenotypes for gene: KMT2D were changed from Kabuki syndrome 1, MIM# 147920; KMT2D-associated syndrome to Kabuki syndrome 1, MIM# 147920; KMT2D-associated syndrome
Intellectual disability syndromic and non-syndromic v0.2671 KMT2D Zornitza Stark Phenotypes for gene: KMT2D were changed from Kabuki syndrome 1, MIM# 147920; KMT2D-associated neurodevelopmental syndrome to Kabuki syndrome 1, MIM# 147920; KMT2D-associated syndrome
Mendeliome v0.3006 KMT2D Zornitza Stark Phenotypes for gene: KMT2D were changed from Kabuki syndrome 1, MIM# 147920; KMT2D-associated neurodevelopmental syndrome to Kabuki syndrome 1, MIM# 147920; KMT2D-associated syndrome
Intellectual disability syndromic and non-syndromic v0.2670 KMT2D Zornitza Stark reviewed gene: KMT2D: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Kabuki syndrome 1, MIM# 147920, KMT2D-associated syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2670 KMT2D Zornitza Stark Deleted their review
Mendeliome v0.3005 KMT2D Zornitza Stark Marked gene: KMT2D as ready
Mendeliome v0.3005 KMT2D Zornitza Stark Gene: kmt2d has been classified as Green List (High Evidence).
Mendeliome v0.3005 KMT2D Zornitza Stark Phenotypes for gene: KMT2D were changed from to Kabuki syndrome 1, MIM# 147920; KMT2D-associated neurodevelopmental syndrome
Mendeliome v0.3004 KMT2D Zornitza Stark Publications for gene: KMT2D were set to
Mendeliome v0.3003 KMT2D Zornitza Stark Mode of inheritance for gene: KMT2D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3002 KMT2D Zornitza Stark reviewed gene: KMT2D: Rating: GREEN; Mode of pathogenicity: None; Publications: 31949313; Phenotypes: Kabuki syndrome 1, MIM# 147920, KMT2D-associated neurodevelopmental syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2670 KMT2D Zornitza Stark Phenotypes for gene: KMT2D were changed from to Kabuki syndrome 1, MIM# 147920; KMT2D-associated neurodevelopmental syndrome
Intellectual disability syndromic and non-syndromic v0.2669 KMT2D Zornitza Stark Publications for gene: KMT2D were set to
Craniosynostosis v0.37 TLK2 Bryony Thompson reviewed gene: TLK2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29861108; Phenotypes: Mental retardation, autosomal dominant 57 MIM#618050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2668 KMT2D Zornitza Stark Mode of inheritance for gene: KMT2D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2667 KMT2D Zornitza Stark reviewed gene: KMT2D: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Kabuki syndrome 1, MIM# 147920, KMT2D-associated neurodevelopmental syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.32 COG4 Zornitza Stark Marked gene: COG4 as ready
Skeletal dysplasia v0.32 COG4 Zornitza Stark Gene: cog4 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.32 COG4 Zornitza Stark Phenotypes for gene: COG4 were changed from Saul-Wilson syndrome, OMIM #618150; Congenital disorder of glycosylation, type IIj, OMIM #613489 to Saul-Wilson syndrome, OMIM #618150
Skeletal dysplasia v0.31 COG4 Zornitza Stark Mode of inheritance for gene: COG4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.31 COG4 Zornitza Stark Mode of inheritance for gene: COG4 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2667 COG4 Zornitza Stark Publications for gene: COG4 were set to
Intellectual disability syndromic and non-syndromic v0.2666 COG4 Zornitza Stark Mode of inheritance for gene: COG4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2665 COG4 Zornitza Stark Deleted their review
Intellectual disability syndromic and non-syndromic v0.2665 COG4 Zornitza Stark reviewed gene: COG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31949312, 30290151, 19494034, 21185756; Phenotypes: Saul-Wilson syndrome, OMIM #618150, Congenital disorder of glycosylation, type IIj, OMIM #613489; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3002 COG4 Zornitza Stark Marked gene: COG4 as ready
Mendeliome v0.3002 COG4 Zornitza Stark Gene: cog4 has been classified as Green List (High Evidence).
Mendeliome v0.3002 COG4 Zornitza Stark Phenotypes for gene: COG4 were changed from to Saul-Wilson syndrome, OMIM #618150; Congenital disorder of glycosylation, type IIj, OMIM #613489
Mendeliome v0.3001 COG4 Zornitza Stark Publications for gene: COG4 were set to
Mendeliome v0.3000 COG4 Zornitza Stark Mode of inheritance for gene: COG4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2999 COG4 Zornitza Stark reviewed gene: COG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31949312, 30290151, 19494034, 21185756; Phenotypes: Saul-Wilson syndrome, OMIM #618150, Congenital disorder of glycosylation, type IIj, OMIM #613489; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.53 COG4 Zornitza Stark Marked gene: COG4 as ready
Congenital Disorders of Glycosylation v0.53 COG4 Zornitza Stark Gene: cog4 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.53 COG4 Zornitza Stark Phenotypes for gene: COG4 were changed from to Congenital disorder of glycosylation, type IIj 613489
Congenital Disorders of Glycosylation v0.52 COG4 Zornitza Stark Publications for gene: COG4 were set to
Congenital Disorders of Glycosylation v0.51 COG4 Zornitza Stark Mode of inheritance for gene: COG4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.50 COG4 Zornitza Stark reviewed gene: COG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 21185756, 19494034; Phenotypes: Congenital disorder of glycosylation, type IIj 613489; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.143 COG4 Zornitza Stark Marked gene: COG4 as ready
Cataract v0.143 COG4 Zornitza Stark Gene: cog4 has been classified as Green List (High Evidence).
