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Prepair 1000+ v1.1097 CYP4F22 Zornitza Stark Phenotypes for gene: CYP4F22 were changed from Ichthyosis, congenital, autosomal recessive 5, 604777 (3) to Ichthyosis, congenital, autosomal recessive 5, MIM#604777
Prepair 1000+ v1.1096 DGKE Zornitza Stark Marked gene: DGKE as ready
Prepair 1000+ v1.1096 DGKE Zornitza Stark Gene: dgke has been classified as Green List (High Evidence).
Prepair 1000+ v1.1096 DGKE Zornitza Stark Phenotypes for gene: DGKE were changed from Nephrotic syndrome, type 7, 615008 (3) to Nephrotic syndrome, type 7, MIM# 615008
Prepair 1000+ v1.1095 DGKE Zornitza Stark Publications for gene: DGKE were set to
Prepair 1000+ v1.1094 DGUOK Zornitza Stark Marked gene: DGUOK as ready
Prepair 1000+ v1.1094 DGUOK Zornitza Stark Gene: dguok has been classified as Green List (High Evidence).
Prepair 1000+ v1.1094 DGUOK Zornitza Stark Phenotypes for gene: DGUOK were changed from Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), 251880 (3) to Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), MIM#251880
Prepair 1000+ v1.1093 DGUOK Zornitza Stark Publications for gene: DGUOK were set to
Prepair 1000+ v1.1092 COL7A1 Zornitza Stark Marked gene: COL7A1 as ready
Prepair 1000+ v1.1092 COL7A1 Zornitza Stark Gene: col7a1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1092 COL7A1 Zornitza Stark Phenotypes for gene: COL7A1 were changed from Epidermolysis bullosa dystrophica, AR, 226600 (3) to Epidermolysis bullosa dystrophica, MIM#226600
Prepair 1000+ v1.1091 COL7A1 Zornitza Stark Publications for gene: COL7A1 were set to
Prepair 1000+ v1.1090 IL12RB1 Zornitza Stark Marked gene: IL12RB1 as ready
Prepair 1000+ v1.1090 IL12RB1 Zornitza Stark Gene: il12rb1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1090 IL12RB1 Zornitza Stark Phenotypes for gene: IL12RB1 were changed from Immunodeficiency 30, 614891 (3) to Immunodeficiency 30, MIM#614891
Prepair 1000+ v1.1089 IL12RB1 Zornitza Stark Publications for gene: IL12RB1 were set to
Prepair 1000+ v1.1088 IL12RB1 Zornitza Stark reviewed gene: IL12RB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 30, MIM# 614891; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1088 DARS Zornitza Stark Marked gene: DARS as ready
Prepair 1000+ v1.1088 DARS Zornitza Stark Gene: dars has been classified as Green List (High Evidence).
Prepair 1000+ v1.1088 DARS Zornitza Stark Publications for gene: DARS were set to
Prepair 1000+ v1.1087 DCHS1 Zornitza Stark Marked gene: DCHS1 as ready
Prepair 1000+ v1.1087 DCHS1 Zornitza Stark Gene: dchs1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1087 DCHS1 Zornitza Stark Publications for gene: DCHS1 were set to
Dyslipidaemia v0.42 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Prepair 1000+ v1.1086 DDX11 Zornitza Stark Marked gene: DDX11 as ready
Prepair 1000+ v1.1086 DDX11 Zornitza Stark Gene: ddx11 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1086 DDX11 Zornitza Stark Phenotypes for gene: DDX11 were changed from Warsaw breakage syndrome, 613398 (3) to Warsaw breakage syndrome, MIM#613398
Prepair 1000+ v1.1085 DDX11 Zornitza Stark Publications for gene: DDX11 were set to
Prepair 1000+ v1.1084 ISCA1 Zornitza Stark Tag for review tag was added to gene: ISCA1.
Prepair 1000+ v1.1084 SCARB2 Zornitza Stark Marked gene: SCARB2 as ready
Prepair 1000+ v1.1084 SCARB2 Zornitza Stark Gene: scarb2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1084 SCARB2 Zornitza Stark Phenotypes for gene: SCARB2 were changed from Epilepsy, progressive myoclonic 4, with or without renal failure, 254900 (3) to Epilepsy, progressive myoclonic 4, with or without renal failure, MIM#254900
Prepair 1000+ v1.1083 SCARB2 Zornitza Stark Publications for gene: SCARB2 were set to
Prepair 1000+ v1.1082 DNAI2 Zornitza Stark Marked gene: DNAI2 as ready
Prepair 1000+ v1.1082 DNAI2 Zornitza Stark Gene: dnai2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1082 DNAI2 Zornitza Stark Phenotypes for gene: DNAI2 were changed from Ciliary dyskinesia, primary, 9, with or without situs inversus, 612444 (3) to Ciliary dyskinesia, primary, 9, with or without situs inversus, MIM#612444
Prepair 1000+ v1.1081 DNAI2 Zornitza Stark Publications for gene: DNAI2 were set to
Prepair 1000+ v1.1080 DNAI2 Zornitza Stark reviewed gene: DNAI2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 9, with or without situs inversus, MIM# 612444; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1080 EIF2B1 Zornitza Stark Marked gene: EIF2B1 as ready
Prepair 1000+ v1.1080 EIF2B1 Zornitza Stark Gene: eif2b1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1080 EIF2B1 Zornitza Stark Phenotypes for gene: EIF2B1 were changed from Leukoencephalopathy with vanishing white matter, 603896 (3) to Leukoencephalopathy with vanishing white matter 1, with or without ovarian failure MIM#603896
Prepair 1000+ v1.1079 EIF2B1 Zornitza Stark Publications for gene: EIF2B1 were set to
Prepair 1000+ v1.1078 ITPR1 Zornitza Stark Marked gene: ITPR1 as ready
Prepair 1000+ v1.1078 ITPR1 Zornitza Stark Gene: itpr1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1078 ITPR1 Zornitza Stark Phenotypes for gene: ITPR1 were changed from Gillespie syndrome, 206700 (3), Autosomal recessive to Gillespie syndrome, MIM#206700
Prepair 1000+ v1.1077 ITPR1 Zornitza Stark Publications for gene: ITPR1 were set to
Prepair 1000+ v1.1076 DPAGT1 Zornitza Stark Marked gene: DPAGT1 as ready
Prepair 1000+ v1.1076 DPAGT1 Zornitza Stark Gene: dpagt1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1076 DPAGT1 Zornitza Stark Phenotypes for gene: DPAGT1 were changed from Myasthenic syndrome, congenital, 13, with tubular aggregates, 614750 (3) to Congenital disorder of glycosylation, type Ij, MIM# 608093; DPAGT1-CDG MONDO:0011964; Myasthenic syndrome, congenital, 13, with tubular aggregates, MIM 614750
Prepair 1000+ v1.1075 DPAGT1 Zornitza Stark Publications for gene: DPAGT1 were set to
Prepair 1000+ v1.1074 SUMF1 Zornitza Stark Marked gene: SUMF1 as ready
Prepair 1000+ v1.1074 SUMF1 Zornitza Stark Gene: sumf1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1074 SUMF1 Zornitza Stark Phenotypes for gene: SUMF1 were changed from Multiple sulfatase deficiency, 272200 (3) to Multiple sulfatase deficiency, MIM#272200
Prepair 1000+ v1.1073 SUMF1 Zornitza Stark Publications for gene: SUMF1 were set to
Prepair 1000+ v1.1072 TAZ Zornitza Stark Marked gene: TAZ as ready
Prepair 1000+ v1.1072 TAZ Zornitza Stark Gene: taz has been classified as Green List (High Evidence).
Prepair 1000+ v1.1072 TAZ Zornitza Stark Phenotypes for gene: TAZ were changed from Barth syndrome, 302060 (3) to Barth syndrome (MIM# 302060)
Prepair 1000+ v1.1071 TAZ Zornitza Stark Publications for gene: TAZ were set to
Prepair 1000+ v1.1070 ENPP1 Zornitza Stark Marked gene: ENPP1 as ready
Prepair 1000+ v1.1070 ENPP1 Zornitza Stark Gene: enpp1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1070 ENPP1 Zornitza Stark Phenotypes for gene: ENPP1 were changed from Hypophosphatemic rickets, autosomal recessive, 2, 613312 (3) to Arterial calcification, generalized, of infancy, 1 MIM#208000; Hypophosphatemic rickets, autosomal recessive, 2 MIM#613312
Prepair 1000+ v1.1069 ENPP1 Zornitza Stark Publications for gene: ENPP1 were set to
Prepair 1000+ v1.1068 EDAR Zornitza Stark Marked gene: EDAR as ready
Prepair 1000+ v1.1068 EDAR Zornitza Stark Gene: edar has been classified as Green List (High Evidence).
Prepair 1000+ v1.1068 EDAR Zornitza Stark Phenotypes for gene: EDAR were changed from Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive, 224900 (3) to autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619
Prepair 1000+ v1.1067 EDAR Zornitza Stark Publications for gene: EDAR were set to
Prepair 1000+ v1.1066 EIF2S3 Zornitza Stark Marked gene: EIF2S3 as ready
Prepair 1000+ v1.1066 EIF2S3 Zornitza Stark Gene: eif2s3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1066 EIF2S3 Zornitza Stark Phenotypes for gene: EIF2S3 were changed from MEHMO syndrome, 300148 (3), X-linked recessive to MEHMO syndrome, MIM# 300148
Prepair 1000+ v1.1065 EIF2S3 Zornitza Stark Publications for gene: EIF2S3 were set to
Genetic Epilepsy v1.101 TRPM7 Zornitza Stark Marked gene: TRPM7 as ready
Genetic Epilepsy v1.101 TRPM7 Zornitza Stark Gene: trpm7 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.101 TRPM7 Zornitza Stark Classified gene: TRPM7 as Green List (high evidence)
Genetic Epilepsy v1.101 TRPM7 Zornitza Stark Gene: trpm7 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.100 TRPM7 Zornitza Stark Classified gene: TRPM7 as Green List (high evidence)
Genetic Epilepsy v1.100 TRPM7 Zornitza Stark Gene: trpm7 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.99 TRPM7 Zornitza Stark gene: TRPM7 was added
gene: TRPM7 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TRPM7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPM7 were set to 35561741; 35712613; 39099563; 37188671
Phenotypes for gene: TRPM7 were set to Familial primary hypomagnesaemia, MONDO:0018100, TRPM7-related
Review for gene: TRPM7 was set to GREEN
Added comment: Protein expressed in the distal tubule, related to TRPM6. Postulated link with hypoMg with secondary hypoCa.
PMID 35561741: two families reported with dominant inheritance. F1: three affected individuals with splicing variant; some supportive functional data. F2: single affected individual, de novo missense variant.
PMID 35712613: de novo missense variant in an individual with hypoMg.
PMID 39099563: three affected individuals with missense variants, all de novo. Probands had DD, two had seizures.
PMID 37188671: mouse model investigating role in HypoMg and seizure-related death.
Sources: Literature
Renal Tubulopathies and related disorders v1.17 TRPM7 Zornitza Stark Deleted their comment
Renal Tubulopathies and related disorders v1.17 TRPM7 Zornitza Stark edited their review of gene: TRPM7: Added comment: PMID 37188671: mouse model investigating role in HypoMg and seizure-related death.; Changed publications: 35561741, 35712613, 39099563, 37188671
Intellectual disability syndromic and non-syndromic v1.49 TRPM7 Zornitza Stark Marked gene: TRPM7 as ready
Intellectual disability syndromic and non-syndromic v1.49 TRPM7 Zornitza Stark Gene: trpm7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.49 TRPM7 Zornitza Stark Phenotypes for gene: TRPM7 were changed from Familial primary hypomagnesemia, MONDO:0018100, TRPM7-related to Familial primary hypomagnesaemia, MONDO:0018100, TRPM7-related
Intellectual disability syndromic and non-syndromic v1.48 TRPM7 Zornitza Stark Classified gene: TRPM7 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.48 TRPM7 Zornitza Stark Gene: trpm7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.47 TRPM7 Zornitza Stark gene: TRPM7 was added
gene: TRPM7 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TRPM7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPM7 were set to 35561741; 35712613; 39099563
Phenotypes for gene: TRPM7 were set to Familial primary hypomagnesemia, MONDO:0018100, TRPM7-related
Review for gene: TRPM7 was set to GREEN
Added comment: Protein expressed in the distal tubule, related to TRPM6. Postulated link with hypoMg with secondary hypoCa.
PMID 35561741: two families reported with dominant inheritance. F1: three affected individuals with splicing variant; some supportive functional data. F2: single affected individual, de novo missense variant.
PMID 35712613: de novo missense variant in an individual with hypoMg.
PMID 39099563: three affected individuals with missense variants, all de novo. Probands had DD, two had seizures.
Sources: Literature
Mendeliome v1.2264 TRPM7 Zornitza Stark Classified gene: TRPM7 as Green List (high evidence)
Mendeliome v1.2264 TRPM7 Zornitza Stark Gene: trpm7 has been classified as Green List (High Evidence).
Mendeliome v1.2263 TRPM7 Zornitza Stark changed review comment from: Protein expressed in the distal tubule, related to TRPM6. Postulated link with hypoMg with secondary hypoCa. PMID 35561741: two families reported with dominant inheritance. F1: three affected individuals with splicing variant; some supportive functional data. F2: single affected individual, de novo missense variant. PMID 35712613: de novo missense variant in an individual with hypoMg. PMID 39099563: three affected individuals with missense variants, all de novo. Probands had DD, two had seizures.; to: Protein expressed in the distal tubule, related to TRPM6. Postulated link with hypoMg with secondary hypoCa. PMID 35561741: two families reported with dominant inheritance. F1: three affected individuals with splicing variant; some supportive functional data. F2: single affected individual, de novo missense variant. PMID 35712613: de novo missense variant in an individual with hypoMg. PMID 39099563: three affected individuals with missense variants, all de novo. Probands had DD, two had seizures.

Overall, Green for association with HypoMg.

Red for ALS and stillbirth.
Mendeliome v1.2263 TRPM7 Zornitza Stark edited their review of gene: TRPM7: Added comment: Protein expressed in the distal tubule, related to TRPM6. Postulated link with hypoMg with secondary hypoCa. PMID 35561741: two families reported with dominant inheritance. F1: three affected individuals with splicing variant; some supportive functional data. F2: single affected individual, de novo missense variant. PMID 35712613: de novo missense variant in an individual with hypoMg. PMID 39099563: three affected individuals with missense variants, all de novo. Probands had DD, two had seizures.; Changed rating: GREEN; Changed publications: 32503408, 31423533, 35561741, 35712613, 39099563; Changed phenotypes: Familial primary hypomagnesemia, MONDO:0018100, TRPM7-related, {Amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to}, MIM# 105500, Cardiac arrhythmia, stillbirth
Renal Tubulopathies and related disorders v1.17 TRPM7 Zornitza Stark Marked gene: TRPM7 as ready
Renal Tubulopathies and related disorders v1.17 TRPM7 Zornitza Stark Gene: trpm7 has been classified as Green List (High Evidence).
Renal Tubulopathies and related disorders v1.17 TRPM7 Zornitza Stark Classified gene: TRPM7 as Green List (high evidence)
Renal Tubulopathies and related disorders v1.17 TRPM7 Zornitza Stark Gene: trpm7 has been classified as Green List (High Evidence).
Renal Tubulopathies and related disorders v1.16 TRPM7 Zornitza Stark changed review comment from: Protein expressed in the distal tubule, related to TRPM6. Postulated link with hypoMg with secondary hypoCa.
PMID 35561741: two families reported with dominant inheritance. F1: three affected individuals with splicing variant; some supportive functional data. F2: single affected individual, de novo missense variant.
PMID 35712613: de novo missense variant in an individual with hypoMg.
PMID 39099563: three affected individuals with missense variants, all de novo.
Sources: Expert Review; to: Protein expressed in the distal tubule, related to TRPM6. Postulated link with hypoMg with secondary hypoCa.
PMID 35561741: two families reported with dominant inheritance. F1: three affected individuals with splicing variant; some supportive functional data. F2: single affected individual, de novo missense variant.
PMID 35712613: de novo missense variant in an individual with hypoMg.
PMID 39099563: three affected individuals with missense variants, all de novo. Probands had DD, two had seizures.
Sources: Expert Review
Prepair 1000+ v1.1064 PYROXD1 Michelle Torres reviewed gene: PYROXD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30345904, 30515627, 27745833, 33694278; Phenotypes: Myopathy, myofibrillar, 8 MIM#617258; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Tubulopathies and related disorders v1.16 TRPM7 Zornitza Stark edited their review of gene: TRPM7: Changed rating: GREEN
Renal Tubulopathies and related disorders v1.16 TRPM7 Zornitza Stark gene: TRPM7 was added
gene: TRPM7 was added to Renal Tubulopathies and related disorders. Sources: Expert Review
Mode of inheritance for gene: TRPM7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPM7 were set to 35561741; 35712613; 39099563
Phenotypes for gene: TRPM7 were set to Familial primary hypomagnesemia, MONDO:0018100, TRPM7-related
Added comment: Protein expressed in the distal tubule, related to TRPM6. Postulated link with hypoMg with secondary hypoCa.
PMID 35561741: two families reported with dominant inheritance. F1: three affected individuals with splicing variant; some supportive functional data. F2: single affected individual, de novo missense variant.
PMID 35712613: de novo missense variant in an individual with hypoMg.
PMID 39099563: three affected individuals with missense variants, all de novo.
Sources: Expert Review
Fetal anomalies v1.305 PIGL Michelle Torres reviewed gene: PIGL: Rating: GREEN; Mode of pathogenicity: None; Publications: 22444671, 31535386, 30023290, 29473937, 28371479, 25706356; Phenotypes: CHIME syndrome MIM#280000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1064 PHYH Michelle Torres reviewed gene: PHYH: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301527, 9326939, 9326940; Phenotypes: Refsum disease MIM#266500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1064 PEX16 Michelle Torres reviewed gene: PEX16: Rating: GREEN; Mode of pathogenicity: None; Publications: 11890679, 9837814, 20647552, 20301621, 30078639; Phenotypes: Peroxisome biogenesis disorder 8A (Zellweger) MIM#614876, Peroxisome biogenesis disorder 8B MIM#614877; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1064 PDHA1 Michelle Torres reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22142326; Phenotypes: Pyruvate dehydrogenase E1-alpha deficiency MIM#312170; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.1064 PDHA1 Michelle Torres Deleted their review
Prepair 1000+ v1.1064 ELP1 Zornitza Stark Marked gene: ELP1 as ready
Prepair 1000+ v1.1064 ELP1 Zornitza Stark Gene: elp1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1064 ELP1 Zornitza Stark Phenotypes for gene: ELP1 were changed from Dysautonomia, familial, 223900 (3) to Dysautonomia, familial MIM#223900; Hereditary sensory and autonomic neuropathy type III (HSAN3)
Prepair 1000+ v1.1063 ELP1 Zornitza Stark Publications for gene: ELP1 were set to
Prepair 1000+ v1.1062 EOGT Zornitza Stark Marked gene: EOGT as ready
Prepair 1000+ v1.1062 EOGT Zornitza Stark Gene: eogt has been classified as Green List (High Evidence).
Prepair 1000+ v1.1062 EOGT Zornitza Stark Phenotypes for gene: EOGT were changed from Adams-Oliver syndrome 4, 615297 (3) to Adams-Oliver syndrome 4, MIM#615297
Prepair 1000+ v1.1061 EOGT Zornitza Stark Publications for gene: EOGT were set to
Prepair 1000+ v1.1060 FANCE Zornitza Stark Marked gene: FANCE as ready
Prepair 1000+ v1.1060 FANCE Zornitza Stark Gene: fance has been classified as Green List (High Evidence).
Prepair 1000+ v1.1060 FANCE Zornitza Stark Phenotypes for gene: FANCE were changed from Fanconi anemia, complementation group E, 600901 (3) to Fanconi anaemia, complementation group E, MIM#600901
Prepair 1000+ v1.1059 FANCE Zornitza Stark Publications for gene: FANCE were set to
Prepair 1000+ v1.1058 FOXN1 Zornitza Stark Marked gene: FOXN1 as ready
Prepair 1000+ v1.1058 FOXN1 Zornitza Stark Gene: foxn1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1058 FOXN1 Zornitza Stark Phenotypes for gene: FOXN1 were changed from T-cell immunodeficiency, congenital alopecia, and nail dystrophy, 601705 (3) to T-cell immunodeficiency, congenital alopecia, and nail dystrophy MIM#601705
Prepair 1000+ v1.1057 FOXN1 Zornitza Stark Publications for gene: FOXN1 were set to
Prepair 1000+ v1.1056 GJA1 Zornitza Stark Marked gene: GJA1 as ready
Prepair 1000+ v1.1056 GJA1 Zornitza Stark Gene: gja1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1056 GJA1 Zornitza Stark Phenotypes for gene: GJA1 were changed from Hypoplastic left heart syndrome 1, 241550 (3) to Craniometaphyseal dysplasia, autosomal recessive MIM#218400; Oculodentodigital dysplasia, autosomal recessive MIM#257850
Prepair 1000+ v1.1055 GJA1 Zornitza Stark Publications for gene: GJA1 were set to
Prepair 1000+ v1.1054 GLIS3 Zornitza Stark Marked gene: GLIS3 as ready
Prepair 1000+ v1.1054 GLIS3 Zornitza Stark Gene: glis3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1054 GLIS3 Zornitza Stark Phenotypes for gene: GLIS3 were changed from Diabetes mellitus, neonatal, with congenital hypothyroidism, 610199 (3) to Diabetes mellitus, neonatal, with congenital hypothyroidism MIM#610199
Prepair 1000+ v1.1053 GLIS3 Zornitza Stark Publications for gene: GLIS3 were set to
Prepair 1000+ v1.1052 GPSM2 Zornitza Stark Marked gene: GPSM2 as ready
Prepair 1000+ v1.1052 GPSM2 Zornitza Stark Gene: gpsm2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1052 GPSM2 Zornitza Stark Phenotypes for gene: GPSM2 were changed from Chudley-McCullough syndrome, 604213 (3) to Chudley-McCullough syndrome, MIM#604213
Prepair 1000+ v1.1051 GPSM2 Zornitza Stark Publications for gene: GPSM2 were set to
Prepair 1000+ v1.1050 GRHPR Zornitza Stark Publications for gene: GRHPR were set to 28569194; 10484776; 10484776; 24116921
Prepair 1000+ v1.1049 HSPG2 Zornitza Stark Marked gene: HSPG2 as ready
Prepair 1000+ v1.1049 HSPG2 Zornitza Stark Gene: hspg2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1049 HSPG2 Zornitza Stark Phenotypes for gene: HSPG2 were changed from Schwartz-Jampel syndrome, type 1, 255800 (3) to Schwartz-Jampel syndrome, type 1, MIM# 255800; Dyssegmental dysplasia, Silverman-Handmaker type, MIM# 224410
Prepair 1000+ v1.1048 HSPG2 Zornitza Stark Publications for gene: HSPG2 were set to
Prepair 1000+ v1.1047 TBX22 Zornitza Stark Marked gene: TBX22 as ready
Prepair 1000+ v1.1047 TBX22 Zornitza Stark Gene: tbx22 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.1047 TBX22 Zornitza Stark Publications for gene: TBX22 were set to
Prepair 1000+ v1.1046 TBX22 Zornitza Stark reviewed gene: TBX22: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v1.1046 IGHMBP2 Zornitza Stark Marked gene: IGHMBP2 as ready
Prepair 1000+ v1.1046 IGHMBP2 Zornitza Stark Gene: ighmbp2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1046 IGHMBP2 Zornitza Stark Phenotypes for gene: IGHMBP2 were changed from Neuronopathy, distal hereditary motor, type VI, 604320 (3) to Neuronopathy, distal hereditary motor, autosomal recessive 1 MIM#604320; Charcot-Marie-Tooth disease, axonal, type 2S MIM#616155
Prepair 1000+ v1.1045 IGHMBP2 Zornitza Stark Publications for gene: IGHMBP2 were set to
Prepair 1000+ v1.1044 IL10RB Zornitza Stark Marked gene: IL10RB as ready
Prepair 1000+ v1.1044 IL10RB Zornitza Stark Gene: il10rb has been classified as Green List (High Evidence).
Prepair 1000+ v1.1044 IL10RB Zornitza Stark Publications for gene: IL10RB were set to 22549091
Prepair 1000+ v1.1043 UBE2T Zornitza Stark Marked gene: UBE2T as ready
Prepair 1000+ v1.1043 UBE2T Zornitza Stark Gene: ube2t has been classified as Green List (High Evidence).
Prepair 1000+ v1.1043 UBE2T Zornitza Stark Phenotypes for gene: UBE2T were changed from Fanconi anemia, complementation group T, 616435 (3) to Fanconi anaemia, complementation group T, MIM#616435
Prepair 1000+ v1.1042 UBE2T Zornitza Stark Publications for gene: UBE2T were set to
Prepair 1000+ v1.1041 KATNB1 Zornitza Stark Marked gene: KATNB1 as ready
Prepair 1000+ v1.1041 KATNB1 Zornitza Stark Gene: katnb1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1041 KATNB1 Zornitza Stark Phenotypes for gene: KATNB1 were changed from Lissencephaly 6, with microcephaly, 616212 (3) to Lissencephaly 6, with microcephaly, MIM#616212
Prepair 1000+ v1.1040 KATNB1 Zornitza Stark Publications for gene: KATNB1 were set to
Prepair 1000+ v1.1039 PDHA1 Michelle Torres reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22142326; Phenotypes: Pyruvate dehydrogenase E1-alpha deficiency MIM#312170; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1039 JUP Zornitza Stark Marked gene: JUP as ready
Prepair 1000+ v1.1039 JUP Zornitza Stark Gene: jup has been classified as Green List (High Evidence).
Prepair 1000+ v1.1039 ORC6 Michelle Torres reviewed gene: ORC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 21358632, 22333897, 25691413, 26139588; Phenotypes: Meier-Gorlin syndrome 3 MIM#613803; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1039 JUP Zornitza Stark Phenotypes for gene: JUP were changed from Naxos disease, 601214 (3) to Naxos disease MIM#601214
Prepair 1000+ v1.1038 JUP Zornitza Stark Publications for gene: JUP were set to
Prepair 1000+ v1.1037 LDHA Zornitza Stark Marked gene: LDHA as ready
Prepair 1000+ v1.1037 LDHA Zornitza Stark Gene: ldha has been classified as Green List (High Evidence).
Prepair 1000+ v1.1037 LDHA Zornitza Stark Phenotypes for gene: LDHA were changed from Glycogen storage disease XI, 612933 (3) to Glycogen storage disease XI MIM#612933
Prepair 1000+ v1.1036 LDHA Zornitza Stark Publications for gene: LDHA were set to
Prepair 1000+ v1.1035 LAMA2 Zornitza Stark Marked gene: LAMA2 as ready
Prepair 1000+ v1.1035 LAMA2 Zornitza Stark Gene: lama2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1035 LAMA2 Zornitza Stark Phenotypes for gene: LAMA2 were changed from Muscular dystrophy, congenital merosin-deficient, 607855 (3) to Muscular dystrophy, congenital, merosin deficient or partially deficient, MIM# 607855; Muscular dystrophy, limb-girdle, autosomal recessive 23, MIM# 618138
Prepair 1000+ v1.1034 LAMA2 Zornitza Stark Publications for gene: LAMA2 were set to
Prepair 1000+ v1.1033 CYB5R3 Zornitza Stark Marked gene: CYB5R3 as ready
Prepair 1000+ v1.1033 CYB5R3 Zornitza Stark Gene: cyb5r3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1033 CYB5R3 Zornitza Stark Phenotypes for gene: CYB5R3 were changed from Methemoglobinemia, type I, 250800 (3) to Methemoglobinaemia, type II (MIM# 250800)
Prepair 1000+ v1.1032 CYB5R3 Zornitza Stark Publications for gene: CYB5R3 were set to
Prepair 1000+ v1.1031 GALC Zornitza Stark Marked gene: GALC as ready
Prepair 1000+ v1.1031 GALC Zornitza Stark Gene: galc has been classified as Green List (High Evidence).
Prepair 1000+ v1.1031 GALC Zornitza Stark Phenotypes for gene: GALC were changed from Krabbe disease, 245200 (3) to Krabbe disease, MIM# 245200; MONDO:0009499
Prepair 1000+ v1.1030 GALC Zornitza Stark Publications for gene: GALC were set to
Prepair 1000+ v1.1029 GORAB Zornitza Stark Marked gene: GORAB as ready
Prepair 1000+ v1.1029 GORAB Zornitza Stark Gene: gorab has been classified as Green List (High Evidence).
Prepair 1000+ v1.1029 GORAB Zornitza Stark Phenotypes for gene: GORAB were changed from Geroderma osteodysplasticum, 231070 (3) to Geroderma osteodysplasticum, MIM#231070; MONDO:0009271
Prepair 1000+ v1.1028 GORAB Zornitza Stark Publications for gene: GORAB were set to
Intellectual disability syndromic and non-syndromic v1.46 TAOK2 Zornitza Stark Marked gene: TAOK2 as ready
Intellectual disability syndromic and non-syndromic v1.46 TAOK2 Zornitza Stark Gene: taok2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.46 TAOK2 Zornitza Stark Classified gene: TAOK2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.46 TAOK2 Zornitza Stark Gene: taok2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.45 TAOK2 Zornitza Stark gene: TAOK2 was added
gene: TAOK2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TAOK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TAOK2 were set to 39737487
Phenotypes for gene: TAOK2 were set to neurodevelopmental disorder, MONDO:0700092, TAOK2-related
Review for gene: TAOK2 was set to GREEN
Added comment: PMID:39737487 reported 10 individuals with monoallelic TAOK2 variants and with a neurodevelopmental disorder.
Sources: Literature
Mendeliome v1.2263 TAOK2 Zornitza Stark Phenotypes for gene: TAOK2 were changed from Generalized verrucosis; abnormal T cell activation; autism to neurodevelopmental disorder, MONDO:0700092, TAOK2-related; Generalized verrucosis; abnormal T cell activation; autism
Mendeliome v1.2262 TAOK2 Zornitza Stark Publications for gene: TAOK2 were set to 28385331; 29467497
Mendeliome v1.2261 TAOK2 Zornitza Stark Classified gene: TAOK2 as Green List (high evidence)
Mendeliome v1.2261 TAOK2 Zornitza Stark Gene: taok2 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.119 LIFR Zornitza Stark Phenotypes for gene: LIFR were changed from CAKUT to CAKUT MONDO:0019719, LIFR-related
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.118 LIFR Zornitza Stark Publications for gene: LIFR were set to 28334964
Prepair 1000+ v1.1027 PHGDH Zornitza Stark Marked gene: PHGDH as ready
Prepair 1000+ v1.1027 PHGDH Zornitza Stark Gene: phgdh has been classified as Green List (High Evidence).
Prepair 1000+ v1.1027 PHGDH Zornitza Stark Phenotypes for gene: PHGDH were changed from Neu-Laxova syndrome1, 256520 (3) to Neu-Laxova syndrome 1 MIM#256520; Phosphoglycerate dehydrogenase deficiency MIM#601815
Prepair 1000+ v1.1026 PHGDH Zornitza Stark Publications for gene: PHGDH were set to
Prepair 1000+ v1.1025 PLOD2 Zornitza Stark Marked gene: PLOD2 as ready
Prepair 1000+ v1.1025 PLOD2 Zornitza Stark Gene: plod2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1025 PLOD2 Zornitza Stark Phenotypes for gene: PLOD2 were changed from Bruck syndrome 2, 609220 (3) to Bruck syndrome 2, MIM#609220
Prepair 1000+ v1.1024 PLOD2 Zornitza Stark Publications for gene: PLOD2 were set to
Prepair 1000+ v1.1023 SDCCAG8 Zornitza Stark Marked gene: SDCCAG8 as ready
Prepair 1000+ v1.1023 SDCCAG8 Zornitza Stark Gene: sdccag8 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1023 SDCCAG8 Zornitza Stark Phenotypes for gene: SDCCAG8 were changed from Bardet-Biedl syndrome 16, 615993 (3) to Bardet-Biedl syndrome 16 (MIM# 615993); Senior-Loken syndrome 7 (MIM# 613615)
Prepair 1000+ v1.1022 SDCCAG8 Zornitza Stark Publications for gene: SDCCAG8 were set to
Prepair 1000+ v1.1021 SLC17A5 Zornitza Stark Marked gene: SLC17A5 as ready
Prepair 1000+ v1.1021 SLC17A5 Zornitza Stark Gene: slc17a5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1021 SLC17A5 Zornitza Stark Phenotypes for gene: SLC17A5 were changed from Sialic acid storage disorder, infantile, 269920 (3) to Sialic acid storage disorder, infantile (MIM#269920)
Prepair 1000+ v1.1020 SLC17A5 Zornitza Stark Publications for gene: SLC17A5 were set to
Prepair 1000+ v1.1019 SLC25A19 Zornitza Stark Marked gene: SLC25A19 as ready
Prepair 1000+ v1.1019 SLC25A19 Zornitza Stark Gene: slc25a19 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1019 SLC25A19 Zornitza Stark Phenotypes for gene: SLC25A19 were changed from Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), 613710 (progressive polyneuropathy type), 613710 to Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type) (MIM#613710); Microcephaly, Amish type (MIM#607196)
Prepair 1000+ v1.1018 SLC25A19 Zornitza Stark Publications for gene: SLC25A19 were set to
Prepair 1000+ v1.1017 SLC25A46 Zornitza Stark Marked gene: SLC25A46 as ready
Prepair 1000+ v1.1017 SLC25A46 Zornitza Stark Gene: slc25a46 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1017 SLC25A46 Zornitza Stark Phenotypes for gene: SLC25A46 were changed from Neuropathy, hereditary motor and sensory, type VIB, 616505 (3), Autosomal recessive to Neuropathy, hereditary motor and sensory, type VIB (MIM# 616505); Pontocerebellar hypoplasia, type 1E (MIM# 619303)
Prepair 1000+ v1.1016 SLC25A46 Zornitza Stark Publications for gene: SLC25A46 were set to
Mendeliome v1.2260 SLC13A1 Zornitza Stark Classified gene: SLC13A1 as Amber List (moderate evidence)
Mendeliome v1.2260 SLC13A1 Zornitza Stark Gene: slc13a1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.300 SLC13A1 Zornitza Stark Publications for gene: SLC13A1 were set to 36175384
Skeletal dysplasia v0.299 SLC13A1 Zornitza Stark Classified gene: SLC13A1 as Amber List (moderate evidence)
Skeletal dysplasia v0.299 SLC13A1 Zornitza Stark Gene: slc13a1 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.1015 STIL Zornitza Stark Marked gene: STIL as ready
Prepair 1000+ v1.1015 STIL Zornitza Stark Gene: stil has been classified as Green List (High Evidence).
Prepair 1000+ v1.1015 STIL Zornitza Stark Phenotypes for gene: STIL were changed from Microcephaly 7, primary, autosomal recessive, 612703 (3) to Microcephaly 7, primary, (MIM# 612703)
Prepair 1000+ v1.1014 STIL Zornitza Stark Publications for gene: STIL were set to
Genetic Epilepsy v1.97 GTF3C3 Chirag Patel gene: GTF3C3 was added
gene: GTF3C3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: GTF3C3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C3 were set to PMID: 39636576
Phenotypes for gene: GTF3C3 were set to Neurodevelopmental disorder MONDO:0700092, GTF3C3-related
Review for gene: GTF3C3 was set to GREEN
Added comment: 12 affected individuals from 7 unrelated families with homozygous or compound heterozygous missense variants in GTF3C3. Presentation with intellectual disability, variable nonfamilial facial features, motor impairments, seizures, and cerebellar/corpus callosum malformations.
Sources: Literature
Genetic Epilepsy v1.97 GTF3C3 Chirag Patel gene: GTF3C3 was added
gene: GTF3C3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: GTF3C3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C3 were set to PMID: 39636576
Phenotypes for gene: GTF3C3 were set to Neurodevelopmental disorder MONDO:0700092, GTF3C3-related
Review for gene: GTF3C3 was set to GREEN
Added comment: 12 affected individuals from 7 unrelated families with homozygous or compound heterozygous missense variants in GTF3C3. Presentation with intellectual disability, variable nonfamilial facial features, motor impairments, seizures, and cerebellar/corpus callosum malformations.
Sources: Literature
Genetic Epilepsy v1.97 GTF3C3 Chirag Patel gene: GTF3C3 was added
gene: GTF3C3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: GTF3C3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C3 were set to PMID: 39636576
Phenotypes for gene: GTF3C3 were set to Neurodevelopmental disorder MONDO:0700092, GTF3C3-related
Added comment: 12 affected individuals from 7 unrelated families with homozygous or compound heterozygous missense variants in GTF3C3. Presentation with intellectual disability, variable nonfamilial facial features, motor impairments, seizures, and cerebellar/corpus callosum malformations.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.44 GTF3C3 Chirag Patel reviewed gene: GTF3C3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39636576; Phenotypes: Neurodevelopmental disorder MONDO:0700092, GTF3C3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v1.85 INPP4A Chirag Patel Classified gene: INPP4A as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.85 INPP4A Chirag Patel Gene: inpp4a has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.85 INPP4A Chirag Patel Classified gene: INPP4A as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.85 INPP4A Chirag Patel Gene: inpp4a has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.85 INPP4A Chirag Patel Classified gene: INPP4A as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.85 INPP4A Chirag Patel Gene: inpp4a has been classified as Green List (High Evidence).
Genetic Epilepsy v1.96 INPP4A Chirag Patel Classified gene: INPP4A as Green List (high evidence)
Genetic Epilepsy v1.96 INPP4A Chirag Patel Gene: inpp4a has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.85 INPP4A Chirag Patel Classified gene: INPP4A as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.85 INPP4A Chirag Patel Gene: inpp4a has been classified as Green List (High Evidence).
Genetic Epilepsy v1.96 INPP4A Chirag Patel Classified gene: INPP4A as Green List (high evidence)
Genetic Epilepsy v1.96 INPP4A Chirag Patel Gene: inpp4a has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.85 INPP4A Chirag Patel Classified gene: INPP4A as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.85 INPP4A Chirag Patel Gene: inpp4a has been classified as Green List (High Evidence).
Genetic Epilepsy v1.96 INPP4A Chirag Patel Classified gene: INPP4A as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.77 INPP4A Chirag Patel Classified gene: INPP4A as Green List (high evidence)
Genetic Epilepsy v1.96 INPP4A Chirag Patel Gene: inpp4a has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.77 INPP4A Chirag Patel Gene: inpp4a has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.85 INPP4A Chirag Patel Classified gene: INPP4A as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.85 INPP4A Chirag Patel Gene: inpp4a has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.77 INPP4A Chirag Patel Classified gene: INPP4A as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.77 INPP4A Chirag Patel Gene: inpp4a has been classified as Green List (High Evidence).
Genetic Epilepsy v1.96 INPP4A Chirag Patel Classified gene: INPP4A as Green List (high evidence)
Genetic Epilepsy v1.96 INPP4A Chirag Patel Gene: inpp4a has been classified as Green List (High Evidence).
Microcephaly v1.294 INPP4A Chirag Patel Classified gene: INPP4A as Green List (high evidence)
Microcephaly v1.294 INPP4A Chirag Patel Gene: inpp4a has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.76 INPP4A Chirag Patel gene: INPP4A was added
gene: INPP4A was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature
Mode of inheritance for gene: INPP4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INPP4A were set to PMID: 39315527
Phenotypes for gene: INPP4A were set to INPP4A-related neurodevelopmental disorder
Review for gene: INPP4A was set to GREEN
Added comment: PMID: 39315527
30 individuals (aged 6 months to 40 years) from 17 unrelated families with biallelic LOF variants in INPP4A gene (11 nonsense or frameshift and 3 missense, mostly exon 4).

Cardinal clinical features include: severe global developmental delay, profound speech impairment, severe-profound intellectual disability, and severe lower limb weakness/paralysis. More variable clinical features include: microcephaly, short stature, cerebellar signs, involuntary movements, axial hypotonia, spasticity, quadriparesis, joint contractures, seizures, visual impairment. Neuroimaging findings vary from normal to features of (ponto)cerebellar hypoplasia, ventriculomegaly, reduced cerebral volume and hypomyelination. A more severe presentation is seen with variants downstream of exon 4.

Preliminary fibroblast cell studies identify disruption of endocytic pathways as the likely mechanism of disease, consistent with previous findings of a role of INPP4A in endocytosis. All mouse models display a phenotype mirroring human INPP4A-related neurodevelopmental disorder entailing a severe movement disorder with inability to walk, a small brain, and poor growth/weight gain.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.84 INPP4A Chirag Patel gene: INPP4A was added
gene: INPP4A was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: INPP4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INPP4A were set to PMID: 39315527
Phenotypes for gene: INPP4A were set to INPP4A-related neurodevelopmental disorder
Review for gene: INPP4A was set to GREEN
Added comment: PMID: 39315527
30 individuals (aged 6 months to 40 years) from 17 unrelated families with biallelic LOF variants in INPP4A gene (11 nonsense or frameshift and 3 missense, mostly exon 4).

Cardinal clinical features include: severe global developmental delay, profound speech impairment, severe-profound intellectual disability, and severe lower limb weakness/paralysis. More variable clinical features include: microcephaly, short stature, cerebellar signs, involuntary movements, axial hypotonia, spasticity, quadriparesis, joint contractures, seizures, visual impairment. Neuroimaging findings vary from normal to features of (ponto)cerebellar hypoplasia, ventriculomegaly, reduced cerebral volume and hypomyelination. A more severe presentation is seen with variants downstream of exon 4.

Preliminary fibroblast cell studies identify disruption of endocytic pathways as the likely mechanism of disease, consistent with previous findings of a role of INPP4A in endocytosis. All mouse models display a phenotype mirroring human INPP4A-related neurodevelopmental disorder entailing a severe movement disorder with inability to walk, a small brain, and poor growth/weight gain.
Sources: Literature
Hereditary Spastic Paraplegia - paediatric v1.86 INPP4A Chirag Patel Classified gene: INPP4A as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v1.86 INPP4A Chirag Patel Gene: inpp4a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.85 INPP4A Chirag Patel gene: INPP4A was added
gene: INPP4A was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: INPP4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INPP4A were set to PMID: 39315527
Phenotypes for gene: INPP4A were set to INPP4A-related neurodevelopmental disorder
Review for gene: INPP4A was set to GREEN
Added comment: PMID: 39315527
30 individuals (aged 6 months to 40 years) from 17 unrelated families with biallelic LOF variants in INPP4A gene (11 nonsense or frameshift and 3 missense, mostly exon 4).

Cardinal clinical features include: severe global developmental delay, profound speech impairment, severe-profound intellectual disability, and severe lower limb weakness/paralysis. More variable clinical features include: microcephaly, short stature, cerebellar signs, involuntary movements, axial hypotonia, spasticity, quadriparesis, joint contractures, seizures, visual impairment. Neuroimaging findings vary from normal to features of (ponto)cerebellar hypoplasia, ventriculomegaly, reduced cerebral volume and hypomyelination. A more severe presentation is seen with variants downstream of exon 4.

Preliminary fibroblast cell studies identify disruption of endocytic pathways as the likely mechanism of disease, consistent with previous findings of a role of INPP4A in endocytosis. All mouse models display a phenotype mirroring human INPP4A-related neurodevelopmental disorder entailing a severe movement disorder with inability to walk, a small brain, and poor growth/weight gain.
Sources: Literature
Microcephaly v1.293 INPP4A Chirag Patel gene: INPP4A was added
gene: INPP4A was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: INPP4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INPP4A were set to PMID: 39315527
Phenotypes for gene: INPP4A were set to INPP4A-related neurodevelopmental disorder
Review for gene: INPP4A was set to GREEN
Added comment: PMID: 39315527
30 individuals (aged 6 months to 40 years) from 17 unrelated families with biallelic LOF variants in INPP4A gene (11 nonsense or frameshift and 3 missense, mostly exon 4).

Cardinal clinical features include: severe global developmental delay, profound speech impairment, severe-profound intellectual disability, and severe lower limb weakness/paralysis. More variable clinical features include: microcephaly, short stature, cerebellar signs, involuntary movements, axial hypotonia, spasticity, quadriparesis, joint contractures, seizures, visual impairment. Neuroimaging findings vary from normal to features of (ponto)cerebellar hypoplasia, ventriculomegaly, reduced cerebral volume and hypomyelination. A more severe presentation is seen with variants downstream of exon 4.

Preliminary fibroblast cell studies identify disruption of endocytic pathways as the likely mechanism of disease, consistent with previous findings of a role of INPP4A in endocytosis. All mouse models display a phenotype mirroring human INPP4A-related neurodevelopmental disorder entailing a severe movement disorder with inability to walk, a small brain, and poor growth/weight gain.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.44 INPP4A Chirag Patel Classified gene: INPP4A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.44 INPP4A Chirag Patel Gene: inpp4a has been classified as Green List (High Evidence).
Genetic Epilepsy v1.95 INPP4A Chirag Patel gene: INPP4A was added
gene: INPP4A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: INPP4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INPP4A were set to PMID: 39315527
Phenotypes for gene: INPP4A were set to INPP4A-related neurodevelopmental disorder
Review for gene: INPP4A was set to GREEN
Added comment: PMID: 39315527
30 individuals (aged 6 months to 40 years) from 17 unrelated families with biallelic LOF variants in INPP4A gene (11 nonsense or frameshift and 3 missense, mostly exon 4).

Cardinal clinical features include: severe global developmental delay, profound speech impairment, severe-profound intellectual disability, and severe lower limb weakness/paralysis. More variable clinical features include: microcephaly, short stature, cerebellar signs, involuntary movements, axial hypotonia, spasticity, quadriparesis, joint contractures, seizures, visual impairment. Neuroimaging findings vary from normal to features of (ponto)cerebellar hypoplasia, ventriculomegaly, reduced cerebral volume and hypomyelination. A more severe presentation is seen with variants downstream of exon 4.

Preliminary fibroblast cell studies identify disruption of endocytic pathways as the likely mechanism of disease, consistent with previous findings of a role of INPP4A in endocytosis. All mouse models display a phenotype mirroring human INPP4A-related neurodevelopmental disorder entailing a severe movement disorder with inability to walk, a small brain, and poor growth/weight gain.
Sources: Literature
Mendeliome v1.2259 INPP4A Chirag Patel Classified gene: INPP4A as Green List (high evidence)
Mendeliome v1.2259 INPP4A Chirag Patel Gene: inpp4a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.43 INPP4A Chirag Patel reviewed gene: INPP4A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39315527; Phenotypes: INPP4A-related neurodevelopmental disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2258 INPP4A Chirag Patel reviewed gene: INPP4A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39315527; Phenotypes: INPP4A-related neurodevelopmental disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1013 SYP Zornitza Stark Marked gene: SYP as ready
Prepair 1000+ v1.1013 SYP Zornitza Stark Gene: syp has been classified as Green List (High Evidence).
Prepair 1000+ v1.1013 SYP Zornitza Stark Phenotypes for gene: SYP were changed from Mental retardation, X-linked 96, 300802 (3) to Intellectual developmental disorder, X-linked 96 (MIM#300802)
Prepair 1000+ v1.1012 SYP Zornitza Stark Publications for gene: SYP were set to
Prepair 1000+ v1.1011 SYP Zornitza Stark reviewed gene: SYP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, X-linked 96 (MIM#300802); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.1011 LIAS Zornitza Stark Marked gene: LIAS as ready
Prepair 1000+ v1.1011 LIAS Zornitza Stark Gene: lias has been classified as Green List (High Evidence).
Prepair 1000+ v1.1011 LIAS Zornitza Stark Phenotypes for gene: LIAS were changed from Pyruvate dehydrogenase lipoic acid synthetase deficiency, 614462 (3) to Hyperglycinaemia, lactic acidosis, and seizures MIM#614462
Prepair 1000+ v1.1010 LIAS Zornitza Stark Publications for gene: LIAS were set to
Prepair 1000+ v1.1009 LPL Zornitza Stark Marked gene: LPL as ready
Prepair 1000+ v1.1009 LPL Zornitza Stark Gene: lpl has been classified as Green List (High Evidence).
Prepair 1000+ v1.1009 LPL Zornitza Stark Phenotypes for gene: LPL were changed from Lipoprotein lipase deficiency, 238600 (3) to Lipoprotein lipase deficiency MIM#238600
Prepair 1000+ v1.1008 LRBA Zornitza Stark Marked gene: LRBA as ready
Prepair 1000+ v1.1008 LRBA Zornitza Stark Gene: lrba has been classified as Green List (High Evidence).
Prepair 1000+ v1.1008 LRBA Zornitza Stark Phenotypes for gene: LRBA were changed from Immunodeficiency, common variable, 8, with autoimmunity, 614700 (3) to Immunodeficiency, common variable, 8, with autoimmunity MIM#614700
Prepair 1000+ v1.1007 LRBA Zornitza Stark Publications for gene: LRBA were set to
Prepair 1000+ v1.1006 MCOLN1 Zornitza Stark Marked gene: MCOLN1 as ready
Prepair 1000+ v1.1006 MCOLN1 Zornitza Stark Gene: mcoln1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1006 MCOLN1 Zornitza Stark Phenotypes for gene: MCOLN1 were changed from Mucolipidosis IV, 252650 (3) to Mucolipidosis IV MIM#252650
Prepair 1000+ v1.1005 MCOLN1 Zornitza Stark Publications for gene: MCOLN1 were set to
Prepair 1000+ v1.1004 MMACHC Zornitza Stark Marked gene: MMACHC as ready
Prepair 1000+ v1.1004 MMACHC Zornitza Stark Gene: mmachc has been classified as Green List (High Evidence).
Prepair 1000+ v1.1004 MMACHC Zornitza Stark Phenotypes for gene: MMACHC were changed from Methylmalonic aciduria and homocystinuria, cblC type, 277400 (3) to Methylmalonic aciduria and homocystinuria, cblC type MIM#277400
Prepair 1000+ v1.1003 MMACHC Zornitza Stark Publications for gene: MMACHC were set to
Prepair 1000+ v1.1002 NAGS Zornitza Stark Marked gene: NAGS as ready
Prepair 1000+ v1.1002 NAGS Zornitza Stark Gene: nags has been classified as Green List (High Evidence).
Prepair 1000+ v1.1002 NAGS Zornitza Stark Phenotypes for gene: NAGS were changed from N-acetylglutamate synthase deficiency, 237310 (3) to N-acetylglutamate synthase deficiency MIM#237310
Prepair 1000+ v1.1001 NAGS Zornitza Stark Publications for gene: NAGS were set to
Prepair 1000+ v1.1000 NDUFS7 Zornitza Stark Marked gene: NDUFS7 as ready
Prepair 1000+ v1.1000 NDUFS7 Zornitza Stark Gene: ndufs7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1000 NDUFS7 Zornitza Stark Phenotypes for gene: NDUFS7 were changed from Leigh syndrome, 256000 (3) to Mitochondrial complex I deficiency, nuclear type 3 MIM#618224
Prepair 1000+ v1.999 NDUFS7 Zornitza Stark Publications for gene: NDUFS7 were set to
Prepair 1000+ v1.998 NKX6-2 Zornitza Stark Marked gene: NKX6-2 as ready
Prepair 1000+ v1.998 NKX6-2 Zornitza Stark Gene: nkx6-2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.998 NKX6-2 Zornitza Stark Phenotypes for gene: NKX6-2 were changed from Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy, 617560 (3) to Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy MIM#617560
Prepair 1000+ v1.997 NKX6-2 Zornitza Stark Publications for gene: NKX6-2 were set to
Prepair 1000+ v1.996 NTRK1 Zornitza Stark Marked gene: NTRK1 as ready
Prepair 1000+ v1.996 NTRK1 Zornitza Stark Gene: ntrk1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.996 NTRK1 Zornitza Stark Phenotypes for gene: NTRK1 were changed from Insensitivity to pain, congenital, with anhidrosis, 256800 (3) to Insensitivity to pain, congenital, with anhidrosis MIM#256800
Prepair 1000+ v1.995 NTRK1 Zornitza Stark Publications for gene: NTRK1 were set to
Prepair 1000+ v1.994 KIAA0586 Zornitza Stark Marked gene: KIAA0586 as ready
Prepair 1000+ v1.994 KIAA0586 Zornitza Stark Gene: kiaa0586 has been classified as Green List (High Evidence).
Prepair 1000+ v1.994 KIAA0586 Zornitza Stark Phenotypes for gene: KIAA0586 were changed from Short-rib thoracic dysplasia 14 with polydactyly, 616546 (3), Autosomal recessive to Short-rib thoracic dysplasia 14 with polydactyly (MIM#616546); Joubert syndrome 23 (MIM#616490)
Prepair 1000+ v1.993 KIAA0586 Zornitza Stark Publications for gene: KIAA0586 were set to
Fetal anomalies v1.305 KDM6B Zornitza Stark Marked gene: KDM6B as ready
Fetal anomalies v1.305 KDM6B Zornitza Stark Gene: kdm6b has been classified as Green List (High Evidence).
Fetal anomalies v1.305 KDM6B Zornitza Stark Classified gene: KDM6B as Green List (high evidence)
Fetal anomalies v1.305 KDM6B Zornitza Stark Gene: kdm6b has been classified as Green List (High Evidence).
Fetal anomalies v1.304 KDM6B Zornitza Stark gene: KDM6B was added
gene: KDM6B was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: KDM6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KDM6B were set to Stolerman neurodevelopmental syndrome, MIM# 618505
Review for gene: KDM6B was set to GREEN
Added comment: Well established gene-disease association. A proportion of individuals have congenital anomalies, including cleft palate, skeletal anomalies and congenital heart disease.
Sources: Expert Review
Mendeliome v1.2258 DDX58 Zornitza Stark Marked gene: DDX58 as ready
Mendeliome v1.2258 DDX58 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is RIGI.
Mendeliome v1.2258 DDX58 Zornitza Stark Gene: ddx58 has been classified as Green List (High Evidence).
Mendeliome v1.2258 DDX58 Zornitza Stark Tag new gene name tag was added to gene: DDX58.
Neuromuscular Superpanel v3.342 Bryony Thompson Changed child panels to: Hereditary Spastic Paraplegia - paediatric; Muscular dystrophy and myopathy_Paediatric; Hereditary Neuropathy_CMT - isolated; Limb-Girdle Muscular Dystrophy and Distal Myopathy; Ataxia - paediatric; Motor Neurone Disease; Gastrointestinal neuromuscular disease; Hereditary Neuropathy - complex; Rhabdomyolysis and Metabolic Myopathy; Ataxia - adult onset; Hereditary Spastic Paraplegia - adult onset; Congenital Myasthenia; Skeletal Muscle Channelopathies
Prepair 1000+ v1.992 KIAA0586 Ee Ming Wong reviewed gene: KIAA0586: Rating: GREEN; Mode of pathogenicity: None; Publications: 26386044, 28125082, 36580738, 39063141; Phenotypes: Short-rib thoracic dysplasia 14 with polydactyly (MIM#616546), Joubert syndrome 23 (MIM#616490); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v1.43 LRRC45 Zornitza Stark Marked gene: LRRC45 as ready
Intellectual disability syndromic and non-syndromic v1.43 LRRC45 Zornitza Stark Gene: lrrc45 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.43 LRRC45 Zornitza Stark Classified gene: LRRC45 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.43 LRRC45 Zornitza Stark Gene: lrrc45 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.42 LRRC45 Zornitza Stark gene: LRRC45 was added
gene: LRRC45 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LRRC45 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC45 were set to 39638757
Phenotypes for gene: LRRC45 were set to Neurodevelopmental disorder MONDO:0700092, LRRC45-related
Review for gene: LRRC45 was set to AMBER
Added comment: Three individuals from two families reported with two homozygous variants, one splice site and the other missense. Features of a neurological ciliopathy with some supportive experimental evidence.
Sources: Literature
Mendeliome v1.2258 LRRC45 Zornitza Stark Marked gene: LRRC45 as ready
Mendeliome v1.2258 LRRC45 Zornitza Stark Gene: lrrc45 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2258 LRRC45 Zornitza Stark Classified gene: LRRC45 as Amber List (moderate evidence)
Mendeliome v1.2258 LRRC45 Zornitza Stark Gene: lrrc45 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2257 LRRC45 Zornitza Stark gene: LRRC45 was added
gene: LRRC45 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LRRC45 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC45 were set to 39638757
Phenotypes for gene: LRRC45 were set to Neurodevelopmental disorder MONDO:0700092, LRRC45-related
Review for gene: LRRC45 was set to AMBER
Added comment: Three individuals from two families reported with two homozygous variants, one splice site and the other missense. Features of a neurological ciliopathy with some supportive experimental evidence.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.41 WASHC3 Zornitza Stark Marked gene: WASHC3 as ready
Intellectual disability syndromic and non-syndromic v1.41 WASHC3 Zornitza Stark Gene: washc3 has been classified as Red List (Low Evidence).
Mendeliome v1.2256 WASHC3 Zornitza Stark Marked gene: WASHC3 as ready
Mendeliome v1.2256 WASHC3 Zornitza Stark Gene: washc3 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.41 WASHC3 Zornitza Stark gene: WASHC3 was added
gene: WASHC3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: WASHC3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: WASHC3 were set to DOI: https://doi.org/10.1016/j.gimo.2024.101915
Phenotypes for gene: WASHC3 were set to neurodevelopmental disorder MONDO:0700092, WASHC3 related
Review for gene: WASHC3 was set to RED
Added comment: One family with de novo missense. Two families with homozygous start loss variant. The functional evidence provided does not directly link to the human phenotype. Given two variants and two different MOIs, RED rating.
Sources: Literature
Mendeliome v1.2256 WASHC3 Zornitza Stark Phenotypes for gene: WASHC3 were changed from neurodevelopmental disorder MONDO:0700092 to neurodevelopmental disorder MONDO:0700092, WASHC3 related
Mendeliome v1.2255 WASHC3 Zornitza Stark Mode of inheritance for gene: WASHC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.2254 WASHC3 Zornitza Stark Classified gene: WASHC3 as Red List (low evidence)
Mendeliome v1.2254 WASHC3 Zornitza Stark Gene: washc3 has been classified as Red List (Low Evidence).
Mendeliome v1.2253 WASHC3 Zornitza Stark reviewed gene: WASHC3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO:0700092, WASHC3 related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.303 LDB1 Zornitza Stark Marked gene: LDB1 as ready
Fetal anomalies v1.303 LDB1 Zornitza Stark Gene: ldb1 has been classified as Green List (High Evidence).
Fetal anomalies v1.303 LDB1 Zornitza Stark Classified gene: LDB1 as Green List (high evidence)
Fetal anomalies v1.303 LDB1 Zornitza Stark Gene: ldb1 has been classified as Green List (High Evidence).
Fetal anomalies v1.302 LDB1 Zornitza Stark gene: LDB1 was added
gene: LDB1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LDB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LDB1 were set to 39680505
Phenotypes for gene: LDB1 were set to Congenital hydrocephalus MONDO:0016349
Review for gene: LDB1 was set to GREEN
Added comment: Exome-wide significant enrichment of LDB1 protein-altering de novo variants (p = 1.11 x 10-15) in a large cerebral ventriculomegaly cohort (>2,697 parent-proband trios). 8 unrelated cases with ventriculomegaly, developmental delay, and dysmorphic features with de novo variants (7 LoF variants truncate LDB1's carboxy-terminal LIM interaction domain & 1 missense).
Sources: Literature
Mendeliome v1.2253 NAV3 Zornitza Stark Marked gene: NAV3 as ready
Mendeliome v1.2253 NAV3 Zornitza Stark Gene: nav3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.40 NAV3 Zornitza Stark Marked gene: NAV3 as ready
Intellectual disability syndromic and non-syndromic v1.40 NAV3 Zornitza Stark Gene: nav3 has been classified as Green List (High Evidence).
Mendeliome v1.2253 NAV3 Zornitza Stark Classified gene: NAV3 as Green List (high evidence)
Mendeliome v1.2253 NAV3 Zornitza Stark Gene: nav3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.40 NAV3 Zornitza Stark Classified gene: NAV3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.40 NAV3 Zornitza Stark Gene: nav3 has been classified as Green List (High Evidence).
Mendeliome v1.2252 NAV3 Zornitza Stark gene: NAV3 was added
gene: NAV3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NAV3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAV3 were set to 39708122; 38977784
Phenotypes for gene: NAV3 were set to Neurodevelopmental disorder, MONDO:0700092, NAV3-related
Review for gene: NAV3 was set to GREEN
Added comment: 17 individuals from 11 families reported with bi-allelic variants and neurodevelopmental phenotypes, including DD/ID and behavioural abnormalities.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.39 NAV3 Zornitza Stark gene: NAV3 was added
gene: NAV3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NAV3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAV3 were set to 39708122; 38977784
Phenotypes for gene: NAV3 were set to Neurodevelopmental disorder, MONDO:0700092, NAV3-related
Review for gene: NAV3 was set to GREEN
Added comment: 17 individuals from 11 families reported with bi-allelic variants and neurodevelopmental phenotypes, including DD/ID and behavioural abnormalities.
Sources: Literature
Cerebellar and Pontocerebellar Hypoplasia v1.75 EEFSEC Zornitza Stark Marked gene: EEFSEC as ready
Cerebellar and Pontocerebellar Hypoplasia v1.75 EEFSEC Zornitza Stark Gene: eefsec has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.75 EEFSEC Zornitza Stark Classified gene: EEFSEC as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.75 EEFSEC Zornitza Stark Gene: eefsec has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.74 EEFSEC Zornitza Stark gene: EEFSEC was added
gene: EEFSEC was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature
Mode of inheritance for gene: EEFSEC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEFSEC were set to 39753114
Phenotypes for gene: EEFSEC were set to Neurodevelopmental disorder, MONDO:0700092, EEFSEC-related
Review for gene: EEFSEC was set to GREEN
Added comment: Nine individuals from 8 unrelated families reported with bi-allelic variants in this gene and progressive neurodevelopmental disorder manifesting with global developmental delay, progressive spasticity, ataxia, and seizures. Cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy. In line with the clinical phenotype, an eEFSec-RNAi Drosophila model displays progressive impairment of motor function, which is reflected in the synaptic defects in this model organisms.
Sources: Literature
Genetic Epilepsy v1.94 EEFSEC Zornitza Stark Marked gene: EEFSEC as ready
Genetic Epilepsy v1.94 EEFSEC Zornitza Stark Gene: eefsec has been classified as Green List (High Evidence).
Genetic Epilepsy v1.94 EEFSEC Zornitza Stark Classified gene: EEFSEC as Green List (high evidence)
Genetic Epilepsy v1.94 EEFSEC Zornitza Stark Gene: eefsec has been classified as Green List (High Evidence).
Ataxia - paediatric v1.30 EEFSEC Zornitza Stark Marked gene: EEFSEC as ready
Ataxia - paediatric v1.30 EEFSEC Zornitza Stark Gene: eefsec has been classified as Green List (High Evidence).
Ataxia - paediatric v1.30 EEFSEC Zornitza Stark Classified gene: EEFSEC as Green List (high evidence)
Ataxia - paediatric v1.30 EEFSEC Zornitza Stark Gene: eefsec has been classified as Green List (High Evidence).
Genetic Epilepsy v1.93 EEFSEC Zornitza Stark gene: EEFSEC was added
gene: EEFSEC was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: EEFSEC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEFSEC were set to 39753114
Phenotypes for gene: EEFSEC were set to Neurodevelopmental disorder, MONDO:0700092, EEFSEC-related
Review for gene: EEFSEC was set to GREEN
Added comment: Nine individuals from 8 unrelated families reported with bi-allelic variants in this gene and progressive neurodevelopmental disorder manifesting with global developmental delay, progressive spasticity, ataxia, and seizures. Cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy. In line with the clinical phenotype, an eEFSec-RNAi Drosophila model displays progressive impairment of motor function, which is reflected in the synaptic defects in this model organisms.
Sources: Literature
Ataxia - paediatric v1.29 EEFSEC Zornitza Stark gene: EEFSEC was added
gene: EEFSEC was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: EEFSEC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEFSEC were set to 39753114
Phenotypes for gene: EEFSEC were set to Neurodevelopmental disorder, MONDO:0700092, EEFSEC-related
Review for gene: EEFSEC was set to GREEN
Added comment: Nine individuals from 8 unrelated families reported with bi-allelic variants in this gene and progressive neurodevelopmental disorder manifesting with global developmental delay, progressive spasticity, ataxia, and seizures. Cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy. In line with the clinical phenotype, an eEFSec-RNAi Drosophila model displays progressive impairment of motor function, which is reflected in the synaptic defects in this model organisms.
Sources: Literature
Regression v0.572 EEFSEC Zornitza Stark Classified gene: EEFSEC as Green List (high evidence)
Regression v0.572 EEFSEC Zornitza Stark Gene: eefsec has been classified as Green List (High Evidence).
Regression v0.572 EEFSEC Zornitza Stark Marked gene: EEFSEC as ready
Regression v0.572 EEFSEC Zornitza Stark Gene: eefsec has been classified as Green List (High Evidence).
Regression v0.572 EEFSEC Zornitza Stark Classified gene: EEFSEC as Green List (high evidence)
Regression v0.572 EEFSEC Zornitza Stark Gene: eefsec has been classified as Green List (High Evidence).
Mendeliome v1.2251 EEFSEC Zornitza Stark Marked gene: EEFSEC as ready
Mendeliome v1.2251 EEFSEC Zornitza Stark Gene: eefsec has been classified as Green List (High Evidence).
Regression v0.571 EEFSEC Zornitza Stark gene: EEFSEC was added
gene: EEFSEC was added to Regression. Sources: Literature
Mode of inheritance for gene: EEFSEC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEFSEC were set to 39753114
Phenotypes for gene: EEFSEC were set to Neurodevelopmental disorder, MONDO:0700092, EEFSEC-related
Review for gene: EEFSEC was set to GREEN
Added comment: Nine individuals from 8 unrelated families reported with bi-allelic variants in this gene and progressive neurodevelopmental disorder manifesting with global developmental delay, progressive spasticity, ataxia, and seizures. Cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy. In line with the clinical phenotype, an eEFSec-RNAi Drosophila model displays progressive impairment of motor function, which is reflected in the synaptic defects in this model organisms.
Sources: Literature
Mendeliome v1.2251 EEFSEC Zornitza Stark Classified gene: EEFSEC as Green List (high evidence)
Mendeliome v1.2251 EEFSEC Zornitza Stark Gene: eefsec has been classified as Green List (High Evidence).
Mendeliome v1.2250 EEFSEC Zornitza Stark gene: EEFSEC was added
gene: EEFSEC was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EEFSEC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEFSEC were set to 39753114
Phenotypes for gene: EEFSEC were set to Neurodevelopmental disorder, MONDO:0700092, EEFSEC-related
Review for gene: EEFSEC was set to GREEN
Added comment: Nine individuals from 8 unrelated families reported with bi-allelic variants in this gene and progressive neurodevelopmental disorder manifesting with global developmental delay, progressive spasticity, ataxia, and seizures. Cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy. In line with the clinical phenotype, an eEFSec-RNAi Drosophila model displays progressive impairment of motor function, which is reflected in the synaptic defects in this model organisms.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.38 EEFSEC Zornitza Stark Marked gene: EEFSEC as ready
Intellectual disability syndromic and non-syndromic v1.38 EEFSEC Zornitza Stark Gene: eefsec has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.38 EEFSEC Zornitza Stark Classified gene: EEFSEC as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.38 EEFSEC Zornitza Stark Gene: eefsec has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.37 EEFSEC Zornitza Stark gene: EEFSEC was added
gene: EEFSEC was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EEFSEC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEFSEC were set to 39753114
Phenotypes for gene: EEFSEC were set to Neurodevelopmental disorder, MONDO:0700092, EEFSEC-related
Review for gene: EEFSEC was set to GREEN
Added comment: Nine individuals from 8 unrelated families reported with bi-allelic variants in this gene and progressive neurodevelopmental disorder manifesting with global developmental delay, progressive spasticity, ataxia, and seizures. Cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy. In line with the clinical phenotype, an eEFSec-RNAi Drosophila model displays progressive impairment of motor function, which is reflected in the synaptic defects in this model organisms.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.337 DAP3 Zornitza Stark Marked gene: DAP3 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.337 DAP3 Zornitza Stark Gene: dap3 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.337 DAP3 Zornitza Stark Classified gene: DAP3 as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.337 DAP3 Zornitza Stark Gene: dap3 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.336 DAP3 Zornitza Stark gene: DAP3 was added
gene: DAP3 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature
Mode of inheritance for gene: DAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DAP3 were set to 39701103
Phenotypes for gene: DAP3 were set to Mitochondrial disease MONDO:0044970, DAP3-related
Review for gene: DAP3 was set to GREEN
Added comment: DAP3 encodes the mitoribosomal small subunit 29 (MRPS29). Five unrelated individuals reported with bi-allelic variants in DAP3 and variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. Assessment of respiratory-chain function and proteomic profiling of fibroblasts from affected individuals demonstrated reduced MRPS29 protein amounts and, consequently, decreased levels of additional protein components of the mitoribosomal small subunit, as well as an associated combined deficiency of complexes I and IV. Lentiviral transduction of fibroblasts from affected individuals with wild-type DAP3 cDNA increased DAP3 mRNA expression and partially rescued protein levels of MRPS7, MRPS9, and complex I and IV subunits, demonstrating the pathogenicity of the DAP3 variants.
Sources: Literature
Deafness_IsolatedAndComplex v1.210 DAP3 Zornitza Stark Marked gene: DAP3 as ready
Deafness_IsolatedAndComplex v1.210 DAP3 Zornitza Stark Gene: dap3 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.210 DAP3 Zornitza Stark Classified gene: DAP3 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.210 DAP3 Zornitza Stark Gene: dap3 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.209 DAP3 Zornitza Stark gene: DAP3 was added
gene: DAP3 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: DAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DAP3 were set to 39701103
Phenotypes for gene: DAP3 were set to Mitochondrial disease MONDO:0044970, DAP3-related
Review for gene: DAP3 was set to GREEN
Added comment: DAP3 encodes the mitoribosomal small subunit 29 (MRPS29). Five unrelated individuals reported with bi-allelic variants in DAP3 and variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. Assessment of respiratory-chain function and proteomic profiling of fibroblasts from affected individuals demonstrated reduced MRPS29 protein amounts and, consequently, decreased levels of additional protein components of the mitoribosomal small subunit, as well as an associated combined deficiency of complexes I and IV. Lentiviral transduction of fibroblasts from affected individuals with wild-type DAP3 cDNA increased DAP3 mRNA expression and partially rescued protein levels of MRPS7, MRPS9, and complex I and IV subunits, demonstrating the pathogenicity of the DAP3 variants.
Sources: Literature
Mendeliome v1.2249 DAP3 Zornitza Stark Marked gene: DAP3 as ready
Mendeliome v1.2249 DAP3 Zornitza Stark Gene: dap3 has been classified as Green List (High Evidence).
Mitochondrial disease v0.966 DAP3 Zornitza Stark Classified gene: DAP3 as Green List (high evidence)
Mitochondrial disease v0.966 DAP3 Zornitza Stark Gene: dap3 has been classified as Green List (High Evidence).
Mendeliome v1.2249 DAP3 Zornitza Stark Classified gene: DAP3 as Green List (high evidence)
Mendeliome v1.2249 DAP3 Zornitza Stark Gene: dap3 has been classified as Green List (High Evidence).
Mitochondrial disease v0.965 DAP3 Zornitza Stark Marked gene: DAP3 as ready
Mitochondrial disease v0.965 DAP3 Zornitza Stark Gene: dap3 has been classified as Green List (High Evidence).
Mendeliome v1.2248 DAP3 Zornitza Stark gene: DAP3 was added
gene: DAP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DAP3 were set to 39701103
Phenotypes for gene: DAP3 were set to Mitochondrial disease MONDO:0044970, DAP3-related
Review for gene: DAP3 was set to GREEN
Added comment: DAP3 encodes the mitoribosomal small subunit 29 (MRPS29). Five unrelated individuals reported with bi-allelic variants in DAP3 and variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. Assessment of respiratory-chain function and proteomic profiling of fibroblasts from affected individuals demonstrated reduced MRPS29 protein amounts and, consequently, decreased levels of additional protein components of the mitoribosomal small subunit, as well as an associated combined deficiency of complexes I and IV. Lentiviral transduction of fibroblasts from affected individuals with wild-type DAP3 cDNA increased DAP3 mRNA expression and partially rescued protein levels of MRPS7, MRPS9, and complex I and IV subunits, demonstrating the pathogenicity of the DAP3 variants.
Sources: Literature
Mitochondrial disease v0.965 DAP3 Zornitza Stark Classified gene: DAP3 as Green List (high evidence)
Mitochondrial disease v0.965 DAP3 Zornitza Stark Gene: dap3 has been classified as Green List (High Evidence).
Mitochondrial disease v0.964 DAP3 Zornitza Stark gene: DAP3 was added
gene: DAP3 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: DAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DAP3 were set to 39701103
Phenotypes for gene: DAP3 were set to Mitochondrial disease MONDO:0044970, DAP3-related
Review for gene: DAP3 was set to GREEN
Added comment: DAP3 encodes the mitoribosomal small subunit 29 (MRPS29).

Five unrelated individuals reported with bi-allelic variants in DAP3 and variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. Assessment of respiratory-chain function and proteomic profiling of fibroblasts from affected individuals demonstrated reduced MRPS29 protein amounts and, consequently, decreased levels of additional protein components of the mitoribosomal small subunit, as well as an associated combined deficiency of complexes I and IV. Lentiviral transduction of fibroblasts from affected individuals with wild-type DAP3 cDNA increased DAP3 mRNA expression and partially rescued protein levels of MRPS7, MRPS9, and complex I and IV subunits, demonstrating the pathogenicity of the DAP3 variants.
Sources: Literature
Fetal anomalies v1.301 PDE12 Zornitza Stark Marked gene: PDE12 as ready
Fetal anomalies v1.301 PDE12 Zornitza Stark Gene: pde12 has been classified as Green List (High Evidence).
Fetal anomalies v1.301 PDE12 Zornitza Stark Classified gene: PDE12 as Green List (high evidence)
Fetal anomalies v1.301 PDE12 Zornitza Stark Gene: pde12 has been classified as Green List (High Evidence).
Fetal anomalies v1.300 PDE12 Zornitza Stark gene: PDE12 was added
gene: PDE12 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PDE12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE12 were set to 39567835
Phenotypes for gene: PDE12 were set to Mitochondrial disease MONDO:0044970, PDE12-related
Review for gene: PDE12 was set to GREEN
Added comment: 3 families (2 consanguineous) with 5 affected individuals with early onset mitochondrial disease presentation (3 liveborn, 2 intrauterine death).
-Family 1: 1 x infant death @3mths (no clinical information), 1 x 7yr old with neonatal respiratory and lactic acidosis, developmental delay, and mitochondrial respiratory chain deficiencies, and marked cytochrome c oxidase (COX) deficiency in muscle.
-Family 2: 1 x neonatal death @2days with metabolic acidosis and lactic acidosis, respiratory failure, lissencephaly, dysgenesis of the corpus callosum and extensive periventricular and subcortical cysts. Normal pyruvate dehydrogenase complex and electron
transfer chain activities in fibroblasts.
-Family 3: 2 x fetuses (13wks and 22wks) with increase nuchal translucency and reduced fetal movements. One had intra-uterine growth retardation, hydrops and cystic hygroma. The other had permanent flexion contractures of four limbs). Western blotting in fetal skeletal muscle showed absent respiratory chain complexes (I, IV, and V).

