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Rhabdomyolysis and Metabolic Myopathy v0.73 ETFDH Zornitza Stark Gene: etfdh has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.73 ETFDH Zornitza Stark Publications for gene: ETFDH were set to
Rhabdomyolysis and Metabolic Myopathy v0.72 GYG1 Zornitza Stark Marked gene: GYG1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.72 GYG1 Zornitza Stark Gene: gyg1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.72 GYG1 Zornitza Stark Publications for gene: GYG1 were set to
Rhabdomyolysis and Metabolic Myopathy v0.71 GYS1 Zornitza Stark Marked gene: GYS1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.71 GYS1 Zornitza Stark Gene: gys1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.71 GYS1 Zornitza Stark Publications for gene: GYS1 were set to
Rhabdomyolysis and Metabolic Myopathy v0.70 TANGO2 Zornitza Stark Marked gene: TANGO2 as ready
Rhabdomyolysis and Metabolic Myopathy v0.70 TANGO2 Zornitza Stark Gene: tango2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.70 TANGO2 Zornitza Stark Publications for gene: TANGO2 were set to
Skeletal Dysplasia_Fetal v0.34 IFT122 Zornitza Stark changed review comment from: Gene-disease association is supported both by case-level data (>10 families reported) and functional data.; to: Gene-disease association is supported both by case-level data (>10 families reported) and functional data. Severe prenatal presentation common.
Skeletal Dysplasia_Fetal v0.34 IFT122 Zornitza Stark Marked gene: IFT122 as ready
Skeletal Dysplasia_Fetal v0.34 IFT122 Zornitza Stark Gene: ift122 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.34 IFT122 Zornitza Stark Phenotypes for gene: IFT122 were changed from to Cranioectodermal dysplasia 1, MIM# 218330; Beemer-Langer syndrome
Skeletal Dysplasia_Fetal v0.33 IFT122 Zornitza Stark Publications for gene: IFT122 were set to
Skeletal Dysplasia_Fetal v0.32 IFT122 Zornitza Stark Mode of inheritance for gene: IFT122 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.31 IFT122 Zornitza Stark reviewed gene: IFT122: Rating: GREEN; Mode of pathogenicity: None; Publications: 20493458, 23826986, 26792575, 29220510, 28370949, 27681595, 27681595; Phenotypes: Cranioectodermal dysplasia 1, MIM# 218330, Beemer-Langer syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal Ciliopathies v0.53 IFT122 Zornitza Stark Marked gene: IFT122 as ready
Skeletal Ciliopathies v0.53 IFT122 Zornitza Stark Gene: ift122 has been classified as Green List (High Evidence).
Skeletal Ciliopathies v0.53 IFT122 Zornitza Stark Phenotypes for gene: IFT122 were changed from to Cranioectodermal dysplasia 1, MIM# 218330; Beemer-Langer syndrome
Skeletal Ciliopathies v0.52 IFT122 Zornitza Stark Publications for gene: IFT122 were set to
Skeletal Ciliopathies v0.51 IFT122 Zornitza Stark Mode of inheritance for gene: IFT122 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Skeletal Ciliopathies v0.50 IFT122 Zornitza Stark reviewed gene: IFT122: Rating: GREEN; Mode of pathogenicity: None; Publications: 29037998, 20493458, 23826986, 26792575, 29220510, 28370949, 27681595, 27681595; Phenotypes: Cranioectodermal dysplasia 1, MIM# 218330, Beemer-Langer syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4833 IFT122 Zornitza Stark Publications for gene: IFT122 were set to 26792575; 28370949; 29037998
Mendeliome v0.4832 IFT122 Zornitza Stark edited their review of gene: IFT122: Changed publications: 29037998, 20493458, 23826986, 26792575, 29220510, 28370949, 27681595, 27681595
Ciliopathies v0.209 IFT122 Zornitza Stark Marked gene: IFT122 as ready
Ciliopathies v0.209 IFT122 Zornitza Stark Gene: ift122 has been classified as Green List (High Evidence).
Ciliopathies v0.209 IFT122 Zornitza Stark Phenotypes for gene: IFT122 were changed from to Cranioectodermal dysplasia 1, MIM# 218330; Beemer-Langer syndrome
Ciliopathies v0.208 IFT122 Zornitza Stark Publications for gene: IFT122 were set to
Ciliopathies v0.207 IFT122 Zornitza Stark Mode of inheritance for gene: IFT122 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.206 IFT122 Zornitza Stark reviewed gene: IFT122: Rating: GREEN; Mode of pathogenicity: None; Publications: 20493458, 23826986, 26792575, 29220510, 28370949, 27681595, 27681595; Phenotypes: Cranioectodermal dysplasia 1, MIM# 218330, Beemer-Langer syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.219 NEK9 Zornitza Stark Marked gene: NEK9 as ready
Arthrogryposis v0.219 NEK9 Zornitza Stark Gene: nek9 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.219 NEK9 Zornitza Stark Classified gene: NEK9 as Amber List (moderate evidence)
Arthrogryposis v0.219 NEK9 Zornitza Stark Gene: nek9 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.218 NEK9 Zornitza Stark gene: NEK9 was added
gene: NEK9 was added to Arthrogryposis. Sources: Expert Review
Mode of inheritance for gene: NEK9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEK9 were set to 26908619; 21271645
Phenotypes for gene: NEK9 were set to Lethal congenital contracture syndrome 10, MIM# 617022; Arthrogryposis, Perthes disease, and upward gaze palsy, MIM# 614262
Review for gene: NEK9 was set to AMBER
Added comment: PMID 26908619: Two Irish traveller families, 5 affected individuals, same homozygous variant identified (founder effect). Limited functional data.