Cataract v0.143 COG4 Zornitza Stark Publications for gene: COG4 were set to Saul-Wilson syndrome, OMIM #618150; Congenital disorder of glycosylation, type IIj, OMIM #613489
Cataract v0.142 COG4 Zornitza Stark Phenotypes for gene: COG4 were changed from PMID: 31949312; 30290151 to Saul-Wilson syndrome, OMIM #618150; Congenital disorder of glycosylation, type IIj, OMIM #613489
Differences of Sex Development v0.30 NR2F2 Zornitza Stark Marked gene: NR2F2 as ready
Differences of Sex Development v0.30 NR2F2 Zornitza Stark Gene: nr2f2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.30 NR2F2 Zornitza Stark Classified gene: NR2F2 as Green List (high evidence)
Differences of Sex Development v0.30 NR2F2 Zornitza Stark Gene: nr2f2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.29 NR2F2 Zornitza Stark gene: NR2F2 was added
gene: NR2F2 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: NR2F2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NR2F2 were set to 29478779; 31687637
Phenotypes for gene: NR2F2 were set to 46,XX disorder of sex development (DSD) and congenital heart defects
Review for gene: NR2F2 was set to GREEN
Added comment: Four unrelated individuals reported. Note two had the same 7bp deletion, c.97_103delCCGCCCG, NM_021005.3, and the third individual had an adjacent deletion, c.103_109delGGCGCCC, NM_021005.3. All three were of very different ancestries, making founder effect unlikely. Fourth individual had a larger deletion encompassing this gene. Gene is also linked with isolated CHD (Congenital heart defects, multiple types, 4, MIM# 615779)
Sources: Expert list
Arthrogryposis v0.58 ADCY6 Chirag Patel Classified gene: ADCY6 as Green List (high evidence)
Arthrogryposis v0.58 ADCY6 Chirag Patel Gene: adcy6 has been classified as Green List (High Evidence).
Arthrogryposis v0.57 ADCY6 Chirag Patel Classified gene: ADCY6 as Green List (high evidence)
Arthrogryposis v0.57 ADCY6 Chirag Patel Gene: adcy6 has been classified as Green List (High Evidence).
Arthrogryposis v0.56 ADCY6 Chirag Patel gene: ADCY6 was added
gene: ADCY6 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: ADCY6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADCY6 were set to PMID: 24319099, 26257172, 31846058
Phenotypes for gene: ADCY6 were set to ?Lethal congenital contracture syndrome 8, OMIM # 616287
Review for gene: ADCY6 was set to GREEN
Added comment: Laquerriere et al. (2014): 2 sibs from a consanguineous family with an axoglial form of lethal congenital contracture syndrome, and homozygous missense ADCY6 mutation (R1116C). The parents were heterozygous for the mutation. Knocked down ADCY6 orthologs in zebrafish showed a loss of myelin basic protein expression in the peripheral nervous system but no defects in Schwann cell migration and axonal growth.

Gonzaga‐Jauregui et al. (2015): 1 patient with congenital hypotonia, distal joint contractures, hypomyelinating neuropathy, and vocal cord paralysis, and a homozygous missense ADCY6 variant. No functional studies. Deceased sister with a similar phenotype with hypotonia, areflexia, and hypomyelinating neuropathy who died at 18 months of respiratory insufficiency.

Agolini et al. (2020): 1 patient with severe form of AMC, with two novel compound heterozygous variants in ADCY6 (parents confirmed carriers), but no functional studies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2665 DSCR3 Chirag Patel gene: DSCR3 was added
gene: DSCR3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DSCR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DSCR3 were set to PMID: 31845315
Phenotypes for gene: DSCR3 were set to Intellectual disability, no OMIM # yet
Review for gene: DSCR3 was set to RED
Added comment: 1 family/2 cousins with cognitive impairment, growth failure, skeletal abnormalities, and distinctive facial features. Both shared the homozygous nonsense variant c.178G>T (p.Glu60*) in the VPS26C gene. This gene encodes VPS26C, a member of the retriever integral membrane protein recycling pathway. The nature of the variant which is predicted to result in loss‐of‐function, expression studies revealing significant reduction in the mutant transcript, and the co‐segregation of the homozygous variant with the phenotype in two affected individuals.
Sources: Literature
Oligodontia v0.5 LEF1 Chirag Patel gene: LEF1 was added
gene: LEF1 was added to Oligodontia. Sources: Literature
Mode of inheritance for gene: LEF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LEF1 were set to PMID: 32022899
Phenotypes for gene: LEF1 were set to Ectodermal dysplasia, no OMIM# yet
Review for gene: LEF1 was set to RED
Added comment: In mice, targeted inactivation of the LEF1 gene results in a complete block of development of multiple ectodermal appendages. One report of two unrelated patients with 4q25 de novo deletion encompassing LEF1 , associated with severe oligodontia of primary and permanent dentition, hypotrichosis and hypohidrosis compatible with hypohidrotic ectodermal dysplasia. So far, no pathogenic variants or variations involving the LEF1 gene have been reported in human.
