Activity

Date Panel Item Activity
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Limb girdle muscular dystrophy v2.3 SMN1 Ian Berry reviewed gene: SMN1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.3 NPR3 Ian Berry gene: NPR3 was added
gene: NPR3 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: NPR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPR3 were set to PMID: 30032985; 10468599
Phenotypes for gene: NPR3 were set to Tall stature; arachnodactyly; extra epiphyses; aortic dilatation
Penetrance for gene: NPR3 were set to unknown
Review for gene: NPR3 was set to GREEN
gene: NPR3 was marked as current diagnostic
Added comment: 4 individuals in 3 families reported with striking phenotypic similarity.
Functional evidence compelling.
Mouse model recapitulates phenotype (including skeletal features).
Sources: Literature
Stickler syndrome v2.3 Sarah Leigh Panel version has been signed off
Diabetes - neonatal onset v2.3 Sarah Leigh Panel version has been signed off
Renal tubulopathies v2.3 Sarah Leigh Panel version has been signed off
Hyperthyroidism v2.3 Sarah Leigh Panel version has been signed off
Cystic kidney disease v2.3 Sarah Leigh Panel version has been signed off
Cataracts v2.3 Sarah Leigh Panel version has been signed off
Short QT syndrome v2.3 Sarah Leigh Panel version has been signed off
Catecholaminergic polymorphic VT v2.3 Sarah Leigh Panel version has been signed off
Optic neuropathy v2.3 Sarah Leigh Panel version has been signed off
Congenital adrenal hypoplasia v2.3 Sarah Leigh Panel version has been signed off
Arrhythmogenic cardiomyopathy v2.5 Sarah Leigh Panel version has been signed off
Cardiomyopathies - including childhood onset v1.5 Sarah Leigh Panel version has been signed off
Skeletal ciliopathies v1.3 Sarah Leigh Panel version has been signed off
Ophthalmological ciliopathies v1.4 Sarah Leigh Panel version has been signed off
Thoracic aortic aneurysm and dissection v1.3 Sarah Leigh Panel version has been signed off
Corneal dystrophies v1.3 Sarah Leigh Panel version has been signed off
Polycystic liver disease interim v1.3 Sarah Leigh Panel version has been signed off
Dilated cardiomyopathy - adult and teen v1.3 Sarah Leigh Panel version has been signed off
Inherited phaeochromocytoma and paraganglioma excluding NF1 v1.3 Sarah Leigh Panel version has been signed off
Endocrine neoplasms v1.3 Sarah Leigh Panel version has been signed off
Primary pigmented nodular adrenocortical disease v1.3 Sarah Leigh Panel version has been signed off
Rare genetic inflammatory skin disorders v1.6 Sarah Leigh Panel version has been signed off
Mosaic skin disorders - deep sequencing v1.3 Sarah Leigh Panel version has been signed off
Vascular skin disorders v1.3 Sarah Leigh Panel version has been signed off
Epidermodysplasia verruciformis v1.3 Sarah Leigh Panel version has been signed off
Cutaneous photosensitivity with a likely genetic cause v1.3 Sarah Leigh Panel version has been signed off
Pigmentary skin disorders v1.3 Sarah Leigh Panel version has been signed off
Multiple monogenic benign skin tumours v1.3 Sarah Leigh Panel version has been signed off
Autosomal recessive primary hypertrophic osteoarthropathy v1.3 Sarah Leigh Panel version has been signed off
Palmoplantar keratodermas v1.3 Sarah Leigh Panel version has been signed off
Ichthyosis and erythrokeratoderma v1.3 Sarah Leigh Panel version has been signed off
Epidermolysis bullosa and congenital skin fragility v1.3 Sarah Leigh Panel version has been signed off
Ectodermal dysplasia v1.4 Sarah Leigh Panel version has been signed off
Familial tumoral calcinosis v1.3 Sarah Leigh Panel version has been signed off
Intellectual disability v3.3 SLC9A7 Zornitza Stark gene: SLC9A7 was added
gene: SLC9A7 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: SLC9A7 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SLC9A7 were set to 30335141
Phenotypes for gene: SLC9A7 were set to Intellectual developmental disorder, X-linked 108; OMIM #301024
Review for gene: SLC9A7 was set to AMBER
Added comment: 6 males from 2 unrelated families with hemizygous missense mutation in the SLC9A7 gene. The mutation segregated with the disorder in the family. In vitro functional expression studies in CHO cells (AP-1 cells) showed that the mutation caused decreased levels of protein expression and reduced oligosaccharide maturation/glycosylation compared to wildtype, indicating impaired posttranslational processing. Subcellular localization studies indicated that protein trafficking was unaffected by the mutation. However, examination of the trans-Golgi compartment suggested a gain-of-function effect and a perturbation of glycosylation of secretory cargo. Serum transferrin studies in 1 patient suggested a glycosylation defect. One to watch.
Sources: Expert list
Lipodystrophy - childhood onset v2.5 Sarah Leigh Panel version has been signed off
Lipodystrophy - childhood onset v2.3 Sarah Leigh Panel version has been signed off
Tumour predisposition - childhood onset v2.3 Rebecca Foulger Panel version has been signed off
Tumour predisposition - childhood onset v2.2 Rebecca Foulger Panel types changed to Rare Disease 100K; GMS Rare Disease; GMS Cancer Germline Virtual; GMS signed-off
Cholestasis v1.3 Sarah Leigh Panel version has been signed off
Bardet Biedl syndrome v1.3 Sarah Leigh Panel version has been signed off
Adult solid tumours cancer susceptibility v2.3 Rebecca Foulger Panel version has been signed off
Leber hereditary optic neuropathy v1.3 Sarah Leigh Panel version has been signed off
Haematological malignancies cancer susceptibility v2.3 Rebecca Foulger Panel version has been signed off
Sarcoma susceptibility v1.3 Rebecca Foulger Panel version has been signed off
Severe early-onset obesity v2.3 Sarah Leigh Panel version has been signed off
Lysosomal storage disorder v1.3 Sarah Leigh Panel version has been signed off
Glycogen storage disease v1.3 Sarah Leigh Panel version has been signed off
Lipoprotein lipase deficiency v1.3 Sarah Leigh Panel version has been signed off
Intellectual disability v3.3 SLC1A1 Zornitza Stark gene: SLC1A1 was added
gene: SLC1A1 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: SLC1A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC1A1 were set to Dicarboxylic aminoaciduria, MIM#222730
Review for gene: SLC1A1 was set to GREEN
gene: SLC1A1 was marked as current diagnostic
Added comment: ID is part of the phenotype of this metabolic disorder.
Sources: Expert list
Intellectual disability v3.3 SKIV2L Zornitza Stark reviewed gene: SKIV2L: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Trichohepatoenteric syndrome 2, MIM# 614602; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.3 SIX5 Zornitza Stark reviewed gene: SIX5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Branchiootorenal syndrome 2 610896; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.3 SIX1 Zornitza Stark reviewed gene: SIX1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Branchiootic syndrome 3, MIM# 608389, Deafness, autosomal dominant 23, MIM# 605192; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neuronal ceroid lipofuscinosis v1.3 Sarah Leigh Panel version has been signed off
Possible mitochondrial disorder - nuclear genes v1.14 Sarah Leigh Panel version has been signed off
Mitochondrial disorder with complex V deficiency v1.3 Sarah Leigh Panel version has been signed off
Mitochondrial disorder with complex IV deficiency v1.3 Sarah Leigh Panel version has been signed off
Mitochondrial disorder with complex III deficiency v1.3 Sarah Leigh Panel version has been signed off
Mitochondrial disorder with complex II deficiency v1.3 Sarah Leigh Panel version has been signed off
Mitochondrial disorder with complex I deficiency v1.3 Sarah Leigh Panel version has been signed off
Mitochondrial DNA maintenance disorder v1.3 Sarah Leigh Panel version has been signed off
Mitochondrial liver disease v1.3 Sarah Leigh Panel version has been signed off
Pyruvate dehydrogenase (PDH) deficiency v1.3 Sarah Leigh Panel version has been signed off
Mitochondrial disorders v2.5 Sarah Leigh Panel version has been signed off
Familial hypercholesterolaemia - targeted panel v1.3 Rebecca Foulger Panel version has been signed off
Familial hypercholesterolaemia - targeted panel v1.2 Rebecca Foulger Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; GMS signed-off
Fetal anomalies v1.3 Rebecca Foulger Panel version has been signed off
Brugada syndrome v2.3 Sarah Leigh Panel version has been signed off
Inborn errors of metabolism v2.4 Sarah Leigh Panel version has been signed off
Intellectual disability v3.3 SH3PXD2B Zornitza Stark reviewed gene: SH3PXD2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Frank-ter Haar syndrome, MIM# 249420; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.3 SFXN4 Zornitza Stark gene: SFXN4 was added
gene: SFXN4 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: SFXN4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SFXN4 were set to 31059822; 24119684
Phenotypes for gene: SFXN4 were set to Combined oxidative phosphorylation deficiency 18, MIM#615578
Review for gene: SFXN4 was set to GREEN
gene: SFXN4 was marked as current diagnostic
Added comment: Three unrelated families reported, mild ID as well as other neurological features are part of the phenotype.
Sources: Expert list
Intellectual disability v3.3 SEC31A Zornitza Stark gene: SEC31A was added
gene: SEC31A was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: SEC31A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEC31A were set to 30464055
Phenotypes for gene: SEC31A were set to Neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies, OMIM #618651
Review for gene: SEC31A was set to AMBER
Added comment: Single family with two affected sibs with functional data (drosophila), one to watch.
Sources: Expert list
Intellectual disability v3.3 SEC23B Zornitza Stark reviewed gene: SEC23B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ?Cowden syndrome 7 616858, Dyserythropoietic anemia, congenital, type II 224100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v3.3 SCN1B Zornitza Stark reviewed gene: SCN1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 52, MIM#617350; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v3.3 SCN11A Zornitza Stark reviewed gene: SCN11A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuropathy, hereditary sensory and autonomic, type VII, MIM#615548; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.3 SCARF2 Zornitza Stark reviewed gene: SCARF2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Van den Ende-Gupta syndrome, MIM# 600920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.3 SCAMP5 Zornitza Stark reviewed gene: SCAMP5: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31439720; Phenotypes: Intellectual disability, seizures, autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v3.3 SBF1 Zornitza Stark gene: SBF1 was added
gene: SBF1 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: SBF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SBF1 were set to 24799518; 23749797; 30039846; 28902413
Phenotypes for gene: SBF1 were set to Charcot-Marie-Tooth disease, type 4B3, MIM# 615284
Review for gene: SBF1 was set to GREEN
Added comment: At least 4 families with multiple affected individuals described. Some have had central features including microcephaly and DD/ID, it is likely this gene causes a mixed picture.
Sources: Expert list
Intellectual disability v3.3 SBDS Zornitza Stark reviewed gene: SBDS: Rating: RED; Mode of pathogenicity: None; Publications: 19906387; Phenotypes: Shwachman-Diamond syndrome, MIM#260400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.3 SARS2 Zornitza Stark gene: SARS2 was added
gene: SARS2 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: SARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARS2 were set to 21255763; 24034276
Phenotypes for gene: SARS2 were set to Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, MIM#613845
Review for gene: SARS2 was set to GREEN
gene: SARS2 was marked as current diagnostic
Added comment: DD/ID is part of the phenotype. Two unrelated families reported, highly specific phenotype.
Sources: Expert list
Intellectual disability v3.3 SALL4 Zornitza Stark reviewed gene: SALL4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Duane-radial ray syndrome, MIM# 607323; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.3 SOX3 Zornitza Stark reviewed gene: SOX3: Rating: AMBER; Mode of pathogenicity: None; Publications: 29175558, 30125608, 12428212, 15800844; Phenotypes: Mental retardation, X-linked, with isolated growth hormone deficiency, MIM#300123, Panhypopituitarism, X-linked, MIM#312000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal dysplasia v2.3 TBXAS1 Tracy Lester edited their review of gene: TBXAS1: Added comment: Variants in the AD form are associated with a bleeding disorder - no evidence of skeletal dysplasia in these patients. Mode of inheritance should just be biallelic for the skeletal dysplasia panel.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital hyperinsulinism v2.1 UCP2 Zornitza Stark gene: UCP2 was added
gene: UCP2 was added to Congenital hyperinsulinism. Sources: Expert list
Mode of inheritance for gene: UCP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UCP2 were set to 19065272
Phenotypes for gene: UCP2 were set to Hyperinsulinism
Review for gene: UCP2 was set to AMBER
Added comment: Two children reported with variants in this gene; however, these were inherited. Functional data (mouse model).
Sources: Expert list
Congenital hyperinsulinism v2.1 NSD1 Zornitza Stark gene: NSD1 was added
gene: NSD1 was added to Congenital hyperinsulinism. Sources: Expert list
Mode of inheritance for gene: NSD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NSD1 were set to 30719864
Phenotypes for gene: NSD1 were set to Sotos syndrome (OMIM#117550)
Review for gene: NSD1 was set to GREEN
gene: NSD1 was marked as current diagnostic
Added comment: Hyperinsulinism is a documented feature of this syndrome: at least 9 individuals with NSD1 variants and hyperinsulinism reported; persistent in 3/9/
Sources: Expert list
Congenital hyperinsulinism v2.1 GPC3 Zornitza Stark reviewed gene: GPC3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Simpson-Golabi-Behmel syndrome, type 1 312870; Mode of inheritance: None
Congenital hyperinsulinism v2.1 AKT2 Zornitza Stark reviewed gene: AKT2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.3 PUM1 Zornitza Stark reviewed gene: PUM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29474920, 25768905; Phenotypes: Spinocerebellar ataxia 47, MIM#617931; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.3 PSAT1 Zornitza Stark reviewed gene: PSAT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26960553, 17436247, 25152457; Phenotypes: Phosphoserine aminotransferase deficiency, MIM# 610992, Neu-Laxova syndrome 2, MIM# 616038; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.3 PRSS56 Zornitza Stark reviewed gene: PRSS56: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Microphthalmia, isolated 6, MIM# 613517; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.3 PROP1 Zornitza Stark reviewed gene: PROP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined, 2, MIM# 262600; Mode of inheritance: None
Intellectual disability v3.3 PRKAR1A Zornitza Stark reviewed gene: PRKAR1A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Acrodysostosis 1, with or without hormone resistance, MIM# 101800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.3 PRDM12 Zornitza Stark reviewed gene: PRDM12: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuropathy, hereditary sensory and autonomic, type VIII, MIM# 616488; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.3 PPP1R12A Zornitza Stark gene: PPP1R12A was added
gene: PPP1R12A was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: PPP1R12A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP1R12A were set to 31883643
Phenotypes for gene: PPP1R12A were set to Intellectual disability; holoprosencephaly; disorder of sex development
Review for gene: PPP1R12A was set to GREEN
gene: PPP1R12A was marked as current diagnostic
Added comment: 12 individuals reported.
Sources: Expert list
Intellectual disability v3.3 PPA2 Zornitza Stark reviewed gene: PPA2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Sudden cardiac failure, infantile, MIM# 617222; Mode of inheritance: None
Common craniosynostosis syndromes v1.3 Eleanor Williams Panel version has been signed off
Amyloidosis v1.3 Eleanor Williams Panel version has been signed off
Amyloidosis v1.2 Eleanor Williams Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; GMS signed-off
Limb disorders v2.3 Eleanor Williams Panel version has been signed off
Skeletal dysplasia v2.3 Eleanor Williams Panel version has been signed off
Intellectual disability v3.3 Rebecca Foulger Panel version has been signed off
Genetic epilepsy syndromes v2.3 Rebecca Foulger Panel version has been signed off
Amelogenesis imperfecta v2.4 Eleanor Williams Panel version has been signed off
Amelogenesis imperfecta v2.3 Eleanor Williams Panel version has been signed off
Amelogenesis imperfecta v2.2 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; GMS signed-off
Arthrogryposis v3.3 Rebecca Foulger Panel version has been signed off
Osteogenesis imperfecta v2.3 Eleanor Williams Panel version has been signed off
Osteogenesis imperfecta v2.2 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; GMS signed-off
Craniosynostosis v2.3 Eleanor Williams Panel version has been signed off
Nephrocalcinosis or nephrolithiasis v2.3 Eleanor Williams Panel version has been signed off
Nephrocalcinosis or nephrolithiasis v2.2 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; GMS signed-off
DDG2P v2.3 Rebecca Foulger Panel version has been signed off
DDG2P v2.2 Rebecca Foulger Panel types changed to GMS Rare Disease; Component Of Super Panel; GMS signed-off
Atypical haemolytic uraemic syndrome v2.3 Eleanor Williams Panel version has been signed off
Atypical haemolytic uraemic syndrome v2.2 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; GMS signed-off
Proteinuric renal disease v2.5 Eleanor Williams Panel version has been signed off
Hearing loss v2.6 Eleanor Williams Panel version has been signed off
Proteinuric renal disease v2.3 Eleanor Williams Panel version has been signed off
Paediatric disorders - additional genes v1.2 Rebecca Foulger Panel version has been signed off
Intellectual disability v3.1 POMK Zornitza Stark gene: POMK was added
gene: POMK was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: POMK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POMK were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, MIM# 615249
Review for gene: POMK was set to GREEN
gene: POMK was marked as current diagnostic
Added comment: ID is part of the phenotype.
Sources: Expert list
Intellectual disability v3.1 POLR1D Zornitza Stark reviewed gene: POLR1D: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Treacher Collins syndrome 2, MIM# 613717; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v3.1 POLR1C Zornitza Stark reviewed gene: POLR1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 26151409; Phenotypes: Leukodystrophy, hypomyelinating, 11, MIM# 616494; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1 POLD1 Zornitza Stark reviewed gene: POLD1: Rating: RED; Mode of pathogenicity: None; Publications: 31449058; Phenotypes: Intellectual disability, immunodeficiency, Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM#615381; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v3.1 POC1B Zornitza Stark reviewed gene: POC1B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cone-rod dystrophy 20 615973; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1 PNPT1 Zornitza Stark reviewed gene: PNPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 13, MIM#614932; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1 PMS2 Zornitza Stark reviewed gene: PMS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mismatch repair cancer syndrome, MIM# 276300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1 PLOD2 Zornitza Stark reviewed gene: PLOD2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bruck syndrome 2 609220; Mode of inheritance: None
Intellectual disability v3.0 PKHD1 Zornitza Stark reviewed gene: PKHD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic kidney disease 4, with or without hepatic disease 263200; Mode of inheritance: None
Intellectual disability v3.0 PKD1L1 Zornitza Stark reviewed gene: PKD1L1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Heterotaxy, visceral, 8, autosomal, MIM# 617205; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 PITX3 Zornitza Stark reviewed gene: PITX3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Anterior segment dysgenesis 1, multiple subtypes, MIM# 107250, cataract; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 PITX2 Zornitza Stark reviewed gene: PITX2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Axenfeld-Rieger syndrome, type 1, MIM# 180500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 PISD Zornitza Stark gene: PISD was added
gene: PISD was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: PISD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PISD were set to 31263216; 30858161
Phenotypes for gene: PISD were set to intellectual disability; cataract; microcephaly; deafness; skeletal dysplasia
Review for gene: PISD was set to GREEN
Added comment: Three unrelated families reported.
Sources: Expert list
Intellectual disability v3.0 PIK3R1 Zornitza Stark reviewed gene: PIK3R1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: SHORT syndrome, MIM#269880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 PIK3C2A Zornitza Stark reviewed gene: PIK3C2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31034465; Phenotypes: Oculoskeletodental syndrome, 618440; Mode of inheritance: None
Intellectual disability v3.0 PIGS Zornitza Stark gene: PIGS was added
gene: PIGS was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: PIGS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGS were set to 30269814
Phenotypes for gene: PIGS were set to Glycosylphosphatidylinositol biosynthesis defect 18, MIM# 618143
Review for gene: PIGS was set to GREEN
gene: PIGS was marked as current diagnostic
Added comment: Three unrelated families reported. Severe neurological phenotype ranging from fetal akinesia to ID/EE.
Sources: Expert list
Paediatric disorders - additional genes v1.1 Rebecca Foulger Panel types changed to GMS Rare Disease; Component Of Super Panel; GMS signed-off
Intellectual disability v3.0 PIGH Zornitza Stark edited their review of gene: PIGH: Added comment: I note this gene is Green on the epilepsy panel, and I agree this family of genes cause similar phenotypes, there is some functional data to support the gene-disease relationship, so we have rated it Green on both panels.; Changed rating: GREEN; Changed publications: 29573052, 29603516
Neurological ciliopathies v1.2 PIBF1 Zornitza Stark reviewed gene: PIBF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26167768, 30858804, 29695797; Phenotypes: Joubert syndrome 33, OMIM #617767; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v3.0 PIBF1 Zornitza Stark gene: PIBF1 was added
gene: PIBF1 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: PIBF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIBF1 were set to 26167768; 30858804; 29695797
Phenotypes for gene: PIBF1 were set to Joubert syndrome 33; OMIM #617767
Review for gene: PIBF1 was set to GREEN
gene: PIBF1 was marked as current diagnostic
Added comment: 7 families altogether: 3 of these are Hutterite and share the same founder variant.
Sources: Expert list
Intellectual disability v3.0 PGM1 Zornitza Stark reviewed gene: PGM1: Rating: RED; Mode of pathogenicity: None; Publications: 24499211; Phenotypes: Congenital disorder of glycosylation, type It, MIM# 614921; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 PET100 Zornitza Stark reviewed gene: PET100: Rating: GREEN; Mode of pathogenicity: None; Publications: 24462369, 25293719, 31406627; Phenotypes: Mitochondrial complex IV deficiency, MIM# 220110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v3.0 PDP1 Zornitza Stark gene: PDP1 was added
gene: PDP1 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: PDP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDP1 were set to 19184109; 15855260; 31392110
Phenotypes for gene: PDP1 were set to Pyruvate dehydrogenase phosphatase deficiency, MIM#608782
Review for gene: PDP1 was set to GREEN
gene: PDP1 was marked as current diagnostic
Added comment: DD/ID is part of the phenotype of this metabolic condition.
Sources: Expert list
Intellectual disability v3.0 PDHB Zornitza Stark gene: PDHB was added
gene: PDHB was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: PDHB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDHB were set to 15138885; 26014431
Phenotypes for gene: PDHB were set to Pyruvate dehydrogenase E1-beta deficiency, MIM#614111
Review for gene: PDHB was set to GREEN
gene: PDHB was marked as current diagnostic
Added comment: DD/ID is a feature of this metabolic disorder.
Sources: Expert list
Intellectual disability v3.0 PDE6G Zornitza Stark reviewed gene: PDE6G: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa 57 613582; Mode of inheritance: None
Intellectual disability v3.0 PDE10A Zornitza Stark gene: PDE10A was added
gene: PDE10A was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: PDE10A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE10A were set to 27058446
Phenotypes for gene: PDE10A were set to Dyskinesia, limb and orofacial, infantile-onset, MIM#616921
Review for gene: PDE10A was set to GREEN
gene: PDE10A was marked as current diagnostic
Added comment: Two unrelated families and functional data (animal model). Note that allelic disorder, Striatal degeneration, autosomal dominant, MIM#616922, is caused by heterozygous variants and ID is not part of the phenotype.
Sources: Expert list
Intellectual disability v3.0 PAX9 Zornitza Stark reviewed gene: PAX9: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Tooth agenesis, selective, 3 604625; Mode of inheritance: None
Intellectual disability v3.0 PAX3 Zornitza Stark reviewed gene: PAX3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Craniofacial-deafness-hand syndrome, MIM#122880, Waardenburg syndrome, type 1, MIM#193500, Waardenburg syndrome, type 3, MIM#148820; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 PAPSS2 Zornitza Stark reviewed gene: PAPSS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Brachyolmia 4 with mild epiphyseal and metaphyseal changes, MIM# 612847; Mode of inheritance: None
Intellectual disability v3.0 PAM16 Zornitza Stark gene: PAM16 was added
gene: PAM16 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: PAM16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAM16 were set to 24786642; 27354339
Phenotypes for gene: PAM16 were set to Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type, MIM#613320
Review for gene: PAM16 was set to GREEN
gene: PAM16 was marked as current diagnostic
Added comment: DD/ID is part of the phenotype of this skeletal dysplasia.
Sources: Expert list
Intellectual disability v3.0 OXR1 Zornitza Stark reviewed gene: OXR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31785787; Phenotypes: Intellectual disability, seizures, cerebellar atrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v3.0 OTULIN Zornitza Stark reviewed gene: OTULIN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099; Mode of inheritance: None
Intellectual disability v3.0 OTOGL Zornitza Stark reviewed gene: OTOGL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 84B, MIM# 614944; Mode of inheritance: None
Intellectual disability v3.0 ORC6 Zornitza Stark edited their review of gene: ORC6: Added comment: Intellect is typically normal.; Changed publications: 26381604; Changed phenotypes: Meier Gorlin syndrome
Intellectual disability v3.0 LZTFL1 Zornitza Stark gene: LZTFL1 was added
gene: LZTFL1 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: LZTFL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LZTFL1 were set to 22510444; 23692385; 27312011
Phenotypes for gene: LZTFL1 were set to Bardet-Biedl syndrome 17, MIM#615994
Review for gene: LZTFL1 was set to GREEN
gene: LZTFL1 was marked as current diagnostic
Added comment: Two unrelated families and functional evidence.
Sources: Expert list
Intellectual disability v3.0 LYRM7 Zornitza Stark gene: LYRM7 was added
gene: LYRM7 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: LYRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LYRM7 were set to Mitochondrial complex III deficiency, nuclear type 8, MIM#615838
Review for gene: LYRM7 was set to GREEN
gene: LYRM7 was marked as current diagnostic
Added comment: Condition is characterised by progressive deterioration but some individuals described as developmentally delayed from birth.
Sources: Expert list
Intellectual disability v3.0 LTBP3 Zornitza Stark reviewed gene: LTBP3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dental anomalies and short stature 601216, Geleophysic dysplasia 3 617809; Mode of inheritance: None
Intellectual disability v3.0 LTBP2 Zornitza Stark reviewed gene: LTBP2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Weill-Marchesani syndrome 3, recessive, MIM# 614819, Glaucoma 3, primary congenital, MIM# 613086, Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma, MIM# 251750; Mode of inheritance: None
Intellectual disability v3.0 LSS Zornitza Stark reviewed gene: LSS: Rating: GREEN; Mode of pathogenicity: None; Publications: 30723320; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 LRRC6 Zornitza Stark reviewed gene: LRRC6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 19, MIM# 614935; Mode of inheritance: None
Intellectual disability v3.0 LRP4 Zornitza Stark reviewed gene: LRP4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cenani-Lenz syndactyly syndrome, MIM# 212780, Sclerosteosis 2, MIM# 614305; Mode of inheritance: None
Intellectual disability v3.0 LMX1B Zornitza Stark reviewed gene: LMX1B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 LMNA Zornitza Stark reviewed gene: LMNA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 LMAN2L Zornitza Stark gene: LMAN2L was added
gene: LMAN2L was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: LMAN2L was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: LMAN2L were set to 31020005; 26566883
Phenotypes for gene: LMAN2L were set to Intellectual disability; epilepsy
Review for gene: LMAN2L was set to AMBER
Added comment: 1 consanguineous family with 7 individuals with ID and epilepsy, with homozygous LMAN2L missense mutation. Segregated with disease in family, and unaffected family members were heterozygous variant carriers. No functional studies.

1 non-consanguineous family with 4 affected with heterozygous frameshift LMAN2L mutation. Segregates in family. Mutation eliminates LMAN2L's endoplasmic reticulum retention signal and mislocalizes the protein from that compartment to the plasma membrane.

Amber or Red.
Sources: Expert list
Intellectual disability v3.0 LIPT1 Zornitza Stark gene: LIPT1 was added
gene: LIPT1 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: LIPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIPT1 were set to 24341803; 24256811; 29681092
Phenotypes for gene: LIPT1 were set to Lipoyltransferase 1 deficiency, MIM#616299
Review for gene: LIPT1 was set to GREEN
gene: LIPT1 was marked as current diagnostic
Added comment: Cognitive development is affected in this metabolic condition.
Sources: Expert list
Intellectual disability v3.0 LIAS Zornitza Stark reviewed gene: LIAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 24334290, 22152680; Phenotypes: Hyperglycinemia, lactic acidosis, and seizures, MIM#614462; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v3.0 LHX4 Zornitza Stark reviewed gene: LHX4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 LHX3 Zornitza Stark reviewed gene: LHX3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined, 3, MIM# 221750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 LGI4 Zornitza Stark reviewed gene: LGI4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis multiplex congenita, neurogenic, with myelin defect, MIM#617468; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 LFNG Zornitza Stark reviewed gene: LFNG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 LEMD3 Zornitza Stark reviewed gene: LEMD3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 LDB3 Zornitza Stark reviewed gene: LDB3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 LAS1L Zornitza Stark reviewed gene: LAS1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 25644381, 25644381; Phenotypes: Wilson-Turner syndrome, MIM# 309585; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Intellectual disability v3.0 LAMB2 Zornitza Stark gene: LAMB2 was added
gene: LAMB2 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: LAMB2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LAMB2 were set to Pierson syndrome, MIM#609049
gene: LAMB2 was marked as current diagnostic
Added comment: Cognitive impairment described in survivors.
Sources: Expert list
Intellectual disability v3.0 KLHL40 Zornitza Stark reviewed gene: KLHL40: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Nemaline myopathy 8, autosomal recessive 615348; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 KLF7 Zornitza Stark gene: KLF7 was added
gene: KLF7 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: KLF7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLF7 were set to 29251763
Phenotypes for gene: KLF7 were set to Intellectual disability
Review for gene: KLF7 was set to GREEN
gene: KLF7 was marked as current diagnostic
Added comment: Four unrelated individuals with de novo missense variants; animal model data supportive.
Sources: Expert list
Intellectual disability v3.0 KLF1 Zornitza Stark reviewed gene: KLF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 KIT Zornitza Stark reviewed gene: KIT: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 KIRREL3 Zornitza Stark reviewed gene: KIRREL3: Rating: RED; Mode of pathogenicity: None; Publications: 19012874; Phenotypes: Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 KIF22 Zornitza Stark reviewed gene: KIF22: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondyloepimetaphyseal dysplasia with joint laxity, type 2 603546; Mode of inheritance: None
Intellectual disability v3.0 KDM6B Zornitza Stark reviewed gene: KDM6B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31124279; Phenotypes: Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v3.0 KDM3B Zornitza Stark reviewed gene: KDM3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 30929739; Phenotypes: Intellectual disability, short stature; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v3.0 KCTD1 Zornitza Stark reviewed gene: KCTD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 KCNQ1 Zornitza Stark reviewed gene: KCNQ1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 KCNN3 Zornitza Stark gene: KCNN3 was added
gene: KCNN3 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: KCNN3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNN3 were set to 31155282
Phenotypes for gene: KCNN3 were set to Zimmermann-Laband syndrome 3; OMIM# 618658
Review for gene: KCNN3 was set to GREEN
gene: KCNN3 was marked as current diagnostic
Added comment: Three unrelated individuals reported.
Sources: Expert list
Intellectual disability v3.0 KCNMA1 Zornitza Stark reviewed gene: KCNMA1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 27567911, 29545233, 26195193, 31427379; Phenotypes: Cerebellar atrophy, developmental delay, and seizures, MIM# 617643, Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, MIM#609446; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 KCNK4 Zornitza Stark reviewed gene: KCNK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 30290154; Phenotypes: Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome 618381; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v3.0 KCND3 Zornitza Stark reviewed gene: KCND3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 19, MIM#607346; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 KCNC3 Zornitza Stark reviewed gene: KCNC3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 13, MIM#605259; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 KBTBD13 Zornitza Stark reviewed gene: KBTBD13: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Nemaline myopathy 6, autosomal dominant, MIM# 609273; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 KAT8 Zornitza Stark reviewed gene: KAT8: Rating: GREEN; Mode of pathogenicity: None; Publications: 31794431; Phenotypes: Intellectual disability, seizures, autism, dysmorphic features; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 JAK3 Zornitza Stark reviewed gene: JAK3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 JAGN1 Zornitza Stark reviewed gene: JAGN1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neutropenia, severe congenital, 6, autosomal recessive 616022; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 JAG1 Zornitza Stark reviewed gene: JAG1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Alagille syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 IRF6 Zornitza Stark reviewed gene: IRF6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 IREB2 Zornitza Stark gene: IREB2 was added
gene: IREB2 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: IREB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IREB2 were set to 30915432; 31243445; 11175792
Phenotypes for gene: IREB2 were set to Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia, MIM#618451
Review for gene: IREB2 was set to GREEN
gene: IREB2 was marked as current diagnostic
Added comment: Two affected individuals from unrelated families with functional evidence including highly specific, concordant phenotype in mice.
Sources: Expert list
Intellectual disability v3.0 IQSEC3 Zornitza Stark gene: IQSEC3 was added
gene: IQSEC3 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: IQSEC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IQSEC3 were set to 31130284
Phenotypes for gene: IQSEC3 were set to Intellectual disability
Review for gene: IQSEC3 was set to AMBER
Added comment: Two unrelated families, no functional data.
Sources: Expert list
Intellectual disability v3.0 IQSEC1 Zornitza Stark reviewed gene: IQSEC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31607425; Phenotypes: Intellectual developmental disorder with short stature and behavioral abnormalities, MIM# 618687; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v3.0 SCN4A Zornitza Stark reviewed gene: SCN4A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperkalemic periodic paralysis, type 2, MIM# 170500, Hypokalemic periodic paralysis, type 2, MIM# 613345, Myasthenic syndrome, congenital, 16, MIM# 614198, Myotonia congenita, atypical, acetazolamide-responsive 608390, Paramyotonia congenita 168300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v3.0 INPPL1 Zornitza Stark reviewed gene: INPPL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Opsismodysplasia, MIM# 258480; Mode of inheritance: None
Intellectual disability v3.0 IMPAD1 Zornitza Stark reviewed gene: IMPAD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Chondrodysplasia with joint dislocations, GPAPP type, MIM# 614078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 IL11RA Zornitza Stark reviewed gene: IL11RA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Craniosynostosis and dental anomalies, MIM# 614188; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 IHH Zornitza Stark reviewed gene: IHH: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Acrocapitofemoral dysplasia, MIM# 607778, Brachydactyly, type A1, MIM# 112500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v3.0 IGF2 Zornitza Stark reviewed gene: IGF2: Rating: RED; Mode of pathogenicity: None; Publications: 31544945, 26154720; Phenotypes: Growth restriction, severe, with distinctive facies, MIM#616489; Mode of inheritance: None
Intellectual disability v3.0 IFT80 Zornitza Stark reviewed gene: IFT80: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 IFT27 Zornitza Stark gene: IFT27 was added
gene: IFT27 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: IFT27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT27 were set to 24488770; 30761183
Phenotypes for gene: IFT27 were set to Bardet-Biedl syndrome 19, MIM#615996
Review for gene: IFT27 was set to AMBER
Added comment: Two families with functional evidence.
Sources: Expert list
Intellectual disability v3.0 IFT122 Zornitza Stark reviewed gene: IFT122: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 IFITM5 Zornitza Stark reviewed gene: IFITM5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 HYLS1 Zornitza Stark reviewed gene: HYLS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hydrolethalus syndrome, MIM#236680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 HYDIN Zornitza Stark reviewed gene: HYDIN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 HYAL1 Zornitza Stark reviewed gene: HYAL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 HSPG2 Zornitza Stark reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Schwartz-Jampel syndrome, type 1, MIM#255800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 HSF4 Zornitza Stark reviewed gene: HSF4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 HSD3B7 Zornitza Stark reviewed gene: HSD3B7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 HR Zornitza Stark reviewed gene: HR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 HPSE2 Zornitza Stark reviewed gene: HPSE2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 HPS1 Zornitza Stark reviewed gene: HPS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 HPGD Zornitza Stark reviewed gene: HPGD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 HOXD13 Zornitza Stark reviewed gene: HOXD13: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 HOXC13 Zornitza Stark reviewed gene: HOXC13: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 HOXA13 Zornitza Stark reviewed gene: HOXA13: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 HNMT Zornitza Stark gene: HNMT was added
gene: HNMT was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: HNMT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HNMT were set to 26206890; 30744146
Phenotypes for gene: HNMT were set to Mental retardation, autosomal recessive 51, MIM#616739
Review for gene: HNMT was set to GREEN
Added comment: 7 individuals from two unrelated families, some functional evidence and other circumstantial evidence linking this gene to brain function. Borderline Amber/Green.
Sources: Expert list
Intellectual disability v3.0 HNF4A Zornitza Stark reviewed gene: HNF4A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 HMGCS2 Zornitza Stark reviewed gene: HMGCS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: HMG-CoA synthase-2 deficiency, MIM# 605911; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 HADHB Zornitza Stark gene: HADHB was added
gene: HADHB was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: HADHB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HADHB were set to Trifunctional protein deficiency, MIM#609015
Review for gene: HADHB was set to GREEN
gene: HADHB was marked as current diagnostic
Added comment: ID is part of the phenotype.
Sources: Expert list
Intellectual disability v3.0 HADH Zornitza Stark reviewed gene: HADH: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: 3-hydroxyacyl-CoA dehydrogenase deficiency, MIM#231530, Hyperinsulinemic hypoglycemia, familial, 4, MIM#609975; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 GUCY2C Zornitza Stark reviewed gene: GUCY2C: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 GRM6 Zornitza Stark reviewed gene: GRM6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 GRIA1 Zornitza Stark reviewed gene: GRIA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v3.0 GRHL3 Zornitza Stark reviewed gene: GRHL3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 GPSM2 Zornitza Stark reviewed gene: GPSM2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Chudley-McCullough syndrome, MIM#604213; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 GPR179 Zornitza Stark reviewed gene: GPR179: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 GPC4 Zornitza Stark gene: GPC4 was added
gene: GPC4 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: GPC4 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: GPC4 were set to 30982611
Phenotypes for gene: GPC4 were set to Keipert syndrome OMIM# 301026
Review for gene: GPC4 was set to GREEN
gene: GPC4 was marked as current diagnostic
Added comment: 10 individuals from 6 families reported, functional studies in mice. Mild to moderate ID part of the phenotype.
Sources: Expert list
Intellectual disability v3.0 GOT2 Zornitza Stark reviewed gene: GOT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31422819; Phenotypes: Epileptic encephalopathy, early infantile, 82, MIM# 618721; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v3.0 GNE Zornitza Stark gene: GNE was added
gene: GNE was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: GNE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GNE were set to Sialuria, MIM#269921
Review for gene: GNE was set to GREEN
gene: GNE was marked as current diagnostic
Added comment: Metabolic disorder with varying degrees of ID being a feature.
Bi-allelic variants cause Nonaka myopathy, MIM#605820
Sources: Expert list
Intellectual disability v3.0 GNAI3 Zornitza Stark reviewed gene: GNAI3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 HDAC4 Zornitza Stark reviewed gene: HDAC4: Rating: AMBER; Mode of pathogenicity: None; Publications: 24715439, 20691407, 31209962; Phenotypes: Brachydactyly mental retardation syndrome, Brachydactyly without intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 GLS Zornitza Stark gene: GLS was added
gene: GLS was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: GLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLS were set to 30970188
Phenotypes for gene: GLS were set to Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412
Review for gene: GLS was set to GREEN
Added comment: Three unrelated individuals described with compound het variants, however, note one of these is a triplet expansion in the 5' UTR.
Sources: Expert list
Genetic epilepsy syndromes v2.0 TRAPPC4 Zornitza Stark reviewed gene: TRAPPC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31794024; Phenotypes: intellectual disability, epilepsy, spasticity, microcephaly; Mode of inheritance: None
Genetic epilepsy syndromes v2.0 TMX2 Zornitza Stark reviewed gene: TMX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31735293, 31586943; Phenotypes: Microcephaly, ID, brain malformations, seizures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v2.0 SNX27 Zornitza Stark reviewed gene: SNX27: Rating: GREEN; Mode of pathogenicity: None; Publications: 25894286, 31721175, 21300787, 23524343; Phenotypes: intellectual disability, seizures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v2.0 PUM1 Zornitza Stark reviewed gene: PUM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29474920, 25768905, 30903679, 31859446; Phenotypes: intellectual disability, epilepsy, Spinocerebellar ataxia 47, MIM# 617931; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic epilepsy syndromes v2.0 PMPCB Zornitza Stark reviewed gene: PMPCB: Rating: GREEN; Mode of pathogenicity: None; Publications: 29576218; Phenotypes: Multiple mitochondrial dysfunctions syndrome 6, MIM# 617954; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v2.0 OXR1 Zornitza Stark reviewed gene: OXR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31785787, 22028674; Phenotypes: Cerebellar hypoplasia/atrophy, epilepsy, and global developmental delay, MIM# 213000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v2.0 NSF Zornitza Stark reviewed gene: NSF: Rating: AMBER; Mode of pathogenicity: None; Publications: 31675180; Phenotypes: Seizures, EEG with burst suppression, Global developmental delay, Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic epilepsy syndromes v2.0 KAT8 Zornitza Stark reviewed gene: KAT8: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31794431; Phenotypes: Intellectual disability, seizures, autism, dysmorphic features; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v3.0 GLMN Zornitza Stark reviewed gene: GLMN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 GLE1 Zornitza Stark reviewed gene: GLE1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 GJB1 Zornitza Stark reviewed gene: GJB1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth neuropathy, X-linked dominant, 1, MIM#302800; Mode of inheritance: None
Intellectual disability v3.0 GJA8 Zornitza Stark reviewed gene: GJA8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 GJA3 Zornitza Stark reviewed gene: GJA3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 GJA1 Zornitza Stark reviewed gene: GJA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Atrioventricular septal defect 3, MIM#600309, Craniometaphyseal dysplasia, autosomal recessive, MIM#218400, Erythrokeratodermia variabilis et progressiva 3, MIM#617525, Hypoplastic left heart syndrome 1, MIM#241550, Oculodentodigital dysplasia, MIM#164200, Oculodentodigital dysplasia, autosomal recessive, MIM#257850, Palmoplantar keratoderma with congenital alopecia, MIM#104100, Syndactyly, type III, MIM# 186100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v3.0 GHR Zornitza Stark reviewed gene: GHR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Growth hormone insensitivity, partial, MIM#604271, Laron dwarfism, MIM#262500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult solid tumours cancer susceptibility v2.1 Ellen McDonagh Panel version has been signed off
Sarcoma susceptibility v1.1 Ellen McDonagh Panel version has been signed off
Haematological malignancies cancer susceptibility v2.1 Ellen McDonagh Panel version has been signed off
Tumour predisposition - childhood onset v2.1 Ellen McDonagh Panel version has been signed off
Intellectual disability v3.0 GDF6 Zornitza Stark reviewed gene: GDF6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 GDF5 Zornitza Stark reviewed gene: GDF5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 GBA2 Zornitza Stark reviewed gene: GBA2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 46, autosomal recessive, MIM#614409; Mode of inheritance: None
Intellectual disability v3.0 GATA6 Zornitza Stark reviewed gene: GATA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 22158542; Phenotypes: Pancreatic agenesis and congenital heart defects, MIM#600001; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 GATA4 Zornitza Stark reviewed gene: GATA4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 GATA2 Zornitza Stark reviewed gene: GATA2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 GAS8 Zornitza Stark reviewed gene: GAS8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 GALK1 Zornitza Stark reviewed gene: GALK1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 GAA Zornitza Stark reviewed gene: GAA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Genetic epilepsy syndromes v2.0 SERPINI1 Zornitza Stark gene: SERPINI1 was added
gene: SERPINI1 was added to Genetic epilepsy syndromes. Sources: Expert list
Mode of inheritance for gene: SERPINI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SERPINI1 were set to 28631894; 25401298; 12103288
Phenotypes for gene: SERPINI1 were set to Encephalopathy, familial, with neuroserpin inclusion bodies MIM#604218
Review for gene: SERPINI1 was set to GREEN
gene: SERPINI1 was marked as current diagnostic
Added comment: >3 unrelated families with progressive myoclonus epilepsy
Sources: Expert list
Genetic epilepsy syndromes v2.0 CERS1 Zornitza Stark reviewed gene: CERS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30800706, 21625621; Phenotypes: Epilepsy, progressive myoclonic, 8 MIM#616230; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v3.0 FZD6 Zornitza Stark reviewed gene: FZD6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 FYCO1 Zornitza Stark reviewed gene: FYCO1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 FXN Zornitza Stark reviewed gene: FXN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 FTL Zornitza Stark reviewed gene: FTL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with brain iron accumulation 3, MIM#606159, Hyperferritinemia-cataract syndrome, MIM#600886, L-ferritin deficiency, dominant and recessive, MIM#615604; Mode of inheritance: None
Intellectual disability v3.0 FRY Zornitza Stark reviewed gene: FRY: Rating: AMBER; Mode of pathogenicity: None; Publications: 31487712, 27457812, 21937992; Phenotypes: Intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 FOXN1 Zornitza Stark reviewed gene: FOXN1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 FOXF1 Zornitza Stark reviewed gene: FOXF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 FOXE3 Zornitza Stark reviewed gene: FOXE3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 FOXE1 Zornitza Stark reviewed gene: FOXE1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 FOXC2 Zornitza Stark reviewed gene: FOXC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 FOXC1 Zornitza Stark reviewed gene: FOXC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 FLVCR1 Zornitza Stark reviewed gene: FLVCR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ataxia, posterior column, with retinitis pigmentosa, MIM#609033; Mode of inheritance: None
Intellectual disability v3.0 FLT4 Zornitza Stark reviewed gene: FLT4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 FLNB Zornitza Stark reviewed gene: FLNB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 FKBP14 Zornitza Stark reviewed gene: FKBP14: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 FHL1 Zornitza Stark reviewed gene: FHL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 FGFR1 Zornitza Stark edited their review of gene: FGFR1: Added comment: Gene causes several phenotypes but this specific phenotype caused by germline variants is associated with significant ID.; Changed publications: 23812909; Changed phenotypes: Hartsfield syndrome, MIM# 615465
Intellectual disability v3.0 TKFC Zornitza Stark gene: TKFC was added
gene: TKFC was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: TKFC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TKFC were set to 32004446
Phenotypes for gene: TKFC were set to Developmental delay; cataracts; liver dysfunction
Review for gene: TKFC was set to AMBER
Added comment: Two unrelated individuals reported.
Sources: Expert list
Genetic epilepsy syndromes v2.0 RALGAPA1 Zornitza Stark gene: RALGAPA1 was added
gene: RALGAPA1 was added to Genetic epilepsy syndromes. Sources: Expert list
Mode of inheritance for gene: RALGAPA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RALGAPA1 were set to 32004447
Phenotypes for gene: RALGAPA1 were set to Intellectual disability; hypotonia; infantile spasms.
Review for gene: RALGAPA1 was set to GREEN
gene: RALGAPA1 was marked as current diagnostic
Added comment: Four unrelated individuals reported.
Sources: Expert list
Intellectual disability v3.0 RALGAPA1 Zornitza Stark gene: RALGAPA1 was added
gene: RALGAPA1 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: RALGAPA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RALGAPA1 were set to 32004447
Phenotypes for gene: RALGAPA1 were set to Intellectual disability; hypotonia; infantile spasms.
Review for gene: RALGAPA1 was set to GREEN
gene: RALGAPA1 was marked as current diagnostic
Added comment: Four unrelated individuals reported.
Sources: Expert list
Intellectual disability v3.0 FGF3 Zornitza Stark reviewed gene: FGF3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, congenital with inner ear agenesis, microtia, and microdontia, MIM#610706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 FGF14 Zornitza Stark reviewed gene: FGF14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 27, MIM# 609307; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v3.0 FGF10 Zornitza Stark reviewed gene: FGF10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 FDFT1 Zornitza Stark reviewed gene: FDFT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29909962; Phenotypes: Squalene synthase deficiency, MIM#618156; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v3.0 FBXW4 Zornitza Stark reviewed gene: FBXW4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 FBP1 Zornitza Stark reviewed gene: FBP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 FBN1 Zornitza Stark reviewed gene: FBN1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 FARSB Zornitza Stark gene: FARSB was added
gene: FARSB was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: FARSB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FARSB were set to 29573043; 1916114; 29979980; 30014610
Phenotypes for gene: FARSB were set to Rajab syndrome, MIM#613658; interstitial lung disease; brain calcifications; microcephaly; intellectual disability
Review for gene: FARSB was set to GREEN
gene: FARSB was marked as current diagnostic
Added comment: 7 unrelated families reported.
Sources: Expert list
Intellectual disability v3.0 FAR1 Zornitza Stark reviewed gene: FAR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25439727; Phenotypes: Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 FAM20A Zornitza Stark reviewed gene: FAM20A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 FAM161A Zornitza Stark reviewed gene: FAM161A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 FAAH2 Zornitza Stark reviewed gene: FAAH2: Rating: RED; Mode of pathogenicity: None; Publications: 25885783; Phenotypes: Neuropsychiatric disorder; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v3.0 FA2H Zornitza Stark reviewed gene: FA2H: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 EYA1 Zornitza Stark reviewed gene: EYA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 EXT2 Zornitza Stark reviewed gene: EXT2: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: Seizures, scoliosis, and macrocephaly syndrome, MIM#616682; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v3.0 EXOSC8 Zornitza Stark gene: EXOSC8 was added
gene: EXOSC8 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: EXOSC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC8 were set to 24989451; 29656927
Phenotypes for gene: EXOSC8 were set to Pontocerebellar hypoplasia, type 1C, MIM#616081
Review for gene: EXOSC8 was set to GREEN
gene: EXOSC8 was marked as current diagnostic
Added comment: Complex neurological phenotype includes ID.
Sources: Expert list
Intellectual disability v3.0 EVC2 Zornitza Stark reviewed gene: EVC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ellis-van Creveld syndrome, MIM#225500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 EVC Zornitza Stark reviewed gene: EVC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ellis-van Creveld syndrome, MIM#225500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 ERMARD Zornitza Stark reviewed gene: ERMARD: Rating: RED; Mode of pathogenicity: None; Publications: 24056535, 27087860; Phenotypes: Periventricular nodular heterotopia 6, MIM#615544; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 ERF Zornitza Stark reviewed gene: ERF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Chitayat syndrome, MIM#617180, Craniosynostosis 4, MIM#600775; Mode of inheritance: None
Intellectual disability v3.0 ERCC4 Zornitza Stark reviewed gene: ERCC4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Xeroderma pigmentosum, group F, MIM#278760, XFE progeroid syndrome, MIM# 610965; Mode of inheritance: None
Intellectual disability v3.0 EOGT Zornitza Stark reviewed gene: EOGT: Rating: RED; Mode of pathogenicity: None; Publications: 31368252; Phenotypes: Adams-Oliver syndrome 4, MIM#615297; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 ENPP1 Zornitza Stark reviewed gene: ENPP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 ELN Zornitza Stark reviewed gene: ELN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Supravalvar aortic stenosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 EIF2A Zornitza Stark gene: EIF2A was added
gene: EIF2A was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: EIF2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF2A were set to 31130284
Phenotypes for gene: EIF2A were set to Intellectual disability; epilepsy
Review for gene: EIF2A was set to AMBER
Added comment: Two unrelated families reported, no functional data.
Sources: Expert list
Intellectual disability v3.0 ATAD3A Zornitza Stark reviewed gene: ATAD3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32004445; Phenotypes: Harel-Yoon syndrome 617183; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v3.0 EDNRA Zornitza Stark reviewed gene: EDNRA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mandibulofacial dysostosis with alopecia, MIM# 616367; Mode of inheritance: None
Intellectual disability v3.0 EDA Zornitza Stark reviewed gene: EDA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 ECEL1 Zornitza Stark reviewed gene: ECEL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 EARS2 Zornitza Stark gene: EARS2 was added
gene: EARS2 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: EARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EARS2 were set to 22492562
Phenotypes for gene: EARS2 were set to Combined oxidative phosphorylation deficiency 12, MIM#614924
Review for gene: EARS2 was set to GREEN
gene: EARS2 was marked as current diagnostic
Added comment: ID is part of the phenotype, particularly in those severely affected.
Sources: Expert list
Intellectual disability v3.0 DYNC2H1 Zornitza Stark reviewed gene: DYNC2H1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Short-rib thoracic dysplasia 3 with or without polydactyly, MIM#613091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 DVL1 Zornitza Stark reviewed gene: DVL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Robinow syndrome, autosomal dominant 2 616331; Mode of inheritance: None
Intellectual disability v3.0 DSTYK Zornitza Stark reviewed gene: DSTYK: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 DSPP Zornitza Stark reviewed gene: DSPP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 DPM3 Zornitza Stark reviewed gene: DPM3: Rating: RED; Mode of pathogenicity: None; Publications: 19576565, 28803818, 30931530, 31469168; Phenotypes: Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15 612937; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 DNM1L Zornitza Stark gene: DNM1L was added
gene: DNM1L was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: DNM1L was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: DNM1L were set to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, MIM#614388
Mode of pathogenicity for gene: DNM1L was set to Other
Review for gene: DNM1L was set to GREEN
gene: DNM1L was marked as current diagnostic
Added comment: Dominant and recessive disease described depending on domain affected; dominant negative effect of heterozygous missense variants. LoF/LoF or LoF/missense for AR variants.
Sources: Expert list
Intellectual disability v3.0 DNAAF4 Zornitza Stark reviewed gene: DNAAF4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 DNAAF3 Zornitza Stark reviewed gene: DNAAF3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 DMP1 Zornitza Stark reviewed gene: DMP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 DLL4 Zornitza Stark reviewed gene: DLL4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 DLL3 Zornitza Stark reviewed gene: DLL3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 DLL1 Zornitza Stark reviewed gene: DLL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31353024; Phenotypes: Intellectual disability, autism, seizures, variable brain abnormalities, scoliosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v3.0 DENND5A Zornitza Stark reviewed gene: DENND5A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27431290, 27866705; Phenotypes: Epileptic encephalopathy, early infantile, 49 617281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 DDOST Zornitza Stark changed review comment from: Single family reported with supportive functional data, Amber at best.; to: Single family reported with supportive functional data, gene is RED on CDG panel.
Intellectual disability v3.0 DDOST Zornitza Stark reviewed gene: DDOST: Rating: RED; Mode of pathogenicity: None; Publications: 22305527; Phenotypes: Congenital disorder of glycosylation, type Ir, MIM# 614507; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 DDB2 Zornitza Stark reviewed gene: DDB2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 DCC Zornitza Stark reviewed gene: DCC: Rating: RED; Mode of pathogenicity: None; Publications: 31697046; Phenotypes: Agenesis of the corpus callosum; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 CYP7B1 Zornitza Stark reviewed gene: CYP7B1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 5A, autosomal recessive, MIM# 270800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 CYP2U1 Zornitza Stark reviewed gene: CYP2U1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 56, autosomal recessive, MIM#615030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 CYP1B1 Zornitza Stark reviewed gene: CYP1B1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 CTU2 Zornitza Stark gene: CTU2 was added
gene: CTU2 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTU2 were set to 27480277; 26633546
Phenotypes for gene: CTU2 were set to Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, MIM#618142
Review for gene: CTU2 was set to GREEN
Added comment: Multiple Saudi families reported with same homozygous variant; founder effect. Severe disorder of infancy.
Sources: Expert list
Intellectual disability v3.0 CTSK Zornitza Stark reviewed gene: CTSK: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 CTSF Zornitza Stark reviewed gene: CTSF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 13, Kufs type, MIM#615362; Mode of inheritance: None
Intellectual disability v3.0 CTNS Zornitza Stark reviewed gene: CTNS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 CRYGD Zornitza Stark Deleted their comment
Intellectual disability v3.0 CRYGD Zornitza Stark commented on gene: CRYGD: ID is not part of the phenotype.
Intellectual disability v3.0 CRYGD Zornitza Stark reviewed gene: CRYGD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 CRYBB3 Zornitza Stark reviewed gene: CRYBB3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 CRYBB2 Zornitza Stark reviewed gene: CRYBB2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 CRYBB1 Zornitza Stark reviewed gene: CRYBB1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 CRYBA1 Zornitza Stark reviewed gene: CRYBA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 CRYAA Zornitza Stark reviewed gene: CRYAA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 CRX Zornitza Stark reviewed gene: CRX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 CRB1 Zornitza Stark commented on gene: CRB1
Intellectual disability v3.0 COMP Zornitza Stark reviewed gene: COMP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 COL9A3 Zornitza Stark reviewed gene: COL9A3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 COL9A2 Zornitza Stark reviewed gene: COL9A2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 COL9A1 Zornitza Stark reviewed gene: COL9A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 COL6A1 Zornitza Stark reviewed gene: COL6A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 COL4A4 Zornitza Stark reviewed gene: COL4A4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 COL4A3 Zornitza Stark reviewed gene: COL4A3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 COL2A1 Zornitza Stark reviewed gene: COL2A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 COL1A1 Zornitza Stark reviewed gene: COL1A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 COL18A1 Zornitza Stark reviewed gene: COL18A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Knobloch syndrome, type 1, MIM#267750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 COL11A1 Zornitza Stark reviewed gene: COL11A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Stickler syndrome, type II, MIM# 604841; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 COL10A1 Zornitza Stark reviewed gene: COL10A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Metaphyseal chondrodysplasia, Schmid type, MIM# 156500; Mode of inheritance: None
Intellectual disability v3.0 CNTNAP1 Zornitza Stark gene: CNTNAP1 was added
gene: CNTNAP1 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: CNTNAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNTNAP1 were set to 28374019; 29511323; 27668699
Phenotypes for gene: CNTNAP1 were set to Hypomyelinating neuropathy, congenital, 3, MIM#618186; Lethal congenital contracture syndrome 7, MIM# 616286
Review for gene: CNTNAP1 was set to GREEN
gene: CNTNAP1 was marked as current diagnostic
Added comment: Multiple affected individuals reported; ID is part of the phenotype.
Sources: Expert list
Intellectual disability v3.0 CLDN19 Zornitza Stark reviewed gene: CLDN19: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypomagnesemia 5, renal, with ocular involvement, MIM# 248190; Mode of inheritance: None
Intellectual disability v3.0 CLCN7 Zornitza Stark reviewed gene: CLCN7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteopetrosis; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v3.0 CIB2 Zornitza Stark reviewed gene: CIB2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 48, MIM# 609439, Usher syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 CHUK Zornitza Stark reviewed gene: CHUK: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cocoon syndrome, MIM# 613630; Mode of inheritance: None
Intellectual disability v3.0 CHSY1 Zornitza Stark reviewed gene: CHSY1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Temtamy preaxial brachydactyly syndrome 605282; Mode of inheritance: None
Intellectual disability v3.0 CHST3 Zornitza Stark reviewed gene: CHST3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondyloepiphyseal dysplasia with congenital joint dislocations, MIM# 143095; Mode of inheritance: None
Intellectual disability v3.0 CHRNG Zornitza Stark reviewed gene: CHRNG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Escobar syndrome, MIM# 265000, Multiple pterygium syndrome, lethal type, MIM# 253290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 CHRDL1 Zornitza Stark reviewed gene: CHRDL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalocornea 1, X-linked, MIM# 309300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v3.0 CHM Zornitza Stark reviewed gene: CHM: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Choroideremia, MIM# 303100; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v3.0 CHD1 Zornitza Stark gene: CHD1 was added
gene: CHD1 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: CHD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD1 were set to 28866611
Phenotypes for gene: CHD1 were set to Pilarowski-Bjornsson syndrome, MIM#617682
Mode of pathogenicity for gene: CHD1 was set to Other
Review for gene: CHD1 was set to GREEN
gene: CHD1 was marked as current diagnostic
Added comment: Six unrelated individuals with heterozygous variants reported. Possible dominant negative mechanism: reported variants are missense, and an individual with a deletion did not have a neurological phenotype.
Sources: Expert list
Intellectual disability v3.0 CEP104 Zornitza Stark reviewed gene: CEP104: Rating: GREEN; Mode of pathogenicity: None; Publications: 26477546; Phenotypes: Joubert syndrome 25, MIM# 616781; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 CDH3 Zornitza Stark reviewed gene: CDH3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ectodermal dysplasia, ectrodactyly, and macular dystrophy 225280, Hypotrichosis, congenital, with juvenile macular dystrophy 601553; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 CDH23 Zornitza Stark reviewed gene: CDH23: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, Usher syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 CDH2 Zornitza Stark reviewed gene: CDH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31585109; Phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v3.0 CCT5 Zornitza Stark reviewed gene: CCT5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuropathy, hereditary sensory, with spastic paraplegia, MIM# 256840; Mode of inheritance: None
Intellectual disability v3.0 CCNO Zornitza Stark reviewed gene: CCNO: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 29, MIM# 615872; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 CCDC88A Zornitza Stark edited their review of gene: CCDC88A: Added comment: Two unrelated families now plus mouse model.; Changed publications: 26917597, 30392057; Set current diagnostic: yes
Intellectual disability v3.0 CCDC65 Zornitza Stark reviewed gene: CCDC65: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 27, MIM# 615504; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 CCDC40 Zornitza Stark reviewed gene: CCDC40: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 15, MIM# 613808; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 CCDC114 Zornitza Stark reviewed gene: CCDC114: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 20, MIM# 615067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 CCDC103 Zornitza Stark reviewed gene: CCDC103: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 17, MIM# 614679; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 CARS2 Zornitza Stark reviewed gene: CARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30139652; Phenotypes: Combined oxidative phosphorylation deficiency 27, MIM#616672; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 EBP Zornitza Stark reviewed gene: EBP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Chondrodysplasia punctata, X-linked dominant MIM#302960, Conradi-Hunermann syndrome, MEND syndrome, MIM#300960; 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
Intellectual disability v3.0 SCN4A Andrea Haworth commented on gene: SCN4A
Proteinuric renal disease v2.0 DGKE Eleanor Williams edited their review of gene: DGKE: Added comment: Associated with Nephrotic syndrome, type 7 #615008 (AR) in OMIM.