PMID 21271645: Another Saudi family described with which 2 sisters and a female cousin who had a similar disorder characterised by arthrogryposis apparent since early childhood, avascular necrosis of the hip (Perthes disease), and upward gaze palsy. Homozygous missense variant segregated with the phenotype. Given the small number of reports, it is unclear whether this represents a distinct association is part of a spectrum with includes the more severe phenotype described in the Irish traveller families.
Sources: Expert Review
Mendeliome v0.4832 NEK9 Zornitza Stark Phenotypes for gene: NEK9 were changed from Lethal congenital contracture syndrome 10, MIM# 617022; Skeletal dysplasia to Lethal congenital contracture syndrome 10, MIM# 617022; Arthrogryposis, Perthes disease, and upward gaze palsy, MIM# 614262; Skeletal dysplasia
Mendeliome v0.4831 NEK9 Zornitza Stark Publications for gene: NEK9 were set to 26908619
Mendeliome v0.4830 NEK9 Zornitza Stark Classified gene: NEK9 as Amber List (moderate evidence)
Mendeliome v0.4830 NEK9 Zornitza Stark Gene: nek9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4829 NEK9 Zornitza Stark edited their review of gene: NEK9: Changed rating: AMBER
Mendeliome v0.4829 NEK9 Zornitza Stark edited their review of gene: NEK9: Added comment: Another Saudi family described with which 2 sisters and a female cousin who had a similar disorder characterised by arthrogryposis apparent since early childhood, avascular necrosis of the hip (Perthes disease), and upward gaze palsy. Homozygous missense variant segregated with the phenotype. Given the small number of reports, it is unclear whether this represents a distinct association is part of a spectrum with includes the more severe phenotype described in the Irish traveller families.; Changed publications: 26908619, 21271645; Changed phenotypes: Lethal congenital contracture syndrome 10, MIM# 617022, Arthrogryposis, Perthes disease, and upward gaze palsy, MIM# 614262, Skeletal dysplasia
Mendeliome v0.4829 TRPM7 Eleanor Williams Deleted their comment
Dystonia and Chorea v0.146 YIF1B Zornitza Stark Marked gene: YIF1B as ready
Dystonia and Chorea v0.146 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Dystonia and Chorea v0.146 YIF1B Zornitza Stark Classified gene: YIF1B as Green List (high evidence)
Dystonia and Chorea v0.146 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Dystonia and Chorea v0.145 YIF1B Zornitza Stark gene: YIF1B was added
gene: YIF1B was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to 32006098; 26077767
Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Review for gene: YIF1B was set to GREEN
Added comment: 6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v0.69 TAZ Zornitza Stark Marked gene: TAZ as ready
Rhabdomyolysis and Metabolic Myopathy v0.69 TAZ Zornitza Stark Gene: taz has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.69 TWNK Zornitza Stark Marked gene: TWNK as ready
Rhabdomyolysis and Metabolic Myopathy v0.69 TWNK Zornitza Stark Gene: twnk has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.69 ETFB Zornitza Stark Marked gene: ETFB as ready
Rhabdomyolysis and Metabolic Myopathy v0.69 ETFB Zornitza Stark Gene: etfb has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.69 ETFB Zornitza Stark Publications for gene: ETFB were set to
Rhabdomyolysis and Metabolic Myopathy v0.68 AHCY Zornitza Stark Marked gene: AHCY as ready
Rhabdomyolysis and Metabolic Myopathy v0.68 AHCY Zornitza Stark Gene: ahcy has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.68 AMACR Zornitza Stark Marked gene: AMACR as ready
Rhabdomyolysis and Metabolic Myopathy v0.68 AMACR Zornitza Stark Gene: amacr has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.68 COL4A1 Zornitza Stark Marked gene: COL4A1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.68 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.68 DGUOK Zornitza Stark Marked gene: DGUOK as ready
Rhabdomyolysis and Metabolic Myopathy v0.68 DGUOK Zornitza Stark Gene: dguok has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.68 DNA2 Zornitza Stark Marked gene: DNA2 as ready
Rhabdomyolysis and Metabolic Myopathy v0.68 DNA2 Zornitza Stark Gene: dna2 has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.68 FKTN Zornitza Stark Marked gene: FKTN as ready
Rhabdomyolysis and Metabolic Myopathy v0.68 FKTN Zornitza Stark Gene: fktn has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.68 KCNJ11 Zornitza Stark Marked gene: KCNJ11 as ready
Rhabdomyolysis and Metabolic Myopathy v0.68 KCNJ11 Zornitza Stark Gene: kcnj11 has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.68 MYH3 Zornitza Stark Marked gene: MYH3 as ready
Rhabdomyolysis and Metabolic Myopathy v0.68 MYH3 Zornitza Stark Gene: myh3 has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.68 PHKB Zornitza Stark Marked gene: PHKB as ready
Rhabdomyolysis and Metabolic Myopathy v0.68 PHKB Zornitza Stark Gene: phkb has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.68 PHKB Zornitza Stark Publications for gene: PHKB were set to
Rhabdomyolysis and Metabolic Myopathy v0.67 PRKAG2 Zornitza Stark Marked gene: PRKAG2 as ready
Rhabdomyolysis and Metabolic Myopathy v0.67 PRKAG2 Zornitza Stark Gene: prkag2 has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.67 SLC25A20 Zornitza Stark Marked gene: SLC25A20 as ready
Rhabdomyolysis and Metabolic Myopathy v0.67 SLC25A20 Zornitza Stark Gene: slc25a20 has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.67 SUCLA2 Zornitza Stark Marked gene: SUCLA2 as ready
Rhabdomyolysis and Metabolic Myopathy v0.67 SUCLA2 Zornitza Stark Gene: sucla2 has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.67 TSEN54 Zornitza Stark Marked gene: TSEN54 as ready
Rhabdomyolysis and Metabolic Myopathy v0.67 TSEN54 Zornitza Stark Gene: tsen54 has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.67 TSEN54 Zornitza Stark Publications for gene: TSEN54 were set to
Rhabdomyolysis and Metabolic Myopathy v0.66 TSFM Zornitza Stark Marked gene: TSFM as ready
Rhabdomyolysis and Metabolic Myopathy v0.66 TSFM Zornitza Stark Gene: tsfm has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.66 TSFM Zornitza Stark Publications for gene: TSFM were set to
Rhabdomyolysis and Metabolic Myopathy v0.65 TTN Zornitza Stark Marked gene: TTN as ready
Rhabdomyolysis and Metabolic Myopathy v0.65 TTN Zornitza Stark Gene: ttn has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.65 TYMP Zornitza Stark Marked gene: TYMP as ready
Rhabdomyolysis and Metabolic Myopathy v0.65 TYMP Zornitza Stark Gene: tymp has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.65 TYMP Zornitza Stark Publications for gene: TYMP were set to
Rhabdomyolysis and Metabolic Myopathy v0.64 PGM1 Zornitza Stark Marked gene: PGM1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.64 PGM1 Zornitza Stark Gene: pgm1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.64 PGM1 Zornitza Stark Phenotypes for gene: PGM1 were changed from Congenital disorder of glycosylation, type It 614921 to Congenital disorder of glycosylation, type It, MIM# 614921
Rhabdomyolysis and Metabolic Myopathy v0.63 PGM1 Zornitza Stark Publications for gene: PGM1 were set to
Craniosynostosis v0.185 GPC3 Zornitza Stark Marked gene: GPC3 as ready
Craniosynostosis v0.185 GPC3 Zornitza Stark Gene: gpc3 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.185 TWIST1 Zornitza Stark Marked gene: TWIST1 as ready
Craniosynostosis v0.185 TWIST1 Zornitza Stark Gene: twist1 has been classified as Green List (High Evidence).
Craniosynostosis v0.185 TWIST1 Zornitza Stark Phenotypes for gene: TWIST1 were changed from to Craniosynostosis 1, MIM# 123100; Saethre-Chotzen syndrome with or without eyelid anomalies, MIM# 101400
Craniosynostosis v0.184 TWIST1 Zornitza Stark Publications for gene: TWIST1 were set to
Craniosynostosis v0.183 TWIST1 Zornitza Stark Mode of inheritance for gene: TWIST1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.182 TWIST1 Zornitza Stark Tag SV/CNV tag was added to gene: TWIST1.
Tag 5'UTR tag was added to gene: TWIST1.
Craniosynostosis v0.182 TWIST1 Zornitza Stark edited their review of gene: TWIST1: Changed publications: 17343269, 9585583, 12116251, 31299755, 30040876
Craniosynostosis v0.182 TWIST1 Zornitza Stark reviewed gene: TWIST1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17343269, 9585583, 12116251; Phenotypes: Craniosynostosis 1, MIM# 123100, Saethre-Chotzen syndrome with or without eyelid anomalies, MIM# 101400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.182 RUNX2 Zornitza Stark Marked gene: RUNX2 as ready
Craniosynostosis v0.182 RUNX2 Zornitza Stark Gene: runx2 has been classified as Green List (High Evidence).
Craniosynostosis v0.182 RUNX2 Zornitza Stark Phenotypes for gene: RUNX2 were changed from to Craniosynostosis
Craniosynostosis v0.181 RUNX2 Zornitza Stark Publications for gene: RUNX2 were set to
Craniosynostosis v0.180 RUNX2 Zornitza Stark Tag SV/CNV tag was added to gene: RUNX2.
Craniosynostosis v0.180 RUNX2 Zornitza Stark Mode of inheritance for gene: RUNX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.179 RUNX2 Zornitza Stark reviewed gene: RUNX2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 32360898, 23348268, 23307468; Phenotypes: Craniosynostosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.179 RECQL4 Zornitza Stark Marked gene: RECQL4 as ready
Craniosynostosis v0.179 RECQL4 Zornitza Stark Gene: recql4 has been classified as Green List (High Evidence).
Craniosynostosis v0.179 RECQL4 Zornitza Stark Phenotypes for gene: RECQL4 were changed from to Baller-Gerold syndrome, MIM# 218600
Craniosynostosis v0.178 RECQL4 Zornitza Stark Mode of inheritance for gene: RECQL4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.177 RECQL4 Zornitza Stark reviewed gene: RECQL4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Baller-Gerold syndrome, MIM# 218600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.177 POR Zornitza Stark Marked gene: POR as ready
Craniosynostosis v0.177 POR Zornitza Stark Gene: por has been classified as Green List (High Evidence).
Craniosynostosis v0.177 POR Zornitza Stark Phenotypes for gene: POR were changed from to Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, MIM# 201750
Craniosynostosis v0.176 POR Zornitza Stark Publications for gene: POR were set to
Craniosynostosis v0.175 POR Zornitza Stark Mode of inheritance for gene: POR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.174 POR Zornitza Stark reviewed gene: POR: Rating: GREEN; Mode of pathogenicity: None; Publications: 26969897, 26670660, 18259105; Phenotypes: Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, MIM# 201750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.174 MSX2 Zornitza Stark Marked gene: MSX2 as ready
Craniosynostosis v0.174 MSX2 Zornitza Stark Gene: msx2 has been classified as Green List (High Evidence).
Craniosynostosis v0.174 MSX2 Zornitza Stark Phenotypes for gene: MSX2 were changed from to Craniosynostosis 2, MIM# 604757
Craniosynostosis v0.173 MSX2 Zornitza Stark Publications for gene: MSX2 were set to
Craniosynostosis v0.172 MSX2 Zornitza Stark Mode of inheritance for gene: MSX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.171 MSX2 Zornitza Stark reviewed gene: MSX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23949913, 27884935, 23918290, 2359311, 22948472, 19533795; Phenotypes: Craniosynostosis 2, MIM# 604757; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4829 IL11RA Zornitza Stark Marked gene: IL11RA as ready
Mendeliome v0.4829 IL11RA Zornitza Stark Gene: il11ra has been classified as Green List (High Evidence).
Mendeliome v0.4829 IL11RA Zornitza Stark Phenotypes for gene: IL11RA were changed from to Craniosynostosis and dental anomalies, MIM# 614188
Mendeliome v0.4828 IL11RA Zornitza Stark Publications for gene: IL11RA were set to
Mendeliome v0.4827 IL11RA Zornitza Stark Mode of inheritance for gene: IL11RA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4826 IL11RA Zornitza Stark reviewed gene: IL11RA: Rating: GREEN; Mode of pathogenicity: None; Publications: 21741611, 32277509, 30811827, 29926465, 24498618; Phenotypes: Craniosynostosis and dental anomalies, MIM# 614188; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.171 IL11RA Zornitza Stark Marked gene: IL11RA as ready
Craniosynostosis v0.171 IL11RA Zornitza Stark Gene: il11ra has been classified as Green List (High Evidence).
Craniosynostosis v0.171 IL11RA Zornitza Stark Phenotypes for gene: IL11RA were changed from to Craniosynostosis and dental anomalies, MIM# 614188
Craniosynostosis v0.170 IL11RA Zornitza Stark Publications for gene: IL11RA were set to
Craniosynostosis v0.169 IL11RA Zornitza Stark Mode of inheritance for gene: IL11RA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.168 IL11RA Zornitza Stark reviewed gene: IL11RA: Rating: GREEN; Mode of pathogenicity: None; Publications: 21741611, 32277509, 30811827, 29926465, 24498618; Phenotypes: Craniosynostosis and dental anomalies, MIM# 614188; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.168 FGFR3 Zornitza Stark Marked gene: FGFR3 as ready
Craniosynostosis v0.168 FGFR3 Zornitza Stark Gene: fgfr3 has been classified as Green List (High Evidence).
Craniosynostosis v0.168 FGFR3 Zornitza Stark Phenotypes for gene: FGFR3 were changed from to Crouzon syndrome with acanthosis nigricans, MIM# 612247; Muenke syndrome, MIM# 602849
Craniosynostosis v0.167 FGFR3 Zornitza Stark Mode of pathogenicity for gene: FGFR3 was changed from to Other
Craniosynostosis v0.166 FGFR3 Zornitza Stark Mode of inheritance for gene: FGFR3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.165 FGFR3 Zornitza Stark reviewed gene: FGFR3: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: Crouzon syndrome with acanthosis nigricans, MIM# 612247, Muenke syndrome, MIM# 602849; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.165 FGFR2 Zornitza Stark Marked gene: FGFR2 as ready
Craniosynostosis v0.165 FGFR2 Zornitza Stark Gene: fgfr2 has been classified as Green List (High Evidence).
Craniosynostosis v0.165 FGFR2 Zornitza Stark Phenotypes for gene: FGFR2 were changed from to Apert syndrome, MIM# 101200; Crouzon syndrome, MIM# 123500; Pfeiffer syndrome, MIM# 101600; Saethre-Chotzen syndrome, MIM# 101400
Craniosynostosis v0.164 FGFR2 Zornitza Stark Mode of pathogenicity for gene: FGFR2 was changed from to Other
Craniosynostosis v0.163 FGFR2 Zornitza Stark Mode of inheritance for gene: FGFR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.162 FGFR2 Zornitza Stark reviewed gene: FGFR2: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: Apert syndrome, MIM# 101200, Crouzon syndrome, MIM# 123500, Pfeiffer syndrome, MIM# 101600, Saethre-Chotzen syndrome, MIM# 101400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.162 ZIC1 Zornitza Stark Marked gene: ZIC1 as ready
Craniosynostosis v0.162 ZIC1 Zornitza Stark Gene: zic1 has been classified as Green List (High Evidence).
Craniosynostosis v0.162 ZIC1 Zornitza Stark Phenotypes for gene: ZIC1 were changed from to Structural brain anomalies with impaired intellectual development and craniosynostosis, MIM# 618736; Craniosynostosis 6, MIM# 616602
Craniosynostosis v0.161 ZIC1 Zornitza Stark Publications for gene: ZIC1 were set to
Craniosynostosis v0.160 ZIC1 Zornitza Stark Mode of inheritance for gene: ZIC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.159 ZIC1 Zornitza Stark reviewed gene: ZIC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26340333, 32975022, 27884935; Phenotypes: Structural brain anomalies with impaired intellectual development and craniosynostosis, MIM# 618736, Craniosynostosis 6, MIM# 616602; Mode of inheritance: None
Craniosynostosis v0.159 FGFR1 Zornitza Stark Marked gene: FGFR1 as ready
Craniosynostosis v0.159 FGFR1 Zornitza Stark Gene: fgfr1 has been classified as Green List (High Evidence).
Craniosynostosis v0.159 FGFR1 Zornitza Stark Phenotypes for gene: FGFR1 were changed from to Pfeiffer syndrome, MIM# 101600; Jackson-Weiss syndrome 123150
Craniosynostosis v0.158 FGFR1 Zornitza Stark Mode of pathogenicity for gene: FGFR1 was changed from to Other
Craniosynostosis v0.157 FGFR1 Zornitza Stark Mode of inheritance for gene: FGFR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.156 FGFR1 Zornitza Stark reviewed gene: FGFR1: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: Pfeiffer syndrome, MIM# 101600, Jackson-Weiss syndrome 123150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.156 FBN1 Zornitza Stark Marked gene: FBN1 as ready
Craniosynostosis v0.156 FBN1 Zornitza Stark Gene: fbn1 has been classified as Green List (High Evidence).
Mendeliome v0.4826 ABCC6 Zornitza Stark Publications for gene: ABCC6 were set to 11536079
Craniosynostosis v0.156 ERF Zornitza Stark Marked gene: ERF as ready
Craniosynostosis v0.156 ERF Zornitza Stark Gene: erf has been classified as Green List (High Evidence).
Craniosynostosis v0.156 ERF Zornitza Stark Phenotypes for gene: ERF were changed from to Craniosynostosis 4, MIM# 600775
Craniosynostosis v0.155 ERF Zornitza Stark Publications for gene: ERF were set to
Craniosynostosis v0.154 ERF Zornitza Stark Mode of inheritance for gene: ERF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.153 ERF Zornitza Stark reviewed gene: ERF: Rating: GREEN; Mode of pathogenicity: None; Publications: 23354439, 26097063, 32370745, 30758909; Phenotypes: Craniosynostosis 4, MIM# 600775; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4825 EFNB1 Zornitza Stark Marked gene: EFNB1 as ready
Mendeliome v0.4825 EFNB1 Zornitza Stark Gene: efnb1 has been classified as Green List (High Evidence).
Mendeliome v0.4825 EFNB1 Zornitza Stark Phenotypes for gene: EFNB1 were changed from to Craniofrontonasal dysplasia, MIM# 304110
Mendeliome v0.4824 EFNB1 Zornitza Stark Publications for gene: EFNB1 were set to
Mendeliome v0.4823 EFNB1 Zornitza Stark Mode of inheritance for gene: EFNB1 was changed from Unknown to Other
Mendeliome v0.4822 EFNB1 Zornitza Stark reviewed gene: EFNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15166289, 18627045, 23335590; Phenotypes: Craniofrontonasal dysplasia, MIM# 304110; Mode of inheritance: Other
Craniosynostosis v0.153 EFNB1 Zornitza Stark Marked gene: EFNB1 as ready
Craniosynostosis v0.153 EFNB1 Zornitza Stark Gene: efnb1 has been classified as Green List (High Evidence).
Craniosynostosis v0.153 EFNB1 Zornitza Stark Phenotypes for gene: EFNB1 were changed from to Craniofrontonasal dysplasia, MIM# 304110
Craniosynostosis v0.152 EFNB1 Zornitza Stark Publications for gene: EFNB1 were set to
Craniosynostosis v0.151 EFNB1 Zornitza Stark Mode of inheritance for gene: EFNB1 was changed from Unknown to Other
Craniosynostosis v0.150 EFNB1 Zornitza Stark reviewed gene: EFNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15166289, 18627045, 23335590,; Phenotypes: Craniofrontonasal dysplasia, MIM# 304110; Mode of inheritance: Other
Additional findings_Paediatric v0.124 AR Kristin Rigbye reviewed gene: AR: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: Androgen insensitivity (MIM#300068), XLR; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Additional findings_Paediatric v0.124 AR Kristin Rigbye Deleted their review
Additional findings_Paediatric v0.124 AR Kristin Rigbye reviewed gene: AR: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Androgen insensitivity (MIM#300068), XLR; Mode of inheritance: None
Mendeliome v0.4822 ABCC6 Kristin Rigbye reviewed gene: ABCC6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28102862; Phenotypes: Pseudoxanthoma elasticum (MIM#264800), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.0 TUBB2B Zornitza Stark gene: TUBB2B was added
gene: TUBB2B was added to Congenital fibrosis of the extraocular muscles. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: TUBB2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB2B were set to 23001566
Phenotypes for gene: TUBB2B were set to Fibrosis of extraocular muscles, congenital; Cortical dysplasia, complex, with other brain malformations 7
Congenital ophthalmoplegia v0.0 GRHL2 Zornitza Stark gene: GRHL2 was added
gene: GRHL2 was added to Congenital fibrosis of the extraocular muscles. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: GRHL2 was set to Unknown
Publications for gene: GRHL2 were set to 29110737
Phenotypes for gene: GRHL2 were set to Fibrosis of extraocular muscles, congenital
Congenital ophthalmoplegia v0.0 COL25A1 Zornitza Stark gene: COL25A1 was added
gene: COL25A1 was added to Congenital fibrosis of the extraocular muscles. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: COL25A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL25A1 were set to 25500261
Phenotypes for gene: COL25A1 were set to Fibrosis of extraocular muscles, congenital, 5; Fibrosis of extraocular muscles, congenital, 5 616219
Congenital ophthalmoplegia v0.0 TUBB3 Zornitza Stark gene: TUBB3 was added
gene: TUBB3 was added to Congenital fibrosis of the extraocular muscles. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: TUBB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB3 were set to 27428177; 20074521
Phenotypes for gene: TUBB3 were set to Fibrosis of extraocular muscles, congenital, 3A 600638; CFEOM3A
Congenital ophthalmoplegia v0.0 PHOX2A Zornitza Stark gene: PHOX2A was added
gene: PHOX2A was added to Congenital fibrosis of the extraocular muscles. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: PHOX2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHOX2A were set to 14597037; 22311481; 11600883
Phenotypes for gene: PHOX2A were set to Fibrosis of extraocular muscles, congenital, 2 602078; Fibrosis of extraocular muscles, congenital, 2
Congenital ophthalmoplegia v0.0 KIF21A Zornitza Stark gene: KIF21A was added
gene: KIF21A was added to Congenital fibrosis of the extraocular muscles. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: KIF21A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF21A were set to 15621876; 15223798; 15621877; 18332320
Phenotypes for gene: KIF21A were set to Fibrosis of extraocular muscles, congenital, 1 135700; Congenital fibrosis of the extraocular muscles; Fibrosis of extraocular muscles, congenital, 3B 135700
Congenital ophthalmoplegia v0.0 Zornitza Stark Added panel Congenital fibrosis of the extraocular muscles
Bleeding and Platelet Disorders v0.204 Zornitza Stark Panel name changed from Bleeding Disorders to Bleeding and Platelet Disorders
Mendeliome v0.4822 AGAP1 Zornitza Stark Marked gene: AGAP1 as ready
Mendeliome v0.4822 AGAP1 Zornitza Stark Gene: agap1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4822 AGAP1 Zornitza Stark Classified gene: AGAP1 as Amber List (moderate evidence)
Mendeliome v0.4822 AGAP1 Zornitza Stark Gene: agap1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4821 AGAP1 Zornitza Stark gene: AGAP1 was added
gene: AGAP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AGAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AGAP1 were set to 31700678; 25666757; 30472483
Phenotypes for gene: AGAP1 were set to Cerebral palsy
Review for gene: AGAP1 was set to AMBER
Added comment: Two individuals reported with de novo variants in this gene and a CP phenotype. Rare variants over-represented in a case-control study. Supportive zebrafish model. Another individual with a deletion (+1 other gene) reported with ID and autism.
Sources: Literature
Cerebral Palsy v0.42 AGAP1 Zornitza Stark Marked gene: AGAP1 as ready
Cerebral Palsy v0.42 AGAP1 Zornitza Stark Gene: agap1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.42 AGAP1 Zornitza Stark Classified gene: AGAP1 as Amber List (moderate evidence)
Cerebral Palsy v0.42 AGAP1 Zornitza Stark Gene: agap1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.41 AGAP1 Zornitza Stark gene: AGAP1 was added
gene: AGAP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: AGAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AGAP1 were set to 31700678; 25666757; 30472483
Phenotypes for gene: AGAP1 were set to Cerebral palsy
Review for gene: AGAP1 was set to AMBER
Added comment: Two individuals reported with de novo variants in this gene and a CP phenotype. Rare variants over-represented in a case-control study. Supportive zebrafish model. Another individual with a deletion (+1 other gene) reported with ID and autism.
Sources: Literature
Cerebral Palsy v0.40 L1CAM Zornitza Stark Marked gene: L1CAM as ready
Cerebral Palsy v0.40 L1CAM Zornitza Stark Gene: l1cam has been classified as Green List (High Evidence).
Cerebral Palsy v0.40 L1CAM Zornitza Stark Phenotypes for gene: L1CAM were changed from to CRASH syndrome, MIM# 303350
Cerebral Palsy v0.39 L1CAM Zornitza Stark Mode of inheritance for gene: L1CAM was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v0.38 L1CAM Zornitza Stark reviewed gene: L1CAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 31700678; Phenotypes: CRASH syndrome, MIM# 303350; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v0.38 NT5C2 Zornitza Stark Marked gene: NT5C2 as ready
Cerebral Palsy v0.38 NT5C2 Zornitza Stark Gene: nt5c2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.38 NT5C2 Zornitza Stark Classified gene: NT5C2 as Green List (high evidence)
Cerebral Palsy v0.38 NT5C2 Zornitza Stark Gene: nt5c2 has been classified as Green List (High Evidence).
Cerebral Palsy v0.37 NT5C2 Zornitza Stark gene: NT5C2 was added
gene: NT5C2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NT5C2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NT5C2 were set to 31700678; 32153630
Phenotypes for gene: NT5C2 were set to Spastic paraplegia 45, autosomal recessive, MIM# 613162
Review for gene: NT5C2 was set to GREEN
Added comment: Overlapping phenotype, two families reported with a CP phenotype.
Sources: Literature
Cerebral Palsy v0.36 KIF1A Zornitza Stark Marked gene: KIF1A as ready
Cerebral Palsy v0.36 KIF1A Zornitza Stark Gene: kif1a has been classified as Green List (High Evidence).
Cerebral Palsy v0.36 KIF1A Zornitza Stark Classified gene: KIF1A as Green List (high evidence)
Cerebral Palsy v0.36 KIF1A Zornitza Stark Gene: kif1a has been classified as Green List (High Evidence).
Cerebral Palsy v0.35 KIF1A Zornitza Stark gene: KIF1A was added
gene: KIF1A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KIF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF1A were set to 31700678
Phenotypes for gene: KIF1A were set to Spastic paraplegia 30, autosomal dominant, MIM# 610357
Review for gene: KIF1A was set to GREEN
Added comment: Overlapping phenotype and at least two individuals identified as part of a CP cohort.
Sources: Literature
Cerebral Palsy v0.34 PROC Zornitza Stark Marked gene: PROC as ready
Cerebral Palsy v0.34 PROC Zornitza Stark Gene: proc has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.34 PROC Zornitza Stark Classified gene: PROC as Amber List (moderate evidence)
Cerebral Palsy v0.34 PROC Zornitza Stark Gene: proc has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.33 PROC Zornitza Stark gene: PROC was added
gene: PROC was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PROC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PROC were set to 31700678; 20187890
Phenotypes for gene: PROC were set to Thrombophilia due to protein C deficiency, autosomal recessive, MIM# 612304
Review for gene: PROC was set to AMBER
Added comment: Bi-allelic PROC variants described in 2 families presenting as complex CP. Other features such as purpura fulminans may be present depending on severity.
Sources: Literature
Cerebral Palsy v0.32 COL4A1 Zornitza Stark Marked gene: COL4A1 as ready
Cerebral Palsy v0.32 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.32 COL4A1 Zornitza Stark Classified gene: COL4A1 as Amber List (moderate evidence)
Cerebral Palsy v0.32 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.31 COL4A1 Zornitza Stark gene: COL4A1 was added
gene: COL4A1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A1 were set to 31700678; 17379824
Phenotypes for gene: COL4A1 were set to {Hemorrhage, intracerebral, susceptibility to}, MIM# 614519
Review for gene: COL4A1 was set to AMBER
Added comment: One individual reported with variant in this gene and a CP phenotype PMID 31700678, and another with recurrent stroke PMID 17379824. However, note variable expressivity and penetrance generally associated with COL4A1 variants, and apply caution.
Sources: Literature
Mendeliome v0.4820 SMN1 Zornitza Stark Marked gene: SMN1 as ready
Mendeliome v0.4820 SMN1 Zornitza Stark Gene: smn1 has been classified as Green List (High Evidence).
Mendeliome v0.4820 SMN1 Zornitza Stark Phenotypes for gene: SMN1 were changed from to Spinal muscular atrophy-1, MIM# 253300
Mendeliome v0.4819 SMN1 Zornitza Stark Publications for gene: SMN1 were set to
Mendeliome v0.4818 SMN1 Zornitza Stark Mode of inheritance for gene: SMN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4817 SMN1 Zornitza Stark Tag SV/CNV tag was added to gene: SMN1.
Mendeliome v0.4817 SMN1 Zornitza Stark reviewed gene: SMN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7813012; Phenotypes: Spinal muscular atrophy-1, MIM# 253300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.48 BUB1B Zornitza Stark Marked gene: BUB1B as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.48 BUB1B Zornitza Stark Gene: bub1b has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.48 BUB1B Zornitza Stark Classified gene: BUB1B as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.48 BUB1B Zornitza Stark Gene: bub1b has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.47 BUB1B Zornitza Stark gene: BUB1B was added
gene: BUB1B was added to Amenorrhoea. Sources: Literature
Mode of inheritance for gene: BUB1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BUB1B were set to 32716490
Phenotypes for gene: BUB1B were set to Premature ovarian failure
Review for gene: BUB1B was set to AMBER
Added comment: There is a well established association between bi-allelic variants and mosaic variegated aneuploidy syndrome, MIM#257300

PMID: 32716490 - Chen et al 2020 - report 2 cases of heterogyzous variants in BUB1B in patients with premature ovarian insufficiency. In the familial case a rare missense variant of BUB1B c.273A>T (p.Gln91His) was shared by all affected individuals. A novel stop-gain variant of BUB1B c.1509T>A (p.Cys503*) was found in one of 200 sporadic POI cases and was found to be paternal in origin. In a mouse model with a loss-of-function mutant of Bub1b, Bub1b+/− female mice presented late-onset subfertility. Complete loss of Bub1b caused embryonic lethality in mice..
Sources: Literature
Mendeliome v0.4817 BUB1B Zornitza Stark Marked gene: BUB1B as ready
Mendeliome v0.4817 BUB1B Zornitza Stark Gene: bub1b has been classified as Green List (High Evidence).
Mendeliome v0.4817 BUB1B Zornitza Stark Phenotypes for gene: BUB1B were changed from to Mosaic variegated aneuploidy syndrome 1, MIM# 257300; Premature ovarian failure
Mendeliome v0.4816 BUB1B Zornitza Stark Publications for gene: BUB1B were set to
Mendeliome v0.4815 BUB1B Zornitza Stark Mode of inheritance for gene: BUB1B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4814 BUB1B Zornitza Stark reviewed gene: BUB1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32716490, 18548531; Phenotypes: Mosaic variegated aneuploidy syndrome 1, MIM# 257300, Premature ovarian failure; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4814 ROM1 Zornitza Stark Marked gene: ROM1 as ready
Mendeliome v0.4814 ROM1 Zornitza Stark Gene: rom1 has been classified as Green List (High Evidence).
Mendeliome v0.4814 ROM1 Zornitza Stark Phenotypes for gene: ROM1 were changed from to Retinitis pigmentosa 7, digenic form, MIM# 608133
Mendeliome v0.4813 ROM1 Zornitza Stark Publications for gene: ROM1 were set to
Mendeliome v0.4812 ROM1 Zornitza Stark Mode of inheritance for gene: ROM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4811 ROM1 Zornitza Stark reviewed gene: ROM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32036094, 8202715, 30630813, 24618324, 20300562; Phenotypes: Retinitis pigmentosa 7, digenic form, MIM# 608133; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4811 FOXC1 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association supported by case-level data and experimental data, including animal models.
Mendeliome v0.4811 FOXC1 Zornitza Stark Marked gene: FOXC1 as ready
Mendeliome v0.4811 FOXC1 Zornitza Stark Gene: foxc1 has been classified as Green List (High Evidence).
Mendeliome v0.4811 FOXC1 Zornitza Stark Phenotypes for gene: FOXC1 were changed from to Axenfeld-Rieger syndrome, type 3, MIM# 602482
Mendeliome v0.4810 FOXC1 Zornitza Stark Publications for gene: FOXC1 were set to
Mendeliome v0.4809 FOXC1 Zornitza Stark Mode of inheritance for gene: FOXC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4808 FOXC1 Zornitza Stark reviewed gene: FOXC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9792859, 10713890, 19668217; Phenotypes: Axenfeld-Rieger syndrome, type 3, MIM# 602482; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hydrocephalus_Ventriculomegaly v0.62 FGFR1 Zornitza Stark Mode of pathogenicity for gene: FGFR1 was changed from to Other
Hydrocephalus_Ventriculomegaly v0.61 FGFR1 Zornitza Stark Phenotypes for gene: FGFR1 were changed from to Pfeiffer syndrome, MIM# 101600
Hydrocephalus_Ventriculomegaly v0.60 FGFR1 Zornitza Stark Mode of inheritance for gene: FGFR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hydrocephalus_Ventriculomegaly v0.59 FGFR1 Zornitza Stark reviewed gene: FGFR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pfeiffer syndrome, MIM# 101600; Mode of inheritance: None
Regression v0.173 ALG14 Zornitza Stark Marked gene: ALG14 as ready
Regression v0.173 ALG14 Zornitza Stark Gene: alg14 has been classified as Green List (High Evidence).
Regression v0.173 ALG14 Zornitza Stark Classified gene: ALG14 as Green List (high evidence)
Regression v0.173 ALG14 Zornitza Stark Gene: alg14 has been classified as Green List (High Evidence).
Regression v0.172 ALG14 Zornitza Stark gene: ALG14 was added
gene: ALG14 was added to Regression. Sources: Expert Review
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 Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036
Review for gene: ALG14 was set to GREEN
Added comment: Three families reported in PMID 28733338 with a neurodegenerative phenotype in infancy.