Sources: Literature
Ectodermal Dysplasia v0.24 LEF1 Chirag Patel gene: LEF1 was added
gene: LEF1 was added to Ectodermal Dysplasia. Sources: Literature
Mode of inheritance for gene: LEF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LEF1 were set to PMID: 32022899
Phenotypes for gene: LEF1 were set to Ectodermal dysplasia, no OMIM# yet
Added comment: In mice, targeted inactivation of the LEF1 gene results in a complete block of development of multiple ectodermal appendages. One report of two unrelated patients with 4q25 de novo deletion encompassing LEF1 , associated with severe oligodontia of primary and permanent dentition, hypotrichosis and hypohidrosis compatible with hypohidrotic ectodermal dysplasia. So far, no pathogenic variants or variations involving the LEF1 gene have been reported in human.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2664 OTUD7A Chirag Patel gene: OTUD7A was added
gene: OTUD7A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: OTUD7A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OTUD7A were set to PMID: 31997314
Phenotypes for gene: OTUD7A were set to Epileptic encephalopathy, no OMIM# yet
Review for gene: OTUD7A was set to RED
Added comment: One patient with severe global developmental delay, language impairment and epileptic encephalopathy. Homozygous OTUD7A missense variant (c.697C>T, p.Leu233Phe), predicted to alter an ultraconserved amino acid, lying within the OTU catalytic domain. Its subsequent segregation analysis revealed that the parents, presenting with learning disability, and brother were heterozygous carriers. Biochemical assays demonstrated that proteasome complex formation and function were significantly reduced in patient‐derived fibroblasts and in OTUD7A knockout HAP1 cell line. We provide evidence that biallelic pathogenic OTUD7A variation is linked to early‐onset epileptic encephalopathy and proteasome dysfunction. Gene lies in the chromosome 15q13.3 region. Heterozygous microdeletions of chromosome 15q13.3 show incomplete penetrance and are associated with a highly variable phenotype that may include intellectual disability, epilepsy, facial dysmorphism and digit anomalies.
Sources: Literature
Genetic Epilepsy v0.714 OTUD7A Chirag Patel gene: OTUD7A was added
gene: OTUD7A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: OTUD7A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OTUD7A were set to PMID: 31997314
Phenotypes for gene: OTUD7A were set to Epileptic encephalopathy, no OMIM# yet
Review for gene: OTUD7A was set to RED
Added comment: One patient with severe global developmental delay, language impairment and epileptic encephalopathy. Homozygous OTUD7A missense variant (c.697C>T, p.Leu233Phe), predicted to alter an ultraconserved amino acid, lying within the OTU catalytic domain. Its subsequent segregation analysis revealed that the parents, presenting with learning disability, and brother were heterozygous carriers. Biochemical assays demonstrated that proteasome complex formation and function were significantly reduced in patient‐derived fibroblasts and in OTUD7A knockout HAP1 cell line. We provide evidence that biallelic pathogenic OTUD7A variation is linked to early‐onset epileptic encephalopathy and proteasome dysfunction. Gene lies in the chromosome 15q13.3 region. Heterozygous microdeletions of chromosome 15q13.3 show incomplete penetrance and are associated with a highly variable phenotype that may include intellectual disability, epilepsy, facial dysmorphism and digit anomalies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2663 GATAD2B Chirag Patel reviewed gene: GATAD2B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31949314; Phenotypes: Mental retardation, autosomal dominant 18, OMIM # 615074; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macrocephaly_Megalencephaly v0.33 GATAD2B Chirag Patel Classified gene: GATAD2B as Green List (high evidence)
Macrocephaly_Megalencephaly v0.33 GATAD2B Chirag Patel Gene: gatad2b has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.32 GATAD2B Chirag Patel gene: GATAD2B was added
gene: GATAD2B was added to Macrocephaly_Megalencephaly. Sources: Literature
Mode of inheritance for gene: GATAD2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GATAD2B were set to PMID: 31949314
Phenotypes for gene: GATAD2B were set to Mental retardation, autosomal dominant 18, OMIM # 615074
Review for gene: GATAD2B was set to GREEN
Added comment: 50 patients reported in series in 2020:
- loss-of-function and missense variants
- clinical features of hypotonia, intellectual disability, strabismus, cardiac defects, characteristic facies, childhood apraxia of speech, and macrocephaly.
Sources: Literature
Craniosynostosis v0.37 SLC25A24 Bryony Thompson Marked gene: SLC25A24 as ready
Craniosynostosis v0.37 SLC25A24 Bryony Thompson Gene: slc25a24 has been classified as Green List (High Evidence).
Craniosynostosis v0.37 SLC25A24 Bryony Thompson Phenotypes for gene: SLC25A24 were changed from to Fontaine progeroid syndrome MIM#612289
Craniosynostosis v0.36 SLC25A24 Bryony Thompson Publications for gene: SLC25A24 were set to
Craniosynostosis v0.35 SLC25A24 Bryony Thompson Mode of inheritance for gene: SLC25A24 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.34 SLC25A24 Bryony Thompson reviewed gene: SLC25A24: Rating: GREEN; Mode of pathogenicity: Other; Publications: 29100093; Phenotypes: Fontaine progeroid syndrome MIM#612289; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2663 KMT2D Chirag Patel changed review comment from: KMT2D missense variants located in a specific region spanning exons 38 and 39 and affecting highly conserved residues cause a novel multiple malformations syndrome distinct from Kabuki syndrome, through a dominant negative mechanism.; to: KMT2D missense variants located in a specific region spanning exons 38 and 39 and affecting highly conserved residues cause a novel multiple malformations syndrome distinct from Kabuki syndrome, through a dominant negative mechanism.