PMID: 23542698 - Lemaire et al 2013 - 9 families identified with homozgyous or compound heterozygous variants in DGKE. All were cases of pediatric-onset aHUS. One variant was found in on both alleles in 3 families (p.Trp322*) and heterozygously in 2 others and the families are thought to have a remote shared ancestry. Three patients from different families developed nephrotic syndrome 3-5 years after disease onset.

PMID: 23274426 - Ozaltin et al 2013 - 3 consanguineous families - 3 different homozygous variants in 9 individuals. Table 1 gives proteinuria levels at onset.; Changed publications: PMID: 23274426, PMID: 23542698
Proteinuric renal disease v2.0 KANK2 Eleanor Williams commented on gene: KANK2: Associated with Nephrotic syndrome, type 16 #617783 (AR) in OMIM.

PMID: 25961457 - Gee et al 2015 - performed homozygosity mapping and whole-exome sequencing in individuals with NS identified recessive mutations in KANK2 in two families with NS. In family A982 of Arab origin, 2 siblings had early-onset SSNS and were found to have a homozygous missense mutation c.541A>G;p.S181G in KANK2. It segregated with the disorder in the family. In an unrelated individual with SSNS (A1751-21), they found a homozygous missense mutation (c.2051C>T;p.S684F) in KANK2. 27 known genes previously linked to SRNS were screened in this individual, but no explanatory mutations were detected. Knockdown of kank2 in zebrafish results in proteinuria which could be partially rescued by wild type human KANK2 mRNA but not either of the mutant mRNAs.

My reading of Table 1 is that there were two cases - one family with two siblings (individuals A982-21 and A982-22) with the same variant, and a second unrelated individual (A1751-21) with a different missense variant.
Proteinuric renal disease v2.0 CD2AP Eleanor Williams changed review comment from: Associated with Glomerulosclerosis, focal segmental, 3 #607832 in OMIM (no inheritance given)

Mouse knockout model supports renal involvement. 2 cases with heterozgous variants and FSGS but only CD2AP looked at. Two familial cases of homozygous variants (in one only CD2AP screened) and FSGS.

PMID: 10514378 - Shih et al 1999 - In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells.

PMID: 12764198 - Kim et al 2003 - CD2AP+/- showed glomerular abnormalities at 9 months of age but not proteinuria. Screened 30 African-Americans with idiopathic FSGS and 15 African-Americans with HIV-associated FSGS for changes in CD2AP. One variant, predicted to affect the splice acceptor of exon 7 in one allele, was found in 2 patients with primary FSGS and expression of the protein was lower in these patients.

PMID:17713465 - Löwik et al 2007 - report a homozygous variant in a proband with primary Focal segmental glomerulosclerosis, from a consanguineous family of Mediterranean ancestry. A homozygous c1834 C>T (R612Stop) variant was found. Both parents were proven to be heterozygous for this mutation. An immunoblot shows no CD2AP expression in the patient carrying the R612Stop mutation homozygously

PMID: 30612599 - Takano et al 2019 - Using WES, they identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. (Abstract only accessed).; to: Associated with Glomerulosclerosis, focal segmental, 3 #607832 in OMIM (no inheritance given)

Mouse knockout model supports renal involvement. 2 cases with heterozgous variants and FSGS but only CD2AP looked at. Two familial cases of homozygous variants (in one only CD2AP screened) and FSGS.

PMID: 10514378 - Shih et al 1999 - In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells.

PMID: 12764198 - Kim et al 2003 - CD2AP+/- showed glomerular abnormalities at 9 months of age but not proteinuria. Screened 30 African-Americans with idiopathic FSGS and 15 African-Americans with HIV-associated FSGS for changes in CD2AP. One variant, predicted to affect the splice acceptor of exon 7 in one allele, was found in 2 patients with primary FSGS and expression of the protein was lower in these patients.

PMID:17713465 - Löwik et al 2007 - report a homozygous variant in a proband with primary Focal segmental glomerulosclerosis, from a consanguineous family of Mediterranean ancestry. A homozygous c1834 C>T (R612Stop) variant was found. Both parents were proven to be heterozygous for this mutation. An immunoblot shows no CD2AP expression in the patient carrying the R612Stop mutation homozygously

PMID: 30612599 - Takano et al 2019 - Using WES, they identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. (Abstract only accessed).
Proteinuric renal disease v2.0 PTPRO Eleanor Williams edited their review of gene: PTPRO: Added comment: Associated with Nephrotic syndrome, type 6 #614196 (AR) in OMIM.

2 families:

PMID: 21722858 - Ozaltin et al 2011 - 2 Turkish families reported, total of 5 individuals. A region of homozygosity was identified in a consangiuneous family with Idiopathic nephrotic syndrome. By direct sequencing of PTPRO a homozygous c.2627+1G>T donor splice-site mutation was identified. In a second family, a c.2745+1G>A donor splice-site mutation in PTPRO was identified. Electron microscopy identified ultrastructural alterations in podocytes in both families.

PMID: 30065916 - Trautmann et al 2018 - PodoNet Registry paper - describes the same families as Ozaltin et al.; Changed publications: PMID: 21722858, PMID: 30065916
Proteinuric renal disease v2.0 CD2AP Eleanor Williams edited their review of gene: CD2AP: Changed publications: 30612599, 17713465, 10514378, 12764198
Proteinuric renal disease v2.0 CD2AP Eleanor Williams changed review comment from: Associated with Glomerulosclerosis, focal segmental, 3 #607832 in OMIM (no inheritance given)

Mouse knockout model supports renal involvement. 2 cases with heterozgous variants and FSGS but only CD2AP looked at. Two familial cases of homozygous variants (in one only CD2AP screened) and FSGS.

PMID: 10514378 - Shih et al 1999 - In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells.

PMID: Kim et al 2003 - CD2AP+/- showed glomerular abnormalities at 9 months of age but not proteinuria. Screened 30 African-Americans with idiopathic FSGS and 15 African-Americans with HIV-associated FSGS for changes in CD2AP. One variant, predicted to affect the splice acceptor of exon 7 in one allele, was found in 2 patients with primary FSGS and expression of the protein was lower in these patients.

PMID:17713465 - Löwik et al 2007 - report a homozygous variant in a proband with primary Focal segmental glomerulosclerosis, from a consanguineous family of Mediterranean ancestry. A homozygous c1834 C>T (R612Stop) variant was found. Both parents were proven to be heterozygous for this mutation. An immunoblot shows no CD2AP expression in the patient carrying the R612Stop mutation homozygously

PMID: 30612599 - Takano et al 2019 - Using WES, they identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. (Abstract only accessed).; to: Associated with Glomerulosclerosis, focal segmental, 3 #607832 in OMIM (no inheritance given)

Mouse knockout model supports renal involvement. 2 cases with heterozgous variants and FSGS but only CD2AP looked at. Two familial cases of homozygous variants (in one only CD2AP screened) and FSGS.

PMID: 10514378 - Shih et al 1999 - In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells.

PMID: 12764198 - Kim et al 2003 - CD2AP+/- showed glomerular abnormalities at 9 months of age but not proteinuria. Screened 30 African-Americans with idiopathic FSGS and 15 African-Americans with HIV-associated FSGS for changes in CD2AP. One variant, predicted to affect the splice acceptor of exon 7 in one allele, was found in 2 patients with primary FSGS and expression of the protein was lower in these patients.

PMID:17713465 - Löwik et al 2007 - report a homozygous variant in a proband with primary Focal segmental glomerulosclerosis, from a consanguineous family of Mediterranean ancestry. A homozygous c1834 C>T (R612Stop) variant was found. Both parents were proven to be heterozygous for this mutation. An immunoblot shows no CD2AP expression in the patient carrying the R612Stop mutation homozygously

PMID: 30612599 - Takano et al 2019 - Using WES, they identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. (Abstract only accessed).
Proteinuric renal disease v2.0 CD2AP Eleanor Williams changed review comment from: Associated with Glomerulosclerosis, focal segmental, 3 #607832 in OMIM (no inheritance given)

Mouse knockout model supports renal effect. 2 cases with heterozgous variants and FSGS but only CD2AP looked at. Two familial cases of homozygous variants (in one only CD2AP screened) and FSGS.

PMID: 10514378 - Shih et al 1999 - In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells.

PMID: Kim et al 2003 - CD2AP+/- showed glomerular abnormalities at 9 months of age but not proteinuria. Screened 30 African-Americans with idiopathic FSGS and 15 African-Americans with HIVE-associated FSGS for changes in CD2AP. One variant, predicted to affect the splice acceptor of exon 7 in one allele, was found in 2 patients with primary FSGS and expression of the protein was lower in these patients.

PMID:17713465 - Löwik et al 2007 - report a homozygous variant in a proband with primary Focal segmental glomerulosclerosis, from a consanguineous family of Mediterranean ancestry. A homozygous c1834 C>T (R612Stop) variant was found. Both parents were proven to be heterozygous for this mutation. An immunoblot shows no CD2AP expression in the patient carrying the R612Stop mutation homozygously

PMID: 30612599 - Takano et al 2019 - Using WES, they identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. (Abstract only accessed).; to: Associated with Glomerulosclerosis, focal segmental, 3 #607832 in OMIM (no inheritance given)

Mouse knockout model supports renal involvement. 2 cases with heterozgous variants and FSGS but only CD2AP looked at. Two familial cases of homozygous variants (in one only CD2AP screened) and FSGS.

PMID: 10514378 - Shih et al 1999 - In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells.

PMID: Kim et al 2003 - CD2AP+/- showed glomerular abnormalities at 9 months of age but not proteinuria. Screened 30 African-Americans with idiopathic FSGS and 15 African-Americans with HIV-associated FSGS for changes in CD2AP. One variant, predicted to affect the splice acceptor of exon 7 in one allele, was found in 2 patients with primary FSGS and expression of the protein was lower in these patients.

PMID:17713465 - Löwik et al 2007 - report a homozygous variant in a proband with primary Focal segmental glomerulosclerosis, from a consanguineous family of Mediterranean ancestry. A homozygous c1834 C>T (R612Stop) variant was found. Both parents were proven to be heterozygous for this mutation. An immunoblot shows no CD2AP expression in the patient carrying the R612Stop mutation homozygously

PMID: 30612599 - Takano et al 2019 - Using WES, they identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. (Abstract only accessed).
Proteinuric renal disease v2.0 CD2AP Eleanor Williams edited their review of gene: CD2AP: Added comment: Associated with Glomerulosclerosis, focal segmental, 3 #607832 in OMIM (no inheritance given)

Mouse knockout model supports renal effect. 2 cases with heterozgous variants and FSGS but only CD2AP looked at. Two familial cases of homozygous variants (in one only CD2AP screened) and FSGS.

PMID: 10514378 - Shih et al 1999 - In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells.

PMID: Kim et al 2003 - CD2AP+/- showed glomerular abnormalities at 9 months of age but not proteinuria. Screened 30 African-Americans with idiopathic FSGS and 15 African-Americans with HIVE-associated FSGS for changes in CD2AP. One variant, predicted to affect the splice acceptor of exon 7 in one allele, was found in 2 patients with primary FSGS and expression of the protein was lower in these patients.

PMID:17713465 - Löwik et al 2007 - report a homozygous variant in a proband with primary Focal segmental glomerulosclerosis, from a consanguineous family of Mediterranean ancestry. A homozygous c1834 C>T (R612Stop) variant was found. Both parents were proven to be heterozygous for this mutation. An immunoblot shows no CD2AP expression in the patient carrying the R612Stop mutation homozygously

PMID: 30612599 - Takano et al 2019 - Using WES, they identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. (Abstract only accessed).; Changed publications: PMID: 30612599, PMID: 17713465
Proteinuric renal disease v2.0 TPRKB Eleanor Williams commented on gene: TPRKB: TPRKB is associated with Galloway-Mowat syndrome 5 #617731 (AR) in OMIM.

PMID: 28805828 - Braun et al 2017 - screened the coding regions of OSGEP, TP53RK, TPRKB and LAGE3 in 907 individuals with early-onset nephrotic syndrome including 91 individuals with GAMOS. Identified 2 biallelic missense variants in TPRKB in 2 families with GAMOS (c.407T>C, p.Leu136Pro and c.446A>6, p.Tyr149Cys). Both sets of parents were heterozgous for the variant. Mouse embryos with knockout of Lage3, Osgep, or Tprkb reproduced the human microcephaly phenotype. No renal phenotype was observed in knockout mice or fish but they hypothesize that this is due to early lethality masking renal involvement that might occur in older animals. Functional studies also showed that knockout of these genes affect cell proliferation.

PMID: 30053862 - Hyun et al 2018 - WES on a family with three GAMOS affected siblings found a homozygous missense mutation (NM_033550, c.194A > T, p.Lys65Met) in 2 siblings (3rd not tested). Parents and an unaffected sibling were heterzygous for the variant. All three patients manifested similar phenotypes, including very early-onset nephrotic syndrome, microcephaly, dysmorphic faces, and early fatality. Renal biopsy performed on one patient revealed focal segmental glomerulosclerosis with severe tubulo-interstitial changes.

Summary: 3 familial cases. Some functional data.
Amyloidosis v1.0 NLRP3 Zornitza Stark gene: NLRP3 was added
gene: NLRP3 was added to Amyloidosis. Sources: Expert list
Mode of inheritance for gene: NLRP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NLRP3 were set to 11687797; 28229991; 27435956; 31057541
Phenotypes for gene: NLRP3 were set to Muckle-Wells syndrome
Review for gene: NLRP3 was set to GREEN
Added comment: Renal amyloidosis described in this disorder.
Sources: Expert list
CAKUT v1.43 NADSYN1 Zornitza Stark gene: NADSYN1 was added
gene: NADSYN1 was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: NADSYN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NADSYN1 were set to 31883644
Phenotypes for gene: NADSYN1 were set to Multiple congenital abnormalities; absent kidneys; cardiac; limb; vertebral
Review for gene: NADSYN1 was set to GREEN
gene: NADSYN1 was marked as current diagnostic
Added comment: Five individuals from four unrelated families.
Sources: Expert list
Proteinuric renal disease v2.0 FN1 Zornitza Stark gene: FN1 was added
gene: FN1 was added to Proteinuric renal disease. Sources: Expert list
Mode of inheritance for gene: FN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FN1 were set to 18268355
Phenotypes for gene: FN1 were set to Glomerulopathy with fibronectin deposits 2, MIM# 601894
Review for gene: FN1 was set to GREEN
gene: FN1 was marked as current diagnostic
Added comment: Six unrelated families reported; mostly a nephrotic picture with some haematuria.
Sources: Expert list
Renal tubulopathies v2.0 CLDN10 Zornitza Stark reviewed gene: CLDN10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: HELIX syndrome, MIM# 617671; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
CAKUT v1.43 CHRNA3 Zornitza Stark gene: CHRNA3 was added
gene: CHRNA3 was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: CHRNA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHRNA3 were set to 31708116
Phenotypes for gene: CHRNA3 were set to CAKUT; dysautonomia
Review for gene: CHRNA3 was set to GREEN
gene: CHRNA3 was marked as current diagnostic
Added comment: Five affected individuals from three unrelated families.
Sources: Expert list
Proteinuric renal disease v2.0 CD151 Zornitza Stark reviewed gene: CD151: Rating: GREEN; Mode of pathogenicity: None; Publications: 15265795, 29138120; Phenotypes: Nephropathy with pretibial epidermolysis bullosa and deafness, MIM#609057; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v3.0 CACNA2D2 Zornitza Stark reviewed gene: CACNA2D2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebellar atrophy with seizures and variable developmental delay, MIM#618501; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v3.0 CA5A Zornitza Stark reviewed gene: CA5A: Rating: RED; Mode of pathogenicity: None; Publications: 26913920; Phenotypes: Hyperammonemia due to carbonic anhydrase VA deficiency, MIM# 615751; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 C8orf37 Zornitza Stark changed review comment from: Two unrelated individuals reported with BBS; note gene has an association with retinal ciliopathies.; to: Two unrelated individuals reported with BBS; note gene has an association with retinal ciliopathies. Suggested rating Amber.
Intellectual disability v3.0 C8orf37 Zornitza Stark reviewed gene: C8orf37: Rating: ; Mode of pathogenicity: None; Publications: 26854863, 27008867; Phenotypes: Bardet-Biedl syndrome 21, MIM#617406; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 C4orf26 Zornitza Stark reviewed gene: C4orf26: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Amelogenesis imperfecta, type IIA4, MIM# 614832; Mode of inheritance: None
Membranoproliferative glomerulonephritis v2.2 C3 Eleanor Williams commented on gene: C3: Green review by Daniel Gale agrees with Green rating and gain of function mode of pathogenicity. Should change the Mode of Pathogenicity to make it clear that Loss of function variants are not associated with the disease phenotype.
Intellectual disability v3.0 C2orf71 Zornitza Stark reviewed gene: C2orf71: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa 54 613428; Mode of inheritance: None
Membranoproliferative glomerulonephritis v2.2 CFB Eleanor Williams changed review comment from: Associated with {Hemolytic uremic syndrome, atypical, susceptibility to, 4} (#612924) in OMIM.

PMID: 28210841 - Alfakeeh et al 2017 - 7-year-old boy has pathological features compatible with IC-MPGN. A heterozygous variant p.Glu566Arg in exon 13 of the CFB gene was found.

PMID: 26283675 - Bu et al 2016 - screened 193 patients using a gene panel facilitate genetic testing in aHUS, TTP, C3GN, and DDD. Report 1 variant found in a patient with aHUS and 3 in patients with C3 glomerulonephritis. Individual patient and variant information not given.

PMID: 25758434 - Imamura et al 2015 - 1 family. Daughter diagnosed with C3 glomerulonephritis, mother treated for membranoproliferative glomerulonephritis, and brother with hypocomplementemia without urinary abnormalities. All 3 found to have heterozygosity for CFB p.S367R that was not present in the unaffected father or younger sister. Other variants were found in the daughter, CFI p.R201S and C3 p.V916I were excluded as in other unaffected individuals or appear in high frequency in other populations. They propose that it is highly likely that p.S367R causes a gain of function in CFB through a structure–function relationship.; to: Associated with {Hemolytic uremic syndrome, atypical, susceptibility to, 4} (#612924) in OMIM.

PMID: 28210841 - Alfakeeh et al 2017 - 7-year-old boy has pathological features compatible with IC-MPGN. A heterozygous variant p.Glu566Arg in exon 13 of the CFB gene was found. Note (added 29-01-2020) - the 52 year old father was found to have the same heterozygous CFB gene variant but showed no evidence of renal function impairment, proteinuria, hematuria, or hemolysis.

PMID: 26283675 - Bu et al 2016 - screened 193 patients using a gene panel facilitate genetic testing in aHUS, TTP, C3GN, and DDD. Report 1 variant found in a patient with aHUS and 3 in patients with C3 glomerulonephritis. Individual patient and variant information not given.

PMID: 25758434 - Imamura et al 2015 - 1 family. Daughter diagnosed with C3 glomerulonephritis, mother treated for membranoproliferative glomerulonephritis, and brother with hypocomplementemia without urinary abnormalities. All 3 found to have heterozygosity for CFB p.S367R that was not present in the unaffected father or younger sister. Other variants were found in the daughter, CFI p.R201S and C3 p.V916I were excluded as in other unaffected individuals or appear in high frequency in other populations. They propose that it is highly likely that p.S367R causes a gain of function in CFB through a structure–function relationship.
Membranoproliferative glomerulonephritis v2.2 CFH Eleanor Williams commented on gene: CFH: Following expert review, the mode of inheritance for this gene on this panel should be updated to BIALLELIC only.
Membranoproliferative glomerulonephritis v2.2 CFI Eleanor Williams edited their review of gene: CFI: Added comment: Only renal phenotype in OMIM this gene is associated with is {Hemolytic uremic syndrome, atypical, susceptibility to, 3} 612923.

Papers cited by the BRIDGE consortium
PMID: 18371543 - Boyer et al 2008 - Patient 1 with atypical hemolytic and uremic syndrome had combined CFH and CFI heterozygous mutations.

PMID: 22456601 - Servais et al 2012 - for 141 patients from 45 centers with a definite diagnosis of primary MPGN I, DDD, or GNC3 they performed direct sequencing of CFH, CFI, or MCP exons and of a set of 10 SNPs within the CFH and MCP genes. 6 patients had heterozygous variants in CFI, 3 of which are reported in patients with MPGN histology (Table 2).

Following expert review rating this gene Red, and review of the literature this gene should be down graded to Amber or Red.; Changed rating: RED
Membranoproliferative glomerulonephritis v2.2 DGKE Eleanor Williams edited their review of gene: DGKE: Added comment: Recent review by Daniel Gale rates the gene green so no change in rating.

Checking mode of inheritance:
PMID: 23274426 - Ozaltin et al 2013 - 3 consanguineous families - 3 different homozygous variants in 9 individuals.
PMID: 28526779 - Azukaitis et al 2017 - review of 24 patients with aHUS/MPGN and variants in DGKE. The 9 cases with MPGN-like renal biopsies are those reported in Ozaltin et al 2013

Other papers cited by BRIDGE review are related to aHUS only (PMID: 23542698 and 21902819)

OMIM lists the mode of inheritance for Nephrotic syndrome, type 7, #615008 as AR.