WES in all 3 families identified 3 different homozygous missense variants in PDE12 gene (p.Tyr155Cys, p.Gly372Glu, and p.Arg41Pro). All variants segregated with disease, were rare in gnomAD, and in silico pathogenicity prediction tools pointed towards a high likelihood of pathogenicity.

PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs. Patient-derived primary fibroblasts demonstrate diminished steady-state levels of PDE12 protein, whilst mitochondrial poly(A)-tail RNA sequencing revealed an accumulation of spuriously polyadenylated mitochondrial RNA, consistent with perturbed function of PDE12 protein.
Sources: Literature
Vascular Malformations_Germline v1.12 LRRC8C Zornitza Stark Marked gene: LRRC8C as ready
Vascular Malformations_Germline v1.12 LRRC8C Zornitza Stark Gene: lrrc8c has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v1.12 LRRC8C Zornitza Stark Classified gene: LRRC8C as Amber List (moderate evidence)
Vascular Malformations_Germline v1.12 LRRC8C Zornitza Stark Gene: lrrc8c has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2247 LRRC8C Zornitza Stark Marked gene: LRRC8C as ready
Mendeliome v1.2247 LRRC8C Zornitza Stark Gene: lrrc8c has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2247 LRRC8C Zornitza Stark Classified gene: LRRC8C as Amber List (moderate evidence)
Mendeliome v1.2247 LRRC8C Zornitza Stark Gene: lrrc8c has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.36 LRRC8C Zornitza Stark Marked gene: LRRC8C as ready
Intellectual disability syndromic and non-syndromic v1.36 LRRC8C Zornitza Stark Gene: lrrc8c has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.36 LRRC8C Zornitza Stark Classified gene: LRRC8C as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.36 LRRC8C Zornitza Stark Gene: lrrc8c has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.963 MT-TV Zornitza Stark edited their review of gene: MT-TV: Added comment: PMID 39468830: multiplex family with spastic paraplegia and homoplasmic variant, m.1661A > G; Changed publications: 39468830; Changed phenotypes: Ataxia, Seizures, Deafness, Spastic paraplegia
Autoimmune Lymphoproliferative Syndrome v0.30 STAT3 Ain Roesley Classified gene: STAT3 as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.30 STAT3 Ain Roesley Gene: stat3 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.29 STAT3 Ain Roesley gene: STAT3 was added
gene: STAT3 was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: STAT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STAT3 were set to 36228738
Phenotypes for gene: STAT3 were set to Autoimmune disease, multisystem, infantile-onset, 1 MIM#615952; STAT3-related early-onset multisystem autoimmune disease MONDO:0014414
Review for gene: STAT3 was set to GREEN
gene: STAT3 was marked as current diagnostic
Added comment: PMID:36228738;
Also known as STAT3 GoF syndrome, this review contains 191 patients with 72 unique variants
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.28 RASGRP1 Ain Roesley Classified gene: RASGRP1 as Amber List (moderate evidence)
Autoimmune Lymphoproliferative Syndrome v0.28 RASGRP1 Ain Roesley Gene: rasgrp1 has been classified as Amber List (Moderate Evidence).
Autoimmune Lymphoproliferative Syndrome v0.27 RASGRP1 Ain Roesley gene: RASGRP1 was added
gene: RASGRP1 was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: RASGRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RASGRP1 were set to 29155103; 39752212
Phenotypes for gene: RASGRP1 were set to Immunodeficiency 64 MIM#618534
Review for gene: RASGRP1 was set to AMBER
gene: RASGRP1 was marked as current diagnostic
Added comment: PMID:29155103; 2 siblings Chet for Thr214Ile and Lys322*

PMID:39752212; 1x hom 'LoF' variant (unable to access paper)

PMID: 39278845; 1x patient from a cohort of autoimmune lymphoproliferative immunodeficiencies. Thr312Ala. did not indicate if homozygous or single hit

Amber due to quality of papers/journals
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.26 PRKCD Ain Roesley Marked gene: PRKCD as ready
Autoimmune Lymphoproliferative Syndrome v0.26 PRKCD Ain Roesley Gene: prkcd has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.26 PRKCD Ain Roesley Classified gene: PRKCD as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.26 PRKCD Ain Roesley Gene: prkcd has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.25 PRKCD Ain Roesley gene: PRKCD was added
gene: PRKCD was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: PRKCD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRKCD were set to 37794137
Phenotypes for gene: PRKCD were set to Autoimmune lymphoproliferative syndrome, type III MIM#615559
Review for gene: PRKCD was set to GREEN
gene: PRKCD was marked as current diagnostic
Added comment: PMID:37794137; lit review with >10 families
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.24 LRBA Ain Roesley Marked gene: LRBA as ready
Autoimmune Lymphoproliferative Syndrome v0.24 LRBA Ain Roesley Gene: lrba has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.24 LRBA Ain Roesley Classified gene: LRBA as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.24 LRBA Ain Roesley Gene: lrba has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.23 LRBA Ain Roesley gene: LRBA was added
gene: LRBA was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: LRBA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRBA were set to 38302222; 25931386
Phenotypes for gene: LRBA were set to Immunodeficiency, common variable, 8, with autoimmunity MIM#614700
Review for gene: LRBA was set to GREEN
gene: LRBA was marked as current diagnostic
Added comment: PMID:38302222; 5x in Center for Chronic Immunodeficiency in Freiburg, Germany database

PMID:25931386; 2 families in the report + 6 others in review table
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.22 CTLA4 Ain Roesley Marked gene: CTLA4 as ready
Autoimmune Lymphoproliferative Syndrome v0.22 CTLA4 Ain Roesley Gene: ctla4 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.22 CTLA4 Ain Roesley Classified gene: CTLA4 as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.22 CTLA4 Ain Roesley Gene: ctla4 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.21 CTLA4 Ain Roesley gene: CTLA4 was added
gene: CTLA4 was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: CTLA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTLA4 were set to 39060684; 38302222
Phenotypes for gene: CTLA4 were set to Immune dysregulation with autoimmunity, immunodeficiency, and lymphoproliferation MIM#616100; autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency MONDO:0014493
Review for gene: CTLA4 was set to GREEN
gene: CTLA4 was marked as current diagnostic
Added comment: PMID: 39060684; 3x individuals. 1x missense, 1x splice 1x PTC

PMID:38302222; 9x in Center for Chronic Immunodeficiency in Freiburg, Germany database
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.20 ADA2 Ain Roesley Marked gene: ADA2 as ready
Autoimmune Lymphoproliferative Syndrome v0.20 ADA2 Ain Roesley Gene: ada2 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.20 ADA2 Ain Roesley Classified gene: ADA2 as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.20 ADA2 Ain Roesley Gene: ada2 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.19 ADA2 Ain Roesley gene: ADA2 was added
gene: ADA2 was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: ADA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADA2 were set to 39060684; 29271561; 30692987; 34721429
Phenotypes for gene: ADA2 were set to Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome MIM#615688
Review for gene: ADA2 was set to GREEN
gene: ADA2 was marked as current diagnostic
Added comment: PMID:39060684; 1x individual hom for Gly358Arg. 4x path in clinvar

PMID:29271561; 1x individual hom for c.882-2A>G. 5-year-old female who presented with features that mimicked autoimmune lymphoproliferative syndrome (ALPS) in the absence of classic features of DADA2

PMID:34721429; 2 sibs Chet for Leu188Phe and Thr187Pro and both had complete absence of inosine, an adenosine-derived product.
Leu188Phe is absent in gnomad v4 and clinvar. high conservation + 0.9 REVEL
Thr187Pro 1 het 0 homs in v4 and 1x clinvar citing this paper high conservation + 0.7 REVEL

PMID:30692987 ; 1x Chet Tyr456Cys and Trp399*. The missense 1x LP in clinvar by Invitae and 2 hets 0 homs in v4. high conservation + REVEL 0.7
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v0.18 NRAS Ain Roesley Marked gene: NRAS as ready
Autoimmune Lymphoproliferative Syndrome v0.18 NRAS Ain Roesley Gene: nras has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.18 NRAS Ain Roesley Classified gene: NRAS as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v0.18 NRAS Ain Roesley Gene: nras has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v0.17 NRAS Ain Roesley gene: NRAS was added
gene: NRAS was added to Autoimmune Lymphoproliferative Syndrome. Sources: Literature
Mode of inheritance for gene: NRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NRAS were set to 39060684; 17517660; 33011939
Phenotypes for gene: NRAS were set to autoimmune lymphoproliferative syndrome type 4 MONDO:0013767
Review for gene: NRAS was set to GREEN
gene: NRAS was marked as current diagnostic
Added comment: PMID:39060684; 1x individual with Gly13Asp

PMID:17517660; 1x de novo GoF variant Gly13Asp.
NB: PMID:21079152 states that the paper above is a somatic variant. However, lymphoblasts, monocytes, and buccal epithelial cells, all demonstrating a heterozygous variant

PMID:33011939; review with 11x individuals
Gly13Asp, Gly12Val, Gly12Ser, Gly13Cys
Sources: Literature
Prepair 1000+ v1.992 NTRK1 Michelle Torres reviewed gene: NTRK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10233776, 19250380, 10861667, 10982191, 20301726, 20089052; Phenotypes: Insensitivity to pain, congenital, with anhidrosis MIM#256800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 NPC1 Michelle Torres reviewed gene: NPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301473, 32138288; Phenotypes: Niemann-Pick disease, type C1 MIM#257220, Niemann-Pick disease, type D MIM#257220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 NKX6-2 Michelle Torres reviewed gene: NKX6-2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28575651, 15601927, 32246862, 32004679, 30285346; Phenotypes: Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy MIM#617560; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v1.83 MYMX Chirag Patel Classified gene: MYMX as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.83 MYMX Chirag Patel Gene: mymx has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.82 MYMX Chirag Patel Classified gene: MYMX as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.82 MYMX Chirag Patel Gene: mymx has been classified as Green List (High Evidence).
Mendeliome v1.2246 MYMX Chirag Patel Classified gene: MYMX as Green List (high evidence)
Mendeliome v1.2246 MYMX Chirag Patel Gene: mymx has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.81 MYMX Chirag Patel reviewed gene: MYMX: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39668186; Phenotypes: congenital myopathy MONDO:0019952, congenital myopathy with facial palsy, growth restriction, and dysmorphism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2245 MYMX Chirag Patel reviewed gene: MYMX: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39668186; Phenotypes: congenital myopathy MONDO:0019952, congenital myopathy with facial palsy, growth restriction, and dysmorphism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 NDUFS7 Michelle Torres reviewed gene: NDUFS7: Rating: GREEN; Mode of pathogenicity: None; Publications: 17604671, 17275378, 10360771, 22644603; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3 MIM#618224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2245 DDX53 Chirag Patel Classified gene: DDX53 as Green List (high evidence)
Mendeliome v1.2245 DDX53 Chirag Patel Gene: ddx53 has been classified as Green List (High Evidence).
Mendeliome v1.2244 DDX53 Chirag Patel gene: DDX53 was added
gene: DDX53 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DDX53 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: DDX53 were set to PMID: 39706195
Phenotypes for gene: DDX53 were set to autism spectrum disorder MONDO:0005258
Review for gene: DDX53 was set to GREEN
Added comment: The DDX53 gene is a single-exon RNA helicase which lies intronic to PTCHD1-AS (a multi-isoform long noncoding RNA (lncRNA) at the Xp22.11 locus. It is thought to play a role in RNA decay, RNA processing, ribosome biogenesis, and translation initiation. 9 affected males and 3 affected females from 9 unrelated families with ASD and rare, predicted damaging or loss-of-function variants in DDX53 (including a gene deletion involving DDX53 and exons of the noncoding RNA PTCHD1-AS). A further 26 individuals with ASD were identified (from Autism Speaks MSSNG and Simons Foundation Autism Research Initiative) with 19 rare, damaging DDX53 variations (mostly maternally inherited). No functional evidence.
Sources: Literature
Autism v0.205 DDX53 Chirag Patel Classified gene: DDX53 as Green List (high evidence)
Autism v0.205 DDX53 Chirag Patel Gene: ddx53 has been classified as Green List (High Evidence).
Autism v0.204 DDX53 Chirag Patel gene: DDX53 was added
gene: DDX53 was added to Autism. Sources: Literature
Mode of inheritance for gene: DDX53 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: DDX53 were set to PMID: 39706195
Phenotypes for gene: DDX53 were set to autism spectrum disorder MONDO:0005258
Review for gene: DDX53 was set to GREEN
Added comment: The DDX53 gene is a single-exon RNA helicase which lies intronic to PTCHD1-AS (a multi-isoform long noncoding RNA (lncRNA) at the Xp22.11 locus. It is thought to play a role in RNA decay, RNA processing, ribosome biogenesis, and translation initiation.

9 affected males and 3 affected females from 9 unrelated families with ASD and rare, predicted damaging or loss-of-function variants in DDX53 (including a gene deletion involving DDX53 and exons of the noncoding RNA PTCHD1-AS). A further 26 individuals with ASD were identified (from Autism Speaks MSSNG and Simons Foundation Autism Research Initiative) with 19 rare, damaging DDX53 variations (mostly maternally inherited). No functional evidence.
Sources: Literature
Prepair 1000+ v1.992 NAGS Michelle Torres reviewed gene: NAGS: Rating: GREEN; Mode of pathogenicity: None; Publications: 12594532, 17421020, 12459178, 12754705, 9877039; Phenotypes: N-acetylglutamate synthase deficiency MIM#237310; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 MMACHC Michelle Torres reviewed gene: MMACHC: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301503; Phenotypes: Methylmalonic aciduria and homocystinuria, cblC type MIM#277400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 MCOLN1 Michelle Torres reviewed gene: MCOLN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33963976, 32604955; Phenotypes: Mucolipidosis IV MIM#252650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 MCCC1 Michelle Torres reviewed gene: MCCC1: Rating: RED; Mode of pathogenicity: None; Publications: 31730530, 39188588; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 LRBA Michelle Torres reviewed gene: LRBA: Rating: GREEN; Mode of pathogenicity: None; Publications: 22608502, 22721650, 25468195, 26206937, 33155142; Phenotypes: Immunodeficiency, common variable, 8, with autoimmunity MIM#614700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 LPL Michelle Torres reviewed gene: LPL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lipoprotein lipase deficiency MIM#238600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 LIAS Michelle Torres reviewed gene: LIAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 22152680, 24334290, 26108146; Phenotypes: Hyperglycinemia, lactic acidosis, and seizures MIM#614462; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 SYP Ee Ming Wong reviewed gene: SYP: Rating: AMBER; Mode of pathogenicity: None; Publications: 23966691, 19377476; Phenotypes: Intellectual developmental disorder, X-linked 96 (MIM#300802); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Prepair 1000+ v1.992 STIL Ee Ming Wong changed review comment from: - More than 10 unrelated families reported.
- Onset at birth
- PMID: 24485834; 29352115: Complete loss of STIL is not compatible with life. Genetic mutations in human STIL result in
1. residual expression or
2. stabilization of STIL: PTCs that delete of the critical C-terminal KEN Box domain involved in Anaphase-Promoting-Complex/Cyclosome (APC/C)-mediated degradation of STIL5 were shown to result in mutant STIL stabilization and accumulation and subsequent centriole amplification. Demonstrated for p.(Val1219X) and p.(Gln1239X), suggested gain of function.; to: - More than 10 unrelated families reported.
- Onset at birth
- PMID: 24485834; 29352115: Complete loss of STIL is not compatible with life. Genetic mutations in human STIL result in
1. residual expression or
2. stabilization of mutant STIL: PTCs that delete of the critical C-terminal KEN Box domain involved in Anaphase-Promoting-Complex/Cyclosome (APC/C)-mediated degradation of STIL5 were shown to result in mutant STIL stabilization and accumulation and subsequent centriole amplification. Demonstrated for p.(Val1219X) and p.(Gln1239X), suggested gain of function.
Prepair 1000+ v1.992 STIL Ee Ming Wong reviewed gene: STIL: Rating: GREEN; Mode of pathogenicity: None; Publications: 19215732, 22989186, 25218063, 33132204, 32677750, 29230157, 29352115, 24485834; Phenotypes: Microcephaly 7, primary, (MIM# 612703); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 SLC25A46 Ee Ming Wong reviewed gene: SLC25A46: Rating: GREEN; Mode of pathogenicity: None; Publications: 26168012, 27543974, 30178502; Phenotypes: Neuropathy, hereditary motor and sensory, type VIB (MIM# 616505), Pontocerebellar hypoplasia, type 1E (MIM# 619303); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 SLC25A19 Ee Ming Wong reviewed gene: SLC25A19: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301539, 31095747; Phenotypes: Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type) (MIM#613710), Microcephaly, Amish type (MIM#607196); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 SLC17A5 Ee Ming Wong reviewed gene: SLC17A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 10947946, 5516337, 33862140; Phenotypes: Sialic acid storage disorder, infantile (MIM#269920); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Congenital Heart Defect v0.429 RBFOX2 Ain Roesley Phenotypes for gene: RBFOX2 were changed from RBFOX2-related congenital heart disorder (MONDO:0100557) to RBFOX2-related congenital heart disorder (MONDO:0100557)
Congenital Heart Defect v0.428 RBFOX2 Ain Roesley Phenotypes for gene: RBFOX2 were changed from Congenital heart disease MONDO:0005453, RBFOX2-related to RBFOX2-related congenital heart disorder (MONDO:0100557)
Fetal anomalies v1.299 RBFOX2 Ain Roesley Phenotypes for gene: RBFOX2 were changed from Congenital heart disease MONDO:0005453, RBFOX2-related to RBFOX2-related congenital heart disorder (MONDO:0100557)
Mendeliome v1.2243 RBFOX2 Ain Roesley Phenotypes for gene: RBFOX2 were changed from Congenital heart disease MONDO:0005453, RBFOX2-related to RBFOX2-related congenital heart disorder (MONDO:0100557)
Prepair 1000+ v1.992 SDCCAG8 Ee Ming Wong reviewed gene: SDCCAG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 22819833, 20835237, 32432520, 22626039, 31534065, 26968886; Phenotypes: Bardet-Biedl syndrome 16 (MIM# 615993), Senior-Loken syndrome 7 (MIM# 613615); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 SDCCAG8 Ee Ming Wong Deleted their review
Prepair 1000+ v1.992 SDCCAG8 Ee Ming Wong reviewed gene: SDCCAG8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 16 (MIM# 615993); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 PLOD2 Shakira Heerah reviewed gene: PLOD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22689593, 12881513, 33664768, 33778323, 29178448; Phenotypes: Bruck syndrome 2, MIM#609220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 PHGDH Shakira Heerah reviewed gene: PHGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 39638571, 37964427, 24836451, 25152457, 11055895, 19235232; Phenotypes: Neu-Laxova syndrome 1 MIM#256520, Phosphoglycerate dehydrogenase deficiency MIM#601815; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.298 RBFOX2 Zornitza Stark Phenotypes for gene: RBFOX2 were changed from to Congenital heart disease MONDO:0005453, RBFOX2-related
Fetal anomalies v1.297 RBFOX2 Zornitza Stark Classified gene: RBFOX2 as Green List (high evidence)
Fetal anomalies v1.297 RBFOX2 Zornitza Stark Gene: rbfox2 has been classified as Green List (High Evidence).
Fetal anomalies v1.296 RBFOX2 Zornitza Stark reviewed gene: RBFOX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital heart disease MONDO:0005453, RBFOX2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2242 RBFOX2 Zornitza Stark Phenotypes for gene: RBFOX2 were changed from Hypoplastic left heart syndrome (HLHS) MONDO:0004933 to Congenital heart disease MONDO:0005453, RBFOX2-related
Mendeliome v1.2241 RBFOX2 Zornitza Stark Classified gene: RBFOX2 as Green List (high evidence)
Mendeliome v1.2241 RBFOX2 Zornitza Stark Gene: rbfox2 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.427 RBFOX2 Zornitza Stark Phenotypes for gene: RBFOX2 were changed from Hypoplastic left heart syndrome (HLHS) MONDO:0004933 to Congenital heart disease MONDO:0005453, RBFOX2-related
Congenital Heart Defect v0.426 RBFOX2 Zornitza Stark Classified gene: RBFOX2 as Green List (high evidence)
Congenital Heart Defect v0.426 RBFOX2 Zornitza Stark Gene: rbfox2 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.425 RBFOX2 Zornitza Stark edited their review of gene: RBFOX2: Added comment: STRONG by ClinGen. At least 5 unrelated families and supportive zebrafish model.; Changed rating: GREEN; Changed phenotypes: Congenital heart disease MONDO:0005453, RBFOX2-related
Intellectual disability syndromic and non-syndromic v1.35 CCT3 Zornitza Stark reviewed gene: CCT3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech or visual impairment and brain hypomyelination, MIM# 621034; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v1.92 CCT3 Zornitza Stark Phenotypes for gene: CCT3 were changed from neurodevelopmental disorder MONDO:0700092, CCT3-related to Neurodevelopmental disorder with speech or visual impairment and brain hypomyelination, MIM# 621034
Genetic Epilepsy v1.91 CCT3 Zornitza Stark reviewed gene: CCT3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech or visual impairment and brain hypomyelination, MIM# 621034; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2240 CCT3 Zornitza Stark Phenotypes for gene: CCT3 were changed from neurodevelopmental disorder MONDO:0700092, CCT3-related to Neurodevelopmental disorder with speech or visual impairment and brain hypomyelination, MIM# 621034
Mendeliome v1.2239 CCT3 Zornitza Stark reviewed gene: CCT3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech or visual impairment and brain hypomyelination, MIM# 621034; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.35 TCP1 Zornitza Stark Phenotypes for gene: TCP1 were changed from neurodevelopmental disorder MONDO:0700092, TCP1-related to Intellectual developmental disorder with polymicrogyria and seizures, MIM# 621021
Intellectual disability syndromic and non-syndromic v1.34 TCP1 Zornitza Stark reviewed gene: TCP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with polymicrogyria and seizures, MIM# 621021; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v1.91 TCP1 Zornitza Stark Phenotypes for gene: TCP1 were changed from neurodevelopmental disorder MONDO:0700092, TCP1-related to Intellectual developmental disorder with polymicrogyria and seizures, MIM# 621021
Genetic Epilepsy v1.90 TCP1 Zornitza Stark reviewed gene: TCP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with polymicrogyria and seizures, MIM# 621021; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2239 TCP1 Zornitza Stark Phenotypes for gene: TCP1 were changed from neurodevelopmental disorder MONDO:0700092, TCP1-related to Intellectual developmental disorder with polymicrogyria and seizures, MIM# 621021
Mendeliome v1.2238 TCP1 Zornitza Stark reviewed gene: TCP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with polymicrogyria and seizures, MIM# 621021; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polymicrogyria and Schizencephaly v0.195 TCP1 Zornitza Stark Phenotypes for gene: TCP1 were changed from neurodevelopmental disorder MONDO:0700092, TCP1-related to Intellectual developmental disorder with polymicrogyria and seizures, MIM# 621021
Polymicrogyria and Schizencephaly v0.194 TCP1 Zornitza Stark reviewed gene: TCP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with polymicrogyria and seizures, MIM# 621021; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.117 LIFR Renee Santoreneos reviewed gene: LIFR: Rating: GREEN; Mode of pathogenicity: None; Publications: 38025229; Phenotypes: CAKUT; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.2238 TAOK2 Achchuthan Shanmugasundram reviewed gene: TAOK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 39737487; Phenotypes: neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.992 GORAB Clare Hunt reviewed gene: GORAB: Rating: GREEN; Mode of pathogenicity: None; Publications: 19681135, 9018419, 18348262; Phenotypes: Geroderma osteodysplasticum, MIM#231070, MONDO:0009271; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 GALC Clare Hunt reviewed gene: GALC: Rating: GREEN; Mode of pathogenicity: None; Publications: 20886637, 21070211, 30899093, 24252386; Phenotypes: Krabbe disease, MIM# 245200, MONDO:0009499; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 CYB5R3 Ee Ming Wong reviewed gene: CYB5R3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31898843, 38303731; Phenotypes: Methemoglobinemia, type II (MIM# 250800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 LAMA2 Lauren Thomas reviewed gene: LAMA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30055037; Phenotypes: Muscular dystrophy, congenital, merosin deficient or partially deficient, MIM# 607855, Muscular dystrophy, limb-girdle, autosomal recessive 23, MIM# 618138; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 LDHA Michelle Torres reviewed gene: LDHA: Rating: GREEN; Mode of pathogenicity: None; Publications: 36292720; Phenotypes: Glycogen storage disease XI MIM#612933; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 KCNE1 Michelle Torres reviewed gene: KCNE1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Jervell and Lange-Nielsen syndrome 2, MIM#612347; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 JUP Michelle Torres reviewed gene: JUP: Rating: GREEN; Mode of pathogenicity: None; Publications: 34587761; Phenotypes: Naxos disease MIM#601214; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 KATNB1 Lauren Thomas reviewed gene: KATNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25521378, 25521379, 26640080; Phenotypes: Lissencephaly 6, with microcephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 UBE2T Ee Ming Wong reviewed gene: UBE2T: Rating: GREEN; Mode of pathogenicity: None; Publications: 32646888, 26119737, 26046368, 26085575; Phenotypes: Fanconi anemia, complementation group T (MIM#616435); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 IL10RB Michelle Torres reviewed gene: IL10RB: Rating: GREEN; Mode of pathogenicity: None; Publications: 19890111, 21519361, 35187668, 31096038; Phenotypes: Inflammatory bowel disease 25, early onset, autosomal recessive MIM#612567; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 IGHMBP2 Michelle Torres reviewed gene: IGHMBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34785121, 25439726; Phenotypes: Neuronopathy, distal hereditary motor, autosomal recessive 1 MIM#604320, Charcot-Marie-Tooth disease, axonal, type 2S MIM#616155; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 TBX22 Ee Ming Wong changed review comment from: 1. Cleft palate with ankyloglossia (MIM# 303400)
- More than 10 families reported with cleft palate/ankyloglossia and variants in this gene.
- PMID:36901693 - Characterised by a cleft palate phenotype that is most often present in males and ranges from a high-arched palate, bifid uvula, submucous cleft palate, soft cleft palate, to complete cleft palate
- OMIM, PMID:36901693 - Ankyloglossia/ bifid uvula/cleft palate reported in heterozygous females
- Overall mild phenotype although PMID: 21375406 describes 1x TBX22 hemizygous individual with unilateral complete cleft lip and palate, ankyloglossia, hypodontia of the left maxillary second premolar, carpal bone anomalies, and hypoplastic thumb of the right hand. No other genes were tested.

2. Abruzzo-Erickson syndrome, MIM# 302905
PMID:22784330 - Single family reported with Abruzzo-Erickson syndrome, a syndromic form of cleft palate. Did not find additional reports on this phenotype; to: 1. Cleft palate with ankyloglossia (MIM# 303400)
- More than 10 families reported with cleft palate/ankyloglossia and variants in this gene.
- PMID:36901693 - Characterised by a cleft palate phenotype that is most often present in males and ranges from a high-arched palate, bifid uvula, submucous cleft palate, soft cleft palate, to complete cleft palate
- OMIM, PMID:36901693 - Ankyloglossia/ bifid uvula/cleft palate reported in heterozygous females
- Overall mild phenotype although PMID: 21375406 describes 1x TBX22 hemizygous individual with unilateral complete cleft lip and palate, ankyloglossia, hypodontia of the left maxillary second premolar, carpal bone anomalies, and hypoplastic thumb of the right hand. No other genes were tested.

2. Abruzzo-Erickson syndrome, MIM# 302905
PMID:22784330 - Single family reported with Abruzzo-Erickson syndrome, a syndromic form of cleft palate. Did not find additional reports on this phenotype
Prepair 1000+ v1.992 TBX22 Ee Ming Wong reviewed gene: TBX22: Rating: AMBER; Mode of pathogenicity: None; Publications: 36901693, 22784330, 21375406; Phenotypes: Cleft palate with ankyloglossia (MIM# 303400); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Prepair 1000+ v1.992 HSPG2 Michelle Torres reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37761893; Phenotypes: Schwartz-Jampel syndrome, type 1, MIM# 255800, Dyssegmental dysplasia, Silverman-Handmaker type, MIM# 224410; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 GRHPR Michelle Torres reviewed gene: GRHPR: Rating: AMBER; Mode of pathogenicity: None; Publications: 20301742, 28569194; Phenotypes: Hyperoxaluria, primary, type II MIM#260000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 GPSM2 Michelle Torres reviewed gene: GPSM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20602914, 22578326, 28387217, 27180139, 27064331; Phenotypes: Chudley-McCullough syndrome MIM#604213; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 GLIS3 Michelle Torres reviewed gene: GLIS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21139041, 35410112, 35394098, 34093443; Phenotypes: Diabetes mellitus, neonatal, with congenital hypothyroidism MIM#610199; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 GJA1 Michelle Torres reviewed gene: GJA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23951358, 29902798, 34035645; Phenotypes: Craniometaphyseal dysplasia, autosomal recessive MIM#218400, Oculodentodigital dysplasia, autosomal recessive MIM#257850; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2238 RBFOX2 Jonathon Bradshaw reviewed gene: RBFOX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26785492, 27670201, 32368696, 27485310, 25205790, 35137168, 26785492, 28991257; Phenotypes: RBFOX2-related congenital heart disorder (MONDO:0100557); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.2238 RBFOX2 Jonathon Bradshaw Deleted their review
Mendeliome v1.2238 RBFOX2 Jonathon Bradshaw changed review comment from: - PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (1x nonsense, 1x frameshift, 1x canonical splice variants). All 3 probands have hypoplastic left heart syndrome (HLHS) and no extra-cardiac features. Same cohort later included in PMID: 32368696, listed one additional de novo variant in this gene (missense variant) in a patient with conotruncal defects (CTDs).

- PMID: 28991257: Same research consortium as above, an additional splice variant observed in a singleton from the CHD cohort identified as a LoF predicted heterozygous mutation.

- PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492.

- PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing.

- PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS.

- PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.

- 2x NMD-predicted de novo individuals with cardiac defects have been observed (internal data).

- ClinVar: one current pathogenic entry: c.523dup (p.Ser175fs). This patient had a complex congenital cardiac defect, choreiform movement disorder, developmental delay, a clotting disorder, intermittent cyanosis, chronic lung disease, low muscle tone, short stature and failure to gain weight, mild dysmorphisms, and mild joint laxity. Brain MRI shows a stable chronic infarction, stable cerebral volume loss, and ex-vacuo prominence of ventricles (personal communication).

- ClinGen has curated this gene. Strong association and evidence supporting LoF as a mechanism of disease.; to: - PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (1x nonsense, 1x frameshift, 1x canonical splice variants). All 3 probands have hypoplastic left heart syndrome (HLHS) and no extra-cardiac features. Same cohort later included in PMID: 32368696, listed one additional de novo variant in this gene (missense variant) in a patient with conotruncal defects (CTDs).

- PMID: 28991257: Same research consortium as above, an additional splice variant observed in a singleton from the CHD cohort identified as a LoF predicted heterozygous mutation.

- PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492.

- PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing.

- PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS.

- PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.

- 2x NMD-predicted de novo individuals with cardiac defects have been observed (internal data).

- ClinVar: one current pathogenic entry: c.523dup (p.Ser175fs). This patient had a complex congenital cardiac defect, choreiform movement disorder, developmental delay, a clotting disorder, intermittent cyanosis, chronic lung disease, low muscle tone, short stature and failure to gain weight, mild dysmorphisms, and mild joint laxity. Brain MRI shows a stable chronic infarction, stable cerebral volume loss, and ex-vacuo prominence of ventricles (personal communication).

- ClinGen has curated this gene. Strong association and evidence supporting LoF as a mechanism of disease.
Mendeliome v1.2238 RBFOX2 Jonathon Bradshaw reviewed gene: RBFOX2: Rating: GREEN; Mode of pathogenicity: None; Publications: (PMID: 26785492, 27670201, 32368696, 27485310, 25205790, 35137168, 26785492, 28991257); Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Prepair 1000+ v1.992 FOXN1 Michelle Torres reviewed gene: FOXN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10206641, 20978268, 20978268, 28636882, 31566583, 31447097; Phenotypes: T-cell immunodeficiency, congenital alopecia, and nail dystrophy MIM#601705; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 FANCE Michelle Torres reviewed gene: FANCE: Rating: GREEN; Mode of pathogenicity: None; Publications: 11001585, 31586946, 7662964, 9382107, 9147877, 10205272; Phenotypes: Fanconi anemia, complementation group E MIM#600901; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 EOGT Michelle Torres reviewed gene: EOGT: Rating: GREEN; Mode of pathogenicity: None; Publications: 31368252, 23522784, 29924900; Phenotypes: Adams-Oliver syndrome 4 MIM#615297; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 ELP1 Clare Hunt changed review comment from: From OMIM; Hereditary sensory and autonomic neuropathy type III (HSAN3) is an autosomal recessive neurodegenerative disorder with onset soon after birth. Affected individuals show progressive symptoms resulting from depletion of sensory proprioceptive and autonomic neurons. Features include gastrointestinal dysfunction, gastroesophageal reflux, vomiting crises, recurrent pneumonia, seizures, gait abnormalities with loss of ambulation, kyphoscoliosis, postural hypotension, hypertension crises, absence of fungiform papillae on the tongue, decreased deep tendon reflexes, defective lacrimation, and impaired pain and temperature perception. The disorder is inevitably fatal, with only 50% of patients reaching 40 years of age.

HSAN3 has a high carrier frequency in the Ashkenazi Jewish population (summary by Morini et al., 2016).

Gene previously referred to as IKBKAP gene (ELP1; 603722) located on chromosome 9q31. Also previously referred to as Riley-Day syndrome.
From Mendeliome; AR dysautonomia: the condition is predominantly caused by homozygosity of c.2204+6T>C (major familial dysautonomia AJ haplotype - causes tissue-specific exon 20 skipping) in Ashkenazi Jewish individuals. Other variants have been reported in association with the disease.; to: From OMIM; Hereditary sensory and autonomic neuropathy type III (HSAN3) is an autosomal recessive neurodegenerative disorder with onset soon after birth. Affected individuals show progressive symptoms resulting from depletion of sensory proprioceptive and autonomic neurons. Features include gastrointestinal dysfunction, gastroesophageal reflux, vomiting crises, recurrent pneumonia, seizures, gait abnormalities with loss of ambulation, kyphoscoliosis, postural hypotension, hypertension crises, absence of fungiform papillae on the tongue, decreased deep tendon reflexes, defective lacrimation, and impaired pain and temperature perception. The disorder is inevitably fatal, with only 50% of patients reaching 40 years of age.

HSAN3 has a high carrier frequency in the Ashkenazi Jewish population (summary by Morini et al., 2016).

Gene previously referred to as IKBKAP gene (ELP1; 603722) located on chromosome 9q31.

From Mendeliome; AR dysautonomia: the condition is predominantly caused by homozygosity of c.2204+6T>C (major familial dysautonomia AJ haplotype - causes tissue-specific exon 20 skipping) in Ashkenazi Jewish individuals. Other variants have been reported in association with the disease.
Prepair 1000+ v1.992 ELP1 Clare Hunt changed review comment from: From OMIM; Hereditary sensory and autonomic neuropathy type III (HSAN3) is an autosomal recessive neurodegenerative disorder with onset soon after birth. Affected individuals show progressive symptoms resulting from depletion of sensory proprioceptive and autonomic neurons. Features include gastrointestinal dysfunction, gastroesophageal reflux, vomiting crises, recurrent pneumonia, seizures, gait abnormalities with loss of ambulation, kyphoscoliosis, postural hypotension, hypertension crises, absence of fungiform papillae on the tongue, decreased deep tendon reflexes, defective lacrimation, and impaired pain and temperature perception. The disorder is inevitably fatal, with only 50% of patients reaching 40 years of age. HSAN3 has a high carrier frequency in the Ashkenazi Jewish population (summary by Morini et al., 2016).

Gene previously referred to as IKBKAP gene (ELP1; 603722) located on chromosome 9q31. Also previously referred to as Riley-Day syndrome.; to: From OMIM; Hereditary sensory and autonomic neuropathy type III (HSAN3) is an autosomal recessive neurodegenerative disorder with onset soon after birth. Affected individuals show progressive symptoms resulting from depletion of sensory proprioceptive and autonomic neurons. Features include gastrointestinal dysfunction, gastroesophageal reflux, vomiting crises, recurrent pneumonia, seizures, gait abnormalities with loss of ambulation, kyphoscoliosis, postural hypotension, hypertension crises, absence of fungiform papillae on the tongue, decreased deep tendon reflexes, defective lacrimation, and impaired pain and temperature perception. The disorder is inevitably fatal, with only 50% of patients reaching 40 years of age.

HSAN3 has a high carrier frequency in the Ashkenazi Jewish population (summary by Morini et al., 2016).

Gene previously referred to as IKBKAP gene (ELP1; 603722) located on chromosome 9q31. Also previously referred to as Riley-Day syndrome.
From Mendeliome; AR dysautonomia: the condition is predominantly caused by homozygosity of c.2204+6T>C (major familial dysautonomia AJ haplotype - causes tissue-specific exon 20 skipping) in Ashkenazi Jewish individuals. Other variants have been reported in association with the disease.
Prepair 1000+ v1.992 ELP1 Clare Hunt reviewed gene: ELP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11179021, 4322121, 16777588, 30905397; Phenotypes: Dysautonomia, familial MIM#223900, Hereditary sensory and autonomic neuropathy type III (HSAN3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 EIF2S3 Clare Hunt reviewed gene: EIF2S3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23063529, 27333055, 28055140; Phenotypes: MEHMO syndrome, MIM# 300148; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.992 EDAR Clare Hunt changed review comment from: Well-established gene-disease association. Hypohidrotic ectodermal dysplasia (HED) is characterised by hypotrichosis (sparseness of scalp and body hair), hypohidrosis (reduced ability to sweat), and hypodontia (congenital absence of teeth). Biallelic loss-of-function variants cause early onset classic HED, whereas monoallelic dominant-negative variants cause mild HED.; to: Well-established gene-disease association. Hypohidrotic ectodermal dysplasia (HED) is characterised by hypotrichosis (sparseness of scalp and body hair), hypohidrosis (reduced ability to sweat), and hypodontia (congenital absence of teeth). Biallelic loss-of-function variants cause early onset classic HED, whereas monoallelic dominant-negative variants cause mild HED.
Prepair 1000+ v1.992 EDAR Clare Hunt reviewed gene: EDAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 10431241, 16435307, 20979233, 23401279; Phenotypes: autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619, autosomal dominant hypohidrotic ectodermal dysplasia MONDO:0015884; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Prepair 1000+ v1.992 ENPP1 Michelle Torres reviewed gene: ENPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36150100; Phenotypes: Arterial calcification, generalized, of infancy, 1 MIM#208000, Hypophosphatemic rickets, autosomal recessive, 2 MIM#613312; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 TAZ Ee Ming Wong reviewed gene: TAZ: Rating: GREEN; Mode of pathogenicity: None; Publications: 25299040; Phenotypes: Barth syndrome (MIM# 302060); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v1.34 EP400 Bryony Thompson Marked gene: EP400 as ready
Intellectual disability syndromic and non-syndromic v1.34 EP400 Bryony Thompson Gene: ep400 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.34 EP400 Bryony Thompson Classified gene: EP400 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.34 EP400 Bryony Thompson Gene: ep400 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.33 EP400 Sangavi Sivagnanasundram gene: EP400 was added
gene: EP400 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EP400 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EP400 were set to 39708813
Phenotypes for gene: EP400 were set to neurodevelopmental disorder with or without early-onset generalized epilepsy - MONDO:0030930
Review for gene: EP400 was set to GREEN
Added comment: 6 unrelated probands presenting with epilepsy with NDD (including ID and DD) had compound heterozygous variants in EP400. They were confirmed in trans and inherited from their asymptomatic parents.

Knockdown of EP400 ortholog in Drosophila showed an increase in seizure-like susceptibility and abnormal neurological behaviour.
Sources: Literature
Vascular Malformations_Germline v1.11 LRRC8C Sangavi Sivagnanasundram gene: LRRC8C was added
gene: LRRC8C was added to Vascular Malformations_Germline. Sources: Literature
Mode of inheritance for gene: LRRC8C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LRRC8C were set to 39623139
Phenotypes for gene: LRRC8C were set to TIMES syndrome MIM#621056
Mode of pathogenicity for gene: LRRC8C was set to Other
Review for gene: LRRC8C was set to AMBER
Added comment: TIMES syndrome is a multisystem disorder characterised by considerable phenotypic variability, but overlapping features include telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature. Patients exhibit striking cutis marmorata in infancy.

Two individuals from unrelated families presenting with similar features consistent with TIMES syndrome.
Leu400IlefsTer8 and Val390Leu variants were identified however the proposed mechanism of disease is GoF.
Supporting in vitro functional assay was conducted however further evidence is required to upgrade the gene classification.
Sources: Literature
Genetic Epilepsy v1.90 EP400 Bryony Thompson Marked gene: EP400 as ready
Genetic Epilepsy v1.90 EP400 Bryony Thompson Gene: ep400 has been classified as Green List (High Evidence).
Prepair 1000+ v1.992 SUMF1 Ee Ming Wong reviewed gene: SUMF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30896912; Phenotypes: Multiple sulfatase deficiency (MIM#272200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v1.90 EP400 Bryony Thompson Classified gene: EP400 as Green List (high evidence)
Genetic Epilepsy v1.90 EP400 Bryony Thompson Gene: ep400 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.33 LRRC8C Sangavi Sivagnanasundram gene: LRRC8C was added
gene: LRRC8C was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LRRC8C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LRRC8C were set to 39623139
Phenotypes for gene: LRRC8C were set to TIMES syndrome MIM#621056
Mode of pathogenicity for gene: LRRC8C was set to Other
Review for gene: LRRC8C was set to AMBER
Added comment: TIMES syndrome is a multisystem disorder characterised by considerable phenotypic variability, but overlapping features include telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature. Patients exhibit striking cutis marmorata in infancy.

Two individuals from unrelated families presenting with similar features consistent with TIMES syndrome.
Leu400IlefsTer8 and Val390Leu variants were identified however the proposed mechanism of disease is GoF.
Supporting in vitro functional assay was conducted however further evidence is required to upgrade the gene classification.
Sources: Literature
Mendeliome v1.2238 EP400 Bryony Thompson Marked gene: EP400 as ready
Mendeliome v1.2238 EP400 Bryony Thompson Gene: ep400 has been classified as Green List (High Evidence).
Mendeliome v1.2238 EP400 Bryony Thompson Classified gene: EP400 as Green List (high evidence)
Mendeliome v1.2238 EP400 Bryony Thompson Gene: ep400 has been classified as Green List (High Evidence).
Mendeliome v1.2237 LRRC8C Sangavi Sivagnanasundram changed review comment from: TIMES syndrome is a multisystem disorder characterised by considerable phenotypic variability, but overlapping features include telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature. Patients exhibit striking cutis marmorata in infancy.

Two individuals from unrelated families presenting with similar features consistent with TIMES syndrome.
Leu400IlefsTer8 and Val390Leu variants were identified however the proposed mechanism of disease is GoF.
Sources: Literature; to: TIMES syndrome is a multisystem disorder characterised by considerable phenotypic variability, but overlapping features include telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature. Patients exhibit striking cutis marmorata in infancy.

Two individuals from unrelated families presenting with similar features consistent with TIMES syndrome.
Leu400IlefsTer8 and Val390Leu variants were identified however the proposed mechanism of disease is GoF.
Supporting in vitro functional assay was conducted however further evidence is required to upgrade the gene classification.
Sources: Literature
Mendeliome v1.2237 LRRC8C Sangavi Sivagnanasundram edited their review of gene: LRRC8C: Changed rating: AMBER
Prepair 1000+ v1.992 DPAGT1 Clare Hunt reviewed gene: DPAGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12872255, 22304930, 22742743, 16870884; Phenotypes: Congenital disorder of glycosylation, type Ij, MIM# 608093, DPAGT1-CDG MONDO:0011964, Myasthenic syndrome, congenital, 13, with tubular aggregates, MIM 614750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 ITPR1 Lauren Thomas reviewed gene: ITPR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27108797, 31340402, 30242502, 29169895; Phenotypes: Gillespie syndrome, MIM# 206700; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v1.992 EIF2B1 Michelle Torres reviewed gene: EIF2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34745209; Phenotypes: Leukoencephalopathy with vanishing white matter 1, with or without ovarian failure MIM#603896; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 DNAI2 Clare Hunt reviewed gene: DNAI2: Rating: AMBER; Mode of pathogenicity: None; Publications: 18950741; Phenotypes: Ciliary dyskinesia, primary, 9, with or without situs inversus, MIM# 612444; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v1.89 EP400 Sangavi Sivagnanasundram gene: EP400 was added
gene: EP400 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: EP400 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EP400 were set to 39708813
Phenotypes for gene: EP400 were set to neurodevelopmental disorder with or without early-onset generalized epilepsy - MONDO:0030930
Review for gene: EP400 was set to GREEN
Added comment: 6 unrelated probands presenting with epilepsy with NDD had compound heterozygous variants in EP400. They were confirmed in trans and inherited from their asymptomatic parents.

Knockdown of EP400 ortholog in Drosophila showed an increase in seizure-like susceptibility and abnormal neurological behaviour.
Sources: Literature
Mendeliome v1.2237 EP400 Sangavi Sivagnanasundram gene: EP400 was added
gene: EP400 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EP400 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EP400 were set to 39708813
Phenotypes for gene: EP400 were set to neurodevelopmental disorder with or without early-onset generalized epilepsy - MONDO:0030930
Review for gene: EP400 was set to GREEN
Added comment: 6 unrelated probands presenting with epilepsy with NDD had compound heterozygous variants in EP400. They were confirmed in trans and inherited from their asymptomatic parents.

Knockdown of EP400 ortholog in Drosophila showed an increase in seizure-like susceptibility and abnormal neurological behaviour.
Sources: Literature
Prepair 1000+ v1.992 SCARB2 Ee Ming Wong reviewed gene: SCARB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26677510, 35346091; Phenotypes: Epilepsy, progressive myoclonic 4, with or without renal failure (MIM #254900); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 EFNB1 Michelle Torres reviewed gene: EFNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15166289, 18627045, 23335590; Phenotypes: Craniofrontonasal dysplasia MIM#304110; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.992 ISCA1 Lauren Thomas changed review comment from: Multiple mitochondrial dysfunctions syndrome-5 (MMDS5) is an autosomal recessive disorder characterized mainly by progressive neurologic deterioration beginning in early infancy. Affected individuals have essentially no psychomotor development and have early-onset seizures with neurologic decline and spasticity. Brain imaging shows severe leukodystrophy with evidence of dys- or delayed myelination. Death usually occurs in early childhood.

HGNC approved symbol/name: ISCA1
Is the phenotype(s) severe and onset <18yo? Yes
Known technical challenges? No
Gene reported in 3 independent families: Yes; to: Multiple mitochondrial dysfunctions syndrome-5 (MMDS5) is an autosomal recessive disorder characterized mainly by progressive neurologic deterioration beginning in early infancy. Affected individuals have essentially no psychomotor development and have early-onset seizures with neurologic decline and spasticity. Brain imaging shows severe leukodystrophy with evidence of dys- or delayed myelination. Death usually occurs in early childhood.

HGNC approved symbol/name: ISCA1
Is the phenotype(s) severe and onset <18yo? Yes
Known technical challenges? No
Gene reported in 3 independent families: Yes

Most recent case report: PMID 32092383 (4th independent family)
Prepair 1000+ v1.992 ISCA1 Lauren Thomas changed review comment from: Multiple mitochondrial dysfunctions syndrome-5 (MMDS5) is an autosomal recessive disorder characterized mainly by progressive neurologic deterioration beginning in early infancy. Affected individuals have essentially no psychomotor development and have early-onset seizures with neurologic decline and spasticity. Brain imaging shows severe leukodystrophy with evidence of dys- or delayed myelination. Death usually occurs in early childhood.

HGNC approved symbol/name: ISCA1
Is the phenotype(s) severe and onset <18yo? Yes
Known technical challenges? No
Gene reported in 3 independent families: Yes; to: Multiple mitochondrial dysfunctions syndrome-5 (MMDS5) is an autosomal recessive disorder characterized mainly by progressive neurologic deterioration beginning in early infancy. Affected individuals have essentially no psychomotor development and have early-onset seizures with neurologic decline and spasticity. Brain imaging shows severe leukodystrophy with evidence of dys- or delayed myelination. Death usually occurs in early childhood.

HGNC approved symbol/name: ISCA1
Is the phenotype(s) severe and onset <18yo? Yes
Known technical challenges? No
Gene reported in 3 independent families: Yes
Prepair 1000+ v1.992 DDX11 Michelle Torres reviewed gene: DDX11: Rating: GREEN; Mode of pathogenicity: None; Publications: 30216658; Phenotypes: Warsaw breakage syndrome MIM#613398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 ISCA1 Lauren Thomas reviewed gene: ISCA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28356563, 29767723; Phenotypes: Multiple mitochondrial dysfunctions syndrome 5, MIM# 617613; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 DCHS1 Michelle Torres reviewed gene: DCHS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27262615, 22473091, 24056717, 29046692; Phenotypes: Van Maldergem syndrome 1 MIM# 601390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 DARS Michelle Torres reviewed gene: DARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 27816769; Phenotypes: Hypomyelination with brainstem and spinal cord involvement and leg spasticity MIM# 615281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 IL12RB1 Lauren Thomas reviewed gene: IL12RB1: Rating: AMBER; Mode of pathogenicity: None; Publications: 9603733, 9603732, 12591909, 15736007, 23864330; Phenotypes: Immunodeficiency 30, MIM# 614891; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 COL7A1 Michelle Torres reviewed gene: COL7A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31670143, 32506467, 25639640; Phenotypes: Epidermolysis bullosa dystrophica inversa MIM#226600, Epidermolysis bullosa dystrophica, autosomal recessive MIM#226600, Epidermolysis bullosa dystrophica, localisata variant MIM#226600, Epidermolysis bullosa pruriginosa MIM#604129, Epidermolysis bullosa, pretibial MIM#131850, Transient bullous of the newborn MIM#131705; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 DGUOK Clare Hunt reviewed gene: DGUOK: Rating: GREEN; Mode of pathogenicity: None; Publications: 12874104, 15887277, 23043144; Phenotypes: Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), MIM# 251880, Portal hypertension, noncirrhotic, 1, MIM# 617068, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4, MIM# 617070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 DGKE Clare Hunt reviewed gene: DGKE: Rating: GREEN; Mode of pathogenicity: None; Publications: 23274426, 23542698; Phenotypes: Nephrotic syndrome, type 7, MIM# 615008; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 CYP4F22 Clare Hunt reviewed gene: CYP4F22: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, congenital, autosomal recessive 5, MIM# 604777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 CEP78 Michelle Torres reviewed gene: CEP78: Rating: GREEN; Mode of pathogenicity: None; Publications: 35240912; Phenotypes: Cone-rod dystrophy and hearing loss MIM#617236; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 CNGA3 Michelle Torres reviewed gene: CNGA3: Rating: AMBER; Mode of pathogenicity: None; Publications: 36980963; Phenotypes: Achromatopsia 2 MIM#216900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 COL6A3 Michelle Torres reviewed gene: COL6A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301676, 37082441; Phenotypes: Bethlem myopathy 1C MIM#620726, Ullrich congenital muscular dystrophy 1C MIM#620728; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 RCBTB1 Ee Ming Wong reviewed gene: RCBTB1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27486781, 33104391, 33624564; Phenotypes: Retinal dystrophy with or without extraocular anomalies (MIM#617175); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 PTH1R Ee Ming Wong reviewed gene: PTH1R: Rating: GREEN; Mode of pathogenicity: Other; Publications: 15525660, 17164305, 39276366; Phenotypes: Chondrodysplasia, Blomstrand type (MIM#215045), Eiken syndrome (MIM#600002); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 POR Ee Ming Wong changed review comment from: - PORD (P450 oxidoreductase deficiency) is associated with disorders of sex development in both sexes, where Antley-Bixler (ABS) syndrome is the name given to the severe form
- Skeletal abnormalities of the ABS phenotype are frequently observed in individuals with PORD, characterised by craniosynostosis, brachycephaly, radio-ulnar or radio-humeral synostosis, bowed femora, arachnodactyly, midface hypoplasia, proptosis, and choanal stenosis. The severity of malformations varies from mild to moderate and severe.

NB: Only the more severe MIM# has been added to this gene list.; to: - PORD (P450 oxidoreductase deficiency) is associated with disorders of sex development in both sexes, where Antley-Bixler (ABS) syndrome is the name given to the severe form
- Skeletal abnormalities of the ABS phenotype are frequently observed in individuals with PORD, characterised by craniosynostosis, brachycephaly, radio-ulnar or radio-humeral synostosis, bowed femora, arachnodactyly, midface hypoplasia, proptosis, and choanal stenosis. The severity of malformations varies from mild to moderate and severe.
- Congenital onset

NB: Only the more severe MIM# has been added to this gene list.
Prepair 1000+ v1.992 POR Ee Ming Wong reviewed gene: POR: Rating: GREEN; Mode of pathogenicity: None; Publications: 27604308, 20301592, 35842891; Phenotypes: Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (MIM#201750); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 PYCR2 Ee Ming Wong reviewed gene: PYCR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25865492, 27130255; Phenotypes: Leukodystrophy, hypomyelinating 10 (MIM# 616420); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 PMPCA Ee Ming Wong reviewed gene: PMPCA: Rating: GREEN; Mode of pathogenicity: None; Publications: 25808372, 26657514, 33272776, 30617178; Phenotypes: Spinocerebellar ataxia 2 (MIM# 213200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 PKLR Ee Ming Wong reviewed gene: PKLR: Rating: GREEN; Mode of pathogenicity: None; Publications: 1896471, 9160692, 9057665, 16704447, 9090535, 32702739; Phenotypes: Pyruvate Kinase deficiency (MIM# 266200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 PIGT Ee Ming Wong reviewed gene: PIGT: Rating: GREEN; Mode of pathogenicity: None; Publications: 30976099, 25943031, 24906948, 24906948, 24906948, 28728837, 28728837, 28728837; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398, MONDO:0014165; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 PCNT Ee Ming Wong reviewed gene: PCNT: Rating: GREEN; Mode of pathogenicity: None; Publications: 18174396, 12210304, 30922925, 33460028, 32557621, 32267100; Phenotypes: Microcephalic osteodysplastic primordial dwarfism, type II, MIM# 210720, MONDO:0008872; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 PCDH12 Ee Ming Wong reviewed gene: PCDH12: Rating: GREEN; Mode of pathogenicity: None; Publications: 27164683, 30178464; Phenotypes: Diencephalic-mesencephalic junction dysplasia syndrome 1 (MIM# 251280); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 PC Ee Ming Wong changed review comment from: - Well-established gene disease association
- Age of onset: neonatal to early childhood
- Severity: variable severity - three subtypes

1. Type A (infantile form aka North American form): characterized by infantile onset of metabolic and lactic acidosis, delayed motor development, intellectual disability, poor linear growth and/or weight gain, and neurologic findings. Brain anomalies can be noted. Most affected children die in infancy or early childhood.

2. Type B (severe neonatal form aka French form): characterized by neonatal or infantile onset of hypothermia, respiratory distress/failure, vomiting, severe lactic acidosis, hyperammonemia, and often hypoglycemia. Neurologic findings include brain abnormalities, lethargy, hypotonia, and pyramidal and extrapyramidal signs. Death typically occurs by age eight months.

3. Type C (intermittent/attenuated form aka Benign form): characterized by relatively normal or mildly delayed neurologic
development, motor and/or gait abnormalities, (rarely) seizures, episodic movement disorders, and metabolic
acidosis. Life span is unknown but survival into adulthood has been reported.; to: - Well-established gene disease association
- Age of onset: neonatal to early childhood
- Severity: variable severity - three subtypes

1. Type A (infantile form aka North American form): characterized by infantile onset of metabolic and lactic acidosis, delayed motor development, intellectual disability, poor linear growth and/or weight gain, and neurologic findings. Brain anomalies can be noted. Most affected children die in infancy or early childhood.

2. Type B (severe neonatal form aka French form): characterized by neonatal or infantile onset of hypothermia, respiratory distress/failure, vomiting, severe lactic acidosis, hyperammonemia, and often hypoglycemia. Neurologic findings include brain abnormalities, lethargy, hypotonia, and pyramidal and extrapyramidal signs. Death typically occurs by age eight months.

3. Type C (intermittent/attenuated form aka Benign form): characterized by relatively normal or mildly delayed neurologic development, motor and/or gait abnormalities, (rarely) seizures, episodic movement disorders, and metabolic acidosis. Life span is unknown but survival into adulthood has been reported.
Prepair 1000+ v1.992 PC Ee Ming Wong reviewed gene: PC: Rating: GREEN; Mode of pathogenicity: None; Publications: 9585612, 12112657, 20301764; Phenotypes: Pyruvate carboxylase deficiency (MIM#266150); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hydrocephalus_Ventriculomegaly v0.127 ARID1B Bryony Thompson Classified gene: ARID1B as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v0.127 ARID1B Bryony Thompson Gene: arid1b has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.126 ARID1B Bryony Thompson gene: ARID1B was added
gene: ARID1B was added to Hydrocephalus_Ventriculomegaly. Sources: Literature
Mode of inheritance for gene: ARID1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARID1B were set to 39680505
Phenotypes for gene: ARID1B were set to Coffin-Siris syndrome 1 MONDO:0007617
Review for gene: ARID1B was set to GREEN
Added comment: 13 de novo variants were identified in unrelated children (p = 1.80e-17) from a large cerebral ventriculomegaly cohort, including nine LoF variants. Other syndromic features were common.
Sources: Literature
Hydrocephalus_Ventriculomegaly v0.125 LDB1 Bryony Thompson Marked gene: LDB1 as ready
Hydrocephalus_Ventriculomegaly v0.125 LDB1 Bryony Thompson Gene: ldb1 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.125 LDB1 Bryony Thompson Classified gene: LDB1 as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v0.125 LDB1 Bryony Thompson Gene: ldb1 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.124 LDB1 Bryony Thompson gene: LDB1 was added
gene: LDB1 was added to Hydrocephalus_Ventriculomegaly. Sources: Literature
Mode of inheritance for gene: LDB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LDB1 were set to 39680505
Phenotypes for gene: LDB1 were set to Congenital hydrocephalus MONDO:0016349
Review for gene: LDB1 was set to GREEN
Added comment: Exome-wide significant enrichment of LDB1 protein-altering de novo variants (p = 1.11 x 10-15) in a large cerebral ventriculomegaly cohort (>2,697 parent-proband trios). 8 unrelated cases with ventriculomegaly, developmental delay, and dysmorphic features with de novo variants (7 LoF variants truncate LDB1's carboxy-terminal LIM interaction domain & 1 missense).
Sources: Literature
Mendeliome v1.2237 LDB1 Bryony Thompson Marked gene: LDB1 as ready
Mendeliome v1.2237 LDB1 Bryony Thompson Gene: ldb1 has been classified as Green List (High Evidence).
Mendeliome v1.2237 LDB1 Bryony Thompson Classified gene: LDB1 as Green List (high evidence)
Mendeliome v1.2237 LDB1 Bryony Thompson Gene: ldb1 has been classified as Green List (High Evidence).
Mendeliome v1.2236 LDB1 Bryony Thompson gene: LDB1 was added
gene: LDB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LDB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LDB1 were set to 39680505
Phenotypes for gene: LDB1 were set to Congenital hydrocephalus MONDO:0016349
Review for gene: LDB1 was set to GREEN
Added comment: Exome-wide significant enrichment of LDB1 protein-altering de novo variants (p = 1.11 x 10-15) in a large cerebral ventriculomegaly cohort (>2,697 parent-proband trios). 8 unrelated cases with ventriculomegaly, developmental delay, and dysmorphic features with de novo variants (7 LoF variants truncate LDB1's carboxy-terminal LIM interaction domain & 1 missense).
Sources: Literature
Prepair 1000+ v1.992 NPR2 Ee Ming Wong reviewed gene: NPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15146390; Phenotypes: Acromesomelic dysplasia, Maroteaux type (MIM#602875); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 NMNAT1 Ee Ming Wong changed review comment from: Syndromic and non-syndromic causes of LCA are associated with bi-allelic variants in this gene.

Non-syndromic LCA: multiple affected families reported, p.Glu257Lys is a common founder variant.

Syndromic disorder: three families reported, but two are distantly related (shared haplotype). The affected children in those two families were homozygous for 7.4-kb duplication involving the last 2 exons of the NMNAT1 gene, spanning the beginning of intron 3 to the middle of the 3-prime UTR (chr1:10,036,359-10,043,727, GRCh37). The third affected individual was compound het for the duplication and a splicing variant.

Green for non-syndromic LCA (MIM# added to review). No additional affected individuals in the literature (Amber? MIM# has not been added to review).; to: Syndromic and non-syndromic causes of LCA are associated with bi-allelic variants in this gene.

Non-syndromic LCA: multiple affected families reported, p.Glu257Lys is a common founder variant.

Syndromic disorder: three families reported, but two are distantly related (shared haplotype). The affected children in those two families were homozygous for 7.4-kb duplication involving the last 2 exons of the NMNAT1 gene, spanning the beginning of intron 3 to the middle of the 3-prime UTR (chr1:10,036,359-10,043,727, GRCh37). The third affected individual was compound het for the duplication and a splicing variant.

Green for non-syndromic LCA (MIM# added to review). No additional affected individuals in the literature for syndromic LCA (Amber? MIM# has not been added to review).
Prepair 1000+ v1.992 NMNAT1 Ee Ming Wong reviewed gene: NMNAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32533184, 33668384, 22842230, 22842229; Phenotypes: Leber congenital amaurosis 9 (MIM#608553); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 CHST14 Michelle Torres edited their review of gene: CHST14: Added comment: Musculocontractural EDS type 1 (mcEDS) is a rare type of EDS caused by biallelic loss-of-function variants in CHST14 (PMID: 34815299).

Major features are: congenital multiple contractures and characteristic craniofacial features at birth or in early infancy; congenital multiple contractures and characteristic cutaneous features in adolescence and in adulthood (PMID: 34815299).

The CHST14 gene has only 1 exon, therefore PTV variants escape NMD. Missense and in-frame deletion have also been reported with a similar phenotype to that caused by PTV (PMID: 34815299).; Changed rating: GREEN
Prepair 1000+ v1.992 CHST14 Michelle Torres reviewed gene: CHST14: Rating: ; Mode of pathogenicity: None; Publications: 34815299; Phenotypes: Ehlers-Danlos syndrome, musculocontractural type 1 MIM# 601776; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 NFU1 Ee Ming Wong reviewed gene: NFU1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21944046, 22077971, 32747156, 29441221, 36256512; Phenotypes: Multiple mitochondrial dysfunctions syndrome 1 (MIM# 605711), Spastic paraplegia 93 (MIM# 620938); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 CFI Michelle Torres reviewed gene: CFI: Rating: GREEN; Mode of pathogenicity: None; Publications: 28942469; Phenotypes: Complement factor I deficiency MIM#610984; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 NEK1 Ee Ming Wong reviewed gene: NEK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21211617, 22499340, 25492405, 28123176; Phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly (MIM# 263520); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 NDUFS6 Ee Ming Wong reviewed gene: NDUFS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 15372108, 19259137, 30948790; Phenotypes: Mitochondrial complex I deficiency, nuclear type 9 (MIM#618232); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 NBN Ee Ming Wong reviewed gene: NBN: Rating: GREEN; Mode of pathogenicity: None; Publications: 33488600, 33082212; Phenotypes: Nijmegen breakage syndrome (MIM#251260); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 TCAP Crystle Lee changed review comment from: Established for LGMD. Rare muscle disorder characterised by proximal and distal lower limb weakness, calf hypertrophy and loss of ambulation.

Mean age at onset 12.5 years (range 2 to 15 years). Progression to wheelchair in fourth decade (OMIM)
PMID: 37216648: Onset range from 6-35.
PMID: 25724973: Onset in teens. Wheelchair bound by 44.
PMID: 25055047: Reported PTCs in 2 families. In at least one family, with 3 affected family members, one was wheelchair bound state at 21 years of age.

Other similar/more severe LDMG phenotypes included in panel.; to: Established for LGMD. Rare muscle disorder characterised by proximal and distal lower limb weakness, calf hypertrophy and loss of ambulation.

Mean age at onset 12.5 years (range 2 to 15 years). Progression to wheelchair in fourth decade (OMIM)
PMID: 37216648: Onset range from 6-35.
PMID: 25724973: Onset in teens. Wheelchair bound by 44.
PMID: 25055047: Reported PTCs in 2 families. In at least one family, with 3 affected family members, one was wheelchair bound state at 21 years of age.

Other similar/more severe LGMD phenotypes included in panel.
Prepair 1000+ v1.992 TCAP Crystle Lee changed review comment from: Established for LGMD. Rare muscle disorder characterised by proximal and distal lower limb weakness, calf
hypertrophy and loss of ambulation.

Mean age at onset 12.5 years (range 2 to 15 years). Progression to wheelchair in fourth decade (OMIM)
PMID: 37216648: Onset range from 6-35.
PMID: 25724973: Onset in teens. Wheelchair bound by 44.
PMID: 25055047: Reported PTCs in 2 families. In at least one family, with 3 affected family members, one was wheelchair bound state at 21 years of age.

Other similar/more severe LDMG phenotypes included in panel.; to: Established for LGMD. Rare muscle disorder characterised by proximal and distal lower limb weakness, calf hypertrophy and loss of ambulation.

Mean age at onset 12.5 years (range 2 to 15 years). Progression to wheelchair in fourth decade (OMIM)
PMID: 37216648: Onset range from 6-35.
PMID: 25724973: Onset in teens. Wheelchair bound by 44.
PMID: 25055047: Reported PTCs in 2 families. In at least one family, with 3 affected family members, one was wheelchair bound state at 21 years of age.

Other similar/more severe LDMG phenotypes included in panel.
Prepair 1000+ v1.992 TCAP Crystle Lee edited their review of gene: TCAP: Changed rating: GREEN
Prepair 1000+ v1.992 TCAP Crystle Lee reviewed gene: TCAP: Rating: AMBER; Mode of pathogenicity: None; Publications: 37216648, 25724973; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 7, MIM#601954; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 NANS Ee Ming Wong reviewed gene: NANS: Rating: GREEN; Mode of pathogenicity: None; Publications: 8152878, 15726110, 8723082, 27213289, 7551156; Phenotypes: Spondyloepimetaphyseal dysplasia, Camera-Genevieve type (MIM#610442); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 NALCN Ee Ming Wong reviewed gene: NALCN: Rating: GREEN; Mode of pathogenicity: None; Publications: 23749988, 24075186, 3016785; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 (MIM#615419); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 TBC1D24 Crystle Lee reviewed gene: TBC1D24: Rating: GREEN; Mode of pathogenicity: None; Publications: 27281533, 25719194; Phenotypes: Deafness, autosomal recessive 86 MIM#614617, Developmental and epileptic encephalopathy 16 MIM#615338, DOORS syndrome MIM#220500, Epilepsy, rolandic, with proxysmal exercise-induce dystonia and writer's cramp MIM#608105, Myoclonic epilepsy, infantile, familial MIM#605021; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 NAA10 Ee Ming Wong reviewed gene: NAA10: Rating: GREEN; Mode of pathogenicity: None; Publications: 26522270, 34200686, 37130971, 30842225, 2443133134075687; Phenotypes: Ogden syndrome (MIM#300855), Syndromic microphthalmia 1 (MIM#309800); 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
Prepair 1000+ v1.992 STX11 Crystle Lee reviewed gene: STX11: Rating: GREEN; Mode of pathogenicity: None; Publications: 20486178, 16582076; Phenotypes: Hemophagocytic lymphohistiocytosis, familial, 4, MIM#603552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 SQSTM1 Crystle Lee reviewed gene: SQSTM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27545679, 39214971; Phenotypes: Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset, MIM#617145; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 SLC12A6 Crystle Lee reviewed gene: SLC12A6: Rating: GREEN; Mode of pathogenicity: None; Publications: 34706912; Phenotypes: Agenesis of the corpus callosum with peripheral neuropathy, MIM#218000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 SDHAF1 Crystle Lee reviewed gene: SDHAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19465911, 22995659; Phenotypes: Mitochondrial complex II deficiency, nuclear type 2, MIM#619166; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 RMND1 Crystle Lee reviewed gene: RMND1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27412952; Phenotypes: Combined oxidative phosphorylation deficiency 11, MIM#614922; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 MTR Ee Ming Wong reviewed gene: MTR: Rating: GREEN; Mode of pathogenicity: None; Publications: 8968736, 8968737, 9683607, 12068375; Phenotypes: Homocystinuria-megaloblastic anaemia, cblG complementation type, MIM# 250940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 RFXANK Crystle Lee reviewed gene: RFXANK: Rating: GREEN; Mode of pathogenicity: None; Publications: 32875002; Phenotypes: MHC class II deficiency 2, MIM#620815; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 RDH12 Crystle Lee reviewed gene: RDH12: Rating: GREEN; Mode of pathogenicity: None; Publications: 31884613, 19011012, 28471114, 34031043, 35491887; Phenotypes: Leber congenital amaurosis 13, MIM#612712; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 MOCS1 Ee Ming Wong reviewed gene: MOCS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27604308, 9731530; Phenotypes: Molybdenum cofactor deficiency A (MIM#252150); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.992 RARS2 Crystle Lee reviewed gene: RARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38009286, 29881806; Phenotypes: Pontocerebellar hypoplasia, type 6, MIM#611523; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2235 LRRC8C Sangavi Sivagnanasundram gene: LRRC8C was added
gene: LRRC8C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LRRC8C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LRRC8C were set to 39623139
Phenotypes for gene: LRRC8C were set to TIMES syndrome MIM#621056
Mode of pathogenicity for gene: LRRC8C was set to Other
Review for gene: LRRC8C was set to RED
Added comment: TIMES syndrome is a multisystem disorder characterised by considerable phenotypic variability, but overlapping features include telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature. Patients exhibit striking cutis marmorata in infancy.