- 7 unrelated families with choanal atresia, athelia or hypoplastic nipples, branchial sinus abnormalities, neck pits, lacrimal duct anomalies, hearing loss, external ear malformations, and thyroid abnormalities. None of the individuals had intellectual disability.
Intellectual disability syndromic and non-syndromic v0.2663 KMT2D Chirag Patel reviewed gene: KMT2D: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31949313; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v0.30 COG4 Chirag Patel Classified gene: COG4 as Green List (high evidence)
Skeletal dysplasia v0.30 COG4 Chirag Patel Gene: cog4 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.29 COG4 Chirag Patel changed review comment from: Saul-Wilson syndrome (AD)
14 patients reported with DD, skeletal changes, cataracts, and growth retardation (progeriod like)
All have a recurrent de novo heterozygous missense variant (p.Gly516Arg)

Congenital disorder of glycosylation, type IIj (AR)
Sources: Literature; to: Saul-Wilson syndrome (AD)
14 patients reported with DD, skeletal dysplasia changes, cataracts, and growth retardation (progeriod like)
All have a recurrent de novo heterozygous missense variant (p.Gly516Arg)

Congenital disorder of glycosylation, type IIj (AR)
Sources: Literature
Skeletal dysplasia v0.29 COG4 Chirag Patel gene: COG4 was added
gene: COG4 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: COG4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COG4 were set to PMID: 31949312; 30290151
Phenotypes for gene: COG4 were set to Saul-Wilson syndrome, OMIM #618150; Congenital disorder of glycosylation, type IIj, OMIM #613489
Review for gene: COG4 was set to GREEN
Added comment: Saul-Wilson syndrome (AD)
14 patients reported with DD, skeletal changes, cataracts, and growth retardation (progeriod like)
All have a recurrent de novo heterozygous missense variant (p.Gly516Arg)

Congenital disorder of glycosylation, type IIj (AR)
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2663 COG4 Chirag Patel reviewed gene: COG4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31949312, 30290151; Phenotypes: Saul-Wilson syndrome, OMIM #618150, Congenital disorder of glycosylation, type IIj, OMIM #613489; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cataract v0.141 COG4 Chirag Patel Classified gene: COG4 as Green List (high evidence)
Cataract v0.141 COG4 Chirag Patel Gene: cog4 has been classified as Green List (High Evidence).
Cataract v0.140 COG4 Chirag Patel Classified gene: COG4 as Green List (high evidence)
Cataract v0.140 COG4 Chirag Patel Gene: cog4 has been classified as Green List (High Evidence).
Cataract v0.140 COG4 Chirag Patel Classified gene: COG4 as Green List (high evidence)
Cataract v0.140 COG4 Chirag Patel Gene: cog4 has been classified as Green List (High Evidence).
Cataract v0.140 COG4 Chirag Patel Classified gene: COG4 as Green List (high evidence)
Cataract v0.140 COG4 Chirag Patel Gene: cog4 has been classified as Green List (High Evidence).
Cataract v0.140 COG4 Chirag Patel Classified gene: COG4 as Green List (high evidence)
Cataract v0.140 COG4 Chirag Patel Gene: cog4 has been classified as Green List (High Evidence).
Cataract v0.139 COG4 Chirag Patel gene: COG4 was added
gene: COG4 was added to Cataract. Sources: Literature
Mode of inheritance for gene: COG4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COG4 were set to Saul-Wilson syndrome, OMIM #618150; Congenital disorder of glycosylation, type IIj, OMIM #613489
Phenotypes for gene: COG4 were set to PMID: 31949312; 30290151
Review for gene: COG4 was set to GREEN
Added comment: Saul-Wilson syndrome (AD)
14 patients reported with DD, skeletal changes, cataracts, and growth retardation (progeriod like)
All have a recurrent de novo heterozygous missense variant (p.Gly516Arg)

Congenital disorder of glycosylation, type IIj (AR)
Sources: Literature
Catecholaminergic Polymorphic Ventricular Tachycardia v0.26 TECRL Zornitza Stark Marked gene: TECRL as ready
Catecholaminergic Polymorphic Ventricular Tachycardia v0.26 TECRL Zornitza Stark Gene: tecrl has been classified as Green List (High Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.26 TECRL Zornitza Stark Phenotypes for gene: TECRL were changed from CPVT to Ventricular tachycardia, catecholaminergic polymorphic, 3, MIM# 614021
Catecholaminergic Polymorphic Ventricular Tachycardia v0.25 TECRL Zornitza Stark Classified gene: TECRL as Green List (high evidence)
Catecholaminergic Polymorphic Ventricular Tachycardia v0.25 TECRL Zornitza Stark Gene: tecrl has been classified as Green List (High Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.24 CALM1 Zornitza Stark Marked gene: CALM1 as ready
Catecholaminergic Polymorphic Ventricular Tachycardia v0.24 CALM1 Zornitza Stark Gene: calm1 has been classified as Green List (High Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.24 CALM1 Zornitza Stark Phenotypes for gene: CALM1 were changed from to Long QT syndrome 14 616247; Ventricular tachycardia, catecholaminergic polymorphic, 4 614916