Therefore, the mode of inheritance should be updated to BIALLELIC only.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Atypical haemolytic uraemic syndrome v2.1 CFHR5 Eleanor Williams reviewed gene: CFHR5: Rating: AMBER; Mode of pathogenicity: None; Publications: 20513133, 22622361, 30905589, 29500241; Phenotypes: ; Mode of inheritance: None
Atypical haemolytic uraemic syndrome v2.1 ADAMTS13 Eleanor Williams commented on gene: ADAMTS13
Unexplained paediatric onset end-stage renal disease v1.1 BNC2 Eleanor Williams Phenotypes for gene: BNC2 were changed from Posterior urethral valves; PUV; Congenital lower urinary-tract obstruction to Posterior urethral valves; PUV; Congenital lower urinary-tract obstruction; Lower urinary tract obstruction, congenital, 618612
CAKUT v1.43 BNC2 Eleanor Williams Phenotypes for gene: BNC2 were changed from Posterior urethral valves; PUV; Congenital lower urinary-tract obstruction to Posterior urethral valves; PUV; Congenital lower urinary-tract obstruction; Lower urinary tract obstruction, congenital, 618612
Intellectual disability v3.0 C2CD3 Zornitza Stark reviewed gene: C2CD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30097616, 27094867, 26477546, 24997988,; Phenotypes: Orofaciodigital syndrome XIV, MIM# 615948; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v3.0 C19orf12 Zornitza Stark reviewed gene: C19orf12: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with brain iron accumulation 4, MIM#614298; Mode of inheritance: None
Intellectual disability v3.0 BMPR1B Zornitza Stark reviewed gene: BMPR1B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Acromesomelic dysplasia, Demirhan type MIM#609441, Brachydactyly, type A1, D, MIM#616849, Brachydactyly, type A2, MIM# 112600; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v3.0 BMPER Zornitza Stark reviewed gene: BMPER: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Diaphanospondylodysostosis, MIM# 608022; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 BICD2 Zornitza Stark reviewed gene: BICD2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM#615290; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 BHLHA9 Zornitza Stark reviewed gene: BHLHA9: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Syndactyly, mesoaxial synostotic, with phalangeal reduction, MIM# 609432; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 BGN Zornitza Stark reviewed gene: BGN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Meester-Loeys syndrome, MIM# 300989, Spondyloepimetaphyseal dysplasia, X-linked, MIM#300106; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v3.0 BFSP2 Zornitza Stark reviewed gene: BFSP2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cataract 12, multiple types, MIM# 611597; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 BCORL1 Zornitza Stark reviewed gene: BCORL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24123876, 30941876; Phenotypes: Shukla-Vernon syndrome, MIM# 301029; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Intellectual disability v3.0 B9D2 Zornitza Stark gene: B9D2 was added
gene: B9D2 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: B9D2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B9D2 were set to 26092869; 21763481
Phenotypes for gene: B9D2 were set to Joubert syndrome 34, MIM#614175; Meckel syndrome 10, MIM#614175
Review for gene: B9D2 was set to GREEN
gene: B9D2 was marked as current diagnostic
Added comment: Two unrelated individuals with Joubert syndrome and bi-allelic variants reported; single family with two affected individuals also reported with homozygous variant in this gene and more severe Meckel phenotype, overall supporting gene-disease association for a ciliopathy with CNS involvement. ID is part of the phenotype of these conditions.
Sources: Expert list
Intellectual disability v3.0 B9D1 Zornitza Stark reviewed gene: B9D1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24886560, 21493627; Phenotypes: Joubert syndrome 27, MIM#617120, Meckel syndrome 9, MIM#614209; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Structural eye disease v1.2 MYRF Ivone Leong Phenotypes for gene: MYRF were changed from Nanophthalmos to Nanophthalmos; High hyperopia
Structural eye disease v1.1 MYRF Ivone Leong Publications for gene: MYRF were set to 31266062
Anophthalmia or microphthalmia v1.23 MYRF Ivone Leong Classified gene: MYRF as Green List (high evidence)
Anophthalmia or microphthalmia v1.23 MYRF Ivone Leong Added comment: Comment on list classification: Comment on list classification: New gene added by expert reviewer. This gene has been given a Green rating based on the level of evidence to support gene-disease association and also that it is also a Green gene on the GMS Structural eye disease (v1.0, code: 509).
Anophthalmia or microphthalmia v1.23 MYRF Ivone Leong Gene: myrf has been classified as Green List (High Evidence).
Anophthalmia or microphthalmia v1.22 MYRF Ivone Leong Publications for gene: MYRF were set to PMID: 31048900, 31172260, 31700225
Glaucoma (developmental) v1.7 CPAMD8 Ivone Leong Classified gene: CPAMD8 as Green List (high evidence)
Glaucoma (developmental) v1.7 CPAMD8 Ivone Leong Added comment: Comment on list classification: New gene added by expert reviewer. This gene has been given a Green rating based on the level of evidence to support gene-disease association and also that it is also a Green gene on the GMS Structural eye disease (v1.0, code: 509).
Glaucoma (developmental) v1.7 CPAMD8 Ivone Leong Gene: cpamd8 has been classified as Green List (High Evidence).
Bleeding and platelet disorders v1.0 IKZF5 Louise Daugherty reviewed gene: IKZF5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Glaucoma (developmental) v1.6 CPAMD8 Ivone Leong Phenotypes for gene: CPAMD8 were changed from Glaucoma; anterior segment dysgenesis; retinal detachment; cataract to Glaucoma; anterior segment dysgenesis 8, 617319; retinal detachment; cataract
Intellectual disability v3.0 ATP8B1 Zornitza Stark reviewed gene: ATP8B1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cholestasis, benign recurrent intrahepatic, MIM# 243300, Cholestasis, intrahepatic, of pregnancy, 1, MIM#147480, Cholestasis, progressive familial intrahepatic 1, MIM# 211600; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v3.0 ATP6V1B1 Zornitza Stark reviewed gene: ATP6V1B1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Renal tubular acidosis with deafness 267300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 ATP6AP1 Zornitza Stark gene: ATP6AP1 was added
gene: ATP6AP1 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: ATP6AP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ATP6AP1 were set to 27231034
Phenotypes for gene: ATP6AP1 were set to Immunodeficiency 47, MIM#300972
Review for gene: ATP6AP1 was set to GREEN
gene: ATP6AP1 was marked as current diagnostic
Added comment: 11 males from 6 unrelated families with primarily an immunodeficiency disorder; six patients from 3 families who carried the same variant (E346K) had neurologic features, including seizures, mild intellectual disability, and behavioral abnormalities
Sources: Expert list
Intellectual disability v3.0 ATP1A2 Zornitza Stark reviewed gene: ATP1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alternating hemiplegia of childhood 1, MIM# 104290; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v3.0 ATAD1 Zornitza Stark gene: ATAD1 was added
gene: ATAD1 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: ATAD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATAD1 were set to 28180185
Phenotypes for gene: ATAD1 were set to Hyperekplexia 4, MIM#618011
Review for gene: ATAD1 was set to GREEN
Added comment: Severe progressive neurological disorder, severe/profound intellectual disability is a feature
Sources: Expert list
Hearing loss v2.4 SOX2 Zornitza Stark reviewed gene: SOX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30262714, 16932809, 16145681; Phenotypes: Microphthalmia, syndromic 3, MIM# 206900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hearing loss v2.4 SNAI2 Zornitza Stark reviewed gene: SNAI2: Rating: AMBER; Mode of pathogenicity: None; Publications: 12444107, 30936914; Phenotypes: Waardenburg syndrome, type 2D, MIM# 608890; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hearing loss v2.4 SLITRK6 Zornitza Stark reviewed gene: SLITRK6: Rating: GREEN; Mode of pathogenicity: None; Publications: 23543054, 29551497; Phenotypes: Deafness and myopia, MIM#221200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hearing loss v2.4 SIX5 Zornitza Stark reviewed gene: SIX5: Rating: RED; Mode of pathogenicity: None; Publications: 17357085, 24429398, 21280147, 14704431, 17357085, 11950062; Phenotypes: Branchiootorenal syndrome 2, MIM#610896; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hearing loss v2.4 PMP22 Zornitza Stark reviewed gene: PMP22: Rating: AMBER; Mode of pathogenicity: None; Publications: 8355122, 10330345, 12578939; Phenotypes: Charcot-Marie-Tooth disease, type 1E 118300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 ASTN1 Zornitza Stark gene: ASTN1 was added
gene: ASTN1 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: ASTN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASTN1 were set to 29706646; 27431290; 26539891
Phenotypes for gene: ASTN1 were set to Intellectual disability
Review for gene: ASTN1 was set to GREEN
gene: ASTN1 was marked as current diagnostic
Added comment: Three families reported as part of large cohorts albeit proposing multiple novel candidate genes with minimal detail and no functional validation.
Sources: Expert list
Intellectual disability v3.0 ARHGEF6 Zornitza Stark reviewed gene: ARHGEF6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: MENTAL RETARDATION X-LINKED TYPE 46; Mode of inheritance: None
Hearing loss v2.4 FOXI1 Zornitza Stark reviewed gene: FOXI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29242249, 9843211, 17503324; Phenotypes: Enlarged vestibular aqueduct 600791, deafness, renal tubular acidosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hearing loss v2.4 FDXR Zornitza Stark gene: FDXR was added
gene: FDXR was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: FDXR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDXR were set to 28965846
Phenotypes for gene: FDXR were set to Auditory neuropathy and optic atrophy, MIM# 617717
Review for gene: FDXR was set to GREEN
gene: FDXR was marked as current diagnostic
Added comment: 8 individuals from 4 unrelated families reported, onset of symptoms in first/second decades.
Sources: Expert list
Hearing loss v2.4 ESRP1 Zornitza Stark gene: ESRP1 was added
gene: ESRP1 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: ESRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESRP1 were set to 29107558
Phenotypes for gene: ESRP1 were set to Deafness, autosomal recessive 109, MIM# 618013
Review for gene: ESRP1 was set to AMBER
Added comment: Single family reported with affected sibs, mouse model. Amber or Red.
Sources: Expert list
Hearing loss v2.4 COL9A1 Zornitza Stark reviewed gene: COL9A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Stickler syndrome, type IV, MIM#614134; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hearing loss v2.4 COL2A1 Zornitza Stark reviewed gene: COL2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27408751; Phenotypes: Stickler syndrome, type I, MIM108300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hearing loss v2.4 COL11A1 Zornitza Stark reviewed gene: COL11A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30245514; Phenotypes: Stickler syndrome, type II, MIM#604841, Deafness, autosomal dominant 37, MIM#618533; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hearing loss v2.4 CISD2 Zornitza Stark reviewed gene: CISD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25371195; Phenotypes: Wolfram syndrome 2, MIM# 604928; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal superpanel - broad v2.1 Eleanor Williams Panel status changed from internal to public
Renal superpanel - narrow v2.1 Eleanor Williams Panel status changed from internal to public
Renal superpanel - narrow v2.0 Eleanor Williams Added Panel Renal superpanel - narrow
Set child panels to: Membranoproliferative glomerulonephritis; Cystic kidney disease; Haematuria; Atypical haemolytic uraemic syndrome; Renal tubulopathies; Proteinuric renal disease; Nephrocalcinosis or nephrolithiasis; CAKUT; Renal ciliopathies; Tubulointerstitial kidney disease
Set panel types to: Super Panel
Renal superpanel - broad v2.0 Eleanor Williams Added Panel Renal superpanel - broad
Set child panels to: Membranoproliferative glomerulonephritis; Atypical haemolytic uraemic syndrome; Haematuria; Cystic kidney disease; Renal tubulopathies; Nephrocalcinosis or nephrolithiasis; Proteinuric renal disease; Unexplained kidney failure in young people; CAKUT; Extreme early-onset hypertension; Renal ciliopathies; Tubulointerstitial kidney disease; Amyloidosis; Unexplained paediatric onset end-stage renal disease
Set panel types to: Super Panel
Kidneyome_SuperPanel_VCGS v0.2 Eleanor Williams Panel types changed to External Diagnostic Lab
Kidneyome_SuperPanel_VCGS v0.1 Eleanor Williams Panel status changed from internal to public
Kidneyome_SuperPanel_VCGS v0.0 ZIC3 Eleanor Williams gene: ZIC3 was added
gene: ZIC3 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ZIC3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ZIC3 were set to VACTERL association, X-linked, MIM#314390
Kidneyome_SuperPanel_VCGS v0.0 XDH Eleanor Williams gene: XDH was added
gene: XDH was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: XDH was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 WT1 Eleanor Williams gene: WT1 was added
gene: WT1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: WT1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 WNT5A Eleanor Williams gene: WNT5A was added
gene: WNT5A was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: WNT5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: WNT5A were set to Robinow syndrome, autosomal dominant 1, MIM#180700
Kidneyome_SuperPanel_VCGS v0.0 WNK4 Eleanor Williams gene: WNK4 was added
gene: WNK4 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_AldoHypertension v38.1.0,Expert Review Green
Mode of inheritance for gene: WNK4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WNK4 were set to 18179883
Phenotypes for gene: WNK4 were set to SERKAL syndrome; OMIM #611812
Kidneyome_SuperPanel_VCGS v0.0 WNK1 Eleanor Williams gene: WNK1 was added
gene: WNK1 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_AldoHypertension v38.1.0,Expert Review Green
Mode of inheritance for gene: WNK1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 WDR73 Eleanor Williams gene: WDR73 was added
gene: WDR73 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: WDR73 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 WDR60 Eleanor Williams gene: WDR60 was added
gene: WDR60 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: WDR60 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 WDR35 Eleanor Williams gene: WDR35 was added
gene: WDR35 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: WDR35 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 WDR19 Eleanor Williams gene: WDR19 was added
gene: WDR19 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: WDR19 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 WDPCP Eleanor Williams gene: WDPCP was added
gene: WDPCP was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: WDPCP was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 VPS33B Eleanor Williams gene: VPS33B was added
gene: VPS33B was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_Tubulopathies v38.1.0,Expert Review Green
Mode of inheritance for gene: VPS33B was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 VIPAS39 Eleanor Williams gene: VIPAS39 was added
gene: VIPAS39 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_Tubulopathies v38.1.0,Expert Review Green
Mode of inheritance for gene: VIPAS39 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 VDR Eleanor Williams gene: VDR was added
gene: VDR was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CalcPhos v38.1.0,Expert Review Green
Mode of inheritance for gene: VDR was set to Unknown
Phenotypes for gene: VDR were set to Rickets, vitamin D-resistant, type IIA, MIM# 277440
Kidneyome_SuperPanel_VCGS v0.0 UMOD Eleanor Williams gene: UMOD was added
gene: UMOD was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Cystic v38.1.0
Mode of inheritance for gene: UMOD was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TXNDC15 Eleanor Williams gene: TXNDC15 was added
gene: TXNDC15 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: TXNDC15 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TTC8 Eleanor Williams gene: TTC8 was added
gene: TTC8 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: TTC8 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TTC21B Eleanor Williams gene: TTC21B was added
gene: TTC21B was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: TTC21B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTC21B were set to Nephronophthisis 12, MIM#613820
Kidneyome_SuperPanel_VCGS v0.0 TSC2 Eleanor Williams gene: TSC2 was added
gene: TSC2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Cystic v38.1.0
Mode of inheritance for gene: TSC2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TSC1 Eleanor Williams gene: TSC1 was added
gene: TSC1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Cystic v38.1.0
Mode of inheritance for gene: TSC1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TRPM6 Eleanor Williams gene: TRPM6 was added
gene: TRPM6 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Magnesium v38.1.0
Mode of inheritance for gene: TRPM6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPM6 were set to 21669885
Phenotypes for gene: TRPM6 were set to Hypomagnesemia 1, intestinal, MIM#602014
Kidneyome_SuperPanel_VCGS v0.0 TRPC6 Eleanor Williams gene: TRPC6 was added
gene: TRPC6 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TRPC6 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TRAP1 Eleanor Williams gene: TRAP1 was added
gene: TRAP1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TRAP1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TRAF3IP1 Eleanor Williams gene: TRAF3IP1 was added
gene: TRAF3IP1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: TRAF3IP1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TPRKB Eleanor Williams gene: TPRKB was added
gene: TPRKB was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TPRKB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPRKB were set to 28805828; 30053862
Phenotypes for gene: TPRKB were set to Galloway-Mowat syndrome 5, OMIM #617731
Kidneyome_SuperPanel_VCGS v0.0 TP53RK Eleanor Williams gene: TP53RK was added
gene: TP53RK was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TP53RK was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TNS2 Eleanor Williams gene: TNS2 was added
gene: TNS2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: TNS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNS2 were set to 29773874
Phenotypes for gene: TNS2 were set to Nephrotic syndrome
Kidneyome_SuperPanel_VCGS v0.0 TMEM67 Eleanor Williams gene: TMEM67 was added
gene: TMEM67 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: TMEM67 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TMEM237 Eleanor Williams gene: TMEM237 was added
gene: TMEM237 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: TMEM237 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TMEM231 Eleanor Williams gene: TMEM231 was added
gene: TMEM231 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: TMEM231 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TMEM216 Eleanor Williams gene: TMEM216 was added
gene: TMEM216 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: TMEM216 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TMEM138 Eleanor Williams gene: TMEM138 was added
gene: TMEM138 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: TMEM138 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TMEM107 Eleanor Williams gene: TMEM107 was added
gene: TMEM107 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: TMEM107 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TFAP2A Eleanor Williams gene: TFAP2A was added
gene: TFAP2A was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TFAP2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TFAP2A were set to Branchiooculofacial syndrome, MIM# 113620
Kidneyome_SuperPanel_VCGS v0.0 TCTN3 Eleanor Williams gene: TCTN3 was added
gene: TCTN3 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: TCTN3 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TCTN2 Eleanor Williams gene: TCTN2 was added
gene: TCTN2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: TCTN2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TCTN1 Eleanor Williams gene: TCTN1 was added
gene: TCTN1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: TCTN1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TBX18 Eleanor Williams gene: TBX18 was added
gene: TBX18 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TBX18 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TBC1D8B Eleanor Williams gene: TBC1D8B was added
gene: TBC1D8B was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TBC1D8B 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: TBC1D8B were set to 30661770
Phenotypes for gene: TBC1D8B were set to Nephrotic syndrome, type 20, MIM# 301028
Kidneyome_SuperPanel_VCGS v0.0 TBC1D1 Eleanor Williams gene: TBC1D1 was added
gene: TBC1D1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: TBC1D1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBC1D1 were set to 26572137
Phenotypes for gene: TBC1D1 were set to CAKUT
Kidneyome_SuperPanel_VCGS v0.0 STX16 Eleanor Williams gene: STX16 was added
gene: STX16 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_AldoHypertension v38.1.0,Expert Review Green
Mode of inheritance for gene: STX16 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 STRADA Eleanor Williams gene: STRADA was added
gene: STRADA was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Literature
Mode of inheritance for gene: STRADA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STRADA were set to PMID: 30311510, 28688840, 27170158, 17522105
Phenotypes for gene: STRADA were set to Polyhydramnios, megalencephaly, and symptomatic epilepsy; OMIM #611087
Kidneyome_SuperPanel_VCGS v0.0 STRA6 Eleanor Williams gene: STRA6 was added
gene: STRA6 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: STRA6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STRA6 were set to Microphthalmia, isolated, with coloboma 8, MIM#601186
Kidneyome_SuperPanel_VCGS v0.0 SMARCAL1 Eleanor Williams gene: SMARCAL1 was added
gene: SMARCAL1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SMARCAL1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SLIT2 Eleanor Williams gene: SLIT2 was added
gene: SLIT2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLIT2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SLC9A3R1 Eleanor Williams gene: SLC9A3R1 was added
gene: SLC9A3R1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC9A3R1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC9A3R1 were set to 18784102
Phenotypes for gene: SLC9A3R1 were set to Nephrolithiasis/osteoporosis, hypophosphatemic, 2, MIM# 612287
Kidneyome_SuperPanel_VCGS v0.0 SLC7A9 Eleanor Williams gene: SLC7A9 was added
gene: SLC7A9 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_Tubulopathies v38.1.0,Expert Review Green
Mode of inheritance for gene: SLC7A9 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SLC7A7 Eleanor Williams gene: SLC7A7 was added
gene: SLC7A7 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: SLC7A7 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SLC4A4 Eleanor Williams gene: SLC4A4 was added
gene: SLC4A4 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_Tubulopathies v38.1.0,Expert Review Green
Mode of inheritance for gene: SLC4A4 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SLC4A1 Eleanor Williams gene: SLC4A1 was added
gene: SLC4A1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC4A1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SLC3A1 Eleanor Williams gene: SLC3A1 was added
gene: SLC3A1 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_Tubulopathies v38.1.0,Expert Review Green
Mode of inheritance for gene: SLC3A1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SLC34A3 Eleanor Williams gene: SLC34A3 was added
gene: SLC34A3 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC34A3 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SLC34A1 Eleanor Williams gene: SLC34A1 was added
gene: SLC34A1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC34A1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SLC2A9 Eleanor Williams gene: SLC2A9 was added
gene: SLC2A9 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_Tubulopathies v38.1.0,Expert Review Green
Mode of inheritance for gene: SLC2A9 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SLC2A2 Eleanor Williams gene: SLC2A2 was added
gene: SLC2A2 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_Tubulopathies v38.1.0,Expert Review Green
Mode of inheritance for gene: SLC2A2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SLC26A1 Eleanor Williams gene: SLC26A1 was added
gene: SLC26A1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC26A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC26A1 were set to 20160351; 27210743
Phenotypes for gene: SLC26A1 were set to Nephrolithiasis, calcium oxalate, MIM#167030
Kidneyome_SuperPanel_VCGS v0.0 SLC22A12 Eleanor Williams gene: SLC22A12 was added
gene: SLC22A12 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_Tubulopathies v38.1.0,Expert Review Green
Mode of inheritance for gene: SLC22A12 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SLC12A3 Eleanor Williams gene: SLC12A3 was added
gene: SLC12A3 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Magnesium v38.1.0
Mode of inheritance for gene: SLC12A3 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SLC12A1 Eleanor Williams gene: SLC12A1 was added
gene: SLC12A1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC12A1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SIX5 Eleanor Williams gene: SIX5 was added
gene: SIX5 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SIX5 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SIX1 Eleanor Williams gene: SIX1 was added
gene: SIX1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SIX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SIX1 were set to Deafness, autosomal dominant 23, MIM# 605192; Branchiootic syndrome 3, MIM#608389
Kidneyome_SuperPanel_VCGS v0.0 SGPL1 Eleanor Williams gene: SGPL1 was added
gene: SGPL1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SGPL1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SEC61A1 Eleanor Williams gene: SEC61A1 was added
gene: SEC61A1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Tubulointerstitial v38.1.0
Mode of inheritance for gene: SEC61A1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SDCCAG8 Eleanor Williams gene: SDCCAG8 was added
gene: SDCCAG8 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: SDCCAG8 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SCNN1G Eleanor Williams gene: SCNN1G was added
gene: SCNN1G was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_AldoHypertension v38.1.0,Expert Review Green
Mode of inheritance for gene: SCNN1G was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SCNN1B Eleanor Williams gene: SCNN1B was added
gene: SCNN1B was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_AldoHypertension v38.1.0,Expert Review Green
Mode of inheritance for gene: SCNN1B was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SCNN1A Eleanor Williams gene: SCNN1A was added
gene: SCNN1A was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_AldoHypertension v38.1.0,Expert Review Green
Mode of inheritance for gene: SCNN1A was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SCARB2 Eleanor Williams gene: SCARB2 was added
gene: SCARB2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SCARB2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SBDS Eleanor Williams gene: SBDS was added
gene: SBDS was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CalcPhos v38.1.0,Expert Review Green
Mode of inheritance for gene: SBDS was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SARS2 Eleanor Williams gene: SARS2 was added
gene: SARS2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: SARS2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SALL4 Eleanor Williams gene: SALL4 was added
gene: SALL4 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SALL4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SALL4 were set to 20301547
Phenotypes for gene: SALL4 were set to SALL4- related disorders
Kidneyome_SuperPanel_VCGS v0.0 SALL1 Eleanor Williams gene: SALL1 was added
gene: SALL1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SALL1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 RRM2B Eleanor Williams gene: RRM2B was added
gene: RRM2B was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: RRM2B was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 RPGRIP1L Eleanor Williams gene: RPGRIP1L was added
gene: RPGRIP1L was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: RPGRIP1L was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 ROR2 Eleanor Williams gene: ROR2 was added
gene: ROR2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ROR2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 ROBO2 Eleanor Williams gene: ROBO2 was added
gene: ROBO2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ROBO2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 RMND1 Eleanor Williams gene: RMND1 was added
gene: RMND1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: RMND1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 RET Eleanor Williams gene: RET was added
gene: RET was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: RET was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 REN Eleanor Williams gene: REN was added
gene: REN was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: REN was set to BIALLELIC, autosomal or pseudoautosomal
Kidneyome_SuperPanel_VCGS v0.0 PTPRO Eleanor Williams gene: PTPRO was added
gene: PTPRO was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: PTPRO was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 PTH1R Eleanor Williams gene: PTH1R was added
gene: PTH1R was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CalcPhos v38.1.0,Expert Review Green
Mode of inheritance for gene: PTH1R was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 PRKCSH Eleanor Williams gene: PRKCSH was added
gene: PRKCSH was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Cystic v38.1.0
Mode of inheritance for gene: PRKCSH was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 PODXL Eleanor Williams gene: PODXL was added
gene: PODXL was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PODXL was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PODXL were set to PMID: 30523047, 29244787, 28117080, 24048372
Phenotypes for gene: PODXL were set to Nephrotic syndrome
Kidneyome_SuperPanel_VCGS v0.0 PLCE1 Eleanor Williams gene: PLCE1 was added
gene: PLCE1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: PLCE1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 PKHD1 Eleanor Williams gene: PKHD1 was added
gene: PKHD1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Cystic v38.1.0
Mode of inheritance for gene: PKHD1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 PKD2 Eleanor Williams gene: PKD2 was added
gene: PKD2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Cystic v38.1.0
Mode of inheritance for gene: PKD2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 PKD1 Eleanor Williams gene: PKD1 was added
gene: PKD1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Cystic v38.1.0
Mode of inheritance for gene: PKD1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 PHEX Eleanor Williams gene: PHEX was added
gene: PHEX was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PHEX 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: PHEX were set to PMID: 31065622
Phenotypes for gene: PHEX were set to OMIM #307800; Hypophosphatemic rickets, X-linked dominant
Kidneyome_SuperPanel_VCGS v0.0 PDSS2 Eleanor Williams gene: PDSS2 was added
gene: PDSS2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: PDSS2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 PDE3A Eleanor Williams gene: PDE3A was added
gene: PDE3A was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_AldoHypertension v38.1.0,Expert Review Green
Mode of inheritance for gene: PDE3A was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 PCBD1 Eleanor Williams gene: PCBD1 was added
gene: PCBD1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Magnesium v38.1.0
Mode of inheritance for gene: PCBD1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 PBX1 Eleanor Williams gene: PBX1 was added
gene: PBX1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: PBX1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 PAX2 Eleanor Williams gene: PAX2 was added
gene: PAX2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: PAX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAX2 were set to 24676634
Phenotypes for gene: PAX2 were set to Glomerulosclerosis, focal segmental, 7, MIM#616002
Kidneyome_SuperPanel_VCGS v0.0 OSGEP Eleanor Williams gene: OSGEP was added
gene: OSGEP was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: OSGEP was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 OFD1 Eleanor Williams gene: OFD1 was added
gene: OFD1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: OFD1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 OCRL Eleanor Williams gene: OCRL was added
gene: OCRL was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: OCRL was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: OCRL were set to Lowe syndrome, MIM#309000; Dent disease 2, MIM#300555
Kidneyome_SuperPanel_VCGS v0.0 NUP93 Eleanor Williams gene: NUP93 was added
gene: NUP93 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: NUP93 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP93 were set to 26878725
Phenotypes for gene: NUP93 were set to Nephrotic syndrome, type 12, MIM#616892
Kidneyome_SuperPanel_VCGS v0.0 NUP85 Eleanor Williams gene: NUP85 was added
gene: NUP85 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NUP85 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP85 were set to 30179222
Phenotypes for gene: NUP85 were set to Nephrotic syndrome, type 17, MIM#618176
Kidneyome_SuperPanel_VCGS v0.0 NUP133 Eleanor Williams gene: NUP133 was added
gene: NUP133 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NUP133 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP133 were set to 30179222
Phenotypes for gene: NUP133 were set to Nephrotic syndrome, type 18, MIM#618177
Kidneyome_SuperPanel_VCGS v0.0 NUP107 Eleanor Williams gene: NUP107 was added
gene: NUP107 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: NUP107 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 NR3C2 Eleanor Williams gene: NR3C2 was added
gene: NR3C2 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_AldoHypertension v38.1.0,Expert Review Green
Mode of inheritance for gene: NR3C2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 NR3C1 Eleanor Williams gene: NR3C1 was added
gene: NR3C1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: NR3C1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 NPHS2 Eleanor Williams gene: NPHS2 was added
gene: NPHS2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: NPHS2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 NPHS1 Eleanor Williams gene: NPHS1 was added
gene: NPHS1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: NPHS1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 NPHP4 Eleanor Williams gene: NPHP4 was added
gene: NPHP4 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: NPHP4 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 NPHP3 Eleanor Williams gene: NPHP3 was added
gene: NPHP3 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: NPHP3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPHP3 were set to Renal-hepatic-pancreatic dysplasia 1, MIM# 208540
Kidneyome_SuperPanel_VCGS v0.0 NPHP1 Eleanor Williams gene: NPHP1 was added
gene: NPHP1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: NPHP1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 NOTCH2 Eleanor Williams gene: NOTCH2 was added
gene: NOTCH2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: NOTCH2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 NLRP3 Eleanor Williams gene: NLRP3 was added
gene: NLRP3 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: NLRP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NLRP3 were set to 27435956; 28229991; PubMed: 11687797; 31057541
Phenotypes for gene: NLRP3 were set to Muckle-Wells syndrome, MIM#191900
Kidneyome_SuperPanel_VCGS v0.0 NIPBL Eleanor Williams gene: NIPBL was added
gene: NIPBL was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: NIPBL was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 NEK8 Eleanor Williams gene: NEK8 was added
gene: NEK8 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: NEK8 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 NEK1 Eleanor Williams gene: NEK1 was added
gene: NEK1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: NEK1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 NADSYN1 Eleanor Williams gene: NADSYN1 was added
gene: NADSYN1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NADSYN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NADSYN1 were set to 31883644
Phenotypes for gene: NADSYN1 were set to limb; cardiac; absent kidneys; vertebral; Multiple congenital abnormalities
Kidneyome_SuperPanel_VCGS v0.0 MYOCD Eleanor Williams gene: MYOCD was added
gene: MYOCD was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Literature
Mode of inheritance for gene: MYOCD was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYOCD were set to 31513549
Phenotypes for gene: MYOCD were set to cardiomyopathy; Megabladder; congenital heart disease
Kidneyome_SuperPanel_VCGS v0.0 MYO1E Eleanor Williams gene: MYO1E was added
gene: MYO1E was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: MYO1E was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 MYH9 Eleanor Williams gene: MYH9 was added
gene: MYH9 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: MYH9 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 MUT Eleanor Williams gene: MUT was added
gene: MUT was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: MUT was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 MUC1 Eleanor Williams gene: MUC1 was added
gene: MUC1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Cystic v38.1.0
Mode of inheritance for gene: MUC1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 MMACHC Eleanor Williams gene: MMACHC was added
gene: MMACHC was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: MMACHC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MMACHC were set to Methylmalonic aciduria and homocystinuria, cblC type, MIM#277400
Kidneyome_SuperPanel_VCGS v0.0 MKS1 Eleanor Williams gene: MKS1 was added
gene: MKS1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: MKS1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 MKKS Eleanor Williams gene: MKKS was added
gene: MKKS was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: MKKS was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 MAPKBP1 Eleanor Williams gene: MAPKBP1 was added
gene: MAPKBP1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: MAPKBP1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 MAGI2 Eleanor Williams gene: MAGI2 was added
gene: MAGI2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: MAGI2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAGI2 were set to 27932480; 25108225; 25271328
Phenotypes for gene: MAGI2 were set to Nephrotic syndrome, type 15, MIM# 617609
Kidneyome_SuperPanel_VCGS v0.0 MAGED2 Eleanor Williams gene: MAGED2 was added
gene: MAGED2 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_Tubulopathies v38.1.0,Expert Review Green
Mode of inheritance for gene: MAGED2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 LZTFL1 Eleanor Williams gene: LZTFL1 was added
gene: LZTFL1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: LZTFL1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 LYZ Eleanor Williams gene: LYZ was added
gene: LYZ was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: LYZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LYZ were set to 8464497; 15745733,; PubMed: 1808634
Phenotypes for gene: LYZ were set to Amyloidosis, renal, MIM#105200
Kidneyome_SuperPanel_VCGS v0.0 LRP4 Eleanor Williams gene: LRP4 was added
gene: LRP4 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: LRP4 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 LRIG2 Eleanor Williams gene: LRIG2 was added
gene: LRIG2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: LRIG2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 LMX1B Eleanor Williams gene: LMX1B was added
gene: LMX1B was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: LMX1B was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 LIFR Eleanor Williams gene: LIFR was added
gene: LIFR was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: LIFR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LIFR were set to 28334964
Phenotypes for gene: LIFR were set to CAKUT
Kidneyome_SuperPanel_VCGS v0.0 LAMB2 Eleanor Williams gene: LAMB2 was added
gene: LAMB2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: LAMB2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 LAGE3 Eleanor Williams gene: LAGE3 was added
gene: LAGE3 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: LAGE3 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 KYNU Eleanor Williams gene: KYNU was added
gene: KYNU was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: KYNU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KYNU were set to 28792876
Phenotypes for gene: KYNU were set to Vertebral, cardiac, renal, and limb defects syndrome 2, MIM#617661
Kidneyome_SuperPanel_VCGS v0.0 KMT2D Eleanor Williams gene: KMT2D was added
gene: KMT2D was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: KMT2D was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 KLHL3 Eleanor Williams gene: KLHL3 was added
gene: KLHL3 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_AldoHypertension v38.1.0,Expert Review Green
Mode of inheritance for gene: KLHL3 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 KL Eleanor Williams gene: KL was added
gene: KL was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CalcPhos v38.1.0,Expert Review Green
Mode of inheritance for gene: KL was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 KIF7 Eleanor Williams gene: KIF7 was added
gene: KIF7 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: KIF7 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 KIF14 Eleanor Williams gene: KIF14 was added
gene: KIF14 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Literature
Mode of inheritance for gene: KIF14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF14 were set to PMID: 30388224. 24128419
Phenotypes for gene: KIF14 were set to ?Meckel syndrome 12, OMIM #616258; Microcephaly 20, primary, autosomal recessive, OMIM #617914
Kidneyome_SuperPanel_VCGS v0.0 KIAA0753 Eleanor Williams gene: KIAA0753 was added
gene: KIAA0753 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: KIAA0753 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 KIAA0586 Eleanor Williams gene: KIAA0586 was added
gene: KIAA0586 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: KIAA0586 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 KIAA0556 Eleanor Williams gene: KIAA0556 was added
gene: KIAA0556 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: KIAA0556 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 KDM6A Eleanor Williams gene: KDM6A was added
gene: KDM6A was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: KDM6A was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 KCNJ5 Eleanor Williams gene: KCNJ5 was added
gene: KCNJ5 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_AldoHypertension v38.1.0,Expert Review Green
Mode of inheritance for gene: KCNJ5 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 KCNJ10 Eleanor Williams gene: KCNJ10 was added
gene: KCNJ10 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_Tubulopathies v38.1.0,Expert Review Green
Mode of inheritance for gene: KCNJ10 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 KCNJ1 Eleanor Williams gene: KCNJ1 was added
gene: KCNJ1 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_Tubulopathies v38.1.0,Expert Review Green
Mode of inheritance for gene: KCNJ1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 KCNA1 Eleanor Williams gene: KCNA1 was added
gene: KCNA1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Magnesium v38.1.0
Mode of inheritance for gene: KCNA1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 KANK2 Eleanor Williams gene: KANK2 was added
gene: KANK2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: KANK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KANK2 were set to 25961457
Phenotypes for gene: KANK2 were set to Nephrotic syndrome, type 16, MIM#617783
Kidneyome_SuperPanel_VCGS v0.0 JAG1 Eleanor Williams gene: JAG1 was added
gene: JAG1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: JAG1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 ITSN1 Eleanor Williams gene: ITSN1 was added
gene: ITSN1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ITSN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITSN1 were set to PMID: 29773874
Phenotypes for gene: ITSN1 were set to Early childhood SSNS
Kidneyome_SuperPanel_VCGS v0.0 ITGA8 Eleanor Williams gene: ITGA8 was added
gene: ITGA8 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ITGA8 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 ITGA3 Eleanor Williams gene: ITGA3 was added
gene: ITGA3 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ITGA3 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 IQCB1 Eleanor Williams gene: IQCB1 was added
gene: IQCB1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: IQCB1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 INVS Eleanor Williams gene: INVS was added
gene: INVS was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: INVS was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 INPP5E Eleanor Williams gene: INPP5E was added
gene: INPP5E was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: INPP5E was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 INF2 Eleanor Williams gene: INF2 was added
gene: INF2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: INF2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 IFT43 Eleanor Williams gene: IFT43 was added
gene: IFT43 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: IFT43 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 IFT27 Eleanor Williams gene: IFT27 was added
gene: IFT27 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: IFT27 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 IFT172 Eleanor Williams gene: IFT172 was added
gene: IFT172 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: IFT172 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 IFT140 Eleanor Williams gene: IFT140 was added
gene: IFT140 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: IFT140 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 IFT122 Eleanor Williams gene: IFT122 was added
gene: IFT122 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: IFT122 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 HYLS1 Eleanor Williams gene: HYLS1 was added
gene: HYLS1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: HYLS1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 HSD17B4 Eleanor Williams gene: HSD17B4 was added
gene: HSD17B4 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: HSD17B4 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 HSD11B2 Eleanor Williams gene: HSD11B2 was added
gene: HSD11B2 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_AldoHypertension v38.1.0,Expert Review Green
Mode of inheritance for gene: HSD11B2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 HPSE2 Eleanor Williams gene: HPSE2 was added
gene: HPSE2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: HPSE2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 HPRT1 Eleanor Williams gene: HPRT1 was added
gene: HPRT1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: HPRT1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 HOXA13 Eleanor Williams gene: HOXA13 was added
gene: HOXA13 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: HOXA13 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 HOGA1 Eleanor Williams gene: HOGA1 was added
gene: HOGA1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: HOGA1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 HNF4A Eleanor Williams gene: HNF4A was added
gene: HNF4A was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_Tubulopathies v38.1.0,Expert Review Green
Mode of inheritance for gene: HNF4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNF4A were set to 24285859; 31875549; 28458902; 30005691; 22802087
Phenotypes for gene: HNF4A were set to Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young, OMIM #616026; MODY, type I, OMIM # 125850
Kidneyome_SuperPanel_VCGS v0.0 HNF1B Eleanor Williams gene: HNF1B was added
gene: HNF1B was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: HNF1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNF1B were set to 27234911
Phenotypes for gene: HNF1B were set to Renal cysts and diabetes syndrome, MIM#137920
Kidneyome_SuperPanel_VCGS v0.0 HAAO Eleanor Williams gene: HAAO was added
gene: HAAO was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: HAAO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HAAO were set to 28792876
Phenotypes for gene: HAAO were set to Vertebral, cardiac, renal, and limb defects syndrome 1, MIM#617660
Kidneyome_SuperPanel_VCGS v0.0 GSN Eleanor Williams gene: GSN was added
gene: GSN was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GSN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GSN were set to 2176164; 29167514; 8684801; PubMed: 8395367; 6975851
Phenotypes for gene: GSN were set to Amyloidosis, Finnish type, MIM#105200
Kidneyome_SuperPanel_VCGS v0.0 GRIP1 Eleanor Williams gene: GRIP1 was added
gene: GRIP1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: GRIP1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 GRHPR Eleanor Williams gene: GRHPR was added
gene: GRHPR was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: GRHPR was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 GREB1L Eleanor Williams gene: GREB1L was added
gene: GREB1L was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: GREB1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GREB1L were set to 29100091
Phenotypes for gene: GREB1L were set to Renal hypodysplasia/aplasia 3, OMIM# 617805
Kidneyome_SuperPanel_VCGS v0.0 GPC3 Eleanor Williams gene: GPC3 was added
gene: GPC3 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: GPC3 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 GNA11 Eleanor Williams gene: GNA11 was added
gene: GNA11 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CalcPhos v38.1.0,Expert Review Green
Mode of inheritance for gene: GNA11 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 GLI3 Eleanor Williams gene: GLI3 was added
gene: GLI3 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: GLI3 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 GATM Eleanor Williams gene: GATM was added
gene: GATM was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_Tubulopathies v38.1.0,Expert Review Green
Mode of inheritance for gene: GATM was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 GATA3 Eleanor Williams gene: GATA3 was added
gene: GATA3 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: GATA3 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 GANAB Eleanor Williams gene: GANAB was added
gene: GANAB was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Cystic v38.1.0
Mode of inheritance for gene: GANAB was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 GALNT3 Eleanor Williams gene: GALNT3 was added
gene: GALNT3 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CalcPhos v38.1.0,Expert Review Green
Mode of inheritance for gene: GALNT3 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 FXYD2 Eleanor Williams gene: FXYD2 was added
gene: FXYD2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Magnesium v38.1.0
Mode of inheritance for gene: FXYD2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 FREM2 Eleanor Williams gene: FREM2 was added
gene: FREM2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: FREM2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 FREM1 Eleanor Williams gene: FREM1 was added
gene: FREM1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: FREM1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 FRAS1 Eleanor Williams gene: FRAS1 was added
gene: FRAS1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: FRAS1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 FGF23 Eleanor Williams gene: FGF23 was added
gene: FGF23 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CalcPhos v38.1.0,Expert Review Green
Mode of inheritance for gene: FGF23 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 FGA Eleanor Williams gene: FGA was added
gene: FGA was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: FGA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGA were set to 12050338; 8639778; PubMed: 8097946
Phenotypes for gene: FGA were set to Amyloidosis, familial visceral, MIM#105200
Kidneyome_SuperPanel_VCGS v0.0 FAT1 Eleanor Williams gene: FAT1 was added
gene: FAT1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: FAT1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 FAN1 Eleanor Williams gene: FAN1 was added
gene: FAN1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: FAN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAN1 were set to 7847351; 8546134; PubMed: 22772369; 16678356
Phenotypes for gene: FAN1 were set to Interstitial nephritis, karyomegalic
Kidneyome_SuperPanel_VCGS v0.0 FAM58A Eleanor Williams gene: FAM58A was added
gene: FAM58A was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: FAM58A was set to Other
Publications for gene: FAM58A were set to 18297069; 28225384
Phenotypes for gene: FAM58A were set to STAR syndrome, MIM# 300707
Kidneyome_SuperPanel_VCGS v0.0 FAM20A Eleanor Williams gene: FAM20A was added
gene: FAM20A was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: FAM20A was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 FAM111A Eleanor Williams gene: FAM111A was added
gene: FAM111A was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Magnesium v38.1.0
Mode of inheritance for gene: FAM111A was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 FAH Eleanor Williams gene: FAH was added
gene: FAH was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: FAH was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 EYA1 Eleanor Williams gene: EYA1 was added
gene: EYA1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: EYA1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 EXOC3L2 Eleanor Williams gene: EXOC3L2 was added
gene: EXOC3L2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Literature
Mode of inheritance for gene: EXOC3L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC3L2 were set to 28749478; 30327448; 27894351
Phenotypes for gene: EXOC3L2 were set to bone marrow failure; Dandy-Walker malformation; renal dysplasia
Kidneyome_SuperPanel_VCGS v0.0 ENPP1 Eleanor Williams gene: ENPP1 was added
gene: ENPP1 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CalcPhos v38.1.0,Expert Review Green
Mode of inheritance for gene: ENPP1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 EMP2 Eleanor Williams gene: EMP2 was added
gene: EMP2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: EMP2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 EGFR Eleanor Williams gene: EGFR was added
gene: EGFR was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Magnesium v38.1.0
Mode of inheritance for gene: EGFR was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 EGF Eleanor Williams gene: EGF was added
gene: EGF was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Magnesium v38.1.0
Mode of inheritance for gene: EGF was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 DZIP1L Eleanor Williams gene: DZIP1L was added
gene: DZIP1L was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: DZIP1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DZIP1L were set to 28530676
Phenotypes for gene: DZIP1L were set to Polycystic kidney disease 5, MIM#617610
Kidneyome_SuperPanel_VCGS v0.0 DYNC2H1 Eleanor Williams gene: DYNC2H1 was added
gene: DYNC2H1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: DYNC2H1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 DSTYK Eleanor Williams gene: DSTYK was added
gene: DSTYK was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: DSTYK was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 DNAJB11 Eleanor Williams gene: DNAJB11 was added
gene: DNAJB11 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: DNAJB11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNAJB11 were set to 29706351; 29777155
Phenotypes for gene: DNAJB11 were set to Polycystic kidney disease 6 with or without polycystic liver disease, MIM#618061
Kidneyome_SuperPanel_VCGS v0.0 DMP1 Eleanor Williams gene: DMP1 was added
gene: DMP1 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CalcPhos v38.1.0,Expert Review Green
Mode of inheritance for gene: DMP1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 DLC1 Eleanor Williams gene: DLC1 was added
gene: DLC1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: DLC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLC1 were set to 29773874
Phenotypes for gene: DLC1 were set to Neprhotic syndrome
Kidneyome_SuperPanel_VCGS v0.0 DHCR7 Eleanor Williams gene: DHCR7 was added
gene: DHCR7 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHCR7 were set to 10069707; 9678700; 23059950; 3812577
Phenotypes for gene: DHCR7 were set to OMIM #270400; Smith-Lemli-Opitz syndrome
Kidneyome_SuperPanel_VCGS v0.0 DGKE Eleanor Williams gene: DGKE was added
gene: DGKE was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: DGKE was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 DDX59 Eleanor Williams gene: DDX59 was added
gene: DDX59 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: DDX59 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CYP2R1 Eleanor Williams gene: CYP2R1 was added
gene: CYP2R1 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CalcPhos v38.1.0,Expert Review Green
Mode of inheritance for gene: CYP2R1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CYP27B1 Eleanor Williams gene: CYP27B1 was added
gene: CYP27B1 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CalcPhos v38.1.0,Expert Review Green
Mode of inheritance for gene: CYP27B1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CYP24A1 Eleanor Williams gene: CYP24A1 was added
gene: CYP24A1 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CalcPhos v38.1.0,Expert Review Green
Mode of inheritance for gene: CYP24A1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CYP21A2 Eleanor Williams gene: CYP21A2 was added
gene: CYP21A2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: CYP21A2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CYP17A1 Eleanor Williams gene: CYP17A1 was added
gene: CYP17A1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: CYP17A1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CYP11B2 Eleanor Williams gene: CYP11B2 was added
gene: CYP11B2 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_AldoHypertension v38.1.0,Expert Review Green
Mode of inheritance for gene: CYP11B2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CYP11B1 Eleanor Williams gene: CYP11B1 was added
gene: CYP11B1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: CYP11B1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CUL3 Eleanor Williams gene: CUL3 was added
gene: CUL3 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_AldoHypertension v38.1.0,Expert Review Green
Mode of inheritance for gene: CUL3 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CUBN Eleanor Williams gene: CUBN was added
gene: CUBN was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CUBN was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CTU2 Eleanor Williams gene: CTU2 was added
gene: CTU2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green,Expert list
Mode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTU2 were set to 27480277; 26633546
Phenotypes for gene: CTU2 were set to Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome
Kidneyome_SuperPanel_VCGS v0.0 CTNS Eleanor Williams gene: CTNS was added
gene: CTNS was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: CTNS was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CSPP1 Eleanor Williams gene: CSPP1 was added
gene: CSPP1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: CSPP1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CPT2 Eleanor Williams gene: CPT2 was added
gene: CPT2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: CPT2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 COQ8B Eleanor Williams gene: COQ8B was added
gene: COQ8B was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: COQ8B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ8B were set to 24270420
Phenotypes for gene: COQ8B were set to Nephrotic syndrome, type 9, MIM#615573
Kidneyome_SuperPanel_VCGS v0.0 COQ6 Eleanor Williams gene: COQ6 was added
gene: COQ6 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: COQ6 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 COQ2 Eleanor Williams gene: COQ2 was added
gene: COQ2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: COQ2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 COL4A5 Eleanor Williams gene: COL4A5 was added
gene: COL4A5 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: COL4A5 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 COL4A4 Eleanor Williams gene: COL4A4 was added
gene: COL4A4 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: COL4A4 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 COL4A3 Eleanor Williams gene: COL4A3 was added
gene: COL4A3 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: COL4A3 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 COL4A1 Eleanor Williams gene: COL4A1 was added
gene: COL4A1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: COL4A1 were set to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, MIM#611773
Kidneyome_SuperPanel_VCGS v0.0 CNNM2 Eleanor Williams gene: CNNM2 was added
gene: CNNM2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Magnesium v38.1.0
Mode of inheritance for gene: CNNM2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CLDN19 Eleanor Williams gene: CLDN19 was added
gene: CLDN19 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Magnesium v38.1.0
Mode of inheritance for gene: CLDN19 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CLDN16 Eleanor Williams gene: CLDN16 was added
gene: CLDN16 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Magnesium v38.1.0
Mode of inheritance for gene: CLDN16 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CLDN10 Eleanor Williams gene: CLDN10 was added
gene: CLDN10 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_Magnesium v38.1.0
Mode of inheritance for gene: CLDN10 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CLCNKB Eleanor Williams gene: CLCNKB was added
gene: CLCNKB was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CLCNKB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CLCNKB were set to OMIM #607364; Bartter syndrome, type 3
Kidneyome_SuperPanel_VCGS v0.0 CLCNKA Eleanor Williams gene: CLCNKA was added
gene: CLCNKA was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CLCNKA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CLCNKA were set to OMIM #613090; Bartter syndrome, type 4b, digenic
Kidneyome_SuperPanel_VCGS v0.0 CLCN5 Eleanor Williams gene: CLCN5 was added
gene: CLCN5 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CLCN5 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: CLCN5 were set to Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, MIM#308990; Dent disease, MIM#300009
Kidneyome_SuperPanel_VCGS v0.0 CLCN2 Eleanor Williams gene: CLCN2 was added
gene: CLCN2 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_AldoHypertension v38.1.0,Expert Review Green
Mode of inheritance for gene: CLCN2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CHRNA3 Eleanor Williams gene: CHRNA3 was added
gene: CHRNA3 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CHRNA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHRNA3 were set to 31708116
Phenotypes for gene: CHRNA3 were set to dysautonomia; CAKUT
Kidneyome_SuperPanel_VCGS v0.0 CHD7 Eleanor Williams gene: CHD7 was added
gene: CHD7 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CHD7 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CHD1L Eleanor Williams gene: CHD1L was added
gene: CHD1L was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CHD1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD1L were set to 22146311; 24429398
Phenotypes for gene: CHD1L were set to CAKUT
Kidneyome_SuperPanel_VCGS v0.0 CFI Eleanor Williams gene: CFI was added
gene: CFI was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CFI was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CFHR5 Eleanor Williams gene: CFHR5 was added
gene: CFHR5 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CFHR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CFHR5 were set to 30844074; 27490940; 21566112; 24067434; 24334459; 30197990; 20800271
Phenotypes for gene: CFHR5 were set to Nephropathy due to CFHR5 deficiency, MIM#614809
Kidneyome_SuperPanel_VCGS v0.0 CFHR3 Eleanor Williams gene: CFHR3 was added
gene: CFHR3 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CFHR3 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CFHR2 Eleanor Williams gene: CFHR2 was added
gene: CFHR2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CFHR2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CFHR2 were set to 20800271; 23728178; 24334459
Phenotypes for gene: CFHR2 were set to C3 glomerulopathy; IC-MPGN; Immune complex MPGN; C3G
Kidneyome_SuperPanel_VCGS v0.0 CFHR1 Eleanor Williams gene: CFHR1 was added
gene: CFHR1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CFHR1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CFH Eleanor Williams gene: CFH was added
gene: CFH was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CFH was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: CFH were set to Complement factor H deficiency, MIM#609814
Kidneyome_SuperPanel_VCGS v0.0 CFB Eleanor Williams gene: CFB was added
gene: CFB was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CFB was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CEP83 Eleanor Williams gene: CEP83 was added
gene: CEP83 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: CEP83 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CEP55 Eleanor Williams gene: CEP55 was added
gene: CEP55 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert Review
Mode of inheritance for gene: CEP55 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP55 were set to 30622327; 28295209; 28264986
Phenotypes for gene: CEP55 were set to Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM#236500
Kidneyome_SuperPanel_VCGS v0.0 CEP41 Eleanor Williams gene: CEP41 was added
gene: CEP41 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: CEP41 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CEP290 Eleanor Williams gene: CEP290 was added
gene: CEP290 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: CEP290 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CEP164 Eleanor Williams gene: CEP164 was added
gene: CEP164 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: CEP164 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CEP104 Eleanor Williams gene: CEP104 was added
gene: CEP104 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: CEP104 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CENPF Eleanor Williams gene: CENPF was added
gene: CENPF was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CENPF was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CENPF were set to Stromme syndrome, MIM#243605
Kidneyome_SuperPanel_VCGS v0.0 CDC73 Eleanor Williams gene: CDC73 was added
gene: CDC73 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CalcPhos v38.1.0,Expert Review Green
Mode of inheritance for gene: CDC73 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CD46 Eleanor Williams gene: CD46 was added
gene: CD46 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CD46 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CD151 Eleanor Williams gene: CD151 was added
gene: CD151 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CD151 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD151 were set to 29138120; 15265795
Phenotypes for gene: CD151 were set to Nephropathy with pretibial epidermolysis bullosa and deafness, MIM#609057
Kidneyome_SuperPanel_VCGS v0.0 CC2D2A Eleanor Williams gene: CC2D2A was added
gene: CC2D2A was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: CC2D2A was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CASR Eleanor Williams gene: CASR was added
gene: CASR was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CASR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CASR were set to 27234911; 8813042
Phenotypes for gene: CASR were set to Hypocalcemia, autosomal dominant, with Bartter syndrome, MIM#601198
Kidneyome_SuperPanel_VCGS v0.0 CACNA1H Eleanor Williams gene: CACNA1H was added
gene: CACNA1H was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_AldoHypertension v38.1.0,Expert Review Green
Mode of inheritance for gene: CACNA1H was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CACNA1D Eleanor Williams gene: CACNA1D was added
gene: CACNA1D was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_AldoHypertension v38.1.0,Expert Review Green
Mode of inheritance for gene: CACNA1D was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CA2 Eleanor Williams gene: CA2 was added
gene: CA2 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_Tubulopathies v38.1.0,Expert Review Green
Mode of inheritance for gene: CA2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 C3 Eleanor Williams gene: C3 was added
gene: C3 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: C3 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 BSND Eleanor Williams gene: BSND was added
gene: BSND was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: BSND was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BSND were set to 11687798; 27234911
Phenotypes for gene: BSND were set to Bartter syndrome, Type 4a, MIM#602522
Kidneyome_SuperPanel_VCGS v0.0 BNC2 Eleanor Williams gene: BNC2 was added
gene: BNC2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Literature
Mode of inheritance for gene: BNC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BNC2 were set to PMID: 31656805, 31051115
Phenotypes for gene: BNC2 were set to Lower urinary tract obstruction, congenital; OMIM #618612
Kidneyome_SuperPanel_VCGS v0.0 BMP4 Eleanor Williams gene: BMP4 was added
gene: BMP4 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: BMP4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP4 were set to 24131739; 23641053; 30568244; 19685083
Phenotypes for gene: BMP4 were set to CAKUT
Kidneyome_SuperPanel_VCGS v0.0 BCS1L Eleanor Williams gene: BCS1L was added
gene: BCS1L was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_MetabolicRenal v38.1.0
Mode of inheritance for gene: BCS1L was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 BBS9 Eleanor Williams gene: BBS9 was added
gene: BBS9 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: BBS9 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 BBS7 Eleanor Williams gene: BBS7 was added
gene: BBS7 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: BBS7 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 BBS5 Eleanor Williams gene: BBS5 was added
gene: BBS5 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: BBS5 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 BBS4 Eleanor Williams gene: BBS4 was added
gene: BBS4 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: BBS4 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 BBS2 Eleanor Williams gene: BBS2 was added
gene: BBS2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: BBS2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 BBS12 Eleanor Williams gene: BBS12 was added
gene: BBS12 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: BBS12 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 BBS10 Eleanor Williams gene: BBS10 was added
gene: BBS10 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: BBS10 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 BBS1 Eleanor Williams gene: BBS1 was added
gene: BBS1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: BBS1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 B9D2 Eleanor Williams gene: B9D2 was added
gene: B9D2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: B9D2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 AVPR2 Eleanor Williams gene: AVPR2 was added
gene: AVPR2 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_Tubulopathies v38.1.0,Expert Review Green
Mode of inheritance for gene: AVPR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: AVPR2 were set to 9127330; 15872203
Phenotypes for gene: AVPR2 were set to Diabetes insipidus, nephrogenic 304800; Nephrogenic syndrome of inappropriate antidiuresis 300539
Kidneyome_SuperPanel_VCGS v0.0 ATP6V1B1 Eleanor Williams gene: ATP6V1B1 was added
gene: ATP6V1B1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ATP6V1B1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 ATP6V0A4 Eleanor Williams gene: ATP6V0A4 was added
gene: ATP6V0A4 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ATP6V0A4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V0A4 were set to 10973252; 12414817
Phenotypes for gene: ATP6V0A4 were set to Renal tubular acidosis, distal, autosomal recessive, MIM#602722
Kidneyome_SuperPanel_VCGS v0.0 ATP1A1 Eleanor Williams gene: ATP1A1 was added
gene: ATP1A1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ATP1A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP1A1 were set to PMID: 30388404
Phenotypes for gene: ATP1A1 were set to Charcot-Marie-Tooth disease, axonal, type 2DD, OMIM #618036; Hypomagnesemia, seizures, and mental retardation 2, OMIM #618314
Kidneyome_SuperPanel_VCGS v0.0 ARL6 Eleanor Williams gene: ARL6 was added
gene: ARL6 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: ARL6 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 ARL13B Eleanor Williams gene: ARL13B was added
gene: ARL13B was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: ARL13B was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 ARHGDIA Eleanor Williams gene: ARHGDIA was added
gene: ARHGDIA was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ARHGDIA was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 AQP2 Eleanor Williams gene: AQP2 was added
gene: AQP2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: AQP2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: AQP2 were set to 7537761; 11536078
Phenotypes for gene: AQP2 were set to Diabetes insipidus, nephrogenic, MIM#125800
Kidneyome_SuperPanel_VCGS v0.0 APRT Eleanor Williams gene: APRT was added
gene: APRT was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: APRT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APRT were set to 7915931; PubMed: 3680503; 2227934; 1353080
Phenotypes for gene: APRT were set to Adenine phosphoribosyltransferase deficiency, MIM#614723
Kidneyome_SuperPanel_VCGS v0.0 APOE Eleanor Williams gene: APOE was added
gene: APOE was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: APOE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOE were set to 24348079; 28966924; 18077821
Phenotypes for gene: APOE were set to Lipoprotein glomerulopathy, MIM#611771
Kidneyome_SuperPanel_VCGS v0.0 APOA1 Eleanor Williams gene: APOA1 was added
gene: APOA1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: APOA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOA1 were set to 27240838; 29968409; PubMed:31482740
Phenotypes for gene: APOA1 were set to Amyloidosis, 3 or more types, MIM#105200
Kidneyome_SuperPanel_VCGS v0.0 AP2S1 Eleanor Williams gene: AP2S1 was added
gene: AP2S1 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CalcPhos v38.1.0,Expert Review Green
Mode of inheritance for gene: AP2S1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 ANOS1 Eleanor Williams gene: ANOS1 was added
gene: ANOS1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ANOS1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 ANKS6 Eleanor Williams gene: ANKS6 was added
gene: ANKS6 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: ANKS6 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 AMN Eleanor Williams gene: AMN was added
gene: AMN was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: AMN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMN were set to 15024727
Phenotypes for gene: AMN were set to Megaloblastic anemia-1, Norwegian type, MIM#261100
Kidneyome_SuperPanel_VCGS v0.0 ALMS1 Eleanor Williams gene: ALMS1 was added
gene: ALMS1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ALMS1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 AHI1 Eleanor Williams gene: AHI1 was added
gene: AHI1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: AHI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AHI1 were set to 29146704; PubMed: 15322546; 16453322; 15467982
Phenotypes for gene: AHI1 were set to Joubert syndrome 3, MIM#608629
Kidneyome_SuperPanel_VCGS v0.0 AGXT Eleanor Williams gene: AGXT was added
gene: AGXT was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: AGXT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGXT were set to 10453743; PubMed: 1703535; 19479957
Phenotypes for gene: AGXT were set to Hyperoxaluria, primary, type 1, MIM#259900
Kidneyome_SuperPanel_VCGS v0.0 AGTR1 Eleanor Williams gene: AGTR1 was added
gene: AGTR1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: AGTR1 was set to BIALLELIC, autosomal or pseudoautosomal
Kidneyome_SuperPanel_VCGS v0.0 AGT Eleanor Williams gene: AGT was added
gene: AGT was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: AGT was set to BIALLELIC, autosomal or pseudoautosomal
Kidneyome_SuperPanel_VCGS v0.0 ADAMTS9 Eleanor Williams gene: ADAMTS9 was added
gene: ADAMTS9 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ADAMTS9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS9 were set to PMID:30609407
Phenotypes for gene: ADAMTS9 were set to Nephronophthisis-Related Ciliopathy
Kidneyome_SuperPanel_VCGS v0.0 ACTN4 Eleanor Williams gene: ACTN4 was added
gene: ACTN4 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ACTN4 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 ACE Eleanor Williams gene: ACE was added
gene: ACE was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ACE was set to BIALLELIC, autosomal or pseudoautosomal
Kidneyome_SuperPanel_VCGS v0.0 FN1 Eleanor Williams gene: FN1 was added
gene: FN1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: FN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FN1 were set to 18268355
Phenotypes for gene: FN1 were set to Glomerulopathy with fibronectin deposits 2, MIM#601894
Kidneyome_SuperPanel_VCGS v0.0 GLA Eleanor Williams gene: GLA was added
gene: GLA was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GLA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GLA were set to 18033242
Phenotypes for gene: GLA were set to Fairy disease, MIM#301500
Kidneyome_SuperPanel_VCGS v0.0 LCAT Eleanor Williams gene: LCAT was added
gene: LCAT was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: LCAT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LCAT were set to Norum disease, MIM#245900
Kidneyome_SuperPanel_VCGS v0.0 SLC5A2 Eleanor Williams gene: SLC5A2 was added
gene: SLC5A2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SLC5A2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: SLC5A2 were set to Renal glucosuria, MIM#233100
Kidneyome_SuperPanel_VCGS v0.0 CRB2 Eleanor Williams gene: CRB2 was added
gene: CRB2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CRB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRB2 were set to 25557780
Phenotypes for gene: CRB2 were set to Ventriculomegaly with cystic kidney disease, MIM#219730
Kidneyome_SuperPanel_VCGS v0.0 VHL Eleanor Williams gene: VHL was added
gene: VHL was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: VHL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: VHL were set to von Hippel-Lindau syndrome, MIM#193300
Kidneyome_SuperPanel_VCGS v0.0 ACTG2 Eleanor Williams gene: ACTG2 was added
gene: ACTG2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ACTG2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ACTG2 were set to Visceral myopathy, MIM#155310
Kidneyome_SuperPanel_VCGS v0.0 THBD Eleanor Williams gene: THBD was added
gene: THBD was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Amber
Mode of inheritance for gene: THBD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THBD were set to 19625716
Phenotypes for gene: THBD were set to OMIM #612926; {Hemolytic uremic syndrome, atypical, susceptibility to, 6}
Kidneyome_SuperPanel_VCGS v0.0 SRGAP1 Eleanor Williams gene: SRGAP1 was added
gene: SRGAP1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Amber
Mode of inheritance for gene: SRGAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRGAP1 were set to 26026792
Phenotypes for gene: SRGAP1 were set to CAKUT
Kidneyome_SuperPanel_VCGS v0.0 SOX11 Eleanor Williams gene: SOX11 was added
gene: SOX11 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: SOX11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX11 were set to 29459093; 24886874
Phenotypes for gene: SOX11 were set to Congenital abnormalities of the kidneys and urinary tract
Kidneyome_SuperPanel_VCGS v0.0 LAMA5 Eleanor Williams gene: LAMA5 was added
gene: LAMA5 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Amber
Mode of inheritance for gene: LAMA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMA5 were set to 29534211
Phenotypes for gene: LAMA5 were set to Nephrotic syndrome
Kidneyome_SuperPanel_VCGS v0.0 IFT74 Eleanor Williams gene: IFT74 was added
gene: IFT74 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CilioNephronop v38.1.0,Expert Review Amber
Mode of inheritance for gene: IFT74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT74 were set to 27486776
Phenotypes for gene: IFT74 were set to Bardet-Biedl syndrome 20 617119
Kidneyome_SuperPanel_VCGS v0.0 GLIS2 Eleanor Williams gene: GLIS2 was added
gene: GLIS2 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CilioNephronop v38.1.0,Expert Review Amber
Mode of inheritance for gene: GLIS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLIS2 were set to 23559409; 17618285
Phenotypes for gene: GLIS2 were set to Nephronophthisis 7, OMIM#611498
Kidneyome_SuperPanel_VCGS v0.0 FGF20 Eleanor Williams gene: FGF20 was added
gene: FGF20 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: FGF20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FGF20 were set to 22698282
Phenotypes for gene: FGF20 were set to Renal hypodysplasia/aplasia 2, MIM#615721
Kidneyome_SuperPanel_VCGS v0.0 DCDC2 Eleanor Williams gene: DCDC2 was added
gene: DCDC2 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CilioNephronop v38.1.0,Expert Review Amber
Mode of inheritance for gene: DCDC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DCDC2 were set to 25557784
Phenotypes for gene: DCDC2 were set to Nephronophthisis 19, MIM# 616217
Kidneyome_SuperPanel_VCGS v0.0 COQ7 Eleanor Williams gene: COQ7 was added
gene: COQ7 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: COQ7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ7 were set to 28409910; 31240163; 26084283
Phenotypes for gene: COQ7 were set to Coenzyme Q10 deficiency, primary, 8, MIM#616733
Kidneyome_SuperPanel_VCGS v0.0 CEP120 Eleanor Williams gene: CEP120 was added
gene: CEP120 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CilioNephronop v38.1.0,Expert Review Amber
Mode of inheritance for gene: CEP120 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CEP120 were set to Short-rib thoracic dysplasia 13 with or without polydactyly, MIM# 616300
Kidneyome_SuperPanel_VCGS v0.0 CD2AP Eleanor Williams gene: CD2AP was added
gene: CD2AP was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Amber
Mode of inheritance for gene: CD2AP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD2AP were set to 17713465; 30612599
Phenotypes for gene: CD2AP were set to Glomerulosclerosis, focal segmental, 3, OMIM #607832
Kidneyome_SuperPanel_VCGS v0.0 BBIP1 Eleanor Williams gene: BBIP1 was added
gene: BBIP1 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_CilioNephronop v38.1.0,Expert Review Amber
Mode of inheritance for gene: BBIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBIP1 were set to 24026985
Phenotypes for gene: BBIP1 were set to Bardet-Biedl syndrome 18, MIM#615995
Kidneyome_SuperPanel_VCGS v0.0 ANLN Eleanor Williams gene: ANLN was added
gene: ANLN was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Amber
Mode of inheritance for gene: ANLN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANLN were set to 30002222; 24676636
Phenotypes for gene: ANLN were set to Focal segmental glomerulosclerosis 8, OMIM #616032
Kidneyome_SuperPanel_VCGS v0.0 ADCY10 Eleanor Williams gene: ADCY10 was added
gene: ADCY10 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: ADCY10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADCY10 were set to 11932268
Phenotypes for gene: ADCY10 were set to Hypercalciuria, absorptive, susceptibility to, MIM#143870
Kidneyome_SuperPanel_VCGS v0.0 ADAMTS13 Eleanor Williams gene: ADAMTS13 was added
gene: ADAMTS13 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Amber
Mode of inheritance for gene: ADAMTS13 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ADAMTS13 were set to Thrombotic thrombocytopenic purpura, familial, OMIM #274150
Kidneyome_SuperPanel_VCGS v0.0 ZNF423 Eleanor Williams gene: ZNF423 was added
gene: ZNF423 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: ZNF423 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF423 were set to 22863007
Phenotypes for gene: ZNF423 were set to Joubert syndrome 19, OMIM# 614844
Kidneyome_SuperPanel_VCGS v0.0 XPO5 Eleanor Williams gene: XPO5 was added
gene: XPO5 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,Expert list
Mode of inheritance for gene: XPO5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPO5 were set to 26878725
Phenotypes for gene: XPO5 were set to Nephrotic syndrome
Kidneyome_SuperPanel_VCGS v0.0 XPNPEP3 Eleanor Williams gene: XPNPEP3 was added
gene: XPNPEP3 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: XPNPEP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPNPEP3 were set to 20179356
Phenotypes for gene: XPNPEP3 were set to Nephronophthisis-like nephropathy 1, OMIM #613159
Kidneyome_SuperPanel_VCGS v0.0 WDR34 Eleanor Williams gene: WDR34 was added
gene: WDR34 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: WDR34 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR34 were set to Short-rib thoracic dysplasia 11 with or without polydactyly, OMIM #615633
Kidneyome_SuperPanel_VCGS v0.0 VTN Eleanor Williams gene: VTN was added
gene: VTN was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: VTN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VTN were set to 30377230
Phenotypes for gene: VTN were set to Atypical haemolytic uraemic syndrome
Kidneyome_SuperPanel_VCGS v0.0 UPK3A Eleanor Williams gene: UPK3A was added
gene: UPK3A was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: UPK3A was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 TRIM32 Eleanor Williams gene: TRIM32 was added
gene: TRIM32 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: TRIM32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM32 were set to 16606853
Phenotypes for gene: TRIM32 were set to Bardet-Biedl syndrome 11, MIM# 615988
Kidneyome_SuperPanel_VCGS v0.0 TNXB Eleanor Williams gene: TNXB was added
gene: TNXB was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: TNXB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNXB were set to 23620400
Phenotypes for gene: TNXB were set to Vesicoureteral reflux 8, MIM# 615963
Kidneyome_SuperPanel_VCGS v0.0 SOX17 Eleanor Williams gene: SOX17 was added
gene: SOX17 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: SOX17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX17 were set to 20960469
Phenotypes for gene: SOX17 were set to OMIM #613674; Vesicoureteral reflux 3
Kidneyome_SuperPanel_VCGS v0.0 SLC41A1 Eleanor Williams gene: SLC41A1 was added
gene: SLC41A1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: SLC41A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC41A1 were set to 23661805
Phenotypes for gene: SLC41A1 were set to Nephronophthisis; no OMIM number
Kidneyome_SuperPanel_VCGS v0.0 SIX2 Eleanor Williams gene: SIX2 was added
gene: SIX2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: SIX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SIX2 were set to 24429398
Phenotypes for gene: SIX2 were set to CAKUT
Kidneyome_SuperPanel_VCGS v0.0 SEMA3A Eleanor Williams gene: SEMA3A was added
gene: SEMA3A was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: SEMA3A was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 SEC63 Eleanor Williams gene: SEC63 was added
gene: SEC63 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,Expert list
Mode of inheritance for gene: SEC63 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEC63 were set to 15133510
Phenotypes for gene: SEC63 were set to Polycystic liver disease 2, MIM#617004
Kidneyome_SuperPanel_VCGS v0.0 SCLT1 Eleanor Williams gene: SCLT1 was added
gene: SCLT1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,Expert list
Mode of inheritance for gene: SCLT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCLT1 were set to 24285566; 28486600; 30425282; 30237576; 28005958
Phenotypes for gene: SCLT1 were set to Senior-Loken syndrome; Orofaciodigital syndrome type IX
Kidneyome_SuperPanel_VCGS v0.0 POC1B Eleanor Williams gene: POC1B was added
gene: POC1B was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: POC1B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POC1B were set to Cone-rod dystrophy 20, MIM#615973
Kidneyome_SuperPanel_VCGS v0.0 PDE6D Eleanor Williams gene: PDE6D was added
gene: PDE6D was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: PDE6D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE6D were set to 24166846
Phenotypes for gene: PDE6D were set to Joubert syndrome 22, OMIM #615665
Kidneyome_SuperPanel_VCGS v0.0 NUP37 Eleanor Williams gene: NUP37 was added
gene: NUP37 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,Expert list
Mode of inheritance for gene: NUP37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP37 were set to 30179222
Phenotypes for gene: NUP37 were set to Nephrotic syndrome
Kidneyome_SuperPanel_VCGS v0.0 NUP205 Eleanor Williams gene: NUP205 was added
gene: NUP205 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,Expert list
Mode of inheritance for gene: NUP205 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP205 were set to 26878725
Phenotypes for gene: NUP205 were set to Nephrotic syndrome, type 13, MIM#616893
Kidneyome_SuperPanel_VCGS v0.0 NUP160 Eleanor Williams gene: NUP160 was added
gene: NUP160 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NUP160 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP160 were set to 30179222
Phenotypes for gene: NUP160 were set to Nephrotic syndrome, type 19, MIM#618178
Kidneyome_SuperPanel_VCGS v0.0 LMNA Eleanor Williams gene: LMNA was added
gene: LMNA was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: LMNA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LMNA were set to 24080738
Phenotypes for gene: LMNA were set to FSGS; Familial partial lipodystrophy
Kidneyome_SuperPanel_VCGS v0.0 KANK4 Eleanor Williams gene: KANK4 was added
gene: KANK4 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,Expert list
Mode of inheritance for gene: KANK4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KANK4 were set to 25961457
Kidneyome_SuperPanel_VCGS v0.0 KANK1 Eleanor Williams gene: KANK1 was added
gene: KANK1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,Expert list
Mode of inheritance for gene: KANK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KANK1 were set to 25961457
Phenotypes for gene: KANK1 were set to Nephrotic syndrome
Kidneyome_SuperPanel_VCGS v0.0 ITGB4 Eleanor Williams gene: ITGB4 was added
gene: ITGB4 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: ITGB4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITGB4 were set to 10873890
Phenotypes for gene: ITGB4 were set to Epidermolysis bullosa, junctional, with pyloric atresia, MIM#226730
Kidneyome_SuperPanel_VCGS v0.0 IFT81 Eleanor Williams gene: IFT81 was added
gene: IFT81 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: IFT81 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT81 were set to 26275418
Phenotypes for gene: IFT81 were set to Short-rib thoracic dysplasia 19 with or without polydactyly; OMIM #617895
Kidneyome_SuperPanel_VCGS v0.0 IFT57 Eleanor Williams gene: IFT57 was added
gene: IFT57 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: IFT57 was set to Unknown
Phenotypes for gene: IFT57 were set to Orofaciodigital syndrome XVIII, MIM#617927
Kidneyome_SuperPanel_VCGS v0.0 HOXB6 Eleanor Williams gene: HOXB6 was added
gene: HOXB6 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: HOXB6 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 HOXA4 Eleanor Williams gene: HOXA4 was added
gene: HOXA4 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: HOXA4 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 FOXC2 Eleanor Williams gene: FOXC2 was added
gene: FOXC2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: FOXC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXC2 were set to 15523639
Phenotypes for gene: FOXC2 were set to OMIM #153400; Lymphedema-distichiasis syndrome with renal disease and diabetes mellitus
Kidneyome_SuperPanel_VCGS v0.0 FOXC1 Eleanor Williams gene: FOXC1 was added
gene: FOXC1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: FOXC1 was set to Unknown
Phenotypes for gene: FOXC1 were set to Axenfeld-Rieger syndrome, type 3, MIM#602482
Kidneyome_SuperPanel_VCGS v0.0 FGFR3 Eleanor Williams gene: FGFR3 was added
gene: FGFR3 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,Expert list
Mode of inheritance for gene: FGFR3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FGFR3 were set to LADD syndrome, MIM#149730
Kidneyome_SuperPanel_VCGS v0.0 FGFR2 Eleanor Williams gene: FGFR2 was added
gene: FGFR2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: FGFR2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 FGFR1 Eleanor Williams gene: FGFR1 was added
gene: FGFR1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: FGFR1 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 FGF8 Eleanor Williams gene: FGF8 was added
gene: FGF8 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: FGF8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FGF8 were set to OMIM #612702; Hypogonadotropic hypogonadism 6 with or without anosmia
Kidneyome_SuperPanel_VCGS v0.0 FGF10 Eleanor Williams gene: FGF10 was added
gene: FGF10 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: FGF10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FGF10 were set to OMIM #149730; LADD syndrome
Kidneyome_SuperPanel_VCGS v0.0 EZH2 Eleanor Williams gene: EZH2 was added
gene: EZH2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: EZH2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 EVC2 Eleanor Williams gene: EVC2 was added
gene: EVC2 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: EVC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EVC2 were set to Ellis van Creveld syndrome
Kidneyome_SuperPanel_VCGS v0.0 EVC Eleanor Williams gene: EVC was added
gene: EVC was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: EVC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EVC were set to Ellis-van Creveld syndrome, MIM#225500
Kidneyome_SuperPanel_VCGS v0.0 EHHADH Eleanor Williams gene: EHHADH was added
gene: EHHADH was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_Tubulopathies v38.1.0,Expert Review Red
Mode of inheritance for gene: EHHADH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EHHADH were set to 24401050
Phenotypes for gene: EHHADH were set to OMIM#615605; Fanconi renotubular syndrome 3
Kidneyome_SuperPanel_VCGS v0.0 DACT1 Eleanor Williams gene: DACT1 was added
gene: DACT1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,Expert list
Mode of inheritance for gene: DACT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DACT1 were set to 28054444
Phenotypes for gene: DACT1 were set to Townes-Brocks syndrome 2, MIM#617466
Kidneyome_SuperPanel_VCGS v0.0 COQ9 Eleanor Williams gene: COQ9 was added
gene: COQ9 was added to Kidneyome_SuperPanel_VCGS. Sources: KidGen_Tubulopathies v38.1.0,Expert Review Red
Mode of inheritance for gene: COQ9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ9 were set to 11562630
Phenotypes for gene: COQ9 were set to Coenzyme Q10 deficiency, primary, 5; OMIM #614654
Kidneyome_SuperPanel_VCGS v0.0 COQ8A Eleanor Williams gene: COQ8A was added
gene: COQ8A was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: COQ8A was set to Unknown
Phenotypes for gene: COQ8A were set to Coenzyme Q10 deficiency, primary, 4, MIM#612016
Kidneyome_SuperPanel_VCGS v0.0 COL4A2 Eleanor Williams gene: COL4A2 was added
gene: COL4A2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: COL4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: COL4A2 were set to Brain small vessel disease 2, MIM#614483
Kidneyome_SuperPanel_VCGS v0.0 CDX2 Eleanor Williams gene: CDX2 was added
gene: CDX2 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: CDX2 was set to Unknown
Kidneyome_SuperPanel_VCGS v0.0 CDC5L Eleanor Williams gene: CDC5L was added
gene: CDC5L was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,Expert list
Mode of inheritance for gene: CDC5L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDC5L were set to 24429398
Phenotypes for gene: CDC5L were set to Congenital abnormalities of the kidneys and urinary tract
Kidneyome_SuperPanel_VCGS v0.0 CCDC28B Eleanor Williams gene: CCDC28B was added
gene: CCDC28B was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: CCDC28B was set to Other
Phenotypes for gene: CCDC28B were set to {Bardet-Biedl syndrome 1, modifier of}, MIM#209900
Kidneyome_SuperPanel_VCGS v0.0 CBWD1 Eleanor Williams gene: CBWD1 was added
gene: CBWD1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,Literature
Mode of inheritance for gene: CBWD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CBWD1 were set to 31862704
Phenotypes for gene: CBWD1 were set to CAKUT
Kidneyome_SuperPanel_VCGS v0.0 C5orf42 Eleanor Williams gene: C5orf42 was added
gene: C5orf42 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: C5orf42 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: C5orf42 were set to Orofaciodigital syndrome VI, MIM# 277170; Joubert syndrome 17, MIM#614615
Kidneyome_SuperPanel_VCGS v0.0 C2CD3 Eleanor Williams gene: C2CD3 was added
gene: C2CD3 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: C2CD3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: C2CD3 were set to Orofaciodigital syndrome XIV, MIM# 615948
Kidneyome_SuperPanel_VCGS v0.0 BMP7 Eleanor Williams gene: BMP7 was added
gene: BMP7 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,Expert list
Mode of inheritance for gene: BMP7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP7 were set to 24429398
Phenotypes for gene: BMP7 were set to Congenital abnormalities of the kidneys and urinary tract
Kidneyome_SuperPanel_VCGS v0.0 BICC1 Eleanor Williams gene: BICC1 was added
gene: BICC1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: BICC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BICC1 were set to 21922595
Phenotypes for gene: BICC1 were set to {Renal dysplasia, cystic, susceptibility to}; OMIM #601331
Kidneyome_SuperPanel_VCGS v0.0 B9D1 Eleanor Williams gene: B9D1 was added
gene: B9D1 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: B9D1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: B9D1 were set to Meckel syndrome 9, OMIM #614209; Joubert syndrome 27, OMIM #617120
Kidneyome_SuperPanel_VCGS v0.0 ATXN10 Eleanor Williams gene: ATXN10 was added
gene: ATXN10 was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,KidGen_CilioNephronop v38.1.0
Mode of inheritance for gene: ATXN10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATXN10 were set to 21565611
Phenotypes for gene: ATXN10 were set to Nephronophthisis
Kidneyome_SuperPanel_VCGS v0.0 ARHGAP24 Eleanor Williams gene: ARHGAP24 was added
gene: ARHGAP24 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: ARHGAP24 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARHGAP24 were set to 21911940
Phenotypes for gene: ARHGAP24 were set to FSGS
Kidneyome_SuperPanel_VCGS v0.0 APOL1 Eleanor Williams gene: APOL1 was added
gene: APOL1 was added to Kidneyome_SuperPanel_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Red
Mode of inheritance for gene: APOL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOL1 were set to 24206458; 20635188; 20647424
Phenotypes for gene: APOL1 were set to {Glomerulosclerosis, focal segmental, 4, susceptibility to}, MIM#612551
Kidneyome_SuperPanel_VCGS v0.0 ICK Eleanor Williams gene: ICK was added
gene: ICK was added to Kidneyome_SuperPanel_VCGS. Sources: Expert Review Red,Expert list
Mode of inheritance for gene: ICK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ICK were set to 19185282; 27069622
Phenotypes for gene: ICK were set to Endocrine-cerebroosteodysplasia, MIM#612651
Kidneyome_SuperPanel_VCGS v0.0 Eleanor Williams Added panel Kidneyome_SuperPanel_VCGS
Hearing loss v2.4 HOMER2 Eleanor Williams changed review comment from: Provisional association with ?Deafness, autosomal dominant 68 #616707 (AD) in OMIM.

2 families reported:
PMID: 25816005 - Azaiez et al 2015 - one family with post-lingual progressive autosomal dominant non-syndromic hearing loss and a missense variant p.Arg185Pro in HOMER2
PMID: 30047143 - Lue et al 2018 - Chinese family with autosomal dominant, non-syndromic hearing loss and a pathogenic variant c.840_841insC in HOMER2 that leads to a premature stop codon).

Azaiez et al 2015 also report mouse mutants homozygous for the targeted deletion of Homer2 present with early-onset rapidly progressive hearing loss.; to: Provisional association with ?Deafness, autosomal dominant 68 #616707 (AD) in OMIM.

2 families reported:
PMID: 25816005 - Azaiez et al 2015 - one family with post-lingual progressive autosomal dominant non-syndromic hearing loss and a missense variant p.Arg185Pro in HOMER2
PMID: 30047143 - Lue et al 2018 - Chinese family with autosomal dominant, non-syndromic hearing loss and a pathogenic variant c.840_841insC in HOMER2 that leads to a premature stop codon).

Azaiez et al 2015 also report mouse mutants homozygous for the targeted deletion of Homer2 present with early-onset rapidly progressive hearing loss. Age-matched WT and Homer2 +/- animals showed no differences in electrophysiological hearing tests.
Hearing loss v2.4 HOMER2 Eleanor Williams reviewed gene: HOMER2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Additional findings health related v0.108 MEN1 Sarah Leigh changed review comment from: Comment on phenotypes: Clinically relevant transcript NM_000244.3; to: Comment on phenotypes: Clinically relevant transcript NM_000244.3. This has been supersceded by NM_130799.2
Hearing loss v2.4 HARS2 Eleanor Williams edited their review of gene: HARS2: Added comment: 6 new cases, so now 8 independent cases, which is sufficient to rate green.

New cases:

PMID: 31827252 - Demain et al 2019 - 3 unrelated families each with compound heterozygous variants in HARS2 in affected members. All 3 families share the c.1439G>A p.(Arg480His) (NM_012208.3) variant along with other likely pathogenic variants.

PMID: 31449985 - Karstensen et al 2019 - three novel families, compound heterozygous for missense variants in HARS2 and early onset, rapidly progressive hearing impairment in the five affected individuals. Premature ovarian insufficiency was also seen in some individuals.; Changed rating: GREEN
Hearing loss v2.4 EPS8L2 Eleanor Williams reviewed gene: EPS8L2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hearing loss v2.4 ELMOD3 Eleanor Williams reviewed gene: ELMOD3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.0 ANKH Zornitza Stark reviewed gene: ANKH: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Craniometaphyseal dysplasia, MIM#123000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hearing loss v2.4 DMXL2 Eleanor Williams reviewed gene: DMXL2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27657680, 31688942; Phenotypes: ?Deafness, autosomal dominant 71, 617605; Mode of inheritance: None
Hearing loss v2.4 COL4A6 Eleanor Williams edited their review of gene: COL4A6: Changed rating: RED
Hearing loss v2.4 COL4A6 Eleanor Williams changed review comment from: Provisionally associated with ?Deafness, X-linked 6 #300914 (XLR) in OMIM.
Only 1 family reported in PMID: 23714752 - Rost et al 2014 -  a Hungarian three-generation family with X-linked nonsyndromic congenital hearing loss with a missense mutation (c.1771G>A, p.Gly591Ser) in COL4A6 in all affected family members. In situ hybridization and immunostaining demonstrated expression of the COL4A6 homologs in the otic vesicle of the zebrafish and in the murine inner ear, supporting its role in normal ear development and function.

Pubmed search didn’t find any other cases.; to: Provisionally associated with ?Deafness, X-linked 6 #300914 (XLR) in OMIM.
Only 1 family reported in PMID: 23714752 - Rost et al 2014 -  a Hungarian three-generation family with X-linked nonsyndromic congenital hearing loss with a missense mutation (c.1771G>A, p.Gly591Ser) in COL4A6 in all affected family members. In situ hybridization and immunostaining demonstrated expression of the COL4A6 homologs in the otic vesicle of the zebrafish and in the murine inner ear, supporting its role in normal ear development and function.

Pubmed search didn’t find any other cases.
Hearing loss v2.4 COL4A6 Eleanor Williams commented on gene: COL4A6
Hearing loss v2.4 CDC14A Eleanor Williams reviewed gene: CDC14A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29293958, 27259055; Phenotypes: Deafness, autosomal recessive 32, with or without immotile sperm, 608653; Mode of inheritance: None
Hearing loss v2.4 AIFM1 Eleanor Williams reviewed gene: AIFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25986071; Phenotypes: Deafness, X-linked 5, 300614; Mode of inheritance: None
Genetic epilepsy syndromes v2.0 ALKBH8 Zornitza Stark reviewed gene: ALKBH8: Rating: GREEN; Mode of pathogenicity: None; Publications: 31079898; Phenotypes: Intellectual developmental disorder, autosomal recessive 71, MIM# 618504; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v3.0 ALG9 Zornitza Stark reviewed gene: ALG9: Rating: GREEN; Mode of pathogenicity: None; Publications: 28932688; Phenotypes: Congenital disorder of glycosylation, type Il, MIM#608776; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings health related v0.108 VHL Catherine Snow Transcript for gene VHL was changed from ENST00000256474.2 to ENST00000256474.2; NM_000551.3
Additional findings health related v0.107 RET Catherine Snow Transcript for gene RET was changed from ENST00000355710.8 to ENST00000355710.8; NM_020975.4
Additional findings health related v0.106 PCSK9 Catherine Snow Transcript for gene PCSK9 was changed from ENST00000302118.5 to ENST00000302118.5; NM_174936.3
Additional findings health related v0.105 MUTYH Catherine Snow Transcript for gene MUTYH was changed from ENST00000450313.5 to ENST00000450313.5; NM_001128425.1
Additional findings health related v0.104 MSH6 Catherine Snow Transcript for gene MSH6 was changed from ENST00000234420.9 to ENST00000234420.9; NM_000179.2
Additional findings health related v0.103 MSH2 Catherine Snow Transcript for gene MSH2 was changed from ENST00000233146.6 to ENST00000233146.6; NM_000251.2
Additional findings health related v0.102 MLH1 Catherine Snow Transcript for gene MLH1 was changed from ENST00000231790.6 to ENST00000231790.6; NM_000249.3
Additional findings health related v0.101 MEN1 Catherine Snow Transcript for gene MEN1 was changed from None to NM_130799.2; ENST00000312049.10
Additional findings health related v0.99 LDLR Catherine Snow Transcript for gene LDLR was changed from ENST00000558518.5 to ENST00000558518.5; NM_000527.4
Additional findings health related v0.98 CFTR Catherine Snow Transcript for gene CFTR was changed from NM_000492.3 to ENST00000003084.10; NM_000492.3
Additional findings health related v0.97 BRCA2 Catherine Snow Transcript for gene BRCA2 was changed from ENST00000544455.5 to ENST00000544455.5; NM_000059.3
Additional findings health related v0.96 BRCA1 Catherine Snow Transcript for gene BRCA1 was changed from ENST00000357654.8 to ENST00000357654.8; NM_007294.3
Additional findings health related v0.95 APOB Catherine Snow Transcript for gene APOB was changed from ENST00000233242.5 to ENST00000233242.5; NM_000384.2
Additional findings health related v0.94 APC Catherine Snow Transcript for gene APC was changed from ENST00000257430.9 to ENST00000257430.9; NM_000038.5
Additional findings health related v0.93 CFTR Catherine Snow Source Carrier Status was removed from CFTR.
Source Expert Review was added to CFTR.
Transcript for gene CFTR was changed from None to NM_000492.3
Pyruvate dehydrogenase (PDH) deficiency v1.1 Ellen McDonagh Panel version has been signed off
Intellectual disability v3.0 ALG14 Zornitza Stark gene: ALG14 was added
gene: ALG14 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: ALG14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALG14 were set to 30221345; 23404334; 28733338
Phenotypes for gene: ALG14 were set to Myasthenic syndrome, congenital, 15, without tubular aggregates, MIM#616227; Intellectual disability
Review for gene: ALG14 was set to GREEN
gene: ALG14 was marked as current diagnostic
Added comment: 5 individuals from unrelated families described in the literature: one with myasthenic syndrome, no report of ID; second with predominantly ID phenotype; and three more with a neurodegenerative phenotype.
Sources: Expert list
Intellectual disability v3.0 ALDOB Zornitza Stark changed review comment from: Metabolic decompensation on exposure to fructose, including hypoglycaemia, but ID is not an intrinsic feature of this condition.; to: Metabolic decompensation on exposure to fructose, including hypoglycaemia, but ID is not an intrinsic feature of this condition. ID only reported in the absence of treatment.
Intellectual disability v3.0 ALDOB Zornitza Stark reviewed gene: ALDOB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Fructose intolerance, hereditary, MIM# 229600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 AHCY Zornitza Stark reviewed gene: AHCY: Rating: ; Mode of pathogenicity: None; Publications: 31957987, 27671891, 30121674, 28779239; Phenotypes: Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase, MIM#613752; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 AGPS Zornitza Stark reviewed gene: AGPS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Rhizomelic chondrodysplasia punctata, type 3, MIM#600121; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 AGMO Zornitza Stark gene: AGMO was added
gene: AGMO was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: AGMO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGMO were set to 31555905
Phenotypes for gene: AGMO were set to microcephaly; intellectual disability; epilepsy
Review for gene: AGMO was set to GREEN
gene: AGMO was marked as current diagnostic
Added comment: Three unrelated families and functional data.
Sources: Expert list
Intellectual disability v3.0 AGL Zornitza Stark reviewed gene: AGL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Glycogen storage disease IIIa, MIM# 232400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 AFG3L2 Zornitza Stark reviewed gene: AFG3L2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic ataxia 5, autosomal recessive, MIM#614487; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 ADGRG6 Zornitza Stark reviewed gene: ADGRG6: Rating: RED; Mode of pathogenicity: None; Publications: 30549416; Phenotypes: Lethal congenital contracture syndrome 9, OMIM #616503; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 ADD3 Zornitza Stark gene: ADD3 was added
gene: ADD3 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: ADD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADD3 were set to 29768408; 23836506
Phenotypes for gene: ADD3 were set to Cerebral palsy, spastic quadriplegic, 3, MIM#617008
Review for gene: ADD3 was set to GREEN
gene: ADD3 was marked as current diagnostic
Added comment: Four families reported in the literature with bi-allelic variants in this gene causing intellectual disability.
Sources: Expert list
Intellectual disability v3.0 ADCY5 Zornitza Stark reviewed gene: ADCY5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dyskinesia, familial, with facial myokymia, MIM#606703; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.0 ADAMTS10 Zornitza Stark gene: ADAMTS10 was added
gene: ADAMTS10 was added to Intellectual disability. Sources: Expert list
Mode of inheritance for gene: ADAMTS10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ADAMTS10 were set to Weill-Marchesani syndrome 1, recessive, MIM#277600
Review for gene: ADAMTS10 was set to AMBER
Added comment: Mild intellectual disability is described in around 10% of affected individuals.
Sources: Expert list
Intellectual disability v3.0 ACADSB Zornitza Stark reviewed gene: ACADSB: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: 2-methylbutyrylglycinuria, MIM# 610006; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 ABCC6 Zornitza Stark reviewed gene: ABCC6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Arterial calcification, generalized, of infancy, 2, MIM#614473, Pseudoxanthoma elasticum, MIM#264800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.0 ABAT Zornitza Stark reviewed gene: ABAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 10407778, 20052547, 27596361, 28411234,; Phenotypes: GABA-transaminase deficiency, MIM#613163; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic epilepsy syndromes v2.0 SLC39A8 Zornitza Stark gene: SLC39A8 was added
gene: SLC39A8 was added to Genetic epilepsy syndromes. Sources: Expert Review
Mode of inheritance for gene: SLC39A8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A8 were set to 26637978; 26637979
Phenotypes for gene: SLC39A8 were set to Congenital disorder of glycosylation, type IIn , MIM#16721
Review for gene: SLC39A8 was set to GREEN
gene: SLC39A8 was marked as current diagnostic
Added comment: 6 individuals from Hutterite descent and two other unrelated families reported. Seizures reported in 2 Hutterite individuals and also in the other two unrelated families.
Sources: Expert Review
Genetic epilepsy syndromes v2.0 PIGS Zornitza Stark gene: PIGS was added
gene: PIGS was added to Genetic epilepsy syndromes. Sources: Expert list
Mode of inheritance for gene: PIGS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGS were set to 30269814
Phenotypes for gene: PIGS were set to Glycosylphosphatidylinositol biosynthesis defect 18, MIM# 618143
Review for gene: PIGS was set to GREEN
gene: PIGS was marked as current diagnostic
Added comment: Three unrelated families reported. Severe neurological phenotype ranging from fetal akinesia (one family) to ID/EE (two families). Although pregnancies were terminated in one family, features observed in the affected fetuses suggest a severe neurological phenotype and hence we have rated this gene Green on our Epilepsy and our ID panels. I have added the gene to your CDG panel.
Sources: Expert list
Congenital disorders of glycosylation v2.0 PIGS Zornitza Stark gene: PIGS was added
gene: PIGS was added to Congenital disorders of glycosylation. Sources: Expert list
Mode of inheritance for gene: PIGS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGS were set to 30269814
Phenotypes for gene: PIGS were set to Glycosylphosphatidylinositol biosynthesis defect 18 618143
Review for gene: PIGS was set to GREEN
gene: PIGS was marked as current diagnostic
Added comment: Three unrelated families reported. Severe neurological phenotype ranging from fetal akinesia to ID/EE.
Sources: Expert list
Genetic epilepsy syndromes v2.0 WDR45B Zornitza Stark reviewed gene: WDR45B: Rating: GREEN; Mode of pathogenicity: None; Publications: 21937992, 28503735, 27431290; Phenotypes: Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, MIM# 617977; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic epilepsy syndromes v2.0 UGP2 Zornitza Stark reviewed gene: UGP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31820119; Phenotypes: Epileptic encephalopathy, intellectual disability, microcephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Bleeding and platelet disorders v1.0 IKZF5 Kate Downes gene: IKZF5 was added
gene: IKZF5 was added to Bleeding and platelet disorders. Sources: Expert Review,Literature
Mode of inheritance for gene: IKZF5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IKZF5 were set to 1217188
Phenotypes for gene: IKZF5 were set to Thrombocytopenia (HP:0001873), Reduced platelet alpha granules (HP:0012528).
Penetrance for gene: IKZF5 were set to unknown
Mode of pathogenicity for gene: IKZF5 was set to Other
Review for gene: IKZF5 was set to GREEN
Added comment: Lentaigne C, et al., 2019 details the association of thrombocytopenia with missense variants in the IKZF5 transcription factor. Five different missense variants in or near the IKZF5 zinc finger domains are reported in five independent probands. Co-segregation studies indicate that two variants occurred de novo and three co-segregate across large pedigrees.
Mode of pathogenicity is unknown.
Sources: Expert Review, Literature
Genetic epilepsy syndromes v2.0 TUBA8 Zornitza Stark edited their review of gene: TUBA8: Added comment: Another affected individual reported as part of a bigger brain malformations cohort.; Changed publications: 31481326
Genetic epilepsy syndromes v2.0 TRPM3 Zornitza Stark reviewed gene: TRPM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31278393; Phenotypes: Intellectual disability, epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Genetic epilepsy syndromes v2.0 TIMM50 Zornitza Stark Deleted their comment
Genetic epilepsy syndromes v2.0 TIMM50 Zornitza Stark commented on gene: TIMM50: At least 4 families reported, seizures in all reported individuals.
Genetic epilepsy syndromes v2.0 TIMM50 Zornitza Stark edited their review of gene: TIMM50: Added comment: More families reported, supporting gene-disease association; note seizures reported in all.; Changed rating: GREEN; Changed publications: 27573165, 30190335, 31058414
Genetic epilepsy syndromes v2.0 ST3GAL3 Zornitza Stark edited their review of gene: ST3GAL3: Added comment: Additional family reported recently with seizure phenotype.; Changed rating: AMBER; Changed publications: 23252400, 31584066
Genetic epilepsy syndromes v2.0 SLC5A6 Zornitza Stark gene: SLC5A6 was added
gene: SLC5A6 was added to Genetic epilepsy syndromes. Sources: Expert list
Mode of inheritance for gene: SLC5A6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC5A6 were set to 31754459; 27904971
Phenotypes for gene: SLC5A6 were set to Developmental delay; epilepsy; neurodegeneration
Review for gene: SLC5A6 was set to GREEN
gene: SLC5A6 was marked as current diagnostic
Added comment: Two unrelated families reported, functional data and some evidence of response to treatment.
Sources: Expert list
Genetic epilepsy syndromes v2.0 SETD5 Zornitza Stark reviewed gene: SETD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 29484850; Phenotypes: Intellectual disability, autosomal dominant 23 (MIM # 615761); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Genetic epilepsy syndromes v2.0 SETD1B Zornitza Stark edited their review of gene: SETD1B: Added comment: Another individual with a de novo variant in this gene and epilepsy reported in 31440728 bringing the total to three, and possibly two more in 31685013.; Changed rating: GREEN; Changed publications: 29322246, 31440728, 31685013; Changed phenotypes: Epilepsy with myoclonic absences, intellectual disability; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic epilepsy syndromes v2.0 SETD1A Zornitza Stark gene: SETD1A was added
gene: SETD1A was added to Genetic epilepsy syndromes. Sources: Expert list
Mode of inheritance for gene: SETD1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD1A were set to 31197650
Phenotypes for gene: SETD1A were set to Epilepsy
Review for gene: SETD1A was set to GREEN
gene: SETD1A was marked as current diagnostic
Added comment: Four unrelated families reported: in three, the variants occurred de novo, and in the fourth, it segregated with disease. Some functional data.
Sources: Expert list
Genetic epilepsy syndromes v2.0 RNF13 Zornitza Stark reviewed gene: RNF13: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30595371; Phenotypes: Epileptic encephalopathy, early infantile, 73, MIM# 618379; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Genetic epilepsy syndromes v2.0 PTEN Zornitza Stark commented on gene: PTEN: Cowden and BRRS are germline PTEN-related conditions and can present with macrocephaly/neurodevelopmental phenotype in childhood, including ID/autism and sometimes seizures as outlined in the previous reviews. The associated cancer risk makes the condition important to diagnose.