Note there are 2 other families reported, one with myasthenic syndrome, no report of ID; second with predominantly ID phenotype, no repression. ALG14 is part of the UDP-GlcNAc transferase, which catalyzes a key step in endoplasmic reticulum N-linked glycosylation. These may all represent a spectrum of severity for a CDG.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.3061 ALG14 Zornitza Stark Phenotypes for gene: ALG14 were changed from Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031 to Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036
Intellectual disability syndromic and non-syndromic v0.3060 ALG14 Zornitza Stark edited their review of gene: ALG14: Changed phenotypes: intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031, Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036
Mendeliome v0.4808 ALG14 Zornitza Stark Phenotypes for gene: ALG14 were changed from Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Disorder of N-glycosylation to Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036; Disorder of N-glycosylation
Mendeliome v0.4807 ALG14 Zornitza Stark changed review comment from: 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. ALG14 is part of the UDP-GlcNAc transferase, which catalyzes a key step in endoplasmic reticulum N-linked glycosylation; to: 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. ALG14 is part of the UDP-GlcNAc transferase, which catalyzes a key step in endoplasmic reticulum N-linked glycosylation. The three OMIM disorders may represent a spectrum of severity for CDG.
Mendeliome v0.4807 ALG14 Zornitza Stark edited their review of gene: ALG14: Changed phenotypes: Myasthenic syndrome, congenital, 15, without tubular aggregates 616227, Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031, Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036, Disorder of N-glycosylation
Congenital Disorders of Glycosylation v0.170 ALG14 Zornitza Stark Phenotypes for gene: ALG14 were changed from Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Disorder of N-glycosylation to Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036; Disorder of N-glycosylation
Congenital Disorders of Glycosylation v0.169 ALG14 Zornitza Stark edited their review of gene: ALG14: Added comment: Five families reported altogether. Although OMIM has assigned 3 disease entities, it is uncertain whether these are distinct, or represent a spectrum of severity for a CDG.; Changed publications: 30221345, 23404334, 28733338; Changed phenotypes: Myasthenic syndrome, congenital, 15, without tubular aggregates 616227, Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031, Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036, Disorder of N-glycosylation
Mendeliome v0.4807 FOXC1 Eleanor Williams reviewed gene: FOXC1: Rating: ; Mode of pathogenicity: None; Publications: 32720677; Phenotypes: eye and vascular development; Mode of inheritance: None
Mendeliome v0.4807 ROM1 Eleanor Williams reviewed gene: ROM1: Rating: ; Mode of pathogenicity: None; Publications: 32716032; Phenotypes: retinal degeneration; Mode of inheritance: None
Mendeliome v0.4807 BUB1B Eleanor Williams reviewed gene: BUB1B: Rating: ; Mode of pathogenicity: None; Publications: 32716490; Phenotypes: premature ovarian insufficiency; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hydrocephalus_Ventriculomegaly v0.59 FGFR1 Tiong Tan Marked gene: FGFR1 as ready
Hydrocephalus_Ventriculomegaly v0.59 FGFR1 Tiong Tan Gene: fgfr1 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.59 FGFR1 Tiong Tan reviewed gene: FGFR1: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: Pfeiffer syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4807 SMN1 Eleanor Williams reviewed gene: SMN1: Rating: ; Mode of pathogenicity: None; Publications: 32644125, 32644120; Phenotypes: Spinal muscular atrophy; Mode of inheritance: None
Leukodystrophy v0.207 ACER3 Zornitza Stark Marked gene: ACER3 as ready
Leukodystrophy v0.207 ACER3 Zornitza Stark Gene: acer3 has been classified as Amber List (Moderate Evidence).
Leukodystrophy v0.207 ACER3 Zornitza Stark Classified gene: ACER3 as Amber List (moderate evidence)
Leukodystrophy v0.207 ACER3 Zornitza Stark Gene: acer3 has been classified as Amber List (Moderate Evidence).
Leukodystrophy v0.206 ACER3 Zornitza Stark gene: ACER3 was added
gene: ACER3 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: ACER3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACER3 were set to 32816236; 26792856
Phenotypes for gene: ACER3 were set to Leukodystrophy
Review for gene: ACER3 was set to AMBER
Added comment: Two families reported with bi-allelic variants, and paediatric onset progressive leukodystorphy. Functional data demonstrating ACER3 deficiency.
Sources: Literature
Mendeliome v0.4807 ACER3 Zornitza Stark Marked gene: ACER3 as ready
Mendeliome v0.4807 ACER3 Zornitza Stark Gene: acer3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4807 ACER3 Zornitza Stark Phenotypes for gene: ACER3 were changed from to Leukodystrophy
Mendeliome v0.4806 ACER3 Zornitza Stark Publications for gene: ACER3 were set to
Mendeliome v0.4805 ACER3 Zornitza Stark Mode of inheritance for gene: ACER3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4804 ACER3 Zornitza Stark Classified gene: ACER3 as Amber List (moderate evidence)
Mendeliome v0.4804 ACER3 Zornitza Stark Gene: acer3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4803 ACER3 Zornitza Stark edited their review of gene: ACER3: Changed phenotypes: Leukodystrophy
Mendeliome v0.4803 ACER3 Zornitza Stark reviewed gene: ACER3: Rating: AMBER; Mode of pathogenicity: None; Publications: 32816236, 26792856; Phenotypes: Leukodystrphy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.124 HSD3B2 Zornitza Stark Marked gene: HSD3B2 as ready
Additional findings_Paediatric v0.124 HSD3B2 Zornitza Stark Gene: hsd3b2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.124 HSD3B2 Zornitza Stark Classified gene: HSD3B2 as Green List (high evidence)
Additional findings_Paediatric v0.124 HSD3B2 Zornitza Stark Gene: hsd3b2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.123 IL7R Zornitza Stark Marked gene: IL7R as ready
Additional findings_Paediatric v0.123 IL7R Zornitza Stark Gene: il7r has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.123 IL7R Zornitza Stark Classified gene: IL7R as Green List (high evidence)
Additional findings_Paediatric v0.123 IL7R Zornitza Stark Gene: il7r has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.122 HNF4A Zornitza Stark Marked gene: HNF4A as ready
Additional findings_Paediatric v0.122 HNF4A Zornitza Stark Gene: hnf4a has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.122 HNF4A Zornitza Stark Classified gene: HNF4A as Green List (high evidence)
Additional findings_Paediatric v0.122 HNF4A Zornitza Stark Gene: hnf4a has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.121 GABRG2 Zornitza Stark Marked gene: GABRG2 as ready
Additional findings_Paediatric v0.121 GABRG2 Zornitza Stark Added comment: Comment when marking as ready: Molecular diagnosis even in the milder phenotypes has the potential to reduce the need for investigations.
Additional findings_Paediatric v0.121 GABRG2 Zornitza Stark Gene: gabrg2 has been classified as Amber List (Moderate Evidence).
Additional findings_Paediatric v0.121 GABRG2 Zornitza Stark Phenotypes for gene: GABRG2 were changed from vEpilepsy, generalized, with febrile seizures plus, type 3 MIM# 607681; Epileptic encephalopathy, early infantile, 74 MIM# 618396; Febrile seizures, familial, 8 MIM# 607681 to Epilepsy, generalized, with febrile seizures plus, type 3 MIM# 607681; Epileptic encephalopathy, early infantile, 74 MIM# 618396; Febrile seizures, familial, 8 MIM# 607681
Additional findings_Paediatric v0.120 GABRG2 Zornitza Stark Phenotypes for gene: GABRG2 were changed from Epilepsy, childhood absence with febrile seizure to vEpilepsy, generalized, with febrile seizures plus, type 3 MIM# 607681; Epileptic encephalopathy, early infantile, 74 MIM# 618396; Febrile seizures, familial, 8 MIM# 607681
Additional findings_Paediatric v0.119 GABRG2 Zornitza Stark Publications for gene: GABRG2 were set to
Additional findings_Paediatric v0.118 GABRG2 Zornitza Stark Classified gene: GABRG2 as Amber List (moderate evidence)
Additional findings_Paediatric v0.118 GABRG2 Zornitza Stark Gene: gabrg2 has been classified as Amber List (Moderate Evidence).
Additional findings_Paediatric v0.117 FH Zornitza Stark Marked gene: FH as ready
Additional findings_Paediatric v0.117 FH Zornitza Stark Gene: fh has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.117 FH Zornitza Stark Phenotypes for gene: FH were changed from Leiomyomatosis and renal cell cancer; Fumarase deficiency to Fumurase deficiency MIM# 606812
Additional findings_Paediatric v0.116 FH Zornitza Stark Mode of inheritance for gene: FH was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.115 FH Zornitza Stark Classified gene: FH as Green List (high evidence)
Additional findings_Paediatric v0.115 FH Zornitza Stark Gene: fh has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.114 FGFR3 Zornitza Stark Marked gene: FGFR3 as ready
Additional findings_Paediatric v0.114 FGFR3 Zornitza Stark Gene: fgfr3 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.114 FGFR3 Zornitza Stark Classified gene: FGFR3 as Green List (high evidence)
Additional findings_Paediatric v0.114 FGFR3 Zornitza Stark Gene: fgfr3 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.113 FBP1 Zornitza Stark Marked gene: FBP1 as ready
Additional findings_Paediatric v0.113 FBP1 Zornitza Stark Gene: fbp1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.113 FBP1 Zornitza Stark Classified gene: FBP1 as Green List (high evidence)
Additional findings_Paediatric v0.113 FBP1 Zornitza Stark Gene: fbp1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.112 FBN1 Zornitza Stark Marked gene: FBN1 as ready
Additional findings_Paediatric v0.112 FBN1 Zornitza Stark Gene: fbn1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.112 FBN1 Zornitza Stark Classified gene: FBN1 as Green List (high evidence)
Additional findings_Paediatric v0.112 FBN1 Zornitza Stark Gene: fbn1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.111 F7 Zornitza Stark Marked gene: F7 as ready
Additional findings_Paediatric v0.111 F7 Zornitza Stark Gene: f7 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.111 F7 Zornitza Stark Classified gene: F7 as Green List (high evidence)
Additional findings_Paediatric v0.111 F7 Zornitza Stark Gene: f7 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.110 F5 Zornitza Stark Marked gene: F5 as ready
Additional findings_Paediatric v0.110 F5 Zornitza Stark Gene: f5 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.110 F5 Zornitza Stark Phenotypes for gene: F5 were changed from Risk for deep vein thrombosis to Factor V deficiency MIM# 227400; Thrombophilia due to activated protein C resistance MIM# 188055
Additional findings_Paediatric v0.109 F5 Zornitza Stark Mode of inheritance for gene: F5 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Additional findings_Paediatric v0.108 F5 Zornitza Stark Classified gene: F5 as Green List (high evidence)
Additional findings_Paediatric v0.108 F5 Zornitza Stark Gene: f5 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.107 F13B Zornitza Stark Marked gene: F13B as ready
Additional findings_Paediatric v0.107 F13B Zornitza Stark Gene: f13b has been classified as Red List (Low Evidence).
Additional findings_Paediatric v0.107 F13B Zornitza Stark Classified gene: F13B as Red List (low evidence)
Additional findings_Paediatric v0.107 F13B Zornitza Stark Gene: f13b has been classified as Red List (Low Evidence).
Cataract v0.234 COL9A2 Zornitza Stark Marked gene: COL9A2 as ready
Cataract v0.234 COL9A2 Zornitza Stark Gene: col9a2 has been classified as Red List (Low Evidence).
Cataract v0.234 COL9A2 Zornitza Stark Classified gene: COL9A2 as Red List (low evidence)
Cataract v0.234 COL9A2 Zornitza Stark Gene: col9a2 has been classified as Red List (Low Evidence).
Cataract v0.233 COL9A2 Zornitza Stark reviewed gene: COL9A2: Rating: RED; Mode of pathogenicity: None; Publications: 31090205, 21671392; Phenotypes: Stickler syndrome, type V, MIM# 614284; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.233 COL9A2 Natalie Tan gene: COL9A2 was added
gene: COL9A2 was added to Cataract. Sources: Literature
Mode of inheritance for gene: COL9A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL9A2 were set to PMID: 31090205; 21671392; 20686772; 27666725; 15802199; 15710493
Phenotypes for gene: COL9A2 were set to Stickler syndrome, type V, MIM# 614284
Review for gene: COL9A2 was set to GREEN
Added comment: Bi-allelic variants have been associated with Stickler syndrome in three unrelated families. Association is supported by multiple animal models. [Modified review by ZS from Deafness_IsolatedAndComplex panel.]
Sources: Literature
Malignant Hyperthermia Susceptibility v0.12 Bryony Thompson Panel status changed from internal to public
Mendeliome v0.4803 TRPV1 Bryony Thompson Publications for gene: TRPV1 were set to 29930394
Mendeliome v0.4802 TRPV1 Bryony Thompson Classified gene: TRPV1 as Amber List (moderate evidence)
Mendeliome v0.4802 TRPV1 Bryony Thompson Gene: trpv1 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.61 TRPV1 Bryony Thompson Marked gene: TRPV1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.61 TRPV1 Bryony Thompson Gene: trpv1 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.61 TRPV1 Bryony Thompson Classified gene: TRPV1 as Amber List (moderate evidence)
Rhabdomyolysis and Metabolic Myopathy v0.61 TRPV1 Bryony Thompson Gene: trpv1 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.60 TRPV1 Bryony Thompson gene: TRPV1 was added
gene: TRPV1 was added to Rhabdomyolysis RMH. Sources: Literature
Mode of inheritance for gene: TRPV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPV1 were set to 32471784
Phenotypes for gene: TRPV1 were set to Exertional heat stroke; rhabdomyolysis
Review for gene: TRPV1 was set to AMBER
Added comment: Two unrelated cases reported with rhabdomyolysis and supporting in vitro functional assays for the 2 missense variants.
Sources: Literature
Malignant Hyperthermia Susceptibility v0.11 TRPV1 Bryony Thompson changed review comment from: 3 cases with a muscle biopsy sensitive for halothane but not for caffeine, MHSh, and a single case susceptible to both (MHS). One of the MHSh cases was from a family with RYR1-associated myopathy, where the TRPV1 occurred with RYR1 variants. Two of the cases had a clinical diagnosis of malignant hyperthermia and two of the cases had an exertional heat stress episode. Supporting functional assays in HEK293 cells and trpv1 -/- mouse muscle, demonstrated impairment of intracellular Ca2+ signaling.; to: 3 cases with a muscle biopsy sensitive for halothane but not for caffeine, MHSh, and a single case susceptible to both (MHS). One of the MHSh cases was from a family with RYR1-associated myopathy, where the TRPV1 occurred with RYR1 variants. Two of the cases had a clinical diagnosis of malignant hyperthermia and two of the cases had an exertional heat stroke episode. Supporting functional assays in HEK293 cells and trpv1 -/- mouse muscle, demonstrated impairment of intracellular Ca2+ signaling.
Malignant Hyperthermia Susceptibility v0.11 TRPV1 Bryony Thompson edited their review of gene: TRPV1: Changed phenotypes: Malignant hyperthermia susceptibility, exertional heat stroke
Malignant Hyperthermia Susceptibility v0.11 TRPV1 Bryony Thompson Classified gene: TRPV1 as Amber List (moderate evidence)
Malignant Hyperthermia Susceptibility v0.11 TRPV1 Bryony Thompson Gene: trpv1 has been classified as Amber List (Moderate Evidence).
Malignant Hyperthermia Susceptibility v0.10 TRPV1 Bryony Thompson reviewed gene: TRPV1: Rating: AMBER; Mode of pathogenicity: None; Publications: 29930394, 32471784; Phenotypes: Malignant hyperthermia susceptibility, exertional heat stress; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malignant Hyperthermia Susceptibility v0.8 STAC3 Bryony Thompson Marked gene: STAC3 as ready
Malignant Hyperthermia Susceptibility v0.8 STAC3 Bryony Thompson Gene: stac3 has been classified as Green List (High Evidence).
Malignant Hyperthermia Susceptibility v0.8 STAC3 Bryony Thompson Classified gene: STAC3 as Green List (high evidence)
Malignant Hyperthermia Susceptibility v0.8 STAC3 Bryony Thompson Gene: stac3 has been classified as Green List (High Evidence).
Malignant Hyperthermia Susceptibility v0.7 STAC3 Bryony Thompson gene: STAC3 was added
gene: STAC3 was added to Malignant Hyperthermia Susceptibility. Sources: Expert list
Mode of inheritance for gene: STAC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAC3 were set to 30168660; 32898259
Phenotypes for gene: STAC3 were set to Myopathy, congenital, Baily-Bloch MIM#255995
Review for gene: STAC3 was set to GREEN
Added comment: The rarest cause of malignant hyperthermia susceptibility. Currently, MHS has only been identified with the biallelic cases with myopathy. Pathogenic variants impair skeletal muscle excitation–contraction coupling.
Sources: Expert list
Cataract v0.233 COL9A1 Zornitza Stark Marked gene: COL9A1 as ready
Cataract v0.233 COL9A1 Zornitza Stark Gene: col9a1 has been classified as Amber List (Moderate Evidence).
Cataract v0.233 COL9A1 Zornitza Stark Classified gene: COL9A1 as Amber List (moderate evidence)
Cataract v0.233 COL9A1 Zornitza Stark Gene: col9a1 has been classified as Amber List (Moderate Evidence).
Cataract v0.232 COL9A1 Zornitza Stark reviewed gene: COL9A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21421862; Phenotypes: Stickler syndrome, type IV, OMIM# 614134; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Malignant Hyperthermia Susceptibility v0.6 TRPV1 Bryony Thompson gene: TRPV1 was added
gene: TRPV1 was added to Malignant Hyperthermia Susceptibility. Sources: Literature
Mode of inheritance for gene: TRPV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TRPV1 were set to Malignant hyperthermia susceptibility
Malignant Hyperthermia Susceptibility v0.5 CACNB1 Bryony Thompson gene: CACNB1 was added
gene: CACNB1 was added to Malignant Hyperthermia Susceptibility. Sources: Other
Mode of inheritance for gene: CACNB1 was set to Unknown
Phenotypes for gene: CACNB1 were set to Malignant hyperthermia susceptibility
Malignant Hyperthermia Susceptibility v0.4 RYR1 Bryony Thompson edited their review of gene: RYR1: Set current diagnostic: yes
Malignant Hyperthermia Susceptibility v0.4 CACNA1S Bryony Thompson edited their review of gene: CACNA1S: Set current diagnostic: yes
Malignant Hyperthermia Susceptibility v0.4 CACNA1S Bryony Thompson Marked gene: CACNA1S as ready
Malignant Hyperthermia Susceptibility v0.4 CACNA1S Bryony Thompson Gene: cacna1s has been classified as Green List (High Evidence).
Malignant Hyperthermia Susceptibility v0.4 CACNA1S Bryony Thompson Classified gene: CACNA1S as Green List (high evidence)
Malignant Hyperthermia Susceptibility v0.4 CACNA1S Bryony Thompson Gene: cacna1s has been classified as Green List (High Evidence).
Malignant Hyperthermia Susceptibility v0.3 CACNA1S Bryony Thompson gene: CACNA1S was added
gene: CACNA1S was added to Malignant Hyperthermia Susceptibility. Sources: Expert list
Mode of inheritance for gene: CACNA1S was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1S were set to 20301325
Phenotypes for gene: CACNA1S were set to {Malignant hyperthermia susceptibility 5} MIM#601887