Catecholaminergic Polymorphic Ventricular Tachycardia v0.23 CALM1 Zornitza Stark Publications for gene: CALM1 were set to
Catecholaminergic Polymorphic Ventricular Tachycardia v0.22 CALM1 Zornitza Stark Mode of inheritance for gene: CALM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Catecholaminergic Polymorphic Ventricular Tachycardia v0.21 CALM2 Zornitza Stark Marked gene: CALM2 as ready
Catecholaminergic Polymorphic Ventricular Tachycardia v0.21 CALM2 Zornitza Stark Gene: calm2 has been classified as Green List (High Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.21 CALM2 Zornitza Stark Phenotypes for gene: CALM2 were changed from to Long QT syndrome 15 616249; sudden unexplained death; idopathic VF
Catecholaminergic Polymorphic Ventricular Tachycardia v0.20 CALM2 Zornitza Stark Publications for gene: CALM2 were set to
Catecholaminergic Polymorphic Ventricular Tachycardia v0.19 CALM3 Zornitza Stark Publications for gene: CALM3 were set to 27516456
Catecholaminergic Polymorphic Ventricular Tachycardia v0.18 CALM3 Zornitza Stark Classified gene: CALM3 as Amber List (moderate evidence)
Catecholaminergic Polymorphic Ventricular Tachycardia v0.18 CALM3 Zornitza Stark Gene: calm3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2663 ARL13B Zornitza Stark Marked gene: ARL13B as ready
Intellectual disability syndromic and non-syndromic v0.2663 ARL13B Zornitza Stark Gene: arl13b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2663 ARL13B Zornitza Stark Phenotypes for gene: ARL13B were changed from to Joubert syndrome 8, MIM# 612291
Intellectual disability syndromic and non-syndromic v0.2662 ARL13B Zornitza Stark Publications for gene: ARL13B were set to
Intellectual disability syndromic and non-syndromic v0.2661 ARL13B Zornitza Stark Mode of inheritance for gene: ARL13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2660 ARL13B Zornitza Stark reviewed gene: ARL13B: Rating: GREEN; Mode of pathogenicity: None; Publications: 18674751, 25138100, 26092869, 27894351, 29255182, 17488627; Phenotypes: Joubert syndrome 8, MIM# 612291; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.118 ARL13B Zornitza Stark Marked gene: ARL13B as ready
Regression v0.118 ARL13B Zornitza Stark Gene: arl13b has been classified as Red List (Low Evidence).
Regression v0.118 ARL13B Zornitza Stark Phenotypes for gene: ARL13B were changed from to Joubert syndrome 8, MIM# 612291
Regression v0.117 ARL13B Zornitza Stark Classified gene: ARL13B as Red List (low evidence)
Regression v0.117 ARL13B Zornitza Stark Gene: arl13b has been classified as Red List (Low Evidence).
Regression v0.116 ARL13B Zornitza Stark reviewed gene: ARL13B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Joubert syndrome 8, MIM# 612291; Mode of inheritance: None
Renal Ciliopathies and Nephronophthisis v0.106 ARL13B Zornitza Stark Marked gene: ARL13B as ready
Renal Ciliopathies and Nephronophthisis v0.106 ARL13B Zornitza Stark Gene: arl13b has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.106 ARL13B Zornitza Stark Phenotypes for gene: ARL13B were changed from to Joubert syndrome 8, MIM# 612291
Renal Ciliopathies and Nephronophthisis v0.105 ARL13B Zornitza Stark Publications for gene: ARL13B were set to
Renal Ciliopathies and Nephronophthisis v0.104 ARL13B Zornitza Stark Mode of inheritance for gene: ARL13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.103 ARL13B Zornitza Stark reviewed gene: ARL13B: Rating: GREEN; Mode of pathogenicity: None; Publications: 18674751, 25138100, 26092869, 27894351, 29255182, 17488627; Phenotypes: Joubert syndrome 8, MIM# 612291; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2999 ARL13B Zornitza Stark Marked gene: ARL13B as ready
Mendeliome v0.2999 ARL13B Zornitza Stark Gene: arl13b has been classified as Green List (High Evidence).
Mendeliome v0.2999 ARL13B Zornitza Stark Phenotypes for gene: ARL13B were changed from to Joubert syndrome 8, MIM# 612291
Mendeliome v0.2998 ARL13B Zornitza Stark Publications for gene: ARL13B were set to
Mendeliome v0.2997 ARL13B Zornitza Stark Mode of inheritance for gene: ARL13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2996 ARL13B Zornitza Stark Deleted their comment
Mendeliome v0.2996 ARL13B Zornitza Stark edited their review of gene: ARL13B: Added comment: Eight families reported in the literature. Many are homozygous missense variants in consanguineous families with no further supporting evidence, but sufficient number have functional evidence at protein level. Gene has appropriate tissue expression. Zebrafish model: curved tails and cystic kidneys. Hennin mouse model discovered in ENU mutagenesis screen: has polydactyly, ciliary defect, and much more severe neurological phenotype (neural tube defect).; Changed publications: 18674751, 25138100, 26092869, 27894351, 29255182, 17488627
Ciliopathies v0.190 ARL13B Zornitza Stark Marked gene: ARL13B as ready
Ciliopathies v0.190 ARL13B Zornitza Stark Gene: arl13b has been classified as Green List (High Evidence).