There are also somatic PTEN-related conditions such as Proteus, but these are not under consideration for this panel. One of the reviews below refers to AKT1, which is confusing.
Genetic epilepsy syndromes v2.0 NUP214 Zornitza Stark gene: NUP214 was added
gene: NUP214 was added to Genetic epilepsy syndromes. Sources: Expert list
Mode of inheritance for gene: NUP214 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP214 were set to 31178128; 30758658
Phenotypes for gene: NUP214 were set to Encephalopathy, acute, infection-induced, susceptibility to, 9, MIM# 618426; epileptic encephalopathy; developmental regression; microcephaly
Review for gene: NUP214 was set to GREEN
gene: NUP214 was marked as current diagnostic
Added comment: Three unrelated families reported.
Sources: Expert list
Genetic epilepsy syndromes v2.0 NEDD4L Zornitza Stark edited their review of gene: NEDD4L: Added comment: Seizures are a frequently reported feature in this brain development disorder.; Changed publications: 28515470, 23934111, 28212375, 27694961
Genetic epilepsy syndromes v2.0 NEUROD2 Zornitza Stark gene: NEUROD2 was added
gene: NEUROD2 was added to Genetic epilepsy syndromes. Sources: Expert list
Mode of inheritance for gene: NEUROD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NEUROD2 were set to 30323019; 16504944
Phenotypes for gene: NEUROD2 were set to Epileptic encephalopathy, early infantile, 72, MIM# 618374
Review for gene: NEUROD2 was set to GREEN
gene: NEUROD2 was marked as current diagnostic
Added comment: Two unrelated individuals with de novo missense variants in this gene, two animal models.
Sources: Expert list
Genetic epilepsy syndromes v2.0 MTHFS Zornitza Stark reviewed gene: MTHFS: Rating: GREEN; Mode of pathogenicity: None; Publications: 30031689, 31844630, 22303332; Phenotypes: Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination, 618367; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic epilepsy syndromes v2.0 MED17 Zornitza Stark reviewed gene: MED17: Rating: GREEN; Mode of pathogenicity: None; Publications: 30345598; Phenotypes: Microcephaly postnatal progressive with seizures and brain atrophy, 613668; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic epilepsy syndromes v2.0 MAGI2 Zornitza Stark reviewed gene: MAGI2: Rating: RED; Mode of pathogenicity: None; Publications: 31056551; Phenotypes: Epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Childhood onset dystonia or chorea or related movement disorder v1.0 HFE2 Louise Daugherty Tag new-gene-name tag was added to gene: HFE2.
Childhood onset dystonia or chorea or related movement disorder v1.0 HFE2 Louise Daugherty Deleted their comment
Childhood onset dystonia or chorea or related movement disorder v1.0 HFE2 Louise Daugherty commented on gene: HFE2: Added new-gene-name tag, new approved HGNC gene symbol for HFE2 is HJV
Tubulointerstitial kidney disease v1.0 SEC61A1 Zornitza Stark reviewed gene: SEC61A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30586318; Phenotypes: Familial juvenile Hyperuricemic nephropathy-4 MIM 617056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Tubulointerstitial kidney disease v1.0 DNAJB11 Zornitza Stark reviewed gene: DNAJB11: Rating: GREEN; Mode of pathogenicity: None; Publications: 29706351; Phenotypes: Tubulointerstitial disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Unexplained kidney failure in young people v1.82 VIPAS39 Zornitza Stark reviewed gene: VIPAS39: Rating: GREEN; Mode of pathogenicity: None; Publications: 20190753; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 2, MIM# 613404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v2.0 SLC2A2 Zornitza Stark gene: SLC2A2 was added
gene: SLC2A2 was added to Renal tubulopathies. Sources: Expert list
Mode of inheritance for gene: SLC2A2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC2A2 were set to Fanconi-Bickel syndrome, MIM# 227810
Review for gene: SLC2A2 was set to GREEN
Added comment: Well established renal tubulopathy gene.
Sources: Expert list
Genetic epilepsy syndromes v2.0 GRIA2 Zornitza Stark reviewed gene: GRIA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31300657; Phenotypes: Intellectual disability, autism, Rett-like features, epileptic encephalopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Ataxia and cerebellar anomalies - narrow panel v2.0 PTRH2 Louise Daugherty reviewed gene: PTRH2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Rare anaemia v1.0 KIF23 Louise Daugherty commented on gene: KIF23: Substantial support from all four GLHs that this gene should be Green, so will remain Green. However, The gene will be flagged up for discussion at the next iteration (version) of this panel to be used for GMS.
Primary immunodeficiency v2.0 RC3H1 Louise Daugherty reviewed gene: RC3H1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Primary immunodeficiency v2.0 SLC39A7 Louise Daugherty reviewed gene: SLC39A7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Primary immunodeficiency v2.0 PSMB10 Louise Daugherty reviewed gene: PSMB10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Primary immunodeficiency v2.0 SNORA31 Louise Daugherty reviewed gene: SNORA31: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Primary immunodeficiency v2.0 IL6ST Louise Daugherty reviewed gene: IL6ST: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Primary immunodeficiency v2.0 IL6R Louise Daugherty reviewed gene: IL6R: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Primary immunodeficiency v2.0 ZNF341 Louise Daugherty reviewed gene: ZNF341: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Genetic epilepsy syndromes v2.0 GLS Zornitza Stark gene: GLS was added
gene: GLS was added to Genetic epilepsy syndromes. Sources: Expert list
Mode of inheritance for gene: GLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLS were set to 30575854
Phenotypes for gene: GLS were set to Epileptic encephalopathy, early infantile, 71, MIM# 618328
Review for gene: GLS was set to AMBER
Added comment: Three individuals from two unrelated families reported with early neonatal refractory seizures, structural brain abnormalities and oedema; significantly increased glutamine levels.
Sources: Expert list
Genetic epilepsy syndromes v2.0 GABRB1 Zornitza Stark reviewed gene: GABRB1: Rating: ; Mode of pathogenicity: None; Publications: 23934111, 27273810, 31618474; Phenotypes: Epileptic encephalopathy, early infantile, 45, MIM# 617153; Mode of inheritance: None; Current diagnostic: yes
Genetic epilepsy syndromes v2.0 FOXRED1 Zornitza Stark edited their review of gene: FOXRED1: Added comment: A couple more cases reported in the literature in 2019 bringing the total to 6, including another one with seizures are part of the phenotype (31434271).; Changed rating: GREEN; Changed publications: 20858599, 20818383, 31434271
Genetic epilepsy syndromes v2.0 FGFR3 Zornitza Stark edited their review of gene: FGFR3: Added comment: This condition is well documented as being associated with epilepsy. It can be difficult to recognise clinically, particularly in infancy and therefore we consider this gene merits as much inclusion in an Epilepsy panel as other syndromic diagnoses (e.g. EFTUD2 etc).; Changed publications: 24630288, 27485793, 23649205, 12794698
Genetic epilepsy syndromes v2.0 FDFT1 Zornitza Stark reviewed gene: FDFT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29909962; Phenotypes: Squalene synthase deficiency, MIM# 618156; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic epilepsy syndromes v2.0 EXT2 Zornitza Stark reviewed gene: EXT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26246518, 30288735, 30997052; Phenotypes: Seizures, scoliosis, and macrocephaly syndrome, MIM# 616682; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic epilepsy syndromes v2.0 DOLK Zornitza Stark edited their review of gene: DOLK: Added comment: Early presentation with seizures and demise reported in some individuals. Transferrin isoforms are not a reliable test in the newborn period to guide appropriate genomic analysis towards a CDG/metabolic panel; we also note the 25% recurrence risk, and hence we have included this gene as Green on our panel.; Changed publications: 23890587, 28816422, 24144945
Renal ciliopathies v1.0 ADAMTS9 Zornitza Stark gene: ADAMTS9 was added
gene: ADAMTS9 was added to Renal ciliopathies. Sources: Expert list
Mode of inheritance for gene: ADAMTS9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS9 were set to 30609407
Phenotypes for gene: ADAMTS9 were set to Nephronophthisis-Related Ciliopathy
Review for gene: ADAMTS9 was set to GREEN
gene: ADAMTS9 was marked as current diagnostic
Added comment: Two families reported with functional evidence
Sources: Expert list
Genetic epilepsy syndromes v2.0 DMXL2 Zornitza Stark reviewed gene: DMXL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31688942, 30237576; Phenotypes: Epileptic encephalopathy, early infantile, 81, MIM# 618663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic epilepsy syndromes v2.0 DLL1 Zornitza Stark reviewed gene: DLL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31353024; Phenotypes: Intellectual disability, autism, seizures, variable brain abnormalities, scoliosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Genetic epilepsy syndromes v2.0 DEAF1 Zornitza Stark reviewed gene: DEAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30923367; Phenotypes: Dyskinesia, seizures, and intellectual developmental disorder 617171, autosomal dominant mental retardation 24, MIM# 615828; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Multi-organ autoimmune diabetes v1.8 STAT3 Ivone Leong Publications for gene: STAT3 were set to
Genetic epilepsy syndromes v2.0 SCN8A Zornitza Stark reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31625145; Phenotypes: Epileptic encephalopathy, early infantile, 13, MIM# 614558, dominant and recessive; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic epilepsy syndromes v2.0 STXBP1 Zornitza Stark reviewed gene: STXBP1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31855252; Phenotypes: Epileptic encephalopathy, early infantile, 4, MIM#612164; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic epilepsy syndromes v2.0 CPLX1 Zornitza Stark gene: CPLX1 was added
gene: CPLX1 was added to Genetic epilepsy syndromes. Sources: Expert list
Mode of inheritance for gene: CPLX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPLX1 were set to 26539891; 28422131
Phenotypes for gene: CPLX1 were set to Epileptic encephalopathy, early infantile, 63, MIM# 617976
Review for gene: CPLX1 was set to GREEN
gene: CPLX1 was marked as current diagnostic
Added comment: Five individuals from three unrelated families reported in larger neurodevelopmental cohorts.
Sources: Expert list
Genetic epilepsy syndromes v2.0 AGMO Zornitza Stark gene: AGMO was added
gene: AGMO was added to Genetic epilepsy syndromes. Sources: Expert list
Mode of inheritance for gene: AGMO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGMO were set to 31555905; 27000257
Phenotypes for gene: AGMO were set to microcephaly; intellectual disability; epilepsy
Review for gene: AGMO was set to AMBER
Added comment: Three unrelated families reported, though epilepsy not an invariable feature.
Sources: Expert list
Ultra-rare undescribed monogenic disorders v1.1 Ellen McDonagh Panel types changed to Rare Disease 100K
Retinal disorders v2.6 DRAM2 Andrew Webster reviewed gene: DRAM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25983245, 26720460, 31394102; Phenotypes: macular dystrophy, cone-dystrophy, cone-rod dystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency v2.0 ZNF341 Owen Siggs gene: ZNF341 was added
gene: ZNF341 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: ZNF341 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF341 were set to 29907690; 29907691
Phenotypes for gene: ZNF341 were set to Hyper-IgE syndrome
Review for gene: ZNF341 was set to GREEN
Added comment: Ten unrelated families with nonsense or frameshift variants.
Sources: Literature
Primary immunodeficiency v2.0 IL6R Owen Siggs gene: IL6R was added
gene: IL6R was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: IL6R was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL6R were set to 31235509
Phenotypes for gene: IL6R were set to Recurrent infections; Hyper-IgE; Eczema
Review for gene: IL6R was set to GREEN
Added comment: Two unrelated cases with homozygous variants (frameshift or missense) and compelling functional evidence.
Sources: Literature
Primary immunodeficiency v2.0 IL6ST Owen Siggs reviewed gene: IL6ST: Rating: GREEN; Mode of pathogenicity: None; Publications: 28747427, 30309848; Phenotypes: Hyper-IgE syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency v2.0 IL6ST Owen Siggs Deleted their review
Primary immunodeficiency v2.0 IL6ST Owen Siggs gene: IL6ST was added
gene: IL6ST was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: IL6ST was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL6ST were set to 31235509
Phenotypes for gene: IL6ST were set to Recurrent infections; Abnormal acute-phase responses; Elevated IgE; Eczema; Eosinophilia
Review for gene: IL6ST was set to GREEN
Added comment: Two unrelated cases with homozygous variants (nonsense or missense), with functional evidence of causation.
Sources: Literature
Primary immunodeficiency v2.0 SNORA31 Owen Siggs gene: SNORA31 was added
gene: SNORA31 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: SNORA31 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SNORA31 were set to 31806906
Phenotypes for gene: SNORA31 were set to Herpes simplex encephalitis
Review for gene: SNORA31 was set to GREEN
Added comment: Five unrelated families, four heterozygous variants in small nucleolar RNA gene.
Sources: Literature
Primary immunodeficiency v2.0 PSMB10 Owen Siggs gene: PSMB10 was added
gene: PSMB10 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: PSMB10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB10 were set to 31783057
Phenotypes for gene: PSMB10 were set to Proteasome-associated autoinflammatory syndrome
Review for gene: PSMB10 was set to AMBER
Added comment: Single case, homozygous missense variant, good functional experimental support.
Sources: Literature
Multi-organ autoimmune diabetes v1.7 STAT3 Owen Siggs reviewed gene: STAT3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 25038750, 25359994; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary immunodeficiency v2.0 SLC39A7 Owen Siggs gene: SLC39A7 was added
gene: SLC39A7 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: SLC39A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A7 were set to 30718914
Phenotypes for gene: SLC39A7 were set to Agammaglobulinemia; B cell deficiency
Review for gene: SLC39A7 was set to GREEN
Added comment: Six individuals from five families with biallelic missense +/- nonsense variants, phenocopied by mouse models.
Sources: Literature
Primary immunodeficiency v2.0 RC3H1 Owen Siggs gene: RC3H1 was added
gene: RC3H1 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: RC3H1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RC3H1 were set to PMID: 31636267
Phenotypes for gene: RC3H1 were set to Hemophagocytic lymphohistiocytosis
Penetrance for gene: RC3H1 were set to unknown
Added comment: Single case, homozygous nonsense in consanguineous kindred, clinical phenotype resembling HLH (PMID: 31636267). Convincing functional evidence of causation with phenotypic similarities to mouse model. Promote to Green List once second unrelated case identified.
Sources: Literature
Structural eye disease v1.0 MYRF Owen Siggs reviewed gene: MYRF: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31048900, 31172260, 31266062, 31700225; Phenotypes: Nanophthalmos, High hyperopia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Anophthalmia or microphthalmia v1.21 MYRF Owen Siggs changed review comment from: Heterozygous variants in same gene also associated with congenital heart defects (hypoplastic left heart syndrome, scimitar syndrome, septal defects, valvular anomalies), genitourinary anomalies (ambiguous genitalia, hypospadias, cryptorchidism), congenital diaphragmatic hernia, and pulmonary hypoplasia (see 31069960).
Sources: Literature; to: Entry in OMIM (600165) for locus, subsequently ascribed to variants in MYRF in this same family and at least 7 others (PMID: 31048900, 31172260, 31700225, 31266062).

Heterozygous variants in same gene also associated with congenital heart defects (hypoplastic left heart syndrome, scimitar syndrome, septal defects, valvular anomalies), genitourinary anomalies (ambiguous genitalia, hypospadias, cryptorchidism), congenital diaphragmatic hernia, and pulmonary hypoplasia (see 31069960).
Sources: Literature
Glaucoma (developmental) v1.5 CPAMD8 Owen Siggs gene: CPAMD8 was added
gene: CPAMD8 was added to Glaucoma (developmental). Sources: Literature
Mode of inheritance for gene: CPAMD8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPAMD8 were set to DOI: 10.1016/j.ophtha.2019.12.024, PMID: 29556725
Phenotypes for gene: CPAMD8 were set to Glaucoma; anterior segment dysgenesis; retinal detachment; cataract
Penetrance for gene: CPAMD8 were set to unknown
Review for gene: CPAMD8 was set to GREEN
Added comment: Biallelic variants associated with autosomal recessive anterior segment dysgenesis (three published pedigrees; PMID: 27839872), or anterior segment dysgenesis with glaucoma (eight published pedigrees; PMID: 29556725, DOI: 10.1016/j.ophtha.2019.12.024).
Sources: Literature
Anophthalmia or microphthalmia v1.21 MYRF Owen Siggs gene: MYRF was added
gene: MYRF was added to Anophthalmia or microphthalmia. Sources: Literature
Mode of inheritance for gene: MYRF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MYRF were set to PMID: 31048900, 31172260, 31700225
Phenotypes for gene: MYRF were set to Nanophthalmos; high hyperopia
Penetrance for gene: MYRF were set to Complete
Review for gene: MYRF was set to GREEN
Added comment: Heterozygous variants in same gene also associated with congenital heart defects (hypoplastic left heart syndrome, scimitar syndrome, septal defects, valvular anomalies), genitourinary anomalies (ambiguous genitalia, hypospadias, cryptorchidism), congenital diaphragmatic hernia, and pulmonary hypoplasia (see 31069960).
Sources: Literature
Autism v0.15 CHD1 Aleš Maver reviewed gene: CHD1: Rating: RED; Mode of pathogenicity: None; Publications: 28866611; Phenotypes: autism, speech apraxia, developmental delay, facial dysmorphic features; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.2 Rebecca Foulger Panel types changed to External Diagnostic Lab
Nephrocalcinosis or nephrolithiasis v2.0 SLC26A1 Zornitza Stark gene: SLC26A1 was added
gene: SLC26A1 was added to Nephrocalcinosis or nephrolithiasis. Sources: Expert list
Mode of inheritance for gene: SLC26A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC26A1 were set to 27210743; 27210743; 20160351
Phenotypes for gene: SLC26A1 were set to Nephrolithiasis, calcium oxalate, MIM#167030
Review for gene: SLC26A1 was set to GREEN
gene: SLC26A1 was marked as current diagnostic
Added comment: Three unrelated families and a mouse model.
Sources: Expert list
Nephrocalcinosis or nephrolithiasis v2.0 HNF4A Zornitza Stark reviewed gene: HNF4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31875549, 24285859, 22802087, 30005691, 28458902; Phenotypes: Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young, OMIM #616026; Mode of inheritance: None; Current diagnostic: yes
CAKUT v1.41 WNT5A Zornitza Stark gene: WNT5A was added
gene: WNT5A was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: WNT5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: WNT5A were set to Robinow syndrome, autosomal dominant 1, MIM#180700
Review for gene: WNT5A was set to GREEN
gene: WNT5A was marked as current diagnostic
Added comment: Renal anomalies in about a quarter.
Sources: Expert list
CAKUT v1.41 VPS33B chirag patel reviewed gene: VPS33B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
CAKUT v1.41 ZIC3 Zornitza Stark gene: ZIC3 was added
gene: ZIC3 was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: ZIC3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ZIC3 were set to VACTERL association, X-linked, MIM# 314390
Review for gene: ZIC3 was set to GREEN
Added comment: Renal malformations are a feature of VACTERL.
Sources: Expert list
CAKUT v1.41 TBC1D1 chirag patel gene: TBC1D1 was added
gene: TBC1D1 was added to CAKUT. Sources: Literature
Mode of inheritance for gene: TBC1D1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBC1D1 were set to PMID: 26572137
Phenotypes for gene: TBC1D1 were set to CAKUT
Review for gene: TBC1D1 was set to GREEN
Added comment: 1 heterozygous de novo frameshift variant in TBC1D1 in 1 CAKUT.
3 further CAKUT cases with three novel or rare inherited heterozygous TBC1D1 missense variants predicted to be pathogenic. TBC1D1 mutations affected Ser237-phosphorylation or protein stability and thereby act as hypomorphs. Tbc1d1 showed widespread expression in the developing murine urogenital system. A mild CAKUT spectrum phenotype, including anomalies observed in patients carrying TBC1D1 mutations, was found in kidneys of some Tbc1d1 (-/-) mice. Significantly reduced Glut4 levels were detected in kidneys of Tbc1d1 (-/-) mice and the dysplastic kidney of a TBC1D1 mutation carrier versus controls. TBC1D1 and SLC2A4 encoding GLUT4 were highly expressed in human fetal kidney. These data demonstrate heterozygous deactivating TBC1D1 mutations in CAKUT patients with a similar renal and ureteral phenotype, and provide evidence that TBC1D1 mutations may contribute to CAKUT pathogenesis, possibly via a role in glucose homeostasis.
Sources: Literature
CAKUT v1.41 TFAP2A Zornitza Stark gene: TFAP2A was added
gene: TFAP2A was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: TFAP2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TFAP2A were set to Branchiooculofacial syndrome, MIM# 113620
Review for gene: TFAP2A was set to GREEN
Added comment: CAKUT is a feature of the phenotype.
Sources: Expert list
CAKUT v1.41 STRA6 Zornitza Stark gene: STRA6 was added
gene: STRA6 was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: STRA6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STRA6 were set to Microphthalmia, syndromic 9, MIM# 601186
Review for gene: STRA6 was set to GREEN
Added comment: Renal malformations are part of the phenotype.
Sources: Expert list
CAKUT v1.41 SLIT2 Zornitza Stark reviewed gene: SLIT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26026792; Phenotypes: CAKUT; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
CAKUT v1.41 SALL4 chirag patel gene: SALL4 was added
gene: SALL4 was added to CAKUT. Sources: Literature
Mode of inheritance for gene: SALL4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SALL4 were set to PMID: 20301547
Phenotypes for gene: SALL4 were set to SALL4- related disorders
Added comment: Phenotypes include: Duane-radial ray syndrome / Okihiro syndrome; Acro-renal-ocular syndrome; and SALL4-related Holt-Oram syndrome.

Acro-renal-ocular syndrome is established clinically in individuals with the following:
-Radial ray malformations
-Renal abnormalities that can include mild malrotation, ectopia, horseshoe kidney, renal hypoplasia, vesico-ureteral reflux, and bladder diverticula
-Ocular abnormalities that can include ocular coloboma and Duane anomaly
Sources: Literature
CAKUT v1.41 RRM2B Zornitza Stark reviewed gene: RRM2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
CAKUT v1.41 ROR2 Zornitza Stark gene: ROR2 was added
gene: ROR2 was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: ROR2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ROR2 were set to Robinow syndrome, autosomal recessive, MIM# 268310
Review for gene: ROR2 was set to GREEN
gene: ROR2 was marked as current diagnostic
Added comment: Although genital abnormalities are a characteristic feature, renal abnormalities described in ~10%
Sources: Expert list
CAKUT v1.41 RPGRIP1L chirag patel reviewed gene: RPGRIP1L: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
CAKUT v1.41 ROBO2 Zornitza Stark reviewed gene: ROBO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27002985, 24429398, 29194579, 31630547, 27460642; Phenotypes: CAKUT; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
CAKUT v1.41 NOTCH2 chirag patel gene: NOTCH2 was added
gene: NOTCH2 was added to CAKUT. Sources: Literature
Mode of inheritance for gene: NOTCH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH2 were set to PMID: 22105858
Phenotypes for gene: NOTCH2 were set to Alagille syndrome 2; OMIM #610205
Review for gene: NOTCH2 was set to GREEN
Added comment: Renal abnormalities, both structural (small hyperechoic kidney, ureteropelvic obstruction, renal cysts) and functional (most commonly renal tubular acidosis), are found in 39% of affected individuals (73/187) [Kamath et al 2012b, Romero 2018].

Romero R. The renal sequelae of Alagille Syndrome as a Product of Altered Notch Signaling During Kidney Development. In: Kamath, BM and Loomes, KM, eds. Alagille Syndrome: Pathogenesis and Clinical Management. Cham, Switzerland: Springer Nature Switzerland AG; 2018:103-20.
Sources: Literature
CAKUT v1.41 NIPBL Zornitza Stark gene: NIPBL was added
gene: NIPBL was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: NIPBL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NIPBL were set to 8291537
Phenotypes for gene: NIPBL were set to Cornelia de Lange syndrome 1, MIM# 122470
Review for gene: NIPBL was set to GREEN
gene: NIPBL was marked as current diagnostic
Added comment: Renal abnormalities, primarily vesicoureteral reflux, have been reported in 12%
Sources: Expert list
CAKUT v1.41 MYOCD chirag patel gene: MYOCD was added
gene: MYOCD was added to CAKUT. Sources: Literature
Mode of inheritance for gene: MYOCD was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYOCD were set to PMID: 31513549
Phenotypes for gene: MYOCD were set to Megabladder; congenital heart disease; cardiomyopathy
Review for gene: MYOCD was set to GREEN
Added comment: Four unrelated families. Mono allelic disease in males (megabladder), bi-allelic disease in males and females (megabladder and congenital heart disease). Cosegregation of MYOCD variants with the phenotype in 4 unrelated families by in vitro transactivation studies in which pathogenic variants resulted in abrogated SM gene expression and by the finding of megabladder in 2 distinct mouse models with reduced Myocd activity.
Sources: Literature
CAKUT v1.41 LRP4 Zornitza Stark gene: LRP4 was added
gene: LRP4 was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: LRP4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LRP4 were set to Cenani-Lenz syndactyly syndrome, MIM# 212780
Review for gene: LRP4 was set to GREEN
gene: LRP4 was marked as current diagnostic
Added comment: Renal hypoplasia/dysplasia is a recognised feature of this syndrome, and is a feature of the mouse model.
Sources: Expert list
CAKUT v1.41 LIFR chirag patel gene: LIFR was added
gene: LIFR was added to CAKUT. Sources: Literature
Mode of inheritance for gene: LIFR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LIFR were set to PMID: 28334964
Phenotypes for gene: LIFR were set to CAKUT
Review for gene: LIFR was set to GREEN
Added comment: 4 unrelated patients with CAKUT, including functional mouse models.

BUT gene also causes Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome with biallelic mutations.
Sources: Literature
CAKUT v1.41 KMT2D Zornitza Stark gene: KMT2D was added
gene: KMT2D was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: KMT2D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT2D were set to 23535010
Phenotypes for gene: KMT2D were set to Kabuki syndrome 1, MIM# 147920
Review for gene: KMT2D was set to GREEN
gene: KMT2D was marked as current diagnostic
Added comment: Renal malformations are part of the phenotype.
Sources: Expert list
CAKUT v1.41 KDM6A Zornitza Stark gene: KDM6A was added
gene: KDM6A was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: KDM6A was set to Other
Publications for gene: KDM6A were set to 23535010
Phenotypes for gene: KDM6A were set to Kabuki syndrome 2, MIM# 300867
Review for gene: KDM6A was set to GREEN
Added comment: Renal malformations are a recognised feature of this syndrome.
Sources: Expert list
CAKUT v1.41 JAG1 chirag patel gene: JAG1 was added
gene: JAG1 was added to CAKUT. Sources: Literature
Mode of inheritance for gene: JAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JAG1 were set to PMID: 22105858
Phenotypes for gene: JAG1 were set to Alagille syndrome 1; OMIM #118450
Review for gene: JAG1 was set to GREEN
Added comment: Renal abnormalities, both structural (small hyperechoic kidney, ureteropelvic obstruction, renal cysts) and functional (most commonly renal tubular acidosis), are found in 39% of affected individuals (73/187) [Kamath et al 2012b, Romero 2018].

Romero R. The renal sequelae of Alagille Syndrome as a Product of Altered Notch Signaling During Kidney Development. In: Kamath, BM and Loomes, KM, eds. Alagille Syndrome: Pathogenesis and Clinical Management. Cham, Switzerland: Springer Nature Switzerland AG; 2018:103-20.
Sources: Literature
CAKUT v1.41 HOXA13 Zornitza Stark gene: HOXA13 was added
gene: HOXA13 was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: HOXA13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: HOXA13 were set to Hand-foot-uterus syndrome, MIM# 140000
Review for gene: HOXA13 was set to GREEN
gene: HOXA13 was marked as current diagnostic
Added comment: CAKUT is a feature of this condition, variable severity.
Sources: Expert list
CAKUT v1.41 GREB1L Zornitza Stark gene: GREB1L was added
gene: GREB1L was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: GREB1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GREB1L were set to 29100091
Phenotypes for gene: GREB1L were set to Renal hypodysplasia/aplasia 3, MIM# 617805
Review for gene: GREB1L was set to GREEN
gene: GREB1L was marked as current diagnostic
Added comment: At least 16 families described, and mouse model supports gene-disease association.
Sources: Expert list
CAKUT v1.41 GPC3 Zornitza Stark gene: GPC3 was added
gene: GPC3 was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: GPC3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: GPC3 were set to Simpson-Golabi-Behmel syndrome, type 1 312870
Review for gene: GPC3 was set to GREEN
gene: GPC3 was marked as current diagnostic
Added comment: Nephromegaly, multicystic kidneys, hydronephrosis, hydroureter, and duplicated ureters are described features of this syndrome.
Sources: Expert list
CAKUT v1.41 FGF20 Zornitza Stark gene: FGF20 was added
gene: FGF20 was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: FGF20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FGF20 were set to 22698282
Phenotypes for gene: FGF20 were set to Renal hypodysplasia/aplasia 2, MIM#615721
Review for gene: FGF20 was set to AMBER
Added comment: Multiple affected fetuses in a consanguineous family; functional data.
Sources: Expert list
CAKUT v1.41 FAM58A Zornitza Stark gene: FAM58A was added
gene: FAM58A was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: FAM58A was set to Other
Publications for gene: FAM58A were set to 28225384; 18297069
Phenotypes for gene: FAM58A were set to STAR syndrome, MIM# 300707
Review for gene: FAM58A was set to GREEN
gene: FAM58A was marked as current diagnostic
Added comment: XL-dominant disorder, multiple affected families reported, renal malformation are part of the phenotype. Note deletions and sequence variants reported.
Sources: Expert list
CAKUT v1.41 EXOC3L2 chirag patel gene: EXOC3L2 was added
gene: EXOC3L2 was added to CAKUT. Sources: Literature
Mode of inheritance for gene: EXOC3L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC3L2 were set to PMID: 30327448, 28749478, 27894351
Phenotypes for gene: EXOC3L2 were set to Dandy-Walker malformation; renal dysplasia; bone marrow failure
Review for gene: EXOC3L2 was set to GREEN
Added comment: Four individuals from two unrelated families with brain, kidney and bone marrow abnormalities; another described as part of fetal autopsy series, and another in a ciliopathy cohort.
Sources: Literature
CAKUT v1.41 DHCR7 Zornitza Stark edited their review of gene: DHCR7: Changed rating: GREEN
CAKUT v1.41 DHCR7 Zornitza Stark gene: DHCR7 was added
gene: DHCR7 was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHCR7 were set to 3812577; 10069707; 23059950; 9678700
Phenotypes for gene: DHCR7 were set to Smith-Lemli-Opitz syndrome, MIM# 270400
gene: DHCR7 was marked as current diagnostic
Added comment: Approximately 25% of affected individuals have renal anomalies, most commonly renal hypoplasia or agenesis, renal cortical cysts, hydronephrosis, and structural anomalies of the collecting system [Curry et al 1987, Ryan et al 1998, Kratz & Kelley 1999, Nowaczyk et al 2001].
Sources: Expert list
CAKUT v1.41 CTU2 Zornitza Stark gene: CTU2 was added
gene: CTU2 was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTU2 were set to 27480277; 26633546; 31301155
Phenotypes for gene: CTU2 were set to Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, MIM#618142
Review for gene: CTU2 was set to GREEN
gene: CTU2 was marked as current diagnostic
Added comment: Multiple families reported though some share the same founder variant.
Sources: Expert list
CAKUT v1.41 CHD1L Zornitza Stark reviewed gene: CHD1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: CAKUT; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
CAKUT v1.41 CEP55 Zornitza Stark gene: CEP55 was added
gene: CEP55 was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: CEP55 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP55 were set to 30622327
Phenotypes for gene: CEP55 were set to Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM# 236500
Review for gene: CEP55 was set to GREEN
gene: CEP55 was marked as current diagnostic
Added comment: Three families and a zebrafish model support gene-disease association.
Sources: Expert list
CAKUT v1.41 CENPF Zornitza Stark gene: CENPF was added
gene: CENPF was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: CENPF was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CENPF were set to Stromme syndrome, MIM#243605
Review for gene: CENPF was set to GREEN
Added comment: Renal hypodysplasia and hydronephrosis are a feature of this syndrome.
Sources: Expert list
CAKUT v1.41 BMP7 Zornitza Stark gene: BMP7 was added
gene: BMP7 was added to CAKUT. Sources: Expert list
Mode of inheritance for gene: BMP7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP7 were set to 24429398; 7590254
Phenotypes for gene: BMP7 were set to CAKUT
Review for gene: BMP7 was set to RED
Added comment: Single patient reported in a large series; mouse model supports pathogenicity.
Sources: Expert list
CAKUT v1.41 BMP4 Zornitza Stark reviewed gene: BMP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 30568244, 24131739, 23641053, 19685083; Phenotypes: CAKUT; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v2.0 SCUBE3 Eleanor Williams changed review comment from: A variant in this gene has been found in a 100K proband as potentially being the cause of a skeletal dysplasia.; to: A variant in this gene has been found in a 100K proband as potentially being the cause of a skeletal dysplasia.
Skeletal dysplasia v2.0 SCUBE3 Eleanor Williams commented on gene: SCUBE3
Cardiomyopathies - including childhood onset v1.3 PDLIM3 Eleanor Williams Added comment: Comment on publications: Adding PMID: 25163546 Haas et al 2015 Atlas of the clinical genetics of human dilated cardiomyopathy. Reports a frameshift variant in PDLIM3
Cardiomyopathies - including childhood onset v1.3 PDLIM3 Eleanor Williams Publications for gene: PDLIM3 were set to
Hearing loss v2.4 KCNQ4 Ellen McDonagh Tag watchlist was removed from gene: KCNQ4.
Hearing loss v2.4 MITF Ellen McDonagh Tag watchlist was removed from gene: MITF.
Undiagnosed metabolic disorders v1.413 DPM3 Louise Daugherty Tag watchlist was removed from gene: DPM3.
Undiagnosed metabolic disorders v1.413 DPM3 Louise Daugherty commented on gene: DPM3
Undiagnosed metabolic disorders v1.413 ATAD3A Louise Daugherty commented on gene: ATAD3A
Undiagnosed metabolic disorders v1.413 ATAD3A Louise Daugherty Tag watchlist was removed from gene: ATAD3A.
Thoracic aortic aneurysm or dissection v1.112 SMAD2 Louise Daugherty Tag watchlist was removed from gene: SMAD2.
Thoracic aortic aneurysm or dissection v1.112 SMAD2 Louise Daugherty commented on gene: SMAD2
Retinal disorders v2.6 TUB Louise Daugherty commented on gene: TUB
Retinal disorders v2.6 TUB Louise Daugherty Tag watchlist was removed from gene: TUB.
Retinal disorders v2.6 ABCA4 Louise Daugherty Tag watchlist was removed from gene: ABCA4.
Radial dysplasia v1.7 ZIC3 Louise Daugherty commented on gene: ZIC3
Radial dysplasia v1.7 ZIC3 Louise Daugherty Tag watchlist was removed from gene: ZIC3.
Primary lymphoedema v2.0 PTPN14 Louise Daugherty commented on gene: PTPN14
Primary immunodeficiency v2.0 CDCA7 Louise Daugherty Tag watchlist was removed from gene: CDCA7.
Primary immunodeficiency v2.0 CDCA7 Louise Daugherty commented on gene: CDCA7: As a result of watchlist tag audit the watchlist tag was removed from CDCA7- this is now a green gene with sufficient evidence/review
Mitochondrial disorders v2.3 TIMM50 Louise Daugherty Tag watchlist was removed from gene: TIMM50.
Mitochondrial disorders v2.3 TIMM50 Louise Daugherty commented on gene: TIMM50
Mitochondrial disorders v2.3 MTFMT Louise Daugherty Tag watchlist was removed from gene: MTFMT.
Mitochondrial disorders v2.3 MTFMT Louise Daugherty commented on gene: MTFMT
Mitochondrial disorders v2.3 LYRM7 Louise Daugherty Tag watchlist was removed from gene: LYRM7.
Mitochondrial disorders v2.3 LYRM7 Louise Daugherty commented on gene: LYRM7
Mitochondrial disorders v2.3 FDX2 Louise Daugherty Tag watchlist was removed from gene: FDX2.
Mitochondrial disorders v2.3 FDX2 Louise Daugherty commented on gene: FDX2: As a result of watchlist tag audit the watchlist tag was removed from FDX2- this is now a green gene with sufficient evidence/review
Mitochondrial disorders v2.3 COQ9 Louise Daugherty commented on gene: COQ9
Mitochondrial disorders v2.3 ATPAF2 Louise Daugherty commented on gene: ATPAF2
Intellectual disability v3.0 ZSWIM6 Louise Daugherty commented on gene: ZSWIM6
Intellectual disability v3.0 ZSWIM6 Louise Daugherty Tag watchlist was removed from gene: ZSWIM6.
Intellectual disability v3.0 UFM1 Louise Daugherty Tag watchlist was removed from gene: UFM1.
Undiagnosed metabolic disorders v1.413 FMO3 Rebecca Foulger commented on gene: FMO3
Undiagnosed metabolic disorders v1.413 FMO3 Rebecca Foulger Tag treatable tag was added to gene: FMO3.
Intellectual disability v3.0 TRMT1 Louise Daugherty Tag watchlist was removed from gene: TRMT1.
Intellectual disability v3.0 TRMT1 Louise Daugherty commented on gene: TRMT1
Undiagnosed metabolic disorders v1.413 FMO3 Rebecca Foulger Phenotypes for gene: FMO3 were changed from Trimethylaminuria (Disorders and variants of enzymes that oxidise xenobiotics other than cytochrome P450) to Trimethylaminuria, 602079
Intellectual disability v3.0 TRAF7 Louise Daugherty Tag watchlist was removed from gene: TRAF7.
Undiagnosed metabolic disorders v1.412 FMO3 Rebecca Foulger Publications for gene: FMO3 were set to 27604308
Intellectual disability v3.0 TRAF7 Louise Daugherty commented on gene: TRAF7
Intellectual disability v3.0 TCF20 Louise Daugherty edited their review of gene: TCF20: Changed rating: GREEN
Intellectual disability v3.0 TCF20 Louise Daugherty Tag watchlist was removed from gene: TCF20.
Intellectual disability v3.0 TCF20 Louise Daugherty commented on gene: TCF20: As a result of watchlist tag audit the watchlist tag was removed from TCF20 this is now a green gene with sufficient evidence/review
Intellectual disability v3.0 SYNJ1 Louise Daugherty Tag watchlist was removed from gene: SYNJ1.
Intellectual disability v3.0 SYNJ1 Louise Daugherty commented on gene: SYNJ1
Intellectual disability v3.0 SLC6A9 Louise Daugherty edited their review of gene: SLC6A9: Changed rating: GREEN
Intellectual disability v3.0 SLC6A9 Louise Daugherty Tag watchlist was removed from gene: SLC6A9.
Intellectual disability v3.0 SLC6A9 Louise Daugherty commented on gene: SLC6A9: As a result of watchlist tag audit the watchlist tag was removed from SLC6A9- this is now a green gene with sufficient evidence/review
Intellectual disability v3.0 SETD1B Louise Daugherty Tag watchlist was removed from gene: SETD1B.
Intellectual disability v3.0 SETD1B Louise Daugherty commented on gene: SETD1B: As a result of watchlist tag audit the watchlist tag was removed from SETD1B- this is now a green gene with sufficient evidence/review
Intellectual disability v3.0 RLIM Louise Daugherty commented on gene: RLIM: As a result of watchlist tag audit the watchlist tag was removed from RLIM- this is now a green gene with sufficient evidence/review
Intellectual disability v3.0 RLIM Louise Daugherty Tag watchlist was removed from gene: RLIM.
Intellectual disability v3.0 MSL3 Louise Daugherty commented on gene: MSL3: As a result of watchlist tag audit the watchlist tag was removed from MSL3- this is now a green gene with sufficient evidence/review
Intellectual disability v3.0 MSL3 Louise Daugherty Tag watchlist was removed from gene: MSL3.
Intellectual disability v3.0 MSL3 Louise Daugherty commented on gene: MSL3: As a result of watchlist tag audit the watchlist tag was removed from MSL3- this is now a green gene with sufficient evidence/review
Intellectual disability v3.0 MED25 Louise Daugherty Tag watchlist was removed from gene: MED25.
Intellectual disability v3.0 MED25 Louise Daugherty commented on gene: MED25: As a result of watchlist tag audit the watchlist tag was removed from MED25- this is now a green gene with sufficient evidence/review
Intellectual disability v3.0 KDM1A Louise Daugherty Tag watchlist was removed from gene: KDM1A.
Intellectual disability v3.0 KDM1A Louise Daugherty commented on gene: KDM1A: As a result of watchlist tag audit the watchlist tag was removed from KDM1A- this is now a green gene with sufficient evidence/review
Intellectual disability v3.0 GRIA2 Louise Daugherty Tag watchlist was removed from gene: GRIA2.
Intellectual disability v3.0 GRIA2 Louise Daugherty commented on gene: GRIA2: As a result of watchlist tag audit the watchlist tag was removed from GRIA2- this is now a green gene with sufficient evidence/review
Intellectual disability v3.0 DLG4 Louise Daugherty Tag watchlist was removed from gene: DLG4.
Intellectual disability v3.0 DLG4 Louise Daugherty commented on gene: DLG4
Intellectual disability v3.0 CTDP1 Louise Daugherty Tag watchlist was removed from gene: CTDP1.
Intellectual disability v3.0 CTDP1 Louise Daugherty commented on gene: CTDP1
Intellectual disability v3.0 CSNK2A1 Louise Daugherty Tag watchlist was removed from gene: CSNK2A1.
Intellectual disability v3.0 CSNK2A1 Louise Daugherty commented on gene: CSNK2A1
Intellectual disability v3.0 CLCN4 Louise Daugherty Tag watchlist was removed from gene: CLCN4.
Intellectual disability v3.0 CLCN4 Louise Daugherty commented on gene: CLCN4
Intellectual disability v3.0 ALG11 Louise Daugherty Tag watchlist was removed from gene: ALG11.
Intellectual disability v3.0 ALG11 Louise Daugherty commented on gene: ALG11
Hypertrophic cardiomyopathy - teen and adult v2.1 JPH2 Louise Daugherty Tag watchlist was removed from gene: JPH2.
Hypertrophic cardiomyopathy - teen and adult v2.1 JPH2 Louise Daugherty commented on gene: JPH2
Hypertrophic cardiomyopathy - teen and adult v2.1 FLNC Louise Daugherty Tag watchlist was removed from gene: FLNC.
Hypertrophic cardiomyopathy - teen and adult v2.1 FLNC Louise Daugherty commented on gene: FLNC
Hereditary spastic paraplegia v1.213 KIF1A Louise Daugherty Tag watchlist was removed from gene: KIF1A.
Hereditary spastic paraplegia v1.213 KIF1A Louise Daugherty commented on gene: KIF1A
Hereditary spastic paraplegia - childhood onset v2.7 KIF1A Louise Daugherty Deleted their comment
Hereditary spastic paraplegia - childhood onset v2.7 KIF1A Louise Daugherty commented on gene: KIF1A: As a result of watchlist tag audit the watchlist tag was removed from KIF1A- this is now a green gene with sufficient evidence/review
Hereditary neuropathy v1.368 SYT2 Louise Daugherty commented on gene: SYT2: As a result of watchlist tag audit the watchlist tag was kept as still relevant to this gene, it was made green on this panel as it represents a broad phenotype
Hereditary neuropathy v1.368 SBF1 Louise Daugherty Tag watchlist was removed from gene: SBF1.
Hereditary neuropathy v1.368 SBF1 Louise Daugherty commented on gene: SBF1: As a result of watchlist tag audit the watchlist tag was removed from SBF1- this is now a green gene with sufficient evidence/review
Growth failure in early childhood v1.3 IGF2 Louise Daugherty Tag watchlist was removed from gene: IGF2.
Growth failure in early childhood v1.3 IGF2 Louise Daugherty commented on gene: IGF2
Genetic epilepsy syndromes v2.0 NPRL2 Louise Daugherty Tag watchlist was removed from gene: NPRL2.
Genetic epilepsy syndromes v2.0 NPRL2 Louise Daugherty commented on gene: NPRL2
Genetic epilepsy syndromes v2.0 KIAA1109 Louise Daugherty Tag watchlist was removed from gene: KIAA1109.
Genetic epilepsy syndromes v2.0 KIAA1109 Louise Daugherty commented on gene: KIAA1109
Genetic epilepsy syndromes v2.0 KCNQ5 Louise Daugherty Tag watchlist was removed from gene: KCNQ5.
Genetic epilepsy syndromes v2.0 KCNQ5 Louise Daugherty commented on gene: KCNQ5
Genetic epilepsy syndromes v2.0 HNRNPR Louise Daugherty Tag watchlist was removed from gene: HNRNPR.
Genetic epilepsy syndromes v2.0 HNRNPR Louise Daugherty commented on gene: HNRNPR
Genetic epilepsy syndromes v2.0 GOT2 Louise Daugherty commented on gene: GOT2
Genetic epilepsy syndromes v2.0 GOT2 Louise Daugherty Tag watchlist was removed from gene: GOT2.
Genetic epilepsy syndromes v2.0 EIF2B3 Louise Daugherty Tag watchlist was removed from gene: EIF2B3.
Genetic epilepsy syndromes v2.0 EIF2B3 Louise Daugherty commented on gene: EIF2B3
Genetic epilepsy syndromes v2.0 EIF2B1 Louise Daugherty Tag watchlist was removed from gene: EIF2B1.
Genetic epilepsy syndromes v2.0 EIF2B1 Louise Daugherty commented on gene: EIF2B1
Genetic epilepsy syndromes v2.0 CSNK2B Louise Daugherty Tag watchlist was removed from gene: CSNK2B.
Genetic epilepsy syndromes v2.0 CSNK2B Louise Daugherty commented on gene: CSNK2B
Genetic epilepsy syndromes v2.0 CNPY3 Louise Daugherty Tag watchlist was removed from gene: CNPY3.
Genetic epilepsy syndromes v2.0 CNPY3 Louise Daugherty commented on gene: CNPY3
Genetic epilepsy syndromes v2.0 ARV1 Louise Daugherty Tag watchlist was removed from gene: ARV1.
Genetic epilepsy syndromes v2.0 ARV1 Louise Daugherty commented on gene: ARV1
Genetic epilepsy syndromes v2.0 AFF3 Louise Daugherty changed review comment from: As a result of watchlist tag audit the watchlist tag was removed from AFF3- this is now a green gene. Preprint information is now available Voisin et al, 2019; to: As a result of watchlist tag audit the watchlist tag was removed from AFF3- this is now a green gene. Preprint information is now available Voisin et al, 2019 https://www.biorxiv.org/content/10.1101/693937v1
Genetic epilepsy syndromes v2.0 AFF3 Louise Daugherty Tag watchlist was removed from gene: AFF3.
Genetic epilepsy syndromes v2.0 AFF3 Louise Daugherty commented on gene: AFF3
Congenital myopathy v2.0 MYPN Louise Daugherty Tag watchlist was removed from gene: MYPN.
Congenital myopathy v2.0 MYPN Louise Daugherty commented on gene: MYPN: As a result of watchlist tag audit the watchlist tag was removed from MYPN- this is now a green gene.
Congenital myopathy v2.0 CCDC78 Louise Daugherty Tag watchlist was removed from gene: CCDC78.
Congenital myopathy v2.0 CCDC78 Louise Daugherty commented on gene: CCDC78: As a result of watchlist tag audit the watchlist tag was removed from CCDC78- this is now a green gene.
Intellectual disability v3.0 VAMP1 Louise Daugherty Tag watchlist was removed from gene: VAMP1.
Intellectual disability v3.0 VAMP1 Louise Daugherty commented on gene: VAMP1: As a result of watchlist tag audit the watchlist tag was removed from VAMP1- this is now a green gene.
Congenital myaesthenic syndrome v2.0 VAMP1 Louise Daugherty Tag watchlist was removed from gene: VAMP1.
Congenital myaesthenic syndrome v2.0 VAMP1 Louise Daugherty commented on gene: VAMP1: As a result of watchlist tag audit the watchlist tag was removed from VAMP1- this is now a green gene.
Congenital adrenal hypoplasia v2.0 SGPL1 Louise Daugherty Tag watchlist was removed from gene: SGPL1.
Congenital adrenal hypoplasia v2.0 SGPL1 Louise Daugherty commented on gene: SGPL1
Cerebellar hypoplasia v1.39 SMPD4 Louise Daugherty Tag watchlist was removed from gene: SMPD4.
Cerebellar hypoplasia v1.39 SMPD4 Louise Daugherty commented on gene: SMPD4: As a result of watchlist tag audit the watchlist tag was removed from SMPD4- this is now a green gene.
Amelogenesis imperfecta v2.0 PEX6 Louise Daugherty Tag watchlist was removed from gene: PEX6.
Amelogenesis imperfecta v2.0 PEX6 Louise Daugherty commented on gene: PEX6
Thoracic aortic aneurysm or dissection v1.112 ADAMTSL4 Ivone Leong Phenotypes for gene: ADAMTSL4 were changed from to Ectopia lentis et pupillae; Ectopia lentis, isolated, autosomal recessive
Thoracic aortic aneurysm or dissection v1.111 ADAMTSL4 Ivone Leong Classified gene: ADAMTSL4 as Green List (high evidence)
Thoracic aortic aneurysm or dissection v1.111 ADAMTSL4 Ivone Leong Added comment: Comment on list classification: Promoted from Red to Green based on expert review from Ellen Thomas (Genomics England Curator).
Thoracic aortic aneurysm or dissection v1.111 ADAMTSL4 Ivone Leong Gene: adamtsl4 has been classified as Green List (High Evidence).
Thoracic aortic aneurysm or dissection v1.110 FLCN Ivone Leong commented on gene: FLCN
Thoracic aortic aneurysm or dissection v1.110 COL1A2 Ivone Leong commented on gene: COL1A2: After consulting with the Genomics England Clinical Team, it was decided that this gene should remain Green on this panel.
Thoracic aortic aneurysm or dissection v1.110 COL1A1 Ivone Leong commented on gene: COL1A1
Congenital hypothyroidism v2.1 TBL1X Ivone Leong Phenotypes for gene: TBL1X were changed from isolated mild-moderate central hypothyroidism to isolated mild-moderate central hypothyroidism; Hypothyroidism, congenital, nongoitrous, 8, 301033
Intellectual disability v3.0 SUPT16H Konstantinos Varvagiannis gene: SUPT16H was added
gene: SUPT16H was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: SUPT16H was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SUPT16H were set to http://dx.doi.org/10.1136/jmedgenet-2019-106193
Phenotypes for gene: SUPT16H were set to Global developmental delay; Intellectual disability; Abnormality of the corpus callosum
Penetrance for gene: SUPT16H were set to Complete
Review for gene: SUPT16H was set to AMBER
Added comment: Bina et al (2020 - http://dx.doi.org/10.1136/jmedgenet-2019-106193) report on 4 unrelated individuals with heterozygous SNVs affecting SUPT16H as well as 1 further with microdeletion spanning this gene.

The phenotype consisted of DD with subsequent ID in a subset of them (ages of the cohort: 2y-14y), autistic features in few, abnormalities of the corpus callosum (for 3 with available MRI images), variable gastrointestinal problems in some, and possibly minor dysmorphic features.

SUPT16H encodes a subunit of the FACT (facilitates chromatin transcription) complex, a chromatin-specific factor required for transcription elongation as well as for DNA replication and repair (OMIM citing Belotserkovskaya et al. 2003 - PMID: 12934006). The 2 subunits of the complex [Spt16 (encoded by SUPT16H) and SSRP1] are essential for histone regulation. As the authors note, Spt16 interacts with the histone dimer H2A-H2B during transcription to allow RNA polymerase access to previously coiled DNA [cited PMIDs : 9489704, 10421373 / A recent study by Liu et al 2019 (PMID: 31775157) appears highly relevant].

SUPT16H has a Z-score of 5.1 in gnomAD and a pLI of 1 (%HI of 22.56 in Decipher).

SNVs :
4 de novo missense SNVs were identified following exome sequencing (NM_007192.3:c.484A>G or I162V / L432P / N571S / R734W), all absent from gnomAD and mostly predicted to be deleterious (I162V predicted benign, tolerated, disease-causing by PolyPhen2, SIFT, MutationTaster respectively and had a CADD score of 13.61). Prior work-up for these individuals (incl. CMA in some / MS-MLPA for Angelman s. in 1 / metabolic investigations) had (probably) not revealed an apparent cause, with small CNVs inherited from healthy parents (a 4q13.3 dup / 20q13.2 del - coordinates not provided).

There were no studies performed for the identified variants.

CNVs :
A 5th individual reported by Bina et al was found to harbor a 2.05 Mb 14q11.2 deletion spanning SUPT16H. The specific deletion also spanned CHD8 while the same individual harbored also a 30.17 Mb duplication of 18p11.32q12.1.

CNVs spanning SUPT16H reported to date, also span the (very) proximal CHD8. [Genomic coordinates (GRCh38) for SUPT16H and CHD8 as provided by OMIM : 14:21,351,471-21,384,018 / 14:21,385,198-21,456,122]. Haploinsufficiency of CHD8 is associated with a distinctive syndrome with overgrowth and ID (Douzgou et al 2019 - PMID: 31001818). The phenotype of SUPT16H-CHD8 duplications is discussed in other studies/reviews. [Smol et al 2020 - PMID: 31823155 / Smyk et al 2016 - PMID: 26834018].

Animal models were not commented on by Bina et al (possibly not available for mouse : http://www.informatics.jax.org/marker/MGI:1890948 / https://www.mousephenotype.org/data/genes/MGI:1890948 ).
Sources: Literature
Genetic epilepsy syndromes v2.0 TET3 Konstantinos Varvagiannis gene: TET3 was added
gene: TET3 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: TET3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TET3 were set to https://doi.org/10.1016/j.ajhg.2019.12.007
Phenotypes for gene: TET3 were set to Global developmental delay; Intellectual disability; Macrocephaly; Growth abnormality; Seizures; Autistic behavior; Abnormality of movement; Abnormality of the face
Penetrance for gene: TET3 were set to Complete
Review for gene: TET3 was set to AMBER
Added comment: Beck et al (2020 - DOI: https://doi.org/10.1016/j.ajhg.2019.12.007) report on individuals with monoallelic de novo or biallelic pathogenic TET3 variants.