Mode of pathogenicity for gene: CACNA1S was set to Other
Review for gene: CACNA1S was set to GREEN
Added comment: Gain of function variants are the second most common cause of malignant hyperthermia susceptibility.
Sources: Expert list
Malignant Hyperthermia Susceptibility v0.2 RYR1 Bryony Thompson Marked gene: RYR1 as ready
Malignant Hyperthermia Susceptibility v0.2 RYR1 Bryony Thompson Gene: ryr1 has been classified as Green List (High Evidence).
Malignant Hyperthermia Susceptibility v0.2 RYR1 Bryony Thompson Classified gene: RYR1 as Green List (high evidence)
Malignant Hyperthermia Susceptibility v0.2 RYR1 Bryony Thompson Gene: ryr1 has been classified as Green List (High Evidence).
Malignant Hyperthermia Susceptibility v0.1 RYR1 Bryony Thompson gene: RYR1 was added
gene: RYR1 was added to Malignant Hyperthermia Susceptibility. Sources: Expert list
Mode of inheritance for gene: RYR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RYR1 were set to 20301325
Phenotypes for gene: RYR1 were set to {Malignant hyperthermia susceptibility 1} MIM#145600
Mode of pathogenicity for gene: RYR1 was set to Other
Review for gene: RYR1 was set to GREEN
Added comment: Gain-of-function RYR1 variants are the most common cause of malignant hyperthermia
Sources: Expert list
Malignant Hyperthermia Susceptibility v0.0 Bryony Thompson Added Panel Malignant Hyperthermia Susceptibility
Set panel types to: Royal Melbourne Hospital; Rare Disease
Cataract v0.232 COL9A1 Natalie Tan gene: COL9A1 was added
gene: COL9A1 was added to Cataract. Sources: Literature
Mode of inheritance for gene: COL9A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL9A1 were set to PMID: 21421862; 16909383
Phenotypes for gene: COL9A1 were set to Stickler syndrome, type IV, MIM#614134
Review for gene: COL9A1 was set to GREEN
Added comment: At least three families reported.
Sources: Literature
Additional findings_Paediatric v0.106 F13B Lilian Downie changed review comment from: Factor XIII deficiency is an autosomal recessive hematologic disorder characterized by increased bleeding and poor wound healing. Most cases of congenital factor XIII deficiency result from mutation in the A subunit. Not reviewed by Babyseq, included in NC NEXUS with the indication for 'intracranial bleeding' but I can't find evidence of childhood onset intracranial bleeding in literature.
Sources: Expert list; to: Factor XIII deficiency is an autosomal recessive hematologic disorder characterized by increased bleeding and poor wound healing. Most cases of congenital factor XIII deficiency result from mutation in the A subunit. Not reviewed by Babyseq, included in NC NEXUS with the indication for 'intracranial bleeding' but I can't find evidence of childhood onset intracranial bleeding in literature, only a milder bleeding phenotype post surgery in heterozygotes? Insufficient evidence for inclusion?
Sources: Expert list
Additional findings_Paediatric v0.106 F13B Lilian Downie gene: F13B was added
gene: F13B was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: F13B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: F13B were set to PMID: 31013569
Phenotypes for gene: F13B were set to Factor XIIIB deficiency MIM# 613235
Review for gene: F13B was set to RED
Added comment: Factor XIII deficiency is an autosomal recessive hematologic disorder characterized by increased bleeding and poor wound healing. Most cases of congenital factor XIII deficiency result from mutation in the A subunit. Not reviewed by Babyseq, included in NC NEXUS with the indication for 'intracranial bleeding' but I can't find evidence of childhood onset intracranial bleeding in literature.
Sources: Expert list
Additional findings_Paediatric v0.106 F5 Lilian Downie reviewed gene: F5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27351627; Phenotypes: Factor V deficiency MIM# 227400, Thrombophilia due to activated protein C resistance MIM# 188055; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Additional findings_Paediatric v0.106 F7 Lilian Downie gene: F7 was added
gene: F7 was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: F7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: F7 were set to Factor VII deficiency MIM# 227500
Review for gene: F7 was set to GREEN
Added comment: Factor VII deficiency is an autosomal recessive bleeding disorder showing variable severity. Not reviewed by Babyseq, included in NC NEXUS list. Bleeding treatable with factor replacement.
Sources: Expert list
Additional findings_Paediatric v0.106 FBN1 Lilian Downie reviewed gene: FBN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: multiple; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.106 FBP1 Lilian Downie gene: FBP1 was added
gene: FBP1 was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: FBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FBP1 were set to Fructose-1,6-bisphosphatase deficiency MIM# 229700
Review for gene: FBP1 was set to GREEN
Added comment: Fructose-1,6-bisphosphatase deficiency is an autosomal recessive disorder characterized by impaired gluconeogenesis. Patients present with hypoglycemia and metabolic acidosis on fasting and may have episodes of hyperventilation, apnea, hypoglycemia, and ketosis. Although the disorder may be lethal in the newborn period, proper treatment yields an excellent prognosis. No reviewed by Babyseq, included in NC NEXUS.
Sources: Expert list
Additional findings_Paediatric v0.106 FGFR3 Lilian Downie reviewed gene: FGFR3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.106 FH Lilian Downie reviewed gene: FH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fumurase deficiency MIM# 606812, Leiomyomatosis and renal cell cancer MIM# 150800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Additional findings_Paediatric v0.106 GABRG2 Lilian Downie reviewed gene: GABRG2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 27864268; Phenotypes: Epilepsy, generalized, with febrile seizures plus, type 3 MIM# 607681, Epileptic encephalopathy, early infantile, 74 MIM# 618396, Febrile seizures, familial, 8 MIM# 607681; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.106 HADH Zornitza Stark Marked gene: HADH as ready
Additional findings_Paediatric v0.106 HADH Zornitza Stark Gene: hadh has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.106 HADH Zornitza Stark Phenotypes for gene: HADH were changed from 3-hydroxyacyl-CoA dehydrogenase deficiency; Hyperinsulinemic hypoglycemia, familial, 4 to Hyperinsulinemic hypoglycemia, familial, 4
Additional findings_Paediatric v0.105 HADH Zornitza Stark Classified gene: HADH as Green List (high evidence)
Additional findings_Paediatric v0.105 HADH Zornitza Stark Gene: hadh has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.104 GIF Zornitza Stark Marked gene: GIF as ready
Additional findings_Paediatric v0.104 GIF Zornitza Stark Gene: gif has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.104 GIF Zornitza Stark Classified gene: GIF as Green List (high evidence)
Additional findings_Paediatric v0.104 GIF Zornitza Stark Gene: gif has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.103 GIF Zornitza Stark reviewed gene: GIF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Additional findings_Paediatric v0.103 GGCX Zornitza Stark Marked gene: GGCX as ready
Additional findings_Paediatric v0.103 GGCX Zornitza Stark Gene: ggcx has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.103 GGCX Zornitza Stark Classified gene: GGCX as Green List (high evidence)
Additional findings_Paediatric v0.103 GGCX Zornitza Stark Gene: ggcx has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.102 GATA2 Zornitza Stark Marked gene: GATA2 as ready
Additional findings_Paediatric v0.102 GATA2 Zornitza Stark Gene: gata2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.102 GATA2 Zornitza Stark Classified gene: GATA2 as Green List (high evidence)
Additional findings_Paediatric v0.102 GATA2 Zornitza Stark Gene: gata2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.101 GATA2 Zornitza Stark reviewed gene: GATA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 21 MIM# 614172, Emberger syndrome MIM# 614038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.101 GATA2 Lilian Downie gene: GATA2 was added
gene: GATA2 was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: GATA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GATA2 were set to PMID: 25397911, 30047422
Phenotypes for gene: GATA2 were set to Immunodeficiency 21 MIM# 614172; Emberger syndrome MIM# 614038
Review for gene: GATA2 was set to AMBER
Added comment: Gene not curated by Babyseq, included in NC NEXUS. This primary immunodeficiency, designated IMD21, DCML, or MONOMAC, is characterized by profoundly decreased or absent monocytes, B lymphocytes, natural killer (NK) lymphocytes, and circulating and tissue dendritic cells (DCs), with little or no effect on T-cell numbers. Clinical features of IMD21 are variable and include susceptibility to disseminated nontuberculous mycobacterial infections, papillomavirus infections, opportunistic fungal infections, and pulmonary alveolar proteinosis. Bone marrow hypocellularity and dysplasia of myeloid, erythroid, and megakaryocytic lineages are present in most patients, as are karyotypic abnormalities, including monosomy 7 and trisomy 8. In the absence of cytogenetic abnormalities or overt dysplasia, hypoplastic bone marrow may initially be diagnosed as aplastic anemia. Bone marrow transplantation is the only cure. Allelic disease with phenotypic overalp lymphoedema with SNHL (Emberger syndrome). Onset of immunodeficiency may not be until later childhood early adulthood.
Sources: Expert list
Polymicrogyria and Schizencephaly v0.152 MAST1 Zornitza Stark Marked gene: MAST1 as ready
Polymicrogyria and Schizencephaly v0.152 MAST1 Zornitza Stark Gene: mast1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.152 MAST1 Zornitza Stark Phenotypes for gene: MAST1 were changed from OMIM#618273 to Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations, MIM# 618273
Polymicrogyria and Schizencephaly v0.151 MAST1 Zornitza Stark Classified gene: MAST1 as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.151 MAST1 Zornitza Stark Gene: mast1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.150 MAST1 Zornitza Stark reviewed gene: MAST1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations, MIM# 618273; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polymicrogyria and Schizencephaly v0.150 PTEN Zornitza Stark changed review comment from: More than 10 individuals reported.; to: More than 10 individuals reported with PMG.
Polymicrogyria and Schizencephaly v0.150 PTEN Zornitza Stark Marked gene: PTEN as ready
Polymicrogyria and Schizencephaly v0.150 PTEN Zornitza Stark Gene: pten has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.150 PTEN Zornitza Stark Phenotypes for gene: PTEN were changed from OMIM#605309 to Macrocephaly/autism syndrome, MIM# 605309
Polymicrogyria and Schizencephaly v0.149 PTEN Zornitza Stark Classified gene: PTEN as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.149 PTEN Zornitza Stark Gene: pten has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.148 PTEN Zornitza Stark reviewed gene: PTEN: Rating: GREEN; Mode of pathogenicity: None; Publications: 32959437; Phenotypes: Macrocephaly/autism syndrome, MIM# 605309; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polymicrogyria and Schizencephaly v0.148 MED25 Zornitza Stark Marked gene: MED25 as ready
Polymicrogyria and Schizencephaly v0.148 MED25 Zornitza Stark Gene: med25 has been classified as Amber List (Moderate Evidence).
Polymicrogyria and Schizencephaly v0.148 MED25 Zornitza Stark Phenotypes for gene: MED25 were changed from OMIM#616449 to Basel-Vanagait-Smirin-Yosef syndrome, MIM# 616449
Polymicrogyria and Schizencephaly v0.147 MED25 Zornitza Stark Classified gene: MED25 as Amber List (moderate evidence)
Polymicrogyria and Schizencephaly v0.147 MED25 Zornitza Stark Gene: med25 has been classified as Amber List (Moderate Evidence).
Polymicrogyria and Schizencephaly v0.146 MED25 Zornitza Stark reviewed gene: MED25: Rating: AMBER; Mode of pathogenicity: None; Publications: 32816121; Phenotypes: Basel-Vanagait-Smirin-Yosef syndrome, MIM# 616449; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.146 MAST1 Chloe Stutterd gene: MAST1 was added
gene: MAST1 was added to Polymicrogyria and Schizencephaly. Sources: Literature
Mode of inheritance for gene: MAST1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST1 were set to 32818970; 30449657
Phenotypes for gene: MAST1 were set to OMIM#618273
Review for gene: MAST1 was set to GREEN
Added comment: Tripathy et al. (PMID:30449657) describe cortical malformation as dysgyria but images consistent with PMG.
Sources: Literature
Polymicrogyria and Schizencephaly v0.146 PTEN Chloe Stutterd gene: PTEN was added
gene: PTEN was added to Polymicrogyria and Schizencephaly. Sources: Literature
Mode of inheritance for gene: PTEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTEN were set to 32959437
Phenotypes for gene: PTEN were set to OMIM#605309
Review for gene: PTEN was set to GREEN
Added comment: Sources: Literature
Polymicrogyria and Schizencephaly v0.146 MED25 Chloe Stutterd gene: MED25 was added
gene: MED25 was added to Polymicrogyria and Schizencephaly. Sources: Literature
Mode of inheritance for gene: MED25 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED25 were set to 32324310; 32816121
Phenotypes for gene: MED25 were set to OMIM#616449
Review for gene: MED25 was set to AMBER
Added comment: Sources: Literature
Holoprosencephaly and septo-optic dysplasia v0.45 KMT2D Zornitza Stark Marked gene: KMT2D as ready
Holoprosencephaly and septo-optic dysplasia v0.45 KMT2D Zornitza Stark Gene: kmt2d has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v0.45 KMT2D Zornitza Stark Classified gene: KMT2D as Green List (high evidence)
Holoprosencephaly and septo-optic dysplasia v0.45 KMT2D Zornitza Stark Gene: kmt2d has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v0.44 KMT2D Zornitza Stark gene: KMT2D was added
gene: KMT2D was added to Holoprosencephaly and septo-optic dysplasia. Sources: Literature
Mode of inheritance for gene: KMT2D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT2D were set to 31846209; 31282990; 32773771
Phenotypes for gene: KMT2D were set to Kabuki syndrome 1, MIM# 147920
Review for gene: KMT2D was set to GREEN
Added comment: Three case reports of HPE in Kabuki syndrome. Association also observed internally, PMID 32773771.
Sources: Literature
Additional findings_Paediatric v0.101 GGCX Lilian Downie gene: GGCX was added
gene: GGCX was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: GGCX was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GGCX were set to Vitamin K-dependent clotting factors, combined deficiency of, 1 MIM# 277450
Review for gene: GGCX was set to GREEN
Added comment: Deficiency of all vitamin K-dependent clotting factors leads to a bleeding tendency that is usually reversed by oral administration of vitamin K. Can cause fatal haemmorhage in the first few weeks of life. Non reviewed by Babyseq, included in NC NEXUS list.
Sources: Expert list
Additional findings_Paediatric v0.101 GIF Lilian Downie gene: GIF was added
gene: GIF was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: GIF was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GIF were set to Intrinsic factor deficiency # 261000
Added comment: Congenital pernicious anemia (PA), or intrinsic factor deficiency, is a rare disorder characterized by the lack of gastric intrinsic factor in the presence of normal acid secretion and mucosal cytology and the absence of GIF antibodies that are found in the acquired form of pernicious anemia. Childhood onset disease treatable with B12 injections. Not reviewed by Babyseq, on NC NEXUS list.
Sources: Expert list
Ciliary Dyskinesia v0.131 AKNA Zornitza Stark reviewed gene: AKNA: Rating: RED; Mode of pathogenicity: None; Publications: 32367404; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.131 ITCH Zornitza Stark Publications for gene: ITCH were set to 20170897
Ciliary Dyskinesia v0.130 ITCH Zornitza Stark edited their review of gene: ITCH: Changed publications: 20170897, 32367404
Mendeliome v0.4800 NUAK2 Zornitza Stark commented on gene: NUAK2: no OMIM# yet
Mendeliome v0.4800 NUAK2 Zornitza Stark edited their review of gene: NUAK2: Changed phenotypes: Anencephaly
Mendeliome v0.4800 NUAK2 Zornitza Stark Phenotypes for gene: NUAK2 were changed from ANENCEPHALY (OMIM#206500) to Anencephaly
Mendeliome v0.4799 NUAK2 Zornitza Stark Mode of inheritance for gene: NUAK2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4798 NUAK2 Zornitza Stark reviewed gene: NUAK2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4798 GOLGA3 Zornitza Stark Publications for gene: GOLGA3 were set to PMID: 23495255
Mendeliome v0.4797 GOLGA3 Zornitza Stark reviewed gene: GOLGA3: Rating: RED; Mode of pathogenicity: None; Publications: 32367404; Phenotypes: ; Mode of inheritance: None
Ciliary Dyskinesia v0.130 GOLGA3 Zornitza Stark Publications for gene: GOLGA3 were set to PMID: 23495255
Ciliary Dyskinesia v0.129 GOLGA3 Zornitza Stark Marked gene: GOLGA3 as ready
Ciliary Dyskinesia v0.129 GOLGA3 Zornitza Stark Gene: golga3 has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.129 GOLGA3 Zornitza Stark Classified gene: GOLGA3 as Red List (low evidence)
Ciliary Dyskinesia v0.129 GOLGA3 Zornitza Stark Gene: golga3 has been classified as Red List (Low Evidence).
Mendeliome v0.4797 ANGPT2 Zornitza Stark Publications for gene: ANGPT2 were set to https://stm.sciencemag.org/content/12/560/eaax8013
Mendeliome v0.4796 ANGPT2 Zornitza Stark edited their review of gene: ANGPT2: Changed publications: 32908006
Congenital Diarrhoea v0.10 AP1S1 Zornitza Stark Marked gene: AP1S1 as ready
Congenital Diarrhoea v0.10 AP1S1 Zornitza Stark Gene: ap1s1 has been classified as Amber List (Moderate Evidence).
Congenital Diarrhoea v0.10 AP1S1 Zornitza Stark Classified gene: AP1S1 as Amber List (moderate evidence)
Congenital Diarrhoea v0.10 AP1S1 Zornitza Stark Gene: ap1s1 has been classified as Amber List (Moderate Evidence).
Congenital Diarrhoea v0.9 AP1S1 Zornitza Stark reviewed gene: AP1S1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.4796 AP1S1 Zornitza Stark Marked gene: AP1S1 as ready
Mendeliome v0.4796 AP1S1 Zornitza Stark Gene: ap1s1 has been classified as Green List (High Evidence).
Mendeliome v0.4796 AP1S1 Zornitza Stark Phenotypes for gene: AP1S1 were changed from to MEDNIK syndrome 609313; non-syndromic congenital intestinal failure
Mendeliome v0.4795 AP1S1 Zornitza Stark Publications for gene: AP1S1 were set to
Mendeliome v0.4794 AP1S1 Zornitza Stark Mode of inheritance for gene: AP1S1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4793 AP1S1 Zornitza Stark reviewed gene: AP1S1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: MEDNIK syndrome 609313; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4793 Zornitza Stark removed gene:NOTCH3 from the panel
Mendeliome v0.4792 Zornitza Stark removed gene:ALS2 from the panel
Congenital Diarrhoea v0.9 AP1S1 Ee Ming Wong changed review comment from: - Established green gene in Ichthyosis, Palmoplantar Keratoderma and Erythrokeratoderma, ID and Hereditary Neuropathy (complex) panels associated with MEDNIK syndrome
- PMID: 32306098 propose a clinical and genetic expansion for AP1S1-associated disease