Two individuals from unrelated families presenting with similar features consistent with TIMES syndrome.
Leu400IlefsTer8 and Val390Leu variants were identified however the proposed mechanism of disease is GoF.
Sources: Literature
Mendeliome v1.2235 WASHC3 Sangavi Sivagnanasundram gene: WASHC3 was added
gene: WASHC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WASHC3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WASHC3 were set to DOI: https://doi.org/10.1016/j.gimo.2024.101915
Phenotypes for gene: WASHC3 were set to neurodevelopmental disorder MONDO:0700092
Review for gene: WASHC3 was set to GREEN
Added comment: Three unrelated families with short stature, distinctive facies and neurodevelopmental abnormalities. Two different rare missense variants were identified between the three families (c.207A>C:p.L69F and c.1A>T, p.M1?).
In vitro functional assay was conducted on both variants showing impaired protein function supportive of disease mechanism.
Sources: Literature
Skeletal dysplasia v0.298 SLC13A1 Sangavi Sivagnanasundram reviewed gene: SLC13A1: Rating: AMBER; Mode of pathogenicity: None; Publications: doi: https://doi.org/10.1016/j.gimo.2024.101958; Phenotypes: sulfation-related bone disorder MONDO:0019688; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2235 SLC13A1 Sangavi Sivagnanasundram reviewed gene: SLC13A1: Rating: AMBER; Mode of pathogenicity: None; Publications: doi: https://doi.org/10.1016/j.gimo.2024.101958; Phenotypes: sulfation-related bone disorder MONDO:0019688; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.33 RICTOR Bryony Thompson Marked gene: RICTOR as ready
Intellectual disability syndromic and non-syndromic v1.33 RICTOR Bryony Thompson Gene: rictor has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.33 RICTOR Bryony Thompson Classified gene: RICTOR as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.33 RICTOR Bryony Thompson Gene: rictor has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.32 RICTOR Bryony Thompson gene: RICTOR was added
gene: RICTOR was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RICTOR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RICTOR were set to 39738822
Phenotypes for gene: RICTOR were set to Neurodevelopmental disorder MONDO:0700092, RICTOR-related
Review for gene: RICTOR was set to GREEN
Added comment: 8 unrelated cases presenting with ID and/or developmental delay with de novo or heterozygous variants inherited from one affected parent, including three missense variants, four loss-of-function variants and one 3 kb deletion encompassing RICTOR. Possible gain of function and loss of function mechanism of disease.
Sources: Literature
Mendeliome v1.2235 RICTOR Bryony Thompson Marked gene: RICTOR as ready
Mendeliome v1.2235 RICTOR Bryony Thompson Gene: rictor has been classified as Green List (High Evidence).
Mendeliome v1.2235 RICTOR Bryony Thompson Classified gene: RICTOR as Green List (high evidence)
Mendeliome v1.2235 RICTOR Bryony Thompson Gene: rictor has been classified as Green List (High Evidence).
Mendeliome v1.2234 RICTOR Bryony Thompson gene: RICTOR was added
gene: RICTOR was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RICTOR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RICTOR were set to 39738822
Phenotypes for gene: RICTOR were set to Neurodevelopmental disorder MONDO:0700092, RICTOR-related
Review for gene: RICTOR was set to GREEN
Added comment: 8 unrelated cases presenting with ID and/or developmental delay with de novo or heterozygous variants inherited from one affected parent, including three missense variants, four loss-of-function variants and one 3 kb deletion encompassing RICTOR. Possible gain of function and loss of function mechanism of disease.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.31 UBR5 Bryony Thompson Marked gene: UBR5 as ready
Intellectual disability syndromic and non-syndromic v1.31 UBR5 Bryony Thompson Gene: ubr5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.31 UBR5 Bryony Thompson Classified gene: UBR5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.31 UBR5 Bryony Thompson Gene: ubr5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.30 UBR5 Bryony Thompson gene: UBR5 was added
gene: UBR5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: UBR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBR5 were set to 39721588
Phenotypes for gene: UBR5 were set to Neurodevelopmental disorder MONDO:0700092, UBR5-related
Review for gene: UBR5 was set to GREEN
Added comment: 29 individuals with a neurodevelopment syndrome (24 de novo variants) with a core phenotype characterised by developmental delay (26/28), autism (16/26), and intellectual disability (56%). Additionally, some individuals presented with epilepsy/seizures (11/27), movement disorders, and/or genital anomalies (35%). Loss of function is the expected mechanism of disease with functional experiments in C. elegans and in vitro ubiquitination assays.
Sources: Literature
Autism v0.203 UBR5 Bryony Thompson Marked gene: UBR5 as ready
Autism v0.203 UBR5 Bryony Thompson Gene: ubr5 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.89 UBR5 Bryony Thompson Marked gene: UBR5 as ready
Genetic Epilepsy v1.89 UBR5 Bryony Thompson Gene: ubr5 has been classified as Green List (High Evidence).
Autism v0.203 UBR5 Bryony Thompson Classified gene: UBR5 as Green List (high evidence)
Autism v0.203 UBR5 Bryony Thompson Gene: ubr5 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.89 UBR5 Bryony Thompson Classified gene: UBR5 as Green List (high evidence)
Genetic Epilepsy v1.89 UBR5 Bryony Thompson Gene: ubr5 has been classified as Green List (High Evidence).
Autism v0.202 UBR5 Bryony Thompson gene: UBR5 was added
gene: UBR5 was added to Autism. Sources: Literature
Mode of inheritance for gene: UBR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBR5 were set to 39721588
Phenotypes for gene: UBR5 were set to Neurodevelopmental disorder MONDO:0700092, UBR5-related
Review for gene: UBR5 was set to GREEN
Added comment: 29 individuals with a neurodevelopment syndrome (24 de novo variants) with a core phenotype characterised by developmental delay (26/28), autism (16/26), and intellectual disability (56%). Additionally, some individuals presented with epilepsy/seizures (11/27), movement disorders, and/or genital anomalies (35%). Loss of function is the expected mechanism of disease with functional experiments in C. elegans and in vitro ubiquitination assays.
Sources: Literature
Genetic Epilepsy v1.88 UBR5 Bryony Thompson gene: UBR5 was added
gene: UBR5 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: UBR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBR5 were set to 39721588
Phenotypes for gene: UBR5 were set to Neurodevelopmental disorder MONDO:0700092, UBR5-related
Review for gene: UBR5 was set to GREEN
Added comment: 29 individuals with a neurodevelopment syndrome (24 de novo variants) with a core phenotype characterised by developmental delay (26/28), autism (16/26), and intellectual disability (56%). Additionally, some individuals presented with epilepsy/seizures (11/27), movement disorders, and/or genital anomalies (35%). Loss of function is the expected mechanism of disease with functional experiments in C. elegans and in vitro ubiquitination assays.
Sources: Literature
Mendeliome v1.2233 UBR5 Bryony Thompson Marked gene: UBR5 as ready
Mendeliome v1.2233 UBR5 Bryony Thompson Gene: ubr5 has been classified as Green List (High Evidence).
Differences of Sex Development v1.2 UBR5 Bryony Thompson Marked gene: UBR5 as ready
Differences of Sex Development v1.2 UBR5 Bryony Thompson Gene: ubr5 has been classified as Green List (High Evidence).
Differences of Sex Development v1.2 UBR5 Bryony Thompson Classified gene: UBR5 as Green List (high evidence)
Differences of Sex Development v1.2 UBR5 Bryony Thompson Gene: ubr5 has been classified as Green List (High Evidence).
Differences of Sex Development v1.1 UBR5 Bryony Thompson gene: UBR5 was added
gene: UBR5 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: UBR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBR5 were set to 39721588
Phenotypes for gene: UBR5 were set to Neurodevelopmental disorder MONDO:0700092, UBR5-related
Review for gene: UBR5 was set to GREEN
Added comment: 29 individuals with a neurodevelopment syndrome (24 de novo variants) with a core phenotype characterised by developmental delay (26/28), autism (16/26), and intellectual disability (56%). Additionally, some individuals presented with epilepsy/seizures (11/27), movement disorders, and/or genital anomalies (35%). Loss of function is the expected mechanism of disease with functional experiments in C. elegans and in vitro ubiquitination assays.
Sources: Literature
Mendeliome v1.2233 UBR5 Bryony Thompson Classified gene: UBR5 as Green List (high evidence)
Mendeliome v1.2233 UBR5 Bryony Thompson Gene: ubr5 has been classified as Green List (High Evidence).
Mendeliome v1.2232 UBR5 Bryony Thompson gene: UBR5 was added
gene: UBR5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UBR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBR5 were set to 39721588
Phenotypes for gene: UBR5 were set to Neurodevelopmental disorder MONDO:0700092, UBR5-related
Review for gene: UBR5 was set to GREEN
Added comment: 29 individuals with a neurodevelopment syndrome (24 de novo variants) with a core phenotype characterised by developmental delay (26/28), autism (16/26), and intellectual disability (56%). Additionally, some individuals presented with epilepsy/seizures (11/27), movement disorders, and/or genital anomalies (35%). Loss of function is the expected mechanism of disease with functional experiments in C. elegans and in vitro ubiquitination assays.
Sources: Literature
Mendeliome v1.2231 MRUPAV_PLIN4 Bryony Thompson Marked STR: MRUPAV_PLIN4 as ready
Mendeliome v1.2231 MRUPAV_PLIN4 Bryony Thompson Str: mrupav_plin4 has been classified as Green List (High Evidence).
Mendeliome v1.2231 MRUPAV_PLIN4 Bryony Thompson Classified STR: MRUPAV_PLIN4 as Green List (high evidence)
Mendeliome v1.2231 MRUPAV_PLIN4 Bryony Thompson Str: mrupav_plin4 has been classified as Green List (High Evidence).
Mendeliome v1.2230 MRUPAV_PLIN4 Bryony Thompson STR: MRUPAV_PLIN4 was added
STR: MRUPAV_PLIN4 was added to Mendeliome. Sources: Literature
STR tags were added to STR: MRUPAV_PLIN4.
Mode of inheritance for STR: MRUPAV_PLIN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: MRUPAV_PLIN4 were set to 32451610; 37145156; 36151849; 35499779
Phenotypes for STR: MRUPAV_PLIN4 were set to myopathy, distal, with rimmed vacuoles MONDO:0014945
Review for STR: MRUPAV_PLIN4 was set to GREEN
STR: MRUPAV_PLIN4 was marked as clinically relevant
Added comment: Expansion of 33-mer (33 amino acids, 99 bp) identified in coding exon 3 (exon 5) of PLIN4 via linkage analysis and long read sequencing in a large Italian cohort with progressive myopathy with specific pathology including rimmed ubiquitin-positive autophagic vacuolation.
Suggested disease name myopathy with rimmed ubiquitin-positive autophagic vacuolation (MRUPAV). An additional 4 unrelated Chinese families/probands were reported. The repeat expansion is not detectable using short-read sequencing.
Normal PLIN4 alleles: 27-31 x 33-mer
Pathogenic: ≥39 x 33-mer
Sources: Literature
Prepair 1000+ v1.992 EARS2 Lilian Downie Marked gene: EARS2 as ready
Prepair 1000+ v1.992 EARS2 Lilian Downie Gene: ears2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.992 EARS2 Lilian Downie Phenotypes for gene: EARS2 were changed from Combined oxidative phosphorylation deficiency 12, 614924 (3) to Combined oxidative phosphorylation deficiency 12 MIM#614924
Prepair 1000+ v1.991 EARS2 Lilian Downie Publications for gene: EARS2 were set to
Prepair 1000+ v1.990 EARS2 Lilian Downie reviewed gene: EARS2: Rating: ; Mode of pathogenicity: None; Publications: 39173847; Phenotypes: Combined oxidative phosphorylation deficiency 12 MIM#614924; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.990 DYM Lilian Downie Marked gene: DYM as ready
Prepair 1000+ v1.990 DYM Lilian Downie Gene: dym has been classified as Green List (High Evidence).
Prepair 1000+ v1.990 DYM Lilian Downie Phenotypes for gene: DYM were changed from Dyggve-Melchior-Clausen disease, 223800 (3) to Dyggve-Melchior-Clausen disease MIM#223800; Smith-McCort dysplasia MIM#607326
Prepair 1000+ v1.989 DYM Lilian Downie Publications for gene: DYM were set to
Prepair 1000+ v1.988 DYM Lilian Downie reviewed gene: DYM: Rating: ; Mode of pathogenicity: None; Publications: 16326827, 38860472, 35477554; Phenotypes: Dyggve-Melchior-Clausen disease MIM#223800, Smith-McCort dysplasia MIM#607326; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.988 DKC1 Lilian Downie Marked gene: DKC1 as ready
Prepair 1000+ v1.988 DKC1 Lilian Downie Gene: dkc1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.988 DKC1 Lilian Downie Phenotypes for gene: DKC1 were changed from Dyskeratosis congenita, X-linked, 305000 (3) to Dyskeratosis congenita, X-linked MIM#305000
Prepair 1000+ v1.987 DKC1 Lilian Downie Publications for gene: DKC1 were set to
Prepair 1000+ v1.986 DKC1 Lilian Downie reviewed gene: DKC1: Rating: ; Mode of pathogenicity: None; Publications: PMID: 20301779; Phenotypes: Dyskeratosis congenita, X-linked MIM#305000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.986 DCAF17 Lilian Downie Marked gene: DCAF17 as ready
Prepair 1000+ v1.986 DCAF17 Lilian Downie Gene: dcaf17 has been classified as Green List (High Evidence).
Prepair 1000+ v1.986 DCAF17 Lilian Downie Phenotypes for gene: DCAF17 were changed from Woodhouse-Sakati syndrome, 241080 (3) to Woodhouse-Sakati syndrome MIM#241080
Prepair 1000+ v1.985 DCAF17 Lilian Downie Publications for gene: DCAF17 were set to
Prepair 1000+ v1.984 DCAF17 Lilian Downie reviewed gene: DCAF17: Rating: GREEN; Mode of pathogenicity: None; Publications: 28542792, 38320940, 30409855, 35876063; Phenotypes: Woodhouse-Sakati syndrome MIM#241080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.984 TMEM107 Kate Scarff reviewed gene: TMEM107: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26518474, 26595381, 26123494; Phenotypes: Orofaciodigital syndrome XVI, MIM #617563; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.984 TAP1 Kate Scarff reviewed gene: TAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30189467, 10074494, 28161407, 36839544, 16087697, 10931128; Phenotypes: MHC class I deficiency 1, MIM #604571; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.984 SPATA7 Kate Scarff reviewed gene: SPATA7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31908400, 32799588; Phenotypes: Leber congenital amaurosis 3, MIM #604232, Retinitis pigmentosa 94, variable age at onset, autosomal recessive, MIM #604232; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.984 SLC4A11 Kate Scarff reviewed gene: SLC4A11: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 20118786, 21203343, 26451371, 17220209, 32884076; Phenotypes: Corneal endothelial dystrophy and perceptive deafness, MIM #217400 (CDPD), Corneal endothelial dystrophy, autosomal recessive, MIM#217700 (CHED2); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.984 SLC4A11 Kate Scarff Deleted their review
Prepair 1000+ v1.984 SLC4A11 Kate Scarff reviewed gene: SLC4A11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Corneal endothelial dystrophy and perceptive deafness, MIM #217400, Corneal endothelial dystrophy, MIM #217700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.984 SLC35D1 Kate Scarff reviewed gene: SLC35D1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17952091, 19508970, 31423530, 38058750, 35934917; Phenotypes: Schneckenbecken dysplasia, MIM #269250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.984 SLC25A38 Kate Scarff reviewed gene: SLC25A38: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34298585, 19412178; Phenotypes: Anemia, sideroblastic, 1, MIM #300751; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.984 SLC16A2 Kate Scarff reviewed gene: SLC16A2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301789, 20083155, 15980113; Phenotypes: Allan-Herndon-Dudley syndrome, MIM #300523; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.984 RP2 Kate Scarff reviewed gene: RP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 10053026, 11462235, 22131869, 8225316, 26143542, 16969763, 14564670; Phenotypes: Retinitis pigmentosa 2, MIM #312600; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.984 WWOX Zornitza Stark Marked gene: WWOX as ready
Prepair 1000+ v1.984 WWOX Zornitza Stark Gene: wwox has been classified as Green List (High Evidence).
Prepair 1000+ v1.984 WWOX Zornitza Stark Phenotypes for gene: WWOX were changed from Epileptic encephalopathy, early infantile, 28, 616211 (3) to Spinocerebellar ataxia, autosomal recessive 12, MIM# 614322; Developmental and epileptic encephalopathy 28, MIM# 616211
Prepair 1000+ v1.983 WWOX Zornitza Stark Publications for gene: WWOX were set to
Prepair 1000+ v1.982 WWOX Zornitza Stark edited their review of gene: WWOX: Changed publications: 33916893
Prepair 1000+ v1.982 WWOX Zornitza Stark reviewed gene: WWOX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia, autosomal recessive 12, MIM# 614322, Developmental and epileptic encephalopathy 28, MIM# 616211; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.982 XPA Zornitza Stark Marked gene: XPA as ready
Prepair 1000+ v1.982 XPA Zornitza Stark Gene: xpa has been classified as Green List (High Evidence).
Prepair 1000+ v1.982 XPA Zornitza Stark Phenotypes for gene: XPA were changed from Xeroderma pigmentosum, group A, 278700 (3) to Xeroderma pigmentosum, group A , MIM#278700
Prepair 1000+ v1.981 XPA Zornitza Stark reviewed gene: XPA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Xeroderma pigmentosum, group A , MIM#278700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.981 ZMPSTE24 Zornitza Stark Marked gene: ZMPSTE24 as ready
Prepair 1000+ v1.981 ZMPSTE24 Zornitza Stark Gene: zmpste24 has been classified as Green List (High Evidence).
Prepair 1000+ v1.981 ZMPSTE24 Zornitza Stark Phenotypes for gene: ZMPSTE24 were changed from Restrictive dermopathy, lethal, 275210 (3) to Mandibuloacral dysplasia with type B lipodystrophy, MIM# 608612; Restrictive dermopathy, lethal, MIM# 275210
Prepair 1000+ v1.980 ZMPSTE24 Zornitza Stark Publications for gene: ZMPSTE24 were set to
Prepair 1000+ v1.979 ZMPSTE24 Zornitza Stark edited their review of gene: ZMPSTE24: Changed phenotypes: Mandibuloacral dysplasia with type B lipodystrophy, MIM# 608612, Restrictive dermopathy, lethal, MIM# 275210
Prepair 1000+ v1.979 ZMPSTE24 Zornitza Stark edited their review of gene: ZMPSTE24: Changed publications: 11923874, 22718200, 29794150, 29208544, 12913070, 27410998, 27409638, 15937076, 16671095, 22718200, 29794150, 24169522
Prepair 1000+ v1.979 ZMPSTE24 Zornitza Stark reviewed gene: ZMPSTE24: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.979 ZNF711 Zornitza Stark Marked gene: ZNF711 as ready
Prepair 1000+ v1.979 ZNF711 Zornitza Stark Gene: znf711 has been classified as Green List (High Evidence).
Prepair 1000+ v1.979 ZNF711 Zornitza Stark Phenotypes for gene: ZNF711 were changed from Mental retardation, X-linked 97, 300803 (3) to Intellectual developmental disorder, X-linked 97, MIM# 300803
Prepair 1000+ v1.978 ZNF711 Zornitza Stark reviewed gene: ZNF711: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, X-linked 97, MIM# 300803; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v1.29 ZNF711 Zornitza Stark Phenotypes for gene: ZNF711 were changed from Mental retardation, X-linked 97; OMIM #300803 to Intellectual developmental disorder, X-linked 97, MIM# 300803
Intellectual disability syndromic and non-syndromic v1.28 ZNF711 Zornitza Stark reviewed gene: ZNF711: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, X-linked 97, MIM# 300803; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.978 RBCK1 Kate Scarff changed review comment from: Characterized by onset in childhood of progressive proximal muscle weakness, resulting in difficulties in ambulation. Most patients also develop progressive dilated cardiomyopathy, which may necessitate cardiac transplant in severe cases. A small subset of patients present with severe immunodeficiency and a hyperinflammatory state in very early childhood.

A 32kb deletion which included the three last exons of TRIB3 and the first four exons of RBCK1 was identified in one family, also had a nonsense mutation (PMID: 23104095).

The nature and localization of the underlying mutation might predict the phenotype, with N-terminal mutations mainly causing immunological dysfunction. In contrast, variants in the middle- or C-terminal regions were presumed to predominantly cause cardiomyopathy and neuromuscular symptoms. Further, it was suggested that truncating variants might generally result in more severe phenotypes than missense mutations. Frameshift mutations beyond the N-terminus
of RBCK1 may lead to a combined phenotype including both myopathy and immunological dysfunction in single
families (PMID: 29260357).; to: Characterized by onset in childhood of progressive proximal muscle weakness, resulting in difficulties in ambulation. Most patients also develop progressive dilated cardiomyopathy, which may necessitate cardiac transplant in severe cases. A small subset of patients present with severe immunodeficiency and a hyperinflammatory state in very early childhood.

A 32kb deletion which included the three last exons of TRIB3 and the first four exons of RBCK1 was identified in one family, also had a nonsense mutation (PMID: 23104095).

The nature and localization of the underlying mutation might predict the phenotype, with N-terminal mutations mainly causing immunological dysfunction. In contrast, variants in the middle- or C-terminal regions were presumed to predominantly cause cardiomyopathy and neuromuscular symptoms. Further, it was suggested that truncating variants might generally result in more severe phenotypes than missense mutations. Frameshift mutations beyond the N-terminus of RBCK1 may lead to a combined phenotype including both myopathy and immunological dysfunction in single families (PMID: 29260357).
Prepair 1000+ v1.978 RBCK1 Kate Scarff reviewed gene: RBCK1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23104095, 23798481, 32187699, 23889995, 29260357; Phenotypes: Polyglucosan body myopathy 1 with or without immunodeficiency, MIM #615895; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 RAX Kate Scarff reviewed gene: RAX: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 14662654, 18783408, 30811539, 24033328, 22736936, 28831107; Phenotypes: Microphthalmia, syndromic 16, MIM #611038; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 RARS Kate Scarff reviewed gene: RARS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31814314, 28905880, 24777941; Phenotypes: Leukodystrophy, hypomyelinating, 9, MIM #616140; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 RAB39B Kate Scarff reviewed gene: RAB39B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25434005, 34761259, 29152164, 20159109; Phenotypes: Intellectual developmental disorder, X-linked 72, MIM #300271; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.978 RAB33B Kate Scarff reviewed gene: RAB33B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35477554, 34000439, 22652534, 28127940, 23042644, 34284742; Phenotypes: Smith-McCort dysplasia 2, MIM #615222; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 PSAP Kate Scarff reviewed gene: PSAP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 10682309, 30632081, 11309366, 19267410, 8554069; Phenotypes: Metachromatic leukodystrophy due to SAP-b deficiency, MIM #249900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 NNT Marta Cifuentes Ochoa reviewed gene: NNT: Rating: GREEN; Mode of pathogenicity: None; Publications: 37352919, 26548497, 22634753, 23474776, 25879317, 26070314, 27129361; Phenotypes: Glucocorticoid deficiency 4, with or without mineralocorticoid deficiency MIM#614736, MONDO:0013874; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 NARS2 Marta Cifuentes Ochoa reviewed gene: NARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25385316, 25807530, 30327238, 28077841, 36252909, 33596490, 38310242; Phenotypes: Combined oxidative phosphorylation deficiency 24 - MIM#616239, MONDO:0014547, ?Deafness, autosomal recessive 94 - MIM#618434, MONDO:0032749; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 PIH1D3 Kate Scarff reviewed gene: PIH1D3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28176794, 28041644, 20301301; Phenotypes: Ciliary dyskinesia, primary, 36, X-linked, MIM #300991; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.978 MMP21 Marta Cifuentes Ochoa reviewed gene: MMP21: Rating: GREEN; Mode of pathogenicity: None; Publications: 26429889, 26437028, 26437029, 36123719, 33240936; Phenotypes: Heterotaxy, visceral, 7, autosomal MIM#616749, MONDO:0014762; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 MID1 Marta Cifuentes Ochoa reviewed gene: MID1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301502, 9354791; Phenotypes: Opitz GBBB syndrome MIM#300000, MONDO:0017138; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.978 PGAP3 Kate Scarff reviewed gene: PGAP3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24439110, 29620724, 30345601, 30217754; Phenotypes: Hyperphosphatasia with mental retardation syndrome 4, MIM# 615716, MONDO:0014318; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 MFSD8 Marta Cifuentes Ochoa reviewed gene: MFSD8: Rating: GREEN; Mode of pathogenicity: None; Publications: 17564970, 19201763, 25227500, 30382371, 35154277; Phenotypes: Ceroid lipofuscinosis, neuronal, 7, MIM# 610951, MONDO:0012588, Macular dystrophy with central cone involvement, MIM# 616170, MONDO:0014515; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 PEX1 Kate Scarff reviewed gene: PEX1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301621, 9398847, 17055079; Phenotypes: Peroxisome biogenesis disorder 1A (Zellweger), MIM #214100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 PGAP2 Shakira Heerah changed review comment from: Strong gene-disease association, multiple unrelated families reported severe intellectual disability.; to: Strong gene-disease association, multiple unrelated families reported severe intellectual disability.
Prepair 1000+ v1.978 PGAP2 Shakira Heerah changed review comment from: Strong gene-disease association, multiple unrelated families reported severe intellectual disability..; to: Strong gene-disease association, multiple unrelated families reported severe intellectual disability.
Prepair 1000+ v1.978 PGAP2 Shakira Heerah reviewed gene: PGAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23561846, 23561847, 31805394, 29119105, 27871432; Phenotypes: Hyperphosphatasia with impaired intellectual development syndrome 3, MIM#614207; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 PGAP2 Shakira Heerah Deleted their review
Prepair 1000+ v1.978 PGAP2 Shakira Heerah reviewed gene: PGAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23561846, 23561847, 31805394, 29119105, 27871432; Phenotypes: Hyperphosphatasia with impaired intellectual development syndrome 3, MIM#614207; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 PEX2 Shakira Heerah reviewed gene: PEX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 14630978, 10528859, 23430938, 1546315; Phenotypes: Peroxisome biogenesis disorder 5A (Zellweger), MIM#614866, Peroxisome biogenesis disorder 5B, MIM#614867; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 PDHB Kate Scarff reviewed gene: PDHB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15138885, 18164639, 26865159, 19924563, 34138529; Phenotypes: Pyruvate dehydrogenase E1-beta deficiency, MIM #614111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 KRT8 Shakira Heerah reviewed gene: KRT8: Rating: RED; Mode of pathogenicity: None; Publications: 15235035, 11372009, 12724528, 9011570; Phenotypes: Cirrhosis, cryptogenic, MIM#215600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Prepair 1000+ v1.978 PAPSS2 Kate Scarff reviewed gene: PAPSS2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22791835, 25594860, 31461705, 23633440; Phenotypes: Brachyolmia 4 with mild epiphyseal and metaphyseal changes, MIM #612847; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 NSDHL Kate Scarff changed review comment from: X-linked recessive disorder characterized by mild to severe cognitive impairment, seizures, microcephaly, cerebral cortical malformations, dysmorphic facial features, and thin body habitus. 25 affected males from three unrelated families have been reported. Heterozygous females are typically unaffected; however, some may experience mild behavior problems such as irritability or aggression. The NSDHL pathogenic variants c.455G>A, c.696_698delGAA, and c.1098dupT have been consistently associated with CK syndrome.

Other phenotype associated with this gene is CHILD syndrome (MIM #308050) not reportable for Prepair1000 as is X-linked dominant, only affects females, lethal before birth in hemizygous males.; to: X-linked recessive disorder characterized by mild to severe cognitive impairment, seizures, microcephaly, cerebral cortical malformations, dysmorphic facial features, and thin body habitus. 25 affected males from three unrelated families have been reported. Heterozygous females are typically unaffected; however, some may experience mild behavior problems such as irritability or aggression. The NSDHL pathogenic variants c.455G>A, c.696_698delGAA, and c.1098dupT have been consistently associated with CK syndrome.

Other phenotype associated with this gene is CHILD syndrome (MIM #308050) not reportable for Prepair1000 as is X-linked dominant, only affects females, lethal before birth in hemizygous males.

See also GeneReviews PMID: 21290788
Prepair 1000+ v1.978 NSDHL Kate Scarff reviewed gene: NSDHL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19842190, 21129721, 34091503, 23042573; Phenotypes: CK syndrome, MIM #300831; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.978 XYLT1 Shakira Heerah reviewed gene: XYLT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30554721, 24581741, 23982343, 39273648; Phenotypes: Desbuquois dysplasia 2, MIM#615777, Baratela-Scott syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 NEXMIF Kate Scarff reviewed gene: NEXMIF: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27358180, 33144681; Phenotypes: Intellectual developmental disorder, 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)
Prepair 1000+ v1.978 NEU1 Kate Scarff reviewed gene: NEU1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11063730, 8985184, 9054950, 39194692; Phenotypes: Sialidosis, type I, MIM #256550, Sialidosis, type II, MIM #256550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 NDUFS2 Kate Scarff reviewed gene: NDUFS2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31411514, 22036843, 20819849, 11220739, 23266820, 31411514; Phenotypes: Mitochondrial complex I deficiency, nuclear type 6, MIM #618228; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.978 FBXO7 Zornitza Stark Marked gene: FBXO7 as ready
Prepair 1000+ v1.978 FBXO7 Zornitza Stark Gene: fbxo7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.978 FBXO7 Zornitza Stark Phenotypes for gene: FBXO7 were changed from Parkinson disease 15, autosomal recessive, 260300 (3) to Parkinson disease 15, autosomal recessive, MIM#260300
Prepair 1000+ v1.977 FBXO7 Zornitza Stark Publications for gene: FBXO7 were set to
Prepair 1000+ v1.976 ERCC8 Zornitza Stark Marked gene: ERCC8 as ready
Prepair 1000+ v1.976 ERCC8 Zornitza Stark Gene: ercc8 has been classified as Green List (High Evidence).
Prepair 1000+ v1.976 ERCC8 Zornitza Stark Phenotypes for gene: ERCC8 were changed from Cockayne syndrome, type A, 216400 (3) to Cockayne syndrome, type A, MIM#216400
Prepair 1000+ v1.975 ERCC8 Zornitza Stark reviewed gene: ERCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cockayne syndrome, type A, MIM#216400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.975 EIF2B2 Zornitza Stark Marked gene: EIF2B2 as ready
Prepair 1000+ v1.975 EIF2B2 Zornitza Stark Gene: eif2b2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.975 EIF2B2 Zornitza Stark Phenotypes for gene: EIF2B2 were changed from Leukoencephalopathy with vanishing white matter, 603896 (3) to Leukoencephalopathy with vanishing white matter 2, with or without ovarian failure, MIM #620312
Prepair 1000+ v1.974 EIF2B2 Zornitza Stark Publications for gene: EIF2B2 were set to
Prepair 1000+ v1.973 DCDC2 Zornitza Stark Marked gene: DCDC2 as ready
Prepair 1000+ v1.973 DCDC2 Zornitza Stark Gene: dcdc2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.973 DCDC2 Zornitza Stark Phenotypes for gene: DCDC2 were changed from Nephronophthisis 19, 616217 (3) to Nephronophthisis 19, MIM #616217; Sclerosing cholangitis, neonatal, MIM #617394
Prepair 1000+ v1.972 DCDC2 Zornitza Stark Publications for gene: DCDC2 were set to
Prepair 1000+ v1.971 CWC27 Zornitza Stark Marked gene: CWC27 as ready
Prepair 1000+ v1.971 CWC27 Zornitza Stark Gene: cwc27 has been classified as Green List (High Evidence).
Prepair 1000+ v1.971 CWC27 Zornitza Stark Phenotypes for gene: CWC27 were changed from Retinitis pigmentosa with or without skeletal anomalies, 250410 (3), Autosomal recessive to Retinitis pigmentosa with or without skeletal anomalies, MIM# 250410
Prepair 1000+ v1.970 CWC27 Zornitza Stark Publications for gene: CWC27 were set to
Prepair 1000+ v1.969 CTSF Zornitza Stark Tag for review tag was added to gene: CTSF.
Prepair 1000+ v1.969 CYBA Lilian Downie Marked gene: CYBA as ready
Prepair 1000+ v1.969 CYBA Lilian Downie Gene: cyba has been classified as Green List (High Evidence).
Prepair 1000+ v1.969 CYBA Lilian Downie Phenotypes for gene: CYBA were changed from Chronic granulomatous disease, autosomal, due to deficiency of CYBA, 233690 (3) to Chronic granulomatous disease 4 MIM#233690
Prepair 1000+ v1.968 CYBA Lilian Downie Publications for gene: CYBA were set to
Prepair 1000+ v1.967 BBS4 Zornitza Stark Marked gene: BBS4 as ready
Prepair 1000+ v1.967 BBS4 Zornitza Stark Gene: bbs4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.967 BBS4 Zornitza Stark Phenotypes for gene: BBS4 were changed from Bardet-Biedl syndrome 4, 615982 (3) to Bardet-Biedl syndrome 4, MIM#615982
Prepair 1000+ v1.966 CYBA Lilian Downie reviewed gene: CYBA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22876374; Phenotypes: Chronic granulomatous disease 4 MIM#233690; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.966 BBS4 Zornitza Stark reviewed gene: BBS4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 4, MIM#615982; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.966 BBS2 Zornitza Stark Marked gene: BBS2 as ready
Prepair 1000+ v1.966 BBS2 Zornitza Stark Gene: bbs2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.966 BBS2 Zornitza Stark Phenotypes for gene: BBS2 were changed from Bardet-Biedl syndrome 2, 615981 (3) to Bardet-Biedl syndrome 2, MIM# 615981
Prepair 1000+ v1.965 BBS2 Zornitza Stark reviewed gene: BBS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 2, MIM# 615981; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.965 ASS1 Zornitza Stark Marked gene: ASS1 as ready
Prepair 1000+ v1.965 ASS1 Zornitza Stark Gene: ass1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.965 ASS1 Zornitza Stark Phenotypes for gene: ASS1 were changed from Citrullinemia, 215700 (3) to Citrullinaemia MIM# 215700
Prepair 1000+ v1.964 ASS1 Zornitza Stark Publications for gene: ASS1 were set to
Prepair 1000+ v1.963 ARX Zornitza Stark Marked gene: ARX as ready
Prepair 1000+ v1.963 ARX Zornitza Stark Gene: arx has been classified as Green List (High Evidence).
Prepair 1000+ v1.963 ARX Zornitza Stark Phenotypes for gene: ARX were changed from Hydranencephaly with abnormal genitalia, 300215 (3) to Developmental and epileptic encephalopathy 1, MIM#30835; Hydranencephaly with abnormal genitalia, MIM#300215; Intellectual developmental disorder, X-linked 29, MIM#300419; Lissencephaly, X-linked 2, MIM#300215; Partington syndrome, MIM#309510; Proud syndrome, MIM#300004
Prepair 1000+ v1.962 ARX Zornitza Stark Publications for gene: ARX were set to
Prepair 1000+ v1.961 ARX Zornitza Stark reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 1 MIM#308350, Hydranencephaly with abnormal genitalia MIM#300215, Lissencephaly, X-linked 2 MIM#300215, Intellectual disability, X-linked 29 and others MIM#300419, Partington syndrome MIM#309510, Proud syndrome MIM#300004; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.961 CHRNE Lilian Downie Phenotypes for gene: CHRNE were changed from Myasthenic syndrome, congenital, 4A, slow-channel, 605809 (3) to Myasthenic syndrome, congenital, 4A, slow-channel MIM#605809; Myasthenic syndrome, congenital, 4B, fast-channel MIM#616324; Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency MIM#608931
Prepair 1000+ v1.960 ALG1 Zornitza Stark Marked gene: ALG1 as ready
Prepair 1000+ v1.960 ALG1 Zornitza Stark Gene: alg1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.960 ALG1 Zornitza Stark Phenotypes for gene: ALG1 were changed from Congenital disorder of glycosylation, type Ik, 608540 (3) to Congenital disorder of glycosylation, type Ik, MIM# 608540
Prepair 1000+ v1.959 CHRNE Lilian Downie Publications for gene: CHRNE were set to
Prepair 1000+ v1.958 ALG1 Zornitza Stark Publications for gene: ALG1 were set to
Prepair 1000+ v1.957 ALDOB Zornitza Stark Marked gene: ALDOB as ready
Prepair 1000+ v1.957 ALDOB Zornitza Stark Gene: aldob has been classified as Green List (High Evidence).
Prepair 1000+ v1.957 ALDOB Zornitza Stark Phenotypes for gene: ALDOB were changed from Fructose intolerance, 229600 (3) to Fructose intolerance, hereditary, MIM# 229600
Prepair 1000+ v1.956 ALDOB Zornitza Stark Publications for gene: ALDOB were set to
Prepair 1000+ v1.955 CD40LG Lilian Downie Publications for gene: CD40LG were set to
Prepair 1000+ v1.954 ALDH5A1 Zornitza Stark Marked gene: ALDH5A1 as ready
Prepair 1000+ v1.954 ALDH5A1 Zornitza Stark Gene: aldh5a1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.954 ALDH5A1 Zornitza Stark Phenotypes for gene: ALDH5A1 were changed from Succinic semialdehyde dehydrogenase deficiency, 271980 (3) to Succinic semialdehyde dehydrogenase deficiency, MIM# 271980
Prepair 1000+ v1.953 ALDH5A1 Zornitza Stark Publications for gene: ALDH5A1 were set to
Prepair 1000+ v1.952 COQ8B Lilian Downie Marked gene: COQ8B as ready
Prepair 1000+ v1.952 COQ8B Lilian Downie Gene: coq8b has been classified as Green List (High Evidence).
Prepair 1000+ v1.952 COQ8B Lilian Downie Publications for gene: COQ8B were set to
Prepair 1000+ v1.951 ADGRV1 Zornitza Stark Marked gene: ADGRV1 as ready
Prepair 1000+ v1.951 ADGRV1 Zornitza Stark Gene: adgrv1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.951 ADGRV1 Zornitza Stark Phenotypes for gene: ADGRV1 were changed from Usher syndrome, type 2C, 605472 (3) to Usher syndrome, type 2C, MIM# 605472
Prepair 1000+ v1.950 COQ8B Lilian Downie reviewed gene: COQ8B: Rating: ; Mode of pathogenicity: None; Publications: PMID: 35483523; Phenotypes: Nephrotic syndrome, type 9 MIM#615573; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.950 ADGRV1 Zornitza Stark Publications for gene: ADGRV1 were set to
Prepair 1000+ v1.949 ADGRG1 Zornitza Stark Marked gene: ADGRG1 as ready
Prepair 1000+ v1.949 ADGRG1 Zornitza Stark Gene: adgrg1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.949 ADGRG1 Zornitza Stark Phenotypes for gene: ADGRG1 were changed from Polymicrogyria, bilateral frontoparietal, 606854 (3) to Polymicrogyria, bilateral frontoparietal, MIM#606854
Prepair 1000+ v1.948 ADGRG1 Zornitza Stark Publications for gene: ADGRG1 were set to
Prepair 1000+ v1.947 ADA2 Zornitza Stark Marked gene: ADA2 as ready
Prepair 1000+ v1.947 ADA2 Zornitza Stark Gene: ada2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.947 ADA2 Zornitza Stark Phenotypes for gene: ADA2 were changed from Polyarteritis nodosa, childhood-onset, 615688 (3) to Vasculitis, autoinflammation, immunodeficiency, and haematologic defects syndrome, MIM# 615688
Prepair 1000+ v1.946 ADA2 Zornitza Stark Publications for gene: ADA2 were set to
Prepair 1000+ v1.945 LARGE1 Zornitza Stark Marked gene: LARGE1 as ready
Prepair 1000+ v1.945 LARGE1 Zornitza Stark Gene: large1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.945 LARGE1 Zornitza Stark Phenotypes for gene: LARGE1 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, 613154 (3) to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, MIM #613154
Prepair 1000+ v1.944 LARGE1 Zornitza Stark Publications for gene: LARGE1 were set to
Prepair 1000+ v1.943 LRP4 Zornitza Stark Marked gene: LRP4 as ready
Prepair 1000+ v1.943 LRP4 Zornitza Stark Gene: lrp4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.943 LRP4 Zornitza Stark Phenotypes for gene: LRP4 were changed from Cenani-Lenz syndactyly syndrome, 212780 (3) to Cenani-Lenz syndactyly syndrome, MIM #212780
Prepair 1000+ v1.942 CHRNE Lilian Downie Marked gene: CHRNE as ready
Prepair 1000+ v1.942 CHRNE Lilian Downie Gene: chrne has been classified as Green List (High Evidence).
Prepair 1000+ v1.942 LRP4 Zornitza Stark Publications for gene: LRP4 were set to
Prepair 1000+ v1.941 CHRNE Lilian Downie reviewed gene: CHRNE: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301347; Phenotypes: Myasthenic syndrome, congenital, 4A, slow-channel MIM#605809, Myasthenic syndrome, congenital, 4B, fast-channel MIM#616324, Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency MIM#608931; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.941 MBOAT7 Zornitza Stark Marked gene: MBOAT7 as ready
Prepair 1000+ v1.941 MBOAT7 Zornitza Stark Gene: mboat7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.941 MBOAT7 Zornitza Stark Phenotypes for gene: MBOAT7 were changed from Mental retardation, autosomal recessive 57, 617188 (3) to Intellectual developmental disorder, autosomal recessive 57, MIM #617188
Prepair 1000+ v1.940 MBOAT7 Zornitza Stark Publications for gene: MBOAT7 were set to
Prepair 1000+ v1.939 MC2R Zornitza Stark Marked gene: MC2R as ready
Prepair 1000+ v1.939 MC2R Zornitza Stark Gene: mc2r has been classified as Green List (High Evidence).
Prepair 1000+ v1.939 MC2R Zornitza Stark Phenotypes for gene: MC2R were changed from Glucocorticoid deficiency, due to ACTH unresponsiveness, 202200 (3) to Glucocorticoid deficiency, due to ACTH unresponsiveness, MIM #202200
Prepair 1000+ v1.938 MC2R Zornitza Stark Publications for gene: MC2R were set to
Prepair 1000+ v1.937 MRAP Zornitza Stark Marked gene: MRAP as ready
Prepair 1000+ v1.937 MRAP Zornitza Stark Gene: mrap has been classified as Green List (High Evidence).
Prepair 1000+ v1.937 MRAP Zornitza Stark Phenotypes for gene: MRAP were changed from Glucocorticoid deficiency 2, 607398 (3) to Glucocorticoid deficiency 2, MIM #607398
Prepair 1000+ v1.936 MRAP Zornitza Stark Publications for gene: MRAP were set to
Prepair 1000+ v1.935 MESP2 Zornitza Stark Marked gene: MESP2 as ready
Prepair 1000+ v1.935 MESP2 Zornitza Stark Gene: mesp2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.935 MESP2 Zornitza Stark Phenotypes for gene: MESP2 were changed from Spondylocostal dysostosis 2, autosomal recessive, 608681 (3) to Spondylocostal dysostosis 2, MIM #608681
Prepair 1000+ v1.934 CD40LG Lilian Downie Marked gene: CD40LG as ready
Prepair 1000+ v1.934 CD40LG Lilian Downie Gene: cd40lg has been classified as Green List (High Evidence).
Prepair 1000+ v1.934 CD40LG Lilian Downie reviewed gene: CD40LG: Rating: GREEN; Mode of pathogenicity: None; Publications: 7679801, 7679206, 8094231, 9933119, 15358621, 15997875, 7678782, 7915248, 15367912, 7518839, 16311023, 9933119, 12402041, 7882172, 33475257; Phenotypes: Immunodeficiency, X-linked, with hyper-IgM MIM# 308230; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.934 MESP2 Zornitza Stark Publications for gene: MESP2 were set to
Prepair 1000+ v1.933 MTRR Zornitza Stark Marked gene: MTRR as ready
Prepair 1000+ v1.933 MTRR Zornitza Stark Gene: mtrr has been classified as Green List (High Evidence).
Prepair 1000+ v1.933 MTRR Zornitza Stark Phenotypes for gene: MTRR were changed from Homocystinuria-megaloblastic anemia, cbl E type, 236270 (3) to Homocystinuria-megaloblastic anaemia, cbl E type, MIM #236270
Prepair 1000+ v1.932 MTRR Zornitza Stark Publications for gene: MTRR were set to
Prepair 1000+ v1.931 PRPS1 Zornitza Stark Marked gene: PRPS1 as ready
Prepair 1000+ v1.931 PRPS1 Zornitza Stark Gene: prps1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.931 PRPS1 Zornitza Stark Phenotypes for gene: PRPS1 were changed from Arts syndrome, 301835 (3) to PRPS1 deficiency disorder MONDO:0100061; Phosphoribosylpyrophosphate synthetase superactivity MIM#300661 MONDO:0010395
Prepair 1000+ v1.930 PRPS1 Zornitza Stark Mode of inheritance for gene: PRPS1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.929 TF Zornitza Stark Marked gene: TF as ready
Prepair 1000+ v1.929 TF Zornitza Stark Gene: tf has been classified as Green List (High Evidence).
Prepair 1000+ v1.929 TF Zornitza Stark Phenotypes for gene: TF were changed from Atransferrinemia MIM#209300 to Atransferrinaemia MIM#209300
Prepair 1000+ v1.928 TF Zornitza Stark Phenotypes for gene: TF were changed from Atransferrinemia, 209300 (3) to Atransferrinemia MIM#209300
Prepair 1000+ v1.927 TF Zornitza Stark Publications for gene: TF were set to
Prepair 1000+ v1.926 NBAS Zornitza Stark Marked gene: NBAS as ready
Prepair 1000+ v1.926 NBAS Zornitza Stark Gene: nbas has been classified as Green List (High Evidence).
Prepair 1000+ v1.926 NBAS Zornitza Stark Phenotypes for gene: NBAS were changed from Short stature, optic nerve atrophy, and Pelger-Huet anomaly, 614800 (3) to Short stature, optic nerve atrophy, and Pelger-Huet anomaly, MIM#614800; Infantile liver failure syndrome 2, MIM#616483
Prepair 1000+ v1.925 NBAS Zornitza Stark Publications for gene: NBAS were set to 20577004; 26073778
Prepair 1000+ v1.924 NBAS Zornitza Stark reviewed gene: NBAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31761904; Phenotypes: Short stature, optic nerve atrophy, and Pelger-Huet anomaly, MIM#614800, Infantile liver failure syndrome 2, MIM#616483; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.924 NBAS Zornitza Stark Publications for gene: NBAS were set to
Prepair 1000+ v1.923 NHEJ1 Zornitza Stark Marked gene: NHEJ1 as ready
Prepair 1000+ v1.923 NHEJ1 Zornitza Stark Gene: nhej1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.923 NHEJ1 Zornitza Stark Phenotypes for gene: NHEJ1 were changed from Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, 611291 (3) to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM#611291
Prepair 1000+ v1.922 NHEJ1 Zornitza Stark Publications for gene: NHEJ1 were set to
Prepair 1000+ v1.921 OCLN Zornitza Stark Marked gene: OCLN as ready
Prepair 1000+ v1.921 OCLN Zornitza Stark Gene: ocln has been classified as Green List (High Evidence).
Prepair 1000+ v1.921 OCLN Zornitza Stark Phenotypes for gene: OCLN were changed from Band-like calcification with simplified gyration and polymicrogyria, 251290 (3) to Pseudo-TORCH syndrome 1, MIM#251290
Prepair 1000+ v1.920 OCLN Zornitza Stark Publications for gene: OCLN were set to
Prepair 1000+ v1.919 PIGO Zornitza Stark reviewed gene: PIGO: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperphosphatasia with impaired intellectual development syndrome 2, MIM#614749; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.919 PIGO Zornitza Stark Marked gene: PIGO as ready
Prepair 1000+ v1.919 PIGO Zornitza Stark Gene: pigo has been classified as Green List (High Evidence).
Prepair 1000+ v1.919 PIGO Zornitza Stark Phenotypes for gene: PIGO were changed from Hyperphosphatasia with mental retardation syndrome 2, 614749 (3) to Hyperphosphatasia with impaired intellectual development syndrome 2, MIM#614749
Prepair 1000+ v1.918 PIGO Zornitza Stark Publications for gene: PIGO were set to
Prepair 1000+ v1.917 COX10 Zornitza Stark Marked gene: COX10 as ready
Prepair 1000+ v1.917 COX10 Zornitza Stark Gene: cox10 has been classified as Green List (High Evidence).
Prepair 1000+ v1.917 COX10 Zornitza Stark Phenotypes for gene: COX10 were changed from Leigh syndrome due to mitochondrial COX4 deficiency, 256000 (3) to Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046
Prepair 1000+ v1.916 COX10 Zornitza Stark Publications for gene: COX10 were set to
Prepair 1000+ v1.915 DCLRE1C Zornitza Stark Marked gene: DCLRE1C as ready
Prepair 1000+ v1.915 DCLRE1C Zornitza Stark Gene: dclre1c has been classified as Green List (High Evidence).
Prepair 1000+ v1.915 DCLRE1C Zornitza Stark Phenotypes for gene: DCLRE1C were changed from Severe combined immunodeficiency, Athabascan type, 602450 (3) to Severe combined immunodeficiency, Athabascan type, MIM# 602450; Omenn syndrome, MIM# 603554
Prepair 1000+ v1.914 DCLRE1C Zornitza Stark Publications for gene: DCLRE1C were set to
Prepair 1000+ v1.913 PROP1 Zornitza Stark Marked gene: PROP1 as ready
Prepair 1000+ v1.913 PROP1 Zornitza Stark Gene: prop1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.913 PROP1 Zornitza Stark Phenotypes for gene: PROP1 were changed from Pituitary hormone deficiency, combined, 2, 262600 (3) to Pituitary hormone deficiency, combined, 2, MIM#262600
Prepair 1000+ v1.912 DOCK6 Zornitza Stark Marked gene: DOCK6 as ready
Prepair 1000+ v1.912 DOCK6 Zornitza Stark Gene: dock6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.912 DOCK6 Zornitza Stark Publications for gene: DOCK6 were set to
Prepair 1000+ v1.911 ELP2 Zornitza Stark Marked gene: ELP2 as ready
Prepair 1000+ v1.911 ELP2 Zornitza Stark Gene: elp2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.911 ELP2 Zornitza Stark Phenotypes for gene: ELP2 were changed from Mental retardation, autosomal recessive 58, 617270 (3) to Intellectual developmental disorder, autosomal recessive 58, MIM# 617270
Prepair 1000+ v1.910 ELP2 Zornitza Stark Publications for gene: ELP2 were set to
Prepair 1000+ v1.909 EMD Zornitza Stark Marked gene: EMD as ready
Prepair 1000+ v1.909 EMD Zornitza Stark Gene: emd has been classified as Green List (High Evidence).
Prepair 1000+ v1.909 EMD Zornitza Stark Phenotypes for gene: EMD were changed from Emery-Dreifuss muscular dystrophy 1, X-linked, 310300 (3) to Emery-Dreifuss muscular dystrophy 1, X-linked, MIM# 310300
Prepair 1000+ v1.908 EMD Zornitza Stark Publications for gene: EMD were set to
Prepair 1000+ v1.907 ETFB Zornitza Stark Marked gene: ETFB as ready
Prepair 1000+ v1.907 ETFB Zornitza Stark Gene: etfb has been classified as Green List (High Evidence).
Prepair 1000+ v1.907 ETFB Zornitza Stark Phenotypes for gene: ETFB were changed from Glutaric acidemia IIB, MIM# 231680 to Glutaric acidaemia IIB, MIM# 231680
Prepair 1000+ v1.906 ETFB Zornitza Stark Phenotypes for gene: ETFB were changed from Glutaric acidemia IIB, 231680 (3) to Glutaric acidemia IIB, MIM# 231680
Prepair 1000+ v1.905 ETFB Zornitza Stark Publications for gene: ETFB were set to
Prepair 1000+ v1.904 NAXE Kate Scarff reviewed gene: NAXE: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27122014, 27616477, 31758406, 34678889, 35637064, 39455596; Phenotypes: Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, MIM #617186; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.904 FBXL4 Zornitza Stark Marked gene: FBXL4 as ready
Prepair 1000+ v1.904 FBXL4 Zornitza Stark Gene: fbxl4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.904 FBXL4 Zornitza Stark Phenotypes for gene: FBXL4 were changed from Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), 615471 (3) to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) MIM#615471
Prepair 1000+ v1.903 FBXL4 Zornitza Stark Publications for gene: FBXL4 were set to
Prepair 1000+ v1.902 FH Zornitza Stark Marked gene: FH as ready
Prepair 1000+ v1.902 FH Zornitza Stark Gene: fh has been classified as Green List (High Evidence).
Prepair 1000+ v1.902 FH Zornitza Stark Phenotypes for gene: FH were changed from Fumarase deficiency, 606812 (3) to Fumarase deficiency, MIM# 606812
Prepair 1000+ v1.901 FH Zornitza Stark Publications for gene: FH were set to
Prepair 1000+ v1.900 FOXRED1 Zornitza Stark Marked gene: FOXRED1 as ready
Prepair 1000+ v1.900 FOXRED1 Zornitza Stark Gene: foxred1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.900 FOXRED1 Zornitza Stark Phenotypes for gene: FOXRED1 were changed from Mitochondrial complex I deficiency, 252010 (3) to Mitochondrial complex I deficiency, nuclear type 19, MIM# 618241
Prepair 1000+ v1.899 FOXRED1 Zornitza Stark Publications for gene: FOXRED1 were set to
Prepair 1000+ v1.898 GBA2 Zornitza Stark Marked gene: GBA2 as ready
Prepair 1000+ v1.898 GBA2 Zornitza Stark Gene: gba2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.898 GBA2 Zornitza Stark Phenotypes for gene: GBA2 were changed from Spastic paraplegia 46, autosomal recessive, 614409 (3) to Spastic paraplegia 46, autosomal recessive, MIM# 614409
Prepair 1000+ v1.897 GBA2 Zornitza Stark Publications for gene: GBA2 were set to
Prepair 1000+ v1.896 GUSB Zornitza Stark Marked gene: GUSB as ready
Prepair 1000+ v1.896 GUSB Zornitza Stark Gene: gusb has been classified as Green List (High Evidence).
Prepair 1000+ v1.896 GUSB Zornitza Stark Phenotypes for gene: GUSB were changed from Mucopolysaccharidosis VII, 253220 (3) to Mucopolysaccharidosis VII, MIM# 253220
Prepair 1000+ v1.895 GUSB Zornitza Stark Publications for gene: GUSB were set to
Prepair 1000+ v1.894 HPS6 Zornitza Stark Marked gene: HPS6 as ready
Prepair 1000+ v1.894 HPS6 Zornitza Stark Gene: hps6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.894 HPS6 Zornitza Stark Phenotypes for gene: HPS6 were changed from Hermansky-Pudlak syndrome 6, 614075 (3) to Hermansky-Pudlak syndrome 6, MIM# 614075
Prepair 1000+ v1.893 HPS6 Zornitza Stark Publications for gene: HPS6 were set to
Prepair 1000+ v1.892 HPS6 Zornitza Stark reviewed gene: HPS6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hermansky-Pudlak syndrome 6, MIM# 614075; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.892 MTRR Kate Scarff reviewed gene: MTRR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301503, 12555939, 15714522, 9501215; Phenotypes: Homocystinuria-megaloblastic anemia, cbl E type, MIM #236270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.892 MESP2 Kate Scarff reviewed gene: MESP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18485326, 15122512, 20301771; Phenotypes: Spondylocostal dysostosis 2, MIM #608681; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Vasculitis v0.86 DNASE1 Zornitza Stark commented on gene: DNASE1: PMIDs 36444430 and 37804110 also refer to DNASE1L3. No additional evidence for DNASE1 identified.
Vasculitis v0.86 DNASE1 Zornitza Stark commented on gene: DNASE1: Similarly PMID: 30008451 reports patient with DNASE1L3 variant rather than DNASE1 variant.
Vasculitis v0.86 DNASE1 Zornitza Stark commented on gene: DNASE1: PMID 34161863: paper reports individual with DNASE1L3 deficiency. DNASE1L3 is already Green on the relevant panel.
Mendeliome v1.2229 P2RY8 Zornitza Stark Marked gene: P2RY8 as ready
Mendeliome v1.2229 P2RY8 Zornitza Stark Gene: p2ry8 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2229 P2RY8 Zornitza Stark Classified gene: P2RY8 as Amber List (moderate evidence)
Mendeliome v1.2229 P2RY8 Zornitza Stark Gene: p2ry8 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2228 P2RY8 Zornitza Stark gene: P2RY8 was added
gene: P2RY8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: P2RY8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: P2RY8 were set to 34889940
Phenotypes for gene: P2RY8 were set to Systemic lupus erythematosus, MONDO:0007915, P2RY8-related
Review for gene: P2RY8 was set to AMBER
Added comment: One de novo variant, p.Leu257Phe, absent from gnomAD v4 identified in an individual with early-onset SLE.

Subsequent search for additional individuals in large cohorts identified:
p. Asn97Lys, inherited from mother, present in 19 individuals in gnomADv4.
p.Glu323Gly identified in 6 Chinese individuals, inheritance not determined, present in 51 individuals in gnomADv4.

Functional data support the role of the gene in immune tolerance. Role in contributing to the development of SLE is plausible, though not necessarily under a monogenic model.
Sources: Literature
Disorders of immune dysregulation v1.3 P2RY8 Zornitza Stark Marked gene: P2RY8 as ready
Disorders of immune dysregulation v1.3 P2RY8 Zornitza Stark Gene: p2ry8 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v1.3 P2RY8 Zornitza Stark Phenotypes for gene: P2RY8 were changed from systemic lupus erythematosis; vasculitis; nephritis to Systemic lupus erythematosus, MONDO:0007915, P2RY8-related
Disorders of immune dysregulation v1.2 P2RY8 Zornitza Stark Classified gene: P2RY8 as Amber List (moderate evidence)
Disorders of immune dysregulation v1.2 P2RY8 Zornitza Stark Gene: p2ry8 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v1.1 P2RY8 Zornitza Stark edited their review of gene: P2RY8: Changed phenotypes: Systemic lupus erythematosus, MONDO:0007915, P2RY8-related
Disorders of immune dysregulation v1.1 P2RY8 Zornitza Stark reviewed gene: P2RY8: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v1.892 MRAP Kate Scarff reviewed gene: MRAP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15654338, 34271604, 38796770, 36777708, 30817990; Phenotypes: Glucocorticoid deficiency 2, MIM #607398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.892 MC2R Kate Scarff reviewed gene: MC2R: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38796770, 8094489, 8227361, 35506146; Phenotypes: Glucocorticoid deficiency, due to ACTH unresponsiveness, MIM #202200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.892 MBOAT7 Kate Scarff reviewed gene: MBOAT7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23097495, 27616480, 33335874, 32645526, 32744787, 31852446, 31282596, 30701556; Phenotypes: Intellectual developmental disorder, autosomal recessive 57, MIM #617188; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2227 PACSIN1 Zornitza Stark Marked gene: PACSIN1 as ready
Mendeliome v1.2227 PACSIN1 Zornitza Stark Gene: pacsin1 has been classified as Red List (Low Evidence).
Mendeliome v1.2227 PACSIN1 Zornitza Stark gene: PACSIN1 was added
gene: PACSIN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PACSIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PACSIN1 were set to 36622335
Phenotypes for gene: PACSIN1 were set to Systemic lupus erythematosus, MONDO:0007915, PACSIN1-related
Review for gene: PACSIN1 was set to RED
Added comment: Single individual with de novo missense variant reported, supportive functional data.
Sources: Literature
Disorders of immune dysregulation v1.1 PACSIN1 Zornitza Stark Marked gene: PACSIN1 as ready
Disorders of immune dysregulation v1.1 PACSIN1 Zornitza Stark Gene: pacsin1 has been classified as Red List (Low Evidence).
Disorders of immune dysregulation v1.1 PACSIN1 Zornitza Stark Classified gene: PACSIN1 as Red List (low evidence)
Disorders of immune dysregulation v1.1 PACSIN1 Zornitza Stark Gene: pacsin1 has been classified as Red List (Low Evidence).
Disorders of immune dysregulation v1.0 PACSIN1 Zornitza Stark reviewed gene: PACSIN1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v1.892 LRP4 Kate Scarff reviewed gene: LRP4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23636941, 20381006, 23664847, 30041615; Phenotypes: Cenani-Lenz syndactyly syndrome, MIM #212780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.892 LARGE1 Kate Scarff reviewed gene: LARGE1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12966029, 19067344, 21248746, 17436019, 19299310; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, MIM #613154; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.892 GUCY2D Zornitza Stark Marked gene: GUCY2D as ready
Prepair 1000+ v1.892 GUCY2D Zornitza Stark Gene: gucy2d has been classified as Green List (High Evidence).
Prepair 1000+ v1.892 GUCY2D Zornitza Stark Phenotypes for gene: GUCY2D were changed from Leber congenital amaurosis 1, 204000 (3) to Leber congenital amaurosis 1, MIM#204000
Prepair 1000+ v1.891 GUCY2D Zornitza Stark Publications for gene: GUCY2D were set to
Prepair 1000+ v1.890 RTEL1 Zornitza Stark Marked gene: RTEL1 as ready
Prepair 1000+ v1.890 RTEL1 Zornitza Stark Gene: rtel1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.890 RTEL1 Zornitza Stark Phenotypes for gene: RTEL1 were changed from Dyskeratosis congenita, autosomal recessive 5, 615190 (3) to Dyskeratosis congenita, autosomal recessive 5, MIM#615190
Prepair 1000+ v1.889 RTEL1 Zornitza Stark Publications for gene: RTEL1 were set to
Prepair 1000+ v1.888 SACS Zornitza Stark Marked gene: SACS as ready
Prepair 1000+ v1.888 SACS Zornitza Stark Added comment: Comment when marking as ready: There is also a relatively common CNV.
Prepair 1000+ v1.888 SACS Zornitza Stark Gene: sacs has been classified as Green List (High Evidence).
Prepair 1000+ v1.888 SACS Zornitza Stark Phenotypes for gene: SACS were changed from Spastic ataxia, Charlevoix-Saguenay type, 270550 (3) to Spastic ataxia, Charlevoix-Saguenay type, MIM#270550
Prepair 1000+ v1.887 SACS Zornitza Stark Publications for gene: SACS were set to
Prepair 1000+ v1.886 SACS Zornitza Stark Tag SV/CNV tag was added to gene: SACS.
Prepair 1000+ v1.886 PIGG Zornitza Stark Marked gene: PIGG as ready
Prepair 1000+ v1.886 PIGG Zornitza Stark Gene: pigg has been classified as Green List (High Evidence).
Prepair 1000+ v1.886 PIGG Zornitza Stark Publications for gene: PIGG were set to
Prepair 1000+ v1.885 PIGG Zornitza Stark reviewed gene: PIGG: Rating: GREEN; Mode of pathogenicity: None; Publications: 26996948; Phenotypes: Neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophy MIM#616917; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.885 HAX1 Zornitza Stark Marked gene: HAX1 as ready
Prepair 1000+ v1.885 HAX1 Zornitza Stark Gene: hax1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.885 HAX1 Zornitza Stark Phenotypes for gene: HAX1 were changed from Neutropenia, severe congenital 3, autosomal recessive, 610738 (3) to Neutropenia, severe congenital 3, autosomal recessive, MIM#610738
Prepair 1000+ v1.884 HAX1 Zornitza Stark Publications for gene: HAX1 were set to
Prepair 1000+ v1.883 HPS4 Zornitza Stark Marked gene: HPS4 as ready
Prepair 1000+ v1.883 HPS4 Zornitza Stark Gene: hps4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.883 HPS4 Zornitza Stark Phenotypes for gene: HPS4 were changed from Hermansky-Pudlak syndrome 4, 614073 (3) to Hermansky-Pudlak syndrome 4, MIM #614073
Prepair 1000+ v1.882 HPS4 Zornitza Stark Publications for gene: HPS4 were set to
Prepair 1000+ v1.881 INPPL1 Zornitza Stark Marked gene: INPPL1 as ready
Prepair 1000+ v1.881 INPPL1 Zornitza Stark Gene: inppl1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.881 INPPL1 Zornitza Stark Phenotypes for gene: INPPL1 were changed from Opsismodysplasia, 258480 (3) to Opsismodysplasia MIM #258480
Prepair 1000+ v1.880 INPPL1 Zornitza Stark Publications for gene: INPPL1 were set to
Prepair 1000+ v1.879 KIF14 Zornitza Stark Marked gene: KIF14 as ready
Prepair 1000+ v1.879 KIF14 Zornitza Stark Gene: kif14 has been classified as Green List (High Evidence).
Prepair 1000+ v1.879 KIF14 Zornitza Stark Phenotypes for gene: KIF14 were changed from Microcephaly 20, primary, autosomal recessive, 617914 (3) to Microcephaly 20, primary, autosomal recessive, MIM #617914
Prepair 1000+ v1.878 KIF14 Zornitza Stark Publications for gene: KIF14 were set to
Prepair 1000+ v1.877 KIF14 Zornitza Stark reviewed gene: KIF14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly 20, primary, autosomal recessive, MIM #617914; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.877 LAMC3 Zornitza Stark Marked gene: LAMC3 as ready
Prepair 1000+ v1.877 LAMC3 Zornitza Stark Gene: lamc3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.877 LAMC3 Zornitza Stark Phenotypes for gene: LAMC3 were changed from Cortical malformations, occipital, 614115 (3) to Cortical malformations, occipital, MIM #614115
Prepair 1000+ v1.876 LAMC3 Zornitza Stark Publications for gene: LAMC3 were set to
Prepair 1000+ v1.875 RIPK4 Zornitza Stark Marked gene: RIPK4 as ready
Prepair 1000+ v1.875 RIPK4 Zornitza Stark Gene: ripk4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.875 RIPK4 Zornitza Stark Phenotypes for gene: RIPK4 were changed from Popliteal pterygium syndrome 2, lethal type, 263650 (3) to Popliteal pterygium syndrome, Bartsocas-Papas type 1, MIM# 263650
Prepair 1000+ v1.874 RIPK4 Zornitza Stark Publications for gene: RIPK4 were set to
Prepair 1000+ v1.873 XIAP Zornitza Stark Marked gene: XIAP as ready
Prepair 1000+ v1.873 XIAP Zornitza Stark Gene: xiap has been classified as Green List (High Evidence).
Prepair 1000+ v1.873 XIAP Zornitza Stark Phenotypes for gene: XIAP were changed from Lymphoproliferative syndrome, X-linked, 2, 300635 (3) to Lymphoproliferative syndorme, X-linked, 2 MIM#300635
Prepair 1000+ v1.872 XIAP Zornitza Stark Publications for gene: XIAP were set to
Prepair 1000+ v1.871 C1QB Zornitza Stark Marked gene: C1QB as ready
Prepair 1000+ v1.871 C1QB Zornitza Stark Gene: c1qb has been classified as Green List (High Evidence).
Prepair 1000+ v1.871 C1QB Zornitza Stark Phenotypes for gene: C1QB were changed from C1q deficiency, 613652 (3) to C1q deficiency, MIM# 613652
Prepair 1000+ v1.870 C1QB Zornitza Stark reviewed gene: C1QB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: C1q deficiency, MIM# 613652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.870 C5orf42 Zornitza Stark Marked gene: C5orf42 as ready
Prepair 1000+ v1.870 C5orf42 Zornitza Stark Gene: c5orf42 has been classified as Green List (High Evidence).
Prepair 1000+ v1.870 C5orf42 Zornitza Stark Phenotypes for gene: C5orf42 were changed from Joubert syndrome 17, 614615 (3) to Joubert syndrome 17, MIM# 614615; Orofaciodigital syndrome VI, MIM# 277170
Prepair 1000+ v1.869 C5orf42 Zornitza Stark Publications for gene: C5orf42 were set to
Prepair 1000+ v1.868 C5orf42 Zornitza Stark Tag new gene name tag was added to gene: C5orf42.
Prepair 1000+ v1.868 C5orf42 Zornitza Stark reviewed gene: C5orf42: Rating: GREEN; Mode of pathogenicity: None; Publications: 22425360, 24178751; Phenotypes: Joubert syndrome 17, MIM# 614615, Orofaciodigital syndrome VI, MIM# 277170; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.868 CC2D1A Zornitza Stark Marked gene: CC2D1A as ready
Prepair 1000+ v1.868 CC2D1A Zornitza Stark Gene: cc2d1a has been classified as Green List (High Evidence).
Prepair 1000+ v1.868 CC2D1A Zornitza Stark Phenotypes for gene: CC2D1A were changed from Mental retardation, autosomal recessive 3, 608443 (3) to Intellectual developmental disorder, autosomal recessive 3, MIM# 608443
Prepair 1000+ v1.867 CC2D1A Zornitza Stark Publications for gene: CC2D1A were set to
Mendeliome v1.2226 CC2D1A Zornitza Stark Phenotypes for gene: CC2D1A were changed from Autosomal recessive mental retardation, (MIM#608443) to Intellectual developmental disorder, autosomal recessive 3, MIM# 608443
Prepair 1000+ v1.866 CC2D1A Zornitza Stark reviewed gene: CC2D1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 25066123; Phenotypes: Intellectual developmental disorder, autosomal recessive 3, MIM# 608443; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2225 CC2D1A Zornitza Stark edited their review of gene: CC2D1A: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 3, MIM# 608443
Prepair 1000+ v1.866 CDH3 Zornitza Stark Marked gene: CDH3 as ready
Prepair 1000+ v1.866 CDH3 Zornitza Stark Gene: cdh3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.866 CDH3 Zornitza Stark Phenotypes for gene: CDH3 were changed from Ectodermal dysplasia, ectrodactyly, and macular dystrophy, 225280 (3) to Ectodermal dysplasia, ectrodactyly, and macular dystrophy, MIM# 225280; Hypotrichosis, congenital, with juvenile macular dystrophy, MIM# 601553
Prepair 1000+ v1.865 CDH3 Zornitza Stark Publications for gene: CDH3 were set to
Prepair 1000+ v1.864 CDH3 Zornitza Stark reviewed gene: CDH3: Rating: GREEN; Mode of pathogenicity: None; Publications: 11544476, 15805154, 28061825, 22140374; Phenotypes: Ectodermal dysplasia, ectrodactyly, and macular dystrophy, MIM# 225280, Hypotrichosis, congenital, with juvenile macular dystrophy, MIM# 601553; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.864 CEP120 Zornitza Stark Marked gene: CEP120 as ready
Prepair 1000+ v1.864 CEP120 Zornitza Stark Gene: cep120 has been classified as Green List (High Evidence).
Prepair 1000+ v1.864 CEP120 Zornitza Stark Phenotypes for gene: CEP120 were changed from Short-rib thoracic dysplasia 13 with or without polydactyly, 616300 (3) to Joubert syndrome 31, MIM# 617761; Short-rib thoracic dysplasia 13 with or without polydactyly, MIM# 616300
Prepair 1000+ v1.863 CEP120 Zornitza Stark Publications for gene: CEP120 were set to
Prepair 1000+ v1.862 CEP120 Zornitza Stark reviewed gene: CEP120: Rating: GREEN; Mode of pathogenicity: None; Publications: 27208211, 33486889, 29847808, 25361962, 27208211; Phenotypes: Joubert syndrome 31, MIM# 617761, Short-rib thoracic dysplasia 13 with or without polydactyly, MIM# 616300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.862 CFD Zornitza Stark Marked gene: CFD as ready
Prepair 1000+ v1.862 CFD Zornitza Stark Gene: cfd has been classified as Green List (High Evidence).
Prepair 1000+ v1.862 CFD Zornitza Stark Phenotypes for gene: CFD were changed from Complement factor D deficiency, 613912 (3) to Complement factor D deficiency, MIM# 613912
Prepair 1000+ v1.861 CFD Zornitza Stark Publications for gene: CFD were set to
Prepair 1000+ v1.860 CFD Zornitza Stark reviewed gene: CFD: Rating: GREEN; Mode of pathogenicity: None; Publications: 11457876, 16527897, 31440263; Phenotypes: Complement factor D deficiency, MIM# 613912; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.860 CHSY1 Zornitza Stark Marked gene: CHSY1 as ready
Prepair 1000+ v1.860 CHSY1 Zornitza Stark Gene: chsy1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.860 CHSY1 Zornitza Stark Phenotypes for gene: CHSY1 were changed from Temtamy preaxial brachydactyly syndrome, 605282 (3) to Temtamy preaxial brachydactyly syndrome, MIM# 605282
Prepair 1000+ v1.859 CHSY1 Zornitza Stark Publications for gene: CHSY1 were set to
Prepair 1000+ v1.858 CHSY1 Zornitza Stark reviewed gene: CHSY1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21129728, 21129727, 24269551; Phenotypes: Temtamy preaxial brachydactyly syndrome, MIM# 605282; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.858 CLCN5 Zornitza Stark Marked gene: CLCN5 as ready
Prepair 1000+ v1.858 CLCN5 Zornitza Stark Gene: clcn5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.858 CLCN5 Zornitza Stark Phenotypes for gene: CLCN5 were changed from Dent disease, 300009 (3) to Dent disease, MIM#300009
Prepair 1000+ v1.857 CLCN5 Zornitza Stark reviewed gene: CLCN5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dent disease, MIM#300009; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.857 CLMP Zornitza Stark Marked gene: CLMP as ready
Prepair 1000+ v1.857 CLMP Zornitza Stark Gene: clmp has been classified as Green List (High Evidence).
Prepair 1000+ v1.857 CLMP Zornitza Stark Phenotypes for gene: CLMP were changed from Congenital short bowel syndrome, 615237 (3) to Congenital short bowel syndrome , MIM#615237
Prepair 1000+ v1.856 CLMP Zornitza Stark Publications for gene: CLMP were set to
Prepair 1000+ v1.855 CLMP Zornitza Stark reviewed gene: CLMP: Rating: GREEN; Mode of pathogenicity: None; Publications: 22155368; Phenotypes: Congenital short bowel syndrome , MIM#615237; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.855 COL6A2 Zornitza Stark Marked gene: COL6A2 as ready
Prepair 1000+ v1.855 COL6A2 Zornitza Stark Gene: col6a2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.855 COL6A2 Zornitza Stark Phenotypes for gene: COL6A2 were changed from Ullrich congenital muscular dystrophy 1, 254090 (3) to Bethlem myopathy 1B, MIM# 620725; Ullrich congenital muscular dystrophy 1B, MIM# 620727
Prepair 1000+ v1.854 COL6A2 Zornitza Stark reviewed gene: COL6A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bethlem myopathy 1B, MIM# 620725, Ullrich congenital muscular dystrophy 1B, MIM# 620727; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.854 CUL4B Zornitza Stark Marked gene: CUL4B as ready
Prepair 1000+ v1.854 CUL4B Zornitza Stark Gene: cul4b has been classified as Green List (High Evidence).
Prepair 1000+ v1.854 CUL4B Zornitza Stark Phenotypes for gene: CUL4B were changed from Mental retardation, X-linked, syndromic 15 (Cabezas type), 300354 (3) to Intellectual developmental disorder, X-linked syndromic, Cabezas type, MIM#300354
Prepair 1000+ v1.853 CUL4B Zornitza Stark Publications for gene: CUL4B were set to
Mendeliome v1.2225 CUL4B Zornitza Stark Phenotypes for gene: CUL4B were changed from Mental retardation, X-linked, syndromic 15 (Cabezas type), MIM# 300354 to Intellectual developmental disorder, X-linked syndromic, Cabezas type, MIM#300354
Prepair 1000+ v1.852 CUL4B Zornitza Stark reviewed gene: CUL4B: Rating: GREEN; Mode of pathogenicity: None; Publications: 17236139, 19377476; Phenotypes: Intellectual developmental disorder, X-linked syndromic, Cabezas type, MIM#300354; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.2224 CUL4B Zornitza Stark edited their review of gene: CUL4B: Changed phenotypes: Intellectual developmental disorder, X-linked syndromic, Cabezas type, MIM#300354
Prepair 1000+ v1.852 DENND5A Zornitza Stark Marked gene: DENND5A as ready
Prepair 1000+ v1.852 DENND5A Zornitza Stark Gene: dennd5a has been classified as Green List (High Evidence).
Prepair 1000+ v1.852 DENND5A Zornitza Stark Phenotypes for gene: DENND5A were changed from Epileptic encephalopathy, early infantile, 49, 617281 (3), Autosomal recessive to Epileptic encephalopathy, early infantile, 49, MIM# 617281
Prepair 1000+ v1.851 DENND5A Zornitza Stark Publications for gene: DENND5A were set to
Prepair 1000+ v1.850 DENND5A Zornitza Stark reviewed gene: DENND5A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27431290, 27866705, 32705489; Phenotypes: Epileptic encephalopathy, early infantile, 49, MIM# 617281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.850 DNAAF1 Zornitza Stark Marked gene: DNAAF1 as ready
Prepair 1000+ v1.850 DNAAF1 Zornitza Stark Gene: dnaaf1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.850 DNAAF1 Zornitza Stark Phenotypes for gene: DNAAF1 were changed from Ciliary dyskinesia, primary, 13, 613193 (3) to Ciliary dyskinesia, primary, 13, MIM# 613193
Prepair 1000+ v1.849 DNAAF1 Zornitza Stark Publications for gene: DNAAF1 were set to
Prepair 1000+ v1.848 DNAAF1 Zornitza Stark reviewed gene: DNAAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19944400, 19944405, 32502479, 29228333, 27261005; Phenotypes: Ciliary dyskinesia, primary, 13, MIM# 613193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.848 DNAJC12 Zornitza Stark Marked gene: DNAJC12 as ready
Prepair 1000+ v1.848 DNAJC12 Zornitza Stark Gene: dnajc12 has been classified as Green List (High Evidence).
Prepair 1000+ v1.848 DNAJC12 Zornitza Stark Phenotypes for gene: DNAJC12 were changed from Hyperphenylalaninemia, mild, non-BH4-deficient, 617384 (3), Autosomal recessive to Hyperphenylalaninemia, mild, non-BH4-deficient, MIM#617384
Prepair 1000+ v1.847 DNAJC12 Zornitza Stark reviewed gene: DNAJC12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperphenylalaninemia, mild, non-BH4-deficient, MIM#617384; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.847 ELAC2 Zornitza Stark Marked gene: ELAC2 as ready
Prepair 1000+ v1.847 ELAC2 Zornitza Stark Gene: elac2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.847 ELAC2 Zornitza Stark Phenotypes for gene: ELAC2 were changed from Combined oxidative phosphorylation deficiency 17, 615440 (3) to Combined oxidative phosphorylation deficiency 17, MIM#615440
Prepair 1000+ v1.846 ELAC2 Zornitza Stark Publications for gene: ELAC2 were set to
Prepair 1000+ v1.845 ELAC2 Zornitza Stark reviewed gene: ELAC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23849775, 31045291; Phenotypes: Combined oxidative phosphorylation deficiency 17, MIM#615440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.845 ERCC6 Zornitza Stark Marked gene: ERCC6 as ready
Prepair 1000+ v1.845 ERCC6 Zornitza Stark Gene: ercc6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.845 ERCC6 Zornitza Stark Phenotypes for gene: ERCC6 were changed from Cockayne syndrome, type B, 133540 (3) to Cockayne spectrum with or without cerebrooculofacioskeletal syndrome MONDO:0100506
Prepair 1000+ v1.844 ERCC6 Zornitza Stark Publications for gene: ERCC6 were set to
Prepair 1000+ v1.843 ERCC6 Zornitza Stark reviewed gene: ERCC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301516; Phenotypes: Cockayne spectrum with or without cerebrooculofacioskeletal syndrome MONDO:0100506; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.843 EXOSC3 Zornitza Stark Marked gene: EXOSC3 as ready
Prepair 1000+ v1.843 EXOSC3 Zornitza Stark Gene: exosc3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.843 EXOSC3 Zornitza Stark Phenotypes for gene: EXOSC3 were changed from Pontocerebellar hypoplasia, type 1B, 614678 (3) to Pontocerebellar hypoplasia, type 1B, MIM# 614678
Prepair 1000+ v1.842 EXOSC3 Zornitza Stark Publications for gene: EXOSC3 were set to
Prepair 1000+ v1.841 EXOSC3 Zornitza Stark reviewed gene: EXOSC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22544365, 23284067, 24524299; Phenotypes: Pontocerebellar hypoplasia, type 1B, MIM# 614678; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.841 FOXE3 Zornitza Stark Marked gene: FOXE3 as ready
Prepair 1000+ v1.841 FOXE3 Zornitza Stark Gene: foxe3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.841 FOXE3 Zornitza Stark Phenotypes for gene: FOXE3 were changed from Aphakia, congenital primary, 610256 (3) to Anterior segment dysgenesis 2, multiple subtypes, MIM# 610256
Prepair 1000+ v1.840 FOXE3 Zornitza Stark Publications for gene: FOXE3 were set to
Prepair 1000+ v1.839 FOXE3 Zornitza Stark reviewed gene: FOXE3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27218149, 21150893, 31884615, 29878917, 29713869; Phenotypes: Anterior segment dysgenesis 2, multiple subtypes, MIM# 610256; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.839 FRRS1L Zornitza Stark Marked gene: FRRS1L as ready
Prepair 1000+ v1.839 FRRS1L Zornitza Stark Gene: frrs1l has been classified as Green List (High Evidence).
Prepair 1000+ v1.839 FRRS1L Zornitza Stark Phenotypes for gene: FRRS1L were changed from Epileptic encephalopathy, early infantile, 37, 616981 (3), Autosomal recessive to Epileptic encephalopathy, early infantile, 37, MIM#616981
Prepair 1000+ v1.838 FRRS1L Zornitza Stark Publications for gene: FRRS1L were set to
Prepair 1000+ v1.837 FRRS1L Zornitza Stark reviewed gene: FRRS1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 27236917, 27239025, 30692144; Phenotypes: Developmental and epileptic encephalopathy, 37 MONDO:0014859; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2224 CRYL1 Andrew Fennell changed review comment from: About 1% of individuals with GJB2-AR NSHL are compound heterozygotes for one GJB2 pathogenic variant and one of several different deletions that include sequences upstream of GJB2 (comprising either GJB6 and portions of CRYL1 or just portions of CRYL1) that delete cis-regulatory regions of GJB2, thereby abolishing GJB2 expression. Occasionally, the deletion also includes GJB2.; to: About 1% of individuals with GJB2-AR NSHL are compound heterozygotes for one GJB2 pathogenic variant and one of several different deletions that include sequences upstream of GJB2 (comprising either GJB6 and portions of CRYL1 or just portions of CRYL1) that delete cis-regulatory regions of GJB2, thereby abolishing GJB2 expression. Occasionally, the deletion also includes GJB2.
See also PMID: 20301449 GeneReviews
Mendeliome v1.2224 CRYL1 Andrew Fennell reviewed gene: CRYL1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30455902; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.837 XIAP Shakira Heerah reviewed gene: XIAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 22228567, 20489057, 17080092, 24942515, 25943627; Phenotypes: Lymphoproliferative syndorme, X-linked, 2 MIM#300635; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.837 RIPK4 Shakira Heerah reviewed gene: RIPK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28940926, 22197489, 22197488, 28416941; Phenotypes: Popliteal pterygium syndrome, Bartsocas-Papas type 1, MIM# 263650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.837 LAMC3 Kate Scarff reviewed gene: LAMC3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34354730, 21572413, 29247375, 26802095; Phenotypes: Cortical malformations, occipital, MIM #614115; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.837 KIF14 Kate Scarff reviewed gene: KIF14: Rating: ; Mode of pathogenicity: None; Publications: PMID: 29343805, 28892560, 24128419; Phenotypes: Microcephaly 20, primary, autosomal recessive, MIM #617914; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.837 INPPL1 Kate Scarff reviewed gene: INPPL1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23273569, 23273567, 34529350; Phenotypes: Opsismodysplasia MIM #258480; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of immune dysregulation v1.0 PACSIN1 Natasha Brown gene: PACSIN1 was added
gene: PACSIN1 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: PACSIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PACSIN1 were set to 36622335
Phenotypes for gene: PACSIN1 were set to systemic lupus erythematosis; vasculitis; nephritis
Penetrance for gene: PACSIN1 were set to unknown
Review for gene: PACSIN1 was set to AMBER
Added comment: PMID: 36622335
One patient denovo novel missense Q59K, severe infantile SLE, with functional validation
Results: We established that PACSIN1 forms a trimolecular complex with tumor necrosis factor receptor-associated factor 4 (TRAF4) and TRAF6 that is important for the regulation of type I IFN. The Q59K mutation in PACSIN1 augments binding to neural Wiskott-Aldrich syndrome protein while it decreases binding to TRAF4, leading to unrestrained TRAF6-mediated activation of type I IFN. Intriguingly, PACSIN1 Q59K increased TLR-7 but not TLR-9 signaling in human cells, leading to elevated expression of IFNβ and IFN-inducible genes. Untreated SLE patients had high PACSIN1 expression in peripheral blood cells that correlated positively with IFN-related genes. Introduction of the Pacsin1 Q59K mutation into mice caused increased surface TLR-7 and TRAIL expression in B cells
Sources: Literature
Disorders of immune dysregulation v1.0 P2RY8 Natasha Brown gene: P2RY8 was added
gene: P2RY8 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: P2RY8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: P2RY8 were set to 34889940
Phenotypes for gene: P2RY8 were set to systemic lupus erythematosis; vasculitis; nephritis
Penetrance for gene: P2RY8 were set to unknown
Review for gene: P2RY8 was set to GREEN
Added comment: PMID: 34889940
Six unrelated pts, rare/ultra rare missense variants with some functional validation
denovo (p.Leu257Phe) x1
N97K (c.291C>G;) x1, inheritance unknown