For both inheritance modes (AR/AD) DD/ID were among the observed features (mild-severe - individuals from families 2, 4 and 6 for whom presence of ID was not commented, relevance to the current panel is suggested from the developmental milestones in the supplement. One individual presented DD without ID). Other features included hypotonia (in 8), ASD/autistic features (in 5), seizures (2 unrelated subjects for each inheritance mode). Postnatal growth abnormalities were observed in many, in most cases involving head size (with/without abnormal stature) and few presented abnormal prenatal growth. Variable movement disorders were observed in some. Some facial features appeared to be more common (eg. long face, tall forehead, etc).

Most were referred for their DD. Extensive prior genetic investigations had (mostly) come out normal (with possible contribution of a 16p11.2 dup in an individual with monoallelic variant or a 16q22 dup in another with biallelic TET3 variants). Monoallelic / biallelic variants in all subjects were identified following exome sequencing.

TET3 encodes a methylcytosine dioxygenase (the TET family consisting of 3 enzymes, TET1, TET2, TET3). These enzymes are involved in DNA demethylation through a series of reactions beginning with the conversion of 5-methyl cytosine [5mc] to 5-hydromethylcytosine [5hmC].

5 individuals from 3 families (1/3 consanguineous) harbored biallelic missense variants. 5 different missense variants were observed. Heterozygous parents appeared to be mildly affected (eg. having learning difficulties, etc).

6 individuals from 5 families harbored monoallelic variants [3 truncating (of which 2 localizing in the last exon), 2 missense SNVs]. In one family the variant was inherited from a similarly affected parent. In all other cases the variant had occured de novo. No additional TET3 variants were identified, with the limitations of WES.

All missense mutations, whether observed in individuals with biallelic or monoallelic variants, were located within the catalytic domain or - for a single variant (NM_001287491.1:c.2254C>T / p.Arg752Cys) - adjacent to it.

Functional studies were carried out only for (all) missense variants observed in individuals with biallelic variants. Conversion of 5mC to 5hmC is the first step in DNA demethylation. In HEK293 cells overexpressing either wt or variants, production of 5hmc was measured. 4/5 missense variants evaluated demonstrated a defect in converting 5mC to 5hmC, Arg752Cys being an exception (as also predicted by its localization).

DD/ID and abnormal growth are also features of disorders of the epigenetic machinery (DNA methylation machinery, histone machinery, chromatin remodelers, other chromatin-associated proteins). Similarly to TET3, both monoallelic and biallelic variants in KDM5B, encoding for another component of the epigenetic machinery, have been identified in individuals with ID.

Mouse models discussed by the authors [several Refs provided though not here reviewed] : The gene has been shown to be highly expressed in oocytes, zygotes and neurons and to play a role in demethylation of the paternal genome after fertilization. (From the MGI: 'mice inheriting a null allele from a germ cell conditional null mother display impaired reprogramming of the paternal genome resulting in reduced embryo viability'). Beck et al also note that Tet3 inhibition or depletion in differentiated neurons can impact synaptic function [PMIDs cited: 25915473, 24757058, 26711116].
Sources: Literature
Intellectual disability v3.0 TET3 Konstantinos Varvagiannis gene: TET3 was added
gene: TET3 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: TET3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TET3 were set to https://doi.org/10.1016/j.ajhg.2019.12.007
Phenotypes for gene: TET3 were set to Global developmental delay; Intellectual disability; Macrocephaly; Growth abnormality; Seizures; Autistic behavior; Abnormality of movement; Abnormality of the face
Penetrance for gene: TET3 were set to Complete
Review for gene: TET3 was set to GREEN
Added comment: Beck et al (2020 - DOI: https://doi.org/10.1016/j.ajhg.2019.12.007) report on individuals with monoallelic de novo or biallelic pathogenic TET3 variants.

For both inheritance modes (AR/AD) DD/ID were among the observed features (mild-severe - individuals from families 2, 4 and 6 for whom presence of ID was not commented, relevance to the current panel is suggested from the developmental milestones in the supplement. One individual presented DD without ID). Other features included hypotonia (in 8), ASD/autistic features (in 5), seizures (2 unrelated subjects for each inheritance mode). Postnatal growth abnormalities were observed in many, in most cases involving head size (with/without abnormal stature) and few presented abnormal prenatal growth. Variable movement disorders were observed in some. Some facial features appeared to be more common (eg. long face, tall forehead, etc).

Most were referred for their DD. Extensive prior genetic investigations had (mostly) come out normal (with possible contribution of a 16p11.2 dup in an individual with monoallelic variant or a 16q22 dup in another with biallelic TET3 variants). Monoallelic / biallelic variants in all subjects were identified following exome sequencing.

TET3 encodes a methylcytosine dioxygenase (the TET family consisting of 3 enzymes, TET1, TET2, TET3). These enzymes are involved in DNA demethylation through a series of reactions beginning with the conversion of 5-methyl cytosine [5mc] to 5-hydromethylcytosine [5hmC].

5 individuals from 3 families (1/3 consanguineous) harbored biallelic missense variants. 5 different missense variants were observed. Heterozygous parents appeared to be mildly affected (eg. having learning difficulties, etc).

6 individuals from 5 families harbored monoallelic variants [3 truncating (of which 2 localizing in the last exon), 2 missense SNVs]. In one family the variant was inherited from a similarly affected parent. In all other cases the variant had occured de novo. No additional TET3 variants were identified, with the limitations of WES.

All missense mutations, whether observed in individuals with biallelic or monoallelic variants, were located within the catalytic domain or - for a single variant (NM_001287491.1:c.2254C>T / p.Arg752Cys) - adjacent to it.

Functional studies were carried out only for (all) missense variants observed in individuals with biallelic variants. Conversion of 5mC to 5hmC is the first step in DNA demethylation. In HEK293 cells overexpressing either wt or variants, production of 5hmc was measured. 4/5 missense variants evaluated demonstrated a defect in converting 5mC to 5hmC, Arg752Cys being an exception (as also predicted by its localization).

DD/ID and abnormal growth are also features of disorders of the epigenetic machinery (DNA methylation machinery, histone machinery, chromatin remodelers, other chromatin-associated proteins). Similarly to TET3, both monoallelic and biallelic variants in KDM5B, encoding for another component of the epigenetic machinery, have been identified in individuals with ID.

Mouse models discussed by the authors [several Refs provided though not here reviewed] : The gene has been shown to be highly expressed in oocytes, zygotes and neurons and to play a role in demethylation of the paternal genome after fertilization. (From the MGI: 'mice inheriting a null allele from a germ cell conditional null mother display impaired reprogramming of the paternal genome resulting in reduced embryo viability'). Beck et al also note that Tet3 inhibition or depletion in differentiated neurons can impact synaptic function [PMIDs cited: 25915473, 24757058, 26711116].
Sources: Literature
Intellectual disability v3.0 PIGP Konstantinos Varvagiannis changed review comment from: Please consider upgrading this gene to Green.

A recent study Vetro et al. (2020 - https://doi.org/10.1212/NXG.0000000000000387) identified 4 additional affected individuals with severe EIEE, belonging to a large inbred family. Following extensive genetic investigations (all of which were non-diagnostic) these subjects were found to harbor in homozygosity the frameshift variant also reported in the 2 previous studies (NM_153681.2:c.456delA / p.Glu153AsnfsTer34 or NM_153682.2:c.384delA / p.Glu129AsnfsTer34). Reduced expression of the GPI-anchor protein CD16 was demonstrated in granulocytes of affected individuals.; to: Please consider upgrading this gene to Green.

In a recent study, Vetro et al. (2020 - https://doi.org/10.1212/NXG.0000000000000387) identified 4 additional affected individuals with severe EIEE, belonging to a large inbred family. Following extensive genetic investigations (all of which were non-diagnostic) these subjects were found to harbor in homozygosity the frameshift variant also reported in the 2 previous studies (NM_153681.2:c.456delA / p.Glu153AsnfsTer34 or NM_153682.2:c.384delA / p.Glu129AsnfsTer34). Reduced expression of the GPI-anchor protein CD16 was demonstrated in granulocytes of affected individuals.
Genetic epilepsy syndromes v2.0 PIGP Konstantinos Varvagiannis edited their review of gene: PIGP: Added comment: Please consider upgrading this gene to Green.

In a recent study, Vetro et al. (2020 - https://doi.org/10.1212/NXG.0000000000000387) identified 4 additional affected individuals with severe EIEE, belonging to a large inbred family. Following extensive genetic investigations (all of which were non-diagnostic) these subjects were found to harbor in homozygosity the frameshift variant also reported in the 2 previous studies (NM_153681.2:c.456delA / p.Glu153AsnfsTer34 or NM_153682.2:c.384delA / p.Glu129AsnfsTer34). Reduced expression of the GPI-anchor protein CD16 was demonstrated in granulocytes of affected individuals.; Changed publications: 28334793, 31139695, https://doi.org/10.1212/NXG.0000000000000387
Intellectual disability v3.0 PIGP Konstantinos Varvagiannis edited their review of gene: PIGP: Added comment: Please consider upgrading this gene to Green.

A recent study Vetro et al. (2020 - https://doi.org/10.1212/NXG.0000000000000387) identified 4 additional affected individuals with severe EIEE, belonging to a large inbred family. Following extensive genetic investigations (all of which were non-diagnostic) these subjects were found to harbor in homozygosity the frameshift variant also reported in the 2 previous studies (NM_153681.2:c.456delA / p.Glu153AsnfsTer34 or NM_153682.2:c.384delA / p.Glu129AsnfsTer34). Reduced expression of the GPI-anchor protein CD16 was demonstrated in granulocytes of affected individuals.; Changed publications: 28334793, 31139695, https://doi.org/10.1212/NXG.0000000000000387
Intellectual disability v3.0 ZNF292 Konstantinos Varvagiannis commented on gene: ZNF292: Correction to the phrase "Manual review of some relevant LoF variants in gnomAD suggested that they represent false positive calls":

Irrespective of the variants identified in their cohort, Mirzaa et al. reviewed many pLoF variants which are listed in gnomAD. The authors suggested that some of these variants may not represent true LoF variants.

Eg. NM_015021.3:c.2690C>A ( https://gnomad.broadinstitute.org/variant/6-87966037-C-A ) which appears to be a stopgain variant (Ser[TCA]>Ter[TAA]) is probably not a true LoF variant. It always occurred in cis (/the same reads) with NM_015021.3:c.2689T>C (Ser[TCA] to Pro[CCA]). This is visible in the IGV graph of gnomAD (url above).

Thus, gnomAD lists 2 single-nucleotide variants affecting the same codon, one next to the other. However, as the 2 SNVs always occurred in cis, this represents a single missense multi-nucleotide variant (Ser[TCA]>Gln[CAA]) [ NM_015021.3(ZNF292_v001):c.2689_2690delinsCA ].

Similar observations were made for other variants seen in gnomAD.
Intellectual disability v3.0 NUS1 Konstantinos Varvagiannis edited their review of gene: NUS1: Added comment: Please consider upgrading this gene (NUS1 is also rated Green in the epilepsy panel).

Den et al (2019 - PMID: 31656175) reported on 2 additional unrelated individuals (aged 17 and 59y) both presenting intellectual disability, epilepsy , involuntary movements, ataxia and scoliosis. Both were found to harbor the same splicing variant in NUS1 (NM_138459.4:c.691+1C>A) following exome sequencing. Using lymphoblastoid cell lines from both individuals it was demonstrated that the variant creates a new splice donor site in exon 3 further creating a new reading frame and producing a premature termination codon [c.601_691del or p.(Arg202Glnfs*9)]. Using cyclohexamide, it was further shown that the mutant mRNA is partially subjected to NMD. [Additional variants identified by exome for the 2 subjects were non diagnostic (/VUS). An SPTAN1 nonsense variant identified in one was inherited from an unaffected parent (dominant-negative mechanism listed in G2P for this gene / in ClinVar all pLoF variants are submitted as VUS)].
-----; Changed rating: GREEN; Changed publications: 25066056, 29100083, 24824130, 30348779, 31656175
Hereditary ataxia v1.205 CACNA2D2 Louise Daugherty Classified gene: CACNA2D2 as Green List (high evidence)
Hereditary ataxia v1.205 CACNA2D2 Louise Daugherty Gene: cacna2d2 has been classified as Green List (High Evidence).
Hereditary ataxia v1.204 CACNA2D2 Louise Daugherty Classified gene: CACNA2D2 as No list
Hereditary ataxia v1.204 CACNA2D2 Louise Daugherty Added comment: Comment on list classification: New gene added to panel by Genomics England clinical team recommendation and upgraded Grey to Green. There is enough evidence to support a Green rating on this panel, confirming biallelic CACNA2D2 variants and pertinent to the corresponding phenotype of Cerebellar anomalies/ataxia/epilepsy/ID.
Hereditary ataxia v1.204 CACNA2D2 Louise Daugherty Gene: cacna2d2 has been removed from the panel.
Hereditary spastic paraplegia v1.213 TFG Louise Daugherty edited their review of gene: TFG: Changed rating: GREEN
Genetic epilepsy syndromes v2.0 CACNA2D2 Louise Daugherty commented on gene: CACNA2D2
Genetic epilepsy syndromes v2.0 CACNA2D2 Louise Daugherty Tag watchlist was removed from gene: CACNA2D2.
Hereditary ataxia v1.203 CACNA2D2 Louise Daugherty Publications for gene: CACNA2D2 were set to PMID: 30410802, PMID: 31402629, PMID: 24358150, PMID: 23339110, PMID: 29997391; PMID : 14660671; PMID: 15331424
Hereditary spastic paraplegia v1.213 TFG Louise Daugherty Classified gene: TFG as Green List (high evidence)
Hereditary spastic paraplegia v1.213 TFG Louise Daugherty Added comment: Comment on list classification: Upgraded gene from Amber to Green due to feedback from Genomics England clinical team, due to re-analysing a few cases for diagnostic discovery there is enough evidence to support a Green rating on this panel.
Hereditary spastic paraplegia v1.213 TFG Louise Daugherty Gene: tfg has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.212 TFG Louise Daugherty Phenotypes for gene: TFG were changed from to Hereditary spastic paraplegia - childhood onset; Intellectual disability; Hereditary spastic paraplegia - adult onset; neuropathy
Hereditary spastic paraplegia v1.211 TFG Louise Daugherty Added comment: Comment on publications: added publications to support upgrading from Amber to Green.
Hereditary spastic paraplegia v1.211 TFG Louise Daugherty Publications for gene: TFG were set to Beetz et al. (2013)
Hereditary neuropathy v1.368 AR_CAG Louise Daugherty Classified STR: AR_CAG as Green List (high evidence)
Hereditary neuropathy v1.368 AR_CAG Louise Daugherty Added comment: Comment on list classification: Upgraded STR from Amber to Green due to feedback from Genomics England clinical team, due to re-analysing a few cases for diagnostic discovery there is enough evidence to support a Green rating on this panel.
Hereditary neuropathy v1.368 AR_CAG Louise Daugherty Str: ar_cag has been classified as Green List (High Evidence).
Hereditary neuropathy v1.367 AR_CAG Louise Daugherty Added comment: Comment on publications: added publications to support upgrading from Amber to Green.
Hereditary neuropathy v1.367 AR_CAG Louise Daugherty Publications for STR: AR_CAG were set to
Thoracic aortic aneurysm or dissection v1.110 ADAMTSL4 Ellen Thomas reviewed gene: ADAMTSL4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ectopia lentis et pupillae, Ectopia lentis, isolated, autosomal recessive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypogonadotropic hypogonadism idiopathic v1.2 NDNF Simon Thomas gene: NDNF was added
gene: NDNF was added to Hypogonadotropic hypogonadism idiopathic. Sources: Literature
Mode of inheritance for gene: NDNF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NDNF were set to PMID: 31883645
Phenotypes for gene: NDNF were set to Congenital hypogonadotropic hypogonadism (CHH)
Penetrance for gene: NDNF were set to unknown
Review for gene: NDNF was set to GREEN
gene: NDNF was marked as current diagnostic
Added comment: Messina et al (Am J Hum Genet Jan 2020) screened NDNF (Neuron-Derived Neurotrophic Factor) because, in common with several IHH genes, it contains a fibronectin-3 (FN3) domain.
Three heterozygous protein-truncating variants and one heterozygous missense variant were identified in a cohort of 240 unrelated IHH patients. The authors also provided supporting evidence from animal models.
Sources: Literature
Membranoproliferative glomerulonephritis v2.2 DGKE Daniel Gale reviewed gene: DGKE: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23274426; Phenotypes: Proteinuria, membranoproliferative glomerulonephritis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Membranoproliferative glomerulonephritis v2.2 CFI Daniel Gale reviewed gene: CFI: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Membranoproliferative glomerulonephritis v2.2 CFH Daniel Gale reviewed gene: CFH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 9312129; Phenotypes: C3 glomerulopathy, Membranoproliferative glomerulonephritis, renal insufficiency, proteinuria; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Membranoproliferative glomerulonephritis v2.2 CFB Daniel Gale reviewed gene: CFB: Rating: RED; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 25758434; Phenotypes: C3 glomerulopathy, Membranoproliferative glomerulonephritis, renal insufficiency, proteinuria; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Membranoproliferative glomerulonephritis v2.2 C3 Daniel Gale reviewed gene: C3: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 20852386, 26471127; Phenotypes: C3 glomerulopathy, Membranoproliferative glomerulonephritis, renal insufficiency, proteinuria; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Congenital disorders of glycosylation v2.0 TMEM165 Rebecca Foulger commented on gene: TMEM165
Congenital disorders of glycosylation v2.0 SLC39A8 Rebecca Foulger commented on gene: SLC39A8
Congenital disorders of glycosylation v2.0 SLC35C1 Rebecca Foulger commented on gene: SLC35C1
Congenital disorders of glycosylation v2.0 SLC35A1 Rebecca Foulger Deleted their comment
Congenital disorders of glycosylation v2.0 SLC35A1 Rebecca Foulger commented on gene: SLC35A1: GlyGen link: https://www.glygen.org/protein_detail.html?uniprot_canonical_ac=P78382-1
Congenital disorders of glycosylation v2.0 SLC35A1 Rebecca Foulger commented on gene: SLC35A1: GlyGen link: https://www.glygen.org/protein_detail.html?uniprot_canonical_ac=P78382-1
Congenital disorders of glycosylation v2.0 SEC23B Rebecca Foulger commented on gene: SEC23B
Congenital disorders of glycosylation v2.0 POMT2 Rebecca Foulger commented on gene: POMT2
Congenital disorders of glycosylation v2.0 POMT1 Rebecca Foulger commented on gene: POMT1
Congenital disorders of glycosylation v2.0 POMGNT1 Rebecca Foulger commented on gene: POMGNT1
Congenital disorders of glycosylation v2.0 PMM2 Rebecca Foulger commented on gene: PMM2
Congenital disorders of glycosylation v2.0 PIGA Rebecca Foulger commented on gene: PIGA
Congenital disorders of glycosylation v2.0 PGM1 Rebecca Foulger commented on gene: PGM1
Congenital disorders of glycosylation v2.0 NGLY1 Rebecca Foulger commented on gene: NGLY1
Congenital disorders of glycosylation v2.0 MOGS Rebecca Foulger commented on gene: MOGS
Congenital disorders of glycosylation v2.0 MGAT2 Rebecca Foulger commented on gene: MGAT2
Congenital disorders of glycosylation v2.0 LARGE1 Rebecca Foulger commented on gene: LARGE1
Congenital disorders of glycosylation v2.0 GNE Rebecca Foulger commented on gene: GNE
Congenital disorders of glycosylation v2.0 GFPT1 Rebecca Foulger commented on gene: GFPT1
Congenital disorders of glycosylation v2.0 GALNT3 Rebecca Foulger commented on gene: GALNT3
Congenital disorders of glycosylation v2.0 FKTN Rebecca Foulger commented on gene: FKTN
Congenital disorders of glycosylation v2.0 FKRP Rebecca Foulger commented on gene: FKRP
Congenital disorders of glycosylation v2.0 EXT2 Rebecca Foulger commented on gene: EXT2
Congenital disorders of glycosylation v2.0 EXT1 Rebecca Foulger commented on gene: EXT1
Congenital disorders of glycosylation v2.0 DPAGT1 Rebecca Foulger commented on gene: DPAGT1
Congenital disorders of glycosylation v2.0 COG8 Rebecca Foulger commented on gene: COG8
Congenital disorders of glycosylation v2.0 COG7 Rebecca Foulger commented on gene: COG7
Congenital disorders of glycosylation v2.0 COG6 Rebecca Foulger commented on gene: COG6
Congenital disorders of glycosylation v2.0 COG5 Rebecca Foulger commented on gene: COG5
Congenital disorders of glycosylation v2.0 COG4 Rebecca Foulger commented on gene: COG4
Congenital disorders of glycosylation v2.0 COG1 Rebecca Foulger commented on gene: COG1
Congenital disorders of glycosylation v2.0 CHSY1 Rebecca Foulger commented on gene: CHSY1
Congenital disorders of glycosylation v2.0 CHST6 Rebecca Foulger commented on gene: CHST6
Congenital disorders of glycosylation v2.0 CHST3 Rebecca Foulger commented on gene: CHST3
Congenital disorders of glycosylation v2.0 CCDC115 Rebecca Foulger commented on gene: CCDC115
Congenital disorders of glycosylation v2.0 B4GALT1 Rebecca Foulger commented on gene: B4GALT1
Congenital disorders of glycosylation v2.0 B3GLCT Rebecca Foulger commented on gene: B3GLCT
Additional findings health related v0.92 APOB Ellen McDonagh Mode of pathogenicity for gene: APOB was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Renal tubulopathies v2.0 HNF4A Zornitza Stark gene: HNF4A was added
gene: HNF4A was added to Renal tubulopathies. Sources: Expert list
Mode of inheritance for gene: HNF4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNF4A were set to 22802087; 24285859; 30005691; 28458902; 31875549
Phenotypes for gene: HNF4A were set to Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young, MIM#616026
Review for gene: HNF4A was set to GREEN
gene: HNF4A was marked as current diagnostic
Added comment: Multiple individuals reported.
Sources: Expert list
Atypical haemolytic uraemic syndrome v2.1 CFHR5 Zornitza Stark gene: CFHR5 was added
gene: CFHR5 was added to Atypical haemolytic uraemic syndrome. Sources: Expert list
Mode of inheritance for gene: CFHR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CFHR5 were set to 22622361
Phenotypes for gene: CFHR5 were set to Nephropathy due to CFHR5 deficiency, MIM# 614809
Review for gene: CFHR5 was set to AMBER
Added comment: There is at least one paper specifically linking variants in this gene with aHUS, not quite sure where this gene belongs.
Sources: Expert list
Atypical haemolytic uraemic syndrome v2.1 ADAMTS13 Zornitza Stark gene: ADAMTS13 was added
gene: ADAMTS13 was added to Atypical haemolytic uraemic syndrome. Sources: Expert list
Mode of inheritance for gene: ADAMTS13 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ADAMTS13 were set to Thrombotic thrombocytopenic purpura, familial, MIM# 274150
Review for gene: ADAMTS13 was set to AMBER
Added comment: It is difficult to know whether to include this gene on an aHUS panel; there is considerable overlap in the clinical features between TTP and HUS, and we have included it in ours.
Sources: Expert list
Proteinuric renal disease v2.0 TPRKB chirag patel reviewed gene: TPRKB: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 28805828, 30053862; Phenotypes: Galloway-Mowat syndrome 5, OMIM #617731; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.0 PTPRO Zornitza Stark reviewed gene: PTPRO: Rating: AMBER; Mode of pathogenicity: None; Publications: 21722858, 30065916; Phenotypes: Nephrotic syndrome, type 6 #614196; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.0 KANK2 Zornitza Stark reviewed gene: KANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25961457; Phenotypes: Nephrotic syndrome, type 16, MIM#617783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.0 DGKE Zornitza Stark reviewed gene: DGKE: Rating: GREEN; Mode of pathogenicity: None; Publications: 23542698, 23274426; Phenotypes: Nephrotic syndrome, type 7, MIM# 615008; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v2.0 CD2AP chirag patel Deleted their review
Proteinuric renal disease v2.0 CD2AP chirag patel reviewed gene: CD2AP: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30612599, 17713465; Phenotypes: Glomerulosclerosis, focal segmental, 3, OMIM #607832; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.0 CD2AP Zornitza Stark reviewed gene: CD2AP: Rating: AMBER; Mode of pathogenicity: None; Publications: 17713465, 30612599; Phenotypes: Glomerulosclerosis, focal segmental, 3 #607832; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.0 APOE Zornitza Stark gene: APOE was added
gene: APOE was added to Proteinuric renal disease. Sources: Expert list
Mode of inheritance for gene: APOE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOE were set to 10432380; 9176854; 18077821
Phenotypes for gene: APOE were set to Lipoprotein glomerulopathy, MIM# 611771
Review for gene: APOE was set to GREEN
Added comment: Specific variants in Japanese/Chinese linked to the development of a glomerulopathy, characterised by proteinuria, renal failure and deposition of lipoprotein thrombi.
Sources: Expert list
Proteinuric renal disease v2.0 AMN Zornitza Stark reviewed gene: AMN: Rating: GREEN; Mode of pathogenicity: None; Publications: 30691194, 26040326; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Palmoplantar keratoderma and erythrokeratodermas v1.17 CTSC Catherine Snow Classified gene: CTSC as Green List (high evidence)
Palmoplantar keratoderma and erythrokeratodermas v1.17 CTSC Catherine Snow Added comment: Comment on list classification: Gene added to panel based on feedback from Genomics England clinician.
Palmoplantar keratoderma and erythrokeratodermas v1.17 CTSC Catherine Snow Gene: ctsc has been classified as Green List (High Evidence).
Palmoplantar keratoderma and erythrokeratodermas v1.16 CTSC Zerin Hyder gene: CTSC was added
gene: CTSC was added to Palmoplantar keratoderma and erythrokeratodermas. Sources: Expert list
Mode of inheritance for gene: CTSC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTSC were set to 10581027; 15585850; 11180012; 10662807
Phenotypes for gene: CTSC were set to Papillon-Lefevre syndrome; Haim-Munk syndrome; Periodontitis 1, juvenile
Penetrance for gene: CTSC were set to unknown
Review for gene: CTSC was set to GREEN
gene: CTSC was marked as current diagnostic
Added comment: This gene was part of an initial gene list collated by Thomas Cullup, GOSH and Veronica Kinsler, UCL, 25.Jan.2019 on behalf of the GMS Skin Specialist Test Group.
CTSC green on GMS panel, upgrade on 100K panel.
Sources: Expert list
Hereditary spastic paraplegia v1.210 TFG Zerin Hyder reviewed gene: TFG: Rating: GREEN; Mode of pathogenicity: None; Publications: 23479643, 27601211, 28124177, 27492651; Phenotypes: Hereditary spastic paraplegia - childhood onset, Intellectual disability, Hereditary spastic paraplegia - adult onset; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.366 AR_CAG Zerin Hyder reviewed STR: AR_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: 8469342, 15851746, 1449253; Phenotypes: Spinal and bulbar muscular atrophy or Kennedy diseases 313200; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic epilepsy syndromes v2.0 ASTN1 Zornitza Stark gene: ASTN1 was added
gene: ASTN1 was added to Genetic epilepsy syndromes. Sources: Expert list
Mode of inheritance for gene: ASTN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASTN1 were set to 29706646; 27431290; 26539891
Phenotypes for gene: ASTN1 were set to Intellectual disability; epilepsy; cortical malformations
Review for gene: ASTN1 was set to GREEN
gene: ASTN1 was marked as current diagnostic
Added comment: Three families reported as part of large cohorts albeit proposing multiple novel candidate genes with minimal detail and no functional validation.
Sources: Expert list
Genetic epilepsy syndromes v2.0 ASNS Zornitza Stark gene: ASNS was added
gene: ASNS was added to Genetic epilepsy syndromes. Sources: Expert list
Mode of inheritance for gene: ASNS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ASNS were set to Asparagine synthetase deficiency, MIM# 615574
Review for gene: ASNS was set to GREEN
Added comment: Encephalopathy, including seizures is a feature of this metabolic condition.
Sources: Expert list
Genetic epilepsy syndromes v2.0 APC2 Zornitza Stark reviewed gene: APC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31585108; Phenotypes: Cortical dysplasia, complex, with other brain malformations 10, MIM#618677; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic epilepsy syndromes v2.0 ADRA2B Zornitza Stark reviewed gene: ADRA2B: Rating: RED; Mode of pathogenicity: None; Publications: 24114805, 21937992; Phenotypes: Cortical myoclonus and epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic epilepsy syndromes v2.0 ADAM22 Zornitza Stark gene: ADAM22 was added
gene: ADAM22 was added to Genetic epilepsy syndromes. Sources: Expert list
Mode of inheritance for gene: ADAM22 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAM22 were set to 27066583; 30237576
Phenotypes for gene: ADAM22 were set to Epileptic encephalopathy, early infantile, 61, MIM# 617933
Review for gene: ADAM22 was set to AMBER
Added comment: Two families reported; the second one as part of a large consanguineous cohort.
Sources: Expert list
Thoracic aortic aneurysm or dissection v1.110 CBS Ivone Leong Classified gene: CBS as Amber List (moderate evidence)
Thoracic aortic aneurysm or dissection v1.110 CBS Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber based on evidence provided by expert reviews.
Thoracic aortic aneurysm or dissection v1.110 CBS Ivone Leong Gene: cbs has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v2.0 RNF113A Konstantinos Varvagiannis gene: RNF113A was added
gene: RNF113A was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: RNF113A 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: RNF113A were set to 25612912; 31880405; 31793730; 29133357; 30506991; 15256591; 24026126; 23555887
Phenotypes for gene: RNF113A were set to ?Trichothiodystrophy 5, nonphotosensitive, 300953
Penetrance for gene: RNF113A were set to Complete
Review for gene: RNF113A was set to GREEN
Added comment: The gene has been reviewed for the ID panel. Seizures have been reported in 4 affected males from 3 families.

From the ID panel:
Nonphotosensitive trichothiodystrophy-5 (TTD5 - #300953) is caused by mutation in the RNF113A gene on Xq24. DD, ID and seizures are part of the phenotype in males. (Several) heterozygous females have not been reported to exhibit these features (DD/ID/seizures) although a single female in the first report had speech/motor delay and learning difficulties.

Corbett et al (2015 - PMID: 25612912) reported on 2 cousins with profound ID and epilepsy among other principal features of the disorder. Linkage analysis (probably low(?) LOD score) localized the gene to a 7.75 Mb region on Xq and subsequent Sanger and exome sequencing identified an RNF113A stopgain variant in both (NM_006978.2:c.901C>T / p.Q301*). Other X-chr variants did not segregate with the disorder. Previously sequencing of other trichothiodystrophy genes (in both) and CMA (X-chromosome BAC array / ISCA CMA) were non-diagnostic. The variant in this family was identified in a previous study (Tarpey et al 2009 - PMID: 19377476) but was 'incorrectly' discarded at the time due to a sequencing error in a control DNA sample (analysis repeated by Corbett et al). The same variant was also reported in 2 fetuses in a later report (PMID: 31793730).

Mendelsohn et al (2019 - PMID: 31880405) reported on 2 unrelated affected males. The 1st presented with severe DD/ID (independent walking at 7y, single words/non-verbal with with special educational needs at 11y), seizures as well as typical features of the disorder. Metabolic work-up (incl. 7-DHCR) and genetic testing (Allagile, PFIC genes, CMA) were non-diagnostic. Duo WES revealed a frameshift variant [c.903_910delGCAGACCCA / p.(Gln302fs*12)] inherited from the mother. Maternal XCI was completely skewed (100:0). The 2nd individual (briefly reported as REQ18-0616 by Monies et al - PMID: 31130284) presented global DD and seizures along with all other core features of the disorder at the age of 16m. Karyotype was normal. Exome revealed a frameshift variant [NM_006978.3:c.897_898delTG / p.(Cys299*)].

Further evidence is based on the role of the RNA113A, being involved in mRNA splicing (/spiceosome function) [Gatti da Silva et al 2018 - PMID: 30506991 & many other Refs] as well in DNA repair (E3 ubiquitin-protein ligase in a mechanism for sensing DNA damage induced by alkylation) [Brickner et al 2017 - PMID: 29133357]. In the latter study, LCLs from individuals harboring Q301* were shown to be hypersensitive to an alkylating agent (MMS) which was also the case for an RNF113A knockdown cell line. The cells had reduced ASCC alkylation repair complex foci formation, which was rescued upon reconstitution of patient cells with wt RNF113A.

Animal models :
Disruption of rnf113a in zebrafish resulted among others in small head and underdeveloped gut (PMID cited : 15256591 - Amsterdam et al) similar to the microcephaly observed in several individuals and/or abnormal gut development/diarrhoea reported in few.
Knockdown of the Drosophila ortholog (mdlc) led to reduced proliferation of neuroblasts. Neuronal differentiation was initiated but not completed. Expression of the full-length human gene rescued the CNS defects (discussed by Mendelsohn et al citing PMID: 24026126 - Carney et al). RNA-seq data from the same study were analyzed by Corbett et al, and differentialy expressed genes were enriched for genes involved in DNA damage response and repair.
Knockdown of RNF-113 in C.elegans sensitises cells to UVA-induced DNA damage. RNF-113 was shown to be involved in interstrand DNA crosslink repair and interact with a RAD51C homolog (PMID cited: 23555887 - Lee et al).

[Please consider upgrade/inclusion in other relevant panels eg. the 'Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome panel' where the gene has red rating].
Sources: Literature
Intellectual disability v3.0 RNF113A Konstantinos Varvagiannis reviewed gene: RNF113A: Rating: GREEN; Mode of pathogenicity: None; Publications: 25612912, 31880405, 31793730, 29133357, 30506991, 15256591, 24026126, 23555887; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Rare multisystem ciliopathy disorders v1.123 PDE6D Zornitza Stark reviewed gene: PDE6D: Rating: AMBER; Mode of pathogenicity: None; Publications: 30423442; Phenotypes: Joubert syndrome type 22 (JBTS22); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal ciliopathies v1.0 SLC41A1 Zornitza Stark gene: SLC41A1 was added
gene: SLC41A1 was added to Renal ciliopathies. Sources: Expert list
Mode of inheritance for gene: SLC41A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC41A1 were set to 23661805
Phenotypes for gene: SLC41A1 were set to Nephronophthisis
Review for gene: SLC41A1 was set to RED
Added comment: Single family reported, functional data.
Sources: Expert list
Renal ciliopathies v1.0 SCLT1 Zornitza Stark gene: SCLT1 was added
gene: SCLT1 was added to Renal ciliopathies. Sources: Expert list
Mode of inheritance for gene: SCLT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCLT1 were set to 28486600; 30425282; 30237576; 28005958; 24285566
Phenotypes for gene: SCLT1 were set to Orofaciodigital syndrome type IX; Senior-Loken syndrome
Review for gene: SCLT1 was set to AMBER
Added comment: Emerging ciliopathy gene, at least one report of renal involvement; mouse model recapitulates phenotype.
Sources: Expert list
Renal ciliopathies v1.0 PDE6D Zornitza Stark reviewed gene: PDE6D: Rating: RED; Mode of pathogenicity: None; Publications: 30423442; Phenotypes: Joubert syndrome 22; Mode of inheritance: None
Renal ciliopathies v1.0 NEK1 Zornitza Stark gene: NEK1 was added
gene: NEK1 was added to Renal ciliopathies. Sources: Expert list
Mode of inheritance for gene: NEK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NEK1 were set to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520
Review for gene: NEK1 was set to GREEN
Added comment: A ciliopathy with a renal phenotype.
Sources: Expert list
Renal ciliopathies v1.0 KIF14 Zornitza Stark reviewed gene: KIF14: Rating: GREEN; Mode of pathogenicity: None; Publications: 30388224; Phenotypes: Microcephaly, renal hypo/dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal ciliopathies v1.0 KIAA0556 Zornitza Stark reviewed gene: KIAA0556: Rating: ; Mode of pathogenicity: None; Publications: 27245168, 26714646; Phenotypes: Joubert syndrome 26; Mode of inheritance: None; Current diagnostic: yes
Renal ciliopathies v1.0 IFT140 chirag patel gene: IFT140 was added
gene: IFT140 was added to Renal ciliopathies. Sources: Expert Review
Mode of inheritance for gene: IFT140 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT140 were set to PMID: 22503633, 23418020, 29706353
Phenotypes for gene: IFT140 were set to Short-rib thoracic dysplasia 9 with or without polydactyly, OMIM #266920 (aka Mainzer-Saldino syndrome)
Review for gene: IFT140 was set to GREEN
Added comment: Renal ciliopathy gene with phenotype of Mainzer-Saldino syndrome.

Nephronophthisis reported in multiple cases, with functional evidence (Patient-iPSC-Derived Kidney Organoids Show Functional Validation of a Ciliopathic Renal Phenotype).
Sources: Expert Review
Renal ciliopathies v1.0 IFT27 Zornitza Stark reviewed gene: IFT27: Rating: GREEN; Mode of pathogenicity: None; Publications: 30761183; Phenotypes: Bardet-Biedl syndrome 19, MIM# 615996; Mode of inheritance: None
Renal ciliopathies v1.0 IFT172 Zornitza Stark gene: IFT172 was added
gene: IFT172 was added to Renal ciliopathies. Sources: Expert list
Mode of inheritance for gene: IFT172 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IFT172 were set to Short-rib thoracic dysplasia 10 with or without polydactyly, MIM# 615630
Review for gene: IFT172 was set to GREEN
Added comment: Nephronophthisis is a recognised feature of this ciliopathy.
Sources: Expert list
Renal ciliopathies v1.0 ICK Zornitza Stark reviewed gene: ICK: Rating: AMBER; Mode of pathogenicity: None; Publications: 19185282, 27069622; Phenotypes: Endocrine-cerebroosteodysplasia, MIM# 612651; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal ciliopathies v1.0 HNF1B Zornitza Stark reviewed gene: HNF1B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Renal ciliopathies v1.0 DHCR7 chirag patel reviewed gene: DHCR7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Renal ciliopathies v1.0 CENPF Zornitza Stark reviewed gene: CENPF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Stromme syndrome, MIM# 243605; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal ciliopathies v1.0 ARMC9 Zornitza Stark commented on gene: ARMC9: Gene not associated with a renal phenotype.
Renal ciliopathies v1.0 ALMS1 Zornitza Stark reviewed gene: ALMS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Alstrom syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal ciliopathies v1.0 ARMC9 Zornitza Stark edited their review of gene: ARMC9: Added comment: Specifically no renal phenotype described with this gene, plus this is a syndromic condition.; Changed rating: RED
Genetic epilepsy syndromes v2.0 MTHFS Konstantinos Varvagiannis gene: MTHFS was added
gene: MTHFS was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: MTHFS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTHFS were set to 30031689; 31844630; 22303332; https://doi.org/10.1007/978-3-642-40337-8_10
Phenotypes for gene: MTHFS were set to Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination, 618367
Penetrance for gene: MTHFS were set to Complete
Review for gene: MTHFS was set to GREEN
Added comment: Biallelic pathogenic MTHFS variants cause Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination (# 618367).

The gene encodes 5,10-Methenyltetrahydrofolate synthetase which catalyzes conversion of 5-formyltetrahydrofolate (5-FTHF or folinic acid) to 5,10-methenyltetrahydrofolate (5,10-MTHF).

At least 3 unrelated individuals have been reported. The phenotype appears to be relevant to both epilepsy and ID gene panels and the role of variants/the gene supported by enzymatic activity studies, 5-FTHF accumulation, 5,10-MTHF levels (low/low-normal), the role of folate metabolism pathway overall and some supporting (metabolic) evidence from the mouse model.
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Rodan et al (2018 - PMID: 30031689) reported on 2 individuals both presenting with microcephaly, severe global DD, epilepsy, progressive spasticity and cerebral hypomyelination upon MRI imaging. Short stature was also feature in both.

The 1st patient was an 8-year-old male who following exome sequencing was found to harbor 2 missense variants each inherited from a carrier parent. (NM_006441.3:c.434G>A / p.R145Q and c.107T>C / p.L36P). A further AFG3L2 indel was not felt to fit with his phenotype (and the onset of the related disorder appears to occur later).

Previous investigations included extensive metabolic testing, CMA, Angelman syndrome methylation analysis, GFAP, POLG1, TYMP sequencing, mitochondrial genome analysis and an XL-ID gene panel (further suggesting relevance of this gene to the current panel) were all non-diagnostic.

CSF 5-MTHF levels were initially on the low-normal range, subsequently found to be decreased (upon folinic acid supplementation) and later normalized upon use of another regimen.

MTHFS activity was measured in control fibroblasts as well as fibroblasts from this individual, with the latter demonstrating no enzyme activity. Accumulation (30x elevation) of 5-FTHF (the substrate of MTHFS) was demonstrated in patient fibroblasts.

The 2nd patient was a 11-year-old male with similar features incl. global DD (standing/walking/single words at/after 4 years of age, limited vocabulary and articulation upon last examination).

Extensive metabolic work-up as well as genetic testing for an epilepsy panel, vanishing white matter disease gene panel, mitochondrial genome as well as specific gene sequencing (LAMA2, POLR3A, POLR3B) were all non-diagnostic. Trio exome revealed 2 MTHFS variants in trans configuration (c.484C>T / p.Q162X and c.434G>A / p.R145Q).
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Romero et al (2019 - PMID: 31844630) reported on a 4-year-old female with congenital microcephaly, severe global DD (nonverbal/nonambulatory at the age of 4), spasticity, epilepsy and cerebral hypomyelination.

Extensive investigations prior to exome sequencing revealed macrocytic anemia, decreased CSF 5-MTHF and elevated neopterin, 2 CNVs of uncertain significance upon CMA with additional long ROH on chr15. Methylation studies were negative. The child was homozygous for c.220C>T / p.R74X (RefSeq is probably NM_006441.3. MTHFS lies on chr15. The parents were unrelated but came from the same town). There were no other candidate variants from the exome analysis.

Both articles discuss extensively the role of the folate metabolism pathway overall in nucleic acid synthesis, AA metabolism, neurotransmitter synthesis, methylation as well as 5-FTHF / 5,10-MTHF in particular in myelin stabilization and DNA synthesis (eg. according to Romero et al. a defect in MTHFS would impair myelin production and also lead to decreased myelin stability).
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A book chapter cited by Rodan et al (in N. Blau et al. (eds.), Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases - DOI: 10.1007/978-3-642-40337-8_10) included limited details on a patient with 'MTHFS gene mutation'. This individual had early speech delay, seizures beginning in infancy, ID, autistic features, recurrent infections and was found to have very low CSF 5-MTHF levels. [Details in p169 and table 10.6 - p173].
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In a mouse model reported by Field et al (2011 - PMID: 22303332), Mthfs was disrupted through insertion of a gene trap vector between the first 2 exons. Heterozygous [Mthfs(gt/+)] mice were fertile and viable. Mthfs protein levels were slightly but not statistically significantly reduced in tissues measured. No homozygous embryos were recovered following intercrosses of heterozygous mice, suggesting that Mthfs is an essential gene. Mouse embryonic fibroblasts from heterozygous mice [Mthfs (gt/+)] exhibited reduced de novo purine biosynthesis, but did not exhibit altered de novo thymidylate biosynthesis. Plasma folate levels were altered in heterozygous mice on a standard (/control) diet.

[Please consider inclusion in other possibly relevant panels e.g. for metabolic disorders]
Sources: Literature
Intellectual disability v3.0 MTHFS Konstantinos Varvagiannis changed review comment from: Biallelic pathogenic MTHFS variants cause Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination (# 618367).

The gene encodes 5,10-Methenyltetrahydrofolate synthetase which catalyzes conversion of 5-formyltetrahydrofolate (5-FTHF or folinic acid) to 5,10-methenyltetrahydrofolate (5,10-MTHF).

At least 3 unrelated individuals have been reported. The phenotype appears to be relevant to both epilepsy and ID gene panels and the role of variants/the gene supported by enzymatic activity studies, 5-FTHF accumulation, 5,10-MTHF levels (low/low-normal), the role of folate metabolism pathway overall and some supporting (metabolic) evidence from the mouse model.
---
Rodan et al (2018 - PMID: 30031689) reported on 2 individuals both presenting with microcephaly, severe global DD, epilepsy, progressive spasticity and cerebral hypomyelination upon MRI imaging. Short stature was also feature in both.

The 1st patient was an 8-year-old male who following exome sequencing was found to harbor 2 missense variants each inherited from a carrier parent. (NM_006441.3:c.434G>A / p.R145Q and c.107T>C / p.L36P). A further AFG3L2 indel was not felt to fit with his phenotype (and the onset of the related disorder appears to occur later).

Previous investigations included extensive metabolic testing, CMA, Angelman syndrome methylation analysis, GFAP, POLG1, TYMP sequencing, mitochondrial genome analysis and an XL-ID gene panel (further suggesting relevance of this gene to the current panel) were all non-diagnostic.

CSF 5-MTHF levels were initially on the low-normal range, subsequently found to be decreased (upon folinic acid supplementation) and later normalized upon use of another regimen.

MTHFS activity was measured in control fibroblasts as well as fibroblasts from this individual, with the latter demonstrating no enzyme activity. Accumulation (30x elevation) of 5-FTHF (the substrate of MTHFS) was demonstrated in patient fibroblasts.

The 2nd patient was a 11-year-old male with similar features incl. global DD (standing/walking/single words at/after 4 years of age, limited vocabulary and articulation upon last examination).

Extensive metabolic work-up as well as genetic testing for an epilepsy panel, vanishing white matter disease gene panel, mitochondrial genome as well as specific gene sequencing (LAMA2, POLR3A, POLR3B) were all non-diagnostic. Trio exome revealed 2 MTHFS variants in trans configuration (c.484C>T / p.Q162X and c.434G>A / p.R145Q).
---
Romero et al (2019 - PMID: 31844630) reported on a 4-year-old female with congenital microcephaly, severe global DD (nonverbal/nonambulatory at the age of 4), spasticity, epilepsy and cerebral hypomyelination.

Extensive investigations prior to exome sequencing revealed macrocytic anemia, decreased CSF 5-MTHF and elevated neopterin, 2 CNVs of uncertain significance upon CMA with additional long ROH on chr15. Methylation studies were negative. The child was homozygous for c.220C>T / p.R74X (RefSeq is probably NM_006441.3. MTHFS lies on chr15. The parents were unrelated but came from the same town). There were no other candidate variants from the exome analysis.

Both articles discuss extensively the role of the folate metabolism pathway overall in nucleic acid synthesis, AA metabolism, neurotransmitter synthesis, methylation as well as 5-FTHF / 5,10-MTHF in particular in myelin stabilization and DNA synthesis (eg. according to Romero et al. a defect in MTHFS would impair myelin production and also lead to decreased myelin stability).
---
A book chapter cited by Rodan et al (in N. Blau et al. (eds.), Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases - DOI: 10.1007/978-3-642-40337-8_10) included limited details on a patient with 'MTHFS gene mutation'. This individual had early speech delay, seizures beginning in infancy, ID, autistic features, recurrent infections and was found to have very low CSF 5-MTHF levels. [Details in p169 and table 10.6 - p173].
---
In a mouse model reported by Field et al (2011 - PMID: 22303332), Mthfs was disrupted through insertion of a gene trap vector between the first 2 exons. Heterozygous [Mthfs(gt/+)] mice were fertile and viable. Mthfs protein levels were slightly but not statistically significantly reduced in tissues measured. No homozygous embryos were recovered following intercrosses of heterozygous mice, suggesting that Mthfs is an essential gene. Mouse embryonic fibroblasts from heterozygous mice [Mthfs (gt/+)] exhibited reduced de novo purine biosynthesis, but did not exhibit altered de novo thymidylate biosynthesis. Plasma folate levels were altered in heterozygous mice on a standard (/control) diet.
Sources: Literature; to: Biallelic pathogenic MTHFS variants cause Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination (# 618367).

The gene encodes 5,10-Methenyltetrahydrofolate synthetase which catalyzes conversion of 5-formyltetrahydrofolate (5-FTHF or folinic acid) to 5,10-methenyltetrahydrofolate (5,10-MTHF).

At least 3 unrelated individuals have been reported. The phenotype appears to be relevant to both epilepsy and ID gene panels and the role of variants/the gene supported by enzymatic activity studies, 5-FTHF accumulation, 5,10-MTHF levels (low/low-normal), the role of folate metabolism pathway overall and some supporting (metabolic) evidence from the mouse model.
---
Rodan et al (2018 - PMID: 30031689) reported on 2 individuals both presenting with microcephaly, severe global DD, epilepsy, progressive spasticity and cerebral hypomyelination upon MRI imaging. Short stature was also feature in both.

The 1st patient was an 8-year-old male who following exome sequencing was found to harbor 2 missense variants each inherited from a carrier parent. (NM_006441.3:c.434G>A / p.R145Q and c.107T>C / p.L36P). A further AFG3L2 indel was not felt to fit with his phenotype (and the onset of the related disorder appears to occur later).

Previous investigations included extensive metabolic testing, CMA, Angelman syndrome methylation analysis, GFAP, POLG1, TYMP sequencing, mitochondrial genome analysis and an XL-ID gene panel (further suggesting relevance of this gene to the current panel) were all non-diagnostic.

CSF 5-MTHF levels were initially on the low-normal range, subsequently found to be decreased (upon folinic acid supplementation) and later normalized upon use of another regimen.

MTHFS activity was measured in control fibroblasts as well as fibroblasts from this individual, with the latter demonstrating no enzyme activity. Accumulation (30x elevation) of 5-FTHF (the substrate of MTHFS) was demonstrated in patient fibroblasts.

The 2nd patient was a 11-year-old male with similar features incl. global DD (standing/walking/single words at/after 4 years of age, limited vocabulary and articulation upon last examination).

Extensive metabolic work-up as well as genetic testing for an epilepsy panel, vanishing white matter disease gene panel, mitochondrial genome as well as specific gene sequencing (LAMA2, POLR3A, POLR3B) were all non-diagnostic. Trio exome revealed 2 MTHFS variants in trans configuration (c.484C>T / p.Q162X and c.434G>A / p.R145Q).
---
Romero et al (2019 - PMID: 31844630) reported on a 4-year-old female with congenital microcephaly, severe global DD (nonverbal/nonambulatory at the age of 4), spasticity, epilepsy and cerebral hypomyelination.

Extensive investigations prior to exome sequencing revealed macrocytic anemia, decreased CSF 5-MTHF and elevated neopterin, 2 CNVs of uncertain significance upon CMA with additional long ROH on chr15. Methylation studies were negative. The child was homozygous for c.220C>T / p.R74X (RefSeq is probably NM_006441.3. MTHFS lies on chr15. The parents were unrelated but came from the same town). There were no other candidate variants from the exome analysis.

Both articles discuss extensively the role of the folate metabolism pathway overall in nucleic acid synthesis, AA metabolism, neurotransmitter synthesis, methylation as well as 5-FTHF / 5,10-MTHF in particular in myelin stabilization and DNA synthesis (eg. according to Romero et al. a defect in MTHFS would impair myelin production and also lead to decreased myelin stability).
---
A book chapter cited by Rodan et al (in N. Blau et al. (eds.), Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases - DOI: 10.1007/978-3-642-40337-8_10) included limited details on a patient with 'MTHFS gene mutation'. This individual had early speech delay, seizures beginning in infancy, ID, autistic features, recurrent infections and was found to have very low CSF 5-MTHF levels. [Details in p169 and table 10.6 - p173].
---
In a mouse model reported by Field et al (2011 - PMID: 22303332), Mthfs was disrupted through insertion of a gene trap vector between the first 2 exons. Heterozygous [Mthfs(gt/+)] mice were fertile and viable. Mthfs protein levels were slightly but not statistically significantly reduced in tissues measured. No homozygous embryos were recovered following intercrosses of heterozygous mice, suggesting that Mthfs is an essential gene. Mouse embryonic fibroblasts from heterozygous mice [Mthfs (gt/+)] exhibited reduced de novo purine biosynthesis, but did not exhibit altered de novo thymidylate biosynthesis. Plasma folate levels were altered in heterozygous mice on a standard (/control) diet.

[Please consider inclusion in other possibly relevant panels e.g. for metabolic disorders]
Sources: Literature
Intellectual disability v3.0 MTHFS Konstantinos Varvagiannis gene: MTHFS was added
gene: MTHFS was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: MTHFS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTHFS were set to 30031689; 31844630; 22303332; https://doi.org/10.1007/978-3-642-40337-8_10
Phenotypes for gene: MTHFS were set to Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination, 618367
Penetrance for gene: MTHFS were set to Complete
Review for gene: MTHFS was set to GREEN
Added comment: Biallelic pathogenic MTHFS variants cause Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination (# 618367).

The gene encodes 5,10-Methenyltetrahydrofolate synthetase which catalyzes conversion of 5-formyltetrahydrofolate (5-FTHF or folinic acid) to 5,10-methenyltetrahydrofolate (5,10-MTHF).

At least 3 unrelated individuals have been reported. The phenotype appears to be relevant to both epilepsy and ID gene panels and the role of variants/the gene supported by enzymatic activity studies, 5-FTHF accumulation, 5,10-MTHF levels (low/low-normal), the role of folate metabolism pathway overall and some supporting (metabolic) evidence from the mouse model.
---
Rodan et al (2018 - PMID: 30031689) reported on 2 individuals both presenting with microcephaly, severe global DD, epilepsy, progressive spasticity and cerebral hypomyelination upon MRI imaging. Short stature was also feature in both.

The 1st patient was an 8-year-old male who following exome sequencing was found to harbor 2 missense variants each inherited from a carrier parent. (NM_006441.3:c.434G>A / p.R145Q and c.107T>C / p.L36P). A further AFG3L2 indel was not felt to fit with his phenotype (and the onset of the related disorder appears to occur later).

Previous investigations included extensive metabolic testing, CMA, Angelman syndrome methylation analysis, GFAP, POLG1, TYMP sequencing, mitochondrial genome analysis and an XL-ID gene panel (further suggesting relevance of this gene to the current panel) were all non-diagnostic.

CSF 5-MTHF levels were initially on the low-normal range, subsequently found to be decreased (upon folinic acid supplementation) and later normalized upon use of another regimen.

MTHFS activity was measured in control fibroblasts as well as fibroblasts from this individual, with the latter demonstrating no enzyme activity. Accumulation (30x elevation) of 5-FTHF (the substrate of MTHFS) was demonstrated in patient fibroblasts.

The 2nd patient was a 11-year-old male with similar features incl. global DD (standing/walking/single words at/after 4 years of age, limited vocabulary and articulation upon last examination).

Extensive metabolic work-up as well as genetic testing for an epilepsy panel, vanishing white matter disease gene panel, mitochondrial genome as well as specific gene sequencing (LAMA2, POLR3A, POLR3B) were all non-diagnostic. Trio exome revealed 2 MTHFS variants in trans configuration (c.484C>T / p.Q162X and c.434G>A / p.R145Q).
---
Romero et al (2019 - PMID: 31844630) reported on a 4-year-old female with congenital microcephaly, severe global DD (nonverbal/nonambulatory at the age of 4), spasticity, epilepsy and cerebral hypomyelination.

Extensive investigations prior to exome sequencing revealed macrocytic anemia, decreased CSF 5-MTHF and elevated neopterin, 2 CNVs of uncertain significance upon CMA with additional long ROH on chr15. Methylation studies were negative. The child was homozygous for c.220C>T / p.R74X (RefSeq is probably NM_006441.3. MTHFS lies on chr15. The parents were unrelated but came from the same town). There were no other candidate variants from the exome analysis.