- 2 consanguineous families, each carrying a homozygous missense AP1S1 variant
- AP1S1 knockout cell line demonstrated tight-junction and polarity abnormalities that were rescued by WT AP1S1, but not the AP1S1 missense muta
Sources: Literature; to: - Established green gene in Ichthyosis, Palmoplantar Keratoderma and Erythrokeratoderma, ID and Hereditary Neuropathy (complex) panels associated with MEDNIK syndrome
- PMID: 32306098 propose a clinical and genetic expansion for AP1S1-associated disease

- 2 consanguineous families, each carrying a homozygous missense AP1S1 variant
- AP1S1 knockout cell line demonstrated tight-junction and polarity abnormalities that were rescued by WT AP1S1, but not the AP1S1 missense muta
Sources: Literature
Congenital Diarrhoea v0.9 AP1S1 Ee Ming Wong gene: AP1S1 was added
gene: AP1S1 was added to Congenital Diarrhoea. Sources: Literature
Mode of inheritance for gene: AP1S1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP1S1 were set to PMID: 32306098
Phenotypes for gene: AP1S1 were set to Non-syndromic congenital intestinal failure
Added comment: - Established green gene in Ichthyosis, Palmoplantar Keratoderma and Erythrokeratoderma, ID and Hereditary Neuropathy (complex) panels associated with MEDNIK syndrome
- PMID: 32306098 propose a clinical and genetic expansion for AP1S1-associated disease

- 2 consanguineous families, each carrying a homozygous missense AP1S1 variant
- AP1S1 knockout cell line demonstrated tight-junction and polarity abnormalities that were rescued by WT AP1S1, but not the AP1S1 missense muta
Sources: Literature
Mendeliome v0.4791 AP1S1 Ee Ming Wong changed review comment from: - Established green gene in Ichthyosis, Palmoplantar Keratoderma and Erythrokeratoderma, ID and Hereditary Neuropathy (complex) panels associated with MEDNIK syndrome
- PMID: 32306098 propose a clinical and genetic expansion for AP1S1-associated disease

- 2 consanguineous families, each carrying a homozygous missense AP1S1 variant
- AP1S1 knockout cell line demonstrated tight-junction and polarity abnormalities that were rescued by WT AP1S1, but not the AP1S1 missense mutants; to: - Established green gene in Ichthyosis, Palmoplantar Keratoderma and Erythrokeratoderma, ID and Hereditary Neuropathy (complex) panels associated with MEDNIK syndrome
- PMID: 32306098 propose a clinical and genetic expansion for AP1S1-associated disease

- 2 consanguineous families, each carrying a homozygous missense AP1S1 variant
- AP1S1 knockout cell line demonstrated tight-junction and polarity abnormalities that were rescued by WT AP1S1, but not the AP1S1 missense mutants
Mendeliome v0.4791 AP1S1 Ee Ming Wong changed review comment from: - 2 consanguineous families, each carrying a homozygous missense AP1S1 variant
- AP1S1 knockout cell line demonstrated tight-junction and polarity abnormalities that were rescued by WT AP1S1, but not the AP1S1 missense mutants; to: - Established green gene in Ichthyosis, Palmoplantar Keratoderma and Erythrokeratoderma, ID and Hereditary Neuropathy (complex) panels associated with MEDNIK syndrome
- PMID: 32306098 propose a clinical and genetic expansion for AP1S1-associated disease

- 2 consanguineous families, each carrying a homozygous missense AP1S1 variant
- AP1S1 knockout cell line demonstrated tight-junction and polarity abnormalities that were rescued by WT AP1S1, but not the AP1S1 missense mutants
Ciliary Dyskinesia v0.128 AKNA Seb Lunke Marked gene: AKNA as ready
Ciliary Dyskinesia v0.128 AKNA Seb Lunke Gene: akna has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.128 AKNA Seb Lunke Classified gene: AKNA as Red List (low evidence)
Ciliary Dyskinesia v0.128 AKNA Seb Lunke Gene: akna has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.127 GOLGA3 Elena Savva gene: GOLGA3 was added
gene: GOLGA3 was added to Ciliary Dyskinesia. Sources: Literature
Mode of inheritance for gene: GOLGA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOLGA3 were set to PMID: 23495255
Phenotypes for gene: GOLGA3 were set to Primary ciliary dyskinesia
Review for gene: GOLGA3 was set to RED
Added comment: https://link.springer.com/article/10.1007/s00439-020-02170-2
Two siblings with a homozygous missense and PCD

PMID: 23495255; null mice have failed spermatogenesis
Sources: Literature
Mendeliome v0.4791 AKNA Seb Lunke Marked gene: AKNA as ready
Mendeliome v0.4791 AKNA Seb Lunke Gene: akna has been classified as Red List (Low Evidence).
Mendeliome v0.4791 GOLGA3 Zornitza Stark Marked gene: GOLGA3 as ready
Mendeliome v0.4791 GOLGA3 Zornitza Stark Gene: golga3 has been classified as Red List (Low Evidence).
Mendeliome v0.4791 GOLGA3 Zornitza Stark Classified gene: GOLGA3 as Red List (low evidence)
Mendeliome v0.4791 GOLGA3 Zornitza Stark Gene: golga3 has been classified as Red List (Low Evidence).
Mendeliome v0.4790 AKNA Seb Lunke Classified gene: AKNA as Red List (low evidence)
Mendeliome v0.4790 AKNA Seb Lunke Gene: akna has been classified as Red List (Low Evidence).
Mendeliome v0.4789 THOC1 Melanie Marty changed review comment from: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and in mouse it induced hair cell apoptosis.
Sources: Literature; to: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the hypomorphic thoc1 in mouse induced hair cell apoptosis.
Sources: Literature
Deafness_IsolatedAndComplex v0.587 THOC1 Melanie Marty changed review comment from: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the and the hypomorphic thoc1 in mouse induced hair cell apoptosis.
Sources: Literature; to: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the hypomorphic thoc1 in mouse induced hair cell apoptosis.
Sources: Literature
Deafness_IsolatedAndComplex v0.587 THOC1 Zornitza Stark Marked gene: THOC1 as ready
Deafness_IsolatedAndComplex v0.587 THOC1 Zornitza Stark Gene: thoc1 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.115 HEXB Bryony Thompson Marked gene: HEXB as ready
Motor Neurone Disease v0.115 HEXB Bryony Thompson Gene: hexb has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.587 THOC1 Zornitza Stark Classified gene: THOC1 as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v0.587 THOC1 Zornitza Stark Gene: thoc1 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.115 HEXB Bryony Thompson Classified gene: HEXB as Green List (high evidence)
Motor Neurone Disease v0.115 HEXB Bryony Thompson Gene: hexb has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.586 THOC1 Melanie Marty changed review comment from: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and in mouse it induced hair cell apoptosis.
Sources: Literature; to: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the and the hypomorphic thoc1 in mouse induced hair cell apoptosis.
Sources: Literature
Mendeliome v0.4789 GOLGA3 Elena Savva gene: GOLGA3 was added
gene: GOLGA3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GOLGA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOLGA3 were set to PMID: 23495255
Phenotypes for gene: GOLGA3 were set to Primary ciliary dyskinesia
Review for gene: GOLGA3 was set to RED
Added comment: https://link.springer.com/article/10.1007/s00439-020-02170-2
Two siblings with a homozygous missense and PCD

PMID: 23495255; null mice have failed spermatogenesis
Sources: Literature
Motor Neurone Disease v0.114 HEXB Bryony Thompson gene: HEXB was added
gene: HEXB was added to Motor Neuron Disease. Sources: Literature
Mode of inheritance for gene: HEXB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEXB were set to 31995250; 24263030
Phenotypes for gene: HEXB were set to Sandhoff disease, infantile, juvenile, and adult forms MIM#268800
Review for gene: HEXB was set to GREEN
Added comment: In cases with adult onset disease, lower motor neuron disorder has been reported as a presenting feature of the condition. Has been reported as a differential diagnosis for ALS/MND.
Sources: Literature
Ciliary Dyskinesia v0.127 ITCH Zornitza Stark Marked gene: ITCH as ready
Ciliary Dyskinesia v0.127 ITCH Zornitza Stark Gene: itch has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.127 ITCH Zornitza Stark Publications for gene: ITCH were set to
Ciliary Dyskinesia v0.126 ITCH Zornitza Stark Classified gene: ITCH as Red List (low evidence)
Ciliary Dyskinesia v0.126 ITCH Zornitza Stark Gene: itch has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.125 ITCH Zornitza Stark reviewed gene: ITCH: Rating: RED; Mode of pathogenicity: None; Publications: 20170897; Phenotypes: Autoimmune disease, multisystem, with facial dysmorphism 613385, primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.113 HEXA Bryony Thompson Marked gene: HEXA as ready
Motor Neurone Disease v0.113 HEXA Bryony Thompson Gene: hexa has been classified as Green List (High Evidence).
Mendeliome v0.4789 PRICKLE3 Seb Lunke Marked gene: PRICKLE3 as ready
Mendeliome v0.4789 PRICKLE3 Seb Lunke Gene: prickle3 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.113 HEXA Bryony Thompson Classified gene: HEXA as Green List (high evidence)
Motor Neurone Disease v0.113 HEXA Bryony Thompson Gene: hexa has been classified as Green List (High Evidence).
Mendeliome v0.4789 PRICKLE3 Seb Lunke Classified gene: PRICKLE3 as Red List (low evidence)
Mendeliome v0.4789 PRICKLE3 Seb Lunke Added comment: Comment on list classification: Single variant only and questionable association due to uncertainty of role around ND4.
Mendeliome v0.4789 PRICKLE3 Seb Lunke Gene: prickle3 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.112 HEXA Bryony Thompson gene: HEXA was added
gene: HEXA was added to Motor Neuron Disease. Sources: Literature
Mode of inheritance for gene: HEXA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEXA were set to 31995250; 31076878
Phenotypes for gene: HEXA were set to GM2-gangliosidosis, several forms or Tay-Sachs disease MIM#272800
Review for gene: HEXA was set to GREEN
Added comment: In cases with adult onset disease, lower motor neuron disorder has been reported as a presenting feature of the condition. Has been reported as a differential diagnosis for ALS/MND.
Sources: Literature
Deafness_IsolatedAndComplex v0.586 THOC1 Melanie Marty gene: THOC1 was added
gene: THOC1 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: THOC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THOC1 were set to 32776944
Phenotypes for gene: THOC1 were set to Nonsyndromic hearing loss
Review for gene: THOC1 was set to AMBER
Added comment: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and in mouse it induced hair cell apoptosis.
Sources: Literature
Ciliary Dyskinesia v0.125 AKNA Elena Savva gene: AKNA was added
gene: AKNA was added to Ciliary Dyskinesia. Sources: Literature
Mode of inheritance for gene: AKNA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AKNA were set to PMID: 21606955
Phenotypes for gene: AKNA were set to Primary ciliary dyskinesia
Review for gene: AKNA was set to RED
Added comment: https://link.springer.com/article/10.1007/s00439-020-02170-2
Two siblings with homozygous PTCs with PCD. Carrier parents and mutation negative siblings (5) was normal.

PMID: 21606955: Null mice have neonatal death with systemic inflammation and alveolar loss
Sources: Literature
Mendeliome v0.4788 AKNA Elena Savva gene: AKNA was added
gene: AKNA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AKNA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AKNA were set to PMID: 21606955
Phenotypes for gene: AKNA were set to Primary ciliary dyskinesia
Review for gene: AKNA was set to RED
Added comment: https://link.springer.com/article/10.1007/s00439-020-02170-2
Two siblings with homozygous PTCs with PCD. Carrier parents and mutation negative siblings (5) was normal.

PMID: 21606955: Null mice have neonatal death with systemic inflammation and alveolar loss
Sources: Literature
Mendeliome v0.4788 THOC1 Zornitza Stark Marked gene: THOC1 as ready
Mendeliome v0.4788 THOC1 Zornitza Stark Gene: thoc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4788 THOC1 Zornitza Stark Classified gene: THOC1 as Amber List (moderate evidence)
Mendeliome v0.4788 THOC1 Zornitza Stark Gene: thoc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4787 GBF1 Seb Lunke Marked gene: GBF1 as ready
Mendeliome v0.4787 GBF1 Seb Lunke Gene: gbf1 has been classified as Green List (High Evidence).
Mendeliome v0.4787 GBF1 Seb Lunke Classified gene: GBF1 as Green List (high evidence)
Mendeliome v0.4787 GBF1 Seb Lunke Gene: gbf1 has been classified as Green List (High Evidence).
Mendeliome v0.4786 THOC1 Melanie Marty changed review comment from: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the induced hair cell apoptosis.
Sources: Literature; to: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and in mouse it induced hair cell apoptosis.
Sources: Literature
Pituitary hormone deficiency v0.6 RNPC3 Zornitza Stark Marked gene: RNPC3 as ready
Pituitary hormone deficiency v0.6 RNPC3 Zornitza Stark Gene: rnpc3 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.6 RNPC3 Zornitza Stark Classified gene: RNPC3 as Amber List (moderate evidence)
Pituitary hormone deficiency v0.6 RNPC3 Zornitza Stark Gene: rnpc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4786 AP1S1 Ee Ming Wong reviewed gene: AP1S1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32306098; Phenotypes: non-syndromic congenital intestinal failure; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.4786 NUAK2 Seb Lunke Classified gene: NUAK2 as Amber List (moderate evidence)
Mendeliome v0.4786 NUAK2 Seb Lunke Gene: nuak2 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.5 RNPC3 Zornitza Stark gene: RNPC3 was added
gene: RNPC3 was added to Pituitary hormone deficiency. Sources: Literature
Mode of inheritance for gene: RNPC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNPC3 were set to 29866761; 32462814
Phenotypes for gene: RNPC3 were set to Growth hormone deficiency
Review for gene: RNPC3 was set to AMBER
Added comment: Two families reported. PMID 29866761: isolated growth deficiency and pituitary hypoplasia. PMID 32462814: growth hormone deficiency, central congenital hypothyroidism, congenital cataract, developmental delay/intellectual deficiency and delayed puberty. Full spectrum of phenotype unclear at present.
Sources: Literature
Ciliary Dyskinesia v0.125 ITCH Elena Savva gene: ITCH was added
gene: ITCH was added to Ciliary Dyskinesia. Sources: Literature
Mode of inheritance for gene: ITCH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITCH were set to Autoimmune disease, multisystem, with facial dysmorphism 613385; primary ciliary dyskinesia
Review for gene: ITCH was set to RED
Added comment: https://link.springer.com/article/10.1007/s00439-020-02170-2

Single patient with biallelic start-loss variant and primary ciliary dyskinesia
Sources: Literature
Mendeliome v0.4785 RNPC3 Zornitza Stark Marked gene: RNPC3 as ready
Mendeliome v0.4785 RNPC3 Zornitza Stark Gene: rnpc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4785 RNPC3 Zornitza Stark Classified gene: RNPC3 as Amber List (moderate evidence)
Mendeliome v0.4785 RNPC3 Zornitza Stark Gene: rnpc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4784 RNPC3 Zornitza Stark gene: RNPC3 was added
gene: RNPC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNPC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNPC3 were set to 29866761; 32462814
Phenotypes for gene: RNPC3 were set to Growth hormone deficiency
Review for gene: RNPC3 was set to AMBER
Added comment: Two families reported. PMID 29866761: isolated growth deficiency and pituitary hypoplasia. PMID 32462814: growth hormone deficiency, central congenital hypothyroidism, congenital cataract, developmental delay/intellectual deficiency and delayed puberty. Full spectrum of phenotype unclear at present.
Sources: Literature
Mendeliome v0.4783 THOC1 Melanie Marty changed review comment from: Missense variant identified and segregated with adulthood-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the induced hair cell apoptosis.
Sources: Literature; to: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the induced hair cell apoptosis.
Sources: Literature
Mendeliome v0.4783 PRICKLE3 Teresa Zhao gene: PRICKLE3 was added
gene: PRICKLE3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRICKLE3 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: PRICKLE3 were set to 32516135
Phenotypes for gene: PRICKLE3 were set to Leber’s hereditary optic neuropathy MIM#535000
Review for gene: PRICKLE3 was set to AMBER
Added comment: Reported as X-linked LHON modifier (c.157C>T, p.Arg53Trp) in PRICKLE3 in 3 Chinese families. All affected individuals carried both ND4 11778G>A and p.Arg53Trp mutations, while subjects bearing only a single mutation exhibited normal vision.