E323G (c.968A>G), in six unrelated SLE patients, all of Chinese ethnicity (note there are several entries in Gnomad for this variant in the SE Asian community) - incomplete penetrance

P2RY8 L257F and N97K variants show reduced inhibition of
AKT and ERK
Sources: Literature
Prepair 1000+ v1.837 HPS4 Kate Scarff reviewed gene: HPS4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12664304, 11836498; Phenotypes: Hermansky-Pudlak syndrome 4, MIM #614073; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Vasculitis v0.86 DNASE1 Natasha Brown edited their review of gene: DNASE1: Changed publications: 36444430, 30008451, 34161863, 37804110; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.837 HAX1 Kate Scarff changed review comment from: Severe congenital neutropenia-3 is an autosomal recessive bone marrow failure disorder characterized by low numbers of neutrophils, increased susceptibility to bacterial and fungal infections, and increased risk of developing myelodysplastic syndrome or acute myeloid leukemia. In addition, patients with HAX1 mutations affecting both isoform A and B of the gene develop neurologic abnormalities; to: Severe congenital neutropenia-3 is an autosomal recessive bone marrow failure disorder characterized by low numbers of neutrophils, increased susceptibility to bacterial and fungal infections, and increased risk of developing myelodysplastic syndrome or acute myeloid leukemia. In addition, patients with HAX1 mutations affecting both isoform A and B of the gene develop neurologic abnormalities.
MIM #610738
Vasculitis v0.86 DNASE1 Natasha Brown changed review comment from: PMID: 36444430
Three affected children from one family with HMZ deletion and functional validation (abstract only)

PMID: 30008451
ES in cohort of SLE onset <5yo, 7unrelated cases, one of which has HMZ FS (c.289_290delAC/p.Thr97Ilefs*2)

PMID: 34161863
Single patient (history of similarly affected sib) early onset lupus at 15m with HMZ (NM_004944.4: c.290_291delCA/p.Thr97Ilefs*2)

PMID: 37804110
Animal model - Dnase1L3 defic causes lupus like phenotype in mice; to: PMID: 36444430
Three affected children from one family with HMZ deletion and functional validation (abstract only)

PMID: 30008451
ES in cohort of SLE onset <5yo, 7unrelated cases, one of which has HMZ FS (c.289_290delAC/p.Thr97Ilefs*2)

PMID: 34161863
Single patient (history of similarly affected sib) early onset lupus at 15m with HMZ (NM_004944.4: c.290_291delCA/p.Thr97Ilefs*2)

PMID: 37804110
Animal model - Dnase1L3 defic causes lupus like phenotype in mice

add to immunological disorders super panel
Vasculitis v0.86 DNASE1 Natasha Brown changed review comment from: PMID: 36444430
Three affected children from one family with HMZ deletion and functional validation (abstract only)

PMID: 30008451
ES in cohort of SLE onset <5yo, 7unrelated cases, one of which has HMZ FS (c.289_290delAC/p.Thr97Ilefs*2)

PMID: 34161863
Single patient (history of similarly affected sib) early onset lupus at 15m with HMZ (NM_004944.4: c.290_291delCA/p.Thr97Ilefs*2)

PMID: 37804110
Animal model - Dnase1L3 defic causes lupus like phenotype in mice; to: PMID: 36444430
Three affected children from one family with HMZ deletion and functional validation (abstract only)

PMID: 30008451
ES in cohort of SLE onset <5yo, 7unrelated cases, one of which has HMZ FS (c.289_290delAC/p.Thr97Ilefs*2)

PMID: 34161863
Single patient (history of similarly affected sib) early onset lupus at 15m with HMZ (NM_004944.4: c.290_291delCA/p.Thr97Ilefs*2)

PMID: 37804110
Animal model - Dnase1L3 defic causes lupus like phenotype in mice
Prepair 1000+ v1.837 HAX1 Kate Scarff reviewed gene: HAX1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17187068, 18611981; Phenotypes: Neutropenia, severe congenital 3; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Vasculitis v0.86 DNASE1 Natasha Brown reviewed gene: DNASE1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: infantile lupus; Mode of inheritance: None
Skeletal dysplasia v0.298 WNT7A Zornitza Stark Marked gene: WNT7A as ready
Skeletal dysplasia v0.298 WNT7A Zornitza Stark Gene: wnt7a has been classified as Green List (High Evidence).
Skeletal dysplasia v0.298 WNT7A Zornitza Stark Phenotypes for gene: WNT7A were changed from Ulna and fibula, absence of, with severe limb deficiency 276820; Fuhrmann syndrome 228930 to Fuhrmann syndrome, MIM# 228930; Ulna and fibula, absence of, with severe limb deficiency, MIM# 276820; Santos syndrome, MIM# 613005
Skeletal dysplasia v0.297 WNT7A Zornitza Stark Publications for gene: WNT7A were set to
Skeletal dysplasia v0.296 WNT7A Zornitza Stark reviewed gene: WNT7A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fuhrmann syndrome, MIM# 228930, Ulna and fibula, absence of, with severe limb deficiency, MIM# 276820, Santos syndrome, MIM# 613005; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.281 WNT7A Zornitza Stark Marked gene: WNT7A as ready
Polydactyly v0.281 WNT7A Zornitza Stark Gene: wnt7a has been classified as Green List (High Evidence).
Polydactyly v0.281 WNT7A Zornitza Stark Phenotypes for gene: WNT7A were changed from to Santos syndrome, MIM# 613005; Fuhrmann syndrome 228930
Polydactyly v0.280 WNT7A Zornitza Stark reviewed gene: WNT7A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Santos syndrome, MIM# 613005, Fuhrmann syndrome 228930; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2224 WNT7A Zornitza Stark Phenotypes for gene: WNT7A were changed from Fuhrmann syndrome, MIM# 228930; Ulna and fibula, absence of, with severe limb deficiency, MIM# 276820 to Fuhrmann syndrome, MIM# 228930; Ulna and fibula, absence of, with severe limb deficiency, MIM# 276820; Santos syndrome, MIM# 613005
Mendeliome v1.2223 WNT7A Zornitza Stark Publications for gene: WNT7A were set to 21344627; 20949531; 16826533
Mendeliome v1.2222 WNT7A Zornitza Stark edited their review of gene: WNT7A: Changed publications: 19012338
Mendeliome v1.2222 WNT7A Zornitza Stark reviewed gene: WNT7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 19012338]; Phenotypes: Santos syndrome, MIM# 613005; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.296 FRYL Zornitza Stark Phenotypes for gene: FRYL were changed from neurodevelopmental disorder MONDO:0700092, FRYL-related to Pan-Chung-Bellen syndrome, MIM# 621049
Fetal anomalies v1.295 FRYL Zornitza Stark edited their review of gene: FRYL: Changed phenotypes: Pan-Chung-Bellen syndrome, MIM# 621049
Intellectual disability syndromic and non-syndromic v1.28 FRYL Zornitza Stark Phenotypes for gene: FRYL were changed from neurodevelopmental disorder MONDO:0700092, FRYL-related to Pan-Chung-Bellen syndrome, MIM# 621049
Intellectual disability syndromic and non-syndromic v1.27 FRYL Zornitza Stark reviewed gene: FRYL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pan-Chung-Bellen syndrome, MIM# 621049; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2222 FRYL Zornitza Stark Phenotypes for gene: FRYL were changed from neurodevelopmental disorder MONDO:0700092, FRYL-related to Pan-Chung-Bellen syndrome, MIM# 621049
Mendeliome v1.2221 FRYL Zornitza Stark reviewed gene: FRYL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pan-Chung-Bellen syndrome, MIM# 621049; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.425 FRYL Zornitza Stark Marked gene: FRYL as ready
Congenital Heart Defect v0.425 FRYL Zornitza Stark Gene: fryl has been classified as Green List (High Evidence).
Congenital Heart Defect v0.425 FRYL Zornitza Stark Phenotypes for gene: FRYL were changed from neurodevelopmental disorder MONDO:0700092, FRYL-related to Pan-Chung-Bellen syndrome, MIM# 621049
Congenital Heart Defect v0.424 FRYL Zornitza Stark reviewed gene: FRYL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pan-Chung-Bellen syndrome, MIM# 621049; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 500+ v1.5 PIGG Ain Roesley Phenotypes for gene: PIGG were changed from Mental retardation, autosomal recessive 53, 616917 (3) to Neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophy MIM#616917
Prepair 1000+ v1.837 PIGG Ain Roesley Phenotypes for gene: PIGG were changed from Mental retardation, autosomal recessive 53, 616917 (3) to Neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophy MIM#616917
Intellectual disability syndromic and non-syndromic v1.27 PIGG Ain Roesley Phenotypes for gene: PIGG were changed from Mental retardation, autosomal recessive 53, MIM#616917 to Neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophy MIM#616917
Genetic Epilepsy v1.87 PIGG Ain Roesley Phenotypes for gene: PIGG were changed from Neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophy MIM#616917 to Neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophy MIM#616917
Genetic Epilepsy v1.86 PIGG Ain Roesley Phenotypes for gene: PIGG were changed from Mental retardation, autosomal recessive 53, MIM#616917 to Neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophy MIM#616917
Mendeliome v1.2221 PIGG Ain Roesley Phenotypes for gene: PIGG were changed from Mental retardation, autosomal recessive 53, MIM#616917 to Neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophy MIM#616917
Bone Marrow Failure v1.111 RAD51 Bryony Thompson Marked gene: RAD51 as ready
Bone Marrow Failure v1.111 RAD51 Bryony Thompson Gene: rad51 has been classified as Red List (Low Evidence).
Bone Marrow Failure v1.111 RAD51 Bryony Thompson gene: RAD51 was added
gene: RAD51 was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: RAD51 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAD51 were set to 26253028; 26681308; 30907510
Phenotypes for gene: RAD51 were set to Fanconi anemia complementation group R MONDO:0014986
Review for gene: RAD51 was set to RED
Added comment: At least 3 unrelated individuals reported with Fanconi Anaemia and de novo missense variants, however, bone marrow failure was not present in any of the individuals reported.
Sources: Expert list
Fetal anomalies v1.295 RFWD3 Bryony Thompson Classified gene: RFWD3 as Amber List (moderate evidence)
Fetal anomalies v1.295 RFWD3 Bryony Thompson Gene: rfwd3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.294 RFWD3 Bryony Thompson reviewed gene: RFWD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 28691929, 38058754; Phenotypes: Fanconi anemia MONDO:0019391; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Chromosome Breakage Disorders v1.21 RFWD3 Bryony Thompson Publications for gene: RFWD3 were set to 28691929
Chromosome Breakage Disorders v1.20 RFWD3 Bryony Thompson Classified gene: RFWD3 as Amber List (moderate evidence)
Chromosome Breakage Disorders v1.20 RFWD3 Bryony Thompson Gene: rfwd3 has been classified as Amber List (Moderate Evidence).
Chromosome Breakage Disorders v1.19 RFWD3 Bryony Thompson reviewed gene: RFWD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 28691929, 38058754; Phenotypes: Fanconi anemia MONDO:0019391; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2220 RFWD3 Bryony Thompson Publications for gene: RFWD3 were set to 28691929
Mendeliome v1.2219 RFWD3 Bryony Thompson Classified gene: RFWD3 as Amber List (moderate evidence)
Mendeliome v1.2219 RFWD3 Bryony Thompson Gene: rfwd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2218 RFWD3 Bryony Thompson reviewed gene: RFWD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 28691929, 38058754; Phenotypes: Fanconi anemia MONDO:0019391; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Radial Ray Abnormalities v1.15 RFWD3 Bryony Thompson Marked gene: RFWD3 as ready
Radial Ray Abnormalities v1.15 RFWD3 Bryony Thompson Gene: rfwd3 has been classified as Amber List (Moderate Evidence).
Radial Ray Abnormalities v1.15 RFWD3 Bryony Thompson Classified gene: RFWD3 as Amber List (moderate evidence)
Radial Ray Abnormalities v1.15 RFWD3 Bryony Thompson Gene: rfwd3 has been classified as Amber List (Moderate Evidence).
Radial Ray Abnormalities v1.14 RFWD3 Bryony Thompson gene: RFWD3 was added
gene: RFWD3 was added to Radial Ray Abnormalities. Sources: Literature
Mode of inheritance for gene: RFWD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFWD3 were set to 28691929; 38058754
Phenotypes for gene: RFWD3 were set to Fanconi anemia MONDO:0019391
Review for gene: RFWD3 was set to AMBER
Added comment: Only 2 families reported, with radial ray defects as part of the phenotype.
Sources: Literature
Bone Marrow Failure v1.110 RFWD3 Bryony Thompson Publications for gene: RFWD3 were set to 28691929
Bone Marrow Failure v1.109 RFWD3 Bryony Thompson Classified gene: RFWD3 as Amber List (moderate evidence)
Bone Marrow Failure v1.109 RFWD3 Bryony Thompson Gene: rfwd3 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.108 RFWD3 Bryony Thompson reviewed gene: RFWD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 28691929, 38058754; Phenotypes: Fanconi anemia MONDO:0019391; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.836 SACS Cassandra Muller reviewed gene: SACS: Rating: GREEN; Mode of pathogenicity: None; Publications: 10655055, 14718706, 12873855]; Phenotypes: Spastic ataxia, Charlevoix-Saguenay type, 270550 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.836 RTEL1 Cassandra Muller reviewed gene: RTEL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23453664; Phenotypes: Dyskeratosis congenita, autosomal recessive 5, 615190 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.836 GUCY2D Kate Scarff changed review comment from: LCA1 is a congenital eye disorder that primarily affects the retina and causes vision loss, nystagmus, and severe retinal dysfunction. People with this disorder typically have severe visual impairment beginning at birth or shortly afterward. The visual impairment tends to be severe and may worsen over time.

Cone-rod dystrophy 6, MIM #601777 is a dominant condition due to heterozygous mutations in GUCY2D, not reportable for Prepair1000+.
Autosomal recessive GUCY2D mutations may cause congenital night blindness with normal acuity and refraction, and unique electroretinography. Progression to mild retinitis pigmentosa may occur. See PMID: 29559409. Not reportable for Prepair1000+ (severity).; to: LCA1 is a congenital eye disorder that primarily affects the retina and causes vision loss, nystagmus, and severe retinal dysfunction. People with this disorder typically have severe visual impairment beginning at birth or shortly afterward. The visual impairment tends to be severe and may worsen over time.

Cone-rod dystrophy 6, MIM #601777 is a dominant condition due to heterozygous mutations in GUCY2D, not reportable for Prepair1000+. See PMID: 35205358
Autosomal recessive GUCY2D mutations may cause congenital night blindness with normal acuity and refraction, and unique electroretinography. Progression to mild retinitis pigmentosa may occur. See PMID: 29559409. Not reportable for Prepair1000+ (severity).
Prepair 1000+ v1.836 GUCY2D Kate Scarff reviewed gene: GUCY2D: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15024725, 35314386; Phenotypes: Leber congenital amaurosis 1, MIM #204000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.836 HPS6 Lauren Thomas reviewed gene: HPS6: Rating: AMBER; Mode of pathogenicity: None; Publications: 12548288, 17041891; Phenotypes: Hermansky-Pudlak syndrome 6, MIM# 614075; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.836 GUSB Lauren Thomas reviewed gene: GUSB: Rating: GREEN; Mode of pathogenicity: None; Publications: 31661765, 32063397; Phenotypes: Mucopolysaccharidosis VII, MIM# 253220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.836 GBA2 Lauren Thomas reviewed gene: GBA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23332916, 23332917, 29524657; Phenotypes: Spastic paraplegia 46, autosomal recessive, MIM# 614409; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.836 FOXRED1 Lauren Thomas reviewed gene: FOXRED1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33613441, 20858599; Phenotypes: Mitochondrial complex I deficiency, nuclear type 19, MIM# 618241; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.836 FH Lauren Thomas reviewed gene: FH: Rating: GREEN; Mode of pathogenicity: None; Publications: 8200987, 20549362, 31746132, 20301679; Phenotypes: Fumarase deficiency, MIM# 606812; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.836 FBXL4 Lauren Thomas reviewed gene: FBXL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28940506, 23993194; Phenotypes: Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) MIM#615471; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.836 ETFB Lauren Thomas reviewed gene: ETFB: Rating: GREEN; Mode of pathogenicity: None; Publications: 7912128, 12815589, 27081516, 12706375, 30626930; Phenotypes: Glutaric acidemia IIB, MIM# 231680; Mode of inheritance: None
Prepair 1000+ v1.836 EMD Lauren Thomas reviewed gene: EMD: Rating: GREEN; Mode of pathogenicity: None; Publications: 21697856, 31802929, 31645980; Phenotypes: Emery-Dreifuss muscular dystrophy 1, X-linked, MIM# 310300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.836 ELP2 Lauren Thomas reviewed gene: ELP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21937992, 25847581, 32573669, 34653680; Phenotypes: Intellectual developmental disorder, autosomal recessive 58, MIM# 617270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.836 DOCK6 Lauren Thomas reviewed gene: DOCK6: Rating: GREEN; Mode of pathogenicity: None; Publications: 21820096, 23522784, 25132448, 25824905; Phenotypes: Adams-Oliver syndrome 2, MIM# 614219; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.836 PROP1 Cassandra Muller reviewed gene: PROP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined, 2, 262600 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.836 DCLRE1C Lauren Thomas reviewed gene: DCLRE1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 19953608, 15699179, 12055248, 34220820; Phenotypes: Severe combined immunodeficiency, Athabascan type, MIM# 602450, Omenn syndrome, MIM# 603554; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.836 COX10 Lauren Thomas reviewed gene: COX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10767350, 12928484, 15455402, 27290639; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.155 ARHGEF18 Sangavi Sivagnanasundram reviewed gene: ARHGEF18: Rating: GREEN; Mode of pathogenicity: None; Publications: 28132693, 23698346; Phenotypes: inherited retinal dystrophy MONDO:0019118; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Stationary Night Blindness v0.23 GNAT1 Sangavi Sivagnanasundram reviewed gene: GNAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: inherited retinal dystrophy MONDO:0019118; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.2218 GNAT1 Sangavi Sivagnanasundram reviewed gene: GNAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: inherited retinal dystrophy MONDO:0019118; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v1.58 PIGF Sangavi Sivagnanasundram reviewed gene: PIGF: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008517; Phenotypes: onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome MONDO:0859161; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v1.86 SLC2A10 Sangavi Sivagnanasundram reviewed gene: SLC2A10: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008487; Phenotypes: arterial tortuosity syndrome MONDO:0008818; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Autoinflammatory Disorders v2.2 NCKAP1L Bryony Thompson Classified gene: NCKAP1L as Green List (high evidence)
Autoinflammatory Disorders v2.2 NCKAP1L Bryony Thompson Gene: nckap1l has been classified as Green List (High Evidence).
Autoinflammatory Disorders v2.1 NCKAP1L Bryony Thompson gene: NCKAP1L was added
gene: NCKAP1L was added to Autoinflammatory Disorders. Sources: Expert list
Mode of inheritance for gene: NCKAP1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NCKAP1L were set to 32647003
Phenotypes for gene: NCKAP1L were set to immunodeficiency 72 with autoinflammation MONDO:0033551
Mendeliome v1.2218 ATG4A Bryony Thompson Marked gene: ATG4A as ready
Mendeliome v1.2218 ATG4A Bryony Thompson Gene: atg4a has been classified as Red List (Low Evidence).
Mendeliome v1.2218 ATG4A Bryony Thompson gene: ATG4A was added
gene: ATG4A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ATG4A 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: ATG4A were set to 33310865
Phenotypes for gene: ATG4A were set to infectious meningitis MONDO:0004796
Review for gene: ATG4A was set to RED
Added comment: Single case with recurrent HSV2 lymphocytic Mollaret’s meningitis heterozygous for a missense variant (p.Leu90Ile).
Sources: Expert list
Defects of intrinsic and innate immunity v1.19 Bryony Thompson Panel name changed from Defects of innate immunity to Defects of intrinsic and innate immunity
Defects of intrinsic and innate immunity v1.17 ZNFX1 Bryony Thompson Classified gene: ZNFX1 as Green List (high evidence)
Defects of intrinsic and innate immunity v1.17 ZNFX1 Bryony Thompson Gene: znfx1 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v1.16 ZNFX1 Bryony Thompson gene: ZNFX1 was added
gene: ZNFX1 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: ZNFX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNFX1 were set to 33872655
Phenotypes for gene: ZNFX1 were set to immunodeficiency 91 and hyperinflammation MONDO:0030491
Defects of intrinsic and innate immunity v1.15 TLR8 Bryony Thompson Marked gene: TLR8 as ready
Defects of intrinsic and innate immunity v1.15 TLR8 Bryony Thompson Gene: tlr8 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v1.15 TLR8 Bryony Thompson Classified gene: TLR8 as Green List (high evidence)
Defects of intrinsic and innate immunity v1.15 TLR8 Bryony Thompson Gene: tlr8 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v1.14 TLR8 Bryony Thompson gene: TLR8 was added
gene: TLR8 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: TLR8 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TLR8 were set to 33512449; 34981838
Phenotypes for gene: TLR8 were set to Immunodeficiency 98 with autoinflammation, X-linked, MIM# 301078
Mode of pathogenicity for gene: TLR8 was set to Other
Review for gene: TLR8 was set to GREEN
gene: TLR8 was marked as current diagnostic
Added comment: TLR signaling pathway deficiency with bacterial susceptibility. Mainly mosaic and gain of function is mechanism of disease
Sources: Expert list
Defects of intrinsic and innate immunity v1.13 POLR3F Bryony Thompson gene: POLR3F was added
gene: POLR3F was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: POLR3F was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR3F were set to 30211253
Phenotypes for gene: POLR3F were set to Immunodeficiency 101 (varicella zoster virus-specific), MIM# 619872
Defects of intrinsic and innate immunity v1.12 POLR3C Bryony Thompson Classified gene: POLR3C as Amber List (moderate evidence)
Defects of intrinsic and innate immunity v1.12 POLR3C Bryony Thompson Gene: polr3c has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v1.11 POLR3C Bryony Thompson gene: POLR3C was added
gene: POLR3C was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: POLR3C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR3C were set to 28783042
Phenotypes for gene: POLR3C were set to varicella zoster infection MONDO:0005608
Defects of intrinsic and innate immunity v1.10 POLR3A Bryony Thompson Classified gene: POLR3A as Amber List (moderate evidence)
Defects of intrinsic and innate immunity v1.10 POLR3A Bryony Thompson Gene: polr3a has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v1.9 POLR3A Bryony Thompson gene: POLR3A was added
gene: POLR3A was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: POLR3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR3A were set to 28783042; 29728610
Phenotypes for gene: POLR3A were set to varicella zoster infection MONDO:0005608
Defects of intrinsic and innate immunity v1.8 IRF3 Bryony Thompson Classified gene: IRF3 as Amber List (moderate evidence)
Defects of intrinsic and innate immunity v1.8 IRF3 Bryony Thompson Gene: irf3 has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v1.7 IRF3 Bryony Thompson gene: IRF3 was added
gene: IRF3 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: IRF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRF3 were set to 26216125; 20660188; 26513235
Phenotypes for gene: IRF3 were set to encephalitis, acute, infection-induced, susceptibility to MONDO:0800174
Defects of intrinsic and innate immunity v1.6 IFNG Bryony Thompson Marked gene: IFNG as ready
Defects of intrinsic and innate immunity v1.6 IFNG Bryony Thompson Gene: ifng has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2217 IFNG Bryony Thompson Publications for gene: IFNG were set to 32163377
Defects of intrinsic and innate immunity v1.6 IFNG Bryony Thompson Classified gene: IFNG as Amber List (moderate evidence)
Defects of intrinsic and innate immunity v1.6 IFNG Bryony Thompson Gene: ifng has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2216 IFNG Bryony Thompson Classified gene: IFNG as Amber List (moderate evidence)
Mendeliome v1.2216 IFNG Bryony Thompson Gene: ifng has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2215 IFNG Bryony Thompson reviewed gene: IFNG: Rating: AMBER; Mode of pathogenicity: None; Publications: 32163377, 38363432; Phenotypes: inherited susceptibility to mycobacterial diseases MONDO:0019146; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v1.5 IFNG Bryony Thompson gene: IFNG was added
gene: IFNG was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: IFNG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFNG were set to 32163377; 38363432
Phenotypes for gene: IFNG were set to inherited susceptibility to mycobacterial diseases MONDO:0019146
Review for gene: IFNG was set to AMBER
Added comment: Now 2 unrelated homozygous cases reported with some supporting functional assays.
Sources: Expert list
Defects of intrinsic and innate immunity v1.4 IFNAR2 Bryony Thompson Classified gene: IFNAR2 as Green List (high evidence)
Defects of intrinsic and innate immunity v1.4 IFNAR2 Bryony Thompson Gene: ifnar2 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v1.3 IFNAR2 Bryony Thompson gene: IFNAR2 was added
gene: IFNAR2 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: IFNAR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFNAR2 were set to 35442417; 26424569
Phenotypes for gene: IFNAR2 were set to immunodeficiency 45 MONDO:0014727
Prepair 1000+ v1.836 PIGO Cassandra Muller reviewed gene: PIGO: Rating: GREEN; Mode of pathogenicity: None; Publications: 22683086, 24417746, 27177984, 28337824, 37927489; Phenotypes: Hyperphosphatasia with impaired intellectual development syndrome 2, 614749 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.836 PIGO Cassandra Muller Deleted their review
Prepair 1000+ v1.836 PIGO Cassandra Muller reviewed gene: PIGO: Rating: GREEN; Mode of pathogenicity: None; Publications: 22683086, 24417746, 27177984, 28337824, 37927489; Phenotypes: Hyperphosphatasia with impaired intellectual development syndrome 2, 614749 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v1.2 IFNAR1 Bryony Thompson Classified gene: IFNAR1 as Green List (high evidence)
Defects of intrinsic and innate immunity v1.2 IFNAR1 Bryony Thompson Gene: ifnar1 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v1.1 IFNAR1 Bryony Thompson gene: IFNAR1 was added
gene: IFNAR1 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: IFNAR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFNAR1 were set to 35442418; 31270247
Phenotypes for gene: IFNAR1 were set to immunodeficiency 106, susceptibility to viral infections MONDO:0030970
Review for gene: IFNAR1 was set to GREEN
gene: IFNAR1 was marked as current diagnostic
Added comment: Severe disease caused by Yellow Fever vaccine and Measles vaccine, severe COVID-19.
Sources: Expert list
Disorders of immune dysregulation v1.0 Bryony Thompson promoted panel to version 1.0
Predominantly Antibody Deficiency v1.0 Bryony Thompson promoted panel to version 1.0
Autoinflammatory Disorders v2.0 Bryony Thompson promoted panel to version 2.0
Autoinflammatory Disorders v1.76 Bryony Thompson Panel name changed from Systemic Autoinflammatory Disease_Periodic Fever to Autoinflammatory Disorders
List of related panels changed from Fever HP:0001945 to Fever HP:0001945;Systemic autoinflammation HP:0033428
Prepair 1000+ v1.836 OCLN Cassandra Muller reviewed gene: OCLN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20727516; Phenotypes: Pseudo-TORCH syndrome 1, 251290 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Autoinflammatory Disorders v1.74 SYK Bryony Thompson Classified gene: SYK as Green List (high evidence)
Autoinflammatory Disorders v1.74 SYK Bryony Thompson Gene: syk has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.73 SYK Bryony Thompson gene: SYK was added
gene: SYK was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Expert list
Mode of inheritance for gene: SYK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SYK were set to 33782605
Phenotypes for gene: SYK were set to immunodeficiency 82 with systemic inflammation MONDO:0030308
Mode of pathogenicity for gene: SYK was set to Other
Mendeliome v1.2215 TMEM173 Bryony Thompson Publications for gene: TMEM173 were set to 25401470; 25029335
Mendeliome v1.2214 TMEM173 Bryony Thompson Mode of inheritance for gene: TMEM173 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.2213 TMEM173 Bryony Thompson reviewed gene: TMEM173: Rating: GREEN; Mode of pathogenicity: Other; Publications: 32673614, 36275728; Phenotypes: STING-associated vasculopathy with onset in infancy MONDO:0014405; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Autoinflammatory Disorders v1.72 TMEM173 Bryony Thompson Publications for gene: TMEM173 were set to 25401470; 25029335
Autoinflammatory Disorders v1.71 TMEM173 Bryony Thompson Mode of inheritance for gene: TMEM173 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Autoinflammatory Disorders v1.70 TMEM173 Bryony Thompson reviewed gene: TMEM173: Rating: GREEN; Mode of pathogenicity: None; Publications: 32673614, 36275728; Phenotypes: STING-associated vasculopathy with onset in infancy MONDO:0014405; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Autoinflammatory Disorders v1.70 SH3BP2 Bryony Thompson Mode of pathogenicity for gene: SH3BP2 was changed from to Other
Autoinflammatory Disorders v1.69 SH3BP2 Bryony Thompson Classified gene: SH3BP2 as Green List (high evidence)
Autoinflammatory Disorders v1.69 SH3BP2 Bryony Thompson Gene: sh3bp2 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.68 SH3BP2 Bryony Thompson Publications for gene: SH3BP2 were set to 26152156; 25705883; 25470448; 25220465
Autoinflammatory Disorders v1.67 SH3BP2 Bryony Thompson edited their review of gene: SH3BP2: Added comment: Cherubism is an autoinflammatory bone disorder caused by heterozygous gain of function variants mainly clustered within the peptide sequence RSPPDG lying between the PH and SH2 domains.; Changed mode of pathogenicity: Other; Changed phenotypes: Cherubism MONDO:0007315
Autoinflammatory Disorders v1.67 SH3BP2 Bryony Thompson reviewed gene: SH3BP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301316; Phenotypes: herubism MONDO:0007315; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoinflammatory Disorders v1.67 RIPK1 Bryony Thompson Marked gene: RIPK1 as ready
Autoinflammatory Disorders v1.67 RIPK1 Bryony Thompson Gene: ripk1 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.67 RIPK1 Bryony Thompson Classified gene: RIPK1 as Green List (high evidence)
Autoinflammatory Disorders v1.67 RIPK1 Bryony Thompson Gene: ripk1 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.66 RIPK1 Bryony Thompson gene: RIPK1 was added
gene: RIPK1 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Expert list
Mode of inheritance for gene: RIPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RIPK1 were set to 31827280; 31827281
Phenotypes for gene: RIPK1 were set to autoinflammation with episodic fever and lymphadenopathy MONDO:0030018
Mode of pathogenicity for gene: RIPK1 was set to Other
Review for gene: RIPK1 was set to GREEN
gene: RIPK1 was marked as current diagnostic
Added comment: Variants involving residue D324 impair caspase-8-mediated cleavage of RIPK1 and lead to RIPK1 activation. At least 5 families reported with D324N/H/Y and a supporting mouse model.
Sources: Expert list
Autoinflammatory Disorders v1.65 PSMD12 Bryony Thompson Classified gene: PSMD12 as Green List (high evidence)
Autoinflammatory Disorders v1.65 PSMD12 Bryony Thompson Gene: psmd12 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.64 PSMD12 Bryony Thompson gene: PSMD12 was added
gene: PSMD12 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Expert list
Mode of inheritance for gene: PSMD12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMD12 were set to 39641441; 35080150; 34906456
Phenotypes for gene: PSMD12 were set to Stankiewicz-Isidor syndrome MONDO:0054591
Review for gene: PSMD12 was set to GREEN
Added comment: STISS cases exhibit high type I IFN scores in peripheral blood-derived immune cells, however only rarely develop typical clinical signs of autoinflammation, including skin lesions and recurrent fever. Proteasome-associated autoinflammatory syndrome (PRAAS) is typically caused by pathogenic variants in components of the proteasome and activation of the type I IFN pathway. Developmental delay is the main feature of STISS and the autoinflammation is subclinical.
Sources: Expert list
Mendeliome v1.2213 GTF3A Bryony Thompson Marked gene: GTF3A as ready
Mendeliome v1.2213 GTF3A Bryony Thompson Gene: gtf3a has been classified as Red List (Low Evidence).
Autoinflammatory Disorders v1.63 POMP Bryony Thompson Classified gene: POMP as Green List (high evidence)
Autoinflammatory Disorders v1.63 POMP Bryony Thompson Gene: pomp has been classified as Green List (High Evidence).
Mendeliome v1.2213 GTF3A Bryony Thompson gene: GTF3A was added
gene: GTF3A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: GTF3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3A were set to 36399538
Phenotypes for gene: GTF3A were set to herpes simplex encephalitis MONDO:0012521
Review for gene: GTF3A was set to RED
Added comment: A single case is reported with common variable immunodeficiency and HSE, and some supporting functional assays.
Sources: Expert list
Autoinflammatory Disorders v1.62 POMP Bryony Thompson gene: POMP was added
gene: POMP was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Expert list
Mode of inheritance for gene: POMP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POMP were set to 29805043
Phenotypes for gene: POMP were set to proteasome-associated autoinflammatory syndrome 2 MONDO:0054700
Autoinflammatory Disorders v1.61 LYN Bryony Thompson Classified gene: LYN as Green List (high evidence)
Autoinflammatory Disorders v1.61 LYN Bryony Thompson Gene: lyn has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.60 LYN Bryony Thompson gene: LYN was added
gene: LYN was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Expert list
Mode of inheritance for gene: LYN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LYN were set to 36932076; 36122175
Phenotypes for gene: LYN were set to Autoinflammatory disease, systemic, with vasculitis MONDO:0957271
Mode of pathogenicity for gene: LYN was set to Other
Autoinflammatory Disorders v1.59 LSM11 Bryony Thompson Marked gene: LSM11 as ready
Autoinflammatory Disorders v1.59 LSM11 Bryony Thompson Gene: lsm11 has been classified as Red List (Low Evidence).
Autoinflammatory Disorders v1.59 LSM11 Bryony Thompson gene: LSM11 was added
gene: LSM11 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Expert list
Mode of inheritance for gene: LSM11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSM11 were set to 33230297
Phenotypes for gene: LSM11 were set to Aicardi-Goutieres syndrome MONDO:0018866
Review for gene: LSM11 was set to RED
Added comment: A single consanguineous family reported so far
Sources: Expert list
Prepair 1000+ v1.836 NHEJ1 Cassandra Muller reviewed gene: NHEJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16439204, 16439205, 37703920; Phenotypes: Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, 611291 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.836 NBAS Cassandra Muller reviewed gene: NBAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 20577004, 26073778; Phenotypes: Short stature, optic nerve atrophy, and Pelger-Huet anomaly, 614800 (3), Infantile liver failure syndrome 2, 616483 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v1.0 Bryony Thompson promoted panel to version 1.0
Defects of intrinsic and innate immunity v0.184 Bryony Thompson Panel types changed to Melbourne Genomics; Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Defects of intrinsic and innate immunity v0.181 TLR7 Bryony Thompson Marked gene: TLR7 as ready
Defects of intrinsic and innate immunity v0.181 TLR7 Bryony Thompson Gene: tlr7 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v0.181 TLR7 Bryony Thompson Classified gene: TLR7 as Green List (high evidence)
Defects of intrinsic and innate immunity v0.181 TLR7 Bryony Thompson Gene: tlr7 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v0.180 TLR7 Bryony Thompson gene: TLR7 was added
gene: TLR7 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: TLR7 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TLR7 were set to 32706371; 35708626
Phenotypes for gene: TLR7 were set to Immunodeficiency 74, COVID-19-related, X-linked MONDO:0026767
Review for gene: TLR7 was set to GREEN
Added comment: At least 7 families with affected hemizygous males. IUIS IEI committee categorise gene under Predisposition to Severe Viral Infection.
Sources: Expert list
Mendeliome v1.2212 TLR4 Bryony Thompson Phenotypes for gene: TLR4 were changed from to Inflammatory bowel disease MONDO:0005265
Mendeliome v1.2211 TLR4 Bryony Thompson Publications for gene: TLR4 were set to
Mendeliome v1.2210 TLR4 Bryony Thompson Mode of inheritance for gene: TLR4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v0.179 TLR4 Bryony Thompson Marked gene: TLR4 as ready
Defects of intrinsic and innate immunity v0.179 TLR4 Bryony Thompson Gene: tlr4 has been classified as Red List (Low Evidence).
Mendeliome v1.2209 TLR4 Bryony Thompson reviewed gene: TLR4: Rating: RED; Mode of pathogenicity: None; Publications: 32042729, 31442584; Phenotypes: Inflammatory bowel disease MONDO:0005265; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v0.179 TLR4 Bryony Thompson gene: TLR4 was added
gene: TLR4 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: TLR4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TLR4 were set to 32042729; 31442584
Phenotypes for gene: TLR4 were set to Inflammatory bowel disease MONDO:0005265
Review for gene: TLR4 was set to RED
Added comment: The IUIS IEI committee has this gene listed as a cause of inflammatory bowel disease under the TLR Signaling Pathway Deficiency categorisation, but I cannot find any reports of Mendelian disease. There are knockout mouse models with ulcerative colitis.
Sources: Expert list
Defects of intrinsic and innate immunity v0.178 SNORA31 Bryony Thompson Classified gene: SNORA31 as Green List (high evidence)
Defects of intrinsic and innate immunity v0.178 SNORA31 Bryony Thompson Gene: snora31 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v0.177 SNORA31 Bryony Thompson gene: SNORA31 was added
gene: SNORA31 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: SNORA31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SNORA31 were set to 31806906
Phenotypes for gene: SNORA31 were set to encephalitis, acute, infection-induced, susceptibility to MONDO:0800174
Mendeliome v1.2209 RNASEL Bryony Thompson Marked gene: RNASEL as ready
Mendeliome v1.2209 RNASEL Bryony Thompson Gene: rnasel has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2209 RNASEL Bryony Thompson Classified gene: RNASEL as Amber List (moderate evidence)
Mendeliome v1.2209 RNASEL Bryony Thompson Gene: rnasel has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v0.176 RNASEL Bryony Thompson Marked gene: RNASEL as ready
Defects of intrinsic and innate immunity v0.176 RNASEL Bryony Thompson Gene: rnasel has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v0.176 RNASEL Bryony Thompson Classified gene: RNASEL as Amber List (moderate evidence)
Defects of intrinsic and innate immunity v0.176 RNASEL Bryony Thompson Gene: rnasel has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2208 RNASEL Bryony Thompson gene: RNASEL was added
gene: RNASEL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNASEL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEL were set to 36538032; 9351818
Phenotypes for gene: RNASEL were set to Multisystem inflammatory syndrome, MONDO:0035375, RNASEL-related
Review for gene: RNASEL was set to AMBER
Added comment: A single case reported with a homozygous variant reported and a supporting null mouse model.
Sources: Literature
Defects of intrinsic and innate immunity v0.175 RNASEL Bryony Thompson gene: RNASEL was added
gene: RNASEL was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: RNASEL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEL were set to 36538032; 9351818
Phenotypes for gene: RNASEL were set to Multisystem inflammatory syndrome, MONDO:0035375, RNASEL-related
Review for gene: RNASEL was set to AMBER
Added comment: A single case reported with a homozygous variant reported and a supporting null mouse model.
Sources: Expert list
Defects of intrinsic and innate immunity v0.174 RIPK3 Bryony Thompson Classified gene: RIPK3 as Amber List (moderate evidence)
Defects of intrinsic and innate immunity v0.174 RIPK3 Bryony Thompson Gene: ripk3 has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v0.173 RIPK3 Bryony Thompson gene: RIPK3 was added
gene: RIPK3 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: RIPK3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIPK3 were set to 37083451
Phenotypes for gene: RIPK3 were set to Hereditary susceptibility to infections, MONDO:0015979, RIPK3-related
Defects of intrinsic and innate immunity v0.172 OAS2 Bryony Thompson Classified gene: OAS2 as Green List (high evidence)
Defects of intrinsic and innate immunity v0.172 OAS2 Bryony Thompson Gene: oas2 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v0.171 OAS2 Bryony Thompson gene: OAS2 was added
gene: OAS2 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: OAS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OAS2 were set to 36538032
Phenotypes for gene: OAS2 were set to Multisystem inflammatory syndrome, MONDO:0035375, OAS2-related
Mendeliome v1.2207 OAS1 Bryony Thompson Added comment: Comment on mode of inheritance: The monoallelic association is definitive (with a GoF mechanism of disease) and biallelic variants (LoF) have only been reported in a single family (limited evidence).
Mendeliome v1.2207 OAS1 Bryony Thompson Mode of inheritance for gene: OAS1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v0.170 OAS1 Bryony Thompson Marked gene: OAS1 as ready
Defects of intrinsic and innate immunity v0.170 OAS1 Bryony Thompson Gene: oas1 has been classified as Red List (Low Evidence).
Mendeliome v1.2206 OAS1 Bryony Thompson reviewed gene: OAS1: Rating: RED; Mode of pathogenicity: None; Publications: 36538032; Phenotypes: Multisystem inflammatory syndrome in children and adults MONDO:0035375; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v0.170 OAS1 Bryony Thompson gene: OAS1 was added
gene: OAS1 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: OAS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OAS1 were set to 36538032
Phenotypes for gene: OAS1 were set to Multisystem inflammatory syndrome in children and adults MONDO:0035375
Review for gene: OAS1 was set to RED
Added comment: A single case with MIS-C with a homozygous LoF (p.Arg47*) variant and a supporting in vitro functional assay.
Sources: Expert list
Defects of intrinsic and innate immunity v0.169 NOS2 Bryony Thompson gene: NOS2 was added
gene: NOS2 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: NOS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NOS2 were set to 31995689
Phenotypes for gene: NOS2 were set to inborn error of immunity MONDO:0003778
Defects of intrinsic and innate immunity v0.168 LY96 Bryony Thompson Marked gene: LY96 as ready
Defects of intrinsic and innate immunity v0.168 LY96 Bryony Thompson Gene: ly96 has been classified as Red List (Low Evidence).
Defects of intrinsic and innate immunity v0.168 LY96 Bryony Thompson gene: LY96 was added
gene: LY96 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: LY96 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LY96 were set to 36462957
Phenotypes for gene: LY96 were set to Inborn error of immunity, MONDO:0003778, LY96-related
Review for gene: LY96 was set to RED
Added comment: Only a single family reported. The IUIS IEI committee categorises this gene as TLR Signaling Pathway Deficiency.
Sources: Expert list
Defects of intrinsic and innate immunity v0.167 IRF9 Bryony Thompson Classified gene: IRF9 as Amber List (moderate evidence)
Defects of intrinsic and innate immunity v0.167 IRF9 Bryony Thompson Gene: irf9 has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v0.166 IRF9 Bryony Thompson gene: IRF9 was added
gene: IRF9 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: IRF9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IRF9 were set to 30826365; 30143481
Phenotypes for gene: IRF9 were set to immunodeficiency 65, susceptibility to viral infections MONDO:0032848
Defects of intrinsic and innate immunity v0.165 IRF4 Bryony Thompson Classified gene: IRF4 as Green List (high evidence)
Defects of intrinsic and innate immunity v0.165 IRF4 Bryony Thompson Gene: irf4 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v0.164 IRF4 Bryony Thompson gene: IRF4 was added
gene: IRF4 was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: IRF4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRF4 were set to 36662884, 36917008, 29537367, 29408330
Phenotypes for gene: IRF4 were set to combined immunodeficiency MONDO:0015131
Review for gene: IRF4 was set to GREEN
gene: IRF4 was marked as current diagnostic
Added comment: IRF4 is a transcription factor involved in the regulation of innate immunity. Definitive gene-disease association - https://search.clinicalgenome.org/CCID:008358. The IUIS IEI committee categorises this gene as other inborn errors of immunity related to leukocytes.
Sources: Expert list
Defects of intrinsic and innate immunity v0.163 IL18BP Bryony Thompson gene: IL18BP was added
gene: IL18BP was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: IL18BP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL18BP were set to 31213488
Phenotypes for gene: IL18BP were set to {?Hepatitis, fulminant viral, susceptibility to} 618549
Defects of intrinsic and innate immunity v0.162 IKBKE Bryony Thompson Marked gene: IKBKE as ready
Defects of intrinsic and innate immunity v0.162 IKBKE Bryony Thompson Gene: ikbke has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v0.162 IKBKE Bryony Thompson Classified gene: IKBKE as Amber List (moderate evidence)
Defects of intrinsic and innate immunity v0.162 IKBKE Bryony Thompson Gene: ikbke has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v0.160 IKBKE Bryony Thompson gene: IKBKE was added
gene: IKBKE was added to Defects of innate immunity. Sources: Expert list
Mode of inheritance for gene: IKBKE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKBKE were set to 37937644
Phenotypes for gene: IKBKE were set to Encephalitis, acute, infection-induced, susceptibility to, MONDO:0800174, IKBKE-related
Prepair 1000+ v1.836 TF Lucy Spencer reviewed gene: TF: Rating: GREEN; Mode of pathogenicity: None; Publications: 32028041; Phenotypes: Atransferrinemia MIM#209300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.836 PRPS1 Lucy Spencer reviewed gene: PRPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: PRPS1 deficiency disorder MONDO:0100061, Phosphoribosylpyrophosphate synthetase superactivity MIM#300661 MONDO:0010395; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.836 FERMT1 Zornitza Stark Marked gene: FERMT1 as ready
Prepair 1000+ v1.836 FERMT1 Zornitza Stark Gene: fermt1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.836 FERMT1 Zornitza Stark Phenotypes for gene: FERMT1 were changed from Kindler syndrome, 173650 (3) to Kindler syndrome, MIM#173650
Prepair 1000+ v1.835 FERMT1 Zornitza Stark Publications for gene: FERMT1 were set to
Prepair 1000+ v1.834 LMAN1 Zornitza Stark Marked gene: LMAN1 as ready
Prepair 1000+ v1.834 LMAN1 Zornitza Stark Gene: lman1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.834 LMAN1 Zornitza Stark Phenotypes for gene: LMAN1 were changed from Combined factor V and VIII deficiency, 227300 (3) to Combined factor V and VIII deficiency, MIM#227300
Prepair 1000+ v1.833 LMAN1 Zornitza Stark Publications for gene: LMAN1 were set to
Prepair 1000+ v1.832 LMAN1 Lucy Spencer reviewed gene: LMAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23852824; Phenotypes: Combined factor V and VIII deficiency MIM#227300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.832 TSHB Zornitza Stark Marked gene: TSHB as ready
Prepair 1000+ v1.832 TSHB Zornitza Stark Gene: tshb has been classified as Green List (High Evidence).
Prepair 1000+ v1.832 TSHB Zornitza Stark Publications for gene: TSHB were set to
Prepair 1000+ v1.831 TSEN54 Zornitza Stark Marked gene: TSEN54 as ready
Prepair 1000+ v1.831 TSEN54 Zornitza Stark Gene: tsen54 has been classified as Green List (High Evidence).
Prepair 1000+ v1.831 TSEN54 Zornitza Stark Phenotypes for gene: TSEN54 were changed from Pontocerebellar hypoplasia type 2A, 277470 (3) to Pontocerebellar hypoplasia type 2A (MIM#277470); Pontocerebellar hypoplasia type 4 (MIM#225753)
Prepair 1000+ v1.830 TSEN54 Zornitza Stark Publications for gene: TSEN54 were set to
Prepair 1000+ v1.829 TPRKB Zornitza Stark Tag for review tag was added to gene: TPRKB.
Prepair 1000+ v1.829 D2HGDH Zornitza Stark Marked gene: D2HGDH as ready
Prepair 1000+ v1.829 D2HGDH Zornitza Stark Gene: d2hgdh has been classified as Green List (High Evidence).
Prepair 1000+ v1.829 D2HGDH Zornitza Stark Phenotypes for gene: D2HGDH were changed from D-2-hydroxyglutaric aciduria, 600721 (3) to D-2-hydroxyglutaric aciduria, MIM#600721
Prepair 1000+ v1.828 D2HGDH Zornitza Stark Publications for gene: D2HGDH were set to
Prepair 1000+ v1.827 CYP11B2 Zornitza Stark Marked gene: CYP11B2 as ready
Prepair 1000+ v1.827 CYP11B2 Zornitza Stark Gene: cyp11b2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.827 CYP11B2 Zornitza Stark Phenotypes for gene: CYP11B2 were changed from Hypoaldosteronism, congenital, due to CMO I deficiency, 203400 (3) to Hypoaldosteronism, congenital, due to CMO I deficiency, MIM#203400
Prepair 1000+ v1.826 CYP11B2 Zornitza Stark Publications for gene: CYP11B2 were set to
Prepair 1000+ v1.825 GJB1 Lucy Spencer reviewed gene: GJB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301548; Phenotypes: Charcot-Marie-Tooth neuropathy, X-linked dominant, 1, MIM#302800; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.825 CUL7 Zornitza Stark Marked gene: CUL7 as ready
Prepair 1000+ v1.825 CUL7 Zornitza Stark Gene: cul7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.825 CUL7 Zornitza Stark Phenotypes for gene: CUL7 were changed from 3-M syndrome 1, 273750 (3) to 3-M syndrome 1, MIM#273750
Prepair 1000+ v1.824 CUL7 Zornitza Stark Publications for gene: CUL7 were set to
Prepair 1000+ v1.823 CLDN19 Zornitza Stark Marked gene: CLDN19 as ready
Prepair 1000+ v1.823 CLDN19 Zornitza Stark Gene: cldn19 has been classified as Green List (High Evidence).
Prepair 1000+ v1.823 CLDN19 Zornitza Stark Phenotypes for gene: CLDN19 were changed from Hypomagnesemia 5, renal, with ocular involvement, 248190 (3) to Hypomagnesaemia 5, renal, with ocular involvement, MIM#248190
Prepair 1000+ v1.822 CLDN19 Zornitza Stark Publications for gene: CLDN19 were set to
Prepair 1000+ v1.821 WHRN Zornitza Stark Marked gene: WHRN as ready
Prepair 1000+ v1.821 WHRN Zornitza Stark Gene: whrn has been classified as Green List (High Evidence).
Prepair 1000+ v1.821 WHRN Zornitza Stark Phenotypes for gene: WHRN were changed from Usher syndrome, type 2D, 611383 (3) to Usher syndrome, type 2D, MIM#611383
Prepair 1000+ v1.820 WHRN Zornitza Stark Publications for gene: WHRN were set to
Prepair 1000+ v1.819 FERMT1 Lucy Spencer reviewed gene: FERMT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26937547; Phenotypes: Kindler syndrome MIM#173650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.819 MYMK Zornitza Stark Marked gene: MYMK as ready
Prepair 1000+ v1.819 MYMK Zornitza Stark Gene: mymk has been classified as Green List (High Evidence).
Prepair 1000+ v1.819 MYMK Zornitza Stark Phenotypes for gene: MYMK were changed from Carey-Fineman-Ziter syndrome, 254940 (3), Autosomal recessive to Carey-Fineman-Ziter syndrome, MIM#254940
Prepair 1000+ v1.818 MYMK Zornitza Stark Publications for gene: MYMK were set to
Prepair 1000+ v1.817 MED25 Zornitza Stark Marked gene: MED25 as ready
Prepair 1000+ v1.817 MED25 Zornitza Stark Gene: med25 has been classified as Green List (High Evidence).
Prepair 1000+ v1.817 MED25 Zornitza Stark Phenotypes for gene: MED25 were changed from Basel-Vanagait-Smirin-Yosef syndrome, 616449 (3) to Basel-Vanagait-Smirin-Yosef syndrome, MIM# 616449; congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome MONDO:0014643
Prepair 1000+ v1.816 MED25 Zornitza Stark Publications for gene: MED25 were set to
Prepair 1000+ v1.815 MED17 Zornitza Stark Marked gene: MED17 as ready
Prepair 1000+ v1.815 MED17 Zornitza Stark Gene: med17 has been classified as Green List (High Evidence).
Prepair 1000+ v1.815 MED17 Zornitza Stark Phenotypes for gene: MED17 were changed from Microcephaly, postnatal progressive, with seizures and brain atrophy, 613668 (3) to Microcephaly, postnatal progressive, with seizures and brain atrophy, MIM#613668
Prepair 1000+ v1.814 MED17 Zornitza Stark Publications for gene: MED17 were set to
Prepair 1000+ v1.813 DOCK8 Zornitza Stark Marked gene: DOCK8 as ready
Prepair 1000+ v1.813 DOCK8 Zornitza Stark Gene: dock8 has been classified as Green List (High Evidence).
Prepair 1000+ v1.813 DOCK8 Zornitza Stark Phenotypes for gene: DOCK8 were changed from Hyper-IgE recurrent infection syndrome, autosomal recessive, 243700 (3) to Hyper-IgE recurrent infection syndrome, autosomal recessive, MIM#243700
Prepair 1000+ v1.812 DOCK8 Zornitza Stark Publications for gene: DOCK8 were set to
Prepair 1000+ v1.811 MANBA Zornitza Stark Marked gene: MANBA as ready
Prepair 1000+ v1.811 MANBA Zornitza Stark Gene: manba has been classified as Green List (High Evidence).
Prepair 1000+ v1.811 MANBA Zornitza Stark Phenotypes for gene: MANBA were changed from Mannosidosis, beta, 248510 (3) to Mannosidosis, beta, MIM#248510
Prepair 1000+ v1.810 ZNHIT3 Lucy Spencer reviewed gene: ZNHIT3: Rating: GREEN; Mode of pathogenicity: None; Publications: 39252897; Phenotypes: PEHO syndrome MIM#260565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.810 DNAI1 Zornitza Stark Marked gene: DNAI1 as ready
Prepair 1000+ v1.810 DNAI1 Zornitza Stark Gene: dnai1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.810 DNAI1 Zornitza Stark Phenotypes for gene: DNAI1 were changed from Ciliary dyskinesia, primary, 1, with or without situs inversus, 244400 (3) to Ciliary dyskinesia, primary, 1, with or without situs inversus, MIM#244400
Prepair 1000+ v1.809 DNAI1 Zornitza Stark Publications for gene: DNAI1 were set to
Prepair 1000+ v1.808 TUSC3 Zornitza Stark Marked gene: TUSC3 as ready
Prepair 1000+ v1.808 TUSC3 Zornitza Stark Gene: tusc3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.808 TUSC3 Zornitza Stark Phenotypes for gene: TUSC3 were changed from Mental retardation, autosomal recessive 7, 611093 (3) to Intellectual developmental disorder, autosomal recessive 7 MIM#611093
Prepair 1000+ v1.807 TUSC3 Zornitza Stark Publications for gene: TUSC3 were set to
Prepair 1000+ v1.806 DNAH11 Zornitza Stark Marked gene: DNAH11 as ready
Prepair 1000+ v1.806 DNAH11 Zornitza Stark Gene: dnah11 has been classified as Green List (High Evidence).
Prepair 1000+ v1.806 DNAH11 Zornitza Stark Phenotypes for gene: DNAH11 were changed from Ciliary dyskinesia, primary, 7, with or without situs inversus, 611884 (3) to Ciliary dyskinesia, primary, 7, with or without situs inversus, MIM#611884
Prepair 1000+ v1.805 DNAH11 Zornitza Stark Publications for gene: DNAH11 were set to
Prepair 1000+ v1.804 LYRM7 Zornitza Stark Marked gene: LYRM7 as ready
Prepair 1000+ v1.804 LYRM7 Zornitza Stark Gene: lyrm7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.804 LYRM7 Zornitza Stark Phenotypes for gene: LYRM7 were changed from Mitochondrial complex III deficiency, nuclear type 8, 615838 (3), Autosomal recessive to Mitochondrial complex III deficiency, nuclear type 8, MIM#615838, Autosomal recessive
Prepair 1000+ v1.803 LYRM7 Zornitza Stark Publications for gene: LYRM7 were set to
Prepair 1000+ v1.802 DLG3 Zornitza Stark Marked gene: DLG3 as ready
Prepair 1000+ v1.802 DLG3 Zornitza Stark Gene: dlg3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.802 DLG3 Zornitza Stark Phenotypes for gene: DLG3 were changed from Mental retardation, X-linked 90, 300850 (3) to Intellectual developmental disorder, X-linked 90 MIM#300850
Prepair 1000+ v1.801 DLG3 Zornitza Stark Publications for gene: DLG3 were set to
Prepair 1000+ v1.800 TUBA8 Zornitza Stark Marked gene: TUBA8 as ready
Prepair 1000+ v1.800 TUBA8 Zornitza Stark Gene: tuba8 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.800 TUBA8 Zornitza Stark Phenotypes for gene: TUBA8 were changed from Polymicrogyria with optic nerve hypoplasia, 613180 (3) to Polymicrogyria with optic nerve hypoplasia MONDO:0013172
Prepair 1000+ v1.799 ZBTB24 Lucy Spencer reviewed gene: ZBTB24: Rating: GREEN; Mode of pathogenicity: None; Publications: 23486536; Phenotypes: Immunodeficiency-centromeric instability-facial anomalies syndrome 2, MIM# 614069, MONDO:0013553; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.799 TUBA8 Zornitza Stark Publications for gene: TUBA8 were set to
Prepair 1000+ v1.798 LRPPRC Zornitza Stark Marked gene: LRPPRC as ready
Prepair 1000+ v1.798 LRPPRC Zornitza Stark Gene: lrpprc has been classified as Green List (High Evidence).
Prepair 1000+ v1.798 LRPPRC Zornitza Stark Phenotypes for gene: LRPPRC were changed from Leigh syndrome, French-Canadian type, 220111 (3) to Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) MIM#220111
Prepair 1000+ v1.797 LRPPRC Zornitza Stark Publications for gene: LRPPRC were set to
Prepair 1000+ v1.796 WNT10A Lucy Spencer reviewed gene: WNT10A: Rating: RED; Mode of pathogenicity: None; Publications: 19559398, 30426266; Phenotypes: Ectodermal dysplasia 16 (odontoonychodermal dysplasia) MIM#257980, Schopf-Schulz-Passarge syndrome MIM#224750, Tooth agenesis, selective, 4 MIM#150400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.796 DDHD2 Zornitza Stark Marked gene: DDHD2 as ready
Prepair 1000+ v1.796 DDHD2 Zornitza Stark Gene: ddhd2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.796 DDHD2 Zornitza Stark Phenotypes for gene: DDHD2 were changed from Spastic paraplegia 54, autosomal recessive, 615033 (3) to Spastic paraplegia 54, autosomal recessive, MIM#615033
Prepair 1000+ v1.795 DDHD2 Zornitza Stark Publications for gene: DDHD2 were set to
Prepair 1000+ v1.794 TRDN Zornitza Stark Marked gene: TRDN as ready
Prepair 1000+ v1.794 TRDN Zornitza Stark Gene: trdn has been classified as Green List (High Evidence).
Prepair 1000+ v1.794 TRDN Zornitza Stark Phenotypes for gene: TRDN were changed from Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness, 615441 (3) to Cardiac arrhythmia syndrome, with or without skeletal muscle weakness MIM#615441; Catecholaminergic polymorphic ventricular tachycardia MONDO:0017990
Prepair 1000+ v1.793 TRDN Zornitza Stark Publications for gene: TRDN were set to
Prepair 1000+ v1.792 MARS2 Zornitza Stark Marked gene: MARS2 as ready
Prepair 1000+ v1.792 MARS2 Zornitza Stark Gene: mars2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.792 MARS2 Zornitza Stark Phenotypes for gene: MARS2 were changed from Spastic ataxia 3, autosomal recessive, 611390 (3) to Combined oxidative phosphorylation deficiency 25; MIM #616430, MONDO:0014636; Spastic ataxia 3, autosomal recessive, MIM #611390, MONDO:0012664
Prepair 1000+ v1.791 MARS2 Zornitza Stark Publications for gene: MARS2 were set to
Prepair 1000+ v1.790 TNFSF11 Zornitza Stark Marked gene: TNFSF11 as ready
Prepair 1000+ v1.790 TNFSF11 Zornitza Stark Gene: tnfsf11 has been classified as Green List (High Evidence).
Prepair 1000+ v1.790 TNFSF11 Zornitza Stark Phenotypes for gene: TNFSF11 were changed from Osteopetrosis, autosomal recessive 2, 259710 (3) to Osteopetrosis, autosomal recessive 2, MIM#259710
Prepair 1000+ v1.789 TNFSF11 Zornitza Stark Publications for gene: TNFSF11 were set to
Prepair 1000+ v1.788 TMEM70 Zornitza Stark Marked gene: TMEM70 as ready
Prepair 1000+ v1.788 TMEM70 Zornitza Stark Gene: tmem70 has been classified as Green List (High Evidence).
Prepair 1000+ v1.788 TMEM70 Zornitza Stark Phenotypes for gene: TMEM70 were changed from Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, 614052 (3) to Mitochondrial disease MONDO:0044970
Prepair 1000+ v1.787 TMEM70 Zornitza Stark Publications for gene: TMEM70 were set to
Prepair 1000+ v1.786 LINS1 Zornitza Stark Marked gene: LINS1 as ready
Prepair 1000+ v1.786 LINS1 Zornitza Stark Gene: lins1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.786 LINS1 Zornitza Stark Phenotypes for gene: LINS1 were changed from Mental retardation, autosomal recessive 27, 614340 (3) to Intellectual developmental disorder, autosomal recessive 2, MIM#614340
Prepair 1000+ v1.785 LINS1 Zornitza Stark Publications for gene: LINS1 were set to
Prepair 1000+ v1.784 LINS1 Zornitza Stark reviewed gene: LINS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.784 VPS45 Lucy Spencer reviewed gene: VPS45: Rating: GREEN; Mode of pathogenicity: None; Publications: 30294941; Phenotypes: Neutropaenia, severe congenital, 5, autosomal recessive, MIM# 615285; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.784 KIF1A Zornitza Stark Marked gene: KIF1A as ready
Prepair 1000+ v1.784 KIF1A Zornitza Stark Gene: kif1a has been classified as Green List (High Evidence).
Prepair 1000+ v1.784 KIF1A Zornitza Stark Phenotypes for gene: KIF1A were changed from Spastic paraplegia 30, autosomal recessive, 610357 (3) to Spastic paraplegia 30, autosomal recessive, MIM#610357
Prepair 1000+ v1.783 KIF1A Zornitza Stark Publications for gene: KIF1A were set to
Prepair 1000+ v1.782 TIMM8A Zornitza Stark Marked gene: TIMM8A as ready
Prepair 1000+ v1.782 TIMM8A Zornitza Stark Gene: timm8a has been classified as Green List (High Evidence).
Prepair 1000+ v1.782 TIMM8A Zornitza Stark Phenotypes for gene: TIMM8A were changed from Jensen syndrome, 311150 (3) to Mohr-Tranebjaerg syndrome MIM#304700
Prepair 1000+ v1.781 TIMM8A Zornitza Stark Publications for gene: TIMM8A were set to
Prepair 1000+ v1.780 STXBP2 Zornitza Stark Marked gene: STXBP2 as ready
Prepair 1000+ v1.780 STXBP2 Zornitza Stark Gene: stxbp2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.780 STXBP2 Zornitza Stark Phenotypes for gene: STXBP2 were changed from Hemophagocytic lymphohistiocytosis, familial, 5, 613101 (3) to Haemophagocytic lymphohistiocytosis, familial, 5, with or without microvillus inclusion disease MIM#613101
Prepair 1000+ v1.779 STXBP2 Zornitza Stark Publications for gene: STXBP2 were set to
Prepair 1000+ v1.778 LZTFL1 Zornitza Stark Marked gene: LZTFL1 as ready
Prepair 1000+ v1.778 LZTFL1 Zornitza Stark Gene: lztfl1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.778 LZTFL1 Zornitza Stark Phenotypes for gene: LZTFL1 were changed from Bardet-Biedl syndrome 17, 615994 (3) to Bardet-Biedl syndrome 17 MIM#615994; MONDO:0014445
Prepair 1000+ v1.777 LZTFL1 Zornitza Stark Publications for gene: LZTFL1 were set to
Prepair 1000+ v1.776 SMS Zornitza Stark Marked gene: SMS as ready
Prepair 1000+ v1.776 SMS Zornitza Stark Gene: sms has been classified as Green List (High Evidence).
Prepair 1000+ v1.776 SMS Zornitza Stark Phenotypes for gene: SMS were changed from Mental retardation, X-linked, Snyder-Robinson type, 309583 (3) to Intellectual developmental disorder, X-linked syndromic, Snyder-Robinson type MIM#309583
Prepair 1000+ v1.775 SMS Zornitza Stark Publications for gene: SMS were set to
Prepair 1000+ v1.774 VARS2 Lucy Spencer reviewed gene: VARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31064326; Phenotypes: Combined oxidative phosphorylation deficiency 20 MIM#615917; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.774 SLC9A6 Zornitza Stark Marked gene: SLC9A6 as ready
Prepair 1000+ v1.774 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.774 SLC9A6 Zornitza Stark Phenotypes for gene: SLC9A6 were changed from Mental retardation, X-linked syndromic, Christianson type to Intellectual developmental disorder, X-linked syndromic, Christianson type MIM#300243
Prepair 1000+ v1.773 SLC9A6 Zornitza Stark Publications for gene: SLC9A6 were set to
Prepair 1000+ v1.772 SLC25A22 Zornitza Stark Marked gene: SLC25A22 as ready
Prepair 1000+ v1.772 SLC25A22 Zornitza Stark Gene: slc25a22 has been classified as Green List (High Evidence).
Prepair 1000+ v1.772 SLC25A22 Zornitza Stark Phenotypes for gene: SLC25A22 were changed from Epileptic encephalopathy, early infantile, 3, 609304 (3) to Epileptic encephalopathy, early infantile, 3, MIM#609304
Prepair 1000+ v1.771 SLC25A22 Zornitza Stark Publications for gene: SLC25A22 were set to
Prepair 1000+ v1.770 SLC25A15 Zornitza Stark Marked gene: SLC25A15 as ready
Prepair 1000+ v1.770 SLC25A15 Zornitza Stark Gene: slc25a15 has been classified as Green List (High Evidence).
Prepair 1000+ v1.770 SLC25A15 Zornitza Stark Phenotypes for gene: SLC25A15 were changed from Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome, MIM#238970 to Hyperornithinaemia-hyperammonaemia-homocitrullinemia syndrome, MIM#238970
Prepair 1000+ v1.769 SLC25A15 Zornitza Stark Phenotypes for gene: SLC25A15 were changed from Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome, 238970 (3) to Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome, MIM#238970
Prepair 1000+ v1.768 SLC25A15 Zornitza Stark Publications for gene: SLC25A15 were set to
Prepair 1000+ v1.767 CKAP2L Zornitza Stark Marked gene: CKAP2L as ready
Prepair 1000+ v1.767 CKAP2L Zornitza Stark Gene: ckap2l has been classified as Green List (High Evidence).
Prepair 1000+ v1.767 CKAP2L Zornitza Stark Phenotypes for gene: CKAP2L were changed from Filippi syndrome, 272440 (3) to Filippi syndrome, MIM#272440
Prepair 1000+ v1.766 CKAP2L Zornitza Stark Publications for gene: CKAP2L were set to
Prepair 1000+ v1.765 CHKB Zornitza Stark Marked gene: CHKB as ready
Prepair 1000+ v1.765 CHKB Zornitza Stark Gene: chkb has been classified as Green List (High Evidence).
Prepair 1000+ v1.765 CHKB Zornitza Stark Phenotypes for gene: CHKB were changed from Muscular dystrophy, congenital, megaconial type, 602541 (3) to Muscular dystrophy, congenital, megaconial type, MIM#602541
Prepair 1000+ v1.764 CHKB Zornitza Stark Publications for gene: CHKB were set to
Prepair 1000+ v1.763 CDK5RAP2 Zornitza Stark Marked gene: CDK5RAP2 as ready
Prepair 1000+ v1.763 CDK5RAP2 Zornitza Stark Gene: cdk5rap2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.763 CDK5RAP2 Zornitza Stark Phenotypes for gene: CDK5RAP2 were changed from Microcephaly 3, primary, autosomal recessive, 604804 (3) to Microcephaly 3, primary, autosomal recessive, MIM#604804
Prepair 1000+ v1.762 CDK5RAP2 Zornitza Stark Publications for gene: CDK5RAP2 were set to
Prepair 1000+ v1.761 TTC7A Lucy Spencer reviewed gene: TTC7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 28936210, 30553809; Phenotypes: Gastrointestinal defects and immunodeficiency syndrome MIM#243150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.761 TSHB Lucy Spencer reviewed gene: TSHB: Rating: GREEN; Mode of pathogenicity: None; Publications: 31384098; Phenotypes: Hypothyroidism, congenital, nongoitrous 4 MIM#275100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.761 TSEN54 Lucy Spencer reviewed gene: TSEN54: Rating: GREEN; Mode of pathogenicity: None; Publications: 20952379; Phenotypes: Pontocerebellar hypoplasia type 2A (MIM#277470), Pontocerebellar hypoplasia type 4 (MIM#225753), ?Pontocerebellar hypoplasia type 5 (MIM#610204); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.761 TPRKB Lucy Spencer changed review comment from: Gene is red on Mackenzie's mission panel but the review itself is green and says "Three unrelated families reported with renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly." this is refering to 3 families all with homozygous missense, p.Lys65Met, p.Tyr149Cys, and p.Leu136Pro.