Both articles discuss extensively the role of the folate metabolism pathway overall in nucleic acid synthesis, AA metabolism, neurotransmitter synthesis, methylation as well as 5-FTHF / 5,10-MTHF in particular in myelin stabilization and DNA synthesis (eg. according to Romero et al. a defect in MTHFS would impair myelin production and also lead to decreased myelin stability).
---
A book chapter cited by Rodan et al (in N. Blau et al. (eds.), Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases - DOI: 10.1007/978-3-642-40337-8_10) included limited details on a patient with 'MTHFS gene mutation'. This individual had early speech delay, seizures beginning in infancy, ID, autistic features, recurrent infections and was found to have very low CSF 5-MTHF levels. [Details in p169 and table 10.6 - p173].
---
In a mouse model reported by Field et al (2011 - PMID: 22303332), Mthfs was disrupted through insertion of a gene trap vector between the first 2 exons. Heterozygous [Mthfs(gt/+)] mice were fertile and viable. Mthfs protein levels were slightly but not statistically significantly reduced in tissues measured. No homozygous embryos were recovered following intercrosses of heterozygous mice, suggesting that Mthfs is an essential gene. Mouse embryonic fibroblasts from heterozygous mice [Mthfs (gt/+)] exhibited reduced de novo purine biosynthesis, but did not exhibit altered de novo thymidylate biosynthesis. Plasma folate levels were altered in heterozygous mice on a standard (/control) diet.
Sources: Literature
Cardiomyopathies - including childhood onset v1.1 CACNA1C Ivone Leong Added comment: Comment on mode of inheritance: MOI has been corrected.
Cardiomyopathies - including childhood onset v1.1 CACNA1C Ivone Leong Mode of inheritance for gene: CACNA1C was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hearing loss v2.4 WBP2 Zornitza Stark gene: WBP2 was added
gene: WBP2 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: WBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WBP2 were set to 26881968
Phenotypes for gene: WBP2 were set to Deafness, autosomal recessive 107, MIM#617639
Review for gene: WBP2 was set to AMBER
Added comment: Two unrelated families identified in a large cohort; supportive animal model data.
Sources: Expert list
Hearing loss v2.4 TOP2B Zornitza Stark gene: TOP2B was added
gene: TOP2B was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: TOP2B was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: TOP2B were set to 31198993
Phenotypes for gene: TOP2B were set to Deafness, autosomal dominant
Added comment: One multigenerational family where variant in this gene segregated with deafness; two additional variants identified in a cohort; supportive animal model data.
Sources: Expert list
Hearing loss v2.4 TMTC2 Zornitza Stark gene: TMTC2 was added
gene: TMTC2 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: TMTC2 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: TMTC2 were set to 29671961; 27311106
Phenotypes for gene: TMTC2 were set to Deafness
Review for gene: TMTC2 was set to AMBER
Added comment: Two unrelated families reported, no functional evidence.
Sources: Expert list
Hearing loss v2.4 SPNS2 Zornitza Stark gene: SPNS2 was added
gene: SPNS2 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: SPNS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPNS2 were set to 30973865; 25356849
Phenotypes for gene: SPNS2 were set to Deafness, autosomal recessive 115, MIM#618457
Review for gene: SPNS2 was set to AMBER
Added comment: Single family reported, mouse model shows progressive hearing loss.
Sources: Expert list
Hearing loss v2.4 SPATC1L Zornitza Stark gene: SPATC1L was added
gene: SPATC1L was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: SPATC1L was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SPATC1L were set to 30177775
Phenotypes for gene: SPATC1L were set to Deafness
Added comment: Two families with compound het variants, and one family with heterozygous variant and dominant pattern of inheritance described, some functional data.
Sources: Expert list
Hearing loss v2.4 ROR1 Zornitza Stark gene: ROR1 was added
gene: ROR1 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: ROR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ROR1 were set to 27162350
Phenotypes for gene: ROR1 were set to Deafness, autosomal recessive 108, MIM#617654
Review for gene: ROR1 was set to AMBER
Added comment: Single family, homozygous missense variant in sibs; mouse model.
Sources: Expert list
Hearing loss v2.4 PPIP5K2 Zornitza Stark gene: PPIP5K2 was added
gene: PPIP5K2 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: PPIP5K2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPIP5K2 were set to 29590114
Phenotypes for gene: PPIP5K2 were set to Deafness, autosomal recessive 100, MIM#618422
Review for gene: PPIP5K2 was set to AMBER
Added comment: Two apparently unrelated families with multiple affecteds segregating a homozygous missense variant; mouse model.
Sources: Expert list
Hearing loss v2.4 PLS1 Zornitza Stark gene: PLS1 was added
gene: PLS1 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: PLS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLS1 were set to 31397523; 31432506; 30872814
Phenotypes for gene: PLS1 were set to Deafness
Review for gene: PLS1 was set to GREEN
gene: PLS1 was marked as current diagnostic
Added comment: non-syndromic deafness in 5 families with mono-allelic variants in this gene, and a mouse model.
Sources: Expert list
Hearing loss v2.4 NARS2 Zornitza Stark reviewed gene: NARS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 25807530, 28077841, 30327238, 25385316; Phenotypes: Deafness, autosomal recessive 94, MIM#618434, Combined oxidative phosphorylation deficiency 24, MIM#616239; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hearing loss v2.4 MPZL2 Zornitza Stark gene: MPZL2 was added
gene: MPZL2 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: MPZL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPZL2 were set to 29982980; 29961571
Phenotypes for gene: MPZL2 were set to Deafness, autosomal recessive 111, MIM#618145
Review for gene: MPZL2 was set to GREEN
Added comment: 16 individuals from 6 unrelated consanguineous families reported with bi-allelic variants in this gene.
Sources: Expert list
Hearing loss v2.4 LMX1A Zornitza Stark reviewed gene: LMX1A: Rating: AMBER; Mode of pathogenicity: None; Publications: 29754270, 29971487; Phenotypes: Deafness, autosomal recessive and autosomal dominant; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hearing loss v2.4 HOMER2 Zornitza Stark gene: HOMER2 was added
gene: HOMER2 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: HOMER2 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: HOMER2 were set to 25816005; 30047143; 25816005
Phenotypes for gene: HOMER2 were set to Deafness, autosomal dominant 68, MIM#616707
Review for gene: HOMER2 was set to GREEN
gene: HOMER2 was marked as current diagnostic
Added comment: Two families reported and a mouse model.
Sources: Expert list
Hearing loss v2.4 HARS2 Zornitza Stark reviewed gene: HARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21464306, 27650058, 31827252, 31486067; Phenotypes: Perrault syndrome, deafness, autosomal recessive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hearing loss v2.4 GJB6 Zornitza Stark reviewed gene: GJB6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hearing loss v2.4 GJB3 Zornitza Stark reviewed gene: GJB3: Rating: RED; Mode of pathogenicity: None; Publications: 9843210; Phenotypes: Deafness, autosomal dominant 2B, MIM#612644; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Hearing loss v2.4 EPS8L2 Zornitza Stark gene: EPS8L2 was added
gene: EPS8L2 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: EPS8L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPS8L2 were set to 26282398; 2391890; 28281779
Phenotypes for gene: EPS8L2 were set to Deafness, autosomal recessive 106, MIM#617637
Review for gene: EPS8L2 was set to GREEN
gene: EPS8L2 was marked as current diagnostic
Added comment: Two unrelated families and a mouse model.
Sources: Expert list
Hearing loss v2.4 ELMOD3 Zornitza Stark reviewed gene: ELMOD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 240396609, 31628468, 30284680, 29713870; Phenotypes: Deafness, autosomal recessive 88, MIM#615429, Deafness, autosomal dominant; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hearing loss v2.4 DMXL2 Zornitza Stark reviewed gene: DMXL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31688942; Phenotypes: Epileptic encephalopathy with deafness; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hearing loss v2.4 COL4A6 Zornitza Stark reviewed gene: COL4A6: Rating: RED; Mode of pathogenicity: None; Publications: 23714752; Phenotypes: Deafness, X-linked 6, MIM#300914; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hearing loss v2.4 CDC14A Zornitza Stark gene: CDC14A was added
gene: CDC14A was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: CDC14A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDC14A were set to 29293958; 27259055
Phenotypes for gene: CDC14A were set to Deafness, autosomal recessive 32, with or without immotile sperm, MIM#608653
Review for gene: CDC14A was set to GREEN
gene: CDC14A was marked as current diagnostic
Added comment: Multiple affected individuals from unrelated families reported, plus animal model data. Likely to present with apparently isolated deafness in children.
Sources: Expert list
Hearing loss v2.4 AIFM1 Zornitza Stark gene: AIFM1 was added
gene: AIFM1 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: AIFM1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: AIFM1 were set to 25986071
Phenotypes for gene: AIFM1 were set to Deafness, X-linked 5, MIM#300614
Review for gene: AIFM1 was set to GREEN
Added comment: More than 10 unrelated families described.
Sources: Expert list
Genetic epilepsy syndromes v2.0 PUM1 Konstantinos Varvagiannis gene: PUM1 was added
gene: PUM1 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: PUM1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PUM1 were set to 29474920; 30903679; 31859446
Phenotypes for gene: PUM1 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of the face; Ataxia; Cryptorchidism
Penetrance for gene: PUM1 were set to unknown
Review for gene: PUM1 was set to GREEN
Added comment: 5 unrelated individuals with de novo pathogenic PUM1 variants have been reported in the literature. DD (5/5), ID (4/5 - relevant severity to the current panel), seizures (4/4 - absence/tonic-clonic, abnormal EEG) and variable other features (incl. facial dysmorphism, ataxia, cryptorchidism) appear to be part of the phenotype. 9 individuals with deletions spanning PUM1 and proximal genes presented similar features.

[1] PMID: 29474920 - Gennarino et al (2018)
[2] PMID: 30903679 - Bonnemason-Carrere et al (2019)
[3] PMID: 31859446 - Voet et al (2019) [with review of the literature]

SNVs in relevant individuals were identified by exome sequencing and were in all cases de novo.

Arg1147Trp was a recurrent variant reported in 3 unrelated subjects with ID and seizures (Refs 1,2,3 / NM_001020658.1:c.3439C>T). A nonsense variant was reported in an additional one with DD, ID, seizures and additional features (c.2509C>T / p.Arg837* - Ref3). One individual with a de novo missense variant (c.3416G>A / p.Arg1139Trp) with DD and ataxia, though without ID was reported in Ref1.

Details on 9 individuals with 0.3 - 5.6 Mb deletions spanning PUM1 and other genes are provided in Ref1. Features also included DD, ID, seizures, ataxia, etc.

Extensive initial investigations were reported for individuals in Refs 2 and 3 (various investigations incl. karyotype, SNP-array, targeted sequencing of OPHN1, KANSL1 or of a small panel of ID genes, biopsies and/or metabolic work-up) to rule out alternative causes. These only revealed a likely benign CNV and a GRIA3 SNV of uncertain significance in the case of an individual harboring the recurrent Arg1147Trp variant [Ref2].

Role of the gene (from OMIM):
Pumilio proteins, such as PUM1, negatively regulate gene expression by repressing translation of mRNAs to which they bind (Lee et al., 2016). A clinically significant PUM1 target is ataxin (ATXN1; 601556), mutation in which causes spinocerebellar ataxia-1 (SCA1; 601556).

Variant studies:
- Arg1147Trp was shown to be associated with normal PUM1 mRNA levels, but reduced (to ~43%) PUM1 protein levels in patient fibroblasts. ATXN1 mRNA and protein levels, as well as protein and/or mRNA levels of other PUM1 targets were shown to be increased (Ref1).
- In Ref1, in vitro transfection assays with wt or mt PUM1 were performed in HEK293T cells to evaluate repression of ATXN1 and E2F3. While overexpression of wt and Arg1147Trp were able to reduce ATXN1 and E2F3 levels, Arg1139Trp was not able to repress ATXN1 or E2F3.
- Upon overexpression in mouse hippocampal neurons, PUM1 missense mutations (among others Arg1139Trp and Arg1147Trp) were shown to alter neuronal morphology.

Overall haploinsufficiency is the proposed mechanism for the disorder for which the acronym PADDAS is used (Pumilio1-associated developmental disability, ataxia and seizure).

Milder mutations reducing PUM1 levels by 25% are associated with adult-onset ataxia without ID (PRCA or Pumilio1-related cerebellar ataxia) [Ref1].

Mouse models:
The role of PUM1 was first suggested in mouse models where Pum1 mutations were shown to lead to a SCA1-like phenotype (PMID cited : 12086639 - Watase et al 2002) further shown to be caused by increased Atxn1 mRNA and protein levels (PMID cited : 25768905 - Gennarino et al 2015).
The mouse model seems to recapitulate several of the features observed in affected individuals : Pum1 homozygous ko mice display among others hyperactivity, progressive cerebellar signs, spontaneous seizures as also observed in affected individuals (PMID cited : 25768905 - Gennarino et al 2015). Cryptorchidism was observed in 2 patients similar to testicular hypoplasia reported in Pum1 ko mice (PMID cited : 22342750 - Chen et al 2012).
- Heterozygous mice were evaluated in Ref1 with 69% or 75% exhibiting spontaneous seizures by the end of 30 or 35 wks respectively, with abnormal EEG activity already by 16 wks.

Additional individuals with PUM1 variants and a relevant phenotype of ID with or without seizures have been reported as part of the DDD study or as external submissions to Decipher and ClinVar :

https://decipher.sanger.ac.uk/search?q=PUM1#research-variants/results [ DDD4K.01387 participant ]
https://decipher.sanger.ac.uk/search?q=pum1#consented-patients/results [ external submission(s) ]
https://www.ncbi.nlm.nih.gov/clinvar/variation/431110/ [ splice-site variant in an individual with ID submitted prior to the 1st publication on the disorder ]
Sources: Literature
Intellectual disability v3.0 PUM1 Konstantinos Varvagiannis commented on gene: PUM1: 5 unrelated individuals with de novo pathogenic PUM1 variants have been reported in the literature. DD (5/5), ID (4/5 - relevant severity to the current panel), seizures (4/4 - absence/tonic-clonic, abnormal EEG) and variable other features (incl. facial dysmorphism, ataxia, cryptorchidism) appear to be part of the phenotype. 9 individuals with deletions spanning PUM1 and proximal genes presented similar features.

[1] PMID: 29474920 - Gennarino et al (2018)
[2] PMID: 30903679 - Bonnemason-Carrere et al (2019)
[3] PMID: 31859446 - Voet et al (2019) [with review of the literature]

SNVs in relevant individuals were identified by exome sequencing and were in all cases de novo.

Arg1147Trp was a recurrent variant reported in 3 unrelated subjects with ID and seizures (Refs 1,2,3 / NM_001020658.1:c.3439C>T). A nonsense variant was reported in an additional one with DD, ID, seizures and additional features (c.2509C>T / p.Arg837* - Ref3). One individual with a de novo missense variant (c.3416G>A / p.Arg1139Trp) with DD and ataxia, though without ID was reported in Ref1.

Details on 9 individuals with 0.3 - 5.6 Mb deletions spanning PUM1 and other genes are provided in Ref1. Features also included DD, ID, seizures, ataxia, etc.

Extensive initial investigations were reported for individuals in Refs 2 and 3 (various investigations incl. karyotype, SNP-array, targeted sequencing of OPHN1, KANSL1 or of a small panel of ID genes, biopsies and/or metabolic work-up) to rule out alternative causes. These only revealed a likely benign CNV and a GRIA3 SNV of uncertain significance in the case of an individual harboring the recurrent Arg1147Trp variant [Ref2].

Role of the gene (from OMIM):
Pumilio proteins, such as PUM1, negatively regulate gene expression by repressing translation of mRNAs to which they bind (Lee et al., 2016). A clinically significant PUM1 target is ataxin (ATXN1; 601556), mutation in which causes spinocerebellar ataxia-1 (SCA1; 601556).

Variant studies:
- Arg1147Trp was shown to be associated with normal PUM1 mRNA levels, but reduced (to ~43%) PUM1 protein levels in patient fibroblasts. ATXN1 mRNA and protein levels, as well as protein and/or mRNA levels of other PUM1 targets were shown to be increased (Ref1).
- In Ref1, in vitro transfection assays with wt or mt PUM1 were performed in HEK293T cells to evaluate repression of ATXN1 and E2F3. While overexpression of wt and Arg1147Trp were able to reduce ATXN1 and E2F3 levels, Arg1139Trp was not able to repress ATXN1 or E2F3.
- Upon overexpression in mouse hippocampal neurons, PUM1 missense mutations (among others Arg1139Trp and Arg1147Trp) were shown to alter neuronal morphology.

Overall haploinsufficiency is the proposed mechanism for the disorder for which the acronym PADDAS is used (Pumilio1-associated developmental disability, ataxia and seizure).

Milder mutations reducing PUM1 levels by 25% are associated with adult-onset ataxia without ID (PRCA or Pumilio1-related cerebellar ataxia) [Ref1].

Mouse models:
The role of PUM1 was first suggested in mouse models where Pum1 mutations were shown to lead to a SCA1-like phenotype (PMID cited : 12086639 - Watase et al 2002) further shown to be caused by increased Atxn1 mRNA and protein levels (PMID cited : 25768905 - Gennarino et al 2015).
The mouse model seems to recapitulate several of the features observed in affected individuals : Pum1 homozygous ko mice display among others hyperactivity, progressive cerebellar signs, spontaneous seizures as also observed in affected individuals (PMID cited : 25768905 - Gennarino et al 2015). Cryptorchidism was observed in 2 patients similar to testicular hypoplasia reported in Pum1 ko mice (PMID cited : 22342750 - Chen et al 2012).
- Heterozygous mice were evaluated in Ref1 with 69% or 75% exhibiting spontaneous seizures by the end of 30 or 35 wks respectively, with abnormal EEG activity already by 16 wks.

Additional individuals with PUM1 variants and a relevant phenotype of ID with or without seizures have been reported as part of the DDD study or as external submissions to Decipher and ClinVar :

https://decipher.sanger.ac.uk/search?q=PUM1#research-variants/results [ DDD4K.01387 participant ]
https://decipher.sanger.ac.uk/search?q=pum1#consented-patients/results [ external submission(s) ]
https://www.ncbi.nlm.nih.gov/clinvar/variation/431110/ [ splice-site variant in an individual with ID submitted prior to the 1st publication on the disorder ]
Intellectual disability v3.0 PUM1 Konstantinos Varvagiannis gene: PUM1 was added
gene: PUM1 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: PUM1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PUM1 were set to 29474920; 30903679; 31859446
Phenotypes for gene: PUM1 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of the face; Ataxia; Cryptorchidism
Penetrance for gene: PUM1 were set to unknown
Review for gene: PUM1 was set to GREEN
Added comment: Please consider inclusion in both ID and epilepsy panels with probably green rating.
Sources: Literature, Radboud University Medical Center, Nijmegen
Fetal hydrops v1.16 PKLR Zornitza Stark gene: PKLR was added
gene: PKLR was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: PKLR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PKLR were set to 29549173; 8285758; 10923218
Phenotypes for gene: PKLR were set to Pyruvate Kinase deficiency
Review for gene: PKLR was set to GREEN
gene: PKLR was marked as current diagnostic
Added comment: PMID 29549173:
A large cohort study (n=233) documented fetal anaemia requiring transfusion in 13% of affected fetuses and hydrops fetalis in 4%.
Sources: Expert list
Fetal hydrops v1.16 PTH1R Zornitza Stark gene: PTH1R was added
gene: PTH1R was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: PTH1R was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTH1R were set to 3975110; 9268097; 8723092
Phenotypes for gene: PTH1R were set to CHONDRODYSPLASIA, BLOMSTRAND TYPE; BOCD
Review for gene: PTH1R was set to GREEN
gene: PTH1R was marked as current diagnostic
Added comment: PMID 3975110
Original case report "The infant was hydropic, showed macroglossia and had very short limbs with normal sized hands and feet"
PMID 9268097
Sibling fetuses were both hydropic at 26 and 33 weeks' gestation.
PMID 8723092:
Both fetuses hydropic, one grossly so.
Sources: Expert list
Fetal anomalies v1.0 AHCY Zornitza Stark gene: AHCY was added
gene: AHCY was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: AHCY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AHCY were set to 30121674; 20852937
Phenotypes for gene: AHCY were set to S-adenosylhomocysteine hydrolase deficiency
Review for gene: AHCY was set to AMBER
Added comment: Please note recent additional report of this condition presenting prenatally with hydrops.
Sources: Expert list
Fetal anomalies v1.0 ALG9 Zornitza Stark reviewed gene: ALG9: Rating: GREEN; Mode of pathogenicity: None; Publications: 26453364, 31420886; Phenotypes: Congenital disorder of glycosylation, type Il, MIM#608776; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v1.0 ATP1A2 Zornitza Stark gene: ATP1A2 was added
gene: ATP1A2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ATP1A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP1A2 were set to 30690204
Phenotypes for gene: ATP1A2 were set to hydrops fetalis; microcephaly; arthrogryposis; extensive cortical malformations
Review for gene: ATP1A2 was set to AMBER
gene: ATP1A2 was marked as current diagnostic
Added comment: Three individuals from two unrelated families reported with balleliic LoF variants in this gene and hydrops/congenital abnormalities. Mouse model is perinatal lethal. This is a distinct phenotype from the mono allelic variants associated with alternating hemiplegia.
Sources: Expert list
Fetal hydrops v1.16 TAZ Zornitza Stark gene: TAZ was added
gene: TAZ was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: TAZ was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TAZ were set to 29476731; 31598953
Phenotypes for gene: TAZ were set to Barth syndrome, MIM#302060
Review for gene: TAZ was set to GREEN
gene: TAZ was marked as current diagnostic
Added comment: Cardiomyopathy is a recognised feature and hydrops has been described in case reports.
Sources: Expert list
Fetal hydrops v1.16 RYR1 Zornitza Stark gene: RYR1 was added
gene: RYR1 was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: RYR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RYR1 were set to 28543167; 26932181
Phenotypes for gene: RYR1 were set to Central core disease, MIM# 117000; Multiple pterygium syndrome
Review for gene: RYR1 was set to GREEN
gene: RYR1 was marked as current diagnostic
Added comment: Severe end of spectrum of RYR1-related disorders can present antenatally, including with hydrops.
Sources: Expert list
Fetal anomalies v1.0 PSAT1 Zornitza Stark reviewed gene: PSAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25152457; Phenotypes: Neu-Laxova syndrome 2, MIM# 616038; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal hydrops v1.16 PSAT1 Zornitza Stark gene: PSAT1 was added
gene: PSAT1 was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: PSAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSAT1 were set to 30838783; 27475004
Phenotypes for gene: PSAT1 were set to Neu-Laxova syndrome 2, MIM# 616038
Review for gene: PSAT1 was set to AMBER
gene: PSAT1 was marked as current diagnostic
Added comment: Unclear how frequently hydrops is a manifestation, skin oedema mentioned in a couple of case reports.
Sources: Expert list
Fetal hydrops v1.16 PHGDH Zornitza Stark gene: PHGDH was added
gene: PHGDH was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: PHGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHGDH were set to 11895570; 11494295
Phenotypes for gene: PHGDH were set to Neu-Laxova syndrome 1, MIM# 256520
Review for gene: PHGDH was set to GREEN
gene: PHGDH was marked as current diagnostic
Added comment: Oedema/hydrops is a presenting feature antenatally.
Sources: Expert list
Fetal hydrops v1.16 MVK Zornitza Stark gene: MVK was added
gene: MVK was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: MVK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MVK were set to 27012807
Phenotypes for gene: MVK were set to Mevalonic aciduria, MIM#610377
Review for gene: MVK was set to GREEN
gene: MVK was marked as current diagnostic
Added comment: Reports of severe prenatal presentations with hydrops for this metabolic condition.
Sources: Expert list
Fetal hydrops v1.16 MUSK Zornitza Stark gene: MUSK was added
gene: MUSK was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: MUSK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MUSK were set to 31750350; 25537362
Phenotypes for gene: MUSK were set to Fetal akinesia deformation sequence 1, MIM# 208150
Review for gene: MUSK was set to GREEN
gene: MUSK was marked as current diagnostic
Added comment: Hydrops/oedema reported in a number of affected individuals with this fetal akinesia condition.
Sources: Expert list
Fetal hydrops v1.16 KMT2D Zornitza Stark gene: KMT2D was added
gene: KMT2D was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: KMT2D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT2D were set to 30293990; 27568880; 15690368
Phenotypes for gene: KMT2D were set to Kabuki syndrome
Review for gene: KMT2D was set to GREEN
gene: KMT2D was marked as current diagnostic
Added comment: There are reports of hydrops fetalis in Kabuki syndrome.
Sources: Expert list
Fetal hydrops v1.16 KLHL40 Zornitza Stark gene: KLHL40 was added
gene: KLHL40 was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: KLHL40 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KLHL40 were set to 25721947
Phenotypes for gene: KLHL40 were set to Nemaline myopathy 8, autosomal recessive, MIM# 615348
Review for gene: KLHL40 was set to AMBER
Added comment: Gene causes fetal akinesia, however can only find one specific report of hydrops.
Sources: Expert list
Rare anaemia v1.0 KIF23 Zornitza Stark reviewed gene: KIF23: Rating: RED; Mode of pathogenicity: None; Publications: 23570799; Phenotypes: Congenital dyserythropoietic anaemia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal hydrops v1.16 GATA1 Zornitza Stark gene: GATA1 was added
gene: GATA1 was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: GATA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GATA1 were set to 10700180
Phenotypes for gene: GATA1 were set to Anaemia, X-linked, with/without neutropaenia and/or platelet abnormalities, MIM#300835
Review for gene: GATA1 was set to GREEN
gene: GATA1 was marked as current diagnostic
Added comment: Can present with severe hydrops in utero requiring transfusion.
Sources: Expert list
Fetal hydrops v1.16 EPHB4 Zornitza Stark gene: EPHB4 was added
gene: EPHB4 was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: EPHB4 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: EPHB4 were set to 2990564; 27400125
Phenotypes for gene: EPHB4 were set to Lymphatic malformation 7, MIM#617300
Review for gene: EPHB4 was set to GREEN
gene: EPHB4 was marked as current diagnostic
Added comment: Three unrelated families reported, hydrops fetalis is a key feature of this condition.
Sources: Expert list
Fetal hydrops v1.16 DOK7 Zornitza Stark gene: DOK7 was added
gene: DOK7 was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: DOK7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOK7 were set to 31880392; 19261599
Phenotypes for gene: DOK7 were set to Fetal akinesia sequence, MIM#618389
Review for gene: DOK7 was set to AMBER
gene: DOK7 was marked as current diagnostic
Added comment: Two unrelated families reported with fetal akinesia deformation sequence, hydrops is a feature. The gene also causes a less severe phenotype (congenital myasthenic syndrome 10), hydrops is not a feature of this.
Sources: Expert list
Fetal hydrops v1.16 DHCR7 Zornitza Stark reviewed gene: DHCR7: Rating: GREEN; Mode of pathogenicity: None; Publications: 14735596, 10215064, 9856557; Phenotypes: Smith-Lemli-Opitz syndrome, MIM#270400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal hydrops v1.16 COL2A1 Zornitza Stark gene: COL2A1 was added
gene: COL2A1 was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: COL2A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: COL2A1 were set to Achondrogenesis, type II or hypochondrogenesis, MIM#200610
Review for gene: COL2A1 was set to GREEN
gene: COL2A1 was marked as current diagnostic
Added comment: Hydrops is a presenting feature of this skeletal dysplasia.
Sources: Expert list
Fetal hydrops v1.16 CHRNG Zornitza Stark gene: CHRNG was added
gene: CHRNG was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: CHRNG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CHRNG were set to Multiple pterygium syndrome, lethal type, MIM#253290
Review for gene: CHRNG was set to GREEN
gene: CHRNG was marked as current diagnostic
Added comment: Typically presents with cystic hygroma/hydrops fetalis.
Sources: Expert list
Fetal hydrops v1.16 CHRND Zornitza Stark gene: CHRND was added
gene: CHRND was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: CHRND was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CHRND were set to Multiple pterygium syndrome, lethal type, MIM#253290
Review for gene: CHRND was set to GREEN
gene: CHRND was marked as current diagnostic
Added comment: Typically presents with cystic hygroma/hydrops fetalis.
Sources: Expert list
Fetal hydrops v1.16 CHRNA1 Zornitza Stark gene: CHRNA1 was added
gene: CHRNA1 was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: CHRNA1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CHRNA1 were set to Multiple pterygium syndrome, lethal type, MIM#253290
Review for gene: CHRNA1 was set to GREEN
gene: CHRNA1 was marked as current diagnostic
Added comment: Typically presents with cystic hygroma/hydrops.
Sources: Expert list
Fetal hydrops v1.16 CDAN1 Zornitza Stark gene: CDAN1 was added
gene: CDAN1 was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: CDAN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDAN1 were set to 30786798; 29668551; 29599085
Phenotypes for gene: CDAN1 were set to Dyserythropoietic anaemia, congenital, type Ia, MIM#224120
Review for gene: CDAN1 was set to GREEN
gene: CDAN1 was marked as current diagnostic
Added comment: Can present with fetal hydrops.
Sources: Expert list
Fetal hydrops v1.16 ATP1A2 Zornitza Stark gene: ATP1A2 was added
gene: ATP1A2 was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: ATP1A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP1A2 were set to 30690204
Phenotypes for gene: ATP1A2 were set to hydrops fetalis; microcephaly; arthrogryposis; extensive cortical malformations
gene: ATP1A2 was marked as current diagnostic
Added comment: Three individuals from two unrelated families reported with bi-allelic LoF variants in this gene and hydrops/congenital abnormalities. Mouse model is perinatal lethal. Please note this is a distinct phenotype from the mono-allelic variants associated with alternating hemiplegia.
Sources: Expert list
Fetal hydrops v1.16 ALG9 Zornitza Stark gene: ALG9 was added
gene: ALG9 was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: ALG9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALG9 were set to 26453364; 31420886
Phenotypes for gene: ALG9 were set to Congenital disorder of glycosylation, type II, MIM#608776
Review for gene: ALG9 was set to GREEN
Added comment: CDGs can present prenatally with hydrops fetalis; please note three patients reported in recent literature review.
Sources: Expert list
Fetal hydrops v1.16 ALG8 Zornitza Stark gene: ALG8 was added
gene: ALG8 was added to Fetal hydrops. Sources: Expert list
Mode of inheritance for gene: ALG8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALG8 were set to 26066342; 31420886
Phenotypes for gene: ALG8 were set to Congenital disorder of glycosylation, type Ih, MIM#608104
Review for gene: ALG8 was set to GREEN
Added comment: CDGs can present prenatally with non-immune hydrops fetalis. Please note these two reviews: one of ALG8-CDG, reporting hydrops in 3/15 patients; and the other reporting hydrops in a range of CDGs.
Sources: Expert list
Fetal hydrops v1.16 ALG1 Zornitza Stark reviewed gene: ALG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31420886; Phenotypes: Congenital disorder of glycosylation, type Ik, MIM#608540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.16 AHCY Zornitza Stark reviewed gene: AHCY: Rating: AMBER; Mode of pathogenicity: None; Publications: 30121674; Phenotypes: S-adenosylhomocysteine hydrolase deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v2.0 DLL1 Konstantinos Varvagiannis gene: DLL1 was added
gene: DLL1 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: DLL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DLL1 were set to 31353024
Phenotypes for gene: DLL1 were set to Global developmental delay; Intellectual disability; Morphological abnormality of the central nervous system; Seizures; Behavioral abnormality; Autism; Scoliosis
Penetrance for gene: DLL1 were set to unknown
Review for gene: DLL1 was set to AMBER
Added comment: Gene added to the ID panel. Epilepsy has been reported in 6 unrelated individuals. Please consider inclusion with amber/green rating.

----

Heterozygous DLL1 pathogenic variants cause Neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures (# 618709).

Fischer-Zirnsak et al (2019 - PMID: 31353024) reported on 15 affected individuals from 12 unrelated families.

Most common features included DD/ID (12/14), ASD (6/14 - belonging to 6 families) or other behavioral abnormalities, seizures (6/14 - from 6 unrelated families) and various brain MRI abnromalities. As commented by OMIM (based on the same ref) "Cognitive function ranges from severely impaired to the ability to attend schools with special assistance". Among other features, scoliosis was observed in 4. The authors could not identify a distinctive facial gestalt.

Variable initial investigations (where discussed/performed - also suggesting relevance to the current panel) included CMA, FMR1, FLNA, mitochondrial DNA analysis and metabolic work-up but had not revealed an alternative cause.

The DLL1 variants were identified by WES (with the exception of a 122-kb microdeletion spanning DLL1 and FAM120B detected by CMA). Nonsense, frame-shift, splice-site variants in positions predicted to result to NMD were identified in most. One individual was found to harbor a missense variant (NM_005618.3:c.536G>T / p.Cys179Phe) and another the aforementioned microdeletion.

The variant in several individuals had occurred as a de novo event. In 2 families, it was inherited from an also affected parent (an unaffected sib was non-carrier) while in 3 families parental studies were not possible/complete.

In frame insertion of 4 residues was demonstrated for a splice site variant, from LCLs of the corresponding individual. For another individual, material was unavailable for mRNA studies. The missense variant affected a cysteine (of the DSL domain) conserved in all Notch ligands while AA changes affecting the same position of JAG1 (another Notch ligand) have been described in patients with Alagille s.

Based on the variants identified and reports of deletions spanning DLL1 in the literature, haploinsufficiency is the proposed underlying mechanism. The gene has also a pLI of 1 and %HI of 4.65.

DLL1 encodes the Delta-like canonical Notch ligand 1. Notch signaling is an established pathway for brain morphogenesis. Previous in vivo and in vitro studies have demonstrated the role of DLL1 in CNS. The gene is highly expressed in neuronal precursor cells during embryogenesis. Expression of Dll1 (and other molecules of the Notch signalling pathway) in an oscillatory/sustained pattern and cell-cell interactions important for this pathway have been demonstrated to play a role in neuronal differentiation. [Most discussed by Fischer-Zirnsak et al with several refs provided / also Gray et al., 1999 - PMID: 10079256 & OMIM].

Animal models as summarized by the authors:
[Mouse] Loss of Dll1 in mice has been shown to increase neuronal differentiation, cause CNS hyperplasia and increased number of neurons (PMIDs cited: 9109488, 12397111, 20081190). Reduced Dll1 expression was associated with scoliosis and mild vertebral defects (cited PMIDs: 19562077, 14960495, 22484060 / among others Dll1 haploinsufficiency and dominant negative models studied). Scoliosis and vertebral segmentation defects were features in 4 and 1 individual, respectively in the cohort of 15.
[Zebrafish] Homozygous mutations in dlA, the zebrafish ortholog, disrupted the Delta-Notch signaling and led to patterning defects in the hindbrain and overproduction of neurons (cited: 15366005).
Sources: Literature
Intellectual disability v3.0 DLL1 Konstantinos Varvagiannis gene: DLL1 was added
gene: DLL1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: DLL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DLL1 were set to 31353024
Phenotypes for gene: DLL1 were set to Global developmental delay; Intellectual disability; Morphological abnormality of the central nervous system; Seizures; Behavioral abnormality; Autism; Scoliosis
Penetrance for gene: DLL1 were set to unknown
Review for gene: DLL1 was set to GREEN
Added comment: Heterozygous DLL1 pathogenic variants cause Neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures (# 618709).

Fischer-Zirnsak et al (2019 - PMID: 31353024) reported on 15 affected individuals from 12 unrelated families.

Most common features included DD/ID (12/14), ASD (6/14 - belonging to 6 families) or other behavioral abnormalities, seizures (6/14 - from 6 unrelated families) and various brain MRI abnromalities. As commented by OMIM (based on the same ref) "Cognitive function ranges from severely impaired to the ability to attend schools with special assistance". Among other features, scoliosis was observed in 4. The authors could not identify a distinctive facial gestalt.

Variable initial investigations (where discussed/performed - also suggesting relevance to the current panel) included CMA, FMR1, FLNA, mitochondrial DNA analysis and metabolic work-up but had not revealed an alternative cause.

The DLL1 variants were identified by WES (with the exception of a 122-kb microdeletion spanning DLL1 and FAM120B detected by CMA). Nonsense, frame-shift, splice-site variants in positions predicted to result to NMD were identified in most. One individual was found to harbor a missense variant (NM_005618.3:c.536G>T / p.Cys179Phe) and another the aforementioned microdeletion.

The variant in several individuals had occurred as a de novo event. In 2 families, it was inherited from an also affected parent (an unaffected sib was non-carrier) while in 3 families parental studies were not possible/complete.

In frame insertion of 4 residues was demonstrated for a splice site variant, from LCLs of the corresponding individual. For another individual, material was unavailable for mRNA studies. The missense variant affected a cysteine (of the DSL domain) conserved in all Notch ligands while AA changes affecting the same position of JAG1 (another Notch ligand) have been described in patients with Alagille s.

Based on the variants identified and reports of deletions spanning DLL1 in the literature, haploinsufficiency is the proposed underlying mechanism. The gene has also a pLI of 1 and %HI of 4.65.

DLL1 encodes the Delta-like canonical Notch ligand 1. Notch signaling is an established pathway for brain morphogenesis. Previous in vivo and in vitro studies have demonstrated the role of DLL1 in CNS. The gene is highly expressed in neuronal precursor cells during embryogenesis. Expression of Dll1 (and other molecules of the Notch signalling pathway) in an oscillatory/sustained pattern and cell-cell interactions important for this pathway have been demonstrated to play a role in neuronal differentiation. [Most discussed by Fischer-Zirnsak et al with several refs provided / also Gray et al., 1999 - PMID: 10079256 & OMIM].

Animal models as summarized by the authors:
[Mouse] Loss of Dll1 in mice has been shown to increase neuronal differentiation, cause CNS hyperplasia and increased number of neurons (PMIDs cited: 9109488, 12397111, 20081190). Reduced Dll1 expression was associated with scoliosis and mild vertebral defects (cited PMIDs: 19562077, 14960495, 22484060 / among others Dll1 haploinsufficiency and dominant negative models studied). Scoliosis and vertebral segmentation defects were features in 4 and 1 individual, respectively in the cohort of 15.
[Zebrafish] Homozygous mutations in dlA, the zebrafish ortholog, disrupted the Delta-Notch signaling and led to patterning defects in the hindbrain and overproduction of neurons (cited: 15366005).

Please consider inclusion in other possibly relevant panels e.g. for ASD.
Sources: Literature
Genetic epilepsy syndromes v2.0 TFE3 Konstantinos Varvagiannis reviewed gene: TFE3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30595499, 31833172, https://doi.org/10.1126/scisignal.aax0926; Phenotypes: Global developmental delay, Intellectual disability, Abnormality of skin pigmentation, Coarse facial features, Seizures; Mode of inheritance: Other
Intellectual disability v3.0 TFE3 Konstantinos Varvagiannis reviewed gene: TFE3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30595499, 31833172, https://doi.org/10.1126/scisignal.aax0926; Phenotypes: Global developmental delay, Intellectual disability, Abnormality of skin pigmentation, Coarse facial features, Seizures; Mode of inheritance: Other
Retinal disorders v2.5 TUBGCP6 Ivone Leong reviewed gene: TUBGCP6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 TUBGCP4 Ivone Leong reviewed gene: TUBGCP4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 TTPA Ivone Leong reviewed gene: TTPA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 TRNT1 Ivone Leong reviewed gene: TRNT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 TREX1 Ivone Leong reviewed gene: TREX1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 SPP2 Ivone Leong reviewed gene: SPP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 SLC25A46 Ivone Leong reviewed gene: SLC25A46: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 SAMD11 Ivone Leong reviewed gene: SAMD11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 RTN4IP1 Ivone Leong reviewed gene: RTN4IP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 RDH11 Ivone Leong reviewed gene: RDH11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 PRDM13 Ivone Leong reviewed gene: PRDM13: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 POMGNT1 Ivone Leong reviewed gene: POMGNT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 POC5 Ivone Leong reviewed gene: POC5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 PNPLA6 Ivone Leong reviewed gene: PNPLA6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 PLK4 Ivone Leong reviewed gene: PLK4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 PGK1 Ivone Leong reviewed gene: PGK1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 PAX2 Ivone Leong reviewed gene: PAX2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 OPN1SW Ivone Leong reviewed gene: OPN1SW: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 NEUROD1 Ivone Leong reviewed gene: NEUROD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 NBAS Ivone Leong reviewed gene: NBAS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 MT-TS2 Ivone Leong reviewed gene: MT-TS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 MT-TP Ivone Leong reviewed gene: MT-TP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 MT-TH Ivone Leong reviewed gene: MT-TH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 MIR204 Ivone Leong reviewed gene: MIR204: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 MAPKAPK3 Ivone Leong reviewed gene: MAPKAPK3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 LAMA1 Ivone Leong reviewed gene: LAMA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 JAG1 Ivone Leong reviewed gene: JAG1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 IFT81 Ivone Leong reviewed gene: IFT81: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 IFT27 Ivone Leong reviewed gene: IFT27: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 IFT172 Ivone Leong reviewed gene: IFT172: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 GNB3 Ivone Leong reviewed gene: GNB3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 EXOSC2 Ivone Leong reviewed gene: EXOSC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 ESPN Ivone Leong reviewed gene: ESPN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 ELOVL1 Ivone Leong reviewed gene: ELOVL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 DRAM2 Ivone Leong reviewed gene: DRAM2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 DMD Ivone Leong reviewed gene: DMD: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 CTNNA1 Ivone Leong reviewed gene: CTNNA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 CLUAP1 Ivone Leong reviewed gene: CLUAP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 CLCC1 Ivone Leong reviewed gene: CLCC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 CEP250 Ivone Leong reviewed gene: CEP250: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 CEP19 Ivone Leong reviewed gene: CEP19: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 CCT2 Ivone Leong reviewed gene: CCT2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 C12orf65 Ivone Leong reviewed gene: C12orf65: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 ATXN7 Ivone Leong reviewed gene: ATXN7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 ASRGL1 Ivone Leong reviewed gene: ASRGL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 ARSG Ivone Leong reviewed gene: ARSG: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 ARL3 Ivone Leong reviewed gene: ARL3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 AHR Ivone Leong reviewed gene: AHR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 AFG3L2 Ivone Leong reviewed gene: AFG3L2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 ADIPOR1 Ivone Leong reviewed gene: ADIPOR1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.5 ABCC6 Ivone Leong reviewed gene: ABCC6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v2.4 REEP6 Ivone Leong Classified gene: REEP6 as Green List (high evidence)
Retinal disorders v2.4 REEP6 Ivone Leong Gene: reep6 has been classified as Green List (High Evidence).
Retinal disorders v2.3 TUBGCP6 Ivone Leong gene: TUBGCP6 was added
gene: TUBGCP6 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: TUBGCP6 was set to
Retinal disorders v2.3 TUBGCP4 Ivone Leong gene: TUBGCP4 was added
gene: TUBGCP4 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: TUBGCP4 was set to
Retinal disorders v2.3 TTPA Ivone Leong gene: TTPA was added
gene: TTPA was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: TTPA was set to
Retinal disorders v2.3 TRNT1 Ivone Leong gene: TRNT1 was added
gene: TRNT1 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: TRNT1 was set to
Retinal disorders v2.3 TREX1 Ivone Leong gene: TREX1 was added
gene: TREX1 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: TREX1 was set to
Retinal disorders v2.3 SPP2 Ivone Leong gene: SPP2 was added
gene: SPP2 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: SPP2 was set to
Retinal disorders v2.3 SLC25A46 Ivone Leong gene: SLC25A46 was added
gene: SLC25A46 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: SLC25A46 was set to
Retinal disorders v2.3 SAMD11 Ivone Leong gene: SAMD11 was added
gene: SAMD11 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: SAMD11 was set to
Retinal disorders v2.3 RTN4IP1 Ivone Leong gene: RTN4IP1 was added
gene: RTN4IP1 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: RTN4IP1 was set to
Retinal disorders v2.3 REEP6 Ivone Leong Source Expert Review Amber was added to REEP6.
Source RetNet was added to REEP6.
Source NHS GMS was added to REEP6.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Retinal disorders v2.3 RDH11 Ivone Leong gene: RDH11 was added
gene: RDH11 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: RDH11 was set to
Retinal disorders v2.3 PRDM13 Ivone Leong gene: PRDM13 was added
gene: PRDM13 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: PRDM13 was set to
Retinal disorders v2.3 POMGNT1 Ivone Leong gene: POMGNT1 was added
gene: POMGNT1 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: POMGNT1 was set to
Retinal disorders v2.3 POC5 Ivone Leong gene: POC5 was added
gene: POC5 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: POC5 was set to
Retinal disorders v2.3 PNPLA6 Ivone Leong gene: PNPLA6 was added
gene: PNPLA6 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: PNPLA6 was set to
Retinal disorders v2.3 PLK4 Ivone Leong gene: PLK4 was added
gene: PLK4 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: PLK4 was set to
Retinal disorders v2.3 PGK1 Ivone Leong gene: PGK1 was added
gene: PGK1 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: PGK1 was set to
Retinal disorders v2.3 PAX2 Ivone Leong gene: PAX2 was added
gene: PAX2 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: PAX2 was set to
Retinal disorders v2.3 OPN1SW Ivone Leong gene: OPN1SW was added
gene: OPN1SW was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: OPN1SW was set to
Retinal disorders v2.3 NEUROD1 Ivone Leong gene: NEUROD1 was added
gene: NEUROD1 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: NEUROD1 was set to
Retinal disorders v2.3 NBAS Ivone Leong gene: NBAS was added
gene: NBAS was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: NBAS was set to
Retinal disorders v2.3 MT-TS2 Ivone Leong gene: MT-TS2 was added
gene: MT-TS2 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Retinal disorders v2.3 MT-TP Ivone Leong gene: MT-TP was added
gene: MT-TP was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene gene: MT-TP was set to MITOCHONDRIAL
Retinal disorders v2.3 MT-TH Ivone Leong gene: MT-TH was added
gene: MT-TH was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene gene: MT-TH was set to MITOCHONDRIAL
Retinal disorders v2.3 MIR204 Ivone Leong gene: MIR204 was added
gene: MIR204 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: MIR204 was set to
Retinal disorders v2.3 MAPKAPK3 Ivone Leong gene: MAPKAPK3 was added
gene: MAPKAPK3 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: MAPKAPK3 was set to
Retinal disorders v2.3 LAMA1 Ivone Leong gene: LAMA1 was added
gene: LAMA1 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: LAMA1 was set to
Retinal disorders v2.3 JAG1 Ivone Leong gene: JAG1 was added
gene: JAG1 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: JAG1 was set to
Retinal disorders v2.3 IFT81 Ivone Leong gene: IFT81 was added
gene: IFT81 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: IFT81 was set to
Retinal disorders v2.3 IFT27 Ivone Leong gene: IFT27 was added
gene: IFT27 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: IFT27 was set to
Retinal disorders v2.3 IFT172 Ivone Leong gene: IFT172 was added
gene: IFT172 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: IFT172 was set to
Retinal disorders v2.3 GNB3 Ivone Leong gene: GNB3 was added
gene: GNB3 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: GNB3 was set to
Retinal disorders v2.3 EXOSC2 Ivone Leong gene: EXOSC2 was added
gene: EXOSC2 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: EXOSC2 was set to
Retinal disorders v2.3 ESPN Ivone Leong gene: ESPN was added
gene: ESPN was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: ESPN was set to
Retinal disorders v2.3 ELOVL1 Ivone Leong gene: ELOVL1 was added
gene: ELOVL1 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: ELOVL1 was set to
Retinal disorders v2.3 DRAM2 Ivone Leong gene: DRAM2 was added
gene: DRAM2 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: DRAM2 was set to
Retinal disorders v2.3 DMD Ivone Leong gene: DMD was added
gene: DMD was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: DMD was set to
Retinal disorders v2.3 CTNNA1 Ivone Leong gene: CTNNA1 was added
gene: CTNNA1 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: CTNNA1 was set to
Retinal disorders v2.3 CLUAP1 Ivone Leong gene: CLUAP1 was added
gene: CLUAP1 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: CLUAP1 was set to
Retinal disorders v2.3 CLCC1 Ivone Leong gene: CLCC1 was added
gene: CLCC1 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: CLCC1 was set to
Retinal disorders v2.3 CEP250 Ivone Leong gene: CEP250 was added
gene: CEP250 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: CEP250 was set to
Retinal disorders v2.3 CEP19 Ivone Leong gene: CEP19 was added
gene: CEP19 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: CEP19 was set to
Retinal disorders v2.3 CCT2 Ivone Leong gene: CCT2 was added
gene: CCT2 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: CCT2 was set to
Retinal disorders v2.3 C12orf65 Ivone Leong gene: C12orf65 was added
gene: C12orf65 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: C12orf65 was set to
Retinal disorders v2.3 ATXN7 Ivone Leong gene: ATXN7 was added
gene: ATXN7 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: ATXN7 was set to
Retinal disorders v2.3 ASRGL1 Ivone Leong gene: ASRGL1 was added
gene: ASRGL1 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: ASRGL1 was set to
Retinal disorders v2.3 ARSG Ivone Leong gene: ARSG was added
gene: ARSG was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: ARSG was set to
Retinal disorders v2.3 ARL3 Ivone Leong gene: ARL3 was added
gene: ARL3 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: ARL3 was set to
Retinal disorders v2.3 AHR Ivone Leong gene: AHR was added
gene: AHR was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: AHR was set to
Retinal disorders v2.3 AFG3L2 Ivone Leong gene: AFG3L2 was added
gene: AFG3L2 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: AFG3L2 was set to
Retinal disorders v2.3 ADIPOR1 Ivone Leong gene: ADIPOR1 was added
gene: ADIPOR1 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: ADIPOR1 was set to
Retinal disorders v2.3 ABCC6 Ivone Leong gene: ABCC6 was added
gene: ABCC6 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS
Mode of inheritance for gene: ABCC6 was set to
Intellectual disability v3.0 MN1 Konstantinos Varvagiannis gene: MN1 was added
gene: MN1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: MN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MN1 were set to 31834374; 31839203; 15870292
Phenotypes for gene: MN1 were set to Central hypotonia; Feeding difficulties; Global developmental delay; Intellectual disability; Hearing impairment; Abnormality of facial skeleton; Craniosynostosis; Abnormality of the face; Abnormality of the cerebellum; Abnormality of the corpus callosum; Polymicrogyria
Penetrance for gene: MN1 were set to Complete
Review for gene: MN1 was set to GREEN
Added comment: Two studies by Mak et al (2019 - PMID: 31834374 / Ref1) and Miyake et al (2019 - PMID: 31839203 / Ref2) provide sufficient evidence for heterozygous MN1 C-terminal truncating variants (predicted to escape NMD - localizing within the last nucleotides of exon 1 or in exon 2) being associated with a distinctive phenotype and DD and ID among the features.

Mak et al also discuss on the phenotype of individuals with variants causing N-terminal truncation or with MN1 deletions (discussed at the end of this review).

Overlapping features for C-terminal truncating variants included hypotonia, feeding difficulties, global DD and ID, hearing loss, cranial shape defects (/craniosynostosis in few), highly suggestive/distinctive facial features (eg. frontal bossing, hypertelorism, downslanting palpebral-fissures, shallow orbits, short upturned nose, low-set/posteriorly rotated/dysplastic ears, etc) and brain MRI abnormalities (eg. rhomboencephalosynapsis or cerebellar dysplasia, polymicrogyria, dysplastic CC).

The majority of the affected individuals were investigated by WES/WGS with a single one tested by targeted MN1 Sanger sequencing due to highly suggestive features. Variable previous investigations incl. CMA in several, gene panel testing (Rasopathies, hearing loss, craniofacial panels, FMR1, etc) and metabolic work were normal in most. In a single case a likely pathogenic ACSL4 also explained part of the phenotype (Ref2). In the majority of these individuals, the variant had occured as a de novo event. Two sibs had inherited the truncating variant from a milder affected mosaic parent. A parental sample was not available for an additional individual.

p.(Arg1295*) or NM_002430.2:c.3883C>T was a recurrent variant, seen in several individuals and in both studies.

Several lines of evidence are provided for the MN1 variants and the role of the gene including:
- For few individuals for whom cell lines were available, variants were shown to escape NMD by cDNA/RT-PCR/RNA-seq [Ref1 & 2].
- The gene has a high expression in fetal brain [Ref2 / fig S2]
- MN1 (* 156100 - MN1 protooncogene, transcriptional regulator) has been proposed to play a role in cell proliferation and shown to act as transcription cofactor (increasing its transactivation capacity in synergy with coactivators EP300 and RAC3) [Discussion and Refs provided in Ref2].
- In vitro studies suggested increased protein stability (upon transfection of wt/mut constructs in HEK293T cells), enhanced MN1 aggregation in nuclei (when wt/mut GFP-tagged MN1 was expressed in HeLa cells), increased inhibitory effect on cell growth (MG63 cells - role of MN1 in cell proliferation discussed above) and retained transactivation activity (upon transient MN1 overexpression of wt/mt MN1 in HEK293T cells) for the variants. These seem to support a gain-of-function effect for the C-terminal truncating variants [Ref2].
- The truncating variants are proposed to raise the fraction of Intrinsically disordered regions (IDRs = regions without fixed tertiary structure) probably contributing to the above effects [Ref2].
- Expression of FLAG-tagged MN1 wt/mut MN1 followed by immunoprecipitation and mass spectrometry analysis (mCAT-Hela cells), provided evidence that MN1 is involved in transcriptional regulation: a. through binding ZBTB24 and RING1 E3 ubiquitin ligase (with mutant MN1 displaying impaired interaction with ZBTB24 and no binding to RING1) and/or b. through interaction with DNA-binding transcription factors PBX1 and PKNOX1. Proper MN1 degradation is proposed to mediate precise transcriptional regulation. [Ref2]
- Transcriptome analysis in LCLs from an affected individual suggested dysregulation of genes relevant to neuronal development (eg. LAMP, ITGA, etc) and GO analysis suggested enrichment for pathways possibly linked to the observed phenotypes [Ref2].
- Discussed in both Refs1/2, homozygous Mn1-ko mice display abnormal skull bone development and die at/shortly after birth as a result of cleft palate. Heterozygous Mn1-ko mice display hypoplastic membranous bones of the cranial skeleton and cleft palate (CP), the latter with incomplete penetrance [Meester-Smoor et al 2005 - PMID: 15870292]. This is thus compatible with the cranial shape defects observed in C-terminal truncations (while CP has been reported in gene deletions, bifid uvula was reported once in C-terminal and N-terminal truncating variants, in the latter case with submucous CP).
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The phenotype of other MN1 variants is discussed by Mak et al (Ref1) :
- 3 individuals with MN1 N-terminal truncating variants (eg. Ser179*, Pro365Thrfs*120, Ser472*) presented speech delay, mild conductive hearing loss and facial features different from C-terminal truncations. None of these individuals had significant ID.
- Microdeletions: One individual (#27) with 130 kb deletion harboring only MN1, presented microcephaly, DD and ID and mildly dysmorphic facial features. Deletions spanning MN1 and other genes (eg a 1.17 Mb deletion in ind. #28) and relevant cases from the literature reviewed, with mild DD/ID, variable palatal defects and/or facial dysmorphisms (distinct from the C-terminal truncating variants) among the frequent findings.

[Please consider inclusion in other possibly relevant gene panels eg. for hearing loss (conductive/sensorineural in 16/20 reported by Mak et al) or craniosynostosis, etc].
Sources: Literature
Intellectual disability v3.0 CXorf56 Konstantinos Varvagiannis gene: CXorf56 was added
gene: CXorf56 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: CXorf56 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: CXorf56 were set to 29374277; 31822863
Phenotypes for gene: CXorf56 were set to ?Mental retardation, X-linked 107, 301013
Penetrance for gene: CXorf56 were set to unknown
Review for gene: CXorf56 was set to AMBER
Added comment: Verkerk et al (2018 - PMID: 29374277) reported on a three-generation family with five males and one female presenting mild non-syndromic ID. Segregation was compatible with X-linked inheritance.

Multipoint linkage analysis with XL microsatellite markers demonstrated a linkage peak at Xq23-24 with LOD score of 3.3. Haplotype analysis and utilization of additional STR markers allowed narrowing to a region of 7.6 Mb containing 92 genes.

WGS in 3 affected males (spanning 3 generations) and 1 unaffected male and application of relevant filters for rare protein affecting variants within this region - present only in affected but absent in the unaffected individual - suggested a CXorf56 frameshift variant in exon 2 [NM_022101.3:c.159_160insTA / p.(Asp54*)] as the only relevant for this phenotype.

Sanger sequencing was performed for 25 family members with all 5 affected males and 1 affected female harboring this insertion and 8 unaffected females (also) shown to be carriers.

X-chromosome inactivation studies demonstrated that unaffected females had skewed inactivation (76-93%) of the variant allele, while the single affected female did not have a skewed XCI pattern (54%).

In EBV-transformed lymphoblasts grown with/without cycloheximide, mRNA levels were shown to be significantly lower in the affected female compared to unaffected ones (and corrected upon treatment with cycloheximide). mRNA levels were also significantly lower in cell lines from an affected male, with expression showing significant increase after treatment with cycloheximide. These results confirmed that nonsense-mediated decay applies.

The variant was absent from ExAC (where CXorf56 has a pLI of 0.93) and 188 healthy Dutch individuals.

The function of CXorf56 is not known. The gene appears to be expressed in brain and a (broad) range of other tissues [ https://gtexportal.org/home/gene/CXORF56 ].

Immunostaining in 8-week old murine brain, showed that the protein is present in the nucleus and cell soma of most neurons in brain cortex and cerebellum. Upon transfection of human CXorf56 cDNA in mouse primary hippocampal neurons, the protein localized in the nucleus, dendrites (co-localizing with Map2) and dendritic spines. As the authors note, the latter may suggest a role in synaptic function.

Overexpression in HEK293T cells demonstrated predominantly nuclear localization.

Mouse : Based on MGI (and an article by Cox et al. - PMID: 20548051 / both cited by the authors) male chimeras hemizygous for a gene trapped allele have abnormal midbrain-hindbrain boundary morphology, decreased forebrain size, while a subset hemizygous for a different gene trapped allele show growth delay [ http://www.informatics.jax.org/marker/MGI:1924894 ].

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Rocha et al (2019 - PMID: 31822863) report on 9 affected individuals with mild to severe ID belonging to 3 unrelated families. Additional features in this cohort - observed in some - included abnormal reflexes, fine tremor, seizures (in 3), abnormal gait, etc.

In the 1st family, 3 males presented with (severe/severe/moderate) ID and 2 females with mild ID. Following a normal CMA and FMR1 testing, trio plus exome sequencing revealed a CXorf56 in-frame deletion [NM_022101.3:c.498_503del / p.(Glu167_Glu168del)]. Sanger sequencing in 9 members, confirmed presence of the variant in one unaffected mother, all her affected sons (2) and daughers(2) and an affected grandson and absence in 2 remaining unaffected daughters. Skewing of XCI was seen in blood cells from affected females (97 and 83%) while the unaffected mother had complete inactivation of the carrier X-chromosome. The authors commented that even minor reductions in CXorf56 (suggested by XCI in affected females) may be detrimental and/or that inactivation for this gene may be different than that of AR gene (which was studied instead) or in other tissues.

In family 2, an affected mother (with learning difficulties) and her 2 sons - the most severely affected presenting moderate ID - harbored a frameshift variant [c.303_304delCTinsACCC / p.(Phe101Leufs*20)].

A male with ID belonging to a 3rd family, for which no further information was available, was found to harbor the c.498_503del variant (also discussed above) as a de novo event.

It has been commented that individuals with Xq24 deletions spanning CXorf56 present with ID, although (all) such deletions reported in the literature also span the neighboring UBE2A gene, associated with Mental retardation, X-linked syndromic, Nascimento-type (MIM #300860).

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In OMIM, the CXorf56-related phenotype is ?Mental retardation, X-linked 107 (# 301013), based only on the report by Verkerk et al.

This gene is included in gene panels for ID offered by some diagnostic laboratories (incl. Radboudumc).

-----

Overall, CXorf56 can be considered for inclusion in the ID panel either with amber (function of the gene unknown, skewed XCI also in affected females in the 2nd reference) or with green rating (several individuals from 4 families, compatible segregation studies and females presenting a milder phenotype than males or unaffected, LOD score in the 1st report, studies confirming lower mRNA levels and NMD, gene expressed in human brain, expression in mouse brain cortex and cerebellum, evidence from transfection studies in mouse hippocampal neurons).

[Note : penetrance was here set to unknown / It was complete for males, incomplete for females].
Sources: Literature, Radboud University Medical Center, Nijmegen
Skeletal dysplasia v2.0 SCUBE3 Zerin Hyder gene: SCUBE3 was added
gene: SCUBE3 was added to Skeletal dysplasia. Sources: Other
Mode of inheritance for gene: SCUBE3 was set to BIALLELIC, autosomal or pseudoautosomal
Penetrance for gene: SCUBE3 were set to unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.1 Ivone Leong Panel status changed from internal to public
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 ADCY10 Ivone Leong gene: ADCY10 was added
gene: ADCY10 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert list,Expert Review Amber
Mode of inheritance for gene: ADCY10 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 XDH Ivone Leong gene: XDH was added
gene: XDH was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: XDH was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 VDR Ivone Leong gene: VDR was added
gene: VDR was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: VDR was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 SLC9A3R1 Ivone Leong gene: SLC9A3R1 was added
gene: SLC9A3R1 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC9A3R1 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 SLC7A9 Ivone Leong gene: SLC7A9 was added
gene: SLC7A9 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC7A9 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 SLC4A1 Ivone Leong gene: SLC4A1 was added
gene: SLC4A1 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC4A1 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 SLC3A1 Ivone Leong gene: SLC3A1 was added
gene: SLC3A1 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC3A1 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 SLC34A3 Ivone Leong gene: SLC34A3 was added
gene: SLC34A3 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC34A3 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 SLC34A1 Ivone Leong gene: SLC34A1 was added
gene: SLC34A1 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC34A1 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 SLC2A9 Ivone Leong gene: SLC2A9 was added
gene: SLC2A9 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC2A9 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 SLC26A1 Ivone Leong gene: SLC26A1 was added
gene: SLC26A1 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC26A1 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 SLC22A12 Ivone Leong gene: SLC22A12 was added
gene: SLC22A12 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC22A12 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 SLC12A1 Ivone Leong gene: SLC12A1 was added
gene: SLC12A1 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: SLC12A1 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 OCRL Ivone Leong gene: OCRL was added
gene: OCRL was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: OCRL was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 KCNJ1 Ivone Leong gene: KCNJ1 was added
gene: KCNJ1 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: KCNJ1 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 HPRT1 Ivone Leong gene: HPRT1 was added
gene: HPRT1 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: HPRT1 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 HOGA1 Ivone Leong gene: HOGA1 was added
gene: HOGA1 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: HOGA1 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 HNF4A Ivone Leong gene: HNF4A was added
gene: HNF4A was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: HNF4A was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 GRHPR Ivone Leong gene: GRHPR was added
gene: GRHPR was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: GRHPR was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 FAM20A Ivone Leong gene: FAM20A was added
gene: FAM20A was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: FAM20A was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 CYP24A1 Ivone Leong gene: CYP24A1 was added
gene: CYP24A1 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CYP24A1 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 CLDN19 Ivone Leong gene: CLDN19 was added
gene: CLDN19 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CLDN19 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 CLDN16 Ivone Leong gene: CLDN16 was added
gene: CLDN16 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CLDN16 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 CLCN5 Ivone Leong gene: CLCN5 was added
gene: CLCN5 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CLCN5 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 CASR Ivone Leong gene: CASR was added
gene: CASR was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CASR was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 CA2 Ivone Leong gene: CA2 was added
gene: CA2 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: CA2 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 ATP6V1B1 Ivone Leong gene: ATP6V1B1 was added
gene: ATP6V1B1 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ATP6V1B1 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 ATP6V0A4 Ivone Leong gene: ATP6V0A4 was added
gene: ATP6V0A4 was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: ATP6V0A4 was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 APRT Ivone Leong gene: APRT was added
gene: APRT was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: APRT was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 AGXT Ivone Leong gene: AGXT was added
gene: AGXT was added to Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS. Sources: Victorian Clinical Genetics Services,Expert Review Green
Mode of inheritance for gene: AGXT was set to Unknown
Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS v0.0 Ivone Leong Added panel Nephrolithiasis and Nephrocalcinosis_KidGen_VCGS
Intellectual disability v3.0 UGP2 Konstantinos Varvagiannis gene: UGP2 was added
gene: UGP2 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: UGP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGP2 were set to 31820119
Phenotypes for gene: UGP2 were set to Seizures; Global developmental delay; Intellectual disability; Feeding difficulties; Abnormality of vision; Abnormality of the face
Penetrance for gene: UGP2 were set to Complete
Review for gene: UGP2 was set to GREEN
Added comment: Perenthaler et al. (2019 - PMID: 31820119) provide evidence that homozygosity for a variant abolishing the start codon of the UGP2 transcript (NM_001001521.1) encoding the predominant (short) protein isoform in brain, leads to a severe epileptic encephalopathy.