Defective assembly, stability, and function of ATP synthase observed using Lymphoblastoid cell lines from one of the families.

This finding indicated that the p.Arg53Trp mutation acted in synergy with the m.11778G>A mutation and deteriorated mitochondrial dysfunctions necessary for the expression of LHON.

Prickle3-deficient mice exhibited pronounced ATPase deficiencies.
Sources: Literature
Mendeliome v0.4783 NUAK2 Seb Lunke Marked gene: NUAK2 as ready
Mendeliome v0.4783 NUAK2 Seb Lunke Gene: nuak2 has been classified as Red List (Low Evidence).
Mendeliome v0.4783 GBF1 Paul De Fazio changed review comment from: Four unrelated families with individuals affected by sporadic or dominant Distal hereditary motor neuropathies (HMNs) or axonal Charcot-Marie-Tooth neuropathy (CMT2). 3 missense variants (1 de novo) and 1 nonsense variant (de novo). Authors observed marked increase in Golgi fragmentation in primary fibroblasts derived from all affected individuals.
Sources: Literature; to: Four unrelated families with individuals affected by sporadic or dominant Distal hereditary motor neuropathies (HMNs) or axonal Charcot-Marie-Tooth neuropathy (CMT2). 3 missense variants (1 de novo) and 1 nonsense variant (de novo).

Age of onset varied from childhood (nonsense variant) to 50s. Authors observed marked increase in Golgi fragmentation in primary fibroblasts derived from all affected individuals.
Sources: Literature
Mendeliome v0.4783 NUAK2 Seb Lunke gene: NUAK2 was added
gene: NUAK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUAK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NUAK2 were set to 32845958
Phenotypes for gene: NUAK2 were set to ANENCEPHALY (OMIM#206500)
Review for gene: NUAK2 was set to AMBER
Added comment: Novel gene described in single consanguineous family with three FDIU and extensive anencephaly. Hom inframe del affecting functional kinase domain, parents confirmed carriers. Good functional data showing loss of enzyme function and mouse model with 40% anencephaly after knock-out.
Sources: Literature
Mendeliome v0.4782 THOC1 Melanie Marty gene: THOC1 was added
gene: THOC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: THOC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THOC1 were set to 32776944
Phenotypes for gene: THOC1 were set to Nonsyndromic hearing loss
Review for gene: THOC1 was set to AMBER
Added comment: Missense variant identified and segregated with adulthood-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the induced hair cell apoptosis.
Sources: Literature
Skeletal dysplasia v0.48 MBTPS1 Zornitza Stark Marked gene: MBTPS1 as ready
Skeletal dysplasia v0.48 MBTPS1 Zornitza Stark Gene: mbtps1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.48 MBTPS1 Zornitza Stark Classified gene: MBTPS1 as Green List (high evidence)
Skeletal dysplasia v0.48 MBTPS1 Zornitza Stark Gene: mbtps1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.47 MBTPS1 Zornitza Stark gene: MBTPS1 was added
gene: MBTPS1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: MBTPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MBTPS1 were set to 32857899; 32420688; 30046013
Phenotypes for gene: MBTPS1 were set to Skeletal dysplasia
Review for gene: MBTPS1 was set to GREEN
Added comment: Three unrelated individuals reported with bi-allelic variants in this gene and a skeletal dysplasia, one described with SRS-like features. Elevated blood lysosomal enzymes are also a feature.
Sources: Literature
Mendeliome v0.4782 MBTPS1 Zornitza Stark Marked gene: MBTPS1 as ready
Mendeliome v0.4782 MBTPS1 Zornitza Stark Gene: mbtps1 has been classified as Green List (High Evidence).
Mendeliome v0.4782 MBTPS1 Zornitza Stark Classified gene: MBTPS1 as Green List (high evidence)
Mendeliome v0.4782 MBTPS1 Zornitza Stark Gene: mbtps1 has been classified as Green List (High Evidence).
Mendeliome v0.4781 MBTPS1 Zornitza Stark gene: MBTPS1 was added
gene: MBTPS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MBTPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MBTPS1 were set to 32857899; 32420688; 30046013
Phenotypes for gene: MBTPS1 were set to Skeletal dysplasia
Review for gene: MBTPS1 was set to GREEN
Added comment: Three unrelated individuals reported with bi-allelic variants in this gene and a skeletal dysplasia, one described with SRS-like features. Elevated blood lysosomal enzymes are also a feature.
Sources: Literature
Mendeliome v0.4780 GBF1 Paul De Fazio gene: GBF1 was added
gene: GBF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GBF1 were set to 32937143
Phenotypes for gene: GBF1 were set to Axonal Neuropathy
Review for gene: GBF1 was set to GREEN
gene: GBF1 was marked as current diagnostic
Added comment: Four unrelated families with individuals affected by sporadic or dominant Distal hereditary motor neuropathies (HMNs) or axonal Charcot-Marie-Tooth neuropathy (CMT2). 3 missense variants (1 de novo) and 1 nonsense variant (de novo). Authors observed marked increase in Golgi fragmentation in primary fibroblasts derived from all affected individuals.
Sources: Literature
Additional findings_Paediatric v0.101 HADH Lilian Downie reviewed gene: HADH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperinsulinemic hypoglycemia, familial, 4; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dilated Cardiomyopathy v0.87 TBX5 Zornitza Stark Marked gene: TBX5 as ready
Dilated Cardiomyopathy v0.87 TBX5 Zornitza Stark Gene: tbx5 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v0.87 TBX5 Zornitza Stark Classified gene: TBX5 as Green List (high evidence)
Dilated Cardiomyopathy v0.87 TBX5 Zornitza Stark Gene: tbx5 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.101 HNF4A Lilian Downie reviewed gene: HNF4A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypoglycaemia, hyperinsulinaemic; Mode of inheritance: None
Dilated Cardiomyopathy v0.86 TBX5 Zornitza Stark gene: TBX5 was added
gene: TBX5 was added to Dilated Cardiomyopathy. Sources: Literature
Mode of inheritance for gene: TBX5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBX5 were set to 32449309; 32236096; 25963046; 25725155
Phenotypes for gene: TBX5 were set to Holt-Oram syndrome, MIM# 142900; Dilated cardiomyopathy
Review for gene: TBX5 was set to GREEN
Added comment: 8 individuals from 4 unrelated families reported in PMID 32449309, relatively mild skeletal manifestations of HOS and DCM a prominent feature in several. Note previous reports, and supportive mouse model.
Sources: Literature
Additional findings_Paediatric v0.101 HSD3B2 Lilian Downie gene: HSD3B2 was added
gene: HSD3B2 was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: HSD3B2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HSD3B2 were set to Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency MIM# 201810
Review for gene: HSD3B2 was set to GREEN
Added comment: Classic 3-beta-hydroxysteroid dehydrogenase deficiency is an autosomal recessive form of CAH characterized by a severe impairment of steroid biosynthesis in both the adrenals and the gonads, resulting in decreased excretion of cortisol and aldosterone and of progesterone, androgens, and estrogens by these tissues. Affected newborns exhibit signs and symptoms of glucocorticoid and mineralocorticoid deficiencies, which may be fatal if not diagnosed and treated early, especially in the severe salt-wasting form. Moreover, male newborns exhibit pseudohermaphroditism with incomplete masculinization of the external genitalia due to an impairment of androgen biosynthesis in the testis. In contrast, affected females exhibit normal sexual differentiation or partial virilization.

Severe treatable neonatal onset disease. No reviwed by babyseq, included in NC NEXUS.
Sources: Expert list
Mendeliome v0.4780 ALS2 Ain Roesley gene: ALS2 was added
gene: ALS2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ALS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALS2 were set to 32214227
Phenotypes for gene: ALS2 were set to Tetraparesis with affection of upper and lower motor neuron
Penetrance for gene: ALS2 were set to unknown
Review for gene: ALS2 was set to RED
Added comment: In a cohort of Palestinian and Israeli Arabs with neurological disorders, a family with 2 affecteds were homozygous for a nonsense variant. Authors classified as likely path by ACMG guidelines
Sources: Literature
Additional findings_Paediatric v0.101 IL7R Lilian Downie gene: IL7R was added
gene: IL7R was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: IL7R was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IL7R were set to Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type MIM#608971
Review for gene: IL7R was set to GREEN
Added comment: SCID - severe neonatal presentation, treatment with BMT. Not reviewed by babyseq, included in NC NEXUS.
Sources: Expert list
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.46 CCDC141 Bryony Thompson Marked gene: CCDC141 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.46 CCDC141 Bryony Thompson Gene: ccdc141 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.46 CCDC141 Bryony Thompson Classified gene: CCDC141 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.46 CCDC141 Bryony Thompson Gene: ccdc141 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.45 CCDC141 Bryony Thompson gene: CCDC141 was added
gene: CCDC141 was added to Amenorrhoea. Sources: Literature
Mode of inheritance for gene: CCDC141 was set to Unknown
Publications for gene: CCDC141 were set to 27014940; 28324054; 25192046
Phenotypes for gene: CCDC141 were set to Anosmic hypogonadotropic hypogonadism
Review for gene: CCDC141 was set to AMBER
Added comment: A consanguineous family had a homozygous nonsense variant, but also had a homozygous missense in FEZF1. 3 other families reported with heterozygous variants, but other variants in other genes present. In an olfactory mouse model, Ccdc141 is expressed in GnRH neurons and olfactory fibers and that knockdown of Ccdc141 reduces GnRH neuronal migration.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.44 POLR3A Bryony Thompson Marked gene: POLR3A as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.44 POLR3A Bryony Thompson Gene: polr3a has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.44 POLR3A Bryony Thompson Classified gene: POLR3A as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.44 POLR3A Bryony Thompson Gene: polr3a has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.43 POLR3A Bryony Thompson gene: POLR3A was added
gene: POLR3A was added to Amenorrhoea. Sources: Literature
Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3A were set to 25339210
Phenotypes for gene: POLR3A were set to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism MIM#607694
Review for gene: POLR3A was set to GREEN
Added comment: PMID: 25339210 - delayed puberty or primary amenorrhea was present in 27/33 patients with POLR3A (81%).
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.42 POLR3B Bryony Thompson Marked gene: POLR3B as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.42 POLR3B Bryony Thompson Gene: polr3b has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.42 POLR3B Bryony Thompson Classified gene: POLR3B as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.42 POLR3B Bryony Thompson Gene: polr3b has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.41 POLR3B Bryony Thompson gene: POLR3B was added
gene: POLR3B was added to Amenorrhoea. Sources: Literature
Mode of inheritance for gene: POLR3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3B were set to 25339210; 27512013; 26113998
Phenotypes for gene: POLR3B were set to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism MIM#614381
Review for gene: POLR3B was set to GREEN
Added comment: Primary amenorrhoea can be a prominent feature of the condition in affected females.
Sources: Literature
Congenital diaphragmatic hernia v0.9 SPECC1L Zornitza Stark Marked gene: SPECC1L as ready
Congenital diaphragmatic hernia v0.9 SPECC1L Zornitza Stark Gene: specc1l has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.9 SPECC1L Zornitza Stark Classified gene: SPECC1L as Green List (high evidence)
Congenital diaphragmatic hernia v0.9 SPECC1L Zornitza Stark Gene: specc1l has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.8 SPECC1L Zornitza Stark gene: SPECC1L was added
gene: SPECC1L was added to Congenital diaphragmatic hernia. Sources: Literature
Mode of inheritance for gene: SPECC1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPECC1L were set to 32954677
Phenotypes for gene: SPECC1L were set to Opitz GBBB syndrome, type II, MIM# 145410
Review for gene: SPECC1L was set to GREEN
Added comment: 5 individuals with CDH and AD Opitz GBBB syndrome caused by SPECC1L variants reported.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.40 GGPS1 Bryony Thompson Marked gene: GGPS1 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.40 GGPS1 Bryony Thompson Gene: ggps1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.40 GGPS1 Bryony Thompson Classified gene: GGPS1 as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.40 GGPS1 Bryony Thompson Gene: ggps1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.39 GGPS1 Bryony Thompson gene: GGPS1 was added
gene: GGPS1 was added to Amenorrhoea. Sources: Literature
Mode of inheritance for gene: GGPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GGPS1 were set to 32403198
Phenotypes for gene: GGPS1 were set to Muscular dystrophy; deafness; ovarian insufficiency
Review for gene: GGPS1 was set to GREEN
Added comment: 6 unrelated families with biallelic variants, where all postpubertal females had primary ovarian insufficiency.
Sources: Literature
Mendeliome v0.4780 QRICH1 Zornitza Stark Marked gene: QRICH1 as ready
Mendeliome v0.4780 QRICH1 Zornitza Stark Gene: qrich1 has been classified as Green List (High Evidence).
Mendeliome v0.4780 QRICH1 Zornitza Stark Phenotypes for gene: QRICH1 were changed from to Ververi-Brady syndrome, MIM#617982
Mendeliome v0.4779 QRICH1 Zornitza Stark Publications for gene: QRICH1 were set to
Mendeliome v0.4778 QRICH1 Zornitza Stark Mode of inheritance for gene: QRICH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4777 QRICH1 Zornitza Stark reviewed gene: QRICH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28692176, 30281152, 33009816; Phenotypes: Ververi-Brady syndrome, MIM#617982; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3060 QRICH1 Zornitza Stark Marked gene: QRICH1 as ready
Intellectual disability syndromic and non-syndromic v0.3060 QRICH1 Zornitza Stark Gene: qrich1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3060 QRICH1 Zornitza Stark Phenotypes for gene: QRICH1 were changed from to Ververi-Brady syndrome, MIM#617982
Intellectual disability syndromic and non-syndromic v0.3059 QRICH1 Zornitza Stark Publications for gene: QRICH1 were set to
Intellectual disability syndromic and non-syndromic v0.3058 QRICH1 Zornitza Stark Mode of inheritance for gene: QRICH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3057 QRICH1 Zornitza Stark reviewed gene: QRICH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28692176, 30281152, 33009816; Phenotypes: Ververi-Brady syndrome, MIM#617982; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.76 SON Zornitza Stark Marked gene: SON as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.76 SON Zornitza Stark Gene: son has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.76 SON Zornitza Stark Classified gene: SON as Green List (high evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.76 SON Zornitza Stark Gene: son has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.75 SON Zornitza Stark gene: SON was added
gene: SON was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Expert Review
Mode of inheritance for gene: SON was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SON were set to 27545680; 27545676; 31005274
Phenotypes for gene: SON were set to ZTTK syndrome, MIM# 617140
Review for gene: SON was set to GREEN
Added comment: ZTTK syndrome is a severe multisystem developmental disorder characterised by intellectual disability, characteristic dysmorphic facial features, hypotonia, poor feeding, poor overall growth, and eye or visual abnormalities. Most individuals also have musculoskeletal abnormalities, and some have congenital defects of the heart and urogenital system. Brain imaging usually shows developmental abnormalities such as gyral changes, cortical and/or cerebellar atrophy, and thin corpus callosum. More than 40 unrelated individuals reported.