There has been at least one more individual reported PMID: 38628357: a three-year-old male with developmental delay, regression, microcephaly, distinctive facial features, skeletal abnormalities, and epilepsy. He also had relapsing nephrotic proteinuria exacerbated by upper respiratory tract infections and progressive renal function decline. He was compound heterozygous for p.(Ser76IlefsTer3) and c.247C>T, p.(Leu83Phe).

Severe early-onset and reported in at least 4 individuals (also green on mendeliome), upgrading to green here.; to: Gene is red on Mackenzie's mission panel but the review itself is green and says "Three unrelated families reported with renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly." this is refering to 3 families all with homozygous missense, p.Lys65Met, p.Tyr149Cys, and p.Leu136Pro (PMIDs: 28805828, 30053862).

There has been at least one more individual reported PMID: 38628357: a three-year-old male with developmental delay, regression, microcephaly, distinctive facial features, skeletal abnormalities, and epilepsy. He also had relapsing nephrotic proteinuria exacerbated by upper respiratory tract infections and progressive renal function decline. He was compound heterozygous for p.(Ser76IlefsTer3) and c.247C>T, p.(Leu83Phe).

Severe early-onset and reported in at least 4 individuals (also green on mendeliome), upgrading to green here.
Prepair 1000+ v1.761 TPRKB Lucy Spencer reviewed gene: TPRKB: Rating: GREEN; Mode of pathogenicity: None; Publications: 38628357, 28805828, 30053862; Phenotypes: Galloway-Mowat syndrome 5, MIM# 617731; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neurodegeneration with brain iron accumulation v1.0 Bryony Thompson promoted panel to version 1.0
Prepair 1000+ v1.761 D2HGDH Karina Sandoval reviewed gene: D2HGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 15609246, 16081310, 31349060, 20020533, 38825343; Phenotypes: D-2-hydroxyglutaric aciduria, MIM#600721; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.761 CLDN19 Karina Sandoval changed review comment from: Dental anomalies on the AI spectrum are a feature of this primarily renal disorder. Macular coloboma is part of the phenotype.

Variable age of onset of deafness, progressive, generally in the first decade.

PMID 27530400 - 9 indiv from 6 families, age at onset of symtpoms ranging from 0-9 years with varying severity of symptoms ranging frrom FTT to polydipsia. Oldest age at CKD diagnosis was 15 years.

PMID 17033971 - 12 patients affected with hypomagnesemia, renal failure, and severe ocular abnormalities. Age at onset of symptoms was 0-8 years.

PMID 22422540 - 23 indiv with familial hypomagnesemia with hypercalciuria and nephrocalcinosis, median age at onset 9.5years. CKD was more frequently observed in patients with CLDN19 mutations: survival without CKD or ESRD was 56% at 20 years of age; to: Dental anomalies on the AI spectrum are a feature of this primarily renal disorder. Macular coloboma is part of the phenotype.

Variable age of onset of deafness, progressive, generally in the first decade.

PMID 27530400 - 9 indiv from 6 families, age at onset of symtpoms ranging from 0-9 years with varying severity of symptoms ranging frrom FTT to polydipsia. Oldest age at CKD diagnosis was 15 years.

PMID 17033971 - 12 patients affected with hypomagnesemia, renal failure, and severe ocular abnormalities. Age at onset of symptoms was 0-8 years.

PMID 22422540 - 23 indiv with familial hypomagnesemia with hypercalciuria and nephrocalcinosis, median age at onset 9.5years. CKD was more frequently observed in patients with CLDN19 mutations: survival without CKD or ESRD was 56% at 20 years of age
Pneumothorax v1.0 Bryony Thompson promoted panel to version 1.0
Pneumothorax v0.21 IPO8 Bryony Thompson Classified gene: IPO8 as Green List (high evidence)
Pneumothorax v0.21 IPO8 Bryony Thompson Gene: ipo8 has been classified as Green List (High Evidence).
Pneumothorax v0.20 IPO8 Bryony Thompson gene: IPO8 was added
gene: IPO8 was added to Pneumothorax. Sources: Expert list
Mode of inheritance for gene: IPO8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IPO8 were set to 20301312
Phenotypes for gene: IPO8 were set to Loeys-Dietz syndrome MONDO:0018954
Review for gene: IPO8 was set to GREEN
gene: IPO8 was marked as current diagnostic
Added comment: Included on this panel because spontaneous pneumothorax can be a feature of LDS.
Sources: Expert list
Pneumothorax v0.19 TGFB3 Bryony Thompson Classified gene: TGFB3 as Green List (high evidence)
Pneumothorax v0.19 TGFB3 Bryony Thompson Added comment: Comment on list classification: Included on this panel because spontaneous pneumothorax can be a feature of LDS.
Pneumothorax v0.19 TGFB3 Bryony Thompson Gene: tgfb3 has been classified as Green List (High Evidence).
Pneumothorax v0.18 TGFB3 Bryony Thompson Publications for gene: TGFB3 were set to 15591413; 25006744; 25835445; 24577266; 26493799; 23161884
Pneumothorax v0.17 TGFBR1 Bryony Thompson Publications for gene: TGFBR1 were set to 16799921; 15591413; 25006744; 26493799; 23161884
Pneumothorax v0.16 TGFBR1 Bryony Thompson Classified gene: TGFBR1 as Green List (high evidence)
Pneumothorax v0.16 TGFBR1 Bryony Thompson Added comment: Comment on list classification: Included on this panel because spontaneous pneumothorax can be a feature of LDS.
Pneumothorax v0.16 TGFBR1 Bryony Thompson Gene: tgfbr1 has been classified as Green List (High Evidence).
Pneumothorax v0.15 SMAD3 Bryony Thompson Marked gene: SMAD3 as ready
Pneumothorax v0.15 SMAD3 Bryony Thompson Gene: smad3 has been classified as Green List (High Evidence).
Pneumothorax v0.15 SMAD3 Bryony Thompson Publications for gene: SMAD3 were set to 25006744; 26493799; 15591413; 23161884
Pneumothorax v0.14 SMAD3 Bryony Thompson Classified gene: SMAD3 as Green List (high evidence)
Pneumothorax v0.14 SMAD3 Bryony Thompson Added comment: Comment on list classification: Included on this panel because spontaneous pneumothorax can be a feature of LDS.
Pneumothorax v0.14 SMAD3 Bryony Thompson Gene: smad3 has been classified as Green List (High Evidence).
Pneumothorax v0.13 SMAD2 Bryony Thompson Publications for gene: SMAD2 were set to 29392890; 26247899; 29707331
Pneumothorax v0.12 SMAD2 Bryony Thompson Classified gene: SMAD2 as Green List (high evidence)
Pneumothorax v0.12 SMAD2 Bryony Thompson Added comment: Comment on list classification: Included on this panel because spontaneous pneumothorax can be a feature of LDS.
Pneumothorax v0.12 SMAD2 Bryony Thompson Gene: smad2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.761 CCNO Zornitza Stark Marked gene: CCNO as ready
Prepair 1000+ v1.761 CCNO Zornitza Stark Gene: ccno has been classified as Green List (High Evidence).
Prepair 1000+ v1.761 CCNO Zornitza Stark Phenotypes for gene: CCNO were changed from Ciliary diskinesia, primary, 29, 615872 (3) to Ciliary diskinesia, primary, 29, MIM#615872
Prepair 1000+ v1.760 CCNO Zornitza Stark Publications for gene: CCNO were set to
Prepair 1000+ v1.759 CC2D2A Zornitza Stark Marked gene: CC2D2A as ready
Prepair 1000+ v1.759 CC2D2A Zornitza Stark Gene: cc2d2a has been classified as Green List (High Evidence).
Prepair 1000+ v1.759 CC2D2A Zornitza Stark Phenotypes for gene: CC2D2A were changed from Joubert syndrome 9, 612285 (3) to COACH syndrome, MIM#216360; Joubert syndrome 9, MIM#612285; Meckel syndrome 6, MIM#612284; Retinitis pigmentosa 93, MIM# 619845
Prepair 1000+ v1.758 CC2D2A Zornitza Stark Publications for gene: CC2D2A were set to
Prepair 1000+ v1.757 C3 Zornitza Stark Marked gene: C3 as ready
Prepair 1000+ v1.757 C3 Zornitza Stark Gene: c3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.757 C3 Zornitza Stark Phenotypes for gene: C3 were changed from C3 deficiency, 613779 (3) to C3 deficiency, MIM#613779
Prepair 1000+ v1.756 C3 Zornitza Stark Publications for gene: C3 were set to
Prepair 1000+ v1.755 CENPJ Zornitza Stark Marked gene: CENPJ as ready
Prepair 1000+ v1.755 CENPJ Zornitza Stark Gene: cenpj has been classified as Green List (High Evidence).
Prepair 1000+ v1.755 CENPJ Zornitza Stark Phenotypes for gene: CENPJ were changed from Microcephaly 6, primary, autosomal recessive, 608393 (3) to Microcephaly 6, primary MIM#608393; Seckel syndrome 4 MIM#613676
Prepair 1000+ v1.754 CENPJ Zornitza Stark Publications for gene: CENPJ were set to
Prepair 1000+ v1.753 CDH11 Zornitza Stark Marked gene: CDH11 as ready
Prepair 1000+ v1.753 CDH11 Zornitza Stark Gene: cdh11 has been classified as Green List (High Evidence).
Prepair 1000+ v1.753 CDH11 Zornitza Stark Phenotypes for gene: CDH11 were changed from Elsahy-Waters syndrome, 211380 (3), Autosomal recessive to Elsahy-Waters syndrome MIM#211380
Prepair 1000+ v1.752 CDH11 Zornitza Stark Publications for gene: CDH11 were set to
Prepair 1000+ v1.751 BBS7 Zornitza Stark Marked gene: BBS7 as ready
Prepair 1000+ v1.751 BBS7 Zornitza Stark Gene: bbs7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.751 BBS7 Zornitza Stark Phenotypes for gene: BBS7 were changed from Bardet-Biedl syndrome 7, 615984 (3) to Bardet-Biedl syndrome 7, MIM# 615984; MONDO:0014435
Prepair 1000+ v1.750 BBS7 Zornitza Stark Publications for gene: BBS7 were set to
Prepair 1000+ v1.749 SLC24A5 Zornitza Stark Marked gene: SLC24A5 as ready
Prepair 1000+ v1.749 SLC24A5 Zornitza Stark Gene: slc24a5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.749 SLC24A5 Zornitza Stark Phenotypes for gene: SLC24A5 were changed from Albinism, oculocutaneous, type VI, 113750 (3) to Albinism, oculocutaneous, type VI, MIM#113750
Prepair 1000+ v1.748 SLC24A5 Zornitza Stark Publications for gene: SLC24A5 were set to
Prepair 1000+ v1.747 SLC22A5 Zornitza Stark Marked gene: SLC22A5 as ready
Prepair 1000+ v1.747 SLC22A5 Zornitza Stark Gene: slc22a5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.747 SLC22A5 Zornitza Stark Phenotypes for gene: SLC22A5 were changed from Carnitine deficiency, systemic primary, 212140 (3) to Carnitine deficiency, systemic primary, MIM# 212140, MONDO:0008919
Prepair 1000+ v1.746 SLC22A5 Zornitza Stark Publications for gene: SLC22A5 were set to
Prepair 1000+ v1.745 SLC16A1 Zornitza Stark Marked gene: SLC16A1 as ready
Prepair 1000+ v1.745 SLC16A1 Zornitza Stark Gene: slc16a1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.745 SLC16A1 Zornitza Stark Phenotypes for gene: SLC16A1 were changed from Monocarboxylate transporter 1 deficiency, 616095 (3) to Monocarboxylate transporter 1 deficiency, MIM#616095
Prepair 1000+ v1.744 SLC16A1 Zornitza Stark Publications for gene: SLC16A1 were set to
Prepair 1000+ v1.743 SH2D1A Zornitza Stark Marked gene: SH2D1A as ready
Prepair 1000+ v1.743 SH2D1A Zornitza Stark Gene: sh2d1a has been classified as Green List (High Evidence).
Prepair 1000+ v1.743 SH2D1A Zornitza Stark Publications for gene: SH2D1A were set to
Prepair 1000+ v1.742 SGSH Zornitza Stark Marked gene: SGSH as ready
Prepair 1000+ v1.742 SGSH Zornitza Stark Gene: sgsh has been classified as Green List (High Evidence).
Prepair 1000+ v1.742 SGSH Zornitza Stark Phenotypes for gene: SGSH were changed from Mucopolysaccharidisis type IIIA (Sanfilippo A), 252900 (3) to Mucopolysaccharidisis type IIIA (Sanfilippo A), MIM#252900
Prepair 1000+ v1.741 SGSH Zornitza Stark Publications for gene: SGSH were set to
Prepair 1000+ v1.740 SCO2 Zornitza Stark Marked gene: SCO2 as ready
Prepair 1000+ v1.740 SCO2 Zornitza Stark Gene: sco2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.740 SCO2 Zornitza Stark Phenotypes for gene: SCO2 were changed from Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, 604377 (3) to Mitochondrial complex IV deficiency, nuclear type 2 MIM#604377
Prepair 1000+ v1.739 SCO2 Zornitza Stark Publications for gene: SCO2 were set to
Prepair 1000+ v1.738 RSPH9 Zornitza Stark Marked gene: RSPH9 as ready
Prepair 1000+ v1.738 RSPH9 Zornitza Stark Gene: rsph9 has been classified as Green List (High Evidence).
Prepair 1000+ v1.738 RSPH9 Zornitza Stark Phenotypes for gene: RSPH9 were changed from Ciliary dyskinesia, primary, 12, 612650 (3) to Ciliary dyskinesia, primary, 12, MIM#612650
Prepair 1000+ v1.737 RSPH9 Zornitza Stark Publications for gene: RSPH9 were set to
Prepair 1000+ v1.736 RAB3GAP2 Zornitza Stark Marked gene: RAB3GAP2 as ready
Prepair 1000+ v1.736 RAB3GAP2 Zornitza Stark Gene: rab3gap2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.736 RAB3GAP2 Zornitza Stark Phenotypes for gene: RAB3GAP2 were changed from Warburg micro syndrome 2, 614225 (3) to Warburg micro syndrome MONDO:0016649
Prepair 1000+ v1.735 RAB3GAP2 Zornitza Stark Publications for gene: RAB3GAP2 were set to
Prepair 1000+ v1.734 QARS Zornitza Stark Marked gene: QARS as ready
Prepair 1000+ v1.734 QARS Zornitza Stark Gene: qars has been classified as Green List (High Evidence).
Prepair 1000+ v1.734 QARS Zornitza Stark Phenotypes for gene: QARS were changed from Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy, 615760 (3) to Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy MIM#615760
Prepair 1000+ v1.733 QARS Zornitza Stark Publications for gene: QARS were set to
Prepair 1000+ v1.732 PRF1 Zornitza Stark Marked gene: PRF1 as ready
Prepair 1000+ v1.732 PRF1 Zornitza Stark Gene: prf1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.732 PRF1 Zornitza Stark Phenotypes for gene: PRF1 were changed from Hemophagocytic lymphohistiocytosis, familial, 2, 603553 (3) to Hemophagocytic lymphohistiocytosis, familial, 2, MIM#603553
Prepair 1000+ v1.731 PRF1 Zornitza Stark Publications for gene: PRF1 were set to
Prepair 1000+ v1.730 CYP11B2 Andrew Coventry reviewed gene: CYP11B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 8439335, 9360501, 15240589, 9814506, 12788848, 8772616; Phenotypes: Hypoaldosteronism, congenital, due to CMO I deficiency MIM#203400, Hypoaldosteronism, congenital, due to CMO II deficiency MIM#610600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.730 CUL7 Andrew Coventry reviewed gene: CUL7: Rating: GREEN; Mode of pathogenicity: None; Publications: 16142236, 19225462, 17675530; Phenotypes: 3-M syndrome 1 MIM#273750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.730 OTULIN Andrew Coventry gene: OTULIN was added
gene: OTULIN was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: OTULIN was set to BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.730 CLDN19 Karina Sandoval reviewed gene: CLDN19: Rating: GREEN; Mode of pathogenicity: None; Publications: 27530400, 17033971, 22422540; Phenotypes: Hypomagnesemia 5, renal, with ocular involvement, MIM#248190; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.730 OXCT1 Andrew Coventry gene: OXCT1 was added
gene: OXCT1 was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: OXCT1 was set to BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.730 HPDL Andrew Coventry gene: HPDL was added
gene: HPDL was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.730 DBR1 Andrew Coventry gene: DBR1 was added
gene: DBR1 was added to Prepair 1000+. Sources: Expert list
Mode of inheritance for gene: DBR1 was set to BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.730 WHRN Andrew Coventry reviewed gene: WHRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 26307081, 26338283, 22147658, 17171570, 21738389, 27117407; Phenotypes: Usher syndrome, type 2D MIM#611383; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.730 MYMK Cassandra Muller reviewed gene: MYMK: Rating: GREEN; Mode of pathogenicity: None; Publications: 28681861; Phenotypes: Carey-Fineman-Ziter syndrome, 254940 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.730 POMT1 Zornitza Stark Marked gene: POMT1 as ready
Prepair 1000+ v1.730 POMT1 Zornitza Stark Gene: pomt1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.730 POMT1 Zornitza Stark Phenotypes for gene: POMT1 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1, 236670 (3) to Myopathy caused by variation in POMT1 MONDO:0700070
Prepair 1000+ v1.729 CTSK Lilian Downie Marked gene: CTSK as ready
Prepair 1000+ v1.729 CTSK Lilian Downie Gene: ctsk has been classified as Green List (High Evidence).
Prepair 1000+ v1.729 CTSK Lilian Downie Publications for gene: CTSK were set to
Prepair 1000+ v1.728 POMT1 Zornitza Stark Publications for gene: POMT1 were set to
Prepair 1000+ v1.727 CTSK Lilian Downie reviewed gene: CTSK: Rating: GREEN; Mode of pathogenicity: None; Publications: 33151655; Phenotypes: Pycnodysostosis MIM#265800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.727 MMAA Zornitza Stark Marked gene: MMAA as ready
Prepair 1000+ v1.727 MMAA Zornitza Stark Gene: mmaa has been classified as Green List (High Evidence).
Prepair 1000+ v1.727 MMAA Zornitza Stark Phenotypes for gene: MMAA were changed from Methylmalonic aciduria, vitamin B12-responsive, 251100 (3) to Methylmalonic aciduria, vitamin B12-responsive, MIM#251100
Prepair 1000+ v1.726 MERTK Zornitza Stark Marked gene: MERTK as ready
Prepair 1000+ v1.726 MERTK Zornitza Stark Gene: mertk has been classified as Green List (High Evidence).
Prepair 1000+ v1.726 MERTK Zornitza Stark Phenotypes for gene: MERTK were changed from Retinitis pigmentosa 38, 613862 (3) to Retinitis pigmentosa 38, MIM#613862
Prepair 1000+ v1.725 MERTK Zornitza Stark Publications for gene: MERTK were set to
Prepair 1000+ v1.724 CHRND Lilian Downie Marked gene: CHRND as ready
Prepair 1000+ v1.724 CHRND Lilian Downie Gene: chrnd has been classified as Green List (High Evidence).
Prepair 1000+ v1.724 CHRND Lilian Downie Phenotypes for gene: CHRND were changed from Myasthenic syndrome, congenital, 3B, fast-channel, 616322 (3) to Multiple pterygium syndrome, lethal type MIM#253290; Myasthenic syndrome, congenital, 3B, fast-channel MIM#616322
Prepair 1000+ v1.723 CHRND Lilian Downie Publications for gene: CHRND were set to
Prepair 1000+ v1.722 MARS Zornitza Stark Marked gene: MARS as ready
Prepair 1000+ v1.722 MARS Zornitza Stark Gene: mars has been classified as Green List (High Evidence).
Prepair 1000+ v1.722 MED25 Marta Cifuentes Ochoa reviewed gene: MED25: Rating: GREEN; Mode of pathogenicity: None; Publications: 25792360, 32816121, 25527630, 30800049, 32324310, 19290556; Phenotypes: Basel-Vanagait-Smirin-Yosef syndrome, MIM# 616449, congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome MONDO:0014643; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.722 MARS Zornitza Stark Phenotypes for gene: MARS were changed from Interstitial lung and liver disease, 615486 (3) to Interstitial lung and liver disease, MIM#615486
Prepair 1000+ v1.721 CHRND Lilian Downie reviewed gene: CHRND: Rating: GREEN; Mode of pathogenicity: None; Publications: 30808424; Phenotypes: Multiple pterygium syndrome, lethal type MIM#253290, Myasthenic syndrome, congenital, 3B, fast-channel MIM#616322; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.721 MARS Zornitza Stark Publications for gene: MARS were set to
Prepair 1000+ v1.720 MARS Zornitza Stark Tag new gene name tag was added to gene: MARS.
Prepair 1000+ v1.720 KCNJ1 Zornitza Stark Marked gene: KCNJ1 as ready
Prepair 1000+ v1.720 KCNJ1 Zornitza Stark Gene: kcnj1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.720 KCNJ1 Zornitza Stark Phenotypes for gene: KCNJ1 were changed from Bartter syndrome, type 2, 241200 (3) to Bartter syndrome, type 2, MIM#241200
Prepair 1000+ v1.719 MED17 Cassandra Muller reviewed gene: MED17: Rating: GREEN; Mode of pathogenicity: None; Publications: 30345598, 33756211, 20950787; Phenotypes: Microcephaly, postnatal progressive, with seizures and brain atrophy, 613668 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.719 CFL2 Lilian Downie Marked gene: CFL2 as ready
Prepair 1000+ v1.719 CFL2 Lilian Downie Gene: cfl2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.719 CFL2 Lilian Downie Publications for gene: CFL2 were set to
Prepair 1000+ v1.718 CFL2 Lilian Downie reviewed gene: CFL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29457652, 17160903, 22560515; Phenotypes: Nemaline myopathy 7, autosomal recessive MIM#610687; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.718 DOCK8 Melanie Marty reviewed gene: DOCK8: Rating: GREEN; Mode of pathogenicity: None; Publications: 19776401, 20622910, 21931011, 26659092, 19898472, 25422492; Phenotypes: Hyper-IgE recurrent infection syndrome, autosomal recessive, MIM# 243700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.718 MANBA Cassandra Muller reviewed gene: MANBA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mannosidosis, beta, 248510 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.718 CCDC88C Lilian Downie Marked gene: CCDC88C as ready
Prepair 1000+ v1.718 CCDC88C Lilian Downie Gene: ccdc88c has been classified as Green List (High Evidence).
Prepair 1000+ v1.718 CCDC88C Lilian Downie Phenotypes for gene: CCDC88C were changed from Hydrocephalus, nonsyndromic, autosomal recessive, 236600 (3) to Hydrocephalus, congenital, 1 MIM#236600
Prepair 1000+ v1.717 CCDC88C Lilian Downie Publications for gene: CCDC88C were set to
Prepair 1000+ v1.716 CCDC88C Lilian Downie reviewed gene: CCDC88C: Rating: GREEN; Mode of pathogenicity: None; Publications: 34092257, 29341397, 23042809, 21031079; Phenotypes: Hydrocephalus, congenital, 1 MIM#236600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.716 DNAI1 Melanie Marty reviewed gene: DNAI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10577904, 11231901, 32502479, 31765523, 30622330; Phenotypes: Ciliary dyskinesia, primary, 1, with or without situs inversus, MIM# 244400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.716 TUSC3 Andrew Coventry reviewed gene: TUSC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18452889, 18455129, 21739581, 27148795, 31606977, 28397838, 18452889, 23825019; Phenotypes: Intellectual developmental disorder, autosomal recessive 7 MIM#611093; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.716 DNAH11 Melanie Marty reviewed gene: DNAH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 12142464, 18022865, 22102620, 32633470, 31879361, 31765523, 31040315; Phenotypes: Ciliary dyskinesia, primary, 7, with or without situs inversus, MIM#611884; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.716 C8orf37 Lilian Downie Marked gene: C8orf37 as ready
Prepair 1000+ v1.716 C8orf37 Lilian Downie Gene: c8orf37 has been classified as Green List (High Evidence).
Prepair 1000+ v1.716 C8orf37 Lilian Downie Phenotypes for gene: C8orf37 were changed from Cone-rod dystrophy 16, 614500 (3) to Cone-rod dystrophy 16, Retinitis pigmentosa 64 MIM#614500
Prepair 1000+ v1.715 C8orf37 Lilian Downie Publications for gene: C8orf37 were set to
Prepair 1000+ v1.714 C8orf37 Lilian Downie reviewed gene: C8orf37: Rating: GREEN; Mode of pathogenicity: None; Publications: 22177090, 25113443, 26865426, 25802487; Phenotypes: Retinitis pigmentosa 64 MIM#614500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.714 LYRM7 Cassandra Muller Deleted their comment
Prepair 1000+ v1.714 LYRM7 Cassandra Muller commented on gene: LYRM7: Well-established gene disease association. Primary mitochondrial disease.
Prepair 1000+ v1.714 LYRM7 Cassandra Muller reviewed gene: LYRM7: Rating: GREEN; Mode of pathogenicity: None; Publications: 26912632, 24014394; Phenotypes: Mitochondrial complex III deficiency, nuclear type 8, 615838 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.714 DLG3 Melanie Marty reviewed gene: DLG3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24721225, 28777483; Phenotypes: Intellectual developmental disorder, X-linked 90 MIM#300850; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.714 IKBKB Zornitza Stark Marked gene: IKBKB as ready
Prepair 1000+ v1.714 IKBKB Zornitza Stark Gene: ikbkb has been classified as Green List (High Evidence).
Prepair 1000+ v1.714 IKBKB Zornitza Stark Phenotypes for gene: IKBKB were changed from Immunodeficiency 15, 615592 (3) to Immunodeficiency 15, MIM#615592
Prepair 1000+ v1.713 IKBKB Zornitza Stark Publications for gene: IKBKB were set to
Prepair 1000+ v1.712 C21orf2 Lilian Downie Marked gene: C21orf2 as ready
Prepair 1000+ v1.712 C21orf2 Lilian Downie Gene: c21orf2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.712 C21orf2 Lilian Downie Phenotypes for gene: C21orf2 were changed from Retinal dystrophy with macular staphyloma, 617547 (3), Autosomal recessive to Retinal dystrophy with macular staphyloma MIM#617547; Spondylometaphyseal dysplasia, axial MIM#602271
Prepair 1000+ v1.711 HPS1 Zornitza Stark reviewed gene: HPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.711 C21orf2 Lilian Downie Publications for gene: C21orf2 were set to
Prepair 1000+ v1.710 HPS1 Zornitza Stark Marked gene: HPS1 as ready
Prepair 1000+ v1.710 HPS1 Zornitza Stark Gene: hps1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.710 HPS1 Zornitza Stark Phenotypes for gene: HPS1 were changed from Hermansky-Pudlak syndrome 1, 203300 (3) to Hermansky-Pudlak syndrome 1, MIM#203300
Prepair 1000+ v1.709 C21orf2 Lilian Downie reviewed gene: C21orf2: Rating: GREEN; Mode of pathogenicity: None; Publications: 39232248, 26974433, 27548899, 28422394; Phenotypes: Retinal dystrophy with macular staphyloma MIM#617547, Spondylometaphyseal dysplasia, axial MIM#602271; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.709 HPS1 Zornitza Stark Publications for gene: HPS1 were set to
Prepair 1000+ v1.708 TUBA8 Andrew Coventry reviewed gene: TUBA8: Rating: RED; Mode of pathogenicity: None; Publications: 34704371; Phenotypes: Polymicrogyria with optic nerve hypoplasia MONDO:0013172; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.708 LRPPRC Cassandra Muller reviewed gene: LRPPRC: Rating: GREEN; Mode of pathogenicity: None; Publications: 12529507, 12529507, 26510951, 21266382; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) 220111 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.708 HPD Zornitza Stark Tag for review tag was added to gene: HPD.
Prepair 1000+ v1.708 DDHD2 Melanie Marty reviewed gene: DDHD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23486545, 24482476, 23176823, 31302745; Phenotypes: Spastic paraplegia 54, autosomal recessive, MIM# 615033; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.708 HFE2 Zornitza Stark Marked gene: HFE2 as ready
Prepair 1000+ v1.708 HFE2 Zornitza Stark Gene: hfe2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.708 HFE2 Zornitza Stark Phenotypes for gene: HFE2 were changed from Hemochromatosis, type 2A, 602390 (3) to Haemochromatosis, type 2A, 602390 (3)
Prepair 1000+ v1.707 TRDN Andrew Coventry reviewed gene: TRDN: Rating: GREEN; Mode of pathogenicity: None; Publications: 31983240, 25922419, 30649896, 22422768; Phenotypes: Cardiac arrhythmia syndrome, with or without skeletal muscle weakness MIM#615441, Catecholaminergic polymorphic ventricular tachycardia MONDO:0017990; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.707 BTD Lilian Downie reviewed gene: BTD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Biotinidase deficiency MIM#253260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.707 GLYCTK Zornitza Stark Marked gene: GLYCTK as ready
Prepair 1000+ v1.707 GLYCTK Zornitza Stark Gene: glyctk has been classified as Green List (High Evidence).
Prepair 1000+ v1.707 GLYCTK Zornitza Stark Phenotypes for gene: GLYCTK were changed from D-glyceric aciduria, 220120 (3) to D-glyceric aciduria, MIM#220120
Prepair 1000+ v1.706 MARS2 Marta Cifuentes Ochoa reviewed gene: MARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25754315, 16672289, 22448145, 22448145, 23250129; Phenotypes: Combined oxidative phosphorylation deficiency 25, MIM #616430, MONDO:0014636, Spastic ataxia 3, autosomal recessive, MIM #611390, MONDO:0012664; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.706 GLYCTK Zornitza Stark Publications for gene: GLYCTK were set to
Prepair 1000+ v1.705 BSND Lilian Downie Marked gene: BSND as ready
Prepair 1000+ v1.705 BSND Lilian Downie Gene: bsnd has been classified as Green List (High Evidence).
Prepair 1000+ v1.705 LHX3 Zornitza Stark Marked gene: LHX3 as ready
Prepair 1000+ v1.705 LHX3 Zornitza Stark Gene: lhx3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.705 LHX3 Zornitza Stark Phenotypes for gene: LHX3 were changed from Pituitary hormone deficiency, combined, 3, 221750 (3) to Pituitary hormone deficiency, combined, 3, MIM# 221750
Prepair 1000+ v1.704 BSND Lilian Downie Publications for gene: BSND were set to
Prepair 1000+ v1.703 LHX3 Zornitza Stark Publications for gene: LHX3 were set to
Prepair 1000+ v1.702 BSND Lilian Downie reviewed gene: BSND: Rating: GREEN; Mode of pathogenicity: None; Publications: 11687798, 19646679, 16572343; Phenotypes: Bartter syndrome, type 4a MIM#602522; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.702 KY Zornitza Stark Marked gene: KY as ready
Prepair 1000+ v1.702 KY Zornitza Stark Gene: ky has been classified as Green List (High Evidence).
Prepair 1000+ v1.702 KY Zornitza Stark Phenotypes for gene: KY were changed from Myopathy, myofibrillar, 7, 617114 (3), Autosomal recessive to Myopathy, myofibrillar, 7 (MIM#617114)
Prepair 1000+ v1.701 TNFSF11 Andrew Coventry reviewed gene: TNFSF11: Rating: GREEN; Mode of pathogenicity: None; Publications: 17632511, 36031188, 32940787, 32048120, 10984520; Phenotypes: Osteopetrosis, autosomal recessive 2 MIM#259710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.701 KY Zornitza Stark Publications for gene: KY were set to
Prepair 1000+ v1.700 LMOD3 Cassandra Muller reviewed gene: LMOD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 25250574, 28815944, 30291184; Phenotypes: Nemaline myopathy 10, 616165 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.700 BCKDHB Lilian Downie Marked gene: BCKDHB as ready
Prepair 1000+ v1.700 BCKDHB Lilian Downie Gene: bckdhb has been classified as Green List (High Evidence).
Prepair 1000+ v1.700 BCKDHB Lilian Downie Phenotypes for gene: BCKDHB were changed from Maple syrup urine disease, type Ib, 248600 (3) to Maple syrup urine disease, type Ib 620698
Prepair 1000+ v1.699 BCKDHB Lilian Downie Publications for gene: BCKDHB were set to
Prepair 1000+ v1.698 BCKDHB Lilian Downie reviewed gene: BCKDHB: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301495, 34883003, 34556729, 34288399; Phenotypes: Maple syrup urine disease, type Ib 620698; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.698 KLHL7 Zornitza Stark Marked gene: KLHL7 as ready
Prepair 1000+ v1.698 KLHL7 Zornitza Stark Gene: klhl7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.698 KLHL7 Zornitza Stark Phenotypes for gene: KLHL7 were changed from PERCHING syndrome, 617055 (3) to PERCHING syndrome, MIM#617055
Prepair 1000+ v1.697 KLHL7 Zornitza Stark Publications for gene: KLHL7 were set to
Prepair 1000+ v1.696 POP1 Zornitza Stark Marked gene: POP1 as ready
Prepair 1000+ v1.696 POP1 Zornitza Stark Gene: pop1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.696 POP1 Zornitza Stark Phenotypes for gene: POP1 were changed from Anauxetic dysplasia 2, 617396 (3), Autosomal recessive to Anauxetic dysplasia 2, MIM#617396
Prepair 1000+ v1.695 TMEM70 Andrew Coventry reviewed gene: TMEM70: Rating: GREEN; Mode of pathogenicity: None; Publications: 18953340, 21147908, 30950220; Phenotypes: Mitochondrial disease MONDO:0044970; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.695 POP1 Zornitza Stark Publications for gene: POP1 were set to
Prepair 1000+ v1.694 POMGNT2 Zornitza Stark Marked gene: POMGNT2 as ready
Prepair 1000+ v1.694 POMGNT2 Zornitza Stark Gene: pomgnt2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.694 LIPT1 Cassandra Muller reviewed gene: LIPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24341803, 29681092, 27977873; Phenotypes: Lipoyltransferase 1 deficiency, 616299 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.694 POMGNT2 Zornitza Stark Phenotypes for gene: POMGNT2 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8, 614830 (3) to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8, 618135; Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8, MIM#618135
Prepair 1000+ v1.693 POMGNT2 Zornitza Stark Publications for gene: POMGNT2 were set to
Prepair 1000+ v1.692 ATP6V0A4 Lilian Downie Marked gene: ATP6V0A4 as ready
Prepair 1000+ v1.692 ATP6V0A4 Lilian Downie Gene: atp6v0a4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.692 ATP6V0A4 Lilian Downie Phenotypes for gene: ATP6V0A4 were changed from Renal tubular acidosis, distal, autosomal recessive, 602722 (3) to Distal renal tubular acidosis 3, with or without sensorineural hearing loss MIM#602722
Prepair 1000+ v1.691 POMC Zornitza Stark Marked gene: POMC as ready
Prepair 1000+ v1.691 POMC Zornitza Stark Gene: pomc has been classified as Green List (High Evidence).
Prepair 1000+ v1.691 POMC Zornitza Stark Phenotypes for gene: POMC were changed from Obesity, adrenal insufficiency, and red hair due to POMC deficiency, 609734 (3) to Obesity, adrenal insufficiency, and red hair due to POMC deficiency, MIM#609734
Prepair 1000+ v1.690 ATP6V0A4 Lilian Downie Publications for gene: ATP6V0A4 were set to
Prepair 1000+ v1.689 POMC Zornitza Stark Publications for gene: POMC were set to
Prepair 1000+ v1.688 ATP6V0A4 Lilian Downie reviewed gene: ATP6V0A4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22872862, 12414817, 29311258; Phenotypes: Distal renal tubular acidosis 3, with or without sensorineural hearing loss MIM#602722; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.688 IARS2 Zornitza Stark Marked gene: IARS2 as ready
Prepair 1000+ v1.688 IARS2 Zornitza Stark Gene: iars2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.688 IARS2 Zornitza Stark Phenotypes for gene: IARS2 were changed from ?Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia to Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, MIM#616007
Prepair 1000+ v1.687 IARS2 Zornitza Stark Publications for gene: IARS2 were set to
Prepair 1000+ v1.686 HINT1 Zornitza Stark Marked gene: HINT1 as ready
Prepair 1000+ v1.686 HINT1 Zornitza Stark Gene: hint1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.686 HINT1 Zornitza Stark Phenotypes for gene: HINT1 were changed from Neuromyotonia and axonal neuropathy, autosomal recessive, 137200 (3) to Neuromyotonia and axonal neuropathy, autosomal recessive, MIM#137200
Prepair 1000+ v1.685 HGSNAT Zornitza Stark Marked gene: HGSNAT as ready
Prepair 1000+ v1.685 HGSNAT Zornitza Stark Gene: hgsnat has been classified as Green List (High Evidence).
Prepair 1000+ v1.685 HGSNAT Zornitza Stark Phenotypes for gene: HGSNAT were changed from Mucopolysaccharidosis type IIIC (Sanfilippo C), 252930 (3) to Mucopolysaccharidosis type IIIC (Sanfilippo C), MIM#252930
Prepair 1000+ v1.684 HGSNAT Zornitza Stark Publications for gene: HGSNAT were set to
Prepair 1000+ v1.683 NDUFAF2 Zornitza Stark Marked gene: NDUFAF2 as ready
Prepair 1000+ v1.683 NDUFAF2 Zornitza Stark Gene: ndufaf2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.683 NDUFAF2 Zornitza Stark Phenotypes for gene: NDUFAF2 were changed from Leigh syndrome, 256000 (3) to Mitochondrial complex I deficiency, nuclear type 10, MIM#618233
Prepair 1000+ v1.682 NDUFAF2 Zornitza Stark Publications for gene: NDUFAF2 were set to
Prepair 1000+ v1.681 LPIN1 Zornitza Stark Marked gene: LPIN1 as ready
Prepair 1000+ v1.681 LPIN1 Zornitza Stark Gene: lpin1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.681 LPIN1 Zornitza Stark Phenotypes for gene: LPIN1 were changed from Myoglobinuria, acute recurrent, autosomal recessive, 268200 (3) to Myoglobinuria, acute recurrent, autosomal recessive, MIM#268200
Prepair 1000+ v1.680 LPIN1 Zornitza Stark Publications for gene: LPIN1 were set to
Prepair 1000+ v1.679 SLC9A3 Lilian Downie Marked gene: SLC9A3 as ready
Prepair 1000+ v1.679 SLC9A3 Lilian Downie Added comment: Comment when marking as ready: Downgrade to RED for severity (mild, children thrive on normal diet)
Prepair 1000+ v1.679 SLC9A3 Lilian Downie Gene: slc9a3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.679 SLC9A3 Lilian Downie Tag for review tag was added to gene: SLC9A3.
Prepair 1000+ v1.679 L2HGDH Zornitza Stark Marked gene: L2HGDH as ready
Prepair 1000+ v1.679 L2HGDH Zornitza Stark Gene: l2hgdh has been classified as Green List (High Evidence).
Prepair 1000+ v1.679 L2HGDH Zornitza Stark Phenotypes for gene: L2HGDH were changed from L-2-hydroxyglutaric aciduria, 236792 (3) to L-2-hydroxyglutaric aciduria, MIM#236792
Prepair 1000+ v1.678 L2HGDH Zornitza Stark Publications for gene: L2HGDH were set to
Prepair 1000+ v1.677 SLC9A3 Lilian Downie Publications for gene: SLC9A3 were set to
Prepair 1000+ v1.676 HEXB Zornitza Stark Marked gene: HEXB as ready
Prepair 1000+ v1.676 HEXB Zornitza Stark Gene: hexb has been classified as Green List (High Evidence).
Prepair 1000+ v1.676 HEXB Zornitza Stark Phenotypes for gene: HEXB were changed from Sandhoff disease, infantile, juvenile, and adult forms, 268800 (3) to Sandhoff disease, infantile, juvenile, and adult forms, MIM#268800
Prepair 1000+ v1.675 HEXB Zornitza Stark Publications for gene: HEXB were set to
Prepair 1000+ v1.674 LRRC6 Lilian Downie Marked gene: LRRC6 as ready
Prepair 1000+ v1.674 LRRC6 Lilian Downie Added comment: Comment when marking as ready: Note alternative gene name DNAAF11
Prepair 1000+ v1.674 LRRC6 Lilian Downie Gene: lrrc6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.674 LRRC6 Lilian Downie Marked gene: LRRC6 as ready
Prepair 1000+ v1.674 LRRC6 Lilian Downie Added comment: Comment when marking as ready: Note alternative gene name DNAAF11
Prepair 1000+ v1.674 LRRC6 Lilian Downie Gene: lrrc6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.674 LRRC6 Lilian Downie Publications for gene: LRRC6 were set to
Prepair 1000+ v1.673 HEPACAM Zornitza Stark Marked gene: HEPACAM as ready
Prepair 1000+ v1.673 HEPACAM Zornitza Stark Gene: hepacam has been classified as Green List (High Evidence).
Prepair 1000+ v1.673 SLC26A2 Lilian Downie Marked gene: SLC26A2 as ready
Prepair 1000+ v1.673 SLC26A2 Lilian Downie Added comment: Comment when marking as ready: ClinGen has curated this gene for 4 split disease entities (see Mondo terms) when curating consider genotype-phenotype
Prepair 1000+ v1.673 SLC26A2 Lilian Downie Gene: slc26a2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.673 HEPACAM Zornitza Stark Phenotypes for gene: HEPACAM were changed from Megalencephalic leukoencephalopathy with subcortical cysts 2A, 613925 (3) to Megalencephalic leukoencephalopathy with subcortical cysts 2A, MIM#613925 (3)
Prepair 1000+ v1.672 HEPACAM Zornitza Stark Publications for gene: HEPACAM were set to
Prepair 1000+ v1.671 HCFC1 Zornitza Stark Marked gene: HCFC1 as ready
Prepair 1000+ v1.671 HCFC1 Zornitza Stark Gene: hcfc1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.671 HCFC1 Zornitza Stark Phenotypes for gene: HCFC1 were changed from Mental retardation, X-linked 3 (methylmalonic acidemia and homocysteinemia, cblX type ), 309541 (3) to Methylmalonic aciduria and homocysteinemia, cblX type, MIM#309541
Prepair 1000+ v1.670 HCFC1 Zornitza Stark Publications for gene: HCFC1 were set to
Prepair 1000+ v1.669 LINS1 Cassandra Muller changed review comment from: Well established gene disease association.; to: Well established gene- condition association.
Prepair 1000+ v1.669 LINS1 Cassandra Muller reviewed gene: LINS1: Rating: ; Mode of pathogenicity: None; Publications: 34450347, 21937992, 32802957, 32499722; Phenotypes: Intellectual developmental disorder, autosomal recessive 2, 614340 (3); Mode of inheritance: None
Prepair 1000+ v1.669 SLC26A2 Lilian Downie Added comment: Comment on phenotypes: ClinGen has split this gene for 4 disease entities as per the Mondo terms. Curation of variants will need to consider the spectrum.
Prepair 1000+ v1.669 SLC26A2 Lilian Downie Phenotypes for gene: SLC26A2 were changed from Achondrogenesis Ib, 600972 (3) to diastrophic dysplasia MONDO:0009107; multiple epiphyseal dysplasia MONDO:0016648; atelosteogenesis type II MONDO:0009727; achondrogenesis type IB MONDO:0010966
Prepair 1000+ v1.668 POLR1C Zornitza Stark Marked gene: POLR1C as ready
Prepair 1000+ v1.668 POLR1C Zornitza Stark Gene: polr1c has been classified as Green List (High Evidence).
Prepair 1000+ v1.668 POLR1C Zornitza Stark Phenotypes for gene: POLR1C were changed from Treacher Collins syndrome 3, 248390 (3) to Leukodystrophy, hypomyelinating, 11 MIM#616494; Treacher Collins syndrome 3 MIM#248390
Prepair 1000+ v1.667 POLR1C Zornitza Stark Publications for gene: POLR1C were set to
Prepair 1000+ v1.666 PEX11B Zornitza Stark Marked gene: PEX11B as ready
Prepair 1000+ v1.666 PEX11B Zornitza Stark Gene: pex11b has been classified as Green List (High Evidence).
Prepair 1000+ v1.666 PEX11B Zornitza Stark Phenotypes for gene: PEX11B were changed from Peroxisome biogenesis disorder 14B, 614920 (3) to Peroxisome biogenesis disorder 14B MIM#614920
Prepair 1000+ v1.665 SLC26A2 Lilian Downie Publications for gene: SLC26A2 were set to
Prepair 1000+ v1.664 PEX11B Zornitza Stark Publications for gene: PEX11B were set to
Prepair 1000+ v1.663 PEX10 Zornitza Stark Marked gene: PEX10 as ready
Prepair 1000+ v1.663 PEX10 Zornitza Stark Gene: pex10 has been classified as Green List (High Evidence).
Prepair 1000+ v1.663 PEX10 Zornitza Stark Phenotypes for gene: PEX10 were changed from Peroxisome biogenesis disorder 6A (Zellweger), 614870 to Peroxisome biogenesis disorder 6A (Zellweger) MIM#614870; Peroxisome biogenesis disorder 6B MIM#614871
Prepair 1000+ v1.662 PEX10 Zornitza Stark Publications for gene: PEX10 were set to
Prepair 1000+ v1.661 JAGN1 Zornitza Stark Marked gene: JAGN1 as ready
Prepair 1000+ v1.661 JAGN1 Zornitza Stark Gene: jagn1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.661 JAGN1 Zornitza Stark Phenotypes for gene: JAGN1 were changed from Neutropenia, severe congenital, 6, autosomal recessive, 616022 (3) to Severe congenital neutropenia 6, MIM# 616022
Prepair 1000+ v1.660 JAGN1 Zornitza Stark Publications for gene: JAGN1 were set to
Prepair 1000+ v1.659 NUP93 Zornitza Stark Marked gene: NUP93 as ready
Prepair 1000+ v1.659 NUP93 Zornitza Stark Gene: nup93 has been classified as Green List (High Evidence).
Prepair 1000+ v1.659 NUP93 Zornitza Stark Phenotypes for gene: NUP93 were changed from Nephrotic syndrome, type 12, 616892 (3), Autosomal recessive to Nephrotic syndrome, type 12 MIM#616892
Prepair 1000+ v1.658 NUP93 Zornitza Stark Publications for gene: NUP93 were set to
Prepair 1000+ v1.657 PDE6C Lilian Downie Marked gene: PDE6C as ready
Prepair 1000+ v1.657 PDE6C Lilian Downie Added comment: Comment when marking as ready: Downgrade to red for severity
Prepair 1000+ v1.657 PDE6C Lilian Downie Gene: pde6c has been classified as Green List (High Evidence).
Prepair 1000+ v1.657 PDE6C Lilian Downie Publications for gene: PDE6C were set to
Prepair 1000+ v1.656 IL10RA Zornitza Stark Marked gene: IL10RA as ready
Prepair 1000+ v1.656 IL10RA Zornitza Stark Gene: il10ra has been classified as Green List (High Evidence).
Prepair 1000+ v1.656 IL10RA Zornitza Stark Phenotypes for gene: IL10RA were changed from Inflammatory bowel disease 28, early onset, autosomal recessive, 613148 (3) to Early onset inflammatory bowel disease 28 (MIM# 613148)
Prepair 1000+ v1.655 IL10RA Zornitza Stark Publications for gene: IL10RA were set to
Prepair 1000+ v1.654 IFT140 Zornitza Stark Marked gene: IFT140 as ready
Prepair 1000+ v1.654 IFT140 Zornitza Stark Gene: ift140 has been classified as Green List (High Evidence).
Prepair 1000+ v1.654 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia 9 with or without polydactyly, 266920 (3) to Short-rib thoracic dysplasia 9 with of without polydactyly (MIM#266920)
Prepair 1000+ v1.653 IFT140 Zornitza Stark Publications for gene: IFT140 were set to
Prepair 1000+ v1.652 NPHP4 Zornitza Stark Marked gene: NPHP4 as ready
Prepair 1000+ v1.652 NPHP4 Zornitza Stark Gene: nphp4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.652 NPHP4 Zornitza Stark Phenotypes for gene: NPHP4 were changed from Senior-Loken syndrome 4, 606996 (3) to Nephronophthisis 4 MONDO:0011752; Nephronophthisis 4 MIM#606966; Senior-Loken syndrome 4 MIM#606996
Prepair 1000+ v1.651 NPHP4 Zornitza Stark Publications for gene: NPHP4 were set to
Prepair 1000+ v1.650 NDUFAF6 Zornitza Stark Marked gene: NDUFAF6 as ready
Prepair 1000+ v1.650 NDUFAF6 Zornitza Stark Gene: ndufaf6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.650 NDUFAF6 Zornitza Stark Phenotypes for gene: NDUFAF6 were changed from Leigh syndrome due to mitochondrial complex I deficiency, 256000 (3) to Leigh syndrome MONDO:0009723; Mitochondrial complex I deficiency, nuclear type 17 MIM#618239
Prepair 1000+ v1.649 NDUFAF6 Zornitza Stark Publications for gene: NDUFAF6 were set to
Prepair 1000+ v1.648 IDS Zornitza Stark Marked gene: IDS as ready
Prepair 1000+ v1.648 IDS Zornitza Stark Gene: ids has been classified as Green List (High Evidence).
Prepair 1000+ v1.648 IDS Zornitza Stark Phenotypes for gene: IDS were changed from Mucopolysaccharidosis II, 309900 (3) to Mucopolysaccharidosis II, MIM# 309900; Hunter syndrome, MONDO:0010674
Prepair 1000+ v1.647 IDS Zornitza Stark Publications for gene: IDS were set to
Prepair 1000+ v1.646 NAGLU Zornitza Stark Marked gene: NAGLU as ready
Prepair 1000+ v1.646 NAGLU Zornitza Stark Gene: naglu has been classified as Green List (High Evidence).
Prepair 1000+ v1.646 NAGLU Zornitza Stark Phenotypes for gene: NAGLU were changed from Mucopolysaccharidosis type IIIB (Sanfilippo B), 252920 (3) to Mucopolysaccharidosis type IIIB (Sanfilippo B) MIM#252920
Prepair 1000+ v1.645 NAGLU Zornitza Stark Publications for gene: NAGLU were set to
Prepair 1000+ v1.644 KIF1A Cassandra Muller reviewed gene: KIF1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 22258533, 21487076; Phenotypes: Spastic paraplegia 30, autosomal recessive, 610357 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.644 MTM1 Zornitza Stark Marked gene: MTM1 as ready
Prepair 1000+ v1.644 MTM1 Zornitza Stark Gene: mtm1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.644 MTM1 Zornitza Stark Phenotypes for gene: MTM1 were changed from Myotubular myopathy, X-linked, 310400 (3) to Myopathy, centronuclear, X-linked MIM#310400
Prepair 1000+ v1.643 CABP4 Lilian Downie Marked gene: CABP4 as ready
Prepair 1000+ v1.643 CABP4 Lilian Downie Added comment: Comment when marking as ready: Downgrade to red for severity
Prepair 1000+ v1.643 CABP4 Lilian Downie Gene: cabp4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.643 MTM1 Zornitza Stark Publications for gene: MTM1 were set to
Genomic newborn screening: BabyScreen+ v1.116 CLN8 Melanie Marty reviewed gene: CLN8: Rating: GREEN; Mode of pathogenicity: None; Publications: 16570191, 15024724; Phenotypes: Ceroid lipofuscinosis, neuronal, 8, MIM# 600143, Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, MIM# 610003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.642 HPRT1 Zornitza Stark Marked gene: HPRT1 as ready
Prepair 1000+ v1.642 HPRT1 Zornitza Stark Gene: hprt1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.642 HPRT1 Zornitza Stark Phenotypes for gene: HPRT1 were changed from Lesch-Nyhan syndrome, 300322 (3) to Lesch-Nyhan syndrome, MIM#300322
Prepair 1000+ v1.641 HPRT1 Zornitza Stark Publications for gene: HPRT1 were set to
Prepair 1000+ v1.640 COG6 Zornitza Stark Marked gene: COG6 as ready
Prepair 1000+ v1.640 COG6 Zornitza Stark Gene: cog6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.640 COG6 Zornitza Stark Publications for gene: COG6 were set to
Prepair 1000+ v1.639 GPT2 Zornitza Stark Marked gene: GPT2 as ready
Prepair 1000+ v1.639 GPT2 Zornitza Stark Gene: gpt2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.639 GPT2 Zornitza Stark Publications for gene: GPT2 were set to
Prepair 1000+ v1.638 MTFMT Zornitza Stark Marked gene: MTFMT as ready
Prepair 1000+ v1.638 MTFMT Zornitza Stark Gene: mtfmt has been classified as Green List (High Evidence).
Prepair 1000+ v1.638 MTFMT Zornitza Stark Phenotypes for gene: MTFMT were changed from Combined oxidative phosphorylation deficiency 15, 614947 (3) to Leigh Syndrome MONDO:0009723
Prepair 1000+ v1.637 MTFMT Zornitza Stark Publications for gene: MTFMT were set to
Prepair 1000+ v1.636 GPC3 Zornitza Stark Marked gene: GPC3 as ready
Prepair 1000+ v1.636 GPC3 Zornitza Stark Gene: gpc3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.636 GPC3 Zornitza Stark Publications for gene: GPC3 were set to
Prepair 1000+ v1.635 GPR143 Lilian Downie Marked gene: GPR143 as ready
Prepair 1000+ v1.635 GPR143 Lilian Downie Added comment: Comment when marking as ready: DOWNGRADE TO RED NOT SEVERE ENOUGH
Prepair 1000+ v1.635 GPR143 Lilian Downie Gene: gpr143 has been classified as Green List (High Evidence).
Prepair 1000+ v1.635 GPR143 Lilian Downie Phenotypes for gene: GPR143 were changed from Ocular albinism, type I, Nettleship-Falls type, 300500 (3) to Nystagmus 6, congenital, X-linked, MIM#300814; Ocular albinism, type I, Nettleship-Falls type, MIM#300500
Prepair 1000+ v1.634 GPR143 Lilian Downie Publications for gene: GPR143 were set to
Prepair 1000+ v1.633 TIMM8A Andrew Coventry reviewed gene: TIMM8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 11803487, 11405816, 7643352; Phenotypes: Mohr-Tranebjaerg syndrome MIM#304700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.633 STXBP2 Andrew Coventry reviewed gene: STXBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19804848, 22451424, 20558610; Phenotypes: Hemophagocytic lymphohistiocytosis, familial, 5, with or without microvillus inclusion disease MIM#613101; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 LZTFL1 Marta Cifuentes Ochoa reviewed gene: LZTFL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22510444, 23692385, 27312011, 22072986, 38801250, 32686083, 37239474; Phenotypes: Bardet-Biedl syndrome 17 MIM#615994, MONDO:0014445; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 SMS Andrew Coventry reviewed gene: SMS: Rating: GREEN; Mode of pathogenicity: None; Publications: 30237987, 34177437, 32838743, 23805436; Phenotypes: Intellectual developmental disorder, X-linked syndromic, Snyder-Robinson type MIM#309583; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.633 SLC9A6 Andrew Coventry changed review comment from: Established gene-disease association. Childhood onset, multi-system, Angelman-like disorder.
Characterised by microcephaly, impaired ocular movements, progressive severe global developmental delay, developmental regression, hypotonia, abnormal movements, and early-onset seizures of variable types.

Female carriers may be either asymptomatic, or more mildly affected than males.
PMID 31192222: describes 20 female carriers from 9 families. Presentations included impairments in visuospatial function, attention, and executive function. Cohort features: Intellectual disability/developmental delay (20%), learning difficulties (31%), speech/language delays (30%), and attention-deficit/hyperactivity disorder (20%).
PMID 35198730: Japanese family where SLC9A6 variant in female carriers segregated with atypical parkinsonism and intellectual disability.

More than 20 unrelated families reported. Functional data including mouse model.; to: Established gene-disease association. Childhood onset, multi-system, Angelman-like disorder in affected males -
characterised by microcephaly, impaired ocular movements, progressive severe global developmental delay, developmental regression, hypotonia, abnormal movements, and early-onset seizures of variable types.

Female carriers may be either asymptomatic, or more mildly affected than males.
PMID 31192222: describes 20 female carriers from 9 families. Presentations included impairments in visuospatial function, attention, and executive function. Cohort features: Intellectual disability/developmental delay (20%), learning difficulties (31%), speech/language delays (30%), and attention-deficit/hyperactivity disorder (20%).
PMID 35198730: Japanese family where SLC9A6 variant in female carriers segregated with atypical parkinsonism and intellectual disability.

More than 20 unrelated families reported. Functional data including mouse model.
Prepair 1000+ v1.633 SLC9A6 Andrew Coventry reviewed gene: SLC9A6: Rating: GREEN; Mode of pathogenicity: None; Publications: 18342287, 19377476, 25044251, 33278113, 32569089, 31879735, 31192222, 35198730; Phenotypes: Intellectual developmental disorder, X-linked syndromic, Christianson type MIM#300243; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.633 SLC9A3 Andrew Coventry reviewed gene: SLC9A3: Rating: AMBER; Mode of pathogenicity: None; Publications: 30633106, 31276831, 26358773, 32227118, 35775128; Phenotypes: Diarrhea 8, secretory sodium, congenital MIM#616868; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 LRRC6 Marta Cifuentes Ochoa reviewed gene: LRRC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 23122589, 23891469, 32622824, 29511670, 38934611, 33577779, 39004944, 31624012; Phenotypes: Ciliary dyskinesia, primary, 19, MIM# 614935, MONDO:0013979; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 LDHB Marta Cifuentes Ochoa reviewed gene: LDHB: Rating: RED; Mode of pathogenicity: None; Publications: 6383647; Phenotypes: Lactate dehydrogenase B deficiency, MIM# 614128; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - adult onset v0.141 LAMB1 Zornitza Stark Phenotypes for gene: LAMB1 were changed from Retinal Vascular Abnormality; mild intellectual disability; white matter lesions; lower limb spasticity to Leukodystrophy, MONDO:0019046, LAMB1-related; Retinal Vascular Abnormality; mild intellectual disability; white matter lesions; lower limb spasticity
Autoinflammatory Disorders v1.58 OTULIN Zornitza Stark Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099 to Autoinflammation, panniculitis, and dermatosis syndrome, autosomal dominant, MIM# 621030; Autoinflammation, panniculitis, and dermatosis syndrome, autosomal recessive, MIM# 617099
Autoinflammatory Disorders v1.57 OTULIN Zornitza Stark edited their review of gene: OTULIN: Changed phenotypes: Autoinflammation, panniculitis, and dermatosis syndrome, autosomal dominant, MIM# 621030, Autoinflammation, panniculitis, and dermatosis syndrome, autosomal recessive, MIM# 617099
Mendeliome v1.2206 OTULIN Zornitza Stark Phenotypes for gene: OTULIN were changed from Services; Australian Genomics) Autoinflammation, panniculitis, and dermatosis syndrome, autosomal dominant, MIM# 621030; Autoinflammation, panniculitis, and dermatosis syndrome, autosomal recessive, MIM# 617099; Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, MIM# 619986 to Autoinflammation, panniculitis, and dermatosis syndrome, autosomal dominant, MIM# 621030; Autoinflammation, panniculitis, and dermatosis syndrome, autosomal recessive, MIM# 617099; Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, MIM# 619986
Mendeliome v1.2205 OTULIN Zornitza Stark Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099; Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, MIM# 619986 to Services; Australian Genomics) Autoinflammation, panniculitis, and dermatosis syndrome, autosomal dominant, MIM# 621030; Autoinflammation, panniculitis, and dermatosis syndrome, autosomal recessive, MIM# 617099; Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, MIM# 619986
Mendeliome v1.2204 OTULIN Zornitza Stark edited their review of gene: OTULIN: Changed phenotypes: Autoinflammation, panniculitis, and dermatosis syndrome, autosomal dominant, MIM# 621030, Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099, Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, MIM# 619986
Prepair 1000+ v1.633 SLC26A2 Andrew Coventry changed review comment from: Well established gene disease association causing skeletal abnormalities of varying severity.
Variants in this gene have been shown to cause achondrogenesis type 1B, atelosteogenesis type 2, diastrophic dysplasia, and recessive multiple epiphyseal dysplasia, which comprise a spectrum of phenotypes (depending on level of residual sulfate transport). Onset/features can often be observed neonatally.
Mouse models present for some phenotypes, and functional studies are present.

Homozygosity or compound heterozygosity for stop codons or transmembrane domain substitutions mostly result in achondrogenesis type IB, whereas other structural or regulatory mutations usually result in one of the less severe phenotypes (PMID: 8723100)

Unsure of phenotypes to list under condition. Clingen includes curations for:
diastrophic dysplasia MONDO:0009107
multiple epiphyseal dysplasia MONDO:0016648
atelosteogenesis type II MONDO:0009727
achondrogenesis type IB MONDO:0010966
OMIM phenotypes (6) listed above.; to: Well established gene disease association causing skeletal abnormalities of varying severity.
Variants in this gene have been shown to cause achondrogenesis type 1B, atelosteogenesis type 2, diastrophic dysplasia, and recessive multiple epiphyseal dysplasia, which comprise a spectrum of phenotypes (depending on level of residual sulfate transport). Onset/features can often be observed neonatally.
Mouse models present for some phenotypes, and functional studies are present.

Homozygosity or compound heterozygosity for stop codons or transmembrane domain substitutions mostly result in achondrogenesis type IB, whereas other structural or regulatory variants usually result in one of the less severe phenotypes (PMID: 8723100)

Unsure of phenotypes to list under condition. Clingen includes curations for:
diastrophic dysplasia MONDO:0009107
multiple epiphyseal dysplasia MONDO:0016648
atelosteogenesis type II MONDO:0009727
achondrogenesis type IB MONDO:0010966
OMIM phenotypes (6) listed above.
Prepair 1000+ v1.633 SLC26A2 Andrew Coventry changed review comment from: Well established gene disease association causing skeletal abnormalities of varying severity.
Variants in this gene have been shown to cause achondrogenesis type 1B, atelosteogenesis type 2, diastrophic dysplasia, and recessive multiple epiphyseal dysplasia, which comprise a spectrum of phenotypes (depending on level of residual sulfate transport). Onset can be neonatal.
Mouse models present for some phenotypes, and functional studies are present.

Homozygosity or compound heterozygosity for stop codons or transmembrane domain substitutions mostly result in achondrogenesis type IB, whereas other structural or regulatory mutations usually result in one of the less severe phenotypes (PMID: 8723100)

Unsure of phenotypes to list under condition. Clingen includes curations for:
diastrophic dysplasia MONDO:0009107
multiple epiphyseal dysplasia MONDO:0016648
atelosteogenesis type II MONDO:0009727
achondrogenesis type IB MONDO:0010966
OMIM phenotypes (6) listed above.; to: Well established gene disease association causing skeletal abnormalities of varying severity.
Variants in this gene have been shown to cause achondrogenesis type 1B, atelosteogenesis type 2, diastrophic dysplasia, and recessive multiple epiphyseal dysplasia, which comprise a spectrum of phenotypes (depending on level of residual sulfate transport). Onset/features can often be observed neonatally.
Mouse models present for some phenotypes, and functional studies are present.

Homozygosity or compound heterozygosity for stop codons or transmembrane domain substitutions mostly result in achondrogenesis type IB, whereas other structural or regulatory mutations usually result in one of the less severe phenotypes (PMID: 8723100)

Unsure of phenotypes to list under condition. Clingen includes curations for:
diastrophic dysplasia MONDO:0009107
multiple epiphyseal dysplasia MONDO:0016648
atelosteogenesis type II MONDO:0009727
achondrogenesis type IB MONDO:0010966
OMIM phenotypes (6) listed above.
Prepair 1000+ v1.633 SLC26A2 Andrew Coventry reviewed gene: SLC26A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301483, 20301689, 11241838, 8723100; Phenotypes: Achondrogenesis Ib MIM#600972, Atelosteogenesis, type II MIM#256050, De la Chapelle dysplasia MIM#256050, Diastrophic dysplasia MIM#222600, Diastrophic dysplasia, broad bone-platyspondylic variant MIM#222600, Epiphyseal dysplasia, multiple, 4 MIM#226900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 SLC25A22 Andrew Coventry reviewed gene: SLC25A22: Rating: GREEN; Mode of pathogenicity: None; Publications: 15592994, 19780765, 24596948, 33821742, 33342683, 31285529; Phenotypes: Developmental and epileptic encephalopathy 3 MIM#609304; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 SLC25A15 Andrew Coventry reviewed gene: SLC25A15: Rating: GREEN; Mode of pathogenicity: None; Publications: 10369256, 19242930; Phenotypes: Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome MIM#238970; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.77 PKHD1 Bryony Thompson Added comment: Comment on mode of inheritance: Biallelic is Green and Monoallelic is Amber
Renal Macrocystic Disease v0.77 PKHD1 Bryony Thompson Mode of inheritance for gene: PKHD1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Renal Macrocystic Disease v0.76 PKHD1 Bryony Thompson edited their review of gene: PKHD1: Changed publications: 39190485, 21945273
Renal Macrocystic Disease v0.76 PKHD1 Bryony Thompson changed review comment from: Emerging evidence of a monoallelic association with polycystic kidney with/without liver cysts. Enrichment of monoallelic PKHD1 LoF variants (P = 2.98e-08, OR 4.07, 95%CI 2.24-6.88) in 100K GP cystic kidney disease cohort. 50 cases, of which 22 were solved (3 ARPKD & 19 PKD1/2), 2 were partially solved (likely ARPKD), 24 were unsolved (4 with predicted deleterious missense in PKD1/2), and 2 were unascertainable.
18/1209 - with only monoallelic PKHD1 as plausible cause. Enrichment in unexplained (n=266) CyKD cases (P = 5.85e-6, OR 2.92, 95% CI 1.69-4.76).
100K GP WGS case-control analysis: cystic kidney disease cohort n=1209 vs ancestry-matched controls n=29,096. Gene-based collapsing rare variant association with SAIGE-GENE (P<2.6e-6).; to: Emerging evidence of a monoallelic association with polycystic kidney with/without liver cysts.
PMID: 39190485 - Enrichment of monoallelic PKHD1 LoF variants (P = 2.98e-08, OR 4.07, 95%CI 2.24-6.88) in 100K GP cystic kidney disease cohort. 50 cases, of which 22 were solved (3 ARPKD & 19 PKD1/2), 2 were partially solved (likely ARPKD), 24 were unsolved (4 with predicted deleterious missense in PKD1/2), and 2 were unascertainable.
18/1209 - with only monoallelic PKHD1 as plausible cause. Enrichment in unexplained (n=266) CyKD cases (P = 5.85e-6, OR 2.92, 95% CI 1.69-4.76).
100K GP WGS case-control analysis: cystic kidney disease cohort n=1209 vs ancestry-matched controls n=29,096. Gene-based collapsing rare variant association with SAIGE-GENE (P<2.6e-6).
PMID: 21945273 - study suggests carrier status for ARPKD is a predisposition to polycystic liver disease and renal involvement. Ultrasound evaluations on 110 parents from 64 independent ARPKD families (85 molecularly confirmed) identified increased medullary echogenicity in 6 (5.5%) and multiple small liver cysts in 10 parents (9%). Ages of the group ranged from 27 to 66 years (39.5 ± 6.8).
Renal Macrocystic Disease v0.76 PKHD1 Bryony Thompson reviewed gene: PKHD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 39190485; Phenotypes: Polycystic kidney disease MONDO:0020642; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Renal Macrocystic Disease v0.76 COL4A5 Bryony Thompson Marked gene: COL4A5 as ready
Renal Macrocystic Disease v0.76 COL4A5 Bryony Thompson Gene: col4a5 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.76 COL4A5 Bryony Thompson Classified gene: COL4A5 as Green List (high evidence)
Renal Macrocystic Disease v0.76 COL4A5 Bryony Thompson Gene: col4a5 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.75 COL4A5 Bryony Thompson gene: COL4A5 was added
gene: COL4A5 was added to Renal Macrocystic Disease. Sources: Literature
Mode of inheritance for gene: COL4A5 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: COL4A5 were set to 38790225; 38680391; 38514012
Phenotypes for gene: COL4A5 were set to Alport syndrome MONDO:0018965
Review for gene: COL4A5 was set to GREEN
gene: COL4A5 was marked as current diagnostic
Added comment: Multiple kidney cysts, usually with normal kidney volume, were found in 37% (26/70) of patients with a genetically confirmed AS (COL4A3-5), mostly ADAS. A few patients' kidney volumes were similar to autosomal dominant polycystic kidney disease. The prevalence of cystic kidney phenotype was significantly higher in patients with AS compared to those with IgA nephropathy (42% vs 19%; P=0.002). The cystic phenotype in the AS patients was associated with an older age and lower eGFR levels. Also, other studies reporting COL4A5 variants in individuals with a cystic kidney disease phenotype.
Sources: Literature
Prepair 1000+ v1.633 CKAP2L Karina Sandoval reviewed gene: CKAP2L: Rating: GREEN; Mode of pathogenicity: None; Publications: 25439729, 33913579, 29473684; Phenotypes: Filippi syndrome MIM#272440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.74 COL4A4 Bryony Thompson Marked gene: COL4A4 as ready
Renal Macrocystic Disease v0.74 COL4A4 Bryony Thompson Gene: col4a4 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.74 COL4A4 Bryony Thompson Classified gene: COL4A4 as Green List (high evidence)
Renal Macrocystic Disease v0.74 COL4A4 Bryony Thompson Gene: col4a4 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.73 COL4A4 Bryony Thompson gene: COL4A4 was added
gene: COL4A4 was added to Renal Macrocystic Disease. Sources: Literature
Mode of inheritance for gene: COL4A4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A4 were set to 38514012
Phenotypes for gene: COL4A4 were set to Alport syndrome MONDO:0018965
Review for gene: COL4A4 was set to GREEN
gene: COL4A4 was marked as current diagnostic
Added comment: Multiple kidney cysts, usually with normal kidney volume, were found in 37% (26/70) of patients with a genetically confirmed AS (COL4A3-5), mostly ADAS. A few patients' kidney volumes were similar to autosomal dominant polycystic kidney disease. The prevalence of cystic kidney phenotype was significantly higher in patients with AS compared to those with IgA nephropathy (42% vs 19%; P=0.002). The cystic phenotype in the AS patients was associated with an older age and lower eGFR levels.
Sources: Literature
Renal Macrocystic Disease v0.72 COL4A3 Bryony Thompson changed review comment from: PMID: 38514012 - Multiple kidney cysts, usually with normal kidney volume, were found in 37% (26/70) of patients with a genetically confirmed AS (COL4A3-5). A few patients' kidney volumes were similar to autosomal dominant polycystic kidney disease. The prevalence of cystic kidney phenotype was significantly higher in patients with AS compared to those with IgA nephropathy (42% vs 19%; P=0.002).

PMID: 39190485 - Enrichment of monoallelic COL4A3 rare variants (P = 1.26e-6, OR 3.02, 95% CI 2.10-4.22) in 100K GP cystic kidney disease cohort. Enrichment in “unsolved” (eg removing PKD1 & PKD2 diagnoses), n=308 (P = 6.83e-7, OR 4.93, 95% CI 2.77-8.11).
15/1209 - 9 are Gly-altering in the collagen triple helix domain, 1 stopgain, & 5 missense/inframe indel. 4 of the COL4A3 cases had liver cysts
100K GP WGS case-control analysis: cystic kidney disease cohort n=1209 vs ancestry-matched controls n=29,096. Gene-based collapsing rare variant association with SAIGE-GENE (P<2.6e-6).
Sources: Literature; to: PMID: 38514012 - Multiple kidney cysts, usually with normal kidney volume, were found in 37% (26/70) of patients with a genetically confirmed AS (COL4A3-5), mostly ADAS. A few patients' kidney volumes were similar to autosomal dominant polycystic kidney disease. The prevalence of cystic kidney phenotype was significantly higher in patients with AS compared to those with IgA nephropathy (42% vs 19%; P=0.002). The cystic phenotype in the AS patients was associated with an older age and lower eGFR levels.