This variant (chr2:64083454A>G / NM_001001521.1:c.1A>G - p.?) is also predicted to result in a substitution of a methionine at position 12 by a valine of the longer UGP2 transcript (NM_006759.3:c.34A>G - p.Met12Val).

The 2 isoforms differ only by 11 amino acids at the N-terminal and are otherwise expected to be functionally equivalent.

The authors provide details on 22 individuals from 15 families (some of which consanguineous).

Features included intractable seizures (in all), absence of developmental milestones (in all), progressive microcephaly, visual impairment. The authors reported also presence of somewhat similar facial features. Some of these individuals passed away early.

Previous work-up in several of them (incl. SNP-array, gene panel testing and metabolic investigations) had not revealed any abnormality, apart from ROH in some individuals. In all cases, the homozygous UGP2 SNV was the only P/LP variant for the neurodevelopmental phenotype following exome/genome sequencing. Segregation studies in affected/unaffected family members were compatible.

Families came from the Netherlands (but mostly from) India, Pakistan and Iran. Presence of a region of homozygosity shared between individuals from different families suggested that the variant might represent a mutation that originated several generations ago (in the area of Balochistan). The variant is present 15x in gnomAD, only in heterozygous state (in Asian mostly, reported once in Ashkenazi Jewish or Europeans) [ https://gnomad.broadinstitute.org/variant/2-64083454-A-G ].

UGP2 encodes UDP-glucose pyrophosphorylase which is an essential enzyme in sugar metabolism, catalyzing conversion of glucose-1-phosphate to UDP-glucose. UDP-glucose, in turn, serves as precursor for production of glycogen by glycogen synthase.

The authors provide several lines of evidence for a the role of the gene in the CNS as well as for the deleterious effect of the specific variant :
- In patient fibroblasts total UGP2 levels were not signifficantly different compared to parent / control fibroblasts, the longer isoform being upregulated (and stable) when the shorter is missing. Immunocytochemistry demonstrated similar localization of UGP2 in the case of mutant or wt cells. Enzymatic activity (/capacity to produce UDP-glucose) was similar between homozygous mut, heterozygous and wt fibroblasts.
- In H9-derived neural stem cells, Western Blot, RT-PCR and qRT-PCR suggested that the short isoform is the predominant one. (In embryonic stem cells, or fibroblasts the ratio between short and long isoform was lower).
- Analysis of RNA-seq data from human fetal tissues suggested that the short isoform is the predominant in brain.
- UGP2 was detected upon immunohistochemistry in fetal brain tissues from first to third trimester of pregnancy while Western Blot confirmed preferential expression of the shorter isoform.
- Homozygous embryonic (ESC) or neural stem cells (NSC) for the variant (knock-in/KI) or for a frameshift variant (knock-out/KO) were generated. Study of NSCs demonstrated reduced total UGP2 protein expression upon Western Blot in the case of KI cells and depleted in KO ones. Transcriptome analysis did not show major transcriptome alterations in KI/KO ESCs compared to wt. In NSC KI/KO cells transcriptome alterations were observed compared to wt with upregulation among others of genes for synaptic processes and genes implicated in epilepsy.
- The absence of UGP2 was shown to result in reduced ability of KO/KI NSCs to produce UDP-glucose, reduced capacity to synthesize glycogen under hypoxia (rescued in the case of KO cells by overexpression of wt or long isoform), defects of protein glycosylation as well as in increased unfolded protein response (/susceptibility to ER stress). These alterations are commented to be possibly implicated in pathogenesis of epilepsy, progressive microcephaly, etc.
- A CRISPR-Cas9 zebrafish model leading with loss of ugp2a and hypomorphic ugp2b (the zebrafish homologs of UGP2) demonstrated abnormal behavior, reduced eye movements and increased frequency/duration of movements upon stimulation with a potent convulsant (suggestive of increased seizure susceptibility).
- UGP knockout in drosophila is lethal while flies compound heterozygous for hypomorphic alleles are viable but show a movement defects due to altered synaptogenesis secondary to glycosylation defects (cited PMID: 27466186).
- The authors make speculations as for the occurrence of a single variant (and not others) eg. absence of UGP2 (in the case of LoF variants affecting both isoforms) would possibly be incompatible with life, Met12Val being tolerable for the long transcript not affecting stability/enzymatic activity (which may not be the case for other substitutions affecting Met12), etc.
Sources: Literature
Genetic epilepsy syndromes v2.0 UGP2 Konstantinos Varvagiannis gene: UGP2 was added
gene: UGP2 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: UGP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGP2 were set to 31820119
Phenotypes for gene: UGP2 were set to Seizures; Global developmental delay; Intellectual disability; Feeding difficulties; Abnormality of vision; Abnormality of the face
Penetrance for gene: UGP2 were set to Complete
Review for gene: UGP2 was set to GREEN
Added comment: Perenthaler et al. (2019 - PMID: 31820119) provide evidence that homozygosity for a variant abolishing the start codon of the UGP2 transcript (NM_001001521.1) encoding the predominant (short) protein isoform in brain, leads to a severe epileptic encephalopathy.

This variant (chr2:64083454A>G / NM_001001521.1:c.1A>G - p.?) is also predicted to result in a substitution of a methionine at position 12 by a valine of the longer UGP2 transcript (NM_006759.3:c.34A>G - p.Met12Val).

The 2 isoforms differ only by 11 amino acids at the N-terminal and are otherwise expected to be functionally equivalent.

The authors provide details on 22 individuals from 15 families (some of which consanguineous).

Features included intractable seizures (in all), absence of developmental milestones (in all), progressive microcephaly, visual impairment. The authors reported also presence of somewhat similar facial features. Some of these individuals passed away early.

Previous work-up in several of them (incl. SNP-array, gene panel testing and metabolic investigations) had not revealed any abnormality, apart from ROH in some individuals. In all cases, the homozygous UGP2 SNV was the only P/LP variant for the neurodevelopmental phenotype following exome/genome sequencing. Segregation studies in affected/unaffected family members were compatible.

Families came from the Netherlands (but mostly from) India, Pakistan and Iran. Presence of a region of homozygosity shared between individuals from different families suggested that the variant might represent a mutation that originated several generations ago (in the area of Balochistan). The variant is present 15x in gnomAD, only in heterozygous state (in Asian mostly, reported once in Ashkenazi Jewish or Europeans) [ https://gnomad.broadinstitute.org/variant/2-64083454-A-G ].

UGP2 encodes UDP-glucose pyrophosphorylase which is an essential enzyme in sugar metabolism, catalyzing conversion of glucose-1-phosphate to UDP-glucose. UDP-glucose, in turn, serves as precursor for production of glycogen by glycogen synthase.

The authors provide several lines of evidence for a the role of the gene in the CNS as well as for the deleterious effect of the specific variant :
- In patient fibroblasts total UGP2 levels were not signifficantly different compared to parent / control fibroblasts, the longer isoform being upregulated (and stable) when the shorter is missing. Immunocytochemistry demonstrated similar localization of UGP2 in the case of mutant or wt cells. Enzymatic activity (/capacity to produce UDP-glucose) was similar between homozygous mut, heterozygous and wt fibroblasts.
- In H9-derived neural stem cells, Western Blot, RT-PCR and qRT-PCR suggested that the short isoform is the predominant one. (In embryonic stem cells, or fibroblasts the ratio between short and long isoform was lower).
- Analysis of RNA-seq data from human fetal tissues suggested that the short isoform is the predominant in brain.
- UGP2 was detected upon immunohistochemistry in fetal brain tissues from first to third trimester of pregnancy while Western Blot confirmed preferential expression of the shorter isoform.
- Homozygous embryonic (ESC) or neural stem cells (NSC) for the variant (knock-in/KI) or for a frameshift variant (knock-out/KO) were generated. Study of NSCs demonstrated reduced total UGP2 protein expression upon Western Blot in the case of KI cells and depleted in KO ones. Transcriptome analysis did not show major transcriptome alterations in KI/KO ESCs compared to wt. In NSC KI/KO cells transcriptome alterations were observed compared to wt with upregulation among others of genes for synaptic processes and genes implicated in epilepsy.
- The absence of UGP2 was shown to result in reduced ability of KO/KI NSCs to produce UDP-glucose, reduced capacity to synthesize glycogen under hypoxia (rescued in the case of KO cells by overexpression of wt or long isoform), defects of protein glycosylation as well as in increased unfolded protein response (/susceptibility to ER stress). These alterations are commented to be possibly implicated in pathogenesis of epilepsy, progressive microcephaly, etc.
- A CRISPR-Cas9 zebrafish model leading with loss of ugp2a and hypomorphic ugp2b (the zebrafish homologs of UGP2) demonstrated abnormal behavior, reduced eye movements and increased frequency/duration of movements upon stimulation with a potent convulsant (suggestive of increased seizure susceptibility).
- UGP knockout in drosophila is lethal while flies compound heterozygous for hypomorphic alleles are viable but show a movement defects due to altered synaptogenesis secondary to glycosylation defects (cited PMID: 27466186).
- The authors make speculations as for the occurrence of a single variant (and not others) eg. absence of UGP2 (in the case of LoF variants affecting both isoforms) would possibly be incompatible with life, Met12Val being tolerable for the long transcript not affecting stability/enzymatic activity (which may not be the case for other substitutions affecting Met12), etc.
Sources: Literature
Inborn errors of metabolism v2.1 PCYT2 Sarah Leigh edited their review of gene: PCYT2: Added comment: Vaz et al. (2019 - PMID: 31637422 - DDD study among the co-authors) report on 5 individuals - from 4 families - with biallelic PCYT2 mutations. The phenotype corresponded to a complex hererditary paraplegia with global DD, regression (4/5), ID (mild in 3/5, severe in 2/5), spastic para-/tetraparesis, epilepsy (5/5 - variable onset 2-16 yrs - focal or tonic-clonic seizures) and progressive cerebral and cerebellar atrophy. Exome sequencing in all revealed biallelic PCYT2 variants, confirmed with Sanger s. in probands and their parents (NM_001184917.2 - corresponding to the canonical transcript used as Ref below): - P1 (Fam1) : 2 missense SNVs in trans configuration, c.730C>T or p.His244Tyr and c.920C>T or p.Pro307Leu - P2 (Fam2 - consanguineous of White British origin), P3 (Fam3 - Consanguineous of Turkish origin), P4,5 (Fam4 - consanguineous, unspecified origin) : homozygosity for c.1129C>T or p.Arg377Ter) affecting the last exon of 8/12 transcripts, including the canonical one. Individuals with the same genotype displayed variable degrees of ID (eg P3 - severe / P2, P4,5 - mild ID). For sibs in Fam4, homozygosity for a missense SACS variant led to consideration of the respective disorder (AR spastic ataxia of Charlevoix-Saguenay) though the variant was predicted to be tolerated in silico and notably the MRI images not suggestive. All variants were absent from / had extremely low AF in public databases, with no homozygotes. Posphatidylethanolamine (PE) is a membrane lipid, particularly enriched in human brain (45% of phospholypid fraction). PE is synthesized either via the CDP-ethanolamine pathway or by decarboxylation of phosphatidylserine in mitochondria. PCYT2 encodes CTP:phosophoethanolamine cytidyltransferase (ET) which is an ubiquitously expressed rate-limiting enzyme for PE biosynthesis in the former pathway. In silico, the 2 missense variants - localizing in the CTP catalytic domain 2 - were predicted to be damaging, as well as to affect protein stability. Fibroblasts of 3 patients (P1, P2, P3) representing all variants were studied: - Enzymatic activity was shown to be significantly reduced (though not absent) compared to controls. Abnormalities were noted upon Western Blot incl. absence in all 3 patients studied of one of the 2 bands normally found in controls (probably representing the longer isoform), reduced intensity in all 3 of another band probably corresponding to a shorter isoform, and presence of an additional band of intermediate molec. mass in patients with the truncating variant. - RT-PCR on mRNA from patient fibroblasts did not reveal (significant) reduction compared to controls. - Lipidomic profile of patient fibroblasts was compatible with the location of the block in the phospholipid biosynthesis pathway and different from controls. The lipidomic profile had similarities with what has been reported for EPT1 deficiency, the enzyme directly downstream of ET. The SELENO1-related phenotype (/EPT1 deficiency) is also highly overlapping. CRISPR-Cas9 was used to generate pcyt2 partial or complete knockout (ko) zebrafish, targeting either the final (ex13) or another exon (ex3) respectively. mRNA expression was shown to be moderately reduced in the first case and severely reduced/absent in the second, compared to wt. Similarly, complete-ko (ex3) led to significantly lower survival, with impaired though somewhat better survival of partial-ko (ex13) zebrafish. Complete knockout of Pcyt2 in mice is embryonically lethal (PMID cited: 17325045) while heterozygous mice develop features of metabolic syndrome (PMID cited: 22764088). Given lethality in knockout zebrafish / mice and the residual activity (15-20%) in patient fibroblasts, the variants reported were thought to be hypomorphic and complete loss of function possibly incompatible with life. PCYT2 is not associated with any phenotype in OMIM/G2P/SysID and not commonly included in gene panels for ID. As a result this gene could included in the ID / epilepsy panels with green (~/>3 indiv/fam/variants with the nonsense found in different populations, consistent phenotype, lipidomics, in silico/in vitro/in vivo evidence) or amber rating. [Please consider inclusion in other possibly relevant panels eg. for metabolic disorders, etc]. Sources: Literature
Konstantinos Varvagiannis (Other), 11 Nov 2019; Changed rating: GREEN
Inborn errors of metabolism v2.1 PCYT2 Sarah Leigh gene: PCYT2 was added
gene: PCYT2 was added to Inborn errors of metabolism. Sources: Literature
Mode of inheritance for gene: PCYT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCYT2 were set to 31637422; 17325045; 22764088
Phenotypes for gene: PCYT2 were set to Global developmental delay; Developmental regression; Intellectual disability; Spastic paraparesis; Seizures; Spastic tetraparesis; Cerebral atrophy; Cerebellar atrophy
Review for gene: PCYT2 was set to RED
Added comment: This gene was added by an external reviewer and rated Green on Hereditary spastic paraplegia gene panel (Version 1.210), and confirmed with Zerin Hyder (Genomics England Clinical Team) that this is appropriate to be Green on the Inborn errors of metabolism panel. The rating of this gene will be changed when the next reiteration of this panel is made.
Sources: Literature
Hereditary ataxia - adult onset v2.0 ADPRHL2 Louise Daugherty Tag new-gene-name tag was added to gene: ADPRHL2.
Hereditary ataxia - adult onset v2.0 ADPRHL2 Louise Daugherty commented on gene: ADPRHL2: Added new-gene-name tag, new approved HGNC gene symbol for ADPRHL2 is ADPRS
Intellectual disability v3.0 ADPRHL2 Louise Daugherty Tag new-gene-name tag was added to gene: ADPRHL2.
Intellectual disability v3.0 ADPRHL2 Louise Daugherty commented on gene: ADPRHL2: Added new-gene-name tag, new approved HGNC gene symbol for ADPRHL2 is ADPRS
Genetic epilepsy syndromes v2.0 ADPRHL2 Louise Daugherty Tag new-gene-name tag was added to gene: ADPRHL2.
Genetic epilepsy syndromes v2.0 ADPRHL2 Louise Daugherty commented on gene: ADPRHL2
DDG2P v2.0 ADPRHL2 Louise Daugherty Tag new-gene-name tag was added to gene: ADPRHL2.
DDG2P v2.0 ADPRHL2 Louise Daugherty commented on gene: ADPRHL2
Palmoplantar keratodermas v1.0 LOR Louise Daugherty Tag new-gene-name tag was added to gene: LOR.
Palmoplantar keratodermas v1.0 LOR Louise Daugherty commented on gene: LOR
Ichthyosis and erythrokeratoderma v1.0 LOR Louise Daugherty Tag new-gene-name tag was added to gene: LOR.
Ichthyosis and erythrokeratoderma v1.0 LOR Louise Daugherty commented on gene: LOR
Childhood onset dystonia or chorea or related movement disorder v1.0 ICK Louise Daugherty Tag new-gene-name tag was added to gene: ICK.
Childhood onset dystonia or chorea or related movement disorder v1.0 ICK Louise Daugherty commented on gene: ICK
Hereditary neuropathy NOT PMP22 copy number v1.0 WARS Louise Daugherty Tag new-gene-name tag was added to gene: WARS.
Hereditary neuropathy NOT PMP22 copy number v1.0 WARS Louise Daugherty commented on gene: WARS: Added new-gene-name tag, new approved HGNC gene symbol for WARS is WARS1
Childhood onset dystonia or chorea or related movement disorder v1.0 MUT Louise Daugherty Tag new-gene-name tag was added to gene: MUT.
Cardiomyopathies - including childhood onset v1.0 MUT Louise Daugherty Tag new-gene-name tag was added to gene: MUT.
Cardiomyopathies - including childhood onset v1.0 MUT Louise Daugherty commented on gene: MUT
Hereditary neuropathy NOT PMP22 copy number v1.0 HARS Louise Daugherty Tag new-gene-name tag was added to gene: HARS.
Childhood onset dystonia or chorea or related movement disorder v1.0 GARS Louise Daugherty Deleted their comment
Childhood onset dystonia or chorea or related movement disorder v1.0 GARS Louise Daugherty Tag new-gene-name tag was added to gene: GARS.
Childhood onset dystonia or chorea or related movement disorder v1.0 GARS Louise Daugherty commented on gene: GARS: Added new-gene-name tag, new approved HGNC gene symbol for GARS is GARS1
Hereditary neuropathy NOT PMP22 copy number v1.0 GARS Louise Daugherty Deleted their comment
Hereditary neuropathy NOT PMP22 copy number v1.0 GARS Louise Daugherty Tag new-gene-name tag was added to gene: GARS.
Hereditary neuropathy NOT PMP22 copy number v1.0 GARS Louise Daugherty commented on gene: GARS: Added new-gene-name tag, new approved HGNC gene symbol for GARS is GARS1
Mitochondrial disorders v2.3 GARS Louise Daugherty Tag new-gene-name tag was added to gene: GARS.
Skeletal dysplasia v2.0 FAM46A Louise Daugherty commented on gene: FAM46A
Skeletal dysplasia v2.0 FAM46A Louise Daugherty Tag new-gene-name tag was added to gene: FAM46A.
Renal ciliopathies v1.0 C5orf42 Louise Daugherty Tag new-gene-name tag was added to gene: C5orf42.
Neurological ciliopathies v1.0 C5orf42 Louise Daugherty Tag new-gene-name tag was added to gene: C5orf42.
Ophthalmological ciliopathies v1.0 C5orf42 Louise Daugherty Tag new-gene-name tag was added to gene: C5orf42.
Childhood onset dystonia or chorea or related movement disorder v1.0 C5orf42 Louise Daugherty Deleted their comment
Childhood onset dystonia or chorea or related movement disorder v1.0 C5orf42 Louise Daugherty Tag new-gene-name tag was added to gene: C5orf42.
Childhood onset dystonia or chorea or related movement disorder v1.0 C5orf42 Louise Daugherty commented on gene: C5orf42: Added new-gene-name tag, new approved HGNC gene symbol for C5orf42 is CPLANE1
Childhood onset dystonia or chorea or related movement disorder v1.0 C21orf2 Louise Daugherty Tag new-gene-name tag was added to gene: C21orf2.
Skeletal ciliopathies v1.0 C21orf2 Louise Daugherty Tag new-gene-name tag was added to gene: C21orf2.
Ophthalmological ciliopathies v1.0 C21orf2 Louise Daugherty Tag new-gene-name tag was added to gene: C21orf2.
Ophthalmological ciliopathies v1.0 C21orf2 Louise Daugherty commented on gene: C21orf2
Inborn errors of metabolism v2.0 C19orf70 Louise Daugherty commented on gene: C19orf70
Inborn errors of metabolism v2.0 C19orf70 Louise Daugherty Tag new-gene-name tag was added to gene: C19orf70.
Mitochondrial disorders v2.3 ATP5L2 Louise Daugherty commented on gene: ATP5L2
Mitochondrial disorders v2.3 ATP5L2 Louise Daugherty Tag new-gene-name tag was added to gene: ATP5L2.
Mitochondrial disorders v2.3 ATP5L Louise Daugherty commented on gene: ATP5L
Mitochondrial disorders v2.3 ATP5L Louise Daugherty Tag new-gene-name tag was added to gene: ATP5L.
Mitochondrial disorders v2.3 ATP5J2 Louise Daugherty commented on gene: ATP5J2
Mitochondrial disorders v2.3 ATP5J2 Louise Daugherty Tag new-gene-name tag was added to gene: ATP5J2.
Mitochondrial disorders v2.3 ATP5H Louise Daugherty commented on gene: ATP5H
Mitochondrial disorders v2.3 ATP5H Louise Daugherty Tag new-gene-name tag was added to gene: ATP5H.
Mitochondrial disorders v2.3 ATP5F1 Louise Daugherty commented on gene: ATP5F1
Mitochondrial disorders v2.3 ATP5F1 Louise Daugherty Tag new-gene-name tag was added to gene: ATP5F1.
Inborn errors of metabolism v2.0 ATP5D Louise Daugherty Tag new-gene-name tag was added to gene: ATP5D.
Cardiomyopathies - including childhood onset v1.0 ATP5D Louise Daugherty Tag new-gene-name tag was added to gene: ATP5D.
Hereditary neuropathy NOT PMP22 copy number v1.0 AARS Louise Daugherty Tag new-gene-name tag was added to gene: AARS.
Hereditary neuropathy NOT PMP22 copy number v1.0 AARS Louise Daugherty commented on gene: AARS: Added new-gene-name tag, new approved HGNC gene symbol for AARS is AARS1
Hereditary neuropathy NOT PMP22 copy number v1.0 SEPT9 Louise Daugherty commented on gene: SEPT9: Added new-gene-name tag, new approved HGNC gene symbol for SEPT9 is SEPTIN9
Hereditary neuropathy NOT PMP22 copy number v1.0 SEPT9 Louise Daugherty Tag new-gene-name tag was added to gene: SEPT9.
Congenital disorders of glycosylation v2.0 TMEM199 Sarah Leigh edited their review of gene: TMEM199: Added comment: Should be promoted from Red to Green, due to feedback from the GMS Metabolic Specialist disease test group: 4 patients from 3 unrelated families reported in the literature. All patients had a type 2 pattern on serum transferrin isoelectric focusing (IEF), indicating abnormal N-glycosylation, as well as abnormal IEF of ApoC-III, indicating abnormal O-glycosylation (PMID:26833330). Ellen McDonagh (Genomics England Curator), 4 Dec 2019.; Changed rating: GREEN; Changed publications: 26833330
Congenital disorders of glycosylation v2.0 DPM2 Sarah Leigh edited their review of gene: DPM2: Added comment: DPM2 should be rated as green due to the following: PMID 23109149 describes 3 children from 2 families with muscular dystrophy-dystroglycanopathy, plus good functional evidence this class of CDG can be associated with CMD - Arianna Tucci (Genomics England Clinical Fellow), Jan. 25, 2017, 4:41 p.m.; Changed rating: GREEN
Genetic epilepsy syndromes v2.0 KAT8 Konstantinos Varvagiannis gene: KAT8 was added
gene: KAT8 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: KAT8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KAT8 were set to 31794431
Phenotypes for gene: KAT8 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of vision; Feeding difficulties; Abnormality of the cardiovascular system; Autism
Penetrance for gene: KAT8 were set to unknown
Review for gene: KAT8 was set to GREEN
Added comment: Heterozygous pathogenic missense KAT8 variants have been reported in individuals with DD, ID and epilepsy. Variants occurred as de novo events within the chromobarrel or the acetyltransferase domain and were all shown to affect H4K16 acetylation, as would be predicted by the gene's function (lysine acetyltransferase). Evidence from brain specific Kat8 knockout in mouse, supports the role of the gene in brain development. One similarly affected individual compound heterozygous for a nonsense and a missense variant (the former affecting subnuclear localization and the latter H4K16ac) was also reported, with carrier relatives being unaffected. Mutations in genes of the MSL/NSL complexes (with which KAT8 forms multisubunit complexes) or genes in other acetyltransferases of the same subfamily (MYST) as KAT8 cause neurodevelopmental disorders [Details provided below].
-----
Li et al. (2019 - PMID: 31794431) report on 8 unrelated individuals with heterozygous de novo pathogenic KAT8 variants, as well as an additional one compound heterozygous for a nonsense and a missense one.

Overlapping phenotype consisted of DD/ID (8/8), seizures/epilepsy (6/8), brain MRI anomalies as well as presence of variable facial dysmorphic features. Less frequent features included abnormal vision (5/8), feeding difficulties (3/8), cardiac anomalies (3/8), autism (in 1).

The (9th) individual with biallelic variants had similar phenotype of DD/ID, epilepsy, autism and dysmorphic facial features. Heterozygous parents and sister, the latter carrier for the missense variant, were all unaffected.

All individuals had undergone exome sequencing, while extensive other investigations for at least 7/9 had only revealed variants of uncertain significance/contribution to the phenotype or were normal.

KAT8 encodes lysine acetyltransferase 8, which acetylates histone H4 at lysine 16 (H4K16). It belongs to the MYST subfamily of lysine acetyltransferases, the other members of which include KAT6A, KAT6B (both involved in neurodevelopmental disorders) and KAT5.

KAT8 forms two stoichiometric multisubunitcomplexes, one with the MSL complex and the other with the NSL. Mutations in genes encoding for subunits of the NSL or MSL complex (eg. KANSL1 and MSL3) are associated with neurodevelopmental disorders.

Overall 6 missense SNVs were reported among the heterozygous patients, p.Tyr90Cys (NM_032188.2:c.269A>G) being a recurrent one seen in 3. The compound heterozygous patient had a missense (c.973C>T / p.Arg325Cys) and a nonsense variant (c.523A>T / p.Lys175*). All missense variants lied either in the chromobarrel domain or the acetyltransferase domain. Variants in the latter domain localized within the KAT8/Mof-specific region or - in the case of the compound heterozygous individual - within the acetyl-CoA binding motif.

FLAG-tagged KAT8 (either wt or for all missense SNVs) was transfected in HEK293 cells with vectors for HA-tagged MSL proteins. While the nonsense variant was difficult to express, missense SNVs were expressed to similar levels to wt, promoted expression of MSL proteins but resulted in defective H4K16 acetylation and to a lesser extent H4K5 acetylation. As a result all missense variants impaired acetylation. This was also the case for chromobarrel domain variants, while expression of a KAT8 lacking the chromobarrel domain confirmed its ability to form complex with the MSL proteins and the impairment of H4K16 acetylation.

The nonsense variant demonstrated abnormal subnuclear localization.

The mouse model provides extensive evidence for the involvement of KAT8 in cerebral development. Cerebrum-specific Kat8 knockout mice presented postnatal growth retardation, hyperactivity/irritability, pre-weaning lethality, and cerebral hypoplasia upon autopsy. Loss of Kat8 reduced the number of neural stem and progenitor cells available for embryonic cerebrocortical development, impaired cell proliferation and stimulated apoptosis. The article also provides additional evidence from mouse model.
Sources: Literature
Intellectual disability v3.0 KAT8 Konstantinos Varvagiannis gene: KAT8 was added
gene: KAT8 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: KAT8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KAT8 were set to 31794431
Phenotypes for gene: KAT8 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of vision; Feeding difficulties; Abnormality of the cardiovascular system; Autism
Penetrance for gene: KAT8 were set to unknown
Review for gene: KAT8 was set to GREEN
Added comment: Heterozygous pathogenic missense KAT8 variants have been reported in individuals with DD, ID and epilepsy. Variants occurred as de novo events within the chromobarrel or the acetyltransferase domain and were all shown to affect H4K16 acetylation, as would be predicted by the gene's function (lysine acetyltransferase). Evidence from brain specific Kat8 knockout in mouse, supports the role of the gene in brain development. One similarly affected individual compound heterozygous for a nonsense and a missense variant (the former affecting subnuclear localization and the latter H4K16ac) was also reported, with carrier relatives being unaffected. Mutations in genes of the MSL/NSL complexes (with which KAT8 forms multisubunit complexes) or genes in other acetyltransferases of the same subfamily (MYST) as KAT8 cause neurodevelopmental disorders [Details provided below].
-----
Li et al. (2019 - PMID: 31794431) report on 8 unrelated individuals with heterozygous de novo pathogenic KAT8 variants, as well as an additional one compound heterozygous for a nonsense and a missense one.

Overlapping phenotype consisted of DD/ID (8/8), seizures/epilepsy (6/8), brain MRI anomalies as well as presence of variable facial dysmorphic features. Less frequent features included abnormal vision (5/8), feeding difficulties (3/8), cardiac anomalies (3/8), autism (in 1).

The (9th) individual with biallelic variants had similar phenotype of DD/ID, epilepsy, autism and dysmorphic facial features. Heterozygous parents and sister, the latter carrier for the missense variant, were all unaffected.

All individuals had undergone exome sequencing, while extensive other investigations for at least 7/9 had only revealed variants of uncertain significance/contribution to the phenotype or were normal.

KAT8 encodes lysine acetyltransferase 8, which acetylates histone H4 at lysine 16 (H4K16). It belongs to the MYST subfamily of lysine acetyltransferases, the other members of which include KAT6A, KAT6B (both involved in neurodevelopmental disorders) and KAT5.

KAT8 forms two stoichiometric multisubunitcomplexes, one with the MSL complex and the other with the NSL. Mutations in genes encoding for subunits of the NSL or MSL complex (eg. KANSL1 and MSL3) are associated with neurodevelopmental disorders.

Overall 6 missense SNVs were reported among the heterozygous patients, p.Tyr90Cys (NM_032188.2:c.269A>G) being a recurrent one seen in 3. The compound heterozygous patient had a missense (c.973C>T / p.Arg325Cys) and a nonsense variant (c.523A>T / p.Lys175*). All missense variants lied either in the chromobarrel domain or the acetyltransferase domain. Variants in the latter domain localized within the KAT8/Mof-specific region or - in the case of the compound heterozygous individual - within the acetyl-CoA binding motif.

FLAG-tagged KAT8 (either wt or for all missense SNVs) was transfected in HEK293 cells with vectors for HA-tagged MSL proteins. While the nonsense variant was difficult to express, missense SNVs were expressed to similar levels to wt, promoted expression of MSL proteins but resulted in defective H4K16 acetylation and to a lesser extent H4K5 acetylation. As a result all missense variants impaired acetylation. This was also the case for chromobarrel domain variants, while expression of a KAT8 lacking the chromobarrel domain confirmed its ability to form complex with the MSL proteins and the impairment of H4K16 acetylation.

The nonsense variant demonstrated abnormal subnuclear localization.

The mouse model provides extensive evidence for the involvement of KAT8 in cerebral development. Cerebrum-specific Kat8 knockout mice presented postnatal growth retardation, hyperactivity/irritability, pre-weaning lethality, and cerebral hypoplasia upon autopsy. Loss of Kat8 reduced the number of neural stem and progenitor cells available for embryonic cerebrocortical development, impaired cell proliferation and stimulated apoptosis. The article also provides additional evidence from mouse model.
Sources: Literature
Genetic epilepsy syndromes v2.0 RARS Konstantinos Varvagiannis gene: RARS was added
gene: RARS was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: RARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RARS were set to 31814314; 28905880; 24777941
Phenotypes for gene: RARS were set to Leukodystrophy, hypomyelinating, 9 616140
Penetrance for gene: RARS were set to Complete
Review for gene: RARS was set to GREEN
Added comment: Biallelic pathogenic RARS1 variants cause Leukodystrophy, hypomyelinating, 9 (# 616140).

The current review was based primarily on PMID: 31814314 (Mendes et al, 2019) providing details on 20 affected individuals from 15 families. 5 of these patients were included in a previous publication (Wolf et al, 2014 - PMID: 24777941) sharing authors with this study.

Clinical presentation and severity can be highly variable. However, among the 15 patients of relevant age (5/20 deceased at an early age), ID was observed in 13 (in 6/13 mild-moderate, in 7/13 severe/profound). Epilepsy was reported in half (10/20) with seizures being refractory to treatment in most and the phenotype corresponding to an infantile epileptic encephalopathy. DD and seizures were the presenting feature in 7 and 5 patients respectively, while in other cases presenting features were less specific (eg. failure to thrive in 1/20, irritabilty in 2/20). As a result the gene appears to be relevant to both DD/ID and epilepsy panels.

RARS1 encodes the cytoplasmic arginyl-tRNA synthetase 1, which is a component of the aminoacyl-tRNA synthetase complex (OMIM and Wolf et al, 2014 - PMID: 24777941). Aminoacyl-tRNA synthetases catalyze the aminoacylation ('charging') of tRNA by (with) their cognate amino acid.

Utilisation of alternative initiation codons, from a single mRNA transcript, results in translation of a long and a short protein isoform (Zheng et al 2006 - PMID: 16430231). The long isoform is needed for the formation of the multi-synthetase complex (MSC), while the short is free in the cytoplasm and does not have any interaction with the MSC. The long isoform appears to be essential for protein synthesis (discussed with several refs provided in PMID: 28905880 - Nafisinia et al, 2017).

The role of variants has been supported in several patients by additional studies - among others :
[PMID 31814314] Impaired Arginyl-tRNA synthetase activity was demonstrated in fibroblasts from 3 patients. Activity was normal in one additional individual compound heterozygous for a variant affecting initiation codon and a missense one. Western blot however demonstrated presence mainly of the short protein isoform. The authors suggest that this isoform possibly contributed to enzymatic activity. The long isoform which is needed for the MSC complex was only represented by a faint band in the Western Blot of the same individual.
[PMID: 28905880] Using fibroblasts from an affected subject homozygous for a missense variant (NM_002887.3:c.5A>G / p.Asp2Gly) and controls, a 75% reduction of the long isoform was shown upon WB. The short isoform was present at similar levels. As the N-terminus (of the long isoform) mediates interaction with the MSC (and AIMP1), assembly of the latter was 99% reduced in patient fibroblasts. Proliferation of patient fibroblasts was significantly reduced when cultured in a medium with limited arginine, a finding which was thought to reflect inefficient protein synthesis.

Mutations in other genes encoding for aminoacyl-tRNA synthetases (eg. AARS1, VARS1) or scaffolding proteins of the multisynthetase complex (eg. AIMP1 and AIMP2) lead to neurodevelopmental disorders with overlapping phenotype [most genes rated green in both the ID and epilepsy panel].
Sources: Literature
Intellectual disability v3.0 RARS Konstantinos Varvagiannis gene: RARS was added
gene: RARS was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: RARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RARS were set to 31814314; 28905880; 24777941
Phenotypes for gene: RARS were set to Cerebral hypomyelination; Global developmental delay; Intellectual disability; Seizures; Cerebral atrophy; Nystagmus; Ataxia; Feeding difficulties
Penetrance for gene: RARS were set to Complete
Review for gene: RARS was set to GREEN
Added comment: Biallelic pathogenic RARS1 variants cause Leukodystrophy, hypomyelinating, 9 (# 616140).

The current review was based primarily on PMID: 31814314 (Mendes et al, 2019) providing details on 20 affected individuals from 15 families. 5 of these patients were included in a previous publication (Wolf et al, 2014 - PMID: 24777941) sharing authors with this study.

Clinical presentation and severity can be highly variable. However, among the 15 patients of relevant age (5/20 deceased at an early age), ID was observed in 13 (in 6/13 mild-moderate, in 7/13 severe/profound). Epilepsy was reported in half (10/20) with seizures being refractory to treatment in most and the phenotype corresponding to an infantile epileptic encephalopathy. DD and seizures were the presenting feature in 7 and 5 patients respectively, while in other cases presenting features were less specific (eg. failure to thrive in 1/20, irritabilty in 2/20). As a result the gene appears to be relevant to both DD/ID and epilepsy panels.

RARS1 encodes the cytoplasmic arginyl-tRNA synthetase 1, which is a component of the aminoacyl-tRNA synthetase complex (OMIM and Wolf et al, 2014 - PMID: 24777941). Aminoacyl-tRNA synthetases catalyze the aminoacylation ('charging') of tRNA by (with) their cognate amino acid.

Utilisation of alternative initiation codons, from a single mRNA transcript, results in translation of a long and a short protein isoform (Zheng et al 2006 - PMID: 16430231). The long isoform is needed for the formation of the multi-synthetase complex (MSC), while the short is free in the cytoplasm and does not have any interaction with the MSC. The long isoform appears to be essential for protein synthesis (discussed with several refs provided in PMID: 28905880 - Nafisinia et al, 2017).

The role of variants has been supported in several patients by additional studies - among others :
[PMID 31814314] Impaired Arginyl-tRNA synthetase activity was demonstrated in fibroblasts from 3 patients. Activity was normal in one additional individual compound heterozygous for a variant affecting initiation codon and a missense one. Western blot however demonstrated presence mainly of the short protein isoform. The authors suggest that this isoform possibly contributed to enzymatic activity. The long isoform which is needed for the MSC complex was only represented by a faint band in the Western Blot of the same individual.
[PMID: 28905880] Using fibroblasts from an affected subject homozygous for a missense variant (NM_002887.3:c.5A>G / p.Asp2Gly) and controls, a 75% reduction of the long isoform was shown upon WB. The short isoform was present at similar levels. As the N-terminus (of the long isoform) mediates interaction with the MSC (and AIMP1), assembly of the latter was 99% reduced in patient fibroblasts. Proliferation of patient fibroblasts was significantly reduced when cultured in a medium with limited arginine, a finding which was thought to reflect inefficient protein synthesis.

Mutations in other genes encoding for aminoacyl-tRNA synthetases (eg. AARS1, VARS1) or scaffolding proteins of the multisynthetase complex (eg. AIMP1 and AIMP2) lead to neurodevelopmental disorders with overlapping phenotype [most genes rated green in both the ID and epilepsy panel].
Sources: Literature
CAKUT v1.41 Ellen McDonagh Panel types changed to Rare Disease 100K
Hereditary neuropathy NOT PMP22 copy number v1.0 Louise Daugherty promoted panel to version 1.0
Hereditary neuropathy NOT PMP22 copy number v0.108 Louise Daugherty Panel types changed to GMS Rare Disease; GMS signed-off
Hereditary neuropathy NOT PMP22 copy number v0.107 ABCA1 Louise Daugherty changed review comment from: Comment on list classification: Changed from Amber to Green - is a very rare condition, the primary feature can be neuropathy so if abnormalities of lipids or tonsils are missed or not present the diagnosis will not be made. However if there is a second panel to go to after the primary neuropathy panel and it is on it then it should still be diagnosed as long as a patient with primary neuropathy only would still be eligible for the more syndromic panel.; to: Comment on list classification: Changed from Amber to Green - recommendation from Genomics England clinical ream - is a very rare condition, the primary feature can be neuropathy so if abnormalities of lipids or tonsils are missed or not present the diagnosis will not be made. However if there is a second panel to go to after the primary neuropathy panel and it is on it then it should still be diagnosed as long as a patient with primary neuropathy only would still be eligible for the more syndromic panel.
Hereditary neuropathy NOT PMP22 copy number v0.107 ABCA1 Louise Daugherty Classified gene: ABCA1 as Green List (high evidence)
Hereditary neuropathy NOT PMP22 copy number v0.107 ABCA1 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green - is a very rare condition, the primary feature can be neuropathy so if abnormalities of lipids or tonsils are missed or not present the diagnosis will not be made. However if there is a second panel to go to after the primary neuropathy panel and it is on it then it should still be diagnosed as long as a patient with primary neuropathy only would still be eligible for the more syndromic panel.
Hereditary neuropathy NOT PMP22 copy number v0.107 ABCA1 Louise Daugherty Gene: abca1 has been classified as Green List (High Evidence).
Hereditary neuropathy NOT PMP22 copy number v0.106 VCP Louise Daugherty Classified gene: VCP as Amber List (moderate evidence)
Hereditary neuropathy NOT PMP22 copy number v0.106 VCP Louise Daugherty Added comment: Comment on list classification: Downgraded from Green to Amber from recommendation from Alex Rossor - only two published cases of VCP and neuropathy. P.Glu185Lys is absent form GNOMAD but p.Glu185Asp is present 4 times. I don’t think there have been any more cases. Might it be better as Amber for neuropathy?
Hereditary neuropathy NOT PMP22 copy number v0.106 VCP Louise Daugherty Gene: vcp has been classified as Amber List (Moderate Evidence).
Rare multisystem ciliopathy Super panel v4.3 Ellen McDonagh Panel types changed to GMS Rare Disease Virtual; Super Panel; GMS signed-off
Cystic kidney disease v2.1 Ivone Leong Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Rare multisystem ciliopathy Super panel v4.2 Ellen McDonagh Panel status changed from internal to public
Rare multisystem ciliopathy disorders v1.123 Ellen McDonagh Panel types changed to Rare Disease 100K
Rare multisystem ciliopathy Super panel v4.1 Ellen McDonagh Panel types changed to GMS Rare Disease Virtual; Super Panel
Primary ovarian insufficiency v1.17 Ellen McDonagh Panel types changed to Rare Disease 100K
Neuromuscular disorders v5.9 Louise Daugherty Panel types changed to GMS Rare Disease Virtual; Super Panel; GMS signed-off
Sudden cardiac death v9.11 Ivone Leong Changed child panels to: Arrhythmogenic cardiomyopathy; Long QT syndrome; Hypertrophic cardiomyopathy - teen and adult; Short QT syndrome; Catecholaminergic polymorphic VT; Brugada syndrome; Dilated cardiomyopathy - adult and teen; Progressive cardiac conduction disease
Intracerebral calcification disorders v1.18 Ellen McDonagh Panel types changed to Rare Disease 100K
Short QT syndrome v2.1 Ivone Leong Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Gastrointestinal neuromuscular disorders v1.11 Ellen McDonagh Panel types changed to Rare Disease 100K
Familial pulmonary fibrosis v1.7 Ellen McDonagh Panel types changed to Rare Disease 100K
Cardiac arrhythmias - additional genes v1.2 Ivone Leong Panel types changed to GMS Rare Disease Virtual; Component Of Super Panel; GMS signed-off
Familial dysautonomia v1.8 Ellen McDonagh Panel types changed to Rare Disease 100K
Dilated cardiomyopathy - adult and teen v1.1 Ivone Leong Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Extreme early-onset hypertension v1.11 Ellen McDonagh Panel types changed to Rare Disease 100K
Familial cerebral small vessel disease v1.7 Louise Daugherty Panel types changed to Rare Disease 100K
Progressive cardiac conduction disease v1.1 Ivone Leong Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Hypertrophic cardiomyopathy - teen and adult v2.1 Ivone Leong Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Brugada syndrome v2.1 Ivone Leong Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Catecholaminergic polymorphic VT v2.1 Ivone Leong Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Long QT syndrome v2.1 Ivone Leong Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Arrhythmogenic cardiomyopathy v2.1 Ivone Leong Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Ataxia and cerebellar anomalies - narrow panel v2.0 PTRH2 Ellen Thomas edited their review of gene: PTRH2: Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.0 PTRH2 Ellen Thomas gene: PTRH2 was added
gene: PTRH2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Other
Mode of inheritance for gene: PTRH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTRH2 were set to 25574476; 28328138
Phenotypes for gene: PTRH2 were set to Infantile-onset multisystem neurologic, endocrine, and pancreatic disease
Added comment: Currently on adult ataxia panel; more suitable for childhood onset panel
Sources: Other
Paediatric disorders v14.2 Rebecca Foulger Panel types changed to GMS Rare Disease Virtual; Super Panel; GMS signed-off
Growth failure in early childhood v1.3 CEP57 Ellen Thomas gene: CEP57 was added
gene: CEP57 was added to Growth failure in early childhood. Sources: Other
Mode of inheritance for gene: CEP57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP57 were set to 24259107; 21552266
Phenotypes for gene: CEP57 were set to Mosaic variegated aneuploidy syndrome 2
Review for gene: CEP57 was set to GREEN
Added comment: Phenotype includes IUGR and growth failure; green on other panels
Sources: Other
Skeletal dysplasia v2.0 Eleanor Williams promoted panel to version 2.0
Skeletal dysplasia v1.343 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; Component Of Super Panel; GMS signed-off
Skeletal dysplasia v1.342 TTC8 Eleanor Williams Classified gene: TTC8 as Green List (high evidence)
Skeletal dysplasia v1.342 TTC8 Eleanor Williams Gene: ttc8 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.341 ALX1 Eleanor Williams Classified gene: ALX1 as Green List (high evidence)
Skeletal dysplasia v1.341 ALX1 Eleanor Williams Added comment: Comment on list classification: Rating green due to association with FRONTONASAL DYSPLASIA TYPE 3. Other Frontonasal dysplasia genes ALX3 and ALX4 have been included on this panel. Including on the panel following the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.341 ALX1 Eleanor Williams Gene: alx1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.340 ALX1 Eleanor Williams commented on gene: ALX1: This gene is provisionally associated with ?Frontonasal dysplasia 3 (#613456) in OMIM. Has a confirmed association with FRONTONASAL DYSPLASIA TYPE 3 in Gene2Phenotype.

PMID: 20451171 - Uz et al. (2010) - 2 families presenting with autosomal-recessive frontonasal dysplasia (FND) characterized by bilateral extreme microphthalmia, bilateral oblique facial cleft, complete cleft palate, hypertelorism, wide nasal bridge with hypoplasia of the ala nasi, and low-set, posteriorly rotated ears in two distinct families. In one family they found a three siblings were affected, and CNV analysis of the critical region showed a homozygous 3.7 Mb deletion containing the ALX1 (CART1) gene. In the second family a homozygous donor-splice-site mutation (c.531+1G > A) in the ALX1 gene was found.

PMID: 27324866 - Ullah et al 2017 - report a consanguineous family from Pakistan with four individuals presenting a milder form of Frontonasal dysplasia. Using exome sequencing, a homozygous splice acceptor site variant has been identified in the ALX1 gene. The affected individuals had ptosis (drooping upper eyelid), small and upslanting palpebral fissures, blepharophimosis, broad nasal root, wide prominent nasal bridge, short and wide nasal ridge, broad columella, smooth philtrum, and mouth protrusion accompanied by teeth protrusion NOTE: no clefting reported in the individuals from this family.