Ciliopathies v0.190 ARL13B Zornitza Stark Phenotypes for gene: ARL13B were changed from to Joubert syndrome 8, MIM# 612291
Ciliopathies v0.189 ARL13B Zornitza Stark Publications for gene: ARL13B were set to
Ciliopathies v0.188 ARL13B Zornitza Stark Mode of inheritance for gene: ARL13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.187 ARL13B Zornitza Stark reviewed gene: ARL13B: Rating: GREEN; Mode of pathogenicity: None; Publications: 18674751, 25138100, 26092869, 27894351, 29255182, 17488627; Phenotypes: Joubert syndrome 8, MIM# 612291; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.83 CENPF Zornitza Stark Marked gene: CENPF as ready
Joubert syndrome and other neurological ciliopathies v0.83 CENPF Zornitza Stark Gene: cenpf has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.83 CENPF Zornitza Stark Classified gene: CENPF as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.83 CENPF Zornitza Stark Gene: cenpf has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.82 ARL13B Zornitza Stark Marked gene: ARL13B as ready
Joubert syndrome and other neurological ciliopathies v0.82 ARL13B Zornitza Stark Gene: arl13b has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.82 ARL13B Zornitza Stark Phenotypes for gene: ARL13B were changed from to Joubert syndrome 8, MIM# 612291
Joubert syndrome and other neurological ciliopathies v0.81 ARL13B Zornitza Stark Publications for gene: ARL13B were set to
Joubert syndrome and other neurological ciliopathies v0.80 ARL13B Zornitza Stark Mode of inheritance for gene: ARL13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.79 ARL13B Zornitza Stark reviewed gene: ARL13B: Rating: GREEN; Mode of pathogenicity: None; Publications: 18674751, 25138100, 26092869, 27894351, 29255182, 17488627; Phenotypes: Joubert syndrome 8, MIM# 612291; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.34 RAB23 Tiong Tan Marked gene: RAB23 as ready
Craniosynostosis v0.34 RAB23 Tiong Tan Gene: rab23 has been classified as Green List (High Evidence).
Craniosynostosis v0.34 RAB23 Tiong Tan Classified gene: RAB23 as Green List (high evidence)
Craniosynostosis v0.34 RAB23 Tiong Tan Gene: rab23 has been classified as Green List (High Evidence).
Craniosynostosis v0.33 RAB23 Tiong Tan gene: RAB23 was added
gene: RAB23 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: RAB23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB23 were set to 17503333
Phenotypes for gene: RAB23 were set to 201000 CARPENTER SYNDROME
Penetrance for gene: RAB23 were set to Complete
Review for gene: RAB23 was set to GREEN
Added comment: Craniosynostosis is an established feature of Carpenter syndrome
Sources: Literature
Craniosynostosis v0.32 HNRNPK Tiong Tan Marked gene: HNRNPK as ready
Craniosynostosis v0.32 HNRNPK Tiong Tan Gene: hnrnpk has been classified as Green List (High Evidence).
Craniosynostosis v0.32 HNRNPK Tiong Tan Classified gene: HNRNPK as Green List (high evidence)
Craniosynostosis v0.32 HNRNPK Tiong Tan Added comment: Comment on list classification: Amazing reviewer
Craniosynostosis v0.32 HNRNPK Tiong Tan Gene: hnrnpk has been classified as Green List (High Evidence).
Craniosynostosis v0.31 HNRNPK Tiong Tan gene: HNRNPK was added
gene: HNRNPK was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: HNRNPK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPK were set to 26173930; 26954065; 29904177
Phenotypes for gene: HNRNPK were set to Au-Kline syndrome
Penetrance for gene: HNRNPK were set to Complete
Review for gene: HNRNPK was set to GREEN
Added comment: Multiple unrelated individuals with Au-Kline (approx 1/3 have craniosynostosis - sagittal, metric, lambdoid)
Sources: Literature
Craniosynostosis v0.30 ESCO2 Tiong Tan Marked gene: ESCO2 as ready
Craniosynostosis v0.30 ESCO2 Tiong Tan Gene: esco2 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.30 ESCO2 Tiong Tan Classified gene: ESCO2 as Amber List (moderate evidence)
Craniosynostosis v0.30 ESCO2 Tiong Tan Gene: esco2 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.29 ESCO2 Tiong Tan gene: ESCO2 was added
gene: ESCO2 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: ESCO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESCO2 were set to 31192177
Phenotypes for gene: ESCO2 were set to 268300 ROBERTS SYNDROME
Penetrance for gene: ESCO2 were set to Complete
Review for gene: ESCO2 was set to AMBER
Added comment: Two unrelated individuals with Roberts syndrome and craniosynostosis
Sources: Literature
Craniosynostosis v0.28 EFNA4 Tiong Tan Marked gene: EFNA4 as ready
Craniosynostosis v0.28 EFNA4 Tiong Tan Gene: efna4 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.28 EFNA4 Tiong Tan Classified gene: EFNA4 as Amber List (moderate evidence)
Craniosynostosis v0.28 EFNA4 Tiong Tan Gene: efna4 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.27 EFNA4 Tiong Tan reviewed gene: EFNA4: Rating: AMBER; Mode of pathogenicity: None; Publications: 29168297, 29215649; Phenotypes: Coronal and metopic craniosynostosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.27 DPH1 Tiong Tan Marked gene: DPH1 as ready
Craniosynostosis v0.27 DPH1 Tiong Tan Gene: dph1 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.27 DPH1 Tiong Tan Classified gene: DPH1 as Amber List (moderate evidence)
Craniosynostosis v0.27 DPH1 Tiong Tan Added comment: Comment on list classification: I agree!