PMID: 39190485 - Enrichment of monoallelic COL4A3 rare variants (P = 1.26e-6, OR 3.02, 95% CI 2.10-4.22) in 100K GP cystic kidney disease cohort. Enrichment in “unsolved” (eg removing PKD1 & PKD2 diagnoses), n=308 (P = 6.83e-7, OR 4.93, 95% CI 2.77-8.11).
15/1209 - 9 are Gly-altering in the collagen triple helix domain, 1 stopgain, & 5 missense/inframe indel. 4 of the COL4A3 cases had liver cysts
100K GP WGS case-control analysis: cystic kidney disease cohort n=1209 vs ancestry-matched controls n=29,096. Gene-based collapsing rare variant association with SAIGE-GENE (P<2.6e-6).
Sources: Literature
Renal Macrocystic Disease v0.72 COL4A3 Bryony Thompson Marked gene: COL4A3 as ready
Renal Macrocystic Disease v0.72 COL4A3 Bryony Thompson Gene: col4a3 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.72 COL4A3 Bryony Thompson Classified gene: COL4A3 as Green List (high evidence)
Renal Macrocystic Disease v0.72 COL4A3 Bryony Thompson Gene: col4a3 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.71 COL4A3 Bryony Thompson gene: COL4A3 was added
gene: COL4A3 was added to Renal Macrocystic Disease. Sources: Literature
Mode of inheritance for gene: COL4A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A3 were set to 39190485; 38514012
Phenotypes for gene: COL4A3 were set to Alport syndrome MONDO:0018965
Review for gene: COL4A3 was set to GREEN
gene: COL4A3 was marked as current diagnostic
Added comment: PMID: 38514012 - Multiple kidney cysts, usually with normal kidney volume, were found in 37% (26/70) of patients with a genetically confirmed AS (COL4A3-5). A few patients' kidney volumes were similar to autosomal dominant polycystic kidney disease. The prevalence of cystic kidney phenotype was significantly higher in patients with AS compared to those with IgA nephropathy (42% vs 19%; P=0.002).

PMID: 39190485 - Enrichment of monoallelic COL4A3 rare variants (P = 1.26e-6, OR 3.02, 95% CI 2.10-4.22) in 100K GP cystic kidney disease cohort. Enrichment in “unsolved” (eg removing PKD1 & PKD2 diagnoses), n=308 (P = 6.83e-7, OR 4.93, 95% CI 2.77-8.11).
15/1209 - 9 are Gly-altering in the collagen triple helix domain, 1 stopgain, & 5 missense/inframe indel. 4 of the COL4A3 cases had liver cysts
100K GP WGS case-control analysis: cystic kidney disease cohort n=1209 vs ancestry-matched controls n=29,096. Gene-based collapsing rare variant association with SAIGE-GENE (P<2.6e-6).
Sources: Literature
Prepair 1000+ v1.633 CHKB Karina Sandoval reviewed gene: CHKB: Rating: GREEN; Mode of pathogenicity: None; Publications: 21665002, 23692895, 24997086; Phenotypes: Muscular dystrophy, congenital, megaconial type, MIM#602541; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 CDK5RAP2 Karina Sandoval reviewed gene: CDK5RAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15793586, 22887808, 23995685, 23726037, 27761245, 20460369, 32677750, 32015000; Phenotypes: Microcephaly 3, primary, autosomal recessive, MIM# 604804, MONDO:0011488; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 CCNO Karina Sandoval reviewed gene: CCNO: Rating: GREEN; Mode of pathogenicity: None; Publications: 24747639, 31765523, 28801648; Phenotypes: Ciliary dyskinesia, primary, 29, MIM#615872, Primary Ciliary Dyskinesia 29, MONDO:0014378; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 CC2D2A Karina Sandoval reviewed gene: CC2D2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 18387594, 18950740, 18513680, 18950740, 19574260, 21725307, 33486889, 22241855, 27081510, 30267408; Phenotypes: COACH syndrome, MIM#216360, Joubert syndrome 9, MIM#612285, Meckel syndrome 6, MIM#612284, Retinitis pigmentosa 93, MIM# 619845; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 C3 Karina Sandoval reviewed gene: C3: Rating: GREEN; Mode of pathogenicity: None; Publications: 15781264, 1944729, 11813855, 26847111; Phenotypes: C3 deficiency MIM#613779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.272 DLAT Zornitza Stark Marked gene: DLAT as ready
Dystonia - complex v0.272 DLAT Zornitza Stark Gene: dlat has been classified as Green List (High Evidence).
Dystonia - complex v0.272 DLAT Zornitza Stark Publications for gene: DLAT were set to
Dystonia - complex v0.271 PDGFB Sangavi Sivagnanasundram changed review comment from: Disease characterised by calcifications predominantly affecting the basal ganglia of the brain however can affect other areas of the brain as well. Affected individuals report abnormal motor symptoms and psychiatric manifestations.

PMID: 36690225 - 24yr with brain calcification and neuropsychiatric symptoms. The affected individual also presented with chorea and dystonia.
A novel homozygous Ser305del variant was identified.

PMID: 34736156 - three unrelated individuals reported across different articles with brain calcification shown on brain imaging along with paroxysmal dystonia.; to: Disease characterised by calcifications predominantly affecting the basal ganglia of the brain however can affect other areas of the brain as well. Affected individuals report abnormal motor symptoms and psychiatric manifestations.

PMID: 36690225 - 24yr with brain calcification and neuropsychiatric symptoms. The affected individual also presented with chorea and dystonia.
A novel homozygous Ser305del variant was identified.

PMID: 34736156 - three unrelated individuals reported across different publications with brain calcification shown on brain imaging along with paroxysmal dystonia.
Dystonia - complex v0.271 FA2H Zornitza Stark Marked gene: FA2H as ready
Dystonia - complex v0.271 FA2H Zornitza Stark Gene: fa2h has been classified as Green List (High Evidence).
Dystonia - complex v0.271 FA2H Zornitza Stark Publications for gene: FA2H were set to
Dystonia - complex v0.270 PDGFB Sangavi Sivagnanasundram reviewed gene: PDGFB: Rating: GREEN; Mode of pathogenicity: None; Publications: 36690225, 34736156; Phenotypes: Primary familial brain calcifications, basal ganglia calcification, idiopathic, 5 MONDO:0014204; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.270 FTL Zornitza Stark Marked gene: FTL as ready
Dystonia - complex v0.270 FTL Zornitza Stark Gene: ftl has been classified as Green List (High Evidence).
Dystonia - complex v0.270 FTL Zornitza Stark Phenotypes for gene: FTL were changed from Neurodegeneration with brain iron accumulation 3 606159 to Neurodegeneration with brain iron accumulation 3, MIM# 606159
Dystonia - complex v0.269 FTL Zornitza Stark Publications for gene: FTL were set to
Dystonia - complex v0.268 GCDH Zornitza Stark Marked gene: GCDH as ready
Dystonia - complex v0.268 GCDH Zornitza Stark Gene: gcdh has been classified as Green List (High Evidence).
Dystonia - complex v0.268 GCDH Zornitza Stark Phenotypes for gene: GCDH were changed from Glutaric aciduria, type 1; Dystonia to glutaryl-CoA dehydrogenase deficiency MONDO:0009281
Dystonia - complex v0.267 GCDH Zornitza Stark Publications for gene: GCDH were set to
Dystonia - complex v0.266 GLB1 Zornitza Stark Marked gene: GLB1 as ready
Dystonia - complex v0.266 GLB1 Zornitza Stark Gene: glb1 has been classified as Green List (High Evidence).
Dystonia - complex v0.266 GLB1 Zornitza Stark Phenotypes for gene: GLB1 were changed from Infantile GM1 gangliosidosis to GM1 gangliosidosis type 3 MONDO:0009262
Dystonia - complex v0.265 GLB1 Zornitza Stark Publications for gene: GLB1 were set to
Dystonia - complex v0.264 HTRA2 Zornitza Stark reviewed gene: HTRA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 3-methylglutaconic aciduria type 8 MONDO:0044723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.264 HTRA2 Zornitza Stark Marked gene: HTRA2 as ready
Dystonia - complex v0.264 HTRA2 Zornitza Stark Gene: htra2 has been classified as Green List (High Evidence).
Dystonia - complex v0.264 HTRA2 Zornitza Stark Phenotypes for gene: HTRA2 were changed from 3-methylglutaconic aciduria, type VIII 617248 to 3-methylglutaconic aciduria type 8 MONDO:0044723
Dystonia - complex v0.263 HTRA2 Zornitza Stark Publications for gene: HTRA2 were set to
Intellectual disability syndromic and non-syndromic v1.26 RUNX1T1 Zornitza Stark Marked gene: RUNX1T1 as ready
Intellectual disability syndromic and non-syndromic v1.26 RUNX1T1 Zornitza Stark Gene: runx1t1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.26 RUNX1T1 Zornitza Stark Publications for gene: RUNX1T1 were set to PMID: 39568205, 19172993, 22644616, 31223340
Intellectual disability syndromic and non-syndromic v1.25 RUNX1T1 Zornitza Stark Phenotypes for gene: RUNX1T1 were changed from Neurodevelopmental disorder MONDO:0700092 to Neurodevelopmental disorder MONDO:0700092, RUNX1T1-related
Mendeliome v1.2204 RUNX1T1 Zornitza Stark Marked gene: RUNX1T1 as ready
Mendeliome v1.2204 RUNX1T1 Zornitza Stark Gene: runx1t1 has been classified as Green List (High Evidence).
Mendeliome v1.2204 RUNX1T1 Zornitza Stark Phenotypes for gene: RUNX1T1 were changed from Neurodevelopmental disorder MONDO:0700092 to Neurodevelopmental disorder MONDO:0700092, RUNX1T1-related
Mendeliome v1.2203 RUNX1T1 Zornitza Stark Publications for gene: RUNX1T1 were set to PMID: 39568205, 19172993, 22644616, 31223340
Mitochondrial disease v0.963 PDE12 Zornitza Stark Marked gene: PDE12 as ready
Mitochondrial disease v0.963 PDE12 Zornitza Stark Gene: pde12 has been classified as Green List (High Evidence).
Mitochondrial disease v0.963 PDE12 Zornitza Stark Phenotypes for gene: PDE12 were changed from Mitochondrial disease MONDO:0044970, PDE12-related to Mitochondrial disease MONDO:0044970, PDE12-related
Mitochondrial disease v0.962 PDE12 Zornitza Stark Phenotypes for gene: PDE12 were changed from Mitochondrial disease MONDO:0044970 to Mitochondrial disease MONDO:0044970, PDE12-related
Mitochondrial disease v0.961 PDE12 Zornitza Stark Classified gene: PDE12 as Green List (high evidence)
Mitochondrial disease v0.961 PDE12 Zornitza Stark Gene: pde12 has been classified as Green List (High Evidence).
Mendeliome v1.2202 PDE12 Zornitza Stark Marked gene: PDE12 as ready
Mendeliome v1.2202 PDE12 Zornitza Stark Gene: pde12 has been classified as Green List (High Evidence).
Mendeliome v1.2202 PDE12 Zornitza Stark Phenotypes for gene: PDE12 were changed from Mitochondrial disease MONDO:0044970 to Mitochondrial disease MONDO:0044970, PDE12-related
Dystonia - complex v0.262 NKX6-2 Zornitza Stark Marked gene: NKX6-2 as ready
Dystonia - complex v0.262 NKX6-2 Zornitza Stark Gene: nkx6-2 has been classified as Green List (High Evidence).
Dystonia - complex v0.262 NKX6-2 Zornitza Stark Phenotypes for gene: NKX6-2 were changed from Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy 617560 to Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy MIM#617560
Dystonia - complex v0.261 NKX6-2 Zornitza Stark Publications for gene: NKX6-2 were set to
Dystonia - complex v0.260 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Dystonia - complex v0.260 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Dystonia - complex v0.260 NPC1 Zornitza Stark Phenotypes for gene: NPC1 were changed from Niemann-Pick disease type C1 to Niemann-Pick disease, type C1 MONDO:0009757
Dystonia - complex v0.259 NPC1 Zornitza Stark Publications for gene: NPC1 were set to
Dystonia - complex v0.258 NPC2 Zornitza Stark Marked gene: NPC2 as ready
Dystonia - complex v0.258 NPC2 Zornitza Stark Gene: npc2 has been classified as Green List (High Evidence).
Dystonia - complex v0.258 NPC2 Zornitza Stark Phenotypes for gene: NPC2 were changed from Niemann-Pick disease type C2; Dystonia to Niemann-Pick disease, type C2 MONDO:0011873; Dystonia
Dystonia - complex v0.257 NPC2 Zornitza Stark Publications for gene: NPC2 were set to
Dystonia - complex v0.256 PANK2 Zornitza Stark Marked gene: PANK2 as ready
Dystonia - complex v0.256 PANK2 Zornitza Stark Gene: pank2 has been classified as Green List (High Evidence).
Dystonia - complex v0.256 PANK2 Zornitza Stark Phenotypes for gene: PANK2 were changed from pantothenate kinase-associated neurodegeneration; Dystonia to pantothenate kinase-associated neurodegeneration MONDO:0009319; Dystonia
Dystonia - complex v0.255 PANK2 Zornitza Stark Publications for gene: PANK2 were set to
Dystonia - complex v0.254 PANK2 Sangavi Sivagnanasundram changed review comment from: Established gene-disease association with affected individuals presenting with generalised or lower limb dystonia.; to: Established gene-disease association with affected individuals presenting with generalised or lower limb dystonia along with other psychiatric/behavioural problems.
Dystonia - complex v0.254 PANK2 Sangavi Sivagnanasundram reviewed gene: PANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15911822; Phenotypes: pantothenate kinase-associated neurodegeneration MONDO:0009319; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.254 NPC2 Sangavi Sivagnanasundram reviewed gene: NPC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34993563, 17470133; Phenotypes: Niemann-Pick disease, type C2 MONDO:0011873; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.254 NPC1 Sangavi Sivagnanasundram reviewed gene: NPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12555942, 20301473; Phenotypes: Niemann-Pick disease, type C1 MONDO:0009757; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.254 NKX6-2 Sangavi Sivagnanasundram reviewed gene: NKX6-2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30285346, 28575651, 28969374; Phenotypes: spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy MONDO:0033043; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2201 PDE12 Chirag Patel Classified gene: PDE12 as Green List (high evidence)
Mendeliome v1.2201 PDE12 Chirag Patel Gene: pde12 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.113 CHUK Chirag Patel Classified gene: CHUK as Green List (high evidence)
Combined Immunodeficiency v1.113 CHUK Chirag Patel Gene: chuk has been classified as Green List (High Evidence).
Mendeliome v1.2200 CHUK Chirag Patel Classified gene: CHUK as Green List (high evidence)
Mendeliome v1.2200 CHUK Chirag Patel Gene: chuk has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.112 CHUK Chirag Patel reviewed gene: CHUK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34533979; Phenotypes: Combined immunodeficiency, MONDO:0015131, CHUK-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2199 CHUK Chirag Patel reviewed gene: CHUK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34533979; Phenotypes: Combined immunodeficiency, MONDO:0015131, CHUK-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2199 PDE12 Chirag Patel gene: PDE12 was added
gene: PDE12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDE12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE12 were set to PMID: 39567835
Phenotypes for gene: PDE12 were set to Mitochondrial disease MONDO:0044970
Review for gene: PDE12 was set to GREEN
Added comment: 3 families (2 consanguineous) with 5 affected individuals with early onset mitochondrial disease presentation (3 liveborn, 2 intrauterine death).
-Family 1: 1 x infant death @3mths (no clinical information), 1 x 7yr old with neonatal respiratory and lactic acidosis, developmental delay, and mitochondrial respiratory chain deficiencies, and marked cytochrome c oxidase (COX) deficiency in muscle.
-Family 2: 1 x neonatal death @2days with metabolic acidosis and lactic acidosis, respiratory failure, lissencephaly, dysgenesis of the corpus callosum and extensive periventricular and subcortical cysts. Normal pyruvate dehydrogenase complex and electron
transfer chain activities in fibroblasts.
-Family 3: 2 x fetuses (13wks and 22wks) with increase nuchal translucency and reduced fetal movements. One had intra-uterine growth retardation, hydrops and cystic hygroma. The other had permanent flexion contractures of four limbs). Western blotting in fetal skeletal muscle showed absent respiratory chain complexes (I, IV, and V).

WES in all 3 families identified 3 different homozygous missense variants in PDE12 gene (p.Tyr155Cys, p.Gly372Glu, and p.Arg41Pro). All variants segregated with disease, were rare in gnomAD, and in silico pathogenicity prediction tools pointed towards a high likelihood of pathogenicity.

PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs. Patient-derived primary fibroblasts demonstrate diminished steady-state levels of PDE12 protein, whilst mitochondrial poly(A)-tail RNA sequencing revealed an accumulation of spuriously polyadenylated mitochondrial RNA, consistent with perturbed function of PDE12 protein.
Sources: Literature
Mendeliome v1.2198 RUNX1T1 Chirag Patel Classified gene: RUNX1T1 as Green List (high evidence)
Mendeliome v1.2198 RUNX1T1 Chirag Patel Gene: runx1t1 has been classified as Green List (High Evidence).
Mendeliome v1.2197 RUNX1T1 Chirag Patel gene: RUNX1T1 was added
gene: RUNX1T1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RUNX1T1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RUNX1T1 were set to PMID: 39568205, 19172993, 22644616, 31223340
Phenotypes for gene: RUNX1T1 were set to Neurodevelopmental disorder MONDO:0700092
Review for gene: RUNX1T1 was set to GREEN
Added comment: RUNX1T1 encodes a transcription regulator for hematopoietic genes and is well-known for its involvement in hematologic malignancies. Germline RUNX1T1 variants may also play a role in human congenital neurodevelopmental disorders.

PMID: 39568205
3 unrelated individuals with developmental delay, learning disability, ASD, ADHD, and dysmorphism (1 x heart defects). Trio WES identified de novo variants in RUNX1T1 gene (1 x nonsense variant in 5' region [p.Gln36Ter], 2 x missense variants in C-terminus [p.Gly412Arg and p.His521Tyr]).

PMID: 19172993
1 individual with mild-moderate ID and congenital heart disease, and chromosome t(5;8)(q32;q21.3) translocation. Molecular characterization revealed that one of the break points was within the RUNX1T1 gene. Analysis of RUNX1T1 expression in human embryonic and fetal tissues suggests a role of RUNX1T1 in brain and heart development.

PMID: 22644616
1 individual with mild ID and dysmorphism, and de novo deletion exons 3-7 in RUNX1T1.

PMID: 31223340
1 individual with ID, anaemia, atrial septal defect, dysmorphism, and seizures. Found to have a 2.1 Mb deletion at 8q21.3q22.1 involving entire RUNX1T1 gene (and 2 adjacent genes - SLC26A7 and TRIQK), and a benign familial 4.3 Mb duplication at 1p22.1p21.3 (present in unaffected healthy brother).
Sources: Literature
Dystonia - complex v0.254 HTRA2 Sangavi Sivagnanasundram reviewed gene: HTRA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27208207, 27696117, 30114719; Phenotypes: 3-methylglutaconic aciduria type 8 MONDO:0044723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.24 RUNX1T1 Chirag Patel Classified gene: RUNX1T1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.24 RUNX1T1 Chirag Patel Gene: runx1t1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.23 RUNX1T1 Chirag Patel gene: RUNX1T1 was added
gene: RUNX1T1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RUNX1T1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RUNX1T1 were set to PMID: 39568205, 19172993, 22644616, 31223340
Phenotypes for gene: RUNX1T1 were set to Neurodevelopmental disorder MONDO:0700092
Review for gene: RUNX1T1 was set to GREEN
Added comment: RUNX1T1 encodes a transcription regulator for hematopoietic genes and is well-known for its involvement in hematologic malignancies. Germline RUNX1T1 variants may also play a role in human congenital neurodevelopmental disorders.

PMID: 39568205
3 unrelated individuals with developmental delay, learning disability, ASD, ADHD, and dysmorphism (1 x heart defects). Trio WES identified de novo variants in RUNX1T1 gene (1 x nonsense variant in 5' region [p.Gln36Ter], 2 x missense variants in C-terminus [p.Gly412Arg and p.His521Tyr]).

PMID: 19172993
1 individual with mild-moderate ID and congenital heart disease, and chromosome t(5;8)(q32;q21.3) translocation. Molecular characterization revealed that one of the break points was within the RUNX1T1 gene. Analysis of RUNX1T1 expression in human embryonic and fetal tissues suggests a role of RUNX1T1 in brain and heart development.

PMID: 22644616
1 individual with mild ID and dysmorphism, and de novo deletion exons 3-7 in RUNX1T1.

PMID: 31223340
1 individual with ID, anaemia, atrial septal defect, dysmorphism, and seizures. Found to have a 2.1 Mb deletion at 8q21.3q22.1 involving entire RUNX1T1 gene (and 2 adjacent genes - SLC26A7 and TRIQK), and a benign familial 4.3 Mb duplication at 1p22.1p21.3 (present in unaffected healthy brother).
Sources: Literature
Mitochondrial disease v0.959 PDE12 Chirag Patel gene: PDE12 was added
gene: PDE12 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: PDE12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE12 were set to PMID: 39567835
Phenotypes for gene: PDE12 were set to Mitochondrial disease MONDO:0044970
Review for gene: PDE12 was set to GREEN
Added comment: 3 families (2 consanguineous) with 5 affected individuals with early onset mitochondrial disease presentation (3 liveborn, 2 intrauterine death).
-Family 1: 1 x infant death @3mths (no clinical information), 1 x 7yr old with neonatal respiratory and lactic acidosis, developmental delay, and mitochondrial respiratory chain deficiencies, and marked cytochrome c oxidase (COX) deficiency in muscle.
-Family 2: 1 x neonatal death @2days with metabolic acidosis and lactic acidosis, respiratory failure, lissencephaly, dysgenesis of the corpus callosum and extensive periventricular and subcortical cysts. Normal pyruvate dehydrogenase complex and electron
transfer chain activities in fibroblasts.
-Family 3: 2 x fetuses (13wks and 22wks) with increase nuchal translucency and reduced fetal movements. One had intra-uterine growth retardation, hydrops and cystic hygroma. The other had permanent flexion contractures of four limbs). Western blotting in fetal skeletal muscle showed absent respiratory chain complexes (I, IV, and V).

WES in all 3 families identified 3 different homozygous missense variants in PDE12 gene (p.Tyr155Cys, p.Gly372Glu, and p.Arg41Pro). All variants segregated with disease, were rare in gnomAD, and in silico pathogenicity prediction tools pointed towards a high likelihood of pathogenicity.

PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs. Patient-derived primary fibroblasts demonstrate diminished steady-state levels of PDE12 protein, whilst mitochondrial poly(A)-tail RNA sequencing revealed an accumulation of spuriously polyadenylated mitochondrial RNA, consistent with perturbed function of PDE12 protein.
Sources: Literature
Mitochondrial disease v0.959 PDE12 Chirag Patel gene: PDE12 was added
gene: PDE12 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: PDE12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE12 were set to PMID: 39567835
Phenotypes for gene: PDE12 were set to Mitochondrial disease MONDO:0044970
Review for gene: PDE12 was set to GREEN
Added comment: 3 families (2 consanguineous) with 5 affected individuals with early onset mitochondrial disease presentation (3 liveborn, 2 intrauterine death).
-Family 1: 1 x infant death @3mths (no clinical information), 1 x 7yr old with neonatal respiratory and lactic acidosis, developmental delay, and mitochondrial respiratory chain deficiencies, and marked cytochrome c oxidase (COX) deficiency in muscle.
-Family 2: 1 x neonatal death @2days with metabolic acidosis and lactic acidosis, respiratory failure, lissencephaly, dysgenesis of the corpus callosum and extensive periventricular and subcortical cysts. Normal pyruvate dehydrogenase complex and electron
transfer chain activities in fibroblasts.
-Family 3: 2 x fetuses (13wks and 22wks) with increase nuchal translucency and reduced fetal movements. One had intra-uterine growth retardation, hydrops and cystic hygroma. The other had permanent flexion contractures of four limbs). Western blotting in fetal skeletal muscle showed absent respiratory chain complexes (I, IV, and V).

WES in all 3 families identified 3 different homozygous missense variants in PDE12 gene (p.Tyr155Cys, p.Gly372Glu, and p.Arg41Pro). All variants segregated with disease, were rare in gnomAD, and in silico pathogenicity prediction tools pointed towards a high likelihood of pathogenicity.

PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs. Patient-derived primary fibroblasts demonstrate diminished steady-state levels of PDE12 protein, whilst mitochondrial poly(A)-tail RNA sequencing revealed an accumulation of spuriously polyadenylated mitochondrial RNA, consistent with perturbed function of PDE12 protein.
Sources: Literature
Dystonia - complex v0.254 GLB1 Sangavi Sivagnanasundram reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24156116, 35937492, 34514040, 1353343; Phenotypes: GM1 gangliosidosis type 3 MONDO:0009262; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 CENPJ Michelle Torres reviewed gene: CENPJ: Rating: GREEN; Mode of pathogenicity: None; Publications: 36334884; Phenotypes: Microcephaly 6, primary MIM#608393, Seckel syndrome 4 MIM#613676; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 CDH11 Michelle Torres reviewed gene: CDH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 29271567; Phenotypes: Elsahy-Waters syndrome MIM#211380; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.254 GCDH Sangavi Sivagnanasundram reviewed gene: GCDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 32777384, 21912879, 31536184; Phenotypes: glutaryl-CoA dehydrogenase deficiency MONDO:0009281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 BBS7 Karina Sandoval reviewed gene: BBS7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12567324, 21937992, 19797195; Phenotypes: Bardet-Biedl syndrome 7, MIM# 615984, MONDO:0014435; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.254 FTL Sangavi Sivagnanasundram reviewed gene: FTL: Rating: GREEN; Mode of pathogenicity: None; Publications: 11438811, 15099026, 12746423, 18413574; Phenotypes: neuroferritinopathy MONDO:0011638; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.254 FA2H Sangavi Sivagnanasundram reviewed gene: FA2H: Rating: GREEN; Mode of pathogenicity: None; Publications: 19068277, 20104589, 20853438, 31135052; Phenotypes: hereditary spastic paraplegia 35 MONDO:0012866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.254 DLAT Sangavi Sivagnanasundram reviewed gene: DLAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 39007626, 20022530, 16049940; Phenotypes: pyruvate dehydrogenase E2 deficiency MONDO:0009502; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2196 CAPZA2 Zornitza Stark Publications for gene: CAPZA2 were set to 32338762
Mendeliome v1.2195 CAPZA2 Zornitza Stark Classified gene: CAPZA2 as Green List (high evidence)
Mendeliome v1.2195 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.22 CAPZA2 Zornitza Stark Phenotypes for gene: CAPZA2 were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, CAPZA2-related
Intellectual disability syndromic and non-syndromic v1.21 CAPZA2 Zornitza Stark Publications for gene: CAPZA2 were set to 32338762
Intellectual disability syndromic and non-syndromic v1.20 CAPZA2 Zornitza Stark Classified gene: CAPZA2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.20 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.56 COL4A1 Zornitza Stark Marked gene: COL4A1 as ready
Spontaneous coronary artery dissection v0.56 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.56 COL4A1 Zornitza Stark Phenotypes for gene: COL4A1 were changed from CORONARY ARTERY DISSECTION, SPONTANEOUS MIM#122455 to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, MIM#611773
Spontaneous coronary artery dissection v0.55 COL4A1 Zornitza Stark Classified gene: COL4A1 as Green List (high evidence)
Spontaneous coronary artery dissection v0.55 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.54 COL4A1 Zornitza Stark reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, MIM#611773; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cholestasis v1.0 Zornitza Stark promoted panel to version 1.0
Prepair 1000+ v1.633 SLC24A5 Andrew Coventry reviewed gene: SLC24A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23364476, 23985994, 26491832; Phenotypes: Albinism, oculocutaneous, type VI MIM#113750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 SLC22A5 Andrew Coventry reviewed gene: SLC22A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 9916797, 10072434, 10051646, 10425211, 10480371, 10679939, 9837751, 23379544, 31399326, 25778941, 17884651, 22420015; Phenotypes: Carnitine deficiency, systemic primary, MIM# 212140, MONDO:0008919; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 SLC16A1 Andrew Coventry reviewed gene: SLC16A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25390740, 20301549, 36082648, 35729663; Phenotypes: Monocarboxylate transporter 1 deficiency MIM#616095; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Prepair 1000+ v1.633 SH2D1A Andrew Coventry reviewed gene: SH2D1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 6306053, 9771704, 11049992, 20301580; Phenotypes: Lymphoproliferative syndrome, X-linked, 1 MIM#308240; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.633 SGSH Andrew Coventry reviewed gene: SGSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 7493035, 9158154, 9401012, 9554748; Phenotypes: Mucopolysaccharidosis type IIIA (Sanfilippo A), MIM# 252900, MONDO:0009655; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 SCO2 Andrew Coventry reviewed gene: SCO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15210538, 18924171, 22231385, 10545952, 10749987; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 2 MIM#604377; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 RSPH9 Andrew Coventry reviewed gene: RSPH9: Rating: GREEN; Mode of pathogenicity: None; Publications: 25789548, 22384920, 23993197, 19200523, 27626380; Phenotypes: Ciliary dyskinesia, primary, 12 MIM#612650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 RPL10 Andrew Coventry reviewed gene: RPL10: Rating: GREEN; Mode of pathogenicity: None; Publications: 25316788, 25846674, 26290468, 29066376, 35876338; Phenotypes: Intellectual developmental disorder, X-linked syndromic 35 MIM#300998; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.633 RAB3GAP2 Andrew Coventry reviewed gene: RAB3GAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16532399, 20967465, 23420520, 32740904, 32376645, 24891604; Phenotypes: Warburg micro syndrome MONDO:0016649; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 QARS Andrew Coventry reviewed gene: QARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 24656866, 27717089, 31618474, 25471517, 25432320, 24656866, 28620870, 25041233, 32042906; Phenotypes: Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy MIM#615760; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Spontaneous coronary artery dissection v0.54 COL4A1 Stephanie Hesselson gene: COL4A1 was added
gene: COL4A1 was added to Spontaneous coronary artery dissection. Sources: Other
Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A1 were set to PMID: 35583931, 35234813, 37248441
Phenotypes for gene: COL4A1 were set to CORONARY ARTERY DISSECTION, SPONTANEOUS MIM#122455
Penetrance for gene: COL4A1 were set to unknown
Review for gene: COL4A1 was set to GREEN
Added comment: It is possible that rare and common variants in COL4A1 contribute to SCAD risk.

5 individuals with SCAD have been found to carry a LP variant:

PMID: 35234813 reports 3x SCAD participants with a LP variant in COL4A1 p.Gly1484Arg, p.Gly495Arg, and p.Gly160Asp

PMID 35583931 reports 2x SCAD participants with LP variants in COL4A1 p.Gly1198Arg and p.Ala1626Gly

In a meta-GWAS for SCAD, the COL4A1/COL4A2 locus accounted for the second largest proportion of heritability for SCAD in the dataset. It contained two independent GWAS signals at this locus. (PMID 37248441)
Sources: Other
Prepair 1000+ v1.633 PRF1 Andrew Coventry reviewed gene: PRF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19595804, 26199792, 30070073, 19487666, 26184781, 10583959, 19487666; Phenotypes: Hemophagocytic lymphohistiocytosis, familial, 2 MIM#603553; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 POMT1 Andrew Coventry reviewed gene: POMT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15792865, 22549409, 31311558, 20065251, 25088310, 19299310, 19299310; Phenotypes: Myopathy caused by variation in POMT1 MONDO:0700070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 IMPG2 Andrew Coventry changed review comment from: Retinitis pigmentosa 56 - is an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. Features include night blindness, progressive visual loss, macular retinal pigment epithelium (RPE) mottling / atrophy, decreased ERG amplitudes (affecting rods more severely than cones), colour vision defect, peripheral visual field loss, central scotoma, retinal blood vessel attenuation, and/or optic disc pallor. These features are largely distinct from the vitelliform macular dystrophy phenotype (MIM#616152).
- biallelic loss-of-function consistently associates with retinitis pigmentosa, while monoallelic loss-of-function consistently associates with vitelliform macular dystrophy.
PMID: 20673862 - 2 families each with 3 affected sibs. Additional 10 index cases identified.
- Those with nonsenses showed early-onset RP, patient with missense variants had a milder maculopathy phenotype.

Further studies and evidence:
Mouse models present exhibiting RP phenotype. (PMID: 38217426 - indicates missense variants had minimal retinal pathology in mice)
Functional study present using patient derived iPS (PMID: 36206764) - confirmed LoF due to lack of expression or lack os post-translational modifications - destabilising outer segments of rods and cones.

ClinGen - curation definitive for AR RP phenotype in association with gene IMPG2, with 10 suspected disease-causing variants scored as part of their curation (five nonsense, one frameshift, one canonical splice site disruption, one in-frame exon deletion, and two missense). Variants curated were in 8 probands (PMID: 24876279, PMID: 20673862, PMID: 31264916, PMID: 34990796).

RP genes already screened for by 1000+, consider above adequate evidence to upgrade to green status for inclusion in v2.; to: Retinitis pigmentosa 56 - is an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. Features include night blindness, progressive visual loss, macular retinal pigment epithelium (RPE) mottling / atrophy, decreased ERG amplitudes (affecting rods more severely than cones), colour vision defect, peripheral visual field loss, central scotoma, retinal blood vessel attenuation, and/or optic disc pallor. These features are largely distinct from the vitelliform macular dystrophy phenotype (MIM#616152).
- biallelic loss-of-function consistently associates with retinitis pigmentosa, while monoallelic loss-of-function consistently associates with vitelliform macular dystrophy.
PMID: 20673862 - 2 families each with 3 affected sibs. Additional 10 index cases identified.
- Those with nonsenses showed early-onset RP, patient with missense variants had a milder maculopathy phenotype.

Age of onset:
PMID 34990796 - 16yo had night blindness and photophobia. Had 22y.o. sibling that was severely affected. Age of initial onset of visual symptoms said to be ~2-4 years of age.
PMID 31264916 - 8y.o. with photophobia and myopia, 4y.o. with light sensitivity. 17yo with poor vision 'since childhood', 17yo with poor vision since birth and poor night vision, 45yo with poor night vision - starting at 6yo and progressing loss of central vision.
PMID 24876279 - age of onset of patients studied: 1, 5, 6, 1, 2, 3, 2, 3, 1, 4, 1, 2, 1, 2, 6, 1, 1. Symptoms variable, including night blindness, decrease of visual acuity, loss of visual field.

Further studies and evidence:
Mouse models present exhibiting RP phenotype. (PMID: 38217426 - indicates missense variants had minimal retinal pathology in mice)
Functional study present using patient derived iPS (PMID: 36206764) - confirmed LoF due to lack of expression or lack os post-translational modifications - destabilising outer segments of rods and cones.

ClinGen - curation definitive for AR RP phenotype in association with gene IMPG2, with 10 suspected disease-causing variants scored as part of their curation (five nonsense, one frameshift, one canonical splice site disruption, one in-frame exon deletion, and two missense). Variants curated were in 8 probands (PMID: 24876279, PMID: 20673862, PMID: 31264916, PMID: 34990796).

RP genes already screened for by 1000+, consider above adequate evidence to upgrade to green status for inclusion in v2.
Intellectual disability syndromic and non-syndromic v1.19 CAPZA2 Chris Ciotta reviewed gene: CAPZA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32338762, 38374166, 35856264; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CAPZA2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.2194 CAPZA2 Chris Ciotta reviewed gene: CAPZA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32338762, 38374166, 35856264; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CAPZA2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v1.85 USP25 Zornitza Stark Marked gene: USP25 as ready
Genetic Epilepsy v1.85 USP25 Zornitza Stark Gene: usp25 has been classified as Green List (High Evidence).
Motor Neurone Disease v1.27 SQSTM1 Bryony Thompson Marked gene: SQSTM1 as ready
Motor Neurone Disease v1.27 SQSTM1 Bryony Thompson Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v1.27 SQSTM1 Bryony Thompson Phenotypes for gene: SQSTM1 were changed from Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 MONDO:0014640 to Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 MONDO:0014640
Motor Neurone Disease v1.26 SQSTM1 Bryony Thompson Phenotypes for gene: SQSTM1 were changed from to Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 MONDO:0014640
Motor Neurone Disease v1.25 SQSTM1 Bryony Thompson Classified gene: SQSTM1 as Amber List (moderate evidence)
Motor Neurone Disease v1.25 SQSTM1 Bryony Thompson Added comment: Comment on list classification: ALS Spectrum Disorders GCEP classify the gene-disease association as Moderate, due to the lack of segregation evidence to support the GDA - https://search.clinicalgenome.org/CCID:006272
Motor Neurone Disease v1.25 SQSTM1 Bryony Thompson Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.85 CCT6A Ain Roesley Classified gene: CCT6A as Amber List (moderate evidence)
Genetic Epilepsy v1.85 CCT6A Ain Roesley Gene: cct6a has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.84 CCT6A Ain Roesley Classified gene: CCT6A as Amber List (moderate evidence)
Genetic Epilepsy v1.84 CCT6A Ain Roesley Gene: cct6a has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.83 CCT6A Ain Roesley Marked gene: CCT6A as ready
Genetic Epilepsy v1.83 CCT6A Ain Roesley Gene: cct6a has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.19 CCT6A Ain Roesley Classified gene: CCT6A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.19 CCT6A Ain Roesley Gene: cct6a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.18 CCT6A Ain Roesley Marked gene: CCT6A as ready
Intellectual disability syndromic and non-syndromic v1.18 CCT6A Ain Roesley Gene: cct6a has been classified as Red List (Low Evidence).
Mendeliome v1.2194 CCT6A Ain Roesley Marked gene: CCT6A as ready
Mendeliome v1.2194 CCT6A Ain Roesley Gene: cct6a has been classified as Green List (High Evidence).
Mendeliome v1.2194 CCT6A Ain Roesley Classified gene: CCT6A as Green List (high evidence)
Mendeliome v1.2194 CCT6A Ain Roesley Gene: cct6a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.18 CCT6A Ain Roesley gene: CCT6A was added
gene: CCT6A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CCT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCT6A were set to 39480921
Phenotypes for gene: CCT6A were set to neurodevelopmental disorder MONDO:0700092, CCT6A-related
Penetrance for gene: CCT6A were set to Complete
Review for gene: CCT6A was set to GREEN
gene: CCT6A was marked as current diagnostic
Added comment: previously known as CCT6

5x individuals including 4x de novo
3x PTCS + 1x +5C>G + 1x missense

4/5 DD/ID
2/5 visual impairment
2/5 seizures
Sources: Literature
Genetic Epilepsy v1.83 CCT6A Ain Roesley gene: CCT6A was added
gene: CCT6A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CCT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCT6A were set to 39480921
Phenotypes for gene: CCT6A were set to neurodevelopmental disorder MONDO:0700092, CCT6A-related
Penetrance for gene: CCT6A were set to Complete
Review for gene: CCT6A was set to AMBER
gene: CCT6A was marked as current diagnostic
Added comment: previously known as CCT6

5x individuals including 4x de novo
3x PTCS + 1x +5C>G + 1x missense

4/5 DD/ID
2/5 visual impairment
2/5 seizures
Sources: Literature
Mendeliome v1.2193 CCT6A Ain Roesley gene: CCT6A was added
gene: CCT6A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCT6A were set to 39480921
Phenotypes for gene: CCT6A were set to neurodevelopmental disorder MONDO:0700092, CCT6A-related
Penetrance for gene: CCT6A were set to Complete
Review for gene: CCT6A was set to GREEN
gene: CCT6A was marked as current diagnostic
Added comment: previously known as CCT6

5x individuals including 4x de novo
3x PTCS + 1x +5C>G + 1x missense

4/5 DD/ID
2/5 visual impairment
2/5 seizures
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.17 TCP1 Ain Roesley Marked gene: TCP1 as ready
Intellectual disability syndromic and non-syndromic v1.17 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.17 TCP1 Ain Roesley Classified gene: TCP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.17 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.17 TCP1 Ain Roesley Classified gene: TCP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.17 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.194 TCP1 Ain Roesley Marked gene: TCP1 as ready
Polymicrogyria and Schizencephaly v0.194 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.194 TCP1 Ain Roesley Classified gene: TCP1 as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.194 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Mendeliome v1.2192 TCP1 Ain Roesley Marked gene: TCP1 as ready
Mendeliome v1.2192 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Mendeliome v1.2192 TCP1 Ain Roesley Marked gene: TCP1 as ready
Mendeliome v1.2192 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.82 TCP1 Ain Roesley Marked gene: TCP1 as ready
Genetic Epilepsy v1.82 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.82 TCP1 Ain Roesley Classified gene: TCP1 as Green List (high evidence)
Genetic Epilepsy v1.82 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.193 TCP1 Ain Roesley gene: TCP1 was added
gene: TCP1 was added to Polymicrogyria and Schizencephaly. Sources: Literature
Mode of inheritance for gene: TCP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TCP1 were set to 39480921
Phenotypes for gene: TCP1 were set to neurodevelopmental disorder MONDO:0700092, TCP1-related
Penetrance for gene: TCP1 were set to Complete
Review for gene: TCP1 was set to GREEN
gene: TCP1 was marked as current diagnostic
Added comment: previously known as CCT1

8x individuals including 5x de novo
6x PTCs + 2x missense

6/8 DD/ID
2/8 visual impairment
6/8 seizures
6/8 polymicrogyria + 1x Ventriculomegaly, white matter hyperintensities
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.16 TCP1 Ain Roesley gene: TCP1 was added
gene: TCP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TCP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TCP1 were set to 39480921
Phenotypes for gene: TCP1 were set to neurodevelopmental disorder MONDO:0700092, TCP1-related
Penetrance for gene: TCP1 were set to Complete
Review for gene: TCP1 was set to GREEN
gene: TCP1 was marked as current diagnostic
Added comment: previously known as CCT1

8x individuals including 5x de novo
6x PTCs + 2x missense

6/8 DD/ID
2/8 visual impairment
6/8 seizures
6/8 polymicrogyria + 1x Ventriculomegaly, white matter hyperintensities
Sources: Literature
Mendeliome v1.2192 TCP1 Ain Roesley Classified gene: TCP1 as Green List (high evidence)
Mendeliome v1.2192 TCP1 Ain Roesley Gene: tcp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.81 TCP1 Ain Roesley gene: TCP1 was added
gene: TCP1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TCP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TCP1 were set to 39480921
Phenotypes for gene: TCP1 were set to neurodevelopmental disorder MONDO:0700092, TCP1-related
Penetrance for gene: TCP1 were set to Complete
Review for gene: TCP1 was set to GREEN
gene: TCP1 was marked as current diagnostic
Added comment: previously known as CCT1

8x individuals including 5x de novo
6x PTCs + 2x missense

6/8 DD/ID
2/8 visual impairment
6/8 seizures
6/8 polymicrogyria + 1x Ventriculomegaly, white matter hyperintensities
Sources: Literature
Mendeliome v1.2191 TCP1 Ain Roesley gene: TCP1 was added
gene: TCP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TCP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TCP1 were set to 39480921
Phenotypes for gene: TCP1 were set to neurodevelopmental disorder MONDO:0700092, TCP1-related
Penetrance for gene: TCP1 were set to Complete
Review for gene: TCP1 was set to GREEN
gene: TCP1 was marked as current diagnostic
Added comment: previously known as CCT1

8x individuals including 5x de novo
6x PTCs + 2x missense

6/8 DD/ID
2/8 visual impairment
6/8 seizures
6/8 polymicrogyria + 1x Ventriculomegaly, white matter hyperintensities
Sources: Literature
Genetic Epilepsy v1.80 CCT3 Ain Roesley Marked gene: CCT3 as ready
Genetic Epilepsy v1.80 CCT3 Ain Roesley Gene: cct3 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.80 CCT3 Ain Roesley Classified gene: CCT3 as Green List (high evidence)
Genetic Epilepsy v1.80 CCT3 Ain Roesley Gene: cct3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.15 CCT3 Ain Roesley Classified gene: CCT3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.15 CCT3 Ain Roesley Gene: cct3 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.79 CCT3 Ain Roesley gene: CCT3 was added
gene: CCT3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CCT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCT3 were set to 39480921
Phenotypes for gene: CCT3 were set to neurodevelopmental disorder MONDO:0700092, CCT3-related
Penetrance for gene: CCT3 were set to Complete
Review for gene: CCT3 was set to GREEN
gene: CCT3 was marked as current diagnostic
Added comment: 4x de novo - 3x PTCs and 1x missense

overlapping phenotypes:
4/4 ID/DD
3/4 visual impairment
2/4 seizures
4/4 Hypomyelination of white matter
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.15 CCT3 Ain Roesley Marked gene: CCT3 as ready
Intellectual disability syndromic and non-syndromic v1.15 CCT3 Ain Roesley Gene: cct3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.15 CCT3 Ain Roesley Classified gene: CCT3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.15 CCT3 Ain Roesley Gene: cct3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.14 CCT3 Ain Roesley gene: CCT3 was added
gene: CCT3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CCT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCT3 were set to 39480921
Phenotypes for gene: CCT3 were set to neurodevelopmental disorder MONDO:0700092, CCT3-related
Penetrance for gene: CCT3 were set to Complete
Review for gene: CCT3 was set to GREEN
gene: CCT3 was marked as current diagnostic
Added comment: 4x de novo - 3x PTCs and 1x missense

overlapping phenotypes:
4/4 ID/DD
3/4 visual impairment
2/4 seizures
4/4 Hypomyelination of white matter
Sources: Literature
Mendeliome v1.2190 CCT3 Ain Roesley Marked gene: CCT3 as ready
Mendeliome v1.2190 CCT3 Ain Roesley Gene: cct3 has been classified as Green List (High Evidence).
Mendeliome v1.2190 CCT3 Ain Roesley Marked gene: CCT3 as ready
Mendeliome v1.2190 CCT3 Ain Roesley Gene: cct3 has been classified as Green List (High Evidence).
Mendeliome v1.2190 CCT3 Ain Roesley Phenotypes for gene: CCT3 were changed from to neurodevelopmental disorder MONDO:0700092, CCT3-related
Mendeliome v1.2189 CCT3 Ain Roesley Classified gene: CCT3 as Green List (high evidence)
Mendeliome v1.2189 CCT3 Ain Roesley Gene: cct3 has been classified as Green List (High Evidence).
Mendeliome v1.2188 CCT3 Ain Roesley gene: CCT3 was added
gene: CCT3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCT3 were set to 39480921
Penetrance for gene: CCT3 were set to Complete
Review for gene: CCT3 was set to GREEN
gene: CCT3 was marked as current diagnostic
Added comment: 4x de novo - 3x PTCs and 1x missense

overlapping phenotypes:
4/4 ID/DD
3/4 visual impairment
2/4 seizures
4/4 Hypomyelination of white matter
Sources: Literature
Cholestasis v0.288 UGT1A1 Zornitza Stark Marked gene: UGT1A1 as ready
Cholestasis v0.288 UGT1A1 Zornitza Stark Gene: ugt1a1 has been classified as Green List (High Evidence).
Cholestasis v0.288 UGT1A1 Zornitza Stark Phenotypes for gene: UGT1A1 were changed from to Crigler-Najjar syndrome, type I MIM#218800; Crigler-Najjar syndrome, type II MIM#606785
Cholestasis v0.287 UGT1A1 Zornitza Stark Mode of inheritance for gene: UGT1A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.286 UGT1A1 Zornitza Stark changed review comment from: Well established gene-disease association. Cholestasis is a key feature.; to: Well established gene-disease association. Unconjugated hyperbilirubinaemia is a key feature.
Cholestasis v0.286 UGT1A1 Zornitza Stark reviewed gene: UGT1A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Crigler-Najjar syndrome, type I MIM#218800, Crigler-Najjar syndrome, type II MIM#606785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.286 TALDO1 Zornitza Stark Marked gene: TALDO1 as ready
Cholestasis v0.286 TALDO1 Zornitza Stark Gene: taldo1 has been classified as Green List (High Evidence).
Cholestasis v0.286 TALDO1 Zornitza Stark Phenotypes for gene: TALDO1 were changed from to Transaldolase deficiency, MIM# 606003
Cholestasis v0.285 TALDO1 Zornitza Stark Mode of inheritance for gene: TALDO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.284 TALDO1 Zornitza Stark reviewed gene: TALDO1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Transaldolase deficiency, MIM# 606003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.284 SLC25A13 Zornitza Stark Marked gene: SLC25A13 as ready
Cholestasis v0.284 SLC25A13 Zornitza Stark Gene: slc25a13 has been classified as Green List (High Evidence).
Cholestasis v0.284 SLC25A13 Zornitza Stark Phenotypes for gene: SLC25A13 were changed from to Citrullinemia, type II, neonatal-onset, MIM# 605814
Cholestasis v0.283 SLC25A13 Zornitza Stark Mode of inheritance for gene: SLC25A13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.282 SLC25A13 Zornitza Stark reviewed gene: SLC25A13: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Citrullinemia, type II, neonatal-onset, MIM# 605814; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.282 PEX6 Zornitza Stark Marked gene: PEX6 as ready
Cholestasis v0.282 PEX6 Zornitza Stark Gene: pex6 has been classified as Green List (High Evidence).
Microcephaly v1.292 Ain Roesley removed gene:CLASP1 from the panel
Microcephaly v1.292 CLASP1 Ain Roesley Source: Literature was removed from gene: CLASP1
Cholestasis v0.282 PEX6 Zornitza Stark Phenotypes for gene: PEX6 were changed from to Peroxisome biogenesis disorder 4A (Zellweger) (MIM#614862)
Cholestasis v0.281 PEX6 Zornitza Stark Mode of inheritance for gene: PEX6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.280 PEX6 Zornitza Stark reviewed gene: PEX6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 4A (Zellweger) (MIM#614862); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.13 CLASP1 Ain Roesley Marked gene: CLASP1 as ready
Intellectual disability syndromic and non-syndromic v1.13 CLASP1 Ain Roesley Gene: clasp1 has been classified as Red List (Low Evidence).
Lissencephaly and Band Heterotopia v1.21 CLASP1 Ain Roesley Marked gene: CLASP1 as ready
Lissencephaly and Band Heterotopia v1.21 CLASP1 Ain Roesley Gene: clasp1 has been classified as Red List (Low Evidence).
Cholestasis v0.280 PEX26 Zornitza Stark Marked gene: PEX26 as ready
Cholestasis v0.280 PEX26 Zornitza Stark Gene: pex26 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.78 CLASP1 Ain Roesley Marked gene: CLASP1 as ready
Genetic Epilepsy v1.78 CLASP1 Ain Roesley Gene: clasp1 has been classified as Red List (Low Evidence).
Cholestasis v0.280 PEX26 Zornitza Stark Phenotypes for gene: PEX26 were changed from to Peroxisome biogenesis disorder 7A (Zellweger) MIM#614872
Cholestasis v0.279 PEX26 Zornitza Stark Mode of inheritance for gene: PEX26 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.278 PEX26 Zornitza Stark reviewed gene: PEX26: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 7A (Zellweger) MIM#614872; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.289 CLASP1 Ain Roesley gene: CLASP1 was added
gene: CLASP1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CLASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLASP1 were set to 39040917
Phenotypes for gene: CLASP1 were set to neurodevelopmental disorder MONDO:0700092, CLASP1-related
Review for gene: CLASP1 was set to RED
gene: CLASP1 was marked as current diagnostic
Added comment: 3 siblings from a consanguineous family, homozygous for p.(Arg1481His)
at birth, all had low weight and microcephaly (< 3-4SD), profound dev delay, spasticity, seizures and lissencephaly

Arg1481His - 3 hets 0 Homs in v4
codon is highly conserved with a high REVEL score 0.83
Sources: Literature
Microcephaly v1.289 CLASP1 Ain Roesley gene: CLASP1 was added
gene: CLASP1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CLASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLASP1 were set to 39040917
Phenotypes for gene: CLASP1 were set to neurodevelopmental disorder MONDO:0700092, CLASP1-related
Review for gene: CLASP1 was set to RED
gene: CLASP1 was marked as current diagnostic
Added comment: 3 siblings from a consanguineous family, homozygous for p.(Arg1481His)
at birth, all had low weight and microcephaly (< 3-4SD), profound dev delay, spasticity, seizures and lissencephaly

Arg1481His - 3 hets 0 Homs in v4
codon is highly conserved with a high REVEL score 0.83
Sources: Literature
Cholestasis v0.278 PEX2 Zornitza Stark Marked gene: PEX2 as ready
Cholestasis v0.278 PEX2 Zornitza Stark Gene: pex2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.13 CLASP1 Ain Roesley gene: CLASP1 was added
gene: CLASP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CLASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLASP1 were set to 39040917
Phenotypes for gene: CLASP1 were set to neurodevelopmental disorder MONDO:0700092, CLASP1-related
Review for gene: CLASP1 was set to RED
gene: CLASP1 was marked as current diagnostic
Added comment: 3 siblings from a consanguineous family, homozygous for p.(Arg1481His)
at birth, all had low weight and microcephaly (< 3-4SD), profound dev delay, spasticity, seizures and lissencephaly

Arg1481His - 3 hets 0 Homs in v4
codon is highly conserved with a high REVEL score 0.83
Sources: Literature
Cholestasis v0.278 PEX2 Zornitza Stark Phenotypes for gene: PEX2 were changed from Peroxisome biogenesis disorder 5A (Zellweger) MIM#614866 to Peroxisome biogenesis disorder 5A (Zellweger) MIM#614866
Lissencephaly and Band Heterotopia v1.21 CLASP1 Ain Roesley gene: CLASP1 was added
gene: CLASP1 was added to Lissencephaly and Band Heterotopia. Sources: Literature
Mode of inheritance for gene: CLASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLASP1 were set to 39040917
Phenotypes for gene: CLASP1 were set to neurodevelopmental disorder MONDO:0700092, CLASP1-related
Review for gene: CLASP1 was set to RED
gene: CLASP1 was marked as current diagnostic
Added comment: 3 siblings from a consanguineous family, homozygous for p.(Arg1481His)
at birth, all had low weight and microcephaly (< 3-4SD), profound dev delay, spasticity, seizures and lissencephaly

Arg1481His - 3 hets 0 Homs in v4
codon is highly conserved with a high REVEL score 0.83
Sources: Literature
Cholestasis v0.278 PEX2 Zornitza Stark Phenotypes for gene: PEX2 were changed from to Peroxisome biogenesis disorder 5A (Zellweger) MIM#614866
Genetic Epilepsy v1.78 CLASP1 Ain Roesley gene: CLASP1 was added
gene: CLASP1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CLASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLASP1 were set to 39040917
Phenotypes for gene: CLASP1 were set to neurodevelopmental disorder MONDO:0700092, CLASP1-related
Review for gene: CLASP1 was set to RED
gene: CLASP1 was marked as current diagnostic
Added comment: 3 siblings from a consanguineous family, homozygous for p.(Arg1481His)
at birth, all had low weight and microcephaly (< 3-4SD), profound dev delay, spasticity, seizures and lissencephaly

Arg1481His - 3 hets 0 Homs in v4
codon is highly conserved with a high REVEL score 0.83
Sources: Literature
Mendeliome v1.2187 CLASP1 Ain Roesley Marked gene: CLASP1 as ready
Mendeliome v1.2187 CLASP1 Ain Roesley Gene: clasp1 has been classified as Red List (Low Evidence).
Mendeliome v1.2187 CLASP1 Ain Roesley gene: CLASP1 was added
gene: CLASP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CLASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLASP1 were set to 39040917
Phenotypes for gene: CLASP1 were set to neurodevelopmental disorder MONDO:0700092, CLASP1-related
Review for gene: CLASP1 was set to RED
gene: CLASP1 was marked as current diagnostic
Added comment: 3 siblings from a consanguineous family, homozygous for p.(Arg1481His)
at birth, all had low weight and microcephaly (< 3-4SD), profound dev delay, spasticity, seizures and lissencephaly