Kidney anomalies are relatively common and include horseshoe kidney, unilateral renal hypoplasia, and renal cysts.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.3057 SON Zornitza Stark Marked gene: SON as ready
Intellectual disability syndromic and non-syndromic v0.3057 SON Zornitza Stark Gene: son has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3057 SON Zornitza Stark Phenotypes for gene: SON were changed from to ZTTK syndrome, MIM# 617140
Intellectual disability syndromic and non-syndromic v0.3056 SON Zornitza Stark Publications for gene: SON were set to
Intellectual disability syndromic and non-syndromic v0.3055 SON Zornitza Stark Mode of inheritance for gene: SON was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3054 SON Zornitza Stark reviewed gene: SON: Rating: GREEN; Mode of pathogenicity: None; Publications: 27545680, 27545676, 31005274; Phenotypes: ZTTK syndrome, MIM# 617140; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4777 GREB1L Zornitza Stark Marked gene: GREB1L as ready
Mendeliome v0.4777 GREB1L Zornitza Stark Gene: greb1l has been classified as Green List (High Evidence).
Mendeliome v0.4777 GREB1L Zornitza Stark Phenotypes for gene: GREB1L were changed from to Renal hypodysplasia/aplasia 3, OMIM# 617805
Mendeliome v0.4776 GREB1L Zornitza Stark Publications for gene: GREB1L were set to
Mendeliome v0.4775 GREB1L Zornitza Stark Mode of inheritance for gene: GREB1L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4774 GREB1L Zornitza Stark reviewed gene: GREB1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 29100091; Phenotypes: Renal hypodysplasia/aplasia 3, OMIM# 617805; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4774 IL1RAP Zornitza Stark Marked gene: IL1RAP as ready
Mendeliome v0.4774 IL1RAP Zornitza Stark Gene: il1rap has been classified as Red List (Low Evidence).
Mendeliome v0.4774 IL1RAP Zornitza Stark gene: IL1RAP was added
gene: IL1RAP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IL1RAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL1RAP were set to 31954058
Phenotypes for gene: IL1RAP were set to Steroid-sensitive nephrotic syndrome
Review for gene: IL1RAP was set to RED
Added comment: A pair of siblings with compound heterozygous variants in this gene and steroid-sensitive nephrotic syndrome. Functional effect of variants demonstrated but mouse model does not have proteinuria.
Sources: Literature
Proteinuria v0.139 IL1RAP Zornitza Stark Marked gene: IL1RAP as ready
Proteinuria v0.139 IL1RAP Zornitza Stark Gene: il1rap has been classified as Red List (Low Evidence).
Proteinuria v0.139 IL1RAP Zornitza Stark gene: IL1RAP was added
gene: IL1RAP was added to Proteinuria. Sources: Literature
Mode of inheritance for gene: IL1RAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL1RAP were set to 31954058
Phenotypes for gene: IL1RAP were set to Steroid-sensitive nephrotic syndrome
Review for gene: IL1RAP was set to RED
Added comment: A pair of siblings with compound heterozygous variants in this gene and steroid-sensitive nephrotic syndrome. Functional effect of variants demonstrated but mouse model does not have proteinuria.
Sources: Literature
Proteinuria v0.138 FAT1 Zornitza Stark Publications for gene: FAT1 were set to 30862798; 26905694
Proteinuria v0.137 FAT1 Zornitza Stark changed review comment from: Another 5 families reported.; to: Another 5 families reported with syndromic proteinuria.
Proteinuria v0.137 FAT1 Zornitza Stark edited their review of gene: FAT1: Added comment: PMID 32902815: bi-allelic variants in association with proteinuria and no syndromic features reported.; Changed publications: 30862798, 32902815
Alternating Hemiplegia and Hemiplegic Migraine v0.21 PRRT2 Zornitza Stark Marked gene: PRRT2 as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.21 PRRT2 Zornitza Stark Gene: prrt2 has been classified as Amber List (Moderate Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.21 PRRT2 Zornitza Stark Phenotypes for gene: PRRT2 were changed from to Convulsions, familial infantile, with paroxysmal choreoathetosis, 602066; Episodic kinesigenic dyskinesia 1, 128200; Seizures, benign familial infantile, 2, 605751
Alternating Hemiplegia and Hemiplegic Migraine v0.20 PRRT2 Zornitza Stark Publications for gene: PRRT2 were set to 22101681; 22744660; 31124310; 26561923
Alternating Hemiplegia and Hemiplegic Migraine v0.19 PRRT2 Zornitza Stark Classified gene: PRRT2 as Amber List (moderate evidence)
Alternating Hemiplegia and Hemiplegic Migraine v0.19 PRRT2 Zornitza Stark Gene: prrt2 has been classified as Amber List (Moderate Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.18 PRRT2 Zornitza Stark reviewed gene: PRRT2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24928127; Phenotypes: Episodic kinesigenic dyskinesia 1, MIM# 128200, Convulsions, familial infantile, with paroxysmal choreoathetosis, MIM# 602066; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.18 PRRT2 Zornitza Stark Publications for gene: PRRT2 were set to
Alternating Hemiplegia and Hemiplegic Migraine v0.17 PRRT2 Zornitza Stark Mode of inheritance for gene: PRRT2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.16 NOTCH3 Zornitza Stark Marked gene: NOTCH3 as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.16 NOTCH3 Zornitza Stark Gene: notch3 has been classified as Amber List (Moderate Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.16 ATP1A3 Zornitza Stark Marked gene: ATP1A3 as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.16 ATP1A3 Zornitza Stark Gene: atp1a3 has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.16 ATP1A3 Zornitza Stark Phenotypes for gene: ATP1A3 were changed from to Alternating hemiplegia of childhood 2, MIM# 614820
Alternating Hemiplegia and Hemiplegic Migraine v0.15 ATP1A3 Zornitza Stark Publications for gene: ATP1A3 were set to
Alternating Hemiplegia and Hemiplegic Migraine v0.14 ATP1A3 Zornitza Stark Mode of inheritance for gene: ATP1A3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.13 ATP1A3 Zornitza Stark reviewed gene: ATP1A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22842232, 22850527, 24842602; Phenotypes: Alternating hemiplegia of childhood 2, MIM# 614820; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.13 ATP1A2 Zornitza Stark Marked gene: ATP1A2 as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.13 ATP1A2 Zornitza Stark Gene: atp1a2 has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.13 ATP1A2 Zornitza Stark Phenotypes for gene: ATP1A2 were changed from to Alternating hemiplegia of childhood 1, MIM# 104290
Alternating Hemiplegia and Hemiplegic Migraine v0.12 ATP1A2 Zornitza Stark Publications for gene: ATP1A2 were set to
Alternating Hemiplegia and Hemiplegic Migraine v0.11 ATP1A2 Zornitza Stark Mode of inheritance for gene: ATP1A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.10 ATP1A2 Zornitza Stark reviewed gene: ATP1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24097848, 21352219, 17435187, 15286158; Phenotypes: Alternating hemiplegia of childhood 1, MIM# 104290; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4773 MRAS Zornitza Stark Publications for gene: MRAS were set to 28289718
Mendeliome v0.4772 MRAS Zornitza Stark Phenotypes for gene: MRAS were changed from Noonan syndrome to Noonan syndrome 11, MIM#618499
Mendeliome v0.4771 MRAS Zornitza Stark edited their review of gene: MRAS: Changed phenotypes: Noonan syndrome 11, MIM#618499
Rasopathy v0.89 MRAS Zornitza Stark Publications for gene: MRAS were set to 28289718
Rasopathy v0.88 MRAS Zornitza Stark Phenotypes for gene: MRAS were changed from Noonan syndrome to Noonan syndrome 11, MIM#618499
Rasopathy v0.87 MRAS Zornitza Stark edited their review of gene: MRAS: Changed phenotypes: Noonan syndrome 11, MIM#618499
Bleeding and Platelet Disorders v0.203 BLOC1S6 Zornitza Stark Classified gene: BLOC1S6 as Amber List (moderate evidence)
Bleeding and Platelet Disorders v0.203 BLOC1S6 Zornitza Stark Gene: bloc1s6 has been classified as Amber List (Moderate Evidence).
Bleeding and Platelet Disorders v0.202 BLOC1S6 Zornitza Stark changed review comment from: At least three unrelated families reported.
Sources: Expert list; to: At least three unrelated families reported, two of the individuals had the same homozygous variant. Note that one of the articles has been retracted due to some of the data having been falsified.
Sources: Expert list
Bleeding and Platelet Disorders v0.202 BLOC1S6 Zornitza Stark edited their review of gene: BLOC1S6: Changed rating: AMBER; Changed phenotypes: Hermansky-pudlak syndrome 9, MIM# 614171
Hereditary Neuropathy v0.87 NEMF Zornitza Stark Mode of inheritance for gene: NEMF was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy v0.86 NEMF Zornitza Stark changed review comment from: Nine individuals from 7 unrelated families reported with a mixed CNS/PNS phenotype. 7/9 had ID, 4/9 had formal assessments demonstrating axonal neuropathy, 3/9 had ataxia; muscular atrophy, hypotonia, respiratory distress, scoliosis also described in some. Three independently generated mouse models had progressive motor neuron degeneration.
Sources: Literature; to: Nine individuals from 7 unrelated families reported with a mixed CNS/PNS phenotype. 7/9 had ID, 4/9 had formal assessments demonstrating axonal neuropathy, 3/9 had ataxia; muscular atrophy, hypotonia, respiratory distress, scoliosis also described in some. Three independently generated mouse models had progressive motor neuron degeneration.

Single individual with de novo variant reported, postulated dominant negative effect. Evidence for mono allelic variants causing disease is limited.
Sources: Literature
Hereditary Neuropathy v0.86 NEMF Zornitza Stark edited their review of gene: NEMF: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4771 NEMF Zornitza Stark Mode of inheritance for gene: NEMF was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4770 NEMF Zornitza Stark changed review comment from: Nine individuals from 7 unrelated families reported with a mixed CNS/PNS phenotype. 7/9 had ID, 4/9 had formal assessments demonstrating axonal neuropathy, 3/9 had ataxia; muscular atrophy, hypotonia, respiratory distress, scoliosis also described in some. Three independently generated mouse models had progressive motor neuron degeneration.
Sources: Literature; to: Nine individuals from 7 unrelated families reported with a mixed CNS/PNS phenotype. 7/9 had ID, 4/9 had formal assessments demonstrating axonal neuropathy, 3/9 had ataxia; muscular atrophy, hypotonia, respiratory distress, scoliosis also described in some. Three independently generated mouse models had progressive motor neuron degeneration.

Single individual with de novo variant reported, postulated dominant negative effect. Evidence for mono allelic variants causing disease is limited.
Sources: Literature
Mendeliome v0.4770 NEMF Zornitza Stark edited their review of gene: NEMF: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3054 NEMF Zornitza Stark Mode of inheritance for gene: NEMF was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3053 NEMF Zornitza Stark edited their review of gene: NEMF: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3053 NEMF Konstantinos Varvagiannis changed review comment from: Biallelic (and possibly monoallelic) pathogenic variants in this gene are associated with DD/ID.

Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. (In one of these 8 cases it could not be ruled out that a de novo and maternally inherited variant were on the same allele, as phase was not determined). A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation.

Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M).

NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides prodduced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation.

The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected).

Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation.

Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration im mice.

Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration).; to: Biallelic (and possibly monoallelic) pathogenic variants in this gene are associated with DD/ID.

Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. (In one of these 8 cases it could not be ruled out that a de novo and maternally inherited variant were on the same allele, as phase was not determined). A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation.

Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M).

NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides produced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation.

The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected).

Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation.

Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration in mice.

Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration).
Intellectual disability syndromic and non-syndromic v0.3053 NEMF Konstantinos Varvagiannis changed review comment from: Biallelic (and possibly monoallelic) pathogenic variants in this gene are associated with DD/ID.

Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. (In one of these 8 cases it could not be ruled out that a de novo and maternally inherited variants were on the same allele, as phase was not been determined). A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation.

Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M).

NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides prodduced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation.

The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected).

Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation.

Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration im mice.

Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration).; to: Biallelic (and possibly monoallelic) pathogenic variants in this gene are associated with DD/ID.

Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. (In one of these 8 cases it could not be ruled out that a de novo and maternally inherited variant were on the same allele, as phase was not determined). A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation.

Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M).

NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides prodduced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation.

The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected).

Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation.

Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration im mice.

Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration).
Intellectual disability syndromic and non-syndromic v0.3053 NEMF Konstantinos Varvagiannis changed review comment from: Biallelic (and possibly monoallelic) pathogenic variants in this gene are associated with DD/ID.

Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. (In one of these 8 cases it could be ruled out that the de novo and maternally inherited variants were on the same allele, as phase was not been determined). A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation.

Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M).

NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides prodduced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation.

The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected).

Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation.

Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration im mice.

Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration).; to: Biallelic (and possibly monoallelic) pathogenic variants in this gene are associated with DD/ID.

Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. (In one of these 8 cases it could not be ruled out that a de novo and maternally inherited variants were on the same allele, as phase was not been determined). A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation.

Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M).

NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides prodduced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation.

The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected).

Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation.

Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration im mice.

Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration).
Intellectual disability syndromic and non-syndromic v0.3053 NEMF Konstantinos Varvagiannis reviewed gene: NEMF: Rating: GREEN; Mode of pathogenicity: None; Publications: 32934225; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Arrhythmogenic Cardiomyopathy v0.45 TMEM43 Zornitza Stark Marked gene: TMEM43 as ready
Arrhythmogenic Cardiomyopathy v0.45 TMEM43 Zornitza Stark Gene: tmem43 has been classified as Green List (High Evidence).
Arrhythmogenic Cardiomyopathy v0.45 TMEM43 Zornitza Stark Phenotypes for gene: TMEM43 were changed from to Arrhythmogenic right ventricular dysplasia 5, MIM# 604400
Arrhythmogenic Cardiomyopathy v0.44 TMEM43 Zornitza Stark Publications for gene: TMEM43 were set to
Arrhythmogenic Cardiomyopathy v0.43 TMEM43 Zornitza Stark Mode of inheritance for gene: TMEM43 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arrhythmogenic Cardiomyopathy v0.42 TMEM43 Zornitza Stark reviewed gene: TMEM43: Rating: GREEN; Mode of pathogenicity: None; Publications: 18313022, 21214875, 23812740, 22725725, 24598986, 29980933; Phenotypes: Arrhythmogenic right ventricular dysplasia 5, MIM# 604400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arrhythmogenic Cardiomyopathy v0.42 DSP Zornitza Stark Marked gene: DSP as ready
Arrhythmogenic Cardiomyopathy v0.42 DSP Zornitza Stark Gene: dsp has been classified as Green List (High Evidence).
Arrhythmogenic Cardiomyopathy v0.42 DSP Zornitza Stark Phenotypes for gene: DSP were changed from to Arrhythmogenic right ventricular dysplasia 8, MIM# 607450
Arrhythmogenic Cardiomyopathy v0.41 DSP Zornitza Stark Publications for gene: DSP were set to
Arrhythmogenic Cardiomyopathy v0.40 DSP Zornitza Stark Mode of inheritance for gene: DSP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arrhythmogenic Cardiomyopathy v0.39 DSP Zornitza Stark reviewed gene: DSP: Rating: GREEN; Mode of pathogenicity: None; Publications: 15941723, 25765472, 23954618, 20864495, 21397041, 24938629, 22240500; Phenotypes: Arrhythmogenic right ventricular dysplasia 8, MIM# 607450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arrhythmogenic Cardiomyopathy v0.39 DSC2 Zornitza Stark Marked gene: DSC2 as ready
Arrhythmogenic Cardiomyopathy v0.39 DSC2 Zornitza Stark Gene: dsc2 has been classified as Green List (High Evidence).
Arrhythmogenic Cardiomyopathy v0.39 DSC2 Zornitza Stark Phenotypes for gene: DSC2 were changed from to Arrhythmogenic right ventricular dysplasia 11, MIM# 610476; Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, MIM# 610476
Arrhythmogenic Cardiomyopathy v0.38 DSC2 Zornitza Stark Publications for gene: DSC2 were set to
Arrhythmogenic Cardiomyopathy v0.37 DSC2 Zornitza Stark Mode of inheritance for gene: DSC2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Arrhythmogenic Cardiomyopathy v0.36 DSC2 Zornitza Stark reviewed gene: DSC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 17963498, 21062920, 23863954, 17186466, 18957847, 17033975, 28339476; Phenotypes: Arrhythmogenic right ventricular dysplasia 11, MIM# 610476, Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, MIM# 610476; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.586 PLS1 Zornitza Stark Phenotypes for gene: PLS1 were changed from Deafness to Deafness, autosomal dominant 76, MIM# 618787
Deafness_IsolatedAndComplex v0.585 PLS1 Zornitza Stark edited their review of gene: PLS1: Changed phenotypes: Deafness, autosomal dominant 76, MIM# 618787
Mendeliome v0.4770 PLS1 Zornitza Stark Phenotypes for gene: PLS1 were changed from Deafness to Deafness, autosomal dominant 76, MIM# 618787
Mendeliome v0.4769 PLS1 Zornitza Stark edited their review of gene: PLS1: Changed phenotypes: Deafness, autosomal dominant 76, MIM# 618787
Mendeliome v0.4769 HOMER2 Zornitza Stark Marked gene: HOMER2 as ready
Mendeliome v0.4769 HOMER2 Zornitza Stark Gene: homer2 has been classified as Green List (High Evidence).
Mendeliome v0.4769 HOMER2 Zornitza Stark Phenotypes for gene: HOMER2 were changed from to Deafness, autosomal dominant 68, MIM# 616707
Mendeliome v0.4768 HOMER2 Zornitza Stark Publications for gene: HOMER2 were set to
Mendeliome v0.4767 HOMER2 Zornitza Stark Mode of inheritance for gene: HOMER2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4766 HOMER2 Zornitza Stark reviewed gene: HOMER2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25816005, 30047143, 25816005; Phenotypes: Deafness, autosomal dominant 68, MIM# 616707; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.585 HOMER2 Zornitza Stark Mode of inheritance for gene: HOMER2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.585 HOMER2 Zornitza Stark Mode of inheritance for gene: HOMER2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.584 HOMER2 Zornitza Stark edited their review of gene: HOMER2: Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Usher Syndrome v0.30 USH1G Zornitza Stark Marked gene: USH1G as ready
Usher Syndrome v0.30 USH1G Zornitza Stark Gene: ush1g has been classified as Green List (High Evidence).
Usher Syndrome v0.30 USH1C Zornitza Stark Publications for gene: USH1C were set to
Usher Syndrome v0.29 PEX6 Zornitza Stark Marked gene: PEX6 as ready
Usher Syndrome v0.29 PEX6 Zornitza Stark Gene: pex6 has been classified as Green List (High Evidence).
Usher Syndrome v0.29 PEX6 Zornitza Stark Publications for gene: PEX6 were set to
Usher Syndrome v0.28 PEX6 Zornitza Stark reviewed gene: PEX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 27302843, 32866347, 31884617, 29676688, 26387595; Phenotypes: Heimler syndrome 2, MIM# 616617; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.584 CEP250 Zornitza Stark Marked gene: CEP250 as ready
Deafness_IsolatedAndComplex v0.584 CEP250 Zornitza Stark Gene: cep250 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.584 CEP250 Zornitza Stark Classified gene: CEP250 as Green List (high evidence)
Deafness_IsolatedAndComplex v0.584 CEP250 Zornitza Stark Gene: cep250 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.583 CEP250 Zornitza Stark gene: CEP250 was added
gene: CEP250 was added to Deafness_IsolatedAndComplex. Sources: Expert list
Mode of inheritance for gene: CEP250 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP250 were set to 24780881; 29718797; 30459346
Phenotypes for gene: CEP250 were set to Cone-rod dystrophy and hearing loss 2, MIM# 618358
Review for gene: CEP250 was set to GREEN
Added comment: Cone-rod dystrophy and hearing loss-2 (CRDHL2) is characterized by retinal dystrophy, with photophobia and progressive reduction in visual acuity, associated with sensorineural hearing loss. Three unrelated families reported.
Sources: Expert list
Deafness_IsolatedAndComplex v0.582 PEX1 Zornitza Stark Marked gene: PEX1 as ready
Deafness_IsolatedAndComplex v0.582 PEX1 Zornitza Stark Gene: pex1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.582 PEX1 Zornitza Stark Classified gene: PEX1 as Green List (high evidence)
Deafness_IsolatedAndComplex v0.582 PEX1 Zornitza Stark Gene: pex1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.581 PEX1 Zornitza Stark gene: PEX1 was added
gene: PEX1 was added to Deafness_IsolatedAndComplex. Sources: Expert list
Mode of inheritance for gene: PEX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX1 were set to 32596134; 31831025; 27872819; 27633571; 27302843
Phenotypes for gene: PEX1 were set to Heimler syndrome 1, MIM# 234580
Review for gene: PEX1 was set to GREEN
Added comment: Heimler syndrome-1 (HMLR1), which represents the mildest end of the peroxisomal biogenesis disorder spectrum, is a rare autosomal recessive disorder characterised by sensorineural hearing loss, enamel hyoplasia of the secondary dentition, nail abnormalities, and retinitis pigmentosa. More than 5 unrelated families reported.
Sources: Expert list
Usher Syndrome v0.28 PEX1 Zornitza Stark Marked gene: PEX1 as ready
Usher Syndrome v0.28 PEX1 Zornitza Stark Gene: pex1 has been classified as Green List (High Evidence).
Usher Syndrome v0.28 PEX1 Zornitza Stark Publications for gene: PEX1 were set to
Usher Syndrome v0.27 PEX1 Zornitza Stark reviewed gene: PEX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32596134, 31831025, 27872819, 27633571, 27302843; Phenotypes: Heimler syndrome 1, MIM# 234580; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Usher Syndrome v0.27 PDZD7 Zornitza Stark Marked gene: PDZD7 as ready
Usher Syndrome v0.27 PDZD7 Zornitza Stark Gene: pdzd7 has been classified as Amber List (Moderate Evidence).
Usher Syndrome v0.27 PDZD7 Zornitza Stark Publications for gene: PDZD7 were set to
Usher Syndrome v0.26 PDZD7 Zornitza Stark Classified gene: PDZD7 as Amber List (moderate evidence)
Usher Syndrome v0.26 PDZD7 Zornitza Stark Gene: pdzd7 has been classified as Amber List (Moderate Evidence).
Usher Syndrome v0.25 PDZD7 Zornitza Stark changed review comment from: Multiple families reported, supportive functional data, including animal model. DEFINITIVE by ClinGen.; to: Association with deafness: Multiple families reported, supportive functional data, including animal model. DEFINITIVE by ClinGen.