Craniosynostosis v0.27 DPH1 Tiong Tan Gene: dph1 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.26 DPH1 Tiong Tan gene: DPH1 was added
gene: DPH1 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: DPH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPH1 were set to 25558065; 26220823
Phenotypes for gene: DPH1 were set to 616901 DEVELOPMENTAL DELAY WITH SHORT STATURE, DYSMORPHIC FACIAL FEATURES, AND SPARSE HAIR
Penetrance for gene: DPH1 were set to Complete
Review for gene: DPH1 was set to AMBER
Added comment: Multiple sibs from two unrelated families with DEDSSH syndrome, of which craniosynostosis was a component in some affected individuals.
Sources: Literature
Craniosynostosis v0.25 CYP26B1 Tiong Tan Marked gene: CYP26B1 as ready
Craniosynostosis v0.25 CYP26B1 Tiong Tan Gene: cyp26b1 has been classified as Green List (High Evidence).
Craniosynostosis v0.25 CYP26B1 Tiong Tan Classified gene: CYP26B1 as Green List (high evidence)
Craniosynostosis v0.25 CYP26B1 Tiong Tan Gene: cyp26b1 has been classified as Green List (High Evidence).
Craniosynostosis v0.24 CYP26B1 Tiong Tan gene: CYP26B1 was added
gene: CYP26B1 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: CYP26B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP26B1 were set to 27410456; 22019272
Phenotypes for gene: CYP26B1 were set to 614416 RADIOHUMERAL FUSIONS WITH OTHER SKELETAL AND CRANIOFACIAL ANOMALIES
Penetrance for gene: CYP26B1 were set to Complete
Review for gene: CYP26B1 was set to GREEN
Added comment: Three unrelated families in two publications, the first of which also demonstrated robust functional work in murine embryos, zebrafish and in vitro assays suggesting aberrant osteoblast-osteocyte transition.
Sources: Literature
Craniosynostosis v0.23 COLEC11 Tiong Tan Marked gene: COLEC11 as ready
Craniosynostosis v0.23 COLEC11 Tiong Tan Gene: colec11 has been classified as Green List (High Evidence).
Craniosynostosis v0.23 COLEC11 Tiong Tan Classified gene: COLEC11 as Green List (high evidence)
Craniosynostosis v0.23 COLEC11 Tiong Tan Gene: colec11 has been classified as Green List (High Evidence).
Craniosynostosis v0.22 COLEC11 Tiong Tan gene: COLEC11 was added
gene: COLEC11 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: COLEC11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COLEC11 were set to 21258343
Phenotypes for gene: COLEC11 were set to 265050 3MC SYNDROME 2
Penetrance for gene: COLEC11 were set to Complete
Review for gene: COLEC11 was set to GREEN
Added comment: Craniosynostosis occurs in 20-30% of individuals with 3MC syndrome
Sources: Literature
Craniosynostosis v0.21 CHST3 Tiong Tan edited their review of gene: CHST3: Changed rating: RED
Craniosynostosis v0.21 CHST3 Tiong Tan Classified gene: CHST3 as Red List (low evidence)
Craniosynostosis v0.21 CHST3 Tiong Tan Gene: chst3 has been classified as Red List (Low Evidence).
Craniosynostosis v0.20 CHST3 Tiong Tan Marked gene: CHST3 as ready
Craniosynostosis v0.20 CHST3 Tiong Tan Gene: chst3 has been classified as Red List (Low Evidence).
Craniosynostosis v0.20 CHST3 Tiong Tan gene: CHST3 was added
gene: CHST3 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: CHST3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHST3 were set to 24300290
Phenotypes for gene: CHST3 were set to 143095 SPONDYLOEPIPHYSEAL DYSPLASIA WITH CONGENITAL JOINT DISLOCATIONS
Penetrance for gene: CHST3 were set to Complete
Review for gene: CHST3 was set to AMBER
Added comment: Single case report of craniosynostosis in single individual with SEDCJD
Sources: Literature
Catecholaminergic Polymorphic Ventricular Tachycardia v0.17 TECRL Ivan Macciocca gene: TECRL was added
gene: TECRL was added to Catecholaminergic Polymorphic Ventricular Tachycardia. Sources: Literature
Mode of inheritance for gene: TECRL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TECRL were set to 17666061; 27861123; 30790670
Phenotypes for gene: TECRL were set to CPVT
Penetrance for gene: TECRL were set to Complete
Review for gene: TECRL was set to GREEN
Added comment: As at 03/06/2020, not assessed by ClinGen for association with CPVT; and is associated with CPVT3 in OMIM. Amber on GEL PanelApp
Homozygous or cpd heterozygous pathogenic variants in TECRL have been identified in patients with CPVT in at least 3 families in the literature with functional evidence.
- 17666061 one consanguineous family with 4 affected relatives (siblings or 1stcousins)
- 27861123 consanguineous family with 8 affected relatives (siblings or 1stcousins)
- 30790670 reported in a single family with one child with features of CPVT
This gene meets criteria for green.