Arg1481His - 3 hets 0 Homs in v4
codon is highly conserved with a high REVEL score 0.83
Sources: Literature
Cholestasis v0.277 PEX2 Zornitza Stark Mode of inheritance for gene: PEX2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.276 PEX2 Zornitza Stark reviewed gene: PEX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 5A (Zellweger) MIM#614866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.276 PEX12 Zornitza Stark Marked gene: PEX12 as ready
Cholestasis v0.276 PEX12 Zornitza Stark Gene: pex12 has been classified as Green List (High Evidence).
Cholestasis v0.276 PEX12 Zornitza Stark Phenotypes for gene: PEX12 were changed from to Peroxisome biogenesis disorder 3A (Zellweger) (MIM#614859)
Cholestasis v0.275 PEX12 Zornitza Stark Mode of inheritance for gene: PEX12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.274 PEX12 Zornitza Stark reviewed gene: PEX12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 3A (Zellweger) (MIM#614859); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.274 PEX1 Zornitza Stark Marked gene: PEX1 as ready
Cholestasis v0.274 PEX1 Zornitza Stark Gene: pex1 has been classified as Green List (High Evidence).
Cholestasis v0.274 PEX1 Zornitza Stark Phenotypes for gene: PEX1 were changed from to Peroxisome biogenesis disorder 1A (Zellweger), MIM# 214100
Cholestasis v0.273 PEX1 Zornitza Stark Mode of inheritance for gene: PEX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.272 PEX1 Zornitza Stark reviewed gene: PEX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 1A (Zellweger), MIM# 214100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.272 NPC2 Zornitza Stark Marked gene: NPC2 as ready
Cholestasis v0.272 NPC2 Zornitza Stark Gene: npc2 has been classified as Green List (High Evidence).
Cholestasis v0.272 NPC2 Zornitza Stark Phenotypes for gene: NPC2 were changed from to Niemann-pick disease, type C2 MIM#607625
Cholestasis v0.271 NPC2 Zornitza Stark Mode of inheritance for gene: NPC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.270 NPC2 Zornitza Stark reviewed gene: NPC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Niemann-pick disease, type C2 MIM#607625; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.270 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Cholestasis v0.270 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Cholestasis v0.270 NPC1 Zornitza Stark Phenotypes for gene: NPC1 were changed from to Niemann-Pick disease, MIM# 257220
Cholestasis v0.269 NPC1 Zornitza Stark Mode of inheritance for gene: NPC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.268 NPC1 Zornitza Stark reviewed gene: NPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Niemann-Pick disease, MIM# 257220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.268 JAG1 Zornitza Stark Marked gene: JAG1 as ready
Cholestasis v0.268 JAG1 Zornitza Stark Gene: jag1 has been classified as Green List (High Evidence).
Cholestasis v0.268 JAG1 Zornitza Stark Phenotypes for gene: JAG1 were changed from to Alagille syndrome, MIM#118450
Cholestasis v0.267 JAG1 Zornitza Stark Mode of inheritance for gene: JAG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cholestasis v0.266 JAG1 Zornitza Stark reviewed gene: JAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alagille syndrome, MIM# 1, 118450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cholestasis v0.266 FAH Zornitza Stark Marked gene: FAH as ready
Cholestasis v0.266 FAH Zornitza Stark Gene: fah has been classified as Green List (High Evidence).
Cholestasis v0.266 FAH Zornitza Stark Phenotypes for gene: FAH were changed from Tyrosinemia, type I, MIM# 276700 to Tyrosinaemia, type I, MIM# 276700
Cholestasis v0.265 FAH Zornitza Stark Phenotypes for gene: FAH were changed from to Tyrosinemia, type I, MIM# 276700
Cholestasis v0.264 FAH Zornitza Stark Mode of inheritance for gene: FAH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.263 FAH Zornitza Stark reviewed gene: FAH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tyrosinemia, type I, MIM# 276700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.263 DCDC2 Zornitza Stark Marked gene: DCDC2 as ready
Cholestasis v0.263 DCDC2 Zornitza Stark Gene: dcdc2 has been classified as Green List (High Evidence).
Cholestasis v0.263 DCDC2 Zornitza Stark Phenotypes for gene: DCDC2 were changed from to Sclerosing cholangitis, neonatal, MIM# 617394
Cholestasis v0.262 DCDC2 Zornitza Stark Publications for gene: DCDC2 were set to
Cholestasis v0.261 DCDC2 Zornitza Stark Mode of inheritance for gene: DCDC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.260 DCDC2 Zornitza Stark edited their review of gene: DCDC2: Added comment: At least 8 families reported. Affected infants have jaundice, cholestasis, acholic stools, and progressive liver dysfunction resulting in fibrosis and cirrhosis; most require liver transplantation in the first few decades of life.; Changed publications: 27319779, 27469900
Cholestasis v0.260 DCDC2 Zornitza Stark reviewed gene: DCDC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sclerosing cholangitis, neonatal, MIM# 617394; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.260 CYP27A1 Zornitza Stark Marked gene: CYP27A1 as ready
Cholestasis v0.260 CYP27A1 Zornitza Stark Gene: cyp27a1 has been classified as Green List (High Evidence).
Cholestasis v0.260 CYP27A1 Zornitza Stark Phenotypes for gene: CYP27A1 were changed from to Cerebrotendinous xanthomatosis, MIM# 213700
Cholestasis v0.259 CYP27A1 Zornitza Stark Mode of inheritance for gene: CYP27A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.258 CYP27A1 Zornitza Stark reviewed gene: CYP27A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebrotendinous xanthomatosis, MIM# 213700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.258 CLDN1 Zornitza Stark Marked gene: CLDN1 as ready
Cholestasis v0.258 CLDN1 Zornitza Stark Gene: cldn1 has been classified as Green List (High Evidence).
Cholestasis v0.258 CLDN1 Zornitza Stark Phenotypes for gene: CLDN1 were changed from to Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis MIM#607626
Cholestasis v0.257 CLDN1 Zornitza Stark Publications for gene: CLDN1 were set to
Cholestasis v0.256 CLDN1 Zornitza Stark Mode of inheritance for gene: CLDN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.255 CLDN1 Zornitza Stark reviewed gene: CLDN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12164927, 11889141, 29146216; Phenotypes: Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis MIM#607626; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.255 CC2D2A Zornitza Stark Marked gene: CC2D2A as ready
Cholestasis v0.255 CC2D2A Zornitza Stark Gene: cc2d2a has been classified as Green List (High Evidence).
Cholestasis v0.255 CC2D2A Zornitza Stark Phenotypes for gene: CC2D2A were changed from to COACH syndrome 2, MIM# 619111; Meckel syndrome 6, MIM#612284
Cholestasis v0.254 CC2D2A Zornitza Stark Mode of inheritance for gene: CC2D2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.253 CC2D2A Zornitza Stark edited their review of gene: CC2D2A: Changed phenotypes: COACH syndrome 2, MIM# 619111, Meckel syndrome 6, MIM#612284
Cholestasis v0.253 CC2D2A Zornitza Stark reviewed gene: CC2D2A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: COACH syndrome 2, MIM# 619111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.253 AMACR Zornitza Stark Marked gene: AMACR as ready
Cholestasis v0.253 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Cholestasis v0.253 AMACR Zornitza Stark Phenotypes for gene: AMACR were changed from to Bile acid synthesis defect, congenital, 4, MIM# 214950
Cholestasis v0.252 AMACR Zornitza Stark Publications for gene: AMACR were set to
Cholestasis v0.251 AMACR Zornitza Stark Mode of inheritance for gene: AMACR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.250 AMACR Zornitza Stark reviewed gene: AMACR: Rating: GREEN; Mode of pathogenicity: None; Publications: 31951345, 24735479, 12512044, 10655068, 34267495, 33047465; Phenotypes: Bile acid synthesis defect, congenital, 4, MIM# 214950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v1.0 Zornitza Stark promoted panel to version 1.0
Osteogenesis Imperfecta and Osteoporosis v0.133 SERPINH1 Zornitza Stark Mode of inheritance for gene: SERPINH1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.133 SERPINH1 Zornitza Stark Mode of inheritance for gene: SERPINH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.132 SERPINH1 Zornitza Stark Publications for gene: SERPINH1 were set to 33524049
Osteogenesis Imperfecta and Osteoporosis v0.132 SERPINH1 Zornitza Stark Publications for gene: SERPINH1 were set to
Osteogenesis Imperfecta and Osteoporosis v0.131 SERPINH1 Zornitza Stark Phenotypes for gene: SERPINH1 were changed from Osteogenesis imperfecta, type X, MIM# 613848 to Osteogenesis imperfecta, type X, MIM# 613848
Osteogenesis Imperfecta and Osteoporosis v0.131 SERPINH1 Zornitza Stark Phenotypes for gene: SERPINH1 were changed from to Osteogenesis imperfecta, type X, MIM# 613848
Osteogenesis Imperfecta and Osteoporosis v0.130 ANO5 Zornitza Stark Marked gene: ANO5 as ready
Osteogenesis Imperfecta and Osteoporosis v0.130 ANO5 Zornitza Stark Gene: ano5 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.130 COL1A1 Zornitza Stark Marked gene: COL1A1 as ready
Osteogenesis Imperfecta and Osteoporosis v0.130 COL1A1 Zornitza Stark Gene: col1a1 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.130 COL1A1 Zornitza Stark Phenotypes for gene: COL1A1 were changed from to combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 MONDO:0030854; Osteogenesis imperfecta type 1 MONDO:0008146; Osteogenesis imperfecta type 2 MONDO:0008147; Osteogenesis imperfecta type 3 MONDO:0009804; Osteogenesis imperfecta type 4; MONDO:0008148
Osteogenesis Imperfecta and Osteoporosis v0.129 COL1A1 Zornitza Stark Publications for gene: COL1A1 were set to
Osteogenesis Imperfecta and Osteoporosis v0.128 COL1A1 Zornitza Stark Mode of inheritance for gene: COL1A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteogenesis Imperfecta and Osteoporosis v0.127 COL1A2 Zornitza Stark Marked gene: COL1A2 as ready
Osteogenesis Imperfecta and Osteoporosis v0.127 COL1A2 Zornitza Stark Gene: col1a2 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.127 COL1A2 Zornitza Stark Phenotypes for gene: COL1A2 were changed from to Osteogenesis imperfecta type 1 MONDO:0008146; Osteogenesis imperfecta type 2 MONDO:0008147; Osteogenesis imperfecta type 3 MONDO:0009804; Osteogenesis imperfecta type 4 MONDO:0008148
Osteogenesis Imperfecta and Osteoporosis v0.126 COL1A2 Zornitza Stark Publications for gene: COL1A2 were set to
Osteogenesis Imperfecta and Osteoporosis v0.125 COL1A2 Zornitza Stark Mode of inheritance for gene: COL1A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteogenesis Imperfecta and Osteoporosis v0.124 FKBP10 Zornitza Stark Marked gene: FKBP10 as ready
Osteogenesis Imperfecta and Osteoporosis v0.124 FKBP10 Zornitza Stark Gene: fkbp10 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.124 FKBP10 Zornitza Stark Phenotypes for gene: FKBP10 were changed from to osteogenesis imperfecta type 11 MONDO:0012592; Bruck syndrome MONDO:0017195
Osteogenesis Imperfecta and Osteoporosis v0.123 FKBP10 Zornitza Stark Publications for gene: FKBP10 were set to
Osteogenesis Imperfecta and Osteoporosis v0.122 FKBP10 Zornitza Stark Mode of inheritance for gene: FKBP10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.121 LRP5 Zornitza Stark Marked gene: LRP5 as ready
Osteogenesis Imperfecta and Osteoporosis v0.121 LRP5 Zornitza Stark Gene: lrp5 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.121 LRP5 Zornitza Stark Phenotypes for gene: LRP5 were changed from to osteoporosis-pseudoglioma syndrome MONDO:0009820
Osteogenesis Imperfecta and Osteoporosis v0.120 LRP5 Zornitza Stark Publications for gene: LRP5 were set to
Osteogenesis Imperfecta and Osteoporosis v0.119 LRP5 Zornitza Stark Mode of inheritance for gene: LRP5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.118 PLS3 Zornitza Stark Marked gene: PLS3 as ready
Osteogenesis Imperfecta and Osteoporosis v0.118 PLS3 Zornitza Stark Gene: pls3 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.118 PLS3 Zornitza Stark Phenotypes for gene: PLS3 were changed from to X-linked osteoporosis with fractures MONDO:0018315
Osteogenesis Imperfecta and Osteoporosis v0.117 PLS3 Zornitza Stark Publications for gene: PLS3 were set to
Osteogenesis Imperfecta and Osteoporosis v0.116 PLS3 Zornitza Stark Mode of inheritance for gene: PLS3 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)
Dystonia - complex v0.254 APTX Zornitza Stark Marked gene: APTX as ready
Dystonia - complex v0.254 APTX Zornitza Stark Gene: aptx has been classified as Green List (High Evidence).
Dystonia - complex v0.254 APTX Zornitza Stark Publications for gene: APTX were set to
Spontaneous coronary artery dissection v0.54 COL3A1 Zornitza Stark Publications for gene: COL3A1 were set to 30071989
Dystonia - complex v0.253 ATP13A2 Zornitza Stark Marked gene: ATP13A2 as ready
Dystonia - complex v0.253 ATP13A2 Zornitza Stark Gene: atp13a2 has been classified as Green List (High Evidence).
Dystonia - complex v0.253 ATP13A2 Zornitza Stark Phenotypes for gene: ATP13A2 were changed from Parkinson disease; Kufor-Rakeb syndrome 606693; Dystonia to Kufor-Rakeb syndrome MIM#606693
Dystonia - complex v0.252 ATP13A2 Zornitza Stark Publications for gene: ATP13A2 were set to
Dystonia - complex v0.251 BCAP31 Zornitza Stark Marked gene: BCAP31 as ready
Dystonia - complex v0.251 BCAP31 Zornitza Stark Gene: bcap31 has been classified as Green List (High Evidence).
Dystonia - complex v0.251 BCAP31 Zornitza Stark Phenotypes for gene: BCAP31 were changed from Deafness, dystonia and cerebellar hypomyelination, 300475 to Deafness, dystonia and cerebellar hypomyelination, MIM#300475
Dystonia - complex v0.250 BCAP31 Zornitza Stark Publications for gene: BCAP31 were set to
Dystonia - complex v0.249 C19orf12 Zornitza Stark Marked gene: C19orf12 as ready
Dystonia - complex v0.249 C19orf12 Zornitza Stark Gene: c19orf12 has been classified as Green List (High Evidence).
Dystonia - complex v0.249 C19orf12 Zornitza Stark Phenotypes for gene: C19orf12 were changed from mitochondrial membrane protein-associated neurodegeneration; neurodegeneration with brain iron accumulation-4; Dystonia to neurodegeneration with brain iron accumulation 4 MONDO:0013674
Dystonia - complex v0.248 C19orf12 Zornitza Stark Publications for gene: C19orf12 were set to
Differences of Sex Development v1.0 Zornitza Stark promoted panel to version 1.0
Differences of Sex Development v0.380 TWNK Zornitza Stark Marked gene: TWNK as ready
Differences of Sex Development v0.380 TWNK Zornitza Stark Gene: twnk has been classified as Green List (High Evidence).
Differences of Sex Development v0.380 TWNK Zornitza Stark Phenotypes for gene: TWNK were changed from Perrault syndrome 5; MIM# 616138 to Perrault syndrome 5, MIM# 616138
Differences of Sex Development v0.379 TWNK Zornitza Stark Publications for gene: TWNK were set to PMID: 25355836, 31852434, 31455392
Differences of Sex Development v0.378 POLR1C Zornitza Stark Marked gene: POLR1C as ready
Differences of Sex Development v0.378 POLR1C Zornitza Stark Gene: polr1c has been classified as Red List (Low Evidence).
Differences of Sex Development v0.378 POLR1C Zornitza Stark Publications for gene: POLR1C were set to PMID: 26151409, 32042905, 33005949, ............22855961
Differences of Sex Development v0.375 AXL Zornitza Stark Marked gene: AXL as ready
Differences of Sex Development v0.375 AXL Zornitza Stark Gene: axl has been classified as Red List (Low Evidence).
Differences of Sex Development v0.375 SOX2 Zornitza Stark Marked gene: SOX2 as ready
Differences of Sex Development v0.375 SOX2 Zornitza Stark Gene: sox2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.375 POLR3B Zornitza Stark Marked gene: POLR3B as ready
Differences of Sex Development v0.375 POLR3B Zornitza Stark Gene: polr3b has been classified as Green List (High Evidence).
Differences of Sex Development v0.375 POLR3B Zornitza Stark Publications for gene: POLR3B were set to PubMed: 27512013, 23355746, 22036171, 22036172, 25339210, 33005949, 22855961
Differences of Sex Development v0.374 POLR3A Zornitza Stark Marked gene: POLR3A as ready
Differences of Sex Development v0.374 POLR3A Zornitza Stark Gene: polr3a has been classified as Green List (High Evidence).
Differences of Sex Development v0.374 POLR3A Zornitza Stark Publications for gene: POLR3A were set to PubMed: 21855841, 25339210, 33005949, 22855961
Differences of Sex Development v0.373 MARS2 Zornitza Stark Marked gene: MARS2 as ready
Differences of Sex Development v0.373 MARS2 Zornitza Stark Gene: mars2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.373 MARS2 Zornitza Stark Publications for gene: MARS2 were set to PMID: 27650058, 21464306, 27087618
Differences of Sex Development v0.372 LARS2 Zornitza Stark Marked gene: LARS2 as ready
Differences of Sex Development v0.372 LARS2 Zornitza Stark Gene: lars2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.372 LARS2 Zornitza Stark Phenotypes for gene: LARS2 were changed from Perrault syndrome 4; MIM# 615300 to Perrault syndrome 4, MIM# 615300
Differences of Sex Development v0.371 LARS2 Zornitza Stark Publications for gene: LARS2 were set to PMID: 32423379, 29205794, 23541342, 30737337, 26657938,
Differences of Sex Development v0.370 IRF6 Zornitza Stark Marked gene: IRF6 as ready
Differences of Sex Development v0.370 IRF6 Zornitza Stark Gene: irf6 has been classified as Green List (High Evidence).
Differences of Sex Development v0.370 HHAT Zornitza Stark Marked gene: HHAT as ready
Differences of Sex Development v0.370 HHAT Zornitza Stark Gene: hhat has been classified as Green List (High Evidence).
Differences of Sex Development v0.370 HHAT Zornitza Stark Publications for gene: HHAT were set to PMID: 24784881, 33749989, 35045414
Differences of Sex Development v0.369 HARS2 Zornitza Stark Marked gene: HARS2 as ready
Differences of Sex Development v0.369 HARS2 Zornitza Stark Gene: hars2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.369 HARS2 Zornitza Stark Publications for gene: HARS2 were set to PMID: 27650058, 21464306, 27087618
Differences of Sex Development v0.368 FREM2 Zornitza Stark Marked gene: FREM2 as ready
Differences of Sex Development v0.368 FREM2 Zornitza Stark Gene: frem2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.368 FREM2 Zornitza Stark Publications for gene: FREM2 were set to PMID: 15838507, 29688405, 18203166, 18671281, 18000968
Differences of Sex Development v0.367 WT1 Zornitza Stark Marked gene: WT1 as ready
Differences of Sex Development v0.367 WT1 Zornitza Stark Gene: wt1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.367 WT1 Zornitza Stark Phenotypes for gene: WT1 were changed from to Wilms tumor, MONDO:0006058; Wilms tumor 1, MONDO:0008679; Wilms tumor, type 1, MIM#194070; Denys-Drash syndrome, MIM#194080; Frasier syndrome, MIM#136680
Differences of Sex Development v0.366 WT1 Zornitza Stark Mode of inheritance for gene: WT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.365 SRY Zornitza Stark Marked gene: SRY as ready
Differences of Sex Development v0.365 SRY Zornitza Stark Gene: sry has been classified as Green List (High Evidence).
Differences of Sex Development v0.365 SRY Zornitza Stark Phenotypes for gene: SRY were changed from to 46XX sex reversal 1, MIM# 400045; 46XY sex reversal 1 , MIM#400044
Differences of Sex Development v0.364 SRY Zornitza Stark Publications for gene: SRY were set to
Differences of Sex Development v0.363 SRY Zornitza Stark Mode of inheritance for gene: SRY 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)
Differences of Sex Development v0.362 SOX9 Zornitza Stark Marked gene: SOX9 as ready
Differences of Sex Development v0.362 SOX9 Zornitza Stark Gene: sox9 has been classified as Green List (High Evidence).
Differences of Sex Development v0.362 SOX9 Zornitza Stark Phenotypes for gene: SOX9 were changed from to Campomelic dysplasia, MIM# 114290; Campomelic dysplasia, MONDO:0007251; Acampomelic campomelic dysplasia, MIM # 114290, 46XX sex reversal 2, MIM# 278850; 46XY sex reversal 10, MIM # 616425
Differences of Sex Development v0.361 SOX9 Zornitza Stark Mode of inheritance for gene: SOX9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.360 FGFR1 Zornitza Stark Marked gene: FGFR1 as ready
Differences of Sex Development v0.360 FGFR1 Zornitza Stark Gene: fgfr1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.360 FGFR1 Zornitza Stark Phenotypes for gene: FGFR1 were changed from to Encephalocraniocutaneous lipomatosis, somatic mosaic 613001; Hartsfield syndrome 615465; Hypogonadotropic hypogonadism 2 with or without anosmia 147950; Osteoglophonic dysplasia 166250
Differences of Sex Development v0.359 FGFR1 Zornitza Stark Publications for gene: FGFR1 were set to
Differences of Sex Development v0.358 FGFR1 Zornitza Stark Mode of inheritance for gene: FGFR1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.357 FGFR2 Zornitza Stark Marked gene: FGFR2 as ready
Differences of Sex Development v0.357 FGFR2 Zornitza Stark Gene: fgfr2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.357 FGFR2 Zornitza Stark Phenotypes for gene: FGFR2 were changed from to Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis,MIM# 207410, Apert syndrome, MIM# 101200, Beare-Stevenson cutis gyrata syndrome, MIM# 123790, Bent bone dysplasia syndrome, MIM# 614592
Differences of Sex Development v0.356 FGFR2 Zornitza Stark Publications for gene: FGFR2 were set to
Differences of Sex Development v0.355 FGFR2 Zornitza Stark Mode of inheritance for gene: FGFR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.354 FSHB Zornitza Stark Marked gene: FSHB as ready
Differences of Sex Development v0.354 FSHB Zornitza Stark Gene: fshb has been classified as Green List (High Evidence).
Differences of Sex Development v0.354 FSHB Zornitza Stark Phenotypes for gene: FSHB were changed from to Hypogonadotropic hypogonadism 24 without anosmia, MIM#229070
Differences of Sex Development v0.353 FSHB Zornitza Stark Publications for gene: FSHB were set to
Differences of Sex Development v0.352 FSHB Zornitza Stark Mode of inheritance for gene: FSHB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.351 FSHR Zornitza Stark Phenotypes for gene: FSHR were changed from to Ovarian dysgenesis 1 MONDO:0024463; Ovarian hyperstimulation syndrome MONDO:0011972
Differences of Sex Development v0.350 FSHR Zornitza Stark Marked gene: FSHR as ready
Differences of Sex Development v0.350 FSHR Zornitza Stark Gene: fshr has been classified as Green List (High Evidence).
Differences of Sex Development v0.350 FSHR Zornitza Stark Publications for gene: FSHR were set to
Differences of Sex Development v0.349 FSHR Zornitza Stark Mode of inheritance for gene: FSHR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dystonia - complex v0.247 COASY Zornitza Stark Marked gene: COASY as ready
Dystonia - complex v0.247 COASY Zornitza Stark Gene: coasy has been classified as Green List (High Evidence).
Dystonia - complex v0.247 COASY Zornitza Stark Phenotypes for gene: COASY were changed from COASY protein-associated neurodegeneration; Neurodegeneration with brain iron accumulation 6 615643 to neurodegeneration with brain iron accumulation 6, MONDO:0014290; Neurodegeneration with brain iron accumulation 6 615643
Dystonia - complex v0.246 COASY Zornitza Stark Publications for gene: COASY were set to
Dystonia - complex v0.245 DCAF17 Zornitza Stark Marked gene: DCAF17 as ready
Dystonia - complex v0.245 DCAF17 Zornitza Stark Gene: dcaf17 has been classified as Green List (High Evidence).
Dystonia - complex v0.245 DCAF17 Zornitza Stark Phenotypes for gene: DCAF17 were changed from Woodhouse-Sakati syndrome; Dystonia to Woodhouse-Sakati syndrome MONDO:0009419; Dystonia
Dystonia - complex v0.244 DCAF17 Zornitza Stark Publications for gene: DCAF17 were set to
Syndromic Retinopathy v0.219 GPATCH11 Zornitza Stark Publications for gene: GPATCH11 were set to
Syndromic Retinopathy v0.218 GPATCH11 Zornitza Stark reviewed gene: GPATCH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 39572588; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.12 GPATCH11 Zornitza Stark Publications for gene: GPATCH11 were set to
Intellectual disability syndromic and non-syndromic v1.11 GPATCH11 Zornitza Stark reviewed gene: GPATCH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 39572588; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2186 GPATCH11 Zornitza Stark Publications for gene: GPATCH11 were set to
Dystonia - complex v0.243 DDC Zornitza Stark Marked gene: DDC as ready
Dystonia - complex v0.243 DDC Zornitza Stark Gene: ddc has been classified as Green List (High Evidence).
Dystonia - complex v0.243 DDC Zornitza Stark Publications for gene: DDC were set to
Paroxysmal Dyskinesia v0.141 ALDH5A1 Zornitza Stark Marked gene: ALDH5A1 as ready
Paroxysmal Dyskinesia v0.141 ALDH5A1 Zornitza Stark Gene: aldh5a1 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.141 ALDH5A1 Zornitza Stark Phenotypes for gene: ALDH5A1 were changed from epilepsy; paroxysmal exercise induced dyskinesia; globus pallidus hyperintensities on MRI to Succinic semialdehyde dehydrogenase deficiency, MIM# 271980
Paroxysmal Dyskinesia v0.140 ALDH5A1 Zornitza Stark Classified gene: ALDH5A1 as Green List (high evidence)
Paroxysmal Dyskinesia v0.140 ALDH5A1 Zornitza Stark Gene: aldh5a1 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.139 ALDH5A1 Zornitza Stark reviewed gene: ALDH5A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Succinic semialdehyde dehydrogenase deficiency, MIM# 271980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paroxysmal Dyskinesia v0.139 SPR Zornitza Stark Marked gene: SPR as ready
Paroxysmal Dyskinesia v0.139 SPR Zornitza Stark Gene: spr has been classified as Amber List (Moderate Evidence).
Paroxysmal Dyskinesia v0.139 SPR Zornitza Stark Phenotypes for gene: SPR were changed from to Dopa-responsive dystonia due to sepiapterin reductase deficiency MONDO:0012994
Paroxysmal Dyskinesia v0.138 SPR Zornitza Stark Publications for gene: SPR were set to
Paroxysmal Dyskinesia v0.137 SPR Zornitza Stark Mode of inheritance for gene: SPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Paroxysmal Dyskinesia v0.136 SPR Zornitza Stark Classified gene: SPR as Amber List (moderate evidence)
Paroxysmal Dyskinesia v0.136 SPR Zornitza Stark Gene: spr has been classified as Amber List (Moderate Evidence).
Paroxysmal Dyskinesia v0.135 SPR Zornitza Stark reviewed gene: SPR: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Dopa-responsive dystonia due to sepiapterin reductase deficiency MONDO:0012994; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paroxysmal Dyskinesia v0.135 KCNJ10 Zornitza Stark Publications for gene: KCNJ10 were set to 38979912
Paroxysmal Dyskinesia v0.134 KCNJ10 Zornitza Stark Mode of inheritance for gene: KCNJ10 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.2185 HMGCS1 Zornitza Stark Marked gene: HMGCS1 as ready
Mendeliome v1.2185 HMGCS1 Zornitza Stark Gene: hmgcs1 has been classified as Green List (High Evidence).
Mendeliome v1.2185 HMGCS1 Zornitza Stark Classified gene: HMGCS1 as Green List (high evidence)
Mendeliome v1.2185 HMGCS1 Zornitza Stark Gene: hmgcs1 has been classified as Green List (High Evidence).
Mendeliome v1.2184 HMGCS1 Zornitza Stark gene: HMGCS1 was added
gene: HMGCS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HMGCS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMGCS1 were set to 39531736
Phenotypes for gene: HMGCS1 were set to Rigid spine syndrome, MONDO:0019951, HMGCS1-related
Review for gene: HMGCS1 was set to GREEN
Added comment: Five individuals from four families reported. All individuals presented with spinal rigidity primarily affecting the cervical and dorsolumbar regions, scoliosis, and respiratory insufficiency. Creatine kinase levels were variably elevated. The clinical course worsened with intercurrent disease or certain drugs in some; one individual died from respiratory failure following infection. Muscle biopsies revealed irregularities in oxidative enzyme staining with occasional internal nuclei and rimmed vacuoles.
HMGCS1 encodes a critical enzyme of the mevalonate pathway. Notably, biallelic hypomorphic variants in downstream enzymes including HMGCR and GGPS1 are associated with muscular dystrophy. Hmgcs1 mutant zebrafish displayed severe early defects, including immobility at 2 days and death by day 3 post-fertilisation and were rescued by HMGCS1 mRNA. Four variants tested (S447P, Q29L M70T, and C268S) have reduced function compared to wildtype HMGCS1 in zebrafish rescue assays
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.81 HMGCS1 Zornitza Stark Marked gene: HMGCS1 as ready
Muscular dystrophy and myopathy_Paediatric v1.81 HMGCS1 Zornitza Stark Gene: hmgcs1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.81 HMGCS1 Zornitza Stark Classified gene: HMGCS1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.81 HMGCS1 Zornitza Stark Gene: hmgcs1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.80 HMGCS1 Zornitza Stark gene: HMGCS1 was added
gene: HMGCS1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: HMGCS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMGCS1 were set to 39531736
Phenotypes for gene: HMGCS1 were set to Rigid spine syndrome, MONDO:0019951, HMGCS1-related
Review for gene: HMGCS1 was set to GREEN
Added comment: Five individuals from four families reported. All individuals presented with spinal rigidity primarily affecting the cervical and dorsolumbar regions, scoliosis, and respiratory insufficiency. Creatine kinase levels were variably elevated. The clinical course worsened with intercurrent disease or certain drugs in some; one individual died from respiratory failure following infection. Muscle biopsies revealed irregularities in oxidative enzyme staining with occasional internal nuclei and rimmed vacuoles.
HMGCS1 encodes a critical enzyme of the mevalonate pathway. Notably, biallelic hypomorphic variants in downstream enzymes including HMGCR and GGPS1 are associated with muscular dystrophy. Hmgcs1 mutant zebrafish displayed severe early defects, including immobility at 2 days and death by day 3 post-fertilisation and were rescued by HMGCS1 mRNA. Four variants tested (S447P, Q29L M70T, and C268S) have reduced function compared to wildtype HMGCS1 in zebrafish rescue assays
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.11 MGA Zornitza Stark Marked gene: MGA as ready
Intellectual disability syndromic and non-syndromic v1.11 MGA Zornitza Stark Gene: mga has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.11 MGA Zornitza Stark Classified gene: MGA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.11 MGA Zornitza Stark Gene: mga has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.10 MGA Zornitza Stark gene: MGA was added
gene: MGA was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MGA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MGA were set to 39600096; 20044811
Phenotypes for gene: MGA were set to Syndromic disease, MONDO:0002254, MGA-related
Review for gene: MGA was set to GREEN
Added comment: Three individuals with de novo LoF variants reported in individuals with ID and congenital anomalies. Zebrafish model supports role of this transcription factor in organogenesis. Note there are previous, less clear reports of association with NDD/CHD. Gene is constrained for LoF variants in gnomad v4; however, note there are ~30 individuals with LoF variants present. Borderline Green/Amber.
Sources: Literature
Mendeliome v1.2183 CMPK2 Zornitza Stark Marked gene: CMPK2 as ready
Mendeliome v1.2183 CMPK2 Zornitza Stark Gene: cmpk2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2183 CMPK2 Zornitza Stark Classified gene: CMPK2 as Amber List (moderate evidence)
Mendeliome v1.2183 CMPK2 Zornitza Stark Gene: cmpk2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2182 CMPK2 Zornitza Stark gene: CMPK2 was added
gene: CMPK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CMPK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CMPK2 were set to 36443312
Phenotypes for gene: CMPK2 were set to bilateral striopallidodentate calcinosis, MONDO:0008947, CMPK2-related
Review for gene: CMPK2 was set to AMBER
Added comment: Three individuals from two unrelated families reported. One family (two sibs) with homozygous start loss variant, and the other family with compound het variants. Adult-onset neurodegenerative disorder. Extensive functional data including mouse model. Evidence of underlying mitochondrial dysfunction.
Sources: Literature
Brain Calcification v1.99 CMPK2 Zornitza Stark Marked gene: CMPK2 as ready
Brain Calcification v1.99 CMPK2 Zornitza Stark Gene: cmpk2 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.99 CMPK2 Zornitza Stark Classified gene: CMPK2 as Amber List (moderate evidence)
Brain Calcification v1.99 CMPK2 Zornitza Stark Gene: cmpk2 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.98 CMPK2 Zornitza Stark gene: CMPK2 was added
gene: CMPK2 was added to Brain Calcification. Sources: Literature
Mode of inheritance for gene: CMPK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CMPK2 were set to 36443312
Phenotypes for gene: CMPK2 were set to bilateral striopallidodentate calcinosis, MONDO:0008947, CMPK2-related
Review for gene: CMPK2 was set to AMBER
Added comment: Three individuals from two unrelated families reported. One family (two sibs) with homozygous start loss variant, and the other family with compound het variants. Adult-onset neurodegenerative disorder. Extensive functional data including mouse model. Evidence of underlying mitochondrial dysfunction.
Sources: Literature
Mitochondrial disease v0.958 CMPK2 Zornitza Stark Classified gene: CMPK2 as Amber List (moderate evidence)
Mitochondrial disease v0.958 CMPK2 Zornitza Stark Gene: cmpk2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.958 CMPK2 Zornitza Stark Marked gene: CMPK2 as ready
Mitochondrial disease v0.958 CMPK2 Zornitza Stark Gene: cmpk2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.958 CMPK2 Zornitza Stark Classified gene: CMPK2 as Amber List (moderate evidence)
Mitochondrial disease v0.958 CMPK2 Zornitza Stark Gene: cmpk2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.957 CMPK2 Zornitza Stark gene: CMPK2 was added
gene: CMPK2 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: CMPK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CMPK2 were set to 36443312
Phenotypes for gene: CMPK2 were set to bilateral striopallidodentate calcinosis, MONDO:0008947, CMPK2-related
Review for gene: CMPK2 was set to AMBER
Added comment: Three individuals from two unrelated families reported. One family (two sibs) with homozygous start loss variant, and the other family with compound het variants. Adult-onset neurodegenerative disorder. Extensive functional data including mouse model. Evidence of underlying mitochondrial dysfunction.
Sources: Literature
Vascular Malformations_Somatic v1.14 MAP3K3 Zornitza Stark Phenotypes for gene: MAP3K3 were changed from Verrucous venous malformation; Cerebral malformation, MONDO:0016054, MAP3K3-related to Verrucous venous malformation; Cerebral cavernous malformations 5, MIM# 621032
Vascular Malformations_Somatic v1.13 MAP3K3 Zornitza Stark reviewed gene: MAP3K3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral cavernous malformations 5, MIM# 621032; Mode of inheritance: None
Mendeliome v1.2181 MAP3K3 Zornitza Stark Phenotypes for gene: MAP3K3 were changed from Cerebral malformation, MONDO:0016054, MAP3K3-related to Cerebral cavernous malformations 5, MIM# 621032
Mendeliome v1.2180 MAP3K3 Zornitza Stark edited their review of gene: MAP3K3: Changed phenotypes: Cerebral cavernous malformations 5, MIM# 621032
Pulmonary Fibrosis_Interstitial Lung Disease v0.84 POLA2 Bryony Thompson Marked gene: POLA2 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.84 POLA2 Bryony Thompson Gene: pola2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.84 POLA2 Bryony Thompson Classified gene: POLA2 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.84 POLA2 Bryony Thompson Gene: pola2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.83 POLA2 Bryony Thompson gene: POLA2 was added
gene: POLA2 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
Mode of inheritance for gene: POLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLA2 were set to 39616267
Phenotypes for gene: POLA2 were set to Telomere biology syndrome MONDO:0100137
Review for gene: POLA2 was set to GREEN
Added comment: Pulmonary fibrosis is a feature of the phenotype in 4 cases from 2 unrelated families with biallelic variants with functional evidence supporting an effect on telomere length. Pulmonary fibrosis is a common feature of telomere biology disorders.
Sources: Literature
Syndromic Retinopathy v0.218 POLA2 Bryony Thompson Marked gene: POLA2 as ready
Syndromic Retinopathy v0.218 POLA2 Bryony Thompson Gene: pola2 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.218 POLA2 Bryony Thompson Classified gene: POLA2 as Green List (high evidence)
Syndromic Retinopathy v0.218 POLA2 Bryony Thompson Gene: pola2 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.217 POLA2 Bryony Thompson gene: POLA2 was added
gene: POLA2 was added to Syndromic Retinopathy. Sources: Literature
Mode of inheritance for gene: POLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLA2 were set to 39616267
Phenotypes for gene: POLA2 were set to Telomere biology syndrome MONDO:0100137
Review for gene: POLA2 was set to GREEN
Added comment: Retinal telangiectasias/exudates (Coats disease) is a feature of the phenotype. 5 cases from 2 unrelated families with biallelic variants with functional evidence supporting an effect on telomere length.
Sources: Literature
Mendeliome v1.2180 POLA2 Bryony Thompson Phenotypes for gene: POLA2 were changed from Telomere biology disorders; Coats plus syndrome MONDO:0012815 to Telomere biology syndrome MONDO:0100137
Bone Marrow Failure v1.108 POLA2 Bryony Thompson Phenotypes for gene: POLA2 were changed from Telomere biology disorders; Coats plus syndrome MONDO:0012815 to Telomere biology syndrome MONDO:0100137
Bone Marrow Failure v1.107 POLA2 Bryony Thompson Marked gene: POLA2 as ready
Bone Marrow Failure v1.107 POLA2 Bryony Thompson Gene: pola2 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.107 POLA2 Bryony Thompson Classified gene: POLA2 as Green List (high evidence)
Bone Marrow Failure v1.107 POLA2 Bryony Thompson Gene: pola2 has been classified as Green List (High Evidence).
Mendeliome v1.2179 POLA2 Bryony Thompson Marked gene: POLA2 as ready
Mendeliome v1.2179 POLA2 Bryony Thompson Gene: pola2 has been classified as Green List (High Evidence).
Mendeliome v1.2179 POLA2 Bryony Thompson Classified gene: POLA2 as Green List (high evidence)
Mendeliome v1.2179 POLA2 Bryony Thompson Gene: pola2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.296 CTGF Bryony Thompson Marked gene: CTGF as ready
Skeletal dysplasia v0.296 CTGF Bryony Thompson Gene: ctgf has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.296 CTGF Bryony Thompson Phenotypes for gene: CTGF were changed from Kyphomelic dysplasia to Kyphomelic dysplasia MONDO:0008881; Spondyloepimetaphyseal dysplasia MONDO:0100510
Skeletal dysplasia v0.295 CTGF Bryony Thompson Classified gene: CTGF as Amber List (moderate evidence)
Skeletal dysplasia v0.295 CTGF Bryony Thompson Gene: ctgf has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.294 CTGF Bryony Thompson reviewed gene: CTGF: Rating: RED; Mode of pathogenicity: None; Publications: 39414788, 20534727; Phenotypes: Spondyloepimetaphyseal dysplasia MONDO:0100510; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2178 CTGF Bryony Thompson Marked gene: CTGF as ready
Mendeliome v1.2178 CTGF Bryony Thompson Gene: ctgf has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2178 CTGF Bryony Thompson Phenotypes for gene: CTGF were changed from Kyphomelic dysplasia to Kyphomelic dysplasia MONDO:0008881; Spondyloepimetaphyseal dysplasia MONDO:0100510
Mendeliome v1.2177 CTGF Bryony Thompson Publications for gene: CTGF were set to 39506047
Mendeliome v1.2176 CTGF Bryony Thompson Classified gene: CTGF as Amber List (moderate evidence)
Mendeliome v1.2176 CTGF Bryony Thompson Gene: ctgf has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2175 CTGF Bryony Thompson edited their review of gene: CTGF: Changed publications: 39414788, 20534727
Mendeliome v1.2175 CTGF Bryony Thompson edited their review of gene: CTGF: Changed publications: 39414788, 39414788
Mendeliome v1.2175 CTGF Bryony Thompson reviewed gene: CTGF: Rating: RED; Mode of pathogenicity: None; Publications: 39414788; Phenotypes: Spondyloepimetaphyseal dysplasia MONDO:0100510; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal Dysplasia_Fetal v0.225 CTGF Bryony Thompson Marked gene: CTGF as ready
Skeletal Dysplasia_Fetal v0.225 CTGF Bryony Thompson Gene: ctgf has been classified as Amber List (Moderate Evidence).
Skeletal Dysplasia_Fetal v0.225 CTGF Bryony Thompson Phenotypes for gene: CTGF were changed from Kyphomelic dysplasia to Kyphomelic dysplasia MONDO:0008881
Skeletal Dysplasia_Fetal v0.224 CTGF Bryony Thompson Classified gene: CTGF as Amber List (moderate evidence)
Skeletal Dysplasia_Fetal v0.224 CTGF Bryony Thompson Gene: ctgf has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.112 GUK1 Bryony Thompson Marked gene: GUK1 as ready
Combined Immunodeficiency v1.112 GUK1 Bryony Thompson Gene: guk1 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.112 GUK1 Bryony Thompson Classified gene: GUK1 as Amber List (moderate evidence)
Combined Immunodeficiency v1.112 GUK1 Bryony Thompson Gene: guk1 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.111 GUK1 Bryony Thompson gene: GUK1 was added
gene: GUK1 was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: GUK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GUK1 were set to 39230499
Phenotypes for gene: GUK1 were set to Mitochondrial DNA depletion syndrome MONDO:0018158, GUK1-related
Review for gene: GUK1 was set to AMBER
Added comment: Three cases from 2 unrelated families with biallelic variants leading to GUK1 deficiency had altered T-lymphocyte profiles, along with ptosis, ophthalmoparesis, myopathic proximal limb weakness, and variable hepatopathy. One additional case in this study had a normal lymphocyte profile.
Sources: Literature
Mitochondrial disease v0.956 GUK1 Bryony Thompson Marked gene: GUK1 as ready
Mitochondrial disease v0.956 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.956 GUK1 Bryony Thompson Classified gene: GUK1 as Green List (high evidence)
Mitochondrial disease v0.956 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.956 GUK1 Bryony Thompson Classified gene: GUK1 as Green List (high evidence)
Mitochondrial disease v0.956 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.955 GUK1 Bryony Thompson gene: GUK1 was added
gene: GUK1 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: GUK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GUK1 were set to 39230499
Phenotypes for gene: GUK1 were set to Mitochondrial DNA depletion syndrome MONDO:0018158, GUK1-related
Review for gene: GUK1 was set to GREEN
Added comment: 4 adult cases from 3 unrelated families with biallelic variants leading to GUK1 deficiency. Cases presented with ptosis, ophthalmoparesis, myopathic proximal limb weakness, variable hepatopathy, and altered T-lymphocyte profiles. Initial manifestations in childhood or adolescence and developed ptosis and skeletal myopathy. mtDNA depletion/deletions are present in muscle biopsies of reduced activities of mitochondrial respiratory chain enzymes in all 4 cases.
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v1.19 GUK1 Bryony Thompson Marked gene: GUK1 as ready
Rhabdomyolysis and Metabolic Myopathy v1.19 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Nucleotide metabolism disorders v0.4 GUK1 Bryony Thompson Marked gene: GUK1 as ready
Nucleotide metabolism disorders v0.4 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Nucleotide metabolism disorders v0.4 GUK1 Bryony Thompson Classified gene: GUK1 as Green List (high evidence)
Nucleotide metabolism disorders v0.4 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Nucleotide metabolism disorders v0.3 GUK1 Bryony Thompson gene: GUK1 was added
gene: GUK1 was added to Nucleotide metabolism disorders. Sources: Literature
Mode of inheritance for gene: GUK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GUK1 were set to 39230499
Phenotypes for gene: GUK1 were set to Mitochondrial DNA depletion syndrome MONDO:0018158, GUK1-related
Review for gene: GUK1 was set to GREEN
Added comment: Guanylate kinase, encoded by GUK1, is a nucleotide monophosphate kinase. 4 adult cases from 3 unrelated families with biallelic variants leading to GUK1 deficiency. Cases presented with ptosis, ophthalmoparesis, myopathic proximal limb weakness, variable hepatopathy, and altered T-lymphocyte profiles. Initial manifestations in childhood or adolescence and developed ptosis and skeletal myopathy. mtDNA depletion/deletions are present in muscle biopsies of reduced activities of mitochondrial respiratory chain enzymes in all 4 cases.
Sources: Literature
Mendeliome v1.2175 GUK1 Bryony Thompson Phenotypes for gene: GUK1 were changed from Mitochondrial DNA depletion syndrome MONDO:0018158 to Mitochondrial DNA depletion syndrome MONDO:0018158, GUK1-related
Rhabdomyolysis and Metabolic Myopathy v1.19 GUK1 Bryony Thompson Classified gene: GUK1 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v1.19 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.18 GUK1 Bryony Thompson gene: GUK1 was added
gene: GUK1 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Literature
Mode of inheritance for gene: GUK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GUK1 were set to 39230499
Phenotypes for gene: GUK1 were set to Mitochondrial DNA depletion syndrome MONDO:0018158, GUK1-related
Review for gene: GUK1 was set to GREEN
Added comment: 4 adult cases from 3 unrelated families with biallelic variants leading to GUK1 deficiency. Cases presented with ptosis, ophthalmoparesis, myopathic proximal limb weakness, variable hepatopathy, and altered T-lymphocyte profiles. Initial manifestations in childhood or adolescence and developed ptosis and skeletal myopathy. mtDNA depletion/deletions are present in muscle biopsies of reduced activities of mitochondrial respiratory chain enzymes in all 4 cases. The condition presents with a mitochondrial myopathy.
Sources: Literature
Mendeliome v1.2174 GUK1 Bryony Thompson Marked gene: GUK1 as ready
Mendeliome v1.2174 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Mendeliome v1.2174 GUK1 Bryony Thompson Classified gene: GUK1 as Green List (high evidence)
Mendeliome v1.2174 GUK1 Bryony Thompson Gene: guk1 has been classified as Green List (High Evidence).
Mendeliome v1.2173 GUK1 Bryony Thompson gene: GUK1 was added
gene: GUK1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GUK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GUK1 were set to 39230499
Phenotypes for gene: GUK1 were set to Mitochondrial DNA depletion syndrome MONDO:0018158
Review for gene: GUK1 was set to GREEN
Added comment: 4 adult cases from 3 unrelated families with biallelic variants leading to GUK1 deficiency. Cases presented with ptosis, ophthalmoparesis, myopathic proximal limb weakness, variable hepatopathy, and altered T-lymphocyte profiles. Initial manifestations in childhood or adolescence and developed ptosis and skeletal myopathy. mtDNA depletion/deletions are present in muscle biopsies of reduced activities of mitochondrial respiratory chain enzymes in all 4 cases.
Sources: Literature
Mendeliome v1.2172 PPP2R2B Bryony Thompson Phenotypes for gene: PPP2R2B were changed from to Neurodevelopmental disorder MONDO:0700092, PPP2R2B-related
Intellectual disability syndromic and non-syndromic v1.9 PPP2R2B Bryony Thompson Marked gene: PPP2R2B as ready
Intellectual disability syndromic and non-syndromic v1.9 PPP2R2B Bryony Thompson Gene: ppp2r2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2171 PPP2R2B Bryony Thompson Publications for gene: PPP2R2B were set to
Intellectual disability syndromic and non-syndromic v1.9 PPP2R2B Bryony Thompson Classified gene: PPP2R2B as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.9 PPP2R2B Bryony Thompson Gene: ppp2r2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2170 PPP2R2B Bryony Thompson Mode of inheritance for gene: PPP2R2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.8 PPP2R2B Bryony Thompson Classified gene: PPP2R2B as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.8 PPP2R2B Bryony Thompson Gene: ppp2r2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2169 PPP2R2B Bryony Thompson Classified gene: PPP2R2B as Amber List (moderate evidence)
Mendeliome v1.2169 PPP2R2B Bryony Thompson Gene: ppp2r2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2168 PPP2R2B Bryony Thompson reviewed gene: PPP2R2B: Rating: AMBER; Mode of pathogenicity: None; Publications: 25356899, 39565297; Phenotypes: Neurodevelopmental disorder MONDO:0700092, PPP2R2B-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.7 PPP2R2B Bryony Thompson gene: PPP2R2B was added
gene: PPP2R2B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PPP2R2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2R2B were set to 25356899; 39565297
Phenotypes for gene: PPP2R2B were set to Neurodevelopmental disorder MONDO:0700092, PPP2R2B-related
Review for gene: PPP2R2B was set to AMBER
Added comment: 5 cases with NDD and heterozygous missense (4/5 confirmed de novo): p.Thr246Lys (unknown inheritance), p.Asn310Lys (confirmed de novo), p.Glu37Lys (confirmed de novo, also had RNU4-2 path de novo Path variant), p.Ile427Thr (confirmed de novo, also had TAOK1 inherited Path variant), p.Arg149Pro (confirmed de novo). 5/5 with intellectual disability and developmental delay, 4/5 with seizures, 2/5 with hearing loss/auditory neuropathy. Study includes in vitro functional assays supporting a possible loss of function mechanism of disease. The 2 missense with additional diagnoses (E37K & I427T) demonstrated a partial reduction in PP2A holoenzyme assembly. Only 3 cases with a possible diagnosis that could be attributed to the PPP2R2B only, and only 2 were confirmed de novo.
Sources: Literature
Mendeliome v1.2168 PPP2R2B Bryony Thompson Deleted their review
Genetic Epilepsy v1.77 PPP2R2B Bryony Thompson Marked gene: PPP2R2B as ready
Genetic Epilepsy v1.77 PPP2R2B Bryony Thompson Gene: ppp2r2b has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.77 PPP2R2B Bryony Thompson Classified gene: PPP2R2B as Amber List (moderate evidence)
Genetic Epilepsy v1.77 PPP2R2B Bryony Thompson Gene: ppp2r2b has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.76 PPP2R2B Bryony Thompson gene: PPP2R2B was added
gene: PPP2R2B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PPP2R2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2R2B were set to 25356899; 39565297
Phenotypes for gene: PPP2R2B were set to Neurodevelopmental disorder MONDO:0700092, PPP2R2B-related
Review for gene: PPP2R2B was set to AMBER
Added comment: 5 cases with NDD and heterozygous missense (4/5 confirmed de novo): p.Thr246Lys (unknown inheritance), p.Asn310Lys (confirmed de novo), p.Glu37Lys (confirmed de novo, also had RNU4-2 path de novo Path variant), p.Ile427Thr (confirmed de novo, also had TAOK1 inherited Path variant), p.Arg149Pro (confirmed de novo). 5/5 with intellectual disability and developmental delay, 4/5 with seizures, 2/5 with hearing loss/auditory neuropathy. Study includes in vitro functional assays supporting a possible loss of function mechanism of disease. The 2 missense with additional diagnoses (E37K & I427T) demonstrated a partial reduction in PP2A holoenzyme assembly. Only 3 cases with a possible diagnosis that could be attributed to the PPP2R2B only, and only 2 were confirmed de novo.
Sources: Literature
Mendeliome v1.2168 PPP2R2B Bryony Thompson Deleted their comment
Mendeliome v1.2168 PPP2R2B Bryony Thompson edited their review of gene: PPP2R2B: Added comment: 5 cases with NDD and heterozygous missense (4/5 confirmed de novo): p.Thr246Lys (unknown inheritance), p.Asn310Lys (confirmed de novo), p.Glu37Lys (confirmed de novo, also had RNU4-2 path de novo Path variant), p.Ile427Thr (confirmed de novo, also had TAOK1 inherited Path variant), p.Arg149Pro (confirmed de novo). 5/5 with intellectual disability and developmental delay, 4/5 with seizures, 2/5 with hearing loss/auditory neuropathy. Study includes in vitro functional assays supporting a possible loss of function mechanism of disease. The 2 missense with additional diagnoses (E37K & I427T) demonstrated a partial reduction in PP2A holoenzyme assembly. Only 3 cases with a possible diagnosis that could be attributed to the PPP2R2B only, and only 2 were confirmed de novo.; Changed rating: AMBER; Changed publications: 25356899, 39565297; Changed phenotypes: Neurodevelopmental disorder MONDO:0700092
Mendeliome v1.2168 PPP2R2B Bryony Thompson Deleted their comment
Early-onset Dementia v1.27 KIF5A Bryony Thompson Marked gene: KIF5A as ready
Early-onset Dementia v1.27 KIF5A Bryony Thompson Gene: kif5a has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v1.27 KIF5A Bryony Thompson Classified gene: KIF5A as Amber List (moderate evidence)
Early-onset Dementia v1.27 KIF5A Bryony Thompson Gene: kif5a has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v1.26 KIF5A Bryony Thompson gene: KIF5A was added
gene: KIF5A was added to Early-onset Dementia. Sources: Other
Mode of inheritance for gene: KIF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5A were set to 33077544; 36604770
Phenotypes for gene: KIF5A were set to Amyotrophic lateral sclerosis, susceptibility to, 25 MONDO:0060670
Mode of pathogenicity for gene: KIF5A was set to Other
Review for gene: KIF5A was set to AMBER
Added comment: ALS-FTD phenotype has been reported in two families with KIF5A variants. The mechanism of disease is likely gain of function.
Sources: Other
Paroxysmal Dyskinesia v0.133 KCNJ10 Shekeeb Mohammad reviewed gene: KCNJ10: Rating: GREEN; Mode of pathogenicity: None; Publications: 38436103, 38436103; Phenotypes: paroxysmal kinesigenic dyskinesia; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Paroxysmal Dyskinesia v0.133 SPR Shekeeb Mohammad reviewed gene: SPR: Rating: AMBER; Mode of pathogenicity: None; Publications: 32591469; Phenotypes: dopamine responsive dystonia, oculogyric crises; Mode of inheritance: None
Paroxysmal Dyskinesia v0.133 PDHA1 Shekeeb Mohammad reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: paroyxsmal exercise induced dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Paroxysmal Dyskinesia v0.133 ALDH5A1 Shekeeb Mohammad gene: ALDH5A1 was added
gene: ALDH5A1 was added to Paroxysmal Dyskinesia. Sources: Literature
Mode of inheritance for gene: ALDH5A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALDH5A1 were set to 17438226; 38499966
Phenotypes for gene: ALDH5A1 were set to epilepsy; paroxysmal exercise induced dyskinesia; globus pallidus hyperintensities on MRI
Review for gene: ALDH5A1 was set to GREEN
gene: ALDH5A1 was marked as current diagnostic
Added comment: Reported cases with paroyxsmal dyskinesia; exercise induced
current patient under my care with isolated paroxysmal dyskinesia without epilepsy with confirmed pathogenic variants in ALDH5A1 and supportive MRI changes.
This is an important differential for Paroxysmal dyskinesia with globus pallidus changes (in addition to ECHS1 and pyruvate dehydrogenase deficiency)
Sources: Literature
Dystonia - complex v0.242 DDC Sangavi Sivagnanasundram reviewed gene: DDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 20505134; Phenotypes: aromatic L-amino acid decarboxylase deficiency MONDO:0012084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2168 GPATCH11 Sangavi Sivagnanasundram edited their review of gene: GPATCH11: Changed phenotypes: early-onset retinal dystrophy with neurological impairment MONDO:0019118
Mendeliome v1.2168 CTGF Sangavi Sivagnanasundram edited their review of gene: CTGF: Changed phenotypes: Kyphomelic dysplasia, skeletal dysplasia MONDO:0018230
Skeletal dysplasia v0.294 CTGF Sangavi Sivagnanasundram edited their review of gene: CTGF: Changed phenotypes: Kyphomelic dysplasia, skeletal dysplasia MONDO:0018230
Dystonia - complex v0.242 DCAF17 Sangavi Sivagnanasundram reviewed gene: DCAF17: Rating: GREEN; Mode of pathogenicity: None; Publications: 18175354, 36185913, 17167799; Phenotypes: Woodhouse-Sakati syndrome MONDO:0009419; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.242 COASY Sangavi Sivagnanasundram reviewed gene: COASY: Rating: GREEN; Mode of pathogenicity: None; Publications: 23447832, 24360804, 27021474; Phenotypes: neurodegeneration with brain iron accumulation 6 MONDO:0014290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.540 WDR47 Bryony Thompson Marked gene: WDR47 as ready
Callosome v0.540 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Callosome v0.540 WDR47 Bryony Thompson Classified gene: WDR47 as Green List (high evidence)
Callosome v0.540 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Mendeliome v1.2168 WDR47 Bryony Thompson Marked gene: WDR47 as ready
Mendeliome v1.2168 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Mendeliome v1.2168 WDR47 Bryony Thompson Classified gene: WDR47 as Green List (high evidence)
Mendeliome v1.2168 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.75 WDR47 Bryony Thompson Marked gene: WDR47 as ready
Genetic Epilepsy v1.75 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Microcephaly v1.288 WDR47 Bryony Thompson Marked gene: WDR47 as ready
Microcephaly v1.288 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Mendeliome v1.2167 WDR47 Bryony Thompson gene: WDR47 was added
gene: WDR47 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WDR47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR47 were set to 39609633; 35474353
Phenotypes for gene: WDR47 were set to Complex neurodevelopmental disorder MONDO:0100038, WDR47-related; Congenital heart disease MONDO:0005453
Review for gene: WDR47 was set to GREEN
Added comment: PMID: 39609633 - 7 cases from 5 unrelated families with biallelic variants and a complex neurodevelopmental syndrome. The most frequent phenotypes were corpus callosum dysgenesis (7/7), microcephaly (7/7), mild to severe intellectual disability (7/7), epilepsy (7/7). Additionally, mouse models recapitulate the human phenotype. Loss of function is the mechanism of disease. Heterozygous parents had no phenotype.

Limited evidence for mono allelic association with congenital heart defects
PMID: 35474353 - rare assumed de novo heterozygous variant (NM_014969.5:c.2056G>A p.(Val686Ile) - 10 hets in gnomAD v4.1) detected in a case with heterotaxy including AVCD, vena azygos continuation, artery lusoria, truncus bicaroticus and polysplenia. Screening of exams for 2,019 individuals with situs inversus totalis, heterotaxy, or isolated CHD detected 2 additional individuals with monoallelic rare missense variants. No functional assays or other supporting evidence. All variants are VUS
Sources: Literature
Genetic Epilepsy v1.75 WDR47 Bryony Thompson Classified gene: WDR47 as Green List (high evidence)
Genetic Epilepsy v1.75 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Microcephaly v1.288 WDR47 Bryony Thompson Classified gene: WDR47 as Green List (high evidence)
Microcephaly v1.288 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Callosome v0.539 WDR47 Bryony Thompson gene: WDR47 was added
gene: WDR47 was added to Callosome. Sources: Literature
Mode of inheritance for gene: WDR47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR47 were set to 39609633
Phenotypes for gene: WDR47 were set to Complex neurodevelopmental disorder MONDO:0100038, WDR47-related
Review for gene: WDR47 was set to GREEN
Added comment: 7 cases from 5 unrelated families with biallelic variants and a complex neurodevelopmental syndrome. The most frequent phenotypes were corpus callosum dysgenesis (7/7), microcephaly (7/7), mild to severe intellectual disability (7/7), epilepsy (7/7). Additionally, mouse models recapitulate the human phenotype. Loss of function is the mechanism of disease. Heterozygous parents had no phenotype.
Sources: Literature
Genetic Epilepsy v1.74 WDR47 Bryony Thompson gene: WDR47 was added
gene: WDR47 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: WDR47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR47 were set to 39609633
Phenotypes for gene: WDR47 were set to Complex neurodevelopmental disorder MONDO:0100038, WDR47-related
Review for gene: WDR47 was set to GREEN
Added comment: 7 cases from 5 unrelated families with biallelic variants and a complex neurodevelopmental syndrome. The most frequent phenotypes were corpus callosum dysgenesis (7/7), microcephaly (7/7), mild to severe intellectual disability (7/7), epilepsy (7/7). Additionally, mouse models recapitulate the human phenotype. Loss of function is the mechanism of disease. Heterozygous parents had no phenotype.
Sources: Literature
Microcephaly v1.287 WDR47 Bryony Thompson gene: WDR47 was added
gene: WDR47 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: WDR47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR47 were set to 39609633
Phenotypes for gene: WDR47 were set to Complex neurodevelopmental disorder MONDO:0100038, WDR47-related
Review for gene: WDR47 was set to GREEN
Added comment: 7 cases from 5 unrelated families with biallelic variants and a complex neurodevelopmental syndrome. The most frequent phenotypes were corpus callosum dysgenesis (7/7), microcephaly (7/7), mild to severe intellectual disability (7/7), epilepsy (7/7). Additionally, mouse models recapitulate the human phenotype. Loss of function is the mechanism of disease. Heterozygous parents had no phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.6 WDR47 Bryony Thompson Marked gene: WDR47 as ready
Intellectual disability syndromic and non-syndromic v1.6 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.6 WDR47 Bryony Thompson Classified gene: WDR47 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.6 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.5 WDR47 Bryony Thompson gene: WDR47 was added
gene: WDR47 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: WDR47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR47 were set to 39609633
Phenotypes for gene: WDR47 were set to Complex neurodevelopmental disorder MONDO:0100038, WDR47-related
Review for gene: WDR47 was set to GREEN
Added comment: 7 cases from 5 unrelated families with biallelic variants and a complex neurodevelopmental syndrome. The most frequent phenotypes were corpus callosum dysgenesis (7/7), microcephaly (7/7), mild to severe intellectual disability (7/7), epilepsy (7/7). Additionally, mouse models recapitulate the human phenotype. Loss of function is the mechanism of disease. Heterozygous parents had no phenotype.
Sources: Literature
Congenital Heart Defect v0.424 WDR47 Bryony Thompson Marked gene: WDR47 as ready
Congenital Heart Defect v0.424 WDR47 Bryony Thompson Gene: wdr47 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.424 WDR47 Bryony Thompson gene: WDR47 was added
gene: WDR47 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: WDR47 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR47 were set to 35474353; 39609633
Phenotypes for gene: WDR47 were set to Congenital heart disease MONDO:0005453
Review for gene: WDR47 was set to RED
Added comment: A rare assumed de novo heterozygous variant (NM_014969.5:c.2056G>A p.(Val686Ile) - 10 hets in gnomAD v4.1) detected in a case with heterotaxy including AVCD, vena azygos continuation, artery lusoria, truncus bicaroticus and polysplenia. Screening of exams for 2,019 individuals with situs inversus totalis, heterotaxy, or isolated CHD detected 2 additional individuals with monoallelic rare missense variants. No functional assays or other supporting evidence. All variants are VUS. In a recent publication of biallelic variants associated with a complex neurodevelopmental syndrome, heterozygous carriers had no phenotype.
Sources: Literature
Differences of Sex Development v0.348 FSHR Chirag Patel reviewed gene: FSHR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16630814, 7553856, 9020851, 9769327, 20087398, 9854118, 12930928, 12930927, 17721928, 26911863; Phenotypes: Ovarian dysgenesis 1 MONDO:0024463, Ovarian hyperstimulation syndrome MONDO:0011972; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.348 FSHB Chirag Patel reviewed gene: FSHB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 8220432, 9280841, 9624193, 9806482, 9271483, 16630814; Phenotypes: Hypogonadotropic hypogonadism 24 without anosmia, MIM#229070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.348 FGFR2 Chirag Patel reviewed gene: FGFR2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29848297, 32879300; Phenotypes: Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis,MIM# 207410, Apert syndrome, MIM# 101200, Beare-Stevenson cutis gyrata syndrome, MIM# 123790, Bent bone dysplasia syndrome, MIM# 614592; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.348 FGFR1 Chirag Patel reviewed gene: FGFR1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18034870, 23812909, 26942290; Phenotypes: Encephalocraniocutaneous lipomatosis, somatic mosaic 613001, Hartsfield syndrome 615465, Hypogonadotropic hypogonadism 2 with or without anosmia 147950, Osteoglophonic dysplasia 166250; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.348 SOX9 Chirag Patel reviewed gene: SOX9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Campomelic dysplasia, MIM# 114290, Campomelic dysplasia, MONDO:0007251, Acampomelic campomelic dysplasia, MIM # 114290, 46XX sex reversal 2, MIM# 278850, 46XY sex reversal 10, MIM # 616425; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.348 SRY Chirag Patel reviewed gene: SRY: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 9143916 15863672; Phenotypes: 46XX sex reversal 1, MIM# 400045, 46XY sex reversal 1 , MIM#400044; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Differences of Sex Development v0.348 WT1 Chirag Patel reviewed gene: WT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Wilms tumor, MONDO:0006058, Wilms tumor 1, MONDO:0008679, Wilms tumor, type 1, MIM#194070, Denys-Drash syndrome, MIM#194080, Frasier syndrome, MIM#136680; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.294 CTGF Sangavi Sivagnanasundram gene: CTGF was added
gene: CTGF was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: CTGF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTGF were set to 39506047
Phenotypes for gene: CTGF were set to Kyphomelic dysplasia
Review for gene: CTGF was set to AMBER
Added comment: CCN2 is the new HGNC approved name.

PMID: 39506047
Three individuals from two unrelated consanguineous families presented with short stature, facial dysmorphism and kyphomelic skeletal dysplasia.

A rare missense variant in family 1 (Cys148Tyr) and novel frameshift variant (Pro260LeufsTer7) in family 2 was identified in homozygous state.
Zebrafish model was also conducted that showed altered body curvature and impaired cartilage formation in craniofacial region resulting in either bent or missing tails.

A missense variant c.443G>A; p.(Cys148Tyr) in exon 3 and a frameshift variant, c.779_786del; p.(Pro260LeufsTer7) in exon 5.
Sources: Literature
Mendeliome v1.2166 CTGF Sangavi Sivagnanasundram changed review comment from: CCN2 is the new HGNC approved name.

PMID: 39506047
Three individuals from two unrelated consanguineous families presented with short stature, facial dysmorphism and kyphomelic skeletal dysplasia.

A rare missense variant in family 1 (Cys148Tyr) and novel frameshift variant (Pro260LeufsTer7) in family 2 was identified in homozygous state.
Zebrafish model was also conducted that showed altered body curvature and impaired cartilage formation in craniofacial region resulting in either bent of missing tails.

A missense variant c.443G>A; p.(Cys148Tyr) in exon 3 and a frameshift variant, c.779_786del; p.(Pro260LeufsTer7) in exon 5.
Sources: Literature; to: CCN2 is the new HGNC approved name.

PMID: 39506047
Three individuals from two unrelated consanguineous families presented with short stature, facial dysmorphism and kyphomelic skeletal dysplasia.

A rare missense variant in family 1 (Cys148Tyr) and novel frameshift variant (Pro260LeufsTer7) in family 2 was identified in homozygous state.
Zebrafish model was also conducted that showed altered body curvature and impaired cartilage formation in craniofacial region resulting in either bent or missing tails.

A missense variant c.443G>A; p.(Cys148Tyr) in exon 3 and a frameshift variant, c.779_786del; p.(Pro260LeufsTer7) in exon 5.
Sources: Literature
Skeletal Dysplasia_Fetal v0.223 CTGF Sangavi Sivagnanasundram gene: CTGF was added
gene: CTGF was added to Skeletal Dysplasia_Fetal. Sources: Literature
Mode of inheritance for gene: CTGF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTGF were set to 39506047
Phenotypes for gene: CTGF were set to Kyphomelic dysplasia
Review for gene: CTGF was set to AMBER
Added comment: CCN2 is the new HGNC approved name.

PMID: 39506047
Three individuals from two unrelated consanguineous families presented with short stature, facial dysmorphism and kyphomelic skeletal dysplasia.

A rare missense variant in family 1 (Cys148Tyr) and novel frameshift variant (Pro260LeufsTer7) in family 2 was identified in homozygous state.
Zebrafish model was also conducted that showed altered body curvature and impaired cartilage formation in craniofacial region resulting in either bent or missing tails.

A missense variant c.443G>A; p.(Cys148Tyr) in exon 3 and a frameshift variant, c.779_786del; p.(Pro260LeufsTer7) in exon 5.
Sources: Literature
Mendeliome v1.2166 CTGF Sangavi Sivagnanasundram gene: CTGF was added
gene: CTGF was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CTGF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTGF were set to 39506047
Phenotypes for gene: CTGF were set to Kyphomelic dysplasia
Review for gene: CTGF was set to AMBER
Added comment: CCN2 is the new HGNC approved name.

PMID: 39506047
Three individuals from two unrelated consanguineous families presented with short stature, facial dysmorphism and kyphomelic skeletal dysplasia.

A rare missense variant in family 1 (Cys148Tyr) and novel frameshift variant (Pro260LeufsTer7) in family 2 was identified in homozygous state.
Zebrafish model was also conducted that showed altered body curvature and impaired cartilage formation in craniofacial region resulting in either bent of missing tails.

A missense variant c.443G>A; p.(Cys148Tyr) in exon 3 and a frameshift variant, c.779_786del; p.(Pro260LeufsTer7) in exon 5.
Sources: Literature
Mendeliome v1.2166 GPATCH11 Sangavi Sivagnanasundram reviewed gene: GPATCH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 39572588; Phenotypes: early-onset retinal dystrophy with neurological impairment; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bone Marrow Failure v1.106 POLA2 Sangavi Sivagnanasundram edited their review of gene: POLA2: Changed rating: GREEN
Bone Marrow Failure v1.106 POLA2 Sangavi Sivagnanasundram gene: POLA2 was added
gene: POLA2 was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: POLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLA2 were set to 39616267
Phenotypes for gene: POLA2 were set to Telomere biology disorders; Coats plus syndrome MONDO:0012815
Added comment: New gene-disease association.

PMID: 39616267 - Five individuals from two unrelated swedish families presenting with clinical phenotype suggestive of a TBD disorder with Coats plus features including retinal and gastrointestinal telangiectasias. Affected individuals also presented with shortened telomeres.

Compound heterozygous variants were identified in both families.
Family A (Ile96Thr;Pro424Leu) - Both variants are present in gnomAD v4.1 but FAF is rare enough for AR condition [c.287 T > C, p.(Ile96Thr) - FAF 0.002%; c.1271 C > T, p.(Pro424Leu) - FAF 0.0002 %]
Family B (Ile96Thr; intragenic SNV resulting in the deletion of the 5’ terminal and exon 1) - same missense as the other family along with an SNV.

In vitro assay using CRISPR/Cas9 genome engineering into HEK293T to assess whether the p.(Ile96Thr) would affect telomere length. The subclones carrying the missense variant showed telomeric shortening of ~4kb compared to the WT subclones.
Sources: Literature
Mendeliome v1.2166 POLA2 Sangavi Sivagnanasundram gene: POLA2 was added
gene: POLA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLA2 were set to 39616267
Phenotypes for gene: POLA2 were set to Telomere biology disorders; Coats plus syndrome MONDO:0012815
Review for gene: POLA2 was set to GREEN
Added comment: New gene-disease association.

PMID: 39616267 - Five individuals from two unrelated swedish families presenting with clinical phenotype suggestive of a TBD disorder with Coats plus features including retinal and gastrointestinal telangiectasias. Affected individuals also presented with shortened telomeres.

Compound heterozygous variants were identified in both families.
Family A (Ile96Thr;Pro424Leu) - Both variants are present in gnomAD v4.1 but FAF is rare enough for AR condition [c.287 T > C, p.(Ile96Thr) - FAF 0.002%; c.1271 C > T, p.(Pro424Leu) - FAF 0.0002 %]
Family B (Ile96Thr; intragenic SNV resulting in the deletion of the 5’ terminal and exon 1) - same missense as the other family along with an SNV.

In vitro assay using CRISPR/Cas9 genome engineering into HEK293T to assess whether the p.(Ile96Thr) would affect telomere length. The subclones carrying the missense variant showed telomeric shortening of ~4kb compared to the WT subclones.
Sources: Literature
Differences of Sex Development v0.348 FRAS1 Zornitza Stark Marked gene: FRAS1 as ready
Differences of Sex Development v0.348 FRAS1 Zornitza Stark Gene: fras1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.348 FRAS1 Zornitza Stark Publications for gene: FRAS1 were set to PMID: 12766769, 18671281, 18000968
Mendeliome v1.2166 FGF8 Zornitza Stark edited their review of gene: FGF8: Added comment: Association with CHD: Two individuals reported but extensive functional data. MODERATE by ClinGen.; Changed publications: 32664970, 7768185, 32664970, 10603341, 19509466, 9462741, 10603341, 12223415; Changed phenotypes: Hypogonadotropic hypogonadism 6 with or without anosmia, MIM# 612702, Hypoplastic femurs and pelvis, MIM#619545, Congenital heart disease MONDO:0005453, FGF8-related
Congenital Heart Defect v0.423 FGF8 Zornitza Stark Marked gene: FGF8 as ready
Congenital Heart Defect v0.423 FGF8 Zornitza Stark Gene: fgf8 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.423 FGF8 Zornitza Stark Classified gene: FGF8 as Amber List (moderate evidence)
Congenital Heart Defect v0.423 FGF8 Zornitza Stark Gene: fgf8 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.422 FGF8 Zornitza Stark gene: FGF8 was added
gene: FGF8 was added to Congenital Heart Defect. Sources: Expert list
Mode of inheritance for gene: FGF8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGF8 were set to 32664970; 7768185; 32664970; 10603341; 19509466; 9462741; 10603341; 12223415
Phenotypes for gene: FGF8 were set to Congenital heart disease MONDO:0005453, FGF8-related
Review for gene: FGF8 was set to AMBER
Added comment: Two individuals reported but extensive functional data. MODERATE by ClinGen.
Sources: Expert list
Differences of Sex Development v0.347 FGF8 Zornitza Stark Marked gene: FGF8 as ready
Differences of Sex Development v0.347 FGF8 Zornitza Stark Gene: fgf8 has been classified as Green List (High Evidence).
Differences of Sex Development v0.347 FGF8 Zornitza Stark Phenotypes for gene: FGF8 were changed from to Hypogonadotropic hypogonadism 6 with or without anosmia, MIM# 612702
Differences of Sex Development v0.346 FGF8 Zornitza Stark Publications for gene: FGF8 were set to
Differences of Sex Development v0.345 FGF8 Zornitza Stark Mode of inheritance for gene: FGF8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.344 FGF8 Zornitza Stark reviewed gene: FGF8: Rating: GREEN; Mode of pathogenicity: None; Publications: 20463092, 18596921, 24280688, 31748124; Phenotypes: Hypogonadotropic hypogonadism 6 with or without anosmia, MIM# 612702; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.344 DHCR7 Zornitza Stark Marked gene: DHCR7 as ready
Differences of Sex Development v0.344 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Green List (High Evidence).
Differences of Sex Development v0.344 DHCR7 Zornitza Stark Phenotypes for gene: DHCR7 were changed from to Smith-Lemli-Opitz syndrome, MIM#270400
Differences of Sex Development v0.343 DHCR7 Zornitza Stark Mode of inheritance for gene: DHCR7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.342 DHCR7 Zornitza Stark reviewed gene: DHCR7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Smith-Lemli-Opitz syndrome, MIM#270400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.342 CTU2 Zornitza Stark Marked gene: CTU2 as ready
Differences of Sex Development v0.342 CTU2 Zornitza Stark Gene: ctu2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.342 CTU2 Zornitza Stark Publications for gene: CTU2 were set to PMID: 27480277, 26633546, 31301155, 38348206
Differences of Sex Development v0.341 CHD7 Zornitza Stark Marked gene: CHD7 as ready
Differences of Sex Development v0.341 CHD7 Zornitza Stark Gene: chd7 has been classified as Green List (High Evidence).
Differences of Sex Development v0.341 CHD7 Zornitza Stark Phenotypes for gene: CHD7 were changed from to Hypogonadotropic hypogonadism 5 with or without anosmia MIM#612370; CHARGE syndrome MIM#214800
Differences of Sex Development v0.340 CHD7 Zornitza Stark Publications for gene: CHD7 were set to
Differences of Sex Development v0.339 CHD7 Zornitza Stark Mode of inheritance for gene: CHD7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.338 CHD7 Zornitza Stark reviewed gene: CHD7: Rating: GREEN; Mode of pathogenicity: None; Publications: 26411921; Phenotypes: Hypogonadotropic hypogonadism 5 with or without anosmia MIM#612370, CHARGE syndrome MIM#214800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.338 CHD4 Zornitza Stark Marked gene: CHD4 as ready
Differences of Sex Development v0.338 CHD4 Zornitza Stark Gene: chd4 has been classified as Green List (High Evidence).
Differences of Sex Development v0.338 CHD4 Zornitza Stark Publications for gene: CHD4 were set to PMID: 31388190, 32881470
Differences of Sex Development v0.337 ATRX Zornitza Stark Marked gene: ATRX as ready
Differences of Sex Development v0.337 ATRX Zornitza Stark Gene: atrx has been classified as Green List (High Evidence).
Differences of Sex Development v0.337 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from to ATR-X-related syndrome MONDO:0016980
Differences of Sex Development v0.336 ATRX Zornitza Stark Mode of inheritance for gene: ATRX 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)
Differences of Sex Development v0.335 ATRX Zornitza Stark reviewed gene: ATRX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ATR-X-related syndrome MONDO:0016980; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Differences of Sex Development v0.335 ARX Zornitza Stark Marked gene: ARX as ready
Differences of Sex Development v0.335 ARX Zornitza Stark Gene: arx has been classified as Green List (High Evidence).
Differences of Sex Development v0.335 ARX Zornitza Stark Phenotypes for gene: ARX were changed from to X-linked lissencephaly with abnormal genitalia, MONDO:0010268
Differences of Sex Development v0.334 ARX Zornitza Stark Publications for gene: ARX were set to
Differences of Sex Development v0.333 ARX Zornitza Stark Mode of inheritance for gene: ARX 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)
Differences of Sex Development v0.332 ARX Zornitza Stark reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: None; Publications: 14722918; Phenotypes: X-linked lissencephaly with abnormal genitalia, MONDO:0010268; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Differences of Sex Development v0.332 AR Zornitza Stark Marked gene: AR as ready
Differences of Sex Development v0.332 AR Zornitza Stark Gene: ar has been classified as Green List (High Evidence).
Differences of Sex Development v0.332 AR Zornitza Stark Phenotypes for gene: AR were changed from to Hypospadias 1, X-linked MIM#30063; Androgen insensitivity MIM#300068; Androgen insensitivity, partial, with or without breast cancer MIM#312300
Differences of Sex Development v0.331 AR Zornitza Stark Publications for gene: AR were set to
Differences of Sex Development v0.330 AR Zornitza Stark Mode of inheritance for gene: AR was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.329 AR Zornitza Stark reviewed gene: AR: Rating: GREEN; Mode of pathogenicity: None; Publications: 22334387; Phenotypes: Hypospadias 1, X-linked MIM#30063, Androgen insensitivity MIM#300068, Androgen insensitivity, partial, with or without breast cancer MIM#312300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.329 AMHR2 Zornitza Stark Marked gene: AMHR2 as ready
Differences of Sex Development v0.329 AMHR2 Zornitza Stark Gene: amhr2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.329 AMHR2 Zornitza Stark Phenotypes for gene: AMHR2 were changed from to Persistent Mullerian duct syndrome, type II MIM#261550
Differences of Sex Development v0.328 AMHR2 Zornitza Stark Publications for gene: AMHR2 were set to
Differences of Sex Development v0.327 AMHR2 Zornitza Stark Mode of inheritance for gene: AMHR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.326 AMHR2 Zornitza Stark reviewed gene: AMHR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34810374; Phenotypes: Persistent Mullerian duct syndrome, type II MIM#261550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Spontaneous coronary artery dissection v0.53 PKD1 Stephanie Hesselson reviewed gene: PKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29650765,33125268,26971055,24303518,19557720,9719186,18992981,26069747,20634758,33969096,28915698; Phenotypes: CORONARY ARTERY DISSECTION SPONTANEOUS MIM#122455, POLYCYSTIC KIDNEY DISEASE 1 WITH OR WITHOUT POLYCYSTIC LIVER DISEASE, PKD1 MIM#173900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.242 C19orf12 Sangavi Sivagnanasundram reviewed gene: C19orf12: Rating: GREEN; Mode of pathogenicity: None; Publications: 21981780, 22508347; Phenotypes: neurodegeneration with brain iron accumulation 4 MONDO:0013674; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.242 BCAP31 Sangavi Sivagnanasundram reviewed gene: BCAP31: Rating: GREEN; Mode of pathogenicity: None; Publications: 24011989, 28332767, 30713915, 31330203, 32652807; Phenotypes: severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome MONDO:0010334; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Dystonia - complex v0.242 ATP13A2 Sangavi Sivagnanasundram reviewed gene: ATP13A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21094623, 20853184, 20310007; Phenotypes: Kufor-Rakeb syndrome MONDO:0011706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.325 Chirag Patel Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Royal Melbourne Hospital; Rare Disease
Differences of Sex Development v0.324 FREM2 Chirag Patel Classified gene: FREM2 as Green List (high evidence)
Differences of Sex Development v0.324 FREM2 Chirag Patel Gene: frem2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.324 FREM2 Chirag Patel Classified gene: FREM2 as Green List (high evidence)
Differences of Sex Development v0.324 FREM2 Chirag Patel Gene: frem2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.323 FREM2 Chirag Patel Classified gene: FREM2 as Green List (high evidence)
Differences of Sex Development v0.323 FREM2 Chirag Patel Gene: frem2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.323 FRAS1 Chirag Patel Classified gene: FRAS1 as Green List (high evidence)
Differences of Sex Development v0.323 FRAS1 Chirag Patel Gene: fras1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.322 FRAS1 Chirag Patel gene: FRAS1 was added
gene: FRAS1 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: FRAS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRAS1 were set to PMID: 12766769, 18671281, 18000968
Phenotypes for gene: FRAS1 were set to Fraser syndrome 1, MIM#219000
Review for gene: FRAS1 was set to GREEN
Added comment: Fraser syndrome is an autosomal recessive malformation disorder. Major criteria include syndactyly, cryptophthalmos spectrum, urinary tract abnormalities, ambiguous genitalia, laryngeal and tracheal anomalies, and positive family history. Minor criteria include anorectal defects, dysplastic ears, skull ossification defects, umbilical abnormalities, and nasal anomalies.
Established gene-disease association.
Sources: Literature
Differences of Sex Development v0.321 FREM2 Chirag Patel gene: FREM2 was added
gene: FREM2 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: FREM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FREM2 were set to PMID: 15838507, 29688405, 18203166, 18671281, 18000968
Phenotypes for gene: FREM2 were set to Fraser syndrome 2, MIM#617666
Review for gene: FREM2 was set to GREEN
Added comment: Fraser syndrome is an autosomal recessive malformation disorder. Major criteria include syndactyly, cryptophthalmos spectrum, urinary tract abnormalities, ambiguous genitalia, laryngeal and tracheal anomalies, and positive family history. Minor criteria include anorectal defects, dysplastic ears, skull ossification defects, umbilical abnormalities, and nasal anomalies.
Established gene-disease association.
Sources: Literature
Differences of Sex Development v0.320 SOX2 Chirag Patel Classified gene: SOX2 as Green List (high evidence)
Differences of Sex Development v0.320 SOX2 Chirag Patel Gene: sox2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.319 SOX2 Chirag Patel gene: SOX2 was added
gene: SOX2 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: SOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX2 were set to PMID: 20301477
Phenotypes for gene: SOX2 were set to Anophthalmia/microphthalmia-esophageal atresia syndrome MONDO:0008799; Microphthalmia, syndromic 3, MIM# 206900; Optic nerve hypoplasia and abnormalities of the central nervous system, MIM# 206900
Review for gene: SOX2 was set to GREEN
Added comment: SOX2 disorder includes anophthalmia and/or microphthalmia, brain malformations, developmental delay / intellectual disability, oesophageal atresia, pituitary hypoplasia, postnatal growth delay, hypotonia, seizures, and spastic or dystonic movements, and hypogonadotropic hypogonadism (manifest as cryptorchidism and micropenis in males, gonadal dysgenesis infrequently in females, and delayed puberty in both sexes). Established gene-disease association.
Sources: Literature
Differences of Sex Development v0.318 IRF6 Chirag Patel Classified gene: IRF6 as Green List (high evidence)
Differences of Sex Development v0.318 IRF6 Chirag Patel Gene: irf6 has been classified as Green List (High Evidence).
Dystonia - complex v0.242 ATM Sangavi Sivagnanasundram reviewed gene: ATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301790, 29436738, 30504431, 22345219; Phenotypes: ataxia telangiectasia MONDO:0008840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.317 IRF6 Chirag Patel gene: IRF6 was added
gene: IRF6 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: IRF6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRF6 were set to PMID: 20301581
Phenotypes for gene: IRF6 were set to Popliteal pterygium syndrome 1, OMIM #119500
Review for gene: IRF6 was set to GREEN
Added comment: IRF6-related disorders span a spectrum from isolated cleft lip and palate and Van der Woude syndrome (VWS) at the mild end to popliteal pterygium syndrome (PPS) at the more severe end.
Established gene-disease association.

Popliteal pterygium syndrome (PPS) features including orofacial anomalies such as lower lip pits, cleft lip and/or palate, and syngnathia, and skin and genital abnormalities including webbing of the lower limbs, syndactyly, hypoplasia of the labia majora/vagina/uterus, cryptorchidism, and bifid or hypoplastic scrotum.
Sources: Literature
Differences of Sex Development v0.316 CHD4 Chirag Patel Classified gene: CHD4 as Green List (high evidence)
Differences of Sex Development v0.316 CHD4 Chirag Patel Gene: chd4 has been classified as Green List (High Evidence).
Differences of Sex Development v0.315 CHD4 Chirag Patel gene: CHD4 was added
gene: CHD4 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: CHD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD4 were set to PMID: 31388190, 32881470
Phenotypes for gene: CHD4 were set to Sifrim-Hitz-Weiss syndrome, MIM #617159
Review for gene: CHD4 was set to GREEN
Added comment: Sifrim-Hitz-Weiss syndrome is an autosomal dominant intellectual developmental disorder with variable congenital defects affecting other systems, including cardiac, skeletal, and urogenital. Some patients may have short stature, enlarged head circumference, hearing loss, and nonspecific dysmorphic facial features. Established gene-disease association.

Hypogonadism is common in males (cryptorchidism and/or microphallus), with hormonal profile consistent with hypogonadotropic hypogonadism.
Sources: Literature
Differences of Sex Development v0.314 POLR1C Chirag Patel gene: POLR1C was added
gene: POLR1C was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: POLR1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR1C were set to PMID: 26151409, 32042905, 33005949
Phenotypes for gene: POLR1C were set to Leukodystrophy, hypomyelinating, 11, OMIM#616494
Review for gene: POLR1C was set to RED
Added comment: Hypomyelinating leukodystrophy-11 (HLD11) is an autosomal recessive neurologic disorder characterized by delayed psychomotor development and other neurologic features associated with hypomyelination on brain imaging. Some patients may have additional nonneurologic features, particularly dental abnormalities and possibly hypogonadotropic hypogonadism.

Thiffault et al. (2015) reported 8 unrelated patients with hypomyelinating leukodystrophy and 13 homozygous or compound heterozygous mutations in the POLR1C gene. All had neurologic abnormalities, including delayed psychomotor development, loss or lack of independent ambulation, abnormal cognition, tremor, ataxia, spasticity, and cerebellar findings. Three had myopia and 3 had dental abnormalities. Six patients were too young to be assessed for hypogonadotropic hypogonadism, and 2 did not have hypogonadism.

Gauquelin et al. (2019) reported 23 patients with hypomyelinating leukodystrophy and 29 different variants (homozygous or compound heterozygous) in the POLR1C gene. Patients too young to comment on hypogonadotropic hypogonadism.
Sources: Literature
Differences of Sex Development v0.314 POLR1C Chirag Patel gene: POLR1C was added
gene: POLR1C was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: POLR1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR1C were set to PMID: 26151409, 32042905, 33005949
Phenotypes for gene: POLR1C were set to Leukodystrophy, hypomyelinating, 11, OMIM#616494
Review for gene: POLR1C was set to RED
Added comment: Hypomyelinating leukodystrophy-11 (HLD11) is an autosomal recessive neurologic disorder characterized by delayed psychomotor development and other neurologic features associated with hypomyelination on brain imaging. Some patients may have additional nonneurologic features, particularly dental abnormalities and possibly hypogonadotropic hypogonadism.

Thiffault et al. (2015) reported 8 unrelated patients with hypomyelinating leukodystrophy and 13 homozygous or compound heterozygous mutations in the POLR1C gene. All had neurologic abnormalities, including delayed psychomotor development, loss or lack of independent ambulation, abnormal cognition, tremor, ataxia, spasticity, and cerebellar findings. Three had myopia and 3 had dental abnormalities. Six patients were too young to be assessed for hypogonadotropic hypogonadism, and 2 did not have hypogonadism.

Gauquelin et al. (2019) reported 23 patients with hypomyelinating leukodystrophy and 29 different variants (homozygous or compound heterozygous) in the POLR1C gene. Patients too young to comment on hypogonadotropic hypogonadism.
Sources: Literature
Differences of Sex Development v0.314 POLR1C Chirag Patel gene: POLR1C was added
gene: POLR1C was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: POLR1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR1C were set to PMID: 26151409, 32042905, 33005949, ............22855961
Phenotypes for gene: POLR1C were set to Leukodystrophy, hypomyelinating, 11, OMIM#616494
Review for gene: POLR1C was set to RED
Added comment: Hypomyelinating leukodystrophy-11 (HLD11) is an autosomal recessive neurologic disorder characterized by delayed psychomotor development and other neurologic features associated with hypomyelination on brain imaging. Some patients may have additional nonneurologic features, particularly dental abnormalities and possibly hypogonadotropic hypogonadism.

Thiffault et al. (2015) reported 8 unrelated patients with hypomyelinating leukodystrophy and 13 homozygous or compound heterozygous mutations in the POLR1C gene. All had neurologic abnormalities, including delayed psychomotor development, loss or lack of independent ambulation, abnormal cognition, tremor, ataxia, spasticity, and cerebellar findings. Three had myopia and 3 had dental abnormalities. Six patients were too young to be assessed for hypogonadotropic hypogonadism, and 2 did not have hypogonadism.

Gauquelin et al. (2019) reported 23 patients with hypomyelinating leukodystrophy and 29 different variants (homozygous or compound heterozygous) in the POLR1C gene. Patients too young to comment on hypogonadotropic hypogonadism.
Sources: Literature
Differences of Sex Development v0.313 POLR3B Chirag Patel Classified gene: POLR3B as Green List (high evidence)
Differences of Sex Development v0.313 POLR3B Chirag Patel Gene: polr3b has been classified as Green List (High Evidence).
Differences of Sex Development v0.312 POLR3A Chirag Patel Classified gene: POLR3A as Green List (high evidence)
Differences of Sex Development v0.312 POLR3A Chirag Patel Gene: polr3a has been classified as Green List (High Evidence).
Differences of Sex Development v0.312 POLR3B Chirag Patel gene: POLR3B was added
gene: POLR3B was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: POLR3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3B were set to PubMed: 27512013, 23355746, 22036171, 22036172, 25339210, 33005949, 22855961
Phenotypes for gene: POLR3B were set to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism; OMIM #614381
Review for gene: POLR3B was set to GREEN
Added comment: Hypomyelinating leukodystrophy-8 (HLD8) is an autosomal recessive neurologic disorder characterized by 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. There is considerable inter- and intrafamilial variability.

Multiples families reported with compound heterozygous mutations in POL3RB gene.

Wolf et al. (2014) performed a cross-sectional observational study of 105 patients with 4H syndrome, including 43 with mutations in the POLR3A gene and 62 with mutations in the POLR3B gene. Delayed puberty/HH, in those old enough to assess, occurred in 81% of patients with POLR3A mutations and in 69% of those with POLR3B mutations.
Sources: Literature
Differences of Sex Development v0.311 POLR3A Chirag Patel gene: POLR3A was added
gene: POLR3A was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3A were set to PubMed: 21855841, 25339210, 33005949, 22855961
Phenotypes for gene: POLR3A were set to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM#607694
Review for gene: POLR3A was set to GREEN
Added comment: Hypomyelinating leukodystrophy-7 (HLD7) is an autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive motor decline manifest as spasticity, ataxia, tremor, and cerebellar signs, as well as mild cognitive regression. Other common features may include hypodontia or oligodontia and hypogonadotropic hypogonadism. There is considerable inter- and intrafamilial variability.

Bernard et al. (2011) identified 14 different mutations in the POLR3A gene (homozygous or compound heterozygous state), in 19 patients from 12 families. The mutations were spread throughout the gene, and there were no obvious genotype/phenotype correlations. Immunoblot analysis showed decreased levels of POLR3A protein in fibroblasts from 4 affected individuals, and decreased levels in the cortex and cerebral white matter of another patient, suggesting that loss of function is responsible for the disorder.