Association with Usher syndrome: only reported in conjunction with other Usher syndrome variants, digenic inheritance model proposed, PMID: 20440071
Usher Syndrome v0.25 PDZD7 Zornitza Stark edited their review of gene: PDZD7: Changed rating: AMBER; Changed publications: 20440071, 19028668, 26416264, 26849169, 27068579, 26445815, 28173822, 24334608; Changed phenotypes: Usher syndrome, type IIC, GPR98/PDZD7 digenic, MIM# 605472, Deafness, autosomal recessive 57, MIM# 618003
Usher Syndrome v0.25 PCDH15 Zornitza Stark Marked gene: PCDH15 as ready
Usher Syndrome v0.25 PCDH15 Zornitza Stark Gene: pcdh15 has been classified as Green List (High Evidence).
Usher Syndrome v0.25 PCDH15 Zornitza Stark Publications for gene: PCDH15 were set to
Usher Syndrome v0.24 CEP78 Zornitza Stark Marked gene: CEP78 as ready
Usher Syndrome v0.24 CEP78 Zornitza Stark Gene: cep78 has been classified as Green List (High Evidence).
Usher Syndrome v0.24 CEP78 Zornitza Stark Publications for gene: CEP78 were set to
Usher Syndrome v0.23 CEP250 Zornitza Stark Marked gene: CEP250 as ready
Usher Syndrome v0.23 CEP250 Zornitza Stark Gene: cep250 has been classified as Green List (High Evidence).
Usher Syndrome v0.23 CEP250 Zornitza Stark Publications for gene: CEP250 were set to
Usher Syndrome v0.22 CEP250 Zornitza Stark reviewed gene: CEP250: Rating: GREEN; Mode of pathogenicity: None; Publications: 24780881, 29718797, 30459346; Phenotypes: Cone-rod dystrophy and hearing loss 2, MIM# 618358; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Usher Syndrome v0.22 CDH23 Zornitza Stark Marked gene: CDH23 as ready
Usher Syndrome v0.22 CDH23 Zornitza Stark Gene: cdh23 has been classified as Green List (High Evidence).
Usher Syndrome v0.22 CDH23 Zornitza Stark Publications for gene: CDH23 were set to
Usher Syndrome v0.21 ADGRV1 Zornitza Stark Marked gene: ADGRV1 as ready
Usher Syndrome v0.21 ADGRV1 Zornitza Stark Gene: adgrv1 has been classified as Green List (High Evidence).
Usher Syndrome v0.21 ADGRV1 Zornitza Stark Phenotypes for gene: ADGRV1 were changed from Usher syndrome, type 2C to Usher syndrome, type 2C, MIM# 605472
Usher Syndrome v0.20 ADGRV1 Zornitza Stark Publications for gene: ADGRV1 were set to
Usher Syndrome v0.19 ABHD12 Zornitza Stark Marked gene: ABHD12 as ready
Usher Syndrome v0.19 ABHD12 Zornitza Stark Gene: abhd12 has been classified as Green List (High Evidence).
Usher Syndrome v0.19 ABHD12 Zornitza Stark Publications for gene: ABHD12 were set to
Deafness_IsolatedAndComplex v0.580 KCNJ10 Zornitza Stark edited their review of gene: KCNJ10: Changed rating: GREEN; Changed phenotypes: SESAME syndrome 612780; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4766 TPRN Zornitza Stark Marked gene: TPRN as ready
Mendeliome v0.4766 TPRN Zornitza Stark Gene: tprn has been classified as Green List (High Evidence).
Mendeliome v0.4766 TPRN Zornitza Stark Phenotypes for gene: TPRN were changed from to Deafness, autosomal recessive 79, MIM# 613307
Mendeliome v0.4765 TPRN Zornitza Stark Publications for gene: TPRN were set to
Mendeliome v0.4764 TPRN Zornitza Stark Mode of inheritance for gene: TPRN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4763 TPRN Zornitza Stark reviewed gene: TPRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 19603065, 20170898, 20170899, 23340767, 25129962, 20170899, 20170899, 27693694, 24285636; Phenotypes: Deafness, autosomal recessive 79, MIM# 613307; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.580 TPRN Zornitza Stark Marked gene: TPRN as ready
Deafness_IsolatedAndComplex v0.580 TPRN Zornitza Stark Gene: tprn has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.580 TPRN Zornitza Stark Phenotypes for gene: TPRN were changed from to Deafness, autosomal recessive 79, MIM# 613307
Deafness_IsolatedAndComplex v0.579 TPRN Zornitza Stark Publications for gene: TPRN were set to
Deafness_IsolatedAndComplex v0.578 TPRN Zornitza Stark Mode of inheritance for gene: TPRN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.577 TPRN Zornitza Stark edited their review of gene: TPRN: Changed phenotypes: Deafness, autosomal recessive 79, MIM# 613307
Deafness_IsolatedAndComplex v0.577 TPRN Zornitza Stark reviewed gene: TPRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 19603065, 20170898, 20170899, 23340767, 25129962, 20170899, 20170899, 27693694, 24285636; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4763 TMC1 Zornitza Stark Marked gene: TMC1 as ready
Mendeliome v0.4763 TMC1 Zornitza Stark Gene: tmc1 has been classified as Green List (High Evidence).
Mendeliome v0.4763 TMC1 Zornitza Stark Phenotypes for gene: TMC1 were changed from to Deafness, autosomal dominant 36, MIM# 606705; Deafness, autosomal recessive 7, MIM# 600974
Mendeliome v0.4762 TMC1 Zornitza Stark Publications for gene: TMC1 were set to
Mendeliome v0.4761 TMC1 Zornitza Stark Mode of inheritance for gene: TMC1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4760 TMC1 Zornitza Stark reviewed gene: TMC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11850618, 17250663, 18616530, 24827932, 11850623, 22105175; Phenotypes: Deafness, autosomal dominant 36, MIM# 606705, Deafness, autosomal recessive 7, MIM# 600974; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.577 TMC1 Zornitza Stark Marked gene: TMC1 as ready
Deafness_IsolatedAndComplex v0.577 TMC1 Zornitza Stark Gene: tmc1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.577 TMC1 Zornitza Stark Phenotypes for gene: TMC1 were changed from to Deafness, autosomal dominant 36, MIM# 606705; Deafness, autosomal recessive 7, MIM# 600974
Deafness_IsolatedAndComplex v0.576 TMC1 Zornitza Stark Publications for gene: TMC1 were set to
Deafness_IsolatedAndComplex v0.575 TMC1 Zornitza Stark Mode of inheritance for gene: TMC1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.574 TMC1 Zornitza Stark reviewed gene: TMC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11850618, 17250663, 18616530, 24827932, 11850623, 22105175; Phenotypes: Deafness, autosomal dominant 36, MIM# 606705, Deafness, autosomal recessive 7, MIM# 600974; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4760 TMIE Zornitza Stark Marked gene: TMIE as ready
Mendeliome v0.4760 TMIE Zornitza Stark Gene: tmie has been classified as Green List (High Evidence).
Mendeliome v0.4760 TMIE Zornitza Stark Phenotypes for gene: TMIE were changed from to Deafness, autosomal recessive 6, MIM# 600971
Mendeliome v0.4759 TMIE Zornitza Stark Mode of inheritance for gene: TMIE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4758 TMIE Zornitza Stark Publications for gene: TMIE were set to
Mendeliome v0.4757 TMIE Zornitza Stark reviewed gene: TMIE: Rating: GREEN; Mode of pathogenicity: None; Publications: 12145746, 19438934, 24416283, 25467981, 25475183, 19934034, 12140191; Phenotypes: Deafness, autosomal recessive 6, MIM# 600971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.574 TMIE Zornitza Stark Marked gene: TMIE as ready
Deafness_IsolatedAndComplex v0.574 TMIE Zornitza Stark Gene: tmie has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.574 TMIE Zornitza Stark Phenotypes for gene: TMIE were changed from to Deafness, autosomal recessive 6, MIM# 600971
Deafness_IsolatedAndComplex v0.573 TMIE Zornitza Stark Publications for gene: TMIE were set to
Deafness_IsolatedAndComplex v0.572 TMIE Zornitza Stark Mode of inheritance for gene: TMIE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.571 TMIE Zornitza Stark reviewed gene: TMIE: Rating: GREEN; Mode of pathogenicity: None; Publications: 12145746, 19438934, 24416283, 25467981, 25475183, 19934034, 12140191; Phenotypes: Deafness, autosomal recessive 6, MIM# 600971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4757 TRIOBP Zornitza Stark Marked gene: TRIOBP as ready
Mendeliome v0.4757 TRIOBP Zornitza Stark Gene: triobp has been classified as Green List (High Evidence).
Mendeliome v0.4757 TRIOBP Zornitza Stark Phenotypes for gene: TRIOBP were changed from to Deafness, autosomal recessive 28, MIM# 609823
Mendeliome v0.4756 TRIOBP Zornitza Stark Publications for gene: TRIOBP were set to
Mendeliome v0.4755 TRIOBP Zornitza Stark Mode of inheritance for gene: TRIOBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4754 TRIOBP Zornitza Stark reviewed gene: TRIOBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 16385458, 16385457, 23226338, 27014650, 24853665, 27344577, 20510926; Phenotypes: Deafness, autosomal recessive 28, MIM# 609823; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.571 TRIOBP Zornitza Stark Marked gene: TRIOBP as ready
Deafness_IsolatedAndComplex v0.571 TRIOBP Zornitza Stark Gene: triobp has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.571 TRIOBP Zornitza Stark Phenotypes for gene: TRIOBP were changed from to Deafness, autosomal recessive 28, MIM# 609823
Deafness_IsolatedAndComplex v0.570 TRIOBP Zornitza Stark Publications for gene: TRIOBP were set to
Deafness_IsolatedAndComplex v0.569 TRIOBP Zornitza Stark Mode of inheritance for gene: TRIOBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.568 TRIOBP Zornitza Stark reviewed gene: TRIOBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 16385458, 16385457, 23226338, 27014650, 24853665, 27344577, 20510926; Phenotypes: Deafness, autosomal recessive 28, MIM# 609823; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.568 USH1C Zornitza Stark Marked gene: USH1C as ready
Deafness_IsolatedAndComplex v0.568 USH1C Zornitza Stark Gene: ush1c has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.568 USH1C Zornitza Stark Phenotypes for gene: USH1C were changed from to Usher syndrome, type 1C, MIM# 276904; Deafness, autosomal recessive 18A, MIM# 602092
Deafness_IsolatedAndComplex v0.567 USH1C Zornitza Stark Publications for gene: USH1C were set to
Deafness_IsolatedAndComplex v0.566 USH1C Zornitza Stark Mode of inheritance for gene: USH1C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.565 USH1C Zornitza Stark reviewed gene: USH1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 10973247, 10973248, 11239869, 21203349, 12107438; Phenotypes: Usher syndrome, type 1C, MIM# 276904, Deafness, autosomal recessive 18A, MIM# 602092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.565 USH1G Zornitza Stark Marked gene: USH1G as ready
Deafness_IsolatedAndComplex v0.565 USH1G Zornitza Stark Gene: ush1g has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.565 USH1G Zornitza Stark Phenotypes for gene: USH1G were changed from to Usher syndrome, type 1G, MIM# 606943
Deafness_IsolatedAndComplex v0.564 USH1G Zornitza Stark Mode of inheritance for gene: USH1G was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.563 USH1G Zornitza Stark reviewed gene: USH1G: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Usher syndrome, type 1G, MIM# 606943; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.563 USH2A Zornitza Stark Marked gene: USH2A as ready
Deafness_IsolatedAndComplex v0.563 USH2A Zornitza Stark Gene: ush2a has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.563 USH2A Zornitza Stark Phenotypes for gene: USH2A were changed from to Usher syndrome, type 2A, MIM# 276901
Deafness_IsolatedAndComplex v0.562 USH2A Zornitza Stark Mode of inheritance for gene: USH2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.561 USH2A Zornitza Stark reviewed gene: USH2A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Usher syndrome, type 2A, MIM# 276901; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4754 STRC Zornitza Stark Marked gene: STRC as ready
Mendeliome v0.4754 STRC Zornitza Stark Gene: strc has been classified as Green List (High Evidence).
Mendeliome v0.4754 STRC Zornitza Stark Phenotypes for gene: STRC were changed from to Deafness, autosomal recessive 16, MIM# 603720
Mendeliome v0.4753 STRC Zornitza Stark Publications for gene: STRC were set to
Mendeliome v0.4752 STRC Zornitza Stark Mode of inheritance for gene: STRC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4751 STRC Zornitza Stark reviewed gene: STRC: Rating: GREEN; Mode of pathogenicity: None; Publications: 11687802, 26011646, 26746617, 20301780; Phenotypes: Deafness, autosomal recessive 16, MIM# 603720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.561 STRC Zornitza Stark Marked gene: STRC as ready
Deafness_IsolatedAndComplex v0.561 STRC Zornitza Stark Gene: strc has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.561 STRC Zornitza Stark Phenotypes for gene: STRC were changed from to Deafness, autosomal recessive 16, MIM# 603720
Deafness_IsolatedAndComplex v0.560 STRC Zornitza Stark Publications for gene: STRC were set to
Deafness_IsolatedAndComplex v0.559 STRC Zornitza Stark Mode of inheritance for gene: STRC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.558 STRC Zornitza Stark Tag SV/CNV tag was added to gene: STRC.
Deafness_IsolatedAndComplex v0.558 STRC Zornitza Stark reviewed gene: STRC: Rating: GREEN; Mode of pathogenicity: None; Publications: 11687802, 26011646, 26746617, 20301780; Phenotypes: Deafness, autosomal recessive 16, MIM# 603720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hydrops fetalis v0.198 ATP1A2 Zornitza Stark Publications for gene: ATP1A2 were set to 30690204
Hydrops fetalis v0.197 ATP1A2 Zornitza Stark edited their review of gene: ATP1A2: Added comment: Two further families reported with this association in PMID 31608932; Changed publications: 30690204, 31608932
Intellectual disability syndromic and non-syndromic v0.3053 NUP188 Zornitza Stark Phenotypes for gene: NUP188 were changed from microcephaly; ID; cataract; structural brain abnormalities; hypoventilation to Sandestig-Stefanova syndrome, 618804; microcephaly; ID; cataract; structural brain abnormalities; hypoventilation
Intellectual disability syndromic and non-syndromic v0.3052 NUP188 Zornitza Stark edited their review of gene: NUP188: Changed phenotypes: Sandestig-Stefanova syndrome, 618804, microcephaly, ID, cataract, structural brain abnormalities, hypoventilation
Microcephaly v0.484 NUP188 Zornitza Stark Phenotypes for gene: NUP188 were changed from microcephaly; ID; cataract; structural brain abnormalities; hypoventilation to Sandestig-Stefanova syndrome, 618804; microcephaly; ID; cataract; structural brain abnormalities; hypoventilation
Microcephaly v0.483 NUP188 Zornitza Stark edited their review of gene: NUP188: Changed phenotypes: Sandestig-Stefanova syndrome, 618804, microcephaly, ID, cataract, structural brain abnormalities, hypoventilation
Mendeliome v0.4751 NUP188 Zornitza Stark Phenotypes for gene: NUP188 were changed from microcephaly; ID; cataract; structural brain abnormalities; hypoventilation to Sandestig-Stefanova syndrome, 618804; microcephaly; ID; cataract; structural brain abnormalities; hypoventilation
Mendeliome v0.4750 NUP188 Zornitza Stark edited their review of gene: NUP188: Changed phenotypes: Sandestig-Stefanova syndrome, 618804, microcephaly, ID, cataract, structural brain abnormalities, hypoventilation
Cataract v0.232 NUP188 Zornitza Stark Phenotypes for gene: NUP188 were changed from microcephaly; ID; cataract; structural brain abnormalities; hypoventilation to Sandestig-Stefanova syndrome, 618804; microcephaly; ID; cataract; structural brain abnormalities; hypoventilation
Cataract v0.231 NUP188 Zornitza Stark edited their review of gene: NUP188: Changed phenotypes: Sandestig-Stefanova syndrome, 618804, microcephaly, ID, cataract, structural brain abnormalities, hypoventilation
Mendeliome v0.4750 SETD1A Zornitza Stark Marked gene: SETD1A as ready
Mendeliome v0.4750 SETD1A Zornitza Stark Gene: setd1a has been classified as Green List (High Evidence).
Mendeliome v0.4750 SETD1A Zornitza Stark Classified gene: SETD1A as Green List (high evidence)
Mendeliome v0.4750 SETD1A Zornitza Stark Gene: setd1a has been classified as Green List (High Evidence).
Mendeliome v0.4749 SETD1A Zornitza Stark gene: SETD1A was added
gene: SETD1A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SETD1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD1A were set to 31197650; 32346159
Phenotypes for gene: SETD1A were set to Epilepsy, early-onset, with or without developmental delay, MIM# 618832
Review for gene: SETD1A was set to GREEN
Added comment: 19 unrelated individuals reported with de novo variants in this gene and a neurodevelopmental phenotype, primarily manifesting and ID and seizures. LOF mechanism supported by functional data. Three mouse models. SNPs in this gene have also been associated with risk of developing schizophrenia.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3052 SETD1A Zornitza Stark Marked gene: SETD1A as ready
Intellectual disability syndromic and non-syndromic v0.3052 SETD1A Zornitza Stark Gene: setd1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3052 SETD1A Zornitza Stark Classified gene: SETD1A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3052 SETD1A Zornitza Stark Gene: setd1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3051 SETD1A Zornitza Stark gene: SETD1A was added
gene: SETD1A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SETD1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD1A were set to 31197650; 32346159
Phenotypes for gene: SETD1A were set to Epilepsy, early-onset, with or without developmental delay, MIM# 618832
Review for gene: SETD1A was set to GREEN
Added comment: 19 unrelated individuals reported with de novo variants in this gene and a neurodevelopmental phenotype, primarily manifesting and ID and seizures. LOF mechanism supported by functional data. Three mouse models.

SNPs in this gene have also been associated with risk of developing schizophrenia.
Sources: Literature
Genetic