Sources: Literature
Craniosynostosis v0.19 B3GAT3 Tiong Tan Classified gene: B3GAT3 as Green List (high evidence)
Craniosynostosis v0.19 B3GAT3 Tiong Tan Gene: b3gat3 has been classified as Green List (High Evidence).
Craniosynostosis v0.18 B3GAT3 Tiong Tan Marked gene: B3GAT3 as ready
Craniosynostosis v0.18 B3GAT3 Tiong Tan Gene: b3gat3 has been classified as Red List (Low Evidence).
Craniosynostosis v0.18 B3GAT3 Tiong Tan gene: B3GAT3 was added
gene: B3GAT3 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: B3GAT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B3GAT3 were set to 31438591
Phenotypes for gene: B3GAT3 were set to 245600 MULTIPLE JOINT DISLOCATIONS, SHORT STATURE, AND CRANIOFACIAL DYSMORPHISM WITH OR WITHOUT CONGENITAL HEART DEFECTS
Penetrance for gene: B3GAT3 were set to Complete
Review for gene: B3GAT3 was set to GREEN
Added comment: Craniosynostosis is a feature of B3GAT3-related joint dislocations. Reported in multiple unrelated individuals and summarised in PMID 31438591 (2019)
Sources: Literature
Craniosynostosis v0.17 ALPL Tiong Tan Classified gene: ALPL as Green List (high evidence)
Craniosynostosis v0.17 ALPL Tiong Tan Added comment: Comment on list classification: Known manifestation of hypophosphatasia. Can precede other features
Craniosynostosis v0.17 ALPL Tiong Tan Gene: alpl has been classified as Green List (High Evidence).
Craniosynostosis v0.17 ALPL Tiong Tan Classified gene: ALPL as Red List (low evidence)
Craniosynostosis v0.17 ALPL Tiong Tan Added comment: Comment on list classification: Known manifestation of hypophosphatasia. Can precede other features
Craniosynostosis v0.17 ALPL Tiong Tan Gene: alpl has been classified as Red List (Low Evidence).
Craniosynostosis v0.16 ALPL Tiong Tan Classified gene: ALPL as Green List (high evidence)
Craniosynostosis v0.16 ALPL Tiong Tan Added comment: Comment on list classification: Known manifestation of hypophosphatasia; can precede other features
Craniosynostosis v0.16 ALPL Tiong Tan Gene: alpl has been classified as Green List (High Evidence).
Craniosynostosis v0.15 ALPL Tiong Tan Marked gene: ALPL as ready
Craniosynostosis v0.15 ALPL Tiong Tan Gene: alpl has been classified as Red List (Low Evidence).
Craniosynostosis v0.15 ALPL Tiong Tan gene: ALPL was added
gene: ALPL was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: ALPL was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ALPL were set to 29405940; 26590809; 30979546; 31754721
Phenotypes for gene: ALPL were set to 241500 HYPOPHOSPHATASIA, INFANTILE
Penetrance for gene: ALPL were set to unknown
Review for gene: ALPL was set to GREEN
Added comment: Sources: Literature
Catecholaminergic Polymorphic Ventricular Tachycardia v0.17 TRDN Ivan Macciocca reviewed gene: TRDN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30649896, 25922419, 22422768; Phenotypes: triadin knockout syndrome, LQTS, CPVT; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.55 ZC4H2 Zornitza Stark Marked gene: ZC4H2 as ready
Arthrogryposis v0.55 ZC4H2 Zornitza Stark Gene: zc4h2 has been classified as Green List (High Evidence).
Arthrogryposis v0.55 ZC4H2 Zornitza Stark Phenotypes for gene: ZC4H2 were changed from to Wieacker-Wolff syndrome (MIM#314580)
Arthrogryposis v0.54 ZC4H2 Zornitza Stark Publications for gene: ZC4H2 were set to
Arthrogryposis v0.53 ZC4H2 Zornitza Stark Mode of inheritance for gene: ZC4H2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Catecholaminergic Polymorphic Ventricular Tachycardia v0.17 CASQ2 Zornitza Stark Marked gene: CASQ2 as ready
Catecholaminergic Polymorphic Ventricular Tachycardia v0.17 CASQ2 Zornitza Stark Gene: casq2 has been classified as Green List (High Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.17 CASQ2 Zornitza Stark Phenotypes for gene: CASQ2 were changed from to Ventricular tachycardia, catecholaminergic polymorphic, 2, MIM# 611938
Catecholaminergic Polymorphic Ventricular Tachycardia v0.16 CASQ2 Zornitza Stark Publications for gene: CASQ2 were set to
Catecholaminergic Polymorphic Ventricular Tachycardia v0.15 CASQ2 Zornitza Stark Mode of inheritance for gene: CASQ2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Catecholaminergic Polymorphic Ventricular Tachycardia v0.14 KCNJ2 Zornitza Stark Marked gene: KCNJ2 as ready
Catecholaminergic Polymorphic Ventricular Tachycardia v0.14 KCNJ2 Zornitza Stark Gene: kcnj2 has been classified as Amber List (Moderate Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.14 KCNJ2 Zornitza Stark Phenotypes for gene: KCNJ2 were changed from to Andersen Tawil syndrome, LQTS
Catecholaminergic Polymorphic Ventricular Tachycardia v0.13 KCNJ2 Zornitza Stark Publications for gene: KCNJ2 were set to