Wolf et al. (2014) performed a cross-sectional observational study of 105 patients with 4H syndrome, including 43 with mutations in the POLR3A gene and 62 with mutations in the POLR3B gene. Delayed puberty/HH, in those old enough to assess, occurred in 81% of patients with POLR3A mutations and in 69% of those with POLR3B mutations.
Sources: Literature
Differences of Sex Development v0.310 HARS2 Chirag Patel Classified gene: HARS2 as Green List (high evidence)
Differences of Sex Development v0.310 HARS2 Chirag Patel Gene: hars2 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.53 COL3A1 Stephanie Hesselson reviewed gene: COL3A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39130004; Phenotypes: CORONARY ARTERY DISSECTION, SPONTANEOUS MIM#122455; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.242 KCNQ2 Bryony Thompson Publications for gene: KCNQ2 were set to 12742592
Dystonia - complex v0.241 KCNQ2 Bryony Thompson Classified gene: KCNQ2 as Amber List (moderate evidence)
Dystonia - complex v0.241 KCNQ2 Bryony Thompson Gene: kcnq2 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.240 KCNQ2 Bryony Thompson edited their review of gene: KCNQ2: Added comment: Now 2 cases have been reported with dystonic features as part of a complex neurological phenotype.; Changed rating: AMBER; Changed publications: 12742592, 32585800
Differences of Sex Development v0.309 HHAT Chirag Patel Classified gene: HHAT as Green List (high evidence)
Differences of Sex Development v0.309 HHAT Chirag Patel Gene: hhat has been classified as Green List (High Evidence).
Differences of Sex Development v0.308 HHAT Chirag Patel gene: HHAT was added
gene: HHAT was added to Differences of Sex Development. Sources: Expert list
Mode of inheritance for gene: HHAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HHAT were set to PMID: 24784881, 33749989, 35045414
Phenotypes for gene: HHAT were set to Nivelon-Nivelon-Mabille syndrome, OMIM:600092
Review for gene: HHAT was set to GREEN
Added comment: 3 individuals from 3 families with 46, XY karyotype and sex reversal, with supportive mouse model reported in 24784881.

PMID:24784881 - Callier et al 2014 - report a family with 2 siblings with Disorder of Sex Development (DSD) and chondrodysplasia (Nivelon-Nivelon-Mabille syndrome). The first sibling (46,XY karyotype) displayed severe dwarfism with generalized chondrodysplasia, a narrow, bell-shaped thorax, micromelia, brachydactyly, severe microcephaly (-7.5 SD at age 16 (PMID:15578577) with cerebellar vermis hypoplasia, facial anomalies, hypoplastic irides, and coloboma of both optic discs. Complete gonadal dysgenesis ( including normal external female genitalia, lack of pubertal development, primary amenorrhea, and hypergonadotrophic hypogonadism) and intellectual disability is also noted. The second sibling (46,XX karyotype) had histologically normal ovaries and similar phenotypic abnormalities including severe dwarfism and generalized chondrodysplasia. Using WES a homozygous missense variant was found NM_001122834:c.860G>T:p.(Gly287Val) in HHAT in the first sibling which is in the conserved MBOAT domain. The parents were heterozygous. They also found that mice lacking functional Hhat show a similar phenotype as the syndromic 46,XY DSD patient including testicular dysgenesis and skeletal defects.

PMID: 33749989 - Pande et al 2021 - report multiple malformations in three pregnancies with a novel biallelic in-frame deletion, c.365_367del; (p.Thr122del), in exon 5 of HHAT in the living proband. She shows severe microphthalmia, microcephaly (−8 SD head circumference at age 7), skeletal dysplasia (narrow bell-shaped thorax, short and angel-shaped epiphyses of hands and feet) and midface retrusion, short columella with a groove at the base, prominent ears, long philtrum, depressed nasal bridge, everted lower lip, and a single central incisor. She also has complete sex reversal (karyotype of 46, XY, normal internal organs including uterus and ovaries.)

PMID: 35045414 - Mazen et al 2022 - report an Egyptian patient with 46,XY DSD (ambiguous genitalia and microcephaly) and a homozygous missense variant in HHAT, which segregated with the phenotype in the family.
Sources: Expert list
Dystonia - complex v0.240 APTX Sangavi Sivagnanasundram reviewed gene: APTX: Rating: GREEN; Mode of pathogenicity: None; Publications: 15876520; Phenotypes: ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia MONDO:0008842; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.307 CTU2 Chirag Patel changed review comment from: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. Other anomalies include corpus callosum agenesis or dysgenesis, septal defects, PDA, hypoplastic right ventricle and joint contractures.

PMID:26633546. Affected members of all 3 families have microcephaly, facial dysmorphia and unilateral renal agenesis. 2/3 families have ambiguous genitalia; however, only 1 family had karyotyping done, which showed normal male karyotype (46 XY). 2/3 had congenital heart disease.

PMID: 27480277. Same variant as PMID:26633546. Affected individuals in this extended family have similar phenotype as PMID:26633546. Patient 1: in addition to microcephaly also has renal anomalies (small kidneys) and possible ambiguous genitalia with normal XY karyotype. Patient 2: cousin of patient 1. In addition to microcephaly did not have renal anomalies and nor ambiguous genitalia. Both patients have congenital heart disease.

PMID: 31301155. 5 new cases, all with microcephaly. 4/5 with renal anomalies, 2/5 with ambiguous genitalia, 4/5 congenital heart disease.

Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs.
Sources: Literature; to: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly.

PMID:26633546. Affected members of all 3 families have microcephaly, facial dysmorphia and unilateral renal agenesis. 2/3 families have ambiguous genitalia; however, only 1 family had karyotyping done, which showed normal male karyotype (46 XY). 2/3 had congenital heart disease.

PMID: 27480277. Same variant as PMID:26633546. Affected individuals in this extended family have similar phenotype as PMID:26633546. Patient 1: in addition to microcephaly also has renal anomalies (small kidneys) and possible ambiguous genitalia with normal XY karyotype. Patient 2: cousin of patient 1. In addition to microcephaly did not have renal anomalies and nor ambiguous genitalia. Both patients have congenital heart disease.

PMID: 31301155. 5 new cases, all with microcephaly. 4/5 with renal anomalies, 2/5 with ambiguous genitalia, 4/5 congenital heart disease.

Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs.
Sources: Literature
Differences of Sex Development v0.307 CTU2 Chirag Patel changed review comment from: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. Other anomalies include corpus callosum agenesis or dysgenesis, septal defects, PDA, hypoplastic right ventricle and joint contractures.

More than 6 families reported, four had the same founder variant. Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs
Sources: Literature; to: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. Other anomalies include corpus callosum agenesis or dysgenesis, septal defects, PDA, hypoplastic right ventricle and joint contractures.

PMID:26633546. Affected members of all 3 families have microcephaly, facial dysmorphia and unilateral renal agenesis. 2/3 families have ambiguous genitalia; however, only 1 family had karyotyping done, which showed normal male karyotype (46 XY). 2/3 had congenital heart disease.

PMID: 27480277. Same variant as PMID:26633546. Affected individuals in this extended family have similar phenotype as PMID:26633546. Patient 1: in addition to microcephaly also has renal anomalies (small kidneys) and possible ambiguous genitalia with normal XY karyotype. Patient 2: cousin of patient 1. In addition to microcephaly did not have renal anomalies and nor ambiguous genitalia. Both patients have congenital heart disease.

PMID: 31301155. 5 new cases, all with microcephaly. 4/5 with renal anomalies, 2/5 with ambiguous genitalia, 4/5 congenital heart disease.

Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs.
Sources: Literature
Differences of Sex Development v0.307 CTU2 Chirag Patel Classified gene: CTU2 as Green List (high evidence)
Differences of Sex Development v0.307 CTU2 Chirag Patel Gene: ctu2 has been classified as Green List (High Evidence).
Dystonia - complex v0.240 ADAR Sangavi Sivagnanasundram reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301648, 24262145; Phenotypes: Aicardi-Goutieres syndrome MONDO:0018866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.306 CTU2 Chirag Patel gene: CTU2 was added
gene: CTU2 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTU2 were set to PMID: 27480277, 26633546, 31301155, 38348206
Phenotypes for gene: CTU2 were set to DREAM-PL syndrome (Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome), MIM#618142
Review for gene: CTU2 was set to GREEN
Added comment: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. Other anomalies include corpus callosum agenesis or dysgenesis, septal defects, PDA, hypoplastic right ventricle and joint contractures.

More than 6 families reported, four had the same founder variant. Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs
Sources: Literature
Differences of Sex Development v0.305 TWNK Chirag Patel Classified gene: TWNK as Green List (high evidence)
Differences of Sex Development v0.305 TWNK Chirag Patel Gene: twnk has been classified as Green List (High Evidence).
Differences of Sex Development v0.305 TWNK Chirag Patel Classified gene: TWNK as Green List (high evidence)
Differences of Sex Development v0.305 TWNK Chirag Patel Gene: twnk has been classified as Green List (High Evidence).
Differences of Sex Development v0.304 TWNK Chirag Patel gene: TWNK was added
gene: TWNK was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: TWNK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TWNK were set to PMID: 25355836, 31852434, 31455392
Phenotypes for gene: TWNK were set to Perrault syndrome 5; MIM# 616138
Review for gene: TWNK was set to GREEN
Added comment: Perrault syndrome-5 (PRLTS5) is an autosomal recessive disorder characterized by progressive ataxia, axonal neuropathy, hyporeflexia, and abnormal eye movements, accompanied by progressive hearing loss and ovarian dysgenesis.

PMID: 25355836: 4 women from 2 unrelated families with Perrault syndrome-5.
2 sisters in each family presented with primary amenorrhea, lack of secondary sexual characteristics, and gonadal dysgenesis; 2 sisters in 1 family showed streak ovaries. Three of the 4 girls had onset of sensorineural hearing loss at 7 to 8 years of age; the fourth had onset of hearing loss at age 13. All 4 patients developed neurologic involvement in the second or third decades, with features including ataxia, nystagmus, hyporeflexia, and sensory axonal neuropathy with distal sensory impairment. WES identified compound heterozygous variants in each family, but functional studies of the variants were not performed.

PMID: 31852434: female with severe bilateral hypoacusis, severe ataxia, polyneuropathy, lower limb spastic paraparesis with pyramidal signs, and gonadal dysgenesis, and compound heterozygous variants in TWNK gene (but functional studies of the variants were not performed).

PMID: 31455392: 3 siblings from one family with childhood-onset bilateral sensorineural hearing impairment, neurological signs (spinocerebellar ataxia, polyneuropathy), and gonadal dysfunction with early cessation of menses in the 2 females. WES identified compound heterozygous pathogenic mutations in the TWNK gene, which segregated with disease.
,
Sources: Literature
Differences of Sex Development v0.303 MARS2 Chirag Patel Classified gene: MARS2 as Green List (high evidence)
Differences of Sex Development v0.303 MARS2 Chirag Patel Gene: mars2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.302 MARS2 Chirag Patel gene: MARS2 was added
gene: MARS2 was added to Differences of Sex Development. Sources: Expert Review
Mode of inheritance for gene: MARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MARS2 were set to PMID: 27650058, 21464306, 27087618
Phenotypes for gene: MARS2 were set to Perrault syndrome 2, MIM# 614926
Review for gene: MARS2 was set to GREEN
Added comment: Perrault syndrome-2 (PRLTS2) is an autosomal recessive disorder characterized by sensorineural deafness in both males and females. Affected females have primary amenorrhea, streak gonads (ovarian dysgenesis), and infertility, whereas affected males show normal pubertal development and are fertile. No neurological abnormalities reported.

PMID: 21464306: five affected siblings from one family with three females with ovarian dysgenesis with primary amenorrhea and streak gonads along with sensorineural hearing loss (two males had normal fertility) had two variants in HARS2 with confirmed biparental inheritance. Functional studies showed that the mutations resulted in decreased enzyme activity, and knockdown of the HARS2 homolog in C. elegans caused severe gonadal defects and infertility.

PMID: 27650058: two unrelated probands with Perrault syndrome with profound deafness and secondary amenorrhoea with gonadal dysgenesis were found to have a homozygous variant in HARS2. These probands were not related but were from the same region in Morocco.

PMID: 27087618: 2 siblings in Turkish family with Perrault syndrome (female sibling had with secondary amenorrhea and gonadal dysgenesis) were found to have a homozygous variant in HARS2. No functional work.
Sources: Expert Review
Differences of Sex Development v0.301 HARS2 Chirag Patel gene: HARS2 was added
gene: HARS2 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: HARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HARS2 were set to PMID: 27650058, 21464306, 27087618
Phenotypes for gene: HARS2 were set to Perrault syndrome 2, MIM# 614926
Review for gene: HARS2 was set to GREEN
Added comment: Perrault syndrome-2 (PRLTS2) is an autosomal recessive disorder characterized by sensorineural deafness in both males and females. Affected females have primary amenorrhea, streak gonads (ovarian dysgenesis), and infertility, whereas affected males show normal pubertal development and are fertile. No neurological abnormalities reported.

PMID: 21464306: five affected siblings from one family with three females with ovarian dysgenesis with primary amenorrhea and streak gonads along with sensorineural hearing loss (two males had normal fertility) had two variants in HARS2 with confirmed biparental inheritance. Functional studies showed that the mutations resulted in decreased enzyme activity, and knockdown of the HARS2 homolog in C. elegans caused severe gonadal defects and infertility.

PMID: 27650058: two unrelated probands with Perrault syndrome with profound deafness and secondary amenorrhoea with gonadal dysgenesis were found to have a homozygous variant in HARS2. These probands were not related but were from the same region in Morocco.

PMID: 27087618: 2 siblings in Turkish family with Perrault syndrome (female sibling had with secondary amenorrhea and gonadal dysgenesis) were found to have a homozygous variant in HARS2. No functional work.
Sources: Literature
Differences of Sex Development v0.300 LARS2 Chirag Patel Classified gene: LARS2 as Green List (high evidence)
Differences of Sex Development v0.300 LARS2 Chirag Patel Gene: lars2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.299 LARS2 Chirag Patel gene: LARS2 was added
gene: LARS2 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: LARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LARS2 were set to PMID: 32423379, 29205794, 23541342, 30737337, 26657938,
Phenotypes for gene: LARS2 were set to Perrault syndrome 4; MIM# 615300
Review for gene: LARS2 was set to GREEN
Added comment: Perrault syndrome-4 (PRLTS4) is an autosomal recessive disorder primarily characterized by early-onset sensorineural hearing loss in both males and females, and premature ovarian failure (POF) due to ovarian dysgenesis in females. Affected individuals may also develop neurologic involvement, including developmental delay or learning difficulties in childhood or onset of progressive movement abnormalities, such as spasticity, in adulthood. Brain imaging may show progressive leukodystrophy. At least 6 families with affected females reported with biallelic variants in LARS2 (mostly missense), which segregated in family. Patient-derived mitochondria showed decreased LARS2 aminoacylation activity (about 50% of controls) in one study.
Sources: Literature
Differences of Sex Development v0.298 ERAL1 Chirag Patel Classified gene: ERAL1 as Amber List (moderate evidence)
Differences of Sex Development v0.298 ERAL1 Chirag Patel Gene: eral1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.297 ERAL1 Chirag Patel reviewed gene: ERAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 28449065; Phenotypes: Perrault syndrome 6, MIM# 617565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 MMAA Ee Ming Wong reviewed gene: MMAA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Methylmalonic aciduria, vitamin B12-responsive, cblA type (MIM#251100); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 MERTK Ee Ming Wong reviewed gene: MERTK: Rating: GREEN; Mode of pathogenicity: None; Publications: 11062461, 17301963, 20300561, 22180149; Phenotypes: Retinitis pigmentosa 38 (MIM#613862); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 MARS Ee Ming Wong reviewed gene: MARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 24103465, 25913036; Phenotypes: Interstitial lung and liver disease, MIM#615486; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 KCNJ1 Cassandra Muller reviewed gene: KCNJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bartter syndrome, type 2, 241200 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 IKBKB Cassandra Muller reviewed gene: IKBKB: Rating: GREEN; Mode of pathogenicity: None; Publications: 24369075, 25216719, 24679846, 32117824, 2513935; Phenotypes: Immunodeficiency 15, 615592 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 HPS1 Cassandra Muller reviewed gene: HPS1: Rating: ; Mode of pathogenicity: None; Publications: 8896559, 9497254, 9705234, 27593200, 31898847; Phenotypes: Hermansky-Pudlak syndrome 1, 203300 (3); Mode of inheritance: None
Prepair 1000+ v1.633 HPD Cassandra Muller reviewed gene: HPD: Rating: AMBER; Mode of pathogenicity: None; Publications: 10942115, 23036342, 37817461, 28649543; Phenotypes: Tyrosinemia, type III, 276710 (3); Mode of inheritance: None
Osteogenesis Imperfecta and Osteoporosis v0.115 PLS3 Sangavi Sivagnanasundram reviewed gene: PLS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24088043; Phenotypes: X-linked osteoporosis with fractures MONDO:0018315; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Osteogenesis Imperfecta and Osteoporosis v0.115 LRP5 Sangavi Sivagnanasundram reviewed gene: LRP5: Rating: GREEN; Mode of pathogenicity: None; Publications: 20034086; Phenotypes: osteoporosis-pseudoglioma syndrome MONDO:0009820; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 HFE2 Cassandra Muller reviewed gene: HFE2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hemochromatosis, type 2A, 602390 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.115 FKBP10 Sangavi Sivagnanasundram reviewed gene: FKBP10: Rating: GREEN; Mode of pathogenicity: None; Publications: 20362275, 20839288; Phenotypes: osteogenesis imperfecta type 11 MONDO:0012592, Bruck syndrome MONDO:0017195; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.115 COL1A2 Sangavi Sivagnanasundram reviewed gene: COL1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301472, 2897363, 8257992, 8401517; Phenotypes: Osteogenesis imperfecta type 1 MONDO:0008146, Osteogenesis imperfecta type 2 MONDO:0008147, Osteogenesis imperfecta type 3 MONDO:0009804, Osteogenesis imperfecta type 4 MONDO:0008148; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteogenesis Imperfecta and Osteoporosis v0.115 COL1A1 Sangavi Sivagnanasundram edited their review of gene: COL1A1: Changed publications: 20301472, 15728585, 17078022, 23692737
Prepair 1000+ v1.633 GLYCTK Cassandra Muller reviewed gene: GLYCTK: Rating: GREEN; Mode of pathogenicity: None; Publications: 20949620, 31837836, 39619776; Phenotypes: D-glyceric aciduria, 220120 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.115 COL1A1 Sangavi Sivagnanasundram reviewed gene: COL1A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15728585, 17078022, 23692737; Phenotypes: combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 MONDO:0030854, Osteogenesis imperfecta type 1 MONDO:0008146, Osteogenesis imperfecta type 2 MONDO:0008147, Osteogenesis imperfecta type 3 MONDO:0009804, Osteogenesis imperfecta type 4, MONDO:0008148; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurodegeneration with brain iron accumulation v0.35 WDR45 Sangavi Sivagnanasundram reviewed gene: WDR45: Rating: GREEN; Mode of pathogenicity: None; Publications: 23447832, 23176820; Phenotypes: X-linked complex neurodevelopmental disorder MONDO:0100148; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Neurodegeneration with brain iron accumulation v0.35 PLA2G6 Sangavi Sivagnanasundram reviewed gene: PLA2G6: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301718, 24745848, 27516098; Phenotypes: PLA2G6-associated neurodegeneration MONDO:0017998; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neurodegeneration with brain iron accumulation v0.35 PANK2 Sangavi Sivagnanasundram reviewed gene: PANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15911822, 22127788; Phenotypes: Neurodegeneration with brain iron accumulation 1 MIM#234200, pantothenate kinase-associated neurodegeneration MONDO:0009319; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Familial hypercholesterolaemia v1.0 Bryony Thompson promoted panel to version 1.0
Congenital Heart Defect v0.421 ROCK2 Bryony Thompson Marked gene: ROCK2 as ready
Congenital Heart Defect v0.421 ROCK2 Bryony Thompson Gene: rock2 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.421 ROCK2 Bryony Thompson Classified gene: ROCK2 as Amber List (moderate evidence)
Congenital Heart Defect v0.421 ROCK2 Bryony Thompson Gene: rock2 has been classified as Amber List (Moderate Evidence).
Neurodegeneration with brain iron accumulation v0.35 FTL Sangavi Sivagnanasundram reviewed gene: FTL: Rating: GREEN; Mode of pathogenicity: None; Publications: 11438811, 12746423, 15099026; Phenotypes: Neurodegeneration with brain iron accumulation 3 MIIM#606159; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2166 ROCK2 Bryony Thompson Marked gene: ROCK2 as ready
Mendeliome v1.2166 ROCK2 Bryony Thompson Gene: rock2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2166 ROCK2 Bryony Thompson Classified gene: ROCK2 as Amber List (moderate evidence)
Mendeliome v1.2166 ROCK2 Bryony Thompson Gene: rock2 has been classified as Amber List (Moderate Evidence).
Familial hypercholesterolaemia v0.46 PCSK9 Bryony Thompson Marked gene: PCSK9 as ready
Familial hypercholesterolaemia v0.46 PCSK9 Bryony Thompson Gene: pcsk9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.4 PPP5C Bryony Thompson Marked gene: PPP5C as ready
Intellectual disability syndromic and non-syndromic v1.4 PPP5C Bryony Thompson Gene: ppp5c has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.4 PPP5C Bryony Thompson Classified gene: PPP5C as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.4 PPP5C Bryony Thompson Gene: ppp5c has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2165 PPP5C Bryony Thompson Marked gene: PPP5C as ready
Mendeliome v1.2165 PPP5C Bryony Thompson Gene: ppp5c has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2165 PPP5C Bryony Thompson Classified gene: PPP5C as Amber List (moderate evidence)
Mendeliome v1.2165 PPP5C Bryony Thompson Gene: ppp5c has been classified as Amber List (Moderate Evidence).
Familial hypercholesterolaemia v0.46 PCSK9 Bryony Thompson Phenotypes for gene: PCSK9 were changed from to hypercholesterolemia, autosomal dominant, 3 MONDO:0011369
Familial hypercholesterolaemia v0.45 PCSK9 Bryony Thompson Publications for gene: PCSK9 were set to
Familial hypercholesterolaemia v0.44 PCSK9 Bryony Thompson Mode of pathogenicity for gene: PCSK9 was changed from to Other
Familial hypercholesterolaemia v0.43 PCSK9 Bryony Thompson Mode of inheritance for gene: PCSK9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial hypercholesterolaemia v0.42 LIPA Bryony Thompson Marked gene: LIPA as ready
Familial hypercholesterolaemia v0.42 LIPA Bryony Thompson Gene: lipa has been classified as Green List (High Evidence).
Familial hypercholesterolaemia v0.42 LIPA Bryony Thompson Phenotypes for gene: LIPA were changed from to Cholesteryl ester storage disease, MIM# 278000; Wolman disease, MIM# 278000; Lysosomal acid lipase deficiency, MONDO:0010204
Familial hypercholesterolaemia v0.41 LIPA Bryony Thompson Publications for gene: LIPA were set to 11487567
Familial hypercholesterolaemia v0.40 LIPA Bryony Thompson Publications for gene: LIPA were set to
Familial hypercholesterolaemia v0.39 LIPA Bryony Thompson Mode of inheritance for gene: LIPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Familial hypercholesterolaemia v0.38 CYP27A1 Bryony Thompson Marked gene: CYP27A1 as ready
Familial hypercholesterolaemia v0.38 CYP27A1 Bryony Thompson Gene: cyp27a1 has been classified as Green List (High Evidence).
Familial hypercholesterolaemia v0.38 CYP27A1 Bryony Thompson Phenotypes for gene: CYP27A1 were changed from to Cerebrotendinous xanthomatosis MONDO:0008948
Familial hypercholesterolaemia v0.37 CYP27A1 Bryony Thompson Classified gene: CYP27A1 as Green List (high evidence)
Familial hypercholesterolaemia v0.37 CYP27A1 Bryony Thompson Added comment: Comment on list classification: Included on this panel as a differential diagnosis for FH, particularly with the presence of xanthomas.
Familial hypercholesterolaemia v0.37 CYP27A1 Bryony Thompson Gene: cyp27a1 has been classified as Green List (High Evidence).
Neurodegeneration with brain iron accumulation v0.35 FA2H Sangavi Sivagnanasundram reviewed gene: FA2H: Rating: GREEN; Mode of pathogenicity: None; Publications: 20853438, 19068277; Phenotypes: hereditary spastic paraplegia 35 MONDO:0012866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Familial hypercholesterolaemia v0.36 CYP27A1 Bryony Thompson Mode of inheritance for gene: CYP27A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Familial hypercholesterolaemia v0.35 APOB Sangavi Sivagnanasundram changed review comment from: Classified as Definitive by ClinGen General Gene Curation GCEP on 14/11/2018 -
https://search.clinicalgenome.org/CCID:004156

Mechanism of disease is LoF that typically impair LDL-C binding to the LDLR.; to: Classified as Definitive by ClinGen General Gene Curation GCEP on 14/11/2018 -
https://search.clinicalgenome.org/CCID:004156
Familial hypercholesterolaemia v0.35 APOB Bryony Thompson Added comment: Comment on mode of pathogenicity: The mechanism for disease involves defective apo B100 on LDL particles that fail to bind to LDLR.
Familial hypercholesterolaemia v0.35 APOB Bryony Thompson Mode of pathogenicity for gene: APOB was changed from to Other
Familial hypercholesterolaemia v0.34 APOB Bryony Thompson Phenotypes for gene: APOB were changed from to hypercholesterolemia, autosomal dominant, type B MONDO:0007751
Familial hypercholesterolaemia v0.33 APOB Bryony Thompson Publications for gene: APOB were set to
Familial hypercholesterolaemia v0.32 APOB Bryony Thompson Mode of inheritance for gene: APOB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial hypercholesterolaemia v0.31 ABCG8 Bryony Thompson Mode of inheritance for gene: ABCG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Familial hypercholesterolaemia v0.30 ABCG8 Bryony Thompson Publications for gene: ABCG8 were set to
Familial hypercholesterolaemia v0.29 ABCG8 Bryony Thompson Phenotypes for gene: ABCG8 were changed from to Sitosterolemia MONDO:0008863
Mendeliome v1.2164 RAB35 Bryony Thompson changed review comment from: PMID: 38432637 - a single case with a neurodevelopmental disorder and a homozygous missense variant (c.80G>A; p.R27H) and supporting in vitro functional assays.
PMID: 36928819 - Posterior probability association (PPA) 0.955 for familial hypercholesterolaemia under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 469 FH cases and 55,033 controls used in BeviMed analysis. A nonsense variant and frameshift enriched in the FH cohort (n=6).
Sources: Literature; to: PMID: 38432637 - a single case with a neurodevelopmental disorder and a homozygous missense variant (c.80G>A; p.R27H) and supporting in vitro functional assays.
PMID: 36928819 - Posterior probability association (PPA) 0.955 for familial hypercholesterolaemia under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 469 FH cases and 55,033 controls used in BeviMed analysis. A nonsense variant and frameshift enriched in the FH cohort (n=6). Cosegergation in 1 affected relative also reported.
Sources: Literature
Mendeliome v1.2164 RAB35 Bryony Thompson Marked gene: RAB35 as ready
Mendeliome v1.2164 RAB35 Bryony Thompson Gene: rab35 has been classified as Red List (Low Evidence).
Mendeliome v1.2164 RAB35 Bryony Thompson gene: RAB35 was added
gene: RAB35 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAB35 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RAB35 were set to 38432637; 36928819
Phenotypes for gene: RAB35 were set to familial hypercholesterolemia MONDO:0005439; neurodevelopmental disorder MONDO:0700092
Review for gene: RAB35 was set to RED
Added comment: PMID: 38432637 - a single case with a neurodevelopmental disorder and a homozygous missense variant (c.80G>A; p.R27H) and supporting in vitro functional assays.
PMID: 36928819 - Posterior probability association (PPA) 0.955 for familial hypercholesterolaemia under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 469 FH cases and 55,033 controls used in BeviMed analysis. A nonsense variant and frameshift enriched in the FH cohort (n=6).
Sources: Literature
Hereditary Neuropathy_CMT - isolated v1.51 ARPC3 Bryony Thompson Marked gene: ARPC3 as ready
Hereditary Neuropathy_CMT - isolated v1.51 ARPC3 Bryony Thompson Gene: arpc3 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy_CMT - isolated v1.51 ARPC3 Bryony Thompson Classified gene: ARPC3 as Amber List (moderate evidence)
Hereditary Neuropathy_CMT - isolated v1.51 ARPC3 Bryony Thompson Gene: arpc3 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy_CMT - isolated v1.50 ARPC3 Bryony Thompson gene: ARPC3 was added
gene: ARPC3 was added to Hereditary Neuropathy_CMT - isolated. Sources: Literature
Mode of inheritance for gene: ARPC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARPC3 were set to 36928819; 26166300
Phenotypes for gene: ARPC3 were set to Charcot-Marie-Tooth disease MONDO:0015626
Review for gene: ARPC3 was set to AMBER
Added comment: Posterior probability association (PPA) 0.995 for Charcot-Marie Tooth disease under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 549 CMT cases and 54,856 controls used in BeviMed analysis. 5 rare variants (missense, splice region, a splice acceptor site) enriched in the CMT cohort (n=14). Additionally, ArpC3 conditional knockout mice fail to ensheath axons causing axon dysfunction.
Sources: Literature
Mendeliome v1.2163 ARPC3 Bryony Thompson Marked gene: ARPC3 as ready
Mendeliome v1.2163 ARPC3 Bryony Thompson Gene: arpc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2163 ARPC3 Bryony Thompson Classified gene: ARPC3 as Amber List (moderate evidence)
Mendeliome v1.2163 ARPC3 Bryony Thompson Gene: arpc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2162 ARPC3 Bryony Thompson gene: ARPC3 was added
gene: ARPC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARPC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARPC3 were set to 36928819; 26166300
Phenotypes for gene: ARPC3 were set to Charcot-Marie-Tooth disease MONDO:0015626
Review for gene: ARPC3 was set to AMBER
Added comment: Posterior probability association (PPA) 0.995 for Charcot-Marie Tooth disease under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 549 CMT cases and 54,856 controls used in BeviMed analysis. 5 rare variants (missense, splice region, a splice acceptor site) enriched in the CMT cohort (n=14).
Additionally, ArpC3 conditional knockout mice fail to ensheath axons causing axon dysfunction.
Sources: Literature
Hypertension and Aldosterone disorders v1.15 USP33 Bryony Thompson changed review comment from: Posterior probability association (PPA) 0.977 for extreme early-onset hypertension under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 2 splice site variants enriched in a renal and urinary tract disorders cohort (n=6).
Sources: Literature; to: Posterior probability association (PPA) 0.977 for extreme early-onset hypertension under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 182 early-onset hypertension cases and 55,305 controls used in BeviMed analysis. 2 splice site variants enriched in a renal and urinary tract disorders cohort (n=6).
Sources: Literature
Mendeliome v1.2161 USP33 Bryony Thompson changed review comment from: Posterior probability association (PPA) 0.977 for extreme early-onset hypertension under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 2 splice site variants enriched in a renal and urinary tract disorders cohort (n=6).
Sources: Literature; to: Posterior probability association (PPA) 0.977 for extreme early-onset hypertension under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 182 early-onset hypertension cases and 55,305 controls used in BeviMed analysis. 2 splice site variants enriched in a renal and urinary tract disorders cohort (n=6).
Sources: Literature
Deafness_IsolatedAndComplex v1.208 FMN1 Bryony Thompson changed review comment from: PMID: 36928819 - Posterior probability association (PPA) between 0.95-0.96 for congenital hearing impairment under a recessive MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. A splice variant (n=3) & frameshift variant (n=1), possibly in 2 cases and possibly in trans (cosegregation in 2 unaffected relatives mentioned)

PMID: 20610440; 19383632; 15202026 - A 263 Kb homozygous deletion of FMN1 has been identified in a single case with oligosyndactyly, radioulnar synostosis, hearing loss and renal defects. Also, a supporting null mouse model with oligosyndactyly. Also, a large duplication including GREM1 reported in association with Cenani–Lenz syndrome.
Sources: Literature; to: PMID: 36928819 - Posterior probability association (PPA) between 0.95-0.96 for congenital hearing impairment under a recessive MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 510 CHI cases assessed and 54,738 controls in BeviMed analysis. A splice variant (n=3) & frameshift variant (n=1), possibly in 2 cases and possibly in trans (cosegregation in 2 unaffected relatives mentioned)

PMID: 20610440; 19383632; 15202026 - A 263 Kb homozygous deletion of FMN1 has been identified in a single case with oligosyndactyly, radioulnar synostosis, hearing loss and renal defects. Also, a supporting null mouse model with oligosyndactyly. Also, a large duplication including GREM1 reported in association with Cenani–Lenz syndrome.
Sources: Literature
Mendeliome v1.2161 FMN1 Bryony Thompson changed review comment from: PMID: 36928819 - Posterior probability association (PPA) between 0.95-0.96 for congenital hearing impairment under a recessive MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. A splice variant (n=3) & frameshift variant (n=1), possibly in 2 cases and possibly in trans (cosegregation in 2 unaffected relatives mentioned); to: PMID: 36928819 - Posterior probability association (PPA) between 0.95-0.96 for congenital hearing impairment under a recessive MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 510 CHI cases assessed and 54,738 controls in BeviMed analysis. A splice variant (n=3) & frameshift variant (n=1), possibly in 2 cases and possibly in trans (cosegregation in 2 unaffected relatives mentioned)
Hypertension and Aldosterone disorders v1.15 USP33 Bryony Thompson Marked gene: USP33 as ready
Hypertension and Aldosterone disorders v1.15 USP33 Bryony Thompson Gene: usp33 has been classified as Red List (Low Evidence).
Mendeliome v1.2161 USP33 Bryony Thompson Classified gene: USP33 as Red List (low evidence)
Mendeliome v1.2161 USP33 Bryony Thompson Gene: usp33 has been classified as Red List (Low Evidence).
Hypertension and Aldosterone disorders v1.15 USP33 Bryony Thompson gene: USP33 was added
gene: USP33 was added to Hypertension and Aldosterone disorders. Sources: Literature
Mode of inheritance for gene: USP33 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: USP33 were set to 36928819
Phenotypes for gene: USP33 were set to Renal hypertension MONDO:0001105
Review for gene: USP33 was set to AMBER
Added comment: Posterior probability association (PPA) 0.977 for extreme early-onset hypertension under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 2 splice site variants enriched in a renal and urinary tract disorders cohort (n=6).
Sources: Literature
Mendeliome v1.2160 USP33 Bryony Thompson Marked gene: USP33 as ready
Mendeliome v1.2160 USP33 Bryony Thompson Gene: usp33 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2160 USP33 Bryony Thompson Classified gene: USP33 as Amber List (moderate evidence)
Mendeliome v1.2160 USP33 Bryony Thompson Gene: usp33 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2159 USP33 Bryony Thompson gene: USP33 was added
gene: USP33 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: USP33 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: USP33 were set to 36928819
Phenotypes for gene: USP33 were set to Renal hypertension MONDO:0001105
Review for gene: USP33 was set to AMBER
Added comment: Posterior probability association (PPA) 0.977 for extreme early-onset hypertension under a dominant MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. 2 splice site variants enriched in a renal and urinary tract disorders cohort (n=6).
Sources: Literature
Incidentalome v0.314 SCN3B Bryony Thompson Classified gene: SCN3B as Red List (low evidence)
Incidentalome v0.314 SCN3B Bryony Thompson Added comment: Comment on list classification: Disputed Brugada syndrome gene
Incidentalome v0.314 SCN3B Bryony Thompson Gene: scn3b has been classified as Red List (Low Evidence).
Incidentalome v0.313 RNASEL Bryony Thompson Marked gene: RNASEL as ready
Incidentalome v0.313 RNASEL Bryony Thompson Gene: rnasel has been classified as Red List (Low Evidence).
Incidentalome v0.313 RNASEL Bryony Thompson Classified gene: RNASEL as Red List (low evidence)
Incidentalome v0.313 RNASEL Bryony Thompson Added comment: Comment on list classification: Reportedly a prostate cancer risk factor. Not associated with Mendelian disease
Incidentalome v0.313 RNASEL Bryony Thompson Gene: rnasel has been classified as Red List (Low Evidence).
Incidentalome v0.312 RBM12 Bryony Thompson Marked gene: RBM12 as ready
Incidentalome v0.312 RBM12 Bryony Thompson Gene: rbm12 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.312 RBM12 Bryony Thompson Classified gene: RBM12 as Amber List (moderate evidence)
Incidentalome v0.312 RBM12 Bryony Thompson Gene: rbm12 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.311 RABL3 Bryony Thompson Publications for gene: RABL3 were set to 31406347
Incidentalome v0.310 RABL3 Bryony Thompson Classified gene: RABL3 as Red List (low evidence)
Incidentalome v0.310 RABL3 Bryony Thompson Added comment: Comment on list classification: One family reported and no replication in other pancreatic cancer cohorts at this point.
Incidentalome v0.310 RABL3 Bryony Thompson Gene: rabl3 has been classified as Red List (Low Evidence).
Incidentalome v0.309 RABL3 Bryony Thompson Classified gene: RABL3 as Red List (low evidence)
Incidentalome v0.309 RABL3 Bryony Thompson Added comment: Comment on list classification: One family reported and no replication in other pancreatic cancer cohorts at this point.
Incidentalome v0.309 RABL3 Bryony Thompson Gene: rabl3 has been classified as Red List (Low Evidence).
Mendeliome v1.2158 UCHL1 Bryony Thompson Marked gene: UCHL1 as ready
Mendeliome v1.2158 UCHL1 Bryony Thompson Gene: uchl1 has been classified as Green List (High Evidence).
Mendeliome v1.2158 UCHL1 Bryony Thompson Classified gene: UCHL1 as Green List (high evidence)
Mendeliome v1.2158 UCHL1 Bryony Thompson Gene: uchl1 has been classified as Green List (High Evidence).
Mendeliome v1.2157 UCHL1 Bryony Thompson reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23359680, 3340629, 28007905, 32656641, 29735986, 28007905, 35986737, 39030458; Phenotypes: Spastic paraplegia 79A, autosomal dominant, MIM# 620221, Spastic paraplegia 79, autosomal recessive, 615491, MONDO:0014209, Neurodegenerative disease, MONDO:0005559, UCHL1-related; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.2157 UCHL1 Bryony Thompson gene: UCHL1 was added
gene: UCHL1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: UCHL1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: UCHL1 were set to 23359680; 3340629; 28007905; 32656641; 29735986; 28007905; 35986737; 39030458
Phenotypes for gene: UCHL1 were set to Spastic paraplegia 79A, autosomal dominant, MIM# 620221; Spastic paraplegia 79, autosomal recessive, 615491; MONDO:0014209; Neurodegenerative disease, MONDO:0005559, UCHL1-related
Neurodegeneration with brain iron accumulation v0.35 DCAF17 Sangavi Sivagnanasundram reviewed gene: DCAF17: Rating: GREEN; Mode of pathogenicity: None; Publications: 28542792, 38320940, 30409855, 35876063; Phenotypes: Woodhouse-Sakati syndrome MONDO:0009419; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Epidermolysis bullosa v1.20 TUFT1 Bryony Thompson Classified gene: TUFT1 as Amber List (moderate evidence)
Epidermolysis bullosa v1.20 TUFT1 Bryony Thompson Gene: tuft1 has been classified as Amber List (Moderate Evidence).
Epidermolysis bullosa v1.18 TUFT1 Bryony Thompson gene: TUFT1 was added
gene: TUFT1 was added to Epidermolysis bullosa. Sources: Literature
Mode of inheritance for gene: TUFT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUFT1 were set to 36689522; 36928819
Phenotypes for gene: TUFT1 were set to Woolly hair-skin fragility syndrome, MIM# 620415
Deafness_IsolatedAndComplex v1.208 FMN1 Bryony Thompson Marked gene: FMN1 as ready
Deafness_IsolatedAndComplex v1.208 FMN1 Bryony Thompson Gene: fmn1 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.208 FMN1 Bryony Thompson Classified gene: FMN1 as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v1.208 FMN1 Bryony Thompson Gene: fmn1 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.207 FMN1 Bryony Thompson gene: FMN1 was added
gene: FMN1 was added to Deafness_IsolatedAndComplex. Sources: Literature
SV/CNV tags were added to gene: FMN1.
Mode of inheritance for gene: FMN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FMN1 were set to 20610440; 19383632; 15202026; 36928819
Phenotypes for gene: FMN1 were set to Hearing loss disorder MONDO:0005365
Review for gene: FMN1 was set to AMBER
Added comment: PMID: 36928819 - Posterior probability association (PPA) between 0.95-0.96 for congenital hearing impairment under a recessive MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. A splice variant (n=3) & frameshift variant (n=1), possibly in 2 cases and possibly in trans (cosegregation in 2 unaffected relatives mentioned)

PMID: 20610440; 19383632; 15202026 - A 263 Kb homozygous deletion of FMN1 has been identified in a single case with oligosyndactyly, radioulnar synostosis, hearing loss and renal defects. Also, a supporting null mouse model with oligosyndactyly. Also, a large duplication including GREM1 reported in association with Cenani–Lenz syndrome.
Sources: Literature
Neurodegeneration with brain iron accumulation v0.35 CP Sangavi Sivagnanasundram reviewed gene: CP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301666, 32235485, 11756598, 10997552; Phenotypes: aceruloplasminemia MONDO:0011426; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.2156 FMN1 Bryony Thompson Publications for gene: FMN1 were set to 20610440; 19383632; 15202026
Mendeliome v1.2155 FMN1 Bryony Thompson Phenotypes for gene: FMN1 were changed from oligosyndactyly; radioulnar synostosis; hearing loss; renal defects to Hearing loss disorder MONDO:0005365
Mendeliome v1.2154 FMN1 Bryony Thompson edited their review of gene: FMN1: Added comment: PMID: 36928819 - Posterior probability association (PPA) between 0.95-0.96 for congenital hearing impairment under a recessive MOI in the 100,000 Genomes project “Rareservoir” using a Bayesian statistical method - BeviMed. A splice variant (n=3) & frameshift variant (n=1), possibly in 2 cases and possibly in trans (cosegregation in 2 unaffected relatives mentioned); Changed publications: 20610440, 19383632, 15202026, 36928819; Changed phenotypes: Hearing loss disorder MONDO:0005365
Neurodegeneration with brain iron accumulation v0.35 COASY Sangavi Sivagnanasundram reviewed gene: COASY: Rating: GREEN; Mode of pathogenicity: None; Publications: 27021474, 24360804, 28489334; Phenotypes: neurodegeneration with brain iron accumulation 6 MONDO:0014290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neurodegeneration with brain iron accumulation v0.35 ATP13A2 Sangavi Sivagnanasundram reviewed gene: ATP13A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22743658, 23447832, 29325618, 20310007; Phenotypes: Kufor-Rakeb syndrome MONDO:0011706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.34 TYROBP Sangavi Sivagnanasundram reviewed gene: TYROBP: Rating: RED; Mode of pathogenicity: None; Publications: 20301376, 25547154; Phenotypes: polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 MONDO:0020749; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.34 TGFB1 Sangavi Sivagnanasundram reviewed gene: TGFB1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 20301335, 30034812, 39014191; Phenotypes: Camurati-Engelmann disease MONDO:0007542; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteopetrosis v0.34 SOST Sangavi Sivagnanasundram reviewed gene: SOST: Rating: GREEN; Mode of pathogenicity: None; Publications: 23079137, 36481973, 33078679, 35208525, 36508511; Phenotypes: sclerosteosis 1 MONDO:0010016; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.34 PTH1R Sangavi Sivagnanasundram reviewed gene: PTH1R: Rating: GREEN; Mode of pathogenicity: None; Publications: 36159186, 37448157, 39327493; Phenotypes: primary failure of tooth eruption MONDO:0007434; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.633 LHX3 Ee Ming Wong reviewed gene: LHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30759489; Phenotypes: Pituitary hormone deficiency, combined, 3 (MIM# 221750); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 KY Ee Ming Wong reviewed gene: KY: Rating: GREEN; Mode of pathogenicity: None; Publications: 27484770, 27485408, 30591934; Phenotypes: Myopathy, myofibrillar, 7 (MIM#617114); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 KLHL7 Ee Ming Wong reviewed gene: KLHL7: Rating: GREEN; Mode of pathogenicity: None; Publications: 31953236, 30300710, 31856884; Phenotypes: PERCHING syndrome (MIM#617055); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 POP1 Crystle Lee reviewed gene: POP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27380734, 28067412; Phenotypes: Anauxetic dysplasia 2, MIM#617396; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 POMGNT2 Crystle Lee edited their review of gene: POMGNT2: Changed rating: GREEN
Prepair 1000+ v1.633 POMGNT2 Crystle Lee reviewed gene: POMGNT2: Rating: ; Mode of pathogenicity: None; Publications: 34301702; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8, 618135, Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8, MIM#618135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 POMC Crystle Lee reviewed gene: POMC: Rating: GREEN; Mode of pathogenicity: None; Publications: 34177811; Phenotypes: Obesity, adrenal insufficiency, and red hair due to POMC deficiency, MIM#609734; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 IARS2 Crystle Lee reviewed gene: IARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30419932; Phenotypes: Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, MIM#616007; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 HINT1 Crystle Lee reviewed gene: HINT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuromyotonia and axonal neuropathy, autosomal recessive, MIM#137200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 HGSNAT Crystle Lee reviewed gene: HGSNAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 32770643; Phenotypes: Mucopolysaccharidosis type IIIC (Sanfilippo C), MIM#252930, Retinitis pigmentosa 73, MIM#616544; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 PDE6C Crystle Lee reviewed gene: PDE6C: Rating: GREEN; Mode of pathogenicity: None; Publications: 33001157, 34720973; Phenotypes: Cone dystrophy 4, MIM#613093; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 NDUFAF2 Crystle Lee reviewed gene: NDUFAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38419071; Phenotypes: Mitochondrial complex I deficiency, nuclear type 10, MIM#618233; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 LPIN1 Crystle Lee reviewed gene: LPIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18817903, 32549891; Phenotypes: Myoglobinuria, acute recurrent, autosomal recessive, MIM#268200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 L2HGDH Crystle Lee edited their review of gene: L2HGDH: Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 L2HGDH Crystle Lee changed review comment from: Well established gene-disease association.

Onset typically in infancy or early childhood, however, reports of milder, adult onset cases have been reported. Patients may present with a wide variety of clinical manifestations.; to: Well established gene-disease association.

Onset typically in infancy or early childhood, however, reports of milder, adult onset cases have been reported. Patients may present with a wide variety of clinical manifestations.
Prepair 1000+ v1.633 L2HGDH Crystle Lee reviewed gene: L2HGDH: Rating: ; Mode of pathogenicity: None; Publications: 39262645, 10399870; Phenotypes: L-2-hydroxyglutaric aciduria, MIM#236792; Mode of inheritance: None
Prepair 1000+ v1.633 HEXB Crystle Lee reviewed gene: HEXB: Rating: GREEN; Mode of pathogenicity: None; Publications: 35711818; Phenotypes: Sandhoff disease, infantile, juvenile, and adult forms, MIM#268800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 HEPACAM Crystle Lee reviewed gene: HEPACAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 21419380; Phenotypes: Megalencephalic leukoencephalopathy with subcortical cysts 2A, MIM#613925; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 HCFC1 Crystle Lee reviewed gene: HCFC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34164576; Phenotypes: Methylmalonic aciduria and homocysteinemia, cblX type, MIM#309541; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.633 GPR143 Crystle Lee reviewed gene: GPR143: Rating: AMBER; Mode of pathogenicity: None; Publications: 30555098, 29761529; Phenotypes: Nystagmus 6, congenital, X-linked, MIM#300814, Ocular albinism, type I, Nettleship-Falls type, MIM#300500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.633 POLR1C Andrew Coventry reviewed gene: POLR1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 26151409, 21131976, 30957429, 32042905; Phenotypes: Leukodystrophy, hypomyelinating, 11 MIM#616494, Treacher Collins syndrome 3 MIM#248390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 PEX11B Andrew Coventry reviewed gene: PEX11B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301621, 22581968, 31724321, 38423277, 39092477, 28129423, 33558817; Phenotypes: Peroxisome biogenesis disorder 14B MIM#614920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 PEX10 Andrew Coventry reviewed gene: PEX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10862081, 21031596, 30640048; Phenotypes: Peroxisome biogenesis disorder 6A (Zellweger) MIM#614870, Peroxisome biogenesis disorder 6B MIM#614871; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 JAGN1 Ee Ming Wong reviewed gene: JAGN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25129144, 37528877; Phenotypes: Severe congenital neutropenia 6, MIM# 616022; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 NUP93 Andrew Coventry reviewed gene: NUP93: Rating: GREEN; Mode of pathogenicity: None; Publications: 26878725, 26878725, 33578576, 30741391, 37762751, 38650033, 37692026, 37845138; Phenotypes: Nephrotic syndrome, type 12 MIM#616892; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.34 LRP5 Sangavi Sivagnanasundram reviewed gene: LRP5: Rating: GREEN; Mode of pathogenicity: None; Publications: 37659026, 26348019, 12054167, 12579474; Phenotypes: autosomal dominant osteopetrosis 1 MONDO:0011877; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.633 IL10RA Ee Ming Wong reviewed gene: IL10RA: Rating: GREEN; Mode of pathogenicity: None; Publications: 19890111, 21519361, 22476154; Phenotypes: Early onset inflammatory bowel disease 28 (MIM# 613148); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 IFT140 Ee Ming Wong reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: 22503633, 23418020, 28288023, 28724397; Phenotypes: Short-rib thoracic dysplasia 9 with of without polydactyly (MIM#266920); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.633 NPHP4 Andrew Coventry reviewed gene: NPHP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12244321, 12205563, 34013113, 23354436, 1577426, 23188109, 23559409; Phenotypes: Nephronophthisis 4 MONDO:0011752, Nephronophthisis 4 MIM#606966, Senior-Loken syndrome 4 MIM#606996; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 NDUFAF6 Andrew Coventry reviewed gene: NDUFAF6: Rating: GREEN; Mode of pathogenicity: None; Publications: 30642748, 18614015, 30642748, 29531337, 27623250, 28639102, 31967322, 32020600, 22019594, 25613900, 26741492, 35664867; Phenotypes: Leigh syndrome MONDO:0009723, Mitochondrial complex I deficiency, nuclear type 17 MIM#618239; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.34 IKBKG Sangavi Sivagnanasundram changed review comment from: A condition that typically only affects males. Variants associated with osteopetrosis are primarily located in exon 10. Reported individuals also presented with mild skin features consistent with IP.

PMID: 20499091 - 6yr boy with multiple phenotypes including mild osteopetrosis.

PMID: 11242109 - 2 unrelated males with osteopetrosis as a presenting phenotype and X420W mutation. In vitro functional assay showed that this variant does not completely abolish IKBKG activity/protein however impairs the function.; to: A condition that typically only affects males. Variants associated with osteopetrosis are primarily located in exon 10. Reported individuals also presented with mild skin features consistent with IP.

PMID: 20499091 - 6yr boy with multiple phenotypes including mild osteopetrosis.

PMID: 11242109 - 2 unrelated males with osteopetrosis as a presenting phenotype and X420W mutation was identified. In vitro functional assay showed that this variant does not completely abolish IKBKG activity/protein however impairs the function.
Osteopetrosis v0.34 IKBKG Sangavi Sivagnanasundram reviewed gene: IKBKG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301645, 20499091, 11242109; Phenotypes: IKBKG-related immunodeficiency with or without ectodermal dysplasia MONDO:0100162, incontinentia pigmenti MONDO:0010631; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.633 IDS Ee Ming Wong reviewed gene: IDS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301451; Phenotypes: Mucopolysaccharidosis II, MIM# 309900, Hunter syndrome, MONDO:0010674; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Prepair 1000+ v1.633 NAGLU Andrew Coventry reviewed gene: NAGLU: Rating: GREEN; Mode of pathogenicity: None; Publications: 25818867, 8650226, 14518829, 18392742, 11668611; Phenotypes: Mucopolysaccharidosis type IIIB (Sanfilippo B) MIM#252920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 MTM1 Andrew Coventry reviewed gene: MTM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10790201, 8640223, 27017278, 26938784, 15725586, 30232666, 37176116, 32805447, 31541013; Phenotypes: Myopathy, centronuclear, X-linked MIM#310400; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.633 HPRT1 Ee Ming Wong reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301328; Phenotypes: Lesch-Nyhan syndrome (MIM#300322); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v1.2154 PPP5C Lucy Spencer gene: PPP5C was added
gene: PPP5C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPP5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP5C were set to 35361529; 25363768; 33057194
Phenotypes for gene: PPP5C were set to Neurodevelopmental disorder, MONDO:0700092, PPP5C-related
Review for gene: PPP5C was set to AMBER
Added comment: PMID: 35361529 - reported a de novo missense in a proband with microcephaly, developmental delay and epilepsy. However, after personal communication with the undiagnosed disease network this proband has since been found to have a different diagnosis with a nonsense and a missense in VARS1 identified, so unclear if the PPP5C variant is contributing to their phenotype.

3 more probands with de novo missense variants have been published in large autism or developmental disorder cohort with limited information (PMIDs: 25363768, 33057194)

An internal VCGS proband with intellectual disability and failure to thrive was also found to have a de novo missense variant in this gene.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.3 PPP5C Lucy Spencer gene: PPP5C was added
gene: PPP5C was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PPP5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP5C were set to 35361529; 25363768; 33057194
Phenotypes for gene: PPP5C were set to Neurodevelopmental disorder, MONDO:0700092, PPP5C-related
Review for gene: PPP5C was set to AMBER
Added comment: PMID: 35361529 - reported a de novo missense in a proband with microcephaly, developmental delay and epilepsy. However, after personal communication with the undiagnosed disease network this proband has since been found to have a different diagnosis with a nonsense and a missense in VARS1 identified, so unclear if the PPP5C variant is contributing to their phenotype.

3 more probands with de novo missense variants have been published in large autism or developmental disorder cohort with limited information (PMIDs: 25363768, 33057194)

An internal VCGS proband with intellectual disability and failure to thrive was also found to have a de novo missense variant in this gene.
Sources: Literature
Osteopetrosis v0.34 AMER1 Sangavi Sivagnanasundram reviewed gene: AMER1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27369646, 33856753, 35186393; Phenotypes: osteopathia striata with cranial sclerosis MONDO:0010310; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral vascular malformations v1.0 Bryony Thompson promoted panel to version 1.0
Cerebral vascular malformations v0.116 COL4A2 Sangavi Sivagnanasundram changed review comment from: 22209247 - COL4A1 form heterotrimers with COL4A2 which results in the cerebral vascular phenotype. No pathogenic variants in COL1A2 have been reported in individuals with a cerebral vascular phenotype.

COL4A2 is typically associated with haemorrhagic strokes with no evidence of any cerebral vascular malformations.; to: 22209247 - COL4A1 form heterotrimers with COL4A2 which results in the cerebral vascular phenotype. No pathogenic variants in COL4A2 have been reported in individuals with a cerebral vascular phenotype.

COL4A2 is typically associated with haemorrhagic strokes with no evidence of any cerebral vascular malformations.
Cerebral vascular malformations v0.116 COL4A2 Sangavi Sivagnanasundram changed review comment from: 22209247 - COL1A1 form heterotrimers with COL2A2 which results in the cerebral vascular phenotype. No pathogenic variants in COL1A2 have been reported in individuals with a cerebral vascular phenotype.

COL2A2 is typically associated with haemorrhagic strokes with no evidence of any cerebral vascular malformations.; to: 22209247 - COL4A1 form heterotrimers with COL4A2 which results in the cerebral vascular phenotype. No pathogenic variants in COL1A2 have been reported in individuals with a cerebral vascular phenotype.

COL4A2 is typically associated with haemorrhagic strokes with no evidence of any cerebral vascular malformations.
Cerebral vascular malformations v0.116 PKD1 Bryony Thompson Classified gene: PKD1 as Green List (high evidence)
Cerebral vascular malformations v0.116 PKD1 Bryony Thompson Gene: pkd1 has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.115 PKD1 Bryony Thompson Classified gene: PKD1 as Amber List (moderate evidence)
Cerebral vascular malformations v0.115 PKD1 Bryony Thompson Gene: pkd1 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v0.114 PCNT Bryony Thompson Marked gene: PCNT as ready
Cerebral vascular malformations v0.114 PCNT Bryony Thompson Gene: pcnt has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.114 PCNT Bryony Thompson Classified gene: PCNT as Green List (high evidence)
Cerebral vascular malformations v0.114 PCNT Bryony Thompson Gene: pcnt has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.113 PCNT Bryony Thompson Publications for gene: PCNT were set to 15368497
Cerebral vascular malformations v0.112 MYH11 Bryony Thompson Marked gene: MYH11 as ready
Cerebral vascular malformations v0.112 MYH11 Bryony Thompson Gene: myh11 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.112 MYH11 Bryony Thompson Publications for gene: MYH11 were set to 16444274; 29263223
Cerebral vascular malformations v0.111 MYH11 Bryony Thompson Classified gene: MYH11 as Red List (low evidence)
Cerebral vascular malformations v0.111 MYH11 Bryony Thompson Gene: myh11 has been classified as Red List (Low Evidence).
Mendeliome v1.2154 MRVI1 Bryony Thompson Marked gene: MRVI1 as ready
Mendeliome v1.2154 MRVI1 Bryony Thompson Gene: mrvi1 has been classified as Red List (Low Evidence).
Mendeliome v1.2154 MRVI1 Bryony Thompson Phenotypes for gene: MRVI1 were changed from moyamoya syndrome to Moyamoya disease MONDO:0016820
Mendeliome v1.2153 MRVI1 Bryony Thompson edited their review of gene: MRVI1: Changed phenotypes: Moyamoya disease MONDO:0016820
Mendeliome v1.2153 MRVI1 Bryony Thompson gene: MRVI1 was added
gene: MRVI1 was added to Mendeliome. Sources: NHS GMS
new gene name tags were added to gene: MRVI1.
Mode of inheritance for gene: MRVI1 was set to Unknown
Publications for gene: MRVI1 were set to 30001348
Phenotypes for gene: MRVI1 were set to moyamoya syndrome
Review for gene: MRVI1 was set to RED
Added comment: A single report of a variant as a possible modifier of NF1-related Moyamoya disease. The SNP rs35857561 segregates co-occurring with NF1 in 2 families and Moyamoya disease. rs35857561 is a common SNP and IRAG1 (new gene name) hasn't been reported in association with Mendelian disease.
Sources: NHS GMS
Cerebral vascular malformations v0.110 MRVI1 Bryony Thompson Marked gene: MRVI1 as ready
Cerebral vascular malformations v0.110 MRVI1 Bryony Thompson Gene: mrvi1 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.110 MRVI1 Bryony Thompson Classified gene: MRVI1 as Red List (low evidence)
Cerebral vascular malformations v0.110 MRVI1 Bryony Thompson Gene: mrvi1 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.109 FLVCR2 Bryony Thompson Classified gene: FLVCR2 as Green List (high evidence)
Cerebral vascular malformations v0.109 FLVCR2 Bryony Thompson Gene: flvcr2 has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.108 FLVCR2 Bryony Thompson reviewed gene: FLVCR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38693257, 32333401, 20206334; Phenotypes: Proliferative vasculopathy and hydranencephaly/hydrocephaly MONDO:0009168; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Cerebral vascular malformations v0.108 CEP152 Bryony Thompson Marked gene: CEP152 as ready
Cerebral vascular malformations v0.108 CEP152 Bryony Thompson Gene: cep152 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.108 CEP152 Bryony Thompson Classified gene: CEP152 as Red List (low evidence)
Cerebral vascular malformations v0.108 CEP152 Bryony Thompson Gene: cep152 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.107 ATR Bryony Thompson Classified gene: ATR as Red List (low evidence)
Cerebral vascular malformations v0.107 ATR Bryony Thompson Gene: atr has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.106 NF1 Bryony Thompson Marked gene: NF1 as ready
Cerebral vascular malformations v0.106 NF1 Bryony Thompson Gene: nf1 has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.106 NF1 Bryony Thompson Classified gene: NF1 as Green List (high evidence)
Cerebral vascular malformations v0.106 NF1 Bryony Thompson Gene: nf1 has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.105 NF1 Bryony Thompson reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39367156, 39380389, 20301288; Phenotypes: Neurofibromatosis type 1 MONDO:0018975; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.2152 DHDDS Zornitza Stark Publications for gene: DHDDS were set to 27343064; 29100083; 21295283; 34382076
Mendeliome v1.2151 DHDDS Zornitza Stark edited their review of gene: DHDDS: Added comment: Bi-allelic variants: ClinGen have lumped the CDG together with the RP -- likely represent a continuum of severity rather than distinct disorders.; Changed publications: 27343064, 29100083, 21295283, 27343064, 21295283, 28130426, 29276052, 32483926, 36046393, 24078709, 28005406, 36046393
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.155 DHDDS Zornitza Stark Phenotypes for gene: DHDDS were changed from Retinitis pigmentosa 59, 613861 to Congenital disorder of glycosylation, type 1bb, MIM# 613861
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.154 DHDDS Zornitza Stark Publications for gene: DHDDS were set to
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.153 DHDDS Zornitza Stark Classified gene: DHDDS as Green List (high evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.153 DHDDS Zornitza Stark Gene: dhdds has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.152 DHDDS Zornitza Stark edited their review of gene: DHDDS: Added comment: ClinGen have lumped the CDG together with the RP -- likely represent a continuum of severity rather than distinct disorders.; Changed rating: GREEN; Changed publications: 27343064, 21295283, 28130426, 29276052, 32483926, 36046393, 24078709, 28005406, 36046393; Changed phenotypes: Congenital disorder of glycosylation, type 1bb, MIM# 613861; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v1.58 DHDDS Zornitza Stark Publications for gene: DHDDS were set to 27343064
Congenital Disorders of Glycosylation v1.57 DHDDS Zornitza Stark Classified gene: DHDDS as Green List (high evidence)
Congenital Disorders of Glycosylation v1.57 DHDDS Zornitza Stark Gene: dhdds has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v1.56 DHDDS Zornitza Stark edited their review of gene: DHDDS: Added comment: ClinGen have lumped the CDG together with the RP -- likely represent a continuum of severity rather than distinct disorders.; Changed rating: GREEN; Changed publications: 27343064, 21295283, 28130426, 29276052, 32483926, 36046393, 24078709, 28005406, 36046393
Osteopetrosis v0.34 FERMT3 Sangavi Sivagnanasundram reviewed gene: FERMT3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19234460, 20357244, 18278053; Phenotypes: leukocyte adhesion deficiency 3 MONDO:0013016; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.34 CTSK Sangavi Sivagnanasundram reviewed gene: CTSK: Rating: GREEN; Mode of pathogenicity: None; Publications: 19232111, 34777883, 32984533, 24269275; Phenotypes: pycnodysostosis MONDO:0009940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.34 ANKH Sangavi Sivagnanasundram reviewed gene: ANKH: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301634, 20358596; Phenotypes: craniometaphyseal dysplasia MONDO:0015465; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 SMAD3 Sangavi Sivagnanasundram reviewed gene: SMAD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 29392890, 26247899; Phenotypes: Loeys-Dietz syndrome 3 MIM#613795; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 SMAD2 Sangavi Sivagnanasundram reviewed gene: SMAD2: Rating: RED; Mode of pathogenicity: None; Publications: 26247899; Phenotypes: Loeys-Dietz syndrome 6 MONDO:0030500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 TSC2 Sangavi Sivagnanasundram reviewed gene: TSC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 36117164, 37800821; Phenotypes: lymphangioleiomyomatosis MONDO:0011705, tuberous sclerosis 2 MONDO:0013199; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 TSC1 Sangavi Sivagnanasundram edited their review of gene: TSC1: Changed rating: AMBER
Pneumothorax v0.11 TSC1 Sangavi Sivagnanasundram changed review comment from: Lymphangioleiomyomatosis (LAM) is the primary pulmonary manifestation of tuberous sclerosis. LAM can cause other pulmonary phenotypes including pneumothorax.
The reported cases in the literature have reported a pneumothorax phenotype secondary to LAM and not as a primary cause when looking at tuberous sclerosis.
There are many reported individuals with a diagnosis of LAM has been reported with pneumothorax. ; to: Lymphangioleiomyomatosis (LAM) is the primary pulmonary manifestation of tuberous sclerosis. LAM can cause other pulmonary phenotypes including pneumothorax.
The reported cases in the literature have reported a pneumothorax phenotype secondary to LAM and not as a primary cause when looking at tuberous sclerosis.
There are many reported individuals with a diagnosis of LAM has been reported with pneumothorax.

This gene would be green when curated against LAM however red when curated against TSC as pneumothorax is a secondary feature.
Pneumothorax v0.11 TSC1 Sangavi Sivagnanasundram edited their review of gene: TSC1: Changed rating: GREEN
Pneumothorax v0.11 TSC1 Sangavi Sivagnanasundram changed review comment from: Lymphangioleiomyomatosis (LAM) is the primary pulmonary manifestation of tuberous sclerosis. LAM can cause other pulmonary phenotypes including pneumothorax.
The reported cases in the literature have reported a pneumothorax phenotype secondary to LAM and not as a primary cause.; to: Lymphangioleiomyomatosis (LAM) is the primary pulmonary manifestation of tuberous sclerosis. LAM can cause other pulmonary phenotypes including pneumothorax.
The reported cases in the literature have reported a pneumothorax phenotype secondary to LAM and not as a primary cause when looking at tuberous sclerosis.
There are many reported individuals with a diagnosis of LAM has been reported with pneumothorax.
Pneumothorax v0.11 TSC1 Sangavi Sivagnanasundram edited their review of gene: TSC1: Changed rating: AMBER
Pneumothorax v0.11 TSC1 Sangavi Sivagnanasundram reviewed gene: TSC1: Rating: RED; Mode of pathogenicity: None; Publications: 27226234, 23729718, 19318672; Phenotypes: tuberous sclerosis 1 MONDO:0008612, lung lymphangioleiomyomatosis MONDO:0006277; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 TGFB2 Sangavi Sivagnanasundram reviewed gene: TGFB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 22772371, 29392890; Phenotypes: Loeys-Dietz syndrome 4 MONDO:0013897; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 TGFBR2 Sangavi Sivagnanasundram reviewed gene: TGFBR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22488992, 26493799; Phenotypes: Loeys-Dietz syndrome 2 MONDO:0012427; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 TGFB2 Sangavi Sivagnanasundram Deleted their review
Pneumothorax v0.11 TGFB2 Sangavi Sivagnanasundram Deleted their comment
Pneumothorax v0.11 TGFB3 Sangavi Sivagnanasundram reviewed gene: TGFB3: Rating: RED; Mode of pathogenicity: None; Publications: 25835445, 31898322; Phenotypes: Loeys-Dietz syndrome MONDO:0018954; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 TGFBR1 Sangavi Sivagnanasundram reviewed gene: TGFBR1: Rating: RED; Mode of pathogenicity: None; Publications: 16799921, 25835445; Phenotypes: Loeys-Dietz syndrome MONDO:0018954; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pneumothorax v0.11 TGFB2 Sangavi Sivagnanasundram reviewed gene: TGFB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26493799, 22488992, 24577266; Phenotypes: Loeys-Dietz syndrome 4 MONDO:0013897; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.633 COG6 Lauren Thomas reviewed gene: COG6: Rating: GREEN; Mode of pathogenicity: None; Publications: 20605848, 23430903, 26260076, 32905044, 32683677, 31420886; Phenotypes: Congenital disorder of glycosylation, type IIl (MIM# 614576); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 GPT2 Kate Scarff reviewed gene: GPT2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27601654, 25758935, 31471722; Phenotypes: Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM #616281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 MTFMT Andrew Coventry reviewed gene: MTFMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 21907147, 23499752, 24461907, 22499348, 30911575; Phenotypes: Leigh Syndrome MONDO:0009723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.633 GPC3 Kate Scarff reviewed gene: GPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301398, 38766979; Phenotypes: Simpson-Golabi-Behmel syndrome, type 1, MIM #312870; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.633 DPH1 Lilian Downie Marked gene: DPH1 as ready
Prepair 1000+ v1.633 DPH1 Lilian Downie Gene: dph1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.633 DPH1 Lilian Downie Publications for gene: DPH1 were set to
Pneumothorax v0.11 SERPINA1 Sangavi Sivagnanasundram reviewed gene: SERPINA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38633947, 20301692; Phenotypes: alpha 1-antitrypsin deficiency MONDO:0013282; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.632 EIF2B5 Lilian Downie Marked gene: EIF2B5 as ready
Prepair 1000+ v1.632 EIF2B5 Lilian Downie Gene: eif2b5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.632 EIF2B5 Lilian Downie Publications for gene: EIF2B5 were set to
Prepair 1000+ v1.631 ESCO2 Lilian Downie Marked gene: ESCO2 as ready
Prepair 1000+ v1.631 ESCO2 Lilian Downie Added comment: Comment when marking as ready: ClinGen review
Prepair 1000+ v1.631 ESCO2 Lilian Downie Gene: esco2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.631 ESCO2 Lilian Downie Added comment: Comment on phenotypes: ClinGen review for Roberts-SC phocolmelia MONDO:0100253 but no reference to Juberg-Hayward syndrome
Prepair 1000+ v1.631 ESCO2 Lilian Downie Phenotypes for gene: ESCO2 were changed from SC phocomelia syndrome, 269000 (3) to Juberg-Hayward syndrome (MIM#216100); Roberts-SC phocomelia syndrome (MIM#268300)
Prepair 1000+ v1.630 ESCO2 Lilian Downie Publications for gene: ESCO2 were set to
Prepair 1000+ v1.629 GAMT Lilian Downie Marked gene: GAMT as ready
Prepair 1000+ v1.629 GAMT Lilian Downie Gene: gamt has been classified as Green List (High Evidence).
Prepair 1000+ v1.629 GAMT Lilian Downie Publications for gene: GAMT were set to
Prepair 1000+ v1.628 GLDC Lilian Downie Marked gene: GLDC as ready
Prepair 1000+ v1.628 GLDC Lilian Downie Gene: gldc has been classified as Green List (High Evidence).
Prepair 1000+ v1.628 GLDC Lilian Downie Publications for gene: GLDC were set to
Prepair 1000+ v1.627 GNS Lilian Downie Marked gene: GNS as ready
Prepair 1000+ v1.627 GNS Lilian Downie Gene: gns has been classified as Green List (High Evidence).
Prepair 1000+ v1.627 GNS Lilian Downie Publications for gene: GNS were set to
Prepair 1000+ v1.626 GPAA1 Lilian Downie Marked gene: GPAA1 as ready
Prepair 1000+ v1.626 GPAA1 Lilian Downie Gene: gpaa1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.626 GPAA1 Lilian Downie Phenotypes for gene: GPAA1 were changed from Glycosylphosphatidylinositol biosynthesis defect 15, 617810 (3), Autosomal recessive to Glycosylphosphatidylinositol biosynthesis defect 15, MIM#617810
Prepair 1000+ v1.625 GPAA1 Lilian Downie Publications for gene: GPAA1 were set to
Prepair 1000+ v1.624 GRM1 Lilian Downie Marked gene: GRM1 as ready
Prepair 1000+ v1.624 GRM1 Lilian Downie Gene: grm1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.624 GRM1 Lilian Downie Publications for gene: GRM1 were set to 22901947; 26308914; 31319223
Prepair 1000+ v1.624 GRM1 Lilian Downie Publications for gene: GRM1 were set to
Prepair 1000+ v1.623 GTF2H5 Lilian Downie Marked gene: GTF2H5 as ready
Prepair 1000+ v1.623 GTF2H5 Lilian Downie Gene: gtf2h5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.623 GTF2H5 Lilian Downie Phenotypes for gene: GTF2H5 were changed from Trichothiodystrophy 3, photosensitive, 616395 (3) to Trichothiodystrophy 3, photosensitive, MIM# 616395
Prepair 1000+ v1.622 GTF2H5 Lilian Downie Publications for gene: GTF2H5 were set to
Prepair 1000+ v1.621 GUCY1A3 Lilian Downie Marked gene: GUCY1A3 as ready
Prepair 1000+ v1.621 GUCY1A3 Lilian Downie Gene: gucy1a3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.621 GUCY1A3 Lilian Downie Publications for gene: GUCY1A3 were set to
Prepair 1000+ v1.620 ATF6 Lilian Downie Marked gene: ATF6 as ready
Prepair 1000+ v1.620 ATF6 Lilian Downie Gene: atf6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.620 ATF6 Lilian Downie Phenotypes for gene: ATF6 were changed from Achromatopsia 7, 616517 (3), Autosomal recessive to Achromatopsia 7, MIM# 616517
Prepair 1000+ v1.619 ATF6 Lilian Downie Publications for gene: ATF6 were set to
Prepair 1000+ v1.618 B4GALNT1 Lilian Downie Marked gene: B4GALNT1 as ready
Prepair 1000+ v1.618 B4GALNT1 Lilian Downie Gene: b4galnt1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.618 B4GALNT1 Lilian Downie Phenotypes for gene: B4GALNT1 were changed from Spastic paraplegia 26, MIM# 609195 to Spastic paraplegia 26, MIM# 609195
Prepair 1000+ v1.617 B4GALNT1 Lilian Downie Phenotypes for gene: B4GALNT1 were changed from Spastic paraplegia 26, autosomal recessive, 609195 (3) to Spastic paraplegia 26, MIM# 609195
Prepair 1000+ v1.616 B4GALNT1 Lilian Downie Publications for gene: B4GALNT1 were set to
Prepair 1000+ v1.615 LARP7 Lilian Downie Marked gene: LARP7 as ready
Prepair 1000+ v1.615 LARP7 Lilian Downie Gene: larp7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.615 LARP7 Lilian Downie Phenotypes for gene: LARP7 were changed from Alazami syndrome, 615071 (3) to Alazami syndrome MIM#615071
Prepair 1000+ v1.614 LARP7 Lilian Downie Publications for gene: LARP7 were set to
Prepair 1000+ v1.613 MMAB Andrew Coventry reviewed gene: MMAB: Rating: GREEN; Mode of pathogenicity: None; Publications: 12471062, 24813872, 16410054; Phenotypes: Methylmalonic aciduria, vitamin B12-responsive, cblB type MIM#251110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.613 FKBP10 Lilian Downie Marked gene: FKBP10 as ready
Prepair 1000+ v1.613 FKBP10 Lilian Downie Gene: fkbp10 has been classified as Green List (High Evidence).
Prepair 1000+ v1.613 FKBP10 Lilian Downie Phenotypes for gene: FKBP10 were changed from Bruck syndrome 1, 259450 (3) to Bruck syndrome MIM#259450; osteogenesis imperfecta, type XI, MIM#610968
Prepair 1000+ v1.612 FKBP10 Lilian Downie Publications for gene: FKBP10 were set to