PMID: 26610632 - Lyons et al 2015 - The “Contemporary” Burmese lineage of cats has a more brachycephalic head type. Offspring from “Contemporary” style mating produced a craniofacial defect in 25% of offspring (Noden and Evans, 1986; Sponenberg and Graf-Webster, 1986). The abnormality is characterized by agenesis of all derivatives of the medial nasal prominence; lateral duplication of most derivatives of the maxillary process; including the canine teeth and whiskers fields; telencephalic meningoencephalocele; and secondary ocular degeneration . The midline facial defect is autosomal recessive, however, carriers of the mutation are more brachycephalic individuals than wildtype, The entire ALX1 CDS sequence was analyzed in ten cats, including five affected Burmese and five controls. A 12 bp deletion (c.496delCTCTCAGGACTG) was identified in the coding region of ALX1. All the unaffected cats in the pedigree were confirmed to be homozygous wild-type or carrier of the 12 bp deletion while all the affected cats were homozygous for the identified variant. The average CDS homology between human and cat is 93.8% and the protein identity is 97.5%.
Skeletal dysplasia v1.340 WDPCP Eleanor Williams Classified gene: WDPCP as Green List (high evidence)
Skeletal dysplasia v1.340 WDPCP Eleanor Williams Added comment: Comment on list classification: Making this gene green as it is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.340 WDPCP Eleanor Williams Gene: wdpcp has been classified as Green List (High Evidence).
Skeletal dysplasia v1.339 WDPCP Eleanor Williams Phenotypes for gene: WDPCP were changed from to ?Congenital heart defects, hamartomas of tongue, and polysyndactyly 217085; ?Bardet-Biedl syndrome 15, 615992
Skeletal dysplasia v1.338 WDPCP Eleanor Williams Publications for gene: WDPCP were set to
Skeletal dysplasia v1.337 WDPCP Eleanor Williams Mode of inheritance for gene: WDPCP was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.336 TTC8 Eleanor Williams Classified gene: TTC8 as Red List (low evidence)
Skeletal dysplasia v1.336 TTC8 Eleanor Williams Added comment: Comment on list classification: Making this gene green as it is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.336 TTC8 Eleanor Williams Gene: ttc8 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.335 TTC8 Eleanor Williams Phenotypes for gene: TTC8 were changed from to Polydactyly; Bardet-Biedl syndrome 8, 615985
Skeletal dysplasia v1.334 TTC8 Eleanor Williams Mode of inheritance for gene: TTC8 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.333 TRIM32 Eleanor Williams Classified gene: TRIM32 as Red List (low evidence)
Skeletal dysplasia v1.333 TRIM32 Eleanor Williams Added comment: Comment on list classification: Keeping this gene red as it is is red on the GMS Bardet Biedl syndrome panel (v1.0). Also associated with Muscular dystrophy, limb-girdle, autosomal recessive 8 but no skeletal phenotype is present in this disorder.
Skeletal dysplasia v1.333 TRIM32 Eleanor Williams Gene: trim32 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.332 TRIM32 Eleanor Williams Phenotypes for gene: TRIM32 were changed from to Bardet-Biedl syndrome 11, 615988; Polydactyly
Skeletal dysplasia v1.331 SDCCAG8 Eleanor Williams Classified gene: SDCCAG8 as Red List (low evidence)
Skeletal dysplasia v1.331 SDCCAG8 Eleanor Williams Added comment: Comment on list classification: This gene is a Bardet-Biedl syndrome gene but polydactyly is not part of the phenotype - see clinical features listed in OMIM https://omim.org/entry/615993. Therefore keeping this gene red on the skeletal dysplasia panel.
Skeletal dysplasia v1.331 SDCCAG8 Eleanor Williams Gene: sdccag8 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.330 SDCCAG8 Eleanor Williams Phenotypes for gene: SDCCAG8 were changed from Senior-Loken syndrome 7, 613615; Bardet-Biedl syndrome 16, 615993 to Bardet-Biedl syndrome 16, 615993
Skeletal dysplasia v1.329 SDCCAG8 Eleanor Williams Phenotypes for gene: SDCCAG8 were changed from to Senior-Loken syndrome 7, 613615; Bardet-Biedl syndrome 16, 615993
Skeletal dysplasia v1.328 SDCCAG8 Eleanor Williams Mode of inheritance for gene: SDCCAG8 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.327 MKKS Eleanor Williams Classified gene: MKKS as Green List (high evidence)
Skeletal dysplasia v1.327 MKKS Eleanor Williams Added comment: Comment on list classification: Making this gene green as it is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.327 MKKS Eleanor Williams Gene: mkks has been classified as Green List (High Evidence).
Skeletal dysplasia v1.326 MKKS Eleanor Williams Phenotypes for gene: MKKS were changed from to Polydactyly; Bardet-Biedl syndrome 6, 605231; McKusick-Kaufman syndrome, 236700
Skeletal dysplasia v1.325 MKKS Eleanor Williams Mode of inheritance for gene: MKKS was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.324 CCDC28B Eleanor Williams Classified gene: CCDC28B as Red List (low evidence)
Skeletal dysplasia v1.324 CCDC28B Eleanor Williams Added comment: Comment on list classification: Keeping this gene on the panel as red as it is red on the GMS Bardet Biedl syndrome panel (v1.0). Modifier gene.
Skeletal dysplasia v1.324 CCDC28B Eleanor Williams Gene: ccdc28b has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.323 CCDC28B Eleanor Williams Mode of inheritance for gene: CCDC28B was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.322 CCDC28B Eleanor Williams Publications for gene: CCDC28B were set to
Skeletal dysplasia v1.321 CCDC28B Eleanor Williams Phenotypes for gene: CCDC28B were changed from to {Bardet-Biedl syndrome 1, modifier of}, 209900
Skeletal dysplasia v1.320 BBS9 Eleanor Williams Classified gene: BBS9 as Green List (high evidence)
Skeletal dysplasia v1.320 BBS9 Eleanor Williams Added comment: Comment on list classification: Making this gene green as it is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.320 BBS9 Eleanor Williams Gene: bbs9 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.319 BBS9 Eleanor Williams Phenotypes for gene: BBS9 were changed from to Polydactyly; Bardet Biedl syndrome 9, 615986
Skeletal dysplasia v1.318 BBS9 Eleanor Williams Mode of inheritance for gene: BBS9 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.317 BBS7 Eleanor Williams Classified gene: BBS7 as Green List (high evidence)
Skeletal dysplasia v1.317 BBS7 Eleanor Williams Gene: bbs7 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.316 BBS7 Eleanor Williams Classified gene: BBS7 as Red List (low evidence)
Skeletal dysplasia v1.316 BBS7 Eleanor Williams Added comment: Comment on list classification: Making this gene green as is is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.316 BBS7 Eleanor Williams Gene: bbs7 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.315 BBS7 Eleanor Williams Phenotypes for gene: BBS7 were changed from to Polydactyly; Bardet-Biedl syndrome 7, 615984
Skeletal dysplasia v1.314 BBS7 Eleanor Williams Mode of inheritance for gene: BBS7 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.313 BBS5 Eleanor Williams Classified gene: BBS5 as Green List (high evidence)
Skeletal dysplasia v1.313 BBS5 Eleanor Williams Added comment: Comment on list classification: Making this gene green as is is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.313 BBS5 Eleanor Williams Gene: bbs5 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.312 BBS5 Eleanor Williams Phenotypes for gene: BBS5 were changed from to Polydactyly; Bardet Biedl syndrome 5, 615983
Skeletal dysplasia v1.311 BBS5 Eleanor Williams Mode of inheritance for gene: BBS5 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.310 BBS4 Eleanor Williams Classified gene: BBS4 as Green List (high evidence)
Skeletal dysplasia v1.310 BBS4 Eleanor Williams Added comment: Comment on list classification: Making this gene green as is is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.310 BBS4 Eleanor Williams Gene: bbs4 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.309 BBS4 Eleanor Williams Phenotypes for gene: BBS4 were changed from to Polydactyly; Bardet-Biedl syndrome 4, 615982
Skeletal dysplasia v1.308 BBS4 Eleanor Williams Mode of inheritance for gene: BBS4 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.307 BBS2 Eleanor Williams Classified gene: BBS2 as Green List (high evidence)
Skeletal dysplasia v1.307 BBS2 Eleanor Williams Added comment: Comment on list classification: Making this gene green as is is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.307 BBS2 Eleanor Williams Gene: bbs2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.306 BBS2 Eleanor Williams Phenotypes for gene: BBS2 were changed from to Polydactyly; Bardet-Biedl syndrome 2, 615981
Skeletal dysplasia v1.305 BBS2 Eleanor Williams Mode of inheritance for gene: BBS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.304 BBS12 Eleanor Williams Classified gene: BBS12 as Green List (high evidence)
Skeletal dysplasia v1.304 BBS12 Eleanor Williams Added comment: Comment on list classification: Making this gene green as is is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.304 BBS12 Eleanor Williams Gene: bbs12 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.303 BBS12 Eleanor Williams Phenotypes for gene: BBS12 were changed from to Polydactyly; Bardet Biedl syndrome 12, 615989
Skeletal dysplasia v1.302 BBS12 Eleanor Williams Mode of inheritance for gene: BBS12 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.301 BBS10 Eleanor Williams Classified gene: BBS10 as Green List (high evidence)
Skeletal dysplasia v1.301 BBS10 Eleanor Williams Added comment: Comment on list classification: Making this gene green as is is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.301 BBS10 Eleanor Williams Gene: bbs10 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.300 BBS10 Eleanor Williams Phenotypes for gene: BBS10 were changed from to Polydactyly; Bardet Biedl syndrome 10, 615987
Skeletal dysplasia v1.299 BBS10 Eleanor Williams Mode of inheritance for gene: BBS10 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.298 BBS1 Eleanor Williams Classified gene: BBS1 as Green List (high evidence)
Skeletal dysplasia v1.298 BBS1 Eleanor Williams Added comment: Comment on list classification: Making this gene green as is is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.298 BBS1 Eleanor Williams Gene: bbs1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.297 BBS1 Eleanor Williams Phenotypes for gene: BBS1 were changed from to Polydactyly; Bardet-Biedl syndrome 1 209900
Skeletal dysplasia v1.297 BBS1 Eleanor Williams Publications for gene: BBS1 were set to
Skeletal dysplasia v1.296 BBS1 Eleanor Williams Mode of inheritance for gene: BBS1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Ectodermal dysplasia v1.1 Catherine Snow Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Autosomal recessive primary hypertrophic osteoarthropathy v1.1 Catherine Snow Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Rare genetic inflammatory skin disorders v1.3 Catherine Snow Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Palmoplantar keratodermas v1.0 Catherine Snow promoted panel to version 1.0
Palmoplantar keratodermas v0.11 Catherine Snow List of related panels changed from to R166
Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Mosaic skin disorders - deep sequencing v1.0 Catherine Snow promoted panel to version 1.0
Mosaic skin disorders - deep sequencing v0.24 Catherine Snow List of related panels changed from to R327
Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Multiple monogenic benign skin tumours v1.0 Ellen McDonagh promoted panel to version 1.0
Multiple monogenic benign skin tumours v0.16 Ellen McDonagh Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v2.0 Louise Daugherty promoted panel to version 2.0
Multiple monogenic benign skin tumours v0.15 Ellen McDonagh List of related panels changed from to R230
Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v1.9 Louise Daugherty List of related panels changed from Cockayne and Xeroderma Pigmentosum-like disorders; Cockayne syndrome; Xeroderma Pigmentosum-like disorders; XP-like disorders to Cockayne and Xeroderma Pigmentosum-like disorders; Cockayne syndrome; Xeroderma Pigmentosum-like disorders; XP-like disorders; R227
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; GMS signed-off
Rare genetic inflammatory skin disorders v1.1 Ellen McDonagh Panel types changed to GMS Rare Disease; Component Of Super Panel; GMS Cancer Germline Virtual; GMS signed-off
Epidermodysplasia verruciformis v1.0 Ellen McDonagh promoted panel to version 1.0
Epidermodysplasia verruciformis v0.15 Ellen McDonagh Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Hypotonic infant v9.1 Rebecca Foulger Panel types changed to GMS Rare Disease Virtual; Super Panel; GMS signed-off
Epidermodysplasia verruciformis v0.14 Ellen McDonagh Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel
Epidermodysplasia verruciformis v0.13 Ellen McDonagh List of related panels changed from to R255
Mosaic skin disorders - deep sequencing v0.23 TEK Catherine Snow Classified gene: TEK as Amber List (moderate evidence)
Mosaic skin disorders - deep sequencing v0.23 TEK Catherine Snow Gene: tek has been classified as Amber List (Moderate Evidence).
Mosaic skin disorders - deep sequencing v0.22 TEK Catherine Snow gene: TEK was added
gene: TEK was added to Mosaic skin disorders - deep sequencing. Sources: Expert Review
Mode of inheritance for gene: TEK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TEK were set to 27519652
Phenotypes for gene: TEK were set to Venous malformations, multiple cutaneous and mucosal, 600195
Review for gene: TEK was set to AMBER
Added comment: As advised by Genomics England clinician - "TEK is currently green on vascular and DDG2P panels, activating germline mutations cause cutaneous mucosal venous malformations, somatic mutations cause blue rubber bleb naevus syndrome. I don’t know how much evidence there is for blood mosaicism detection (versus tissue testing). Soblet et al, 2017, (PMID 27519652), didn’t find the pathogenic variants (identified through tissue testing) with targeted deep sequencing in blue rubber bleb naevus syndrome, but did find one at the 1-5% level in sporadic multifocal vascular malformation (probably all related conditions??). As not much targeted deep sequencing has been done it’s possible this would be a good future one.
Sources: Expert Review
Autosomal recessive primary hypertrophic osteoarthropathy v1.0 Ivone Leong promoted panel to version 1.0
Skeletal dysplasia v1.295 ARL6 Eleanor Williams Classified gene: ARL6 as Green List (high evidence)
Skeletal dysplasia v1.295 ARL6 Eleanor Williams Added comment: Comment on list classification: Making this gene green as is is green on the Limb disorders panel for polydactyly. Including on the advice of Prof Lyn Chitty.
Skeletal dysplasia v1.295 ARL6 Eleanor Williams Gene: arl6 has been classified as Green List (High Evidence).
Autosomal recessive primary hypertrophic osteoarthropathy v0.12 Ivone Leong List of related panels changed from to R167
Panel types changed to GMS Rare Disease; Component Of Super Panel; GMS signed-off
Skeletal dysplasia v1.294 ARL6 Eleanor Williams Phenotypes for gene: ARL6 were changed from to Polydactyly; Bardet-Biedl syndrome 3 600151
Skeletal dysplasia v1.294 ARL6 Eleanor Williams Publications for gene: ARL6 were set to
Skeletal dysplasia v1.293 ARL6 Eleanor Williams Mode of inheritance for gene: ARL6 was changed from to BIALLELIC, autosomal or pseudoautosomal
Ectodermal dysplasia v1.0 Ivone Leong promoted panel to version 1.0
Ectodermal dysplasia v0.36 Ivone Leong List of related panels changed from to R163
Panel types changed to GMS Rare Disease; Component Of Super Panel; GMS signed-off
Vascular skin disorders v1.0 Louise Daugherty promoted panel to version 1.0
Vascular skin disorders v0.39 Louise Daugherty List of related panels changed from to R326
Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Ichthyosis and erythrokeratoderma v1.0 Catherine Snow promoted panel to version 1.0
Rare genetic inflammatory skin disorders v1.0 Ellen McDonagh promoted panel to version 1.0
Ichthyosis and erythrokeratoderma v0.19 Catherine Snow List of related panels changed from to R165
Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Rare genetic inflammatory skin disorders v0.23 Ellen McDonagh List of related panels changed from to R332
Panel types changed to GMS Rare Disease; Component Of Super Panel; GMS signed-off
Fetal anomalies v1.0 Rebecca Foulger promoted panel to version 1.0
Pigmentary skin disorders v1.0 Louise Daugherty promoted panel to version 1.0
Pigmentary skin disorders v0.28 Louise Daugherty List of related panels changed from to R236
Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Fetal anomalies v0.375 Rebecca Foulger Panel types changed to GMS Rare Disease Virtual; GMS signed-off
Cutaneous photosensitivity with a likely genetic cause v1.0 Louise Daugherty promoted panel to version 1.0
Epidermolysis bullosa and congenital skin fragility v1.0 Catherine Snow promoted panel to version 1.0
Epidermolysis bullosa and congenital skin fragility v0.27 Catherine Snow List of related panels changed from to R164
Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Cutaneous photosensitivity with a likely genetic cause v0.12 Louise Daugherty List of related panels changed from to R237
Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Segmental overgrowth disorders v2.0 Ivone Leong promoted panel to version 2.0
Segmental overgrowth disorders v1.11 Ivone Leong List of related panels changed from Regional overgrowth disorders to Regional overgrowth disorders; R110
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; Component Of Super Panel; GMS signed-off
Ichthyosis and erythrokeratoderma v0.18 FLG2 Catherine Snow Classified gene: FLG2 as Green List (high evidence)
Ichthyosis and erythrokeratoderma v0.18 FLG2 Catherine Snow Added comment: Comment on list classification: Sufficient number of variants in OMIM to rate as Green
Ichthyosis and erythrokeratoderma v0.18 FLG2 Catherine Snow Gene: flg2 has been classified as Green List (High Evidence).
White matter disorders - childhood onset v6.3 Louise Daugherty Panel types changed to GMS Rare Disease Virtual; Super Panel; GMS signed-off
Rare genetic inflammatory skin disorders v0.22 KIT Catherine Snow reviewed gene: KIT: Rating: ; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: ; Phenotypes: ; Mode of inheritance: None
Mosaic skin disorders - deep sequencing v0.21 NF2 Catherine Snow Classified gene: NF2 as Green List (high evidence)
Mosaic skin disorders - deep sequencing v0.21 NF2 Catherine Snow Gene: nf2 has been classified as Green List (High Evidence).
White matter disorders and cerebral calcification - narrow panel v1.11 Louise Daugherty Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
White matter disorders and cerebral calcification - narrow panel v1.10 Louise Daugherty Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel
Mosaic skin disorders - deep sequencing v0.20 NF2 Catherine Snow gene: NF2 was added
gene: NF2 was added to Mosaic skin disorders - deep sequencing. Sources: Expert Review
Mode of inheritance for gene: NF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NF2 were set to 29409008
Phenotypes for gene: NF2 were set to NEUROFIBROMATOSIS, TYPE II; NF2
Added comment: Added to panel as advised by Genomics England Clinical Team as NF2 is tested on mosaic panel at GOSH and "targeted NGS can detect low level mosaicism in blood (often tumour tissue is tested if available but some may be detectable with deep sequencing of blood)".
Sources: Expert Review
Childhood onset dystonia or chorea or related movement disorder v1.0 Louise Daugherty promoted panel to version 1.0
Childhood onset dystonia or chorea or related movement disorder v0.259 Louise Daugherty Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; GMS signed-off
Childhood onset dystonia or chorea or related movement disorder v0.258 CP Louise Daugherty commented on gene: CP
Childhood onset dystonia or chorea or related movement disorder v0.258 CHMP2B Louise Daugherty commented on gene: CHMP2B
Childhood onset dystonia or chorea or related movement disorder v0.258 RNASEH2A Louise Daugherty commented on gene: RNASEH2A
Childhood onset dystonia or chorea or related movement disorder v0.258 L2HGDH Louise Daugherty commented on gene: L2HGDH
Childhood onset dystonia or chorea or related movement disorder v0.258 HPRT1 Louise Daugherty commented on gene: HPRT1
Childhood onset dystonia or chorea or related movement disorder v0.258 CIZ1 Louise Daugherty commented on gene: CIZ1
Childhood onset dystonia or chorea or related movement disorder v0.258 AUH Louise Daugherty commented on gene: AUH
Epidermolysis bullosa and congenital skin fragility v0.26 PLOD3 Catherine Snow changed review comment from: PMID: 30463024 reports on an individual with a homozygous missense mutation in PLOD3. In addition to skin blistering, the proband demonstrated extensive joint contractures, skeletal abnormalities and reduced growth.
PMID: 18834968 identified a compound heterozygote in PLOD3 with recessive inheritance. The patient reported had an extremely complex phenotype, including deafness, myopia, arterial ruptures, osteopenia, joint contractures, bone fractures, and cataracts, as well as clinically observed skin blistering, apparently reflecting the deficiency in both lysyl hydroxylation and glycosylation of hydroxylysyl residues.
As only two variants currently reported PLOD3 rated as Amber; to: PMID: 30463024 reports on an individual with a homozygous missense mutation in PLOD3. In addition to skin blistering, the proband demonstrated extensive joint contractures, skeletal abnormalities and reduced growth.
PMID: 18834968 identified a compound heterozygote in PLOD3 with recessive inheritance. The patient reported had an extremely complex phenotype, including deafness, myopia, arterial ruptures, osteopenia, joint contractures, bone fractures, and cataracts, as well as clinically observed skin blistering, apparently reflecting the deficiency in both lysyl hydroxylation and glycosylation of hydroxylysyl residues.
As only two variants currently reported PLOD3 rated as Amber.
Epidermolysis bullosa and congenital skin fragility v0.26 PLOD3 Catherine Snow commented on gene: PLOD3: PMID: 30463024 reports on an individual with a homozygous missense mutation in PLOD3. In addition to skin blistering, the proband demonstrated extensive joint contractures, skeletal abnormalities and reduced growth.
PMID: 18834968 identified a compound heterozygote in PLOD3 with recessive inheritance. The patient reported had an extremely complex phenotype, including deafness, myopia, arterial ruptures, osteopenia, joint contractures, bone fractures, and cataracts, as well as clinically observed skin blistering, apparently reflecting the deficiency in both lysyl hydroxylation and glycosylation of hydroxylysyl residues.
As only two variants currently reported PLOD3 rated as Amber
Childhood onset dystonia or chorea or related movement disorder v0.258 TREX1 Louise Daugherty commented on gene: TREX1
Childhood onset dystonia or chorea or related movement disorder v0.258 TPK1 Louise Daugherty Classified gene: TPK1 as Green List (high evidence)
Childhood onset dystonia or chorea or related movement disorder v0.258 TPK1 Louise Daugherty Added comment: Comment on list classification: Changed from Red to Green as per recommendation from Specialist Test Group (via Robyn Labrum LNGLH). Reported in multiple families
Childhood onset dystonia or chorea or related movement disorder v0.258 TPK1 Louise Daugherty Gene: tpk1 has been classified as Green List (High Evidence).
Childhood onset dystonia or chorea or related movement disorder v0.257 TIMM8A Louise Daugherty commented on gene: TIMM8A
Childhood onset dystonia or chorea or related movement disorder v0.257 TAF1 Louise Daugherty commented on gene: TAF1: Confirmed Green rating - as per recommendation from Specialist Test Group (via Robyn Labrum LNGLH) 12 December 2019.
Childhood onset dystonia or chorea or related movement disorder v0.257 SUOX Louise Daugherty commented on gene: SUOX
Childhood onset dystonia or chorea or related movement disorder v0.257 SAMHD1 Louise Daugherty commented on gene: SAMHD1
Childhood onset dystonia or chorea or related movement disorder v0.257 RNASEH2C Louise Daugherty Tag founder-effect tag was added to gene: RNASEH2C.
Childhood onset dystonia or chorea or related movement disorder v0.257 RNASEH2C Louise Daugherty commented on gene: RNASEH2C
Childhood onset dystonia or chorea or related movement disorder v0.257 RNASEH2B Louise Daugherty commented on gene: RNASEH2B
Childhood onset dystonia or chorea or related movement disorder v0.257 PDHX Louise Daugherty commented on gene: PDHX
Childhood onset dystonia or chorea or related movement disorder v0.257 NPC2 Louise Daugherty commented on gene: NPC2
Childhood onset dystonia or chorea or related movement disorder v0.257 HEXA Louise Daugherty commented on gene: HEXA
Rare genetic inflammatory skin disorders v0.22 NLRP3 Catherine Snow Source Expert Review Green was added to NLRP3.
Added phenotypes FCAS1; CINCA, FAMILIAL COLD AUTOINFLAMMATORY SYNDROME 1; CINCA SYNDROME for gene: NLRP3
Publications for gene NLRP3 were changed from to 11687797; 12032915
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare genetic inflammatory skin disorders v0.22 NLRP1 Catherine Snow Added phenotypes AIADK; AUTOINFLAMMATION WITH ARTHRITIS AND DYSKERATOSIS for gene: NLRP1
Publications for gene NLRP1 were changed from to 27965258
Rare genetic inflammatory skin disorders v0.22 GGCX Catherine Snow Added phenotypes PSEUDOXANTHOMA ELASTICUM-LIKE DISORDER WITH MULTIPLE COAGULATION FACTOR DEFICIENCY for gene: GGCX
Publications for gene GGCX were changed from to 17110937
Rare genetic inflammatory skin disorders v0.22 EGFR Catherine Snow Source Expert Review Green was added to EGFR.
Added phenotypes NISBD2; INFLAMMATORY SKIN AND BOWEL DISEASE, NEONATAL, 2 for gene: EGFR
Publications for gene EGFR were changed from to 24691054; 29899996; 26436111
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare genetic inflammatory skin disorders v0.22 AIRE Catherine Snow Source Expert Review Green was added to AIRE.
Added phenotypes AUTOIMMUNE POLYENDOCRINE SYNDROME, TYPE I, WITH OR WITHOUT REVERSIBLE METAPHYSEAL DYSPLASIA; APS1 for gene: AIRE
Publications for gene AIRE were changed from to 9921903; 9398839
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare genetic inflammatory skin disorders v0.22 ABCC6 Catherine Snow Added phenotypes PSEUDOXANTHOMA ELASTICUM; PXE for gene: ABCC6
Publications for gene ABCC6 were changed from to 10835642
Rare genetic inflammatory skin disorders v0.22 TREX1 Catherine Snow Added phenotypes CHBL1; AICARDI-GOUTIERES SYNDROME 1; AGS1, CHILBLAIN LUPUS 1 for gene: TREX1
Publications for gene TREX1 were changed from to 16845398; 17660818
Rare genetic inflammatory skin disorders v0.22 TMEM173 Catherine Snow Added phenotypes STING-ASSOCIATED VASCULOPATHY, INFANTILE-ONSET; SAVI for gene: TMEM173
Publications for gene TMEM173 were changed from to 25029335
Rare genetic inflammatory skin disorders v0.22 STAT3 Catherine Snow Added phenotypes ADMIO1; HIES1, AUTOIMMUNE DISEASE, MULTISYSTEM, INFANTILE-ONSET, 1; HYPER-IgE RECURRENT INFECTION SYNDROME 1, AUTOSOMAL DOMINANT for gene: STAT3
Publications for gene STAT3 were changed from to 17676033; 25038750
Rare genetic inflammatory skin disorders v0.22 SLC39A4 Catherine Snow Added phenotypes ACRODERMATITIS ENTEROPATHICA, ZINC-DEFICIENCY TYPE; AEZ for gene: SLC39A4
Publications for gene SLC39A4 were changed from to 12068297
Rare genetic inflammatory skin disorders v0.22 SH3PXD2B Catherine Snow Added phenotypes FTHS; FRANK-TER HAAR SYNDROME for gene: SH3PXD2B
Publications for gene SH3PXD2B were changed from to 20137777
Rare genetic inflammatory skin disorders v0.22 SAMHD1 Catherine Snow Added phenotypes AICARDI-GOUTIERES SYNDROME 5; AGS5, CHILBLAIN LUPUS 2; CHBL2 for gene: SAMHD1
Publications for gene SAMHD1 were changed from to 21204240; 19525956
Rare genetic inflammatory skin disorders v0.22 RAG2 Catherine Snow Added phenotypes OMENN SYNDROME for gene: RAG2
Publications for gene RAG2 were changed from to 9630231
Rare genetic inflammatory skin disorders v0.22 RAG1 Catherine Snow Added phenotypes OMENN SYNDROME for gene: RAG1
Publications for gene RAG1 were changed from to 9630231
Rare genetic inflammatory skin disorders v0.22 PSENEN Catherine Snow Added phenotypes ACNINV2; ACNE INVERSA, FAMILIAL, 2, WITH OR WITHOUT DOWLING-DEGOS DISEASE for gene: PSENEN
Rare genetic inflammatory skin disorders v0.22 PSEN1 Catherine Snow Source Expert Review Amber was added to PSEN1.
Added phenotypes ACNE INVERSA, FAMILIAL, 3; ACNINV3 for gene: PSEN1
Publications for gene PSEN1 were changed from to 20929727
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Rare genetic inflammatory skin disorders v0.22 OSMR Catherine Snow Added phenotypes PLCA1; AMYLOIDOSIS, PRIMARY LOCALIZED CUTANEOUS, 1 for gene: OSMR
Publications for gene OSMR were changed from to 18179886
Rare genetic inflammatory skin disorders v0.22 NSDHL Catherine Snow Added phenotypes CONGENITAL HEMIDYSPLASIA WITH ICHTHYOSIFORM ERYTHRODERMA AND LIMB DEFECTS for gene: NSDHL
Publications for gene NSDHL were changed from to 10710235
Rare genetic inflammatory skin disorders v0.22 NOD2 Catherine Snow Added phenotypes BLAUS; BLAU SYNDROME for gene: NOD2
Publications for gene NOD2 were changed from to 11528384
Rare genetic inflammatory skin disorders v0.22 NCSTN Catherine Snow Added phenotypes ACNINV1; ACNE INVERSA, FAMILIAL, 1 for gene: NCSTN
Publications for gene NCSTN were changed from to 20929727
Rare genetic inflammatory skin disorders v0.22 MVD Catherine Snow Added phenotypes POROKERATOSIS 7, MULTIPLE TYPES; POROK7 for gene: MVD
Publications for gene MVD were changed from to 26202976
Rare genetic inflammatory skin disorders v0.22 KRT10 Catherine Snow Source Expert Review Amber was added to KRT10.
Added phenotypes Ichythosis with confetti; Palmoplantar keratoderma; Epidermolytic hyperkeratosis for gene: KRT10
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Rare genetic inflammatory skin disorders v0.22 KRT1 Catherine Snow Source Expert Review Amber was added to KRT1.
Added phenotypes Ichthyosis histrix; Palmoplantar keratoderma; Epidermolytic hyperkeratosis for gene: KRT1
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Rare genetic inflammatory skin disorders v0.22 KIT Catherine Snow Added phenotypes MASTOCYTOSIS, CUTANEOUS; MASTC for gene: KIT
Publications for gene KIT were changed from to 9990072
Rare genetic inflammatory skin disorders v0.22 IL36RN Catherine Snow Added phenotypes PSORIASIS 14, PUSTULAR; PSORS14 for gene: IL36RN
Publications for gene IL36RN were changed from to 22903787
Rare genetic inflammatory skin disorders v0.22 IL1RN Catherine Snow Added phenotypes OMPP; OSTEOMYELITIS, STERILE MULTIFOCAL, WITH PERIOSTITIS AND PUSTULOSIS for gene: IL1RN
Publications for gene IL1RN were changed from to 19494218
Rare genetic inflammatory skin disorders v0.22 IKBKG Catherine Snow Source Expert Review Amber was added to IKBKG.
Added phenotypes Incontinentia pigmenti for gene: IKBKG
Publications for gene IKBKG were changed from to 10839543
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Rare genetic inflammatory skin disorders v0.22 GJB4 Catherine Snow Added phenotypes Erythrokeratodermia variabilis et progressiva 2 for gene: GJB4
Publications for gene GJB4 were changed from to 12648223
Rare genetic inflammatory skin disorders v0.22 GJB3 Catherine Snow Added phenotypes Erythrokeratodermia variabilis et progressiva 1 for gene: GJB3
Publications for gene GJB3 were changed from to 10798362
Rare genetic inflammatory skin disorders v0.22 GJA1 Catherine Snow Added phenotypes ERYTHROKERATODERMIA VARIABILIS ET PROGRESSIVA 3; EKVP3 for gene: GJA1
Publications for gene GJA1 were changed from to 25398053
Rare genetic inflammatory skin disorders v0.22 FLG Catherine Snow Source Expert Review Amber was added to FLG.
Added phenotypes Eczema; Ichthyosis vulgaris 146700; Ichthyosis vulgaris for gene: FLG
Publications for gene FLG were changed from 16444271; 16815158; 17030239; 17291859 to 16550169
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Rare genetic inflammatory skin disorders v0.22 FDPS Catherine Snow Added phenotypes POROKERATOSIS 9, MULTIPLE TYPES for gene: FDPS
Publications for gene FDPS were changed from to 26202976
Rare genetic inflammatory skin disorders v0.22 EDA Catherine Snow Source Expert Review Red was added to EDA.
Added phenotypes ECTODERMAL DYSPLASIA 1, HYPOHIDROTIC, X-LINKED for gene: EDA
Publications for gene EDA were changed from to 9683615
Rating Changed from Green List (high evidence) to Red List (low evidence)
Rare genetic inflammatory skin disorders v0.22 DOCK8 Catherine Snow Added phenotypes Hyper-IgE recurrent infection syndrome, autosomal recessive for gene: DOCK8
Publications for gene DOCK8 were changed from to 19776401
Rare genetic inflammatory skin disorders v0.22 DCLRE1C Catherine Snow Source Expert Review Amber was added to DCLRE1C.
Added phenotypes Omenn syndrome for gene: DCLRE1C
Publications for gene DCLRE1C were changed from to 15731174
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Rare genetic inflammatory skin disorders v0.22 CYBB Catherine Snow Source Expert Review Amber was added to CYBB.
Added phenotypes Chillblain lupus; Discoid lupus erythematosus for gene: CYBB
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Rare genetic inflammatory skin disorders v0.22 CSTA Catherine Snow Source Expert Review Amber was added to CSTA.
Added phenotypes susceptibility to psoriasis; Exfoliative ichthyosis/acral peeling skin syndrome; susceptility to atopic dermatitis for gene: CSTA
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Rare genetic inflammatory skin disorders v0.22 CARD9 Catherine Snow Added phenotypes Deep dermatophytosis for gene: CARD9
Rare genetic inflammatory skin disorders v0.22 CARD14 Catherine Snow Added phenotypes Pityriasis rubra pilaris; susceptibility to psoriasis for gene: CARD14
Publications for gene CARD14 were changed from to 22703878; 22521418
Rare genetic inflammatory skin disorders v0.22 CARD11 Catherine Snow Added phenotypes Immunodeficiency 11B with atopic dermatitis for gene: CARD11
Publications for gene CARD11 were changed from to 28628108
Rare genetic inflammatory skin disorders v0.22 ADA2 Catherine Snow Added phenotypes VAIHS (Polyarteritis nodosa); VASCULITIS, AUTOINFLAMMATION, IMMUNODEFICIENCY, AND HEMATOLOGIC DEFECTS SYNDROME for gene: ADA2
Publications for gene ADA2 were changed from to 24552284
Rare genetic inflammatory skin disorders v0.21 NLRP3 Tom Cullup reviewed gene: NLRP3: Rating: GREEN; Mode of pathogenicity: ; Publications: 11687797, 12032915; Phenotypes: CINCA SYNDROME, CINCA, FAMILIAL COLD AUTOINFLAMMATORY SYNDROME 1, FCAS1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare genetic inflammatory skin disorders v0.21 NLRP1 Tom Cullup reviewed gene: NLRP1: Rating: AMBER; Mode of pathogenicity: ; Publications: 27965258; Phenotypes: AUTOINFLAMMATION WITH ARTHRITIS AND DYSKERATOSIS, AIADK; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 GGCX Tom Cullup reviewed gene: GGCX: Rating: AMBER; Mode of pathogenicity: ; Publications: 17110937; Phenotypes: PSEUDOXANTHOMA ELASTICUM-LIKE DISORDER WITH MULTIPLE COAGULATION FACTOR DEFICIENCY; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 EGFR Tom Cullup reviewed gene: EGFR: Rating: GREEN; Mode of pathogenicity: ; Publications: 24691054, 29899996, 26436111; Phenotypes: INFLAMMATORY SKIN AND BOWEL DISEASE, NEONATAL, 2, NISBD2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 AIRE Tom Cullup reviewed gene: AIRE: Rating: GREEN; Mode of pathogenicity: ; Publications: 9398839, 9921903; Phenotypes: AUTOIMMUNE POLYENDOCRINE SYNDROME, TYPE I, WITH OR WITHOUT REVERSIBLE METAPHYSEAL DYSPLASIA, APS1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 ABCC6 Tom Cullup reviewed gene: ABCC6: Rating: AMBER; Mode of pathogenicity: ; Publications: 10835642; Phenotypes: PSEUDOXANTHOMA ELASTICUM, PXE; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 TREX1 Tom Cullup reviewed gene: TREX1: Rating: GREEN; Mode of pathogenicity: ; Publications: 16845398, 17660818; Phenotypes: AICARDI-GOUTIERES SYNDROME 1, AGS1, CHILBLAIN LUPUS 1, CHBL1; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 TMEM173 Tom Cullup reviewed gene: TMEM173: Rating: GREEN; Mode of pathogenicity: ; Publications: 25029335; Phenotypes: STING-ASSOCIATED VASCULOPATHY, INFANTILE-ONSET, SAVI; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare genetic inflammatory skin disorders v0.21 STAT3 Tom Cullup reviewed gene: STAT3: Rating: GREEN; Mode of pathogenicity: ; Publications: 17676033, 25038750; Phenotypes: HYPER-IgE RECURRENT INFECTION SYNDROME 1, AUTOSOMAL DOMINANT, HIES1, AUTOIMMUNE DISEASE, MULTISYSTEM, INFANTILE-ONSET, 1, ADMIO1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare genetic inflammatory skin disorders v0.21 SLC39A4 Tom Cullup reviewed gene: SLC39A4: Rating: GREEN; Mode of pathogenicity: ; Publications: 12068297; Phenotypes: ACRODERMATITIS ENTEROPATHICA, ZINC-DEFICIENCY TYPE, AEZ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 SH3PXD2B Tom Cullup reviewed gene: SH3PXD2B: Rating: GREEN; Mode of pathogenicity: ; Publications: 20137777; Phenotypes: FRANK-TER HAAR SYNDROME, FTHS; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 SAMHD1 Tom Cullup reviewed gene: SAMHD1: Rating: GREEN; Mode of pathogenicity: ; Publications: 19525956, 21204240; Phenotypes: AICARDI-GOUTIERES SYNDROME 5, AGS5, CHILBLAIN LUPUS 2, CHBL2; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 RAG2 Tom Cullup reviewed gene: RAG2: Rating: GREEN; Mode of pathogenicity: ; Publications: 9630231; Phenotypes: OMENN SYNDROME; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 RAG1 Tom Cullup reviewed gene: RAG1: Rating: GREEN; Mode of pathogenicity: ; Publications: 9630231; Phenotypes: OMENN SYNDROME; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 PSEN1 Tom Cullup reviewed gene: PSEN1: Rating: AMBER; Mode of pathogenicity: ; Publications: 20929727; Phenotypes: ACNE INVERSA, FAMILIAL, 3, ACNINV3; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare genetic inflammatory skin disorders v0.21 OSMR Tom Cullup reviewed gene: OSMR: Rating: GREEN; Mode of pathogenicity: ; Publications: 18179886; Phenotypes: AMYLOIDOSIS, PRIMARY LOCALIZED CUTANEOUS, 1, PLCA1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare genetic inflammatory skin disorders v0.21 NSDHL Tom Cullup reviewed gene: NSDHL: Rating: GREEN; Mode of pathogenicity: ; Publications: 10710235; Phenotypes: CONGENITAL HEMIDYSPLASIA WITH ICHTHYOSIFORM ERYTHRODERMA AND LIMB DEFECTS; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Rare genetic inflammatory skin disorders v0.21 NOD2 Tom Cullup reviewed gene: NOD2: Rating: GREEN; Mode of pathogenicity: ; Publications: 11528384; Phenotypes: BLAU SYNDROME, BLAUS; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare genetic inflammatory skin disorders v0.21 NCSTN Tom Cullup reviewed gene: NCSTN: Rating: GREEN; Mode of pathogenicity: ; Publications: 20929727; Phenotypes: ACNE INVERSA, FAMILIAL, 1, ACNINV1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare genetic inflammatory skin disorders v0.21 MVD Tom Cullup reviewed gene: MVD: Rating: GREEN; Mode of pathogenicity: ; Publications: 26202976; Phenotypes: POROKERATOSIS 7, MULTIPLE TYPES, POROK7; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare genetic inflammatory skin disorders v0.21 KRT10 Tom Cullup reviewed gene: KRT10: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Epidermolytic hyperkeratosis, Palmoplantar keratoderma, Ichythosis with confetti; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare genetic inflammatory skin disorders v0.21 KRT1 Tom Cullup reviewed gene: KRT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Epidermolytic hyperkeratosis, Palmoplantar keratoderma, Ichthyosis histrix; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare genetic inflammatory skin disorders v0.21 KIT Tom Cullup reviewed gene: KIT: Rating: GREEN; Mode of pathogenicity: ; Publications: 9990072; Phenotypes: MASTOCYTOSIS, CUTANEOUS, MASTC; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare genetic inflammatory skin disorders v0.21 IL36RN Tom Cullup reviewed gene: IL36RN: Rating: GREEN; Mode of pathogenicity: ; Publications: 22903787; Phenotypes: PSORIASIS 14, PUSTULAR, PSORS14; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 IL1RN Tom Cullup reviewed gene: IL1RN: Rating: GREEN; Mode of pathogenicity: ; Publications: 19494218; Phenotypes: OSTEOMYELITIS, STERILE MULTIFOCAL, WITH PERIOSTITIS AND PUSTULOSIS, OMPP; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 IKBKG Tom Cullup reviewed gene: IKBKG: Rating: AMBER; Mode of pathogenicity: ; Publications: 10839543; Phenotypes: Incontinentia pigmenti; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Rare genetic inflammatory skin disorders v0.21 GJB4 Tom Cullup reviewed gene: GJB4: Rating: GREEN; Mode of pathogenicity: ; Publications: 12648223; Phenotypes: Erythrokeratodermia variabilis et progressiva 2; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 GJB3 Tom Cullup reviewed gene: GJB3: Rating: GREEN; Mode of pathogenicity: ; Publications: 10798362; Phenotypes: Erythrokeratodermia variabilis et progressiva 1; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 GJA1 Tom Cullup reviewed gene: GJA1: Rating: GREEN; Mode of pathogenicity: ; Publications: 25398053; Phenotypes: ERYTHROKERATODERMIA VARIABILIS ET PROGRESSIVA 3, EKVP3; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 FLG Tom Cullup reviewed gene: FLG: Rating: AMBER; Mode of pathogenicity: ; Publications: 16550169; Phenotypes: Ichthyosis vulgaris, Eczema, Ichthyosis vulgaris 146700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare genetic inflammatory skin disorders v0.21 FDPS Tom Cullup reviewed gene: FDPS: Rating: GREEN; Mode of pathogenicity: ; Publications: 26202976; Phenotypes: POROKERATOSIS 9, MULTIPLE TYPES; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare genetic inflammatory skin disorders v0.21 EDA Tom Cullup reviewed gene: EDA: Rating: RED; Mode of pathogenicity: ; Publications: 9683615; Phenotypes: ECTODERMAL DYSPLASIA 1, HYPOHIDROTIC, X-LINKED; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Rare genetic inflammatory skin disorders v0.21 DOCK8 Tom Cullup reviewed gene: DOCK8: Rating: GREEN; Mode of pathogenicity: ; Publications: 19776401; Phenotypes: Hyper-IgE recurrent infection syndrome, autosomal recessive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 DCLRE1C Tom Cullup reviewed gene: DCLRE1C: Rating: AMBER; Mode of pathogenicity: ; Publications: 15731174; Phenotypes: Omenn syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 CYBB Tom Cullup reviewed gene: CYBB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Chillblain lupus, Discoid lupus erythematosus; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Rare genetic inflammatory skin disorders v0.21 CSTA Tom Cullup reviewed gene: CSTA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: susceptility to atopic dermatitis, Exfoliative ichthyosis/acral peeling skin syndrome, susceptibility to psoriasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 CARD9 Tom Cullup reviewed gene: CARD9: Rating: GREEN; Mode of pathogenicity: ; Publications: 24131138; Phenotypes: Deep dermatophytosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders v0.21 CARD14 Tom Cullup reviewed gene: CARD14: Rating: GREEN; Mode of pathogenicity: ; Publications: 22521418, 22703878; Phenotypes: susceptibility to psoriasis, Pityriasis rubra pilaris; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare genetic inflammatory skin disorders v0.21 CARD11 Tom Cullup reviewed gene: CARD11: Rating: GREEN; Mode of pathogenicity: ; Publications: 28628108; Phenotypes: Immunodeficiency 11B with atopic dermatitis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare genetic inflammatory skin disorders v0.21 ADA2 Tom Cullup reviewed gene: ADA2: Rating: GREEN; Mode of pathogenicity: ; Publications: 24552284; Phenotypes: VASCULITIS, AUTOINFLAMMATION, IMMUNODEFICIENCY, AND HEMATOLOGIC DEFECTS SYNDROME, VAIHS (Polyarteritis nodosa); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Epidermolysis bullosa and congenital skin fragility v0.26 PLOD3 Catherine Snow Publications for gene: PLOD3 were set to 30463024
Ichthyosis and erythrokeratoderma v0.17 SPINK5 Catherine Snow Classified gene: SPINK5 as Green List (high evidence)
Ichthyosis and erythrokeratoderma v0.17 SPINK5 Catherine Snow Added comment: Comment on list classification: Sufficient cases in OMIM to promote to Green
Ichthyosis and erythrokeratoderma v0.17 SPINK5 Catherine Snow Gene: spink5 has been classified as Green List (High Evidence).
Ichthyosis and erythrokeratoderma v0.16 PIGL Catherine Snow Classified gene: PIGL as Green List (high evidence)
Ichthyosis and erythrokeratoderma v0.16 PIGL Catherine Snow Added comment: Comment on list classification: Sufficient cases identified in OMIM
Ichthyosis and erythrokeratoderma v0.16 PIGL Catherine Snow Gene: pigl has been classified as Green List (High Evidence).
Ichthyosis and erythrokeratoderma v0.15 CLDN1 Catherine Snow Classified gene: CLDN1 as Green List (high evidence)
Ichthyosis and erythrokeratoderma v0.15 CLDN1 Catherine Snow Added comment: Comment on list classification: Sufficient cases in OMIM
Ichthyosis and erythrokeratoderma v0.15 CLDN1 Catherine Snow Gene: cldn1 has been classified as Green List (High Evidence).
Ichthyosis and erythrokeratoderma v0.14 LOR Catherine Snow Publications for gene: LOR were set to
Ichthyosis and erythrokeratoderma v0.13 LOR Catherine Snow Classified gene: LOR as Green List (high evidence)
Ichthyosis and erythrokeratoderma v0.13 LOR Catherine Snow Added comment: Comment on list classification: Sufficient number of variants identified in the literature to classify as Green.
Ichthyosis and erythrokeratoderma v0.13 LOR Catherine Snow Gene: lor has been classified as Green List (High Evidence).
Palmoplantar keratodermas v0.10 FLG Catherine Snow Publications for gene: FLG were set to
Ichthyosis and erythrokeratoderma v0.12 FLG Catherine Snow Publications for gene: FLG were set to
Ichthyosis and erythrokeratoderma v0.11 FLG Catherine Snow Classified gene: FLG as Green List (high evidence)
Ichthyosis and erythrokeratoderma v0.11 FLG Catherine Snow Added comment: Comment on list classification: Sufficient evidence and phenotype to be relevant as Green in the panel
Ichthyosis and erythrokeratoderma v0.11 FLG Catherine Snow Gene: flg has been classified as Green List (High Evidence).
Epidermolysis bullosa and congenital skin fragility v0.25 PLOD3 Catherine Snow Publications for gene: PLOD3 were set to
Epidermolysis bullosa and congenital skin fragility v0.24 DSC3 Catherine Snow edited their review of gene: DSC3: Added comment: Ayub et al. (PMID:19765682) identified a homozygous nonsense mutation (c.2129T>G; p.Leu710*) in DSC3 in four siblings from a consanguineous Afghani family who presented with a new genodermatosis affecting hair and skin. PMID:31790667 identifies a further Egyptian individual with skin fragility and Hypotrichosis. As less than 3 unrelated individuals identified DSC3 will currently be rated as Amber.; Changed publications: 19765682, 31790667; Changed phenotypes: ereditary Hypotrichosis, Recurrent Skin Vesicles, skin fragility; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Childhood onset dystonia or chorea or related movement disorder v0.257 GNAL Louise Daugherty Classified gene: GNAL as Green List (high evidence)
Childhood onset dystonia or chorea or related movement disorder v0.257 GNAL Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green as per recommendation from Specialist Test Group (via Robyn Labrum LNGLH) 12 December 2019. Multiple unrelated families
Childhood onset dystonia or chorea or related movement disorder v0.257 GNAL Louise Daugherty Gene: gnal has been classified as Green List (High Evidence).
Ectodermal dysplasia v0.35 KRT83 Catherine Snow Publications for gene: KRT83 were set to
Childhood onset dystonia or chorea or related movement disorder v0.256 FOXRED1 Louise Daugherty commented on gene: FOXRED1: Confirmed Green rating - as per recommendation from Specialist Test Group (via Robyn Labrum LNGLH) 12 December 2019. Also on mitochondrial panel, more of a mitochondrial phenotype but may present early with movement disorder.
Childhood onset dystonia or chorea or related movement disorder v0.256 ARSA Louise Daugherty changed review comment from: Confirmed Green rating - as per recommendation from Specialist Test Group (via Robyn Labrum LNGLH) 12 December 2019; to: Confirmed Green rating - as per recommendation from Specialist Test Group (via Robyn Labrum LNGLH) 12 December 2019. Described in multiple families
Childhood onset dystonia or chorea or related movement disorder v0.256 AFG3L2 Louise Daugherty changed review comment from: Confirmed Green rating - as per recommendation from Specialist Test Group (via Robyn Labrum LNGLH) 12 December 2019; to: Confirmed Green rating - as per recommendation from Specialist Test Group (via Robyn Labrum LNGLH) 12 December 2019. Described in multiple unrelated families
Childhood onset dystonia or chorea or related movement disorder v0.256 ARSA Louise Daugherty commented on gene: ARSA
Paediatric disorders - additional genes v1.0 Rebecca Foulger promoted panel to version 1.0
Childhood onset dystonia or chorea or related movement disorder v0.256 ACTB Louise Daugherty changed review comment from: Comment on list classification: Changed from Amber to Green as per recommendation from Specialist Test Group (via Robyn Labrum LNGLH).
Despite the evidence in the literature not supporting a Green rating the Specialist Test Group still supported a Green rating based on limited evidence – juvenile onset dystonia, only identified in 1 family, twins, brains examined post mortem; to: Comment on list classification: Changed from Amber to Green as per recommendation from Specialist Test Group (via Robyn Labrum LNGLH) 12 December 2019.
Despite the evidence in the literature not supporting a Green rating the Specialist Test Group still supported a Green rating based on limited evidence – juvenile onset dystonia, only identified in 1 family, twins, brains examined post mortem
Childhood onset dystonia or chorea or related movement disorder v0.256 AFG3L2 Louise Daugherty commented on gene: AFG3L2
Paediatric disorders - additional genes v0.47 Rebecca Foulger Panel types changed to GMS Rare Disease Virtual; Component Of Super Panel; GMS signed-off
Childhood onset dystonia or chorea or related movement disorder v0.256 ACTB Louise Daugherty Classified gene: ACTB as Green List (high evidence)
Childhood onset dystonia or chorea or related movement disorder v0.256 ACTB Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green as per recommendation from Specialist Test Group (via Robyn Labrum LNGLH).
Despite the evidence in the literature not supporting a Green rating the Specialist Test Group still supported a Green rating based on limited evidence – juvenile onset dystonia, only identified in 1 family, twins, brains examined post mortem
Childhood onset dystonia or chorea or related movement disorder v0.256 ACTB Louise Daugherty Gene: actb has been classified as Green List (High Evidence).
Childhood onset dystonia or chorea or related movement disorder v0.255 COL6A3 Louise Daugherty Added comment: Comment on mode of inheritance: Changed MOI from recommendation from Specialist Test Group (via Robyn Labrum LNGLH)
Childhood onset dystonia or chorea or related movement disorder v0.255 COL6A3 Louise Daugherty Mode of inheritance for gene: COL6A3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset dystonia or chorea or related movement disorder v0.254 VAMP1 Louise Daugherty Added comment: Comment on mode of inheritance: Changed MOI from recommendation from Specialist Test Group (via Robyn Labrum LNGLH)
Childhood onset dystonia or chorea or related movement disorder v0.254 VAMP1 Louise Daugherty Mode of inheritance for gene: VAMP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset dystonia or chorea or related movement disorder v0.253 SETX Louise Daugherty Added comment: Comment on mode of inheritance: Changed MOI from recommendation from Specialist Test Group (via Robyn Labrum LNGLH)
Childhood onset dystonia or chorea or related movement disorder v0.253 SETX Louise Daugherty Mode of inheritance for gene: SETX was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Inborn errors of metabolism v2.0 Sarah Leigh promoted panel to version 2.0
DDG2P v2.0 Rebecca Foulger promoted panel to version 2.0
Inborn errors of metabolism v1.426 Sarah Leigh Panel types changed to GMS Rare Disease Virtual; Component Of Super Panel; GMS signed-off
DDG2P v1.181 Rebecca Foulger Panel types changed to GMS Rare Disease Virtual; Component Of Super Panel; GMS signed-off
DDG2P v1.180 SHOX Rebecca Foulger changed review comment from: Current G2P MOI is hemizygous for LANGER MESOMELIC DYSPLASIA, and x-linked dominant for LERI-WEILL DYSCHONDROSTEOSIS. Kept PanelApp MOI as BOTH monoallelic and biallelic, based on gene location in Pseudoautosomal region.; to: Due to a Gene2Phenotype update, the current G2P MOI is hemizygous for LANGER MESOMELIC DYSPLASIA, and x-linked dominant for LERI-WEILL DYSCHONDROSTEOSIS. Kept PanelApp MOI as BOTH monoallelic and biallelic, based on gene location in Pseudoautosomal region.
Ophthalmological ciliopathies v1.0 Rebecca Foulger promoted panel to version 1.0
Ophthalmological ciliopathies v0.13 Rebecca Foulger Panel types changed to GMS Rare Disease Virtual; Component Of Super Panel; GMS signed-off
Distal myopathies v1.16 Louise Daugherty Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; Component Of Super Panel; GMS signed-off
Paediatric motor neuronopathies v1.26 Louise Daugherty Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; Component Of Super Panel; GMS signed-off
Rhabdomyolysis and metabolic muscle disorders v1.30 Louise Daugherty Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; Component Of Super Panel; GMS signed-off
DDG2P v1.180 SHOX Eleanor Williams Added comment: Comment on mode of inheritance: Updating mode of inheritance as monoallelic cases tend to be milder e.g. familial short stature / Leri-Weill, whereas biallelic are more severe (Langer mesomelic dysplasia).
DDG2P v1.180 SHOX Eleanor Williams Mode of inheritance for gene: SHOX was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Fetal anomalies v0.374 SHOX Eleanor Williams Added comment: Comment on mode of inheritance: Updating mode of inheritance as monoallelic cases tend to be milder e.g. familial short stature / Leri-Weill, whereas biallelic are more severe (Langer mesomelic dysplasia).
Fetal anomalies v0.374 SHOX Eleanor Williams Mode of inheritance for gene: SHOX was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Limb girdle muscular dystrophy v2.3 Louise Daugherty Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Pigmentary skin disorders v0.27 XRCC2 Catherine Snow Source Expert Review Amber was added to XRCC2.
Added phenotypes FANCONI ANEMIA, COMPLEMENTATION GROUP U; FANCU for gene: XRCC2
Publications for gene XRCC2 were changed from to 22232082
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Pigmentary skin disorders v0.27 WRAP53 Catherine Snow Added phenotypes DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 3; DKCB3 for gene: WRAP53
Publications for gene WRAP53 were changed from to 21205863
Pigmentary skin disorders v0.27 USB1 Catherine Snow Added phenotypes PN; POIKILODERMA WITH NEUTROPENIA for gene: USB1
Publications for gene USB1 were changed from to 20004881
Pigmentary skin disorders v0.27 UBE2T Catherine Snow Added phenotypes FANCT; FANCONI ANEMIA, COMPLEMENTATION GROUP T for gene: UBE2T
Publications for gene UBE2T were changed from to 26046368
Pigmentary skin disorders v0.27 TYRP1 Catherine Snow Added phenotypes OCA3; ALBINISM, OCULOCUTANEOUS, TYPE III for gene: TYRP1
Publications for gene TYRP1 were changed from to 9345097
Pigmentary skin disorders v0.27 TYR Catherine Snow Mode of inheritance for gene TYR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes ALBINISM, OCULOCUTANEOUS, TYPE IA; OCA1B; OCA1A, ALBINISM, OCULOCUTANEOUS, TYPE IB for gene: TYR
Publications for gene TYR were changed from to 18326704
Pigmentary skin disorders v0.27 TSC2 Catherine Snow Added phenotypes TUBEROUS SCLEROSIS 2; TSC2 for gene: TSC2
Publications for gene TSC2 were changed from to 12111193
Pigmentary skin disorders v0.27 TSC1 Catherine Snow Added phenotypes TSC1; TUBEROUS SCLEROSIS 1 for gene: TSC1
Publications for gene TSC1 were changed from to 10227394
Pigmentary skin disorders v0.27 TMC8 Catherine Snow Added phenotypes EPIDERMODYSPLASIA VERRUCIFORMIS, SUSCEPTIBILITY TO, 2; EV2 for gene: TMC8
Publications for gene TMC8 were changed from to 12426567
Pigmentary skin disorders v0.27 TMC6 Catherine Snow Added phenotypes EV1; EPIDERMODYSPLASIA VERRUCIFORMIS, SUSCEPTIBILITY TO, 1 for gene: TMC6
Publications for gene TMC6 were changed from to 12426567
Pigmentary skin disorders v0.27 TINF2 Catherine Snow Added phenotypes DYSKERATOSIS CONGENITA, AUTOSOMAL DOMINANT 3; DKCA3, REVESZ SYNDROME for gene: TINF2
Publications for gene TINF2 were changed from to 21477109; 18252230
Pigmentary skin disorders v0.27 TERT Catherine Snow Added phenotypes DYSKERATOSIS CONGENITA, AUTOSOMAL DOMINANT 2; DKCA2, DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 4, INCLUDED; DKCB4, INCLUDED for gene: TERT
Publications for gene TERT were changed from to 17785587; 18460650
Pigmentary skin disorders v0.27 TERC Catherine Snow Added phenotypes DYSKERATOSIS CONGENITA, AUTOSOMAL DOMINANT 1; DKCA1 for gene: TERC
Publications for gene TERC were changed from to 11574891
Pigmentary skin disorders v0.27 STK11 Catherine Snow Added phenotypes PJS; PEUTZ-JEGHERS SYNDROME for gene: STK11
Publications for gene STK11 were changed from to 9425897
Pigmentary skin disorders v0.27 SPRED1 Catherine Snow Added phenotypes LEGIUS SYNDROME; LGSS for gene: SPRED1
Publications for gene SPRED1 were changed from to 17704776
Pigmentary skin disorders v0.27 SOX18 Catherine Snow Added phenotypes HYPOTRICHOSIS-LYMPHEDEMA-TELANGIECTASIA SYNDROME; HLTS, HYPOTRICHOSIS-LYMPHEDEMA-TELANGIECTASIA-RENAL DEFECT SYNDROME; HLTRS for gene: SOX18
Publications for gene SOX18 were changed from to 12740761
Pigmentary skin disorders v0.27 SOX10 Catherine Snow Added phenotypes WS4C, WAARDENBURG SYNDROME, TYPE 2E; PERIPHERAL DEMYELINATING NEUROPATHY, CENTRAL DYSMYELINATION, WAARDENBURG SYNDROME, AND HIRSCHSPRUNG DISEASE; PCWH, WAARDENBURG SYNDROME, TYPE 4C; WS2E for gene: SOX10
Publications for gene SOX10 were changed from to 9462749; 21965087; 10762540
Pigmentary skin disorders v0.27 SOS2 Catherine Snow Added phenotypes NS9; NOONAN SYNDROME 9 for gene: SOS2
Publications for gene SOS2 were changed from 25795793; 26173643 to 25795793
Pigmentary skin disorders v0.27 SOS1 Catherine Snow Added phenotypes NOONAN SYNDROME 4; NS4 for gene: SOS1
Publications for gene SOS1 were changed from to 17143285
Pigmentary skin disorders v0.27 SLX4 Catherine Snow Added phenotypes FANCP; FANCONI ANEMIA, COMPLEMENTATION GROUP P for gene: SLX4
Publications for gene SLX4 were changed from to 21240277
Pigmentary skin disorders v0.27 SLC45A2 Catherine Snow Added phenotypes OCA4; ALBINISM, OCULOCUTANEOUS, TYPE IV for gene: SLC45A2
Publications for gene SLC45A2 were changed from to 14722913
Pigmentary skin disorders v0.27 SLC29A3 Catherine Snow Added phenotypes HISTIOCYTOSIS-LYMPHADENOPATHY PLUS SYNDROME for gene: SLC29A3
Publications for gene SLC29A3 were changed from to 18940313
Pigmentary skin disorders v0.27 SLC24A5 Catherine Snow Added phenotypes OCA6; ALBINISM, OCULOCUTANEOUS, TYPE VI for gene: SLC24A5
Publications for gene SLC24A5 were changed from to 23364476
Pigmentary skin disorders v0.27 SHOC2 Catherine Snow Added phenotypes NSLH1; NOONAN SYNDROME-LIKE DISORDER WITH LOOSE ANAGEN HAIR 1 for gene: SHOC2
Publications for gene SHOC2 were changed from to 19684605
Pigmentary skin disorders v0.27 SASH1 Catherine Snow Mode of inheritance for gene SASH1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes DUH1; DYSCHROMATOSIS UNIVERSALIS HEREDITARIA 1 for gene: SASH1
Publications for gene SASH1 were changed from to 27659786
Pigmentary skin disorders v0.27 SAMD9 Catherine Snow Added phenotypes NFTC, MIRAGE SYNDROME; TUMORAL CALCINOSIS, NORMOPHOSPHATEMIC, FAMILIAL; MIRAGE for gene: SAMD9
Publications for gene SAMD9 were changed from to 27182967; 16960814
Pigmentary skin disorders v0.27 RIT1 Catherine Snow Added phenotypes NOONAN SYNDROME 8; NS8 for gene: RIT1
Publications for gene RIT1 were changed from to 23791108
Pigmentary skin disorders v0.27 RECQL4 Catherine Snow Added phenotypes RTS2; RAPADILINO SYNDROME, ROTHMUND-THOMSON SYNDROME, TYPE 2 for gene: RECQL4
Publications for gene RECQL4 were changed from to 12952869; 10319867
Pigmentary skin disorders v0.27 RAF1 Catherine Snow Added phenotypes LPRD2, NOONAN SYNDROME 5; LEOPARD SYNDROME 2; NS5 for gene: RAF1
Publications for gene RAF1 were changed from to 17603483
Pigmentary skin disorders v0.27 RAD51C Catherine Snow Source Expert Review Amber was added to RAD51C.
Added phenotypes FANCONI ANEMIA, COMPLEMENTATION GROUP O; FANCO for gene: RAD51C
Publications for gene RAD51C were changed from to 20400963
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Pigmentary skin disorders v0.27 RAB27A Catherine Snow Added phenotypes GS2; GRISCELLI SYNDROME, TYPE 2 for gene: RAB27A
Publications for gene RAB27A were changed from to 10835631
Pigmentary skin disorders v0.27 PTPN11 Catherine Snow Added phenotypes LEOPARD SYNDROME 1; NS1; LPRD1, NOONAN SYNDROME 1 for gene: PTPN11
Publications for gene PTPN11 were changed from to 11704759; 15389709
Pigmentary skin disorders v0.27 PTEN Catherine Snow Added phenotypes COWDEN SYNDROME 1; CWS1 for gene: PTEN
Publications for gene PTEN were changed from to 9140396
Pigmentary skin disorders v0.27 PSENEN Catherine Snow Added phenotypes ACNINV2; ACNE INVERSA, FAMILIAL, 2, WITH OR WITHOUT DOWLING-DEGOS DISEASE for gene: PSENEN
Publications for gene PSENEN were changed from to 20929727
Pigmentary skin disorders v0.27 PRKAR1A Catherine Snow Added phenotypes PPNAD1; CARNEY COMPLEX, TYPE 1; CNC1, PIGMENTED NODULAR ADRENOCORTICAL DISEASE, PRIMARY, 1 for gene: PRKAR1A
Publications for gene PRKAR1A were changed from to 12213893; 10973256
Pigmentary skin disorders v0.27 PPP1CB Catherine Snow Added phenotypes NSLH2; NOONAN SYNDROME-LIKE DISORDER WITH LOOSE ANAGEN HAIR 2 for gene: PPP1CB
Publications for gene PPP1CB were changed from 27681385; 28211982; 27264673 to 27264673
Pigmentary skin disorders v0.27 PORCN Catherine Snow Added phenotypes FOCAL DERMAL HYPOPLASIA; FDH for gene: PORCN
Publications for gene PORCN were changed from to 17546030
Pigmentary skin disorders v0.27 POGLUT1 Catherine Snow Added phenotypes DDD4; DOWLING-DEGOS DISEASE 4 for gene: POGLUT1
Publications for gene POGLUT1 were changed from to 24387993
Pigmentary skin disorders v0.27 POFUT1 Catherine Snow Added phenotypes DDD2; DOWLING-DEGOS DISEASE 2 for gene: POFUT1
Publications for gene POFUT1 were changed from to 23684010
Pigmentary skin disorders v0.27 PMS2 Catherine Snow Added phenotypes MISMATCH REPAIR CANCER SYNDROME, 276300 for gene: PMS2
Publications for gene PMS2 were changed from to 10763829
Pigmentary skin disorders v0.27 PIK3CA Catherine Snow Added phenotypes MCAP; MEGALENCEPHALY-CAPILLARY MALFORMATION-POLYMICROGYRIA SYNDROME for gene: PIK3CA
Publications for gene PIK3CA were changed from to 22729224
Pigmentary skin disorders v0.27 PAX3 Catherine Snow Added phenotypes WAARDENBURG SYNDROME, TYPE 1; WS3; WS1, WAARDENBURG SYNDROME, TYPE 3 for gene: PAX3
Publications for gene PAX3 were changed from to 8533800; 8447316
Pigmentary skin disorders v0.27 PALB2 Catherine Snow Added phenotypes FANCN; FANCONI ANEMIA, COMPLEMENTATION GROUP N for gene: PALB2
Publications for gene PALB2 were changed from to 17200672
Pigmentary skin disorders v0.27 OSMR Catherine Snow Added phenotypes PLCA1; AMYLOIDOSIS, PRIMARY LOCALIZED CUTANEOUS, 1 for gene: OSMR
Publications for gene OSMR were changed from to 18179886
Pigmentary skin disorders v0.27 OCA2 Catherine Snow Added phenotypes OCA2; ALBINISM, OCULOCUTANEOUS, TYPE II for gene: OCA2
Publications for gene OCA2 were changed from to 8302318
Pigmentary skin disorders v0.27 NRAS Catherine Snow Added phenotypes NS6; NOONAN SYNDROME 6 for gene: NRAS
Publications for gene NRAS were changed from to 19966803
Pigmentary skin disorders v0.27 NF2 Catherine Snow Added phenotypes NF2; NEUROFIBROMATOSIS, TYPE II for gene: NF2
Publications for gene NF2 were changed from to 7913580
Pigmentary skin disorders v0.27 NF1 Catherine Snow Added phenotypes NEUROFIBROMATOSIS, TYPE I; NF1 for gene: NF1
Publications for gene NF1 were changed from to 9003501
Pigmentary skin disorders v0.27 MYO5A Catherine Snow Added phenotypes GRISCELLI SYNDROME, TYPE 1; GS1 for gene: MYO5A
Publications for gene MYO5A were changed from to 9207796
Pigmentary skin disorders v0.27 MTOR Catherine Snow Added phenotypes SKS; SMITH-KINGSMORE SYNDROME for gene: MTOR
Publications for gene MTOR were changed from to 27830187
Pigmentary skin disorders v0.27 MSH6 Catherine Snow Added phenotypes MISMATCH REPAIR CANCER SYNDROME, 276300 for gene: MSH6
Publications for gene MSH6 were changed from to 16283678
Pigmentary skin disorders v0.27 MSH2 Catherine Snow Added phenotypes MISMATCH REPAIR CANCER SYNDROME, 276300 for gene: MSH2
Publications for gene MSH2 were changed from to 16372347
Pigmentary skin disorders v0.27 MLH1 Catherine Snow Added phenotypes MISMATCH REPAIR CANCER SYNDROME, 276300 for gene: MLH1
Publications for gene MLH1 were changed from to 17440981
Pigmentary skin disorders v0.27 MITF Catherine Snow Mode of inheritance for gene MITF was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Added phenotypes COMMAD, WAARDENBURG SYNDROME, TYPE 2A; WS2A; COLOBOMA, OSTEOPETROSIS, MICROPHTHALMIA, MACROCEPHALY, ALBINISM, AND DEAFNESS for gene: MITF
Publications for gene MITF were changed from to 27889061; 7874167
Pigmentary skin disorders v0.27 MC1R Catherine Snow Source Expert Review Red was added to MC1R.
Added phenotypes Susceptibility to facial pigmented spots; Susceptibility to congenital melanocytic naevi; Pigmentation; Susceptibility to melanoma for gene: MC1R
Rating Changed from Green List (high evidence) to Red List (low evidence)
Pigmentary skin disorders v0.27 MAP2K2 Catherine Snow Added phenotypes CARDIOFACIOCUTANEOUS SYNDROME 4, 615280 for gene: MAP2K2
Publications for gene MAP2K2 were changed from to 18042262
Pigmentary skin disorders v0.27 MAP2K1 Catherine Snow Added phenotypes CFC3; CARDIOFACIOCUTANEOUS SYNDROME 3 for gene: MAP2K1
Publications for gene MAP2K1 were changed from 21396583; 23321623 to 16439621
Pigmentary skin disorders v0.27 MAD2L2 Catherine Snow Source Expert Review Amber was added to MAD2L2.
Added phenotypes FANCV; FANCONI ANEMIA, COMPLEMENTATION GROUP V for gene: MAD2L2
Publications for gene MAD2L2 were changed from to 27500492
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Pigmentary skin disorders v0.27 LZTR1 Catherine Snow Added phenotypes NOONAN SYNDROME 10; NS2; NS10, NOONAN SYNDROME 2 for gene: LZTR1
Publications for gene LZTR1 were changed from 25795793; 29469822 to 29469822; 25795793
Pigmentary skin disorders v0.27 LYST Catherine Snow Added phenotypes CHEDIAK-HIGASHI SYNDROME; CHS for gene: LYST
Publications for gene LYST were changed from to 8896560
Pigmentary skin disorders v0.27 KRT5 Catherine Snow Mode of inheritance for gene KRT5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes DOWLING-DEGOS DISEASE 1; DDD1 for gene: KRT5
Publications for gene KRT5 were changed from to 16465624
Pigmentary skin disorders v0.27 KRT14 Catherine Snow Added phenotypes DPR; DERMATOPATHIA PIGMENTOSA RETICULARIS for gene: KRT14
Publications for gene KRT14 were changed from to 16960809
Pigmentary skin disorders v0.27 KRT10 Catherine Snow Added phenotypes CRIE; ERYTHRODERMA, ICHTHYOSIFORM, CONGENITAL RETICULAR for gene: KRT10
Publications for gene KRT10 were changed from to 7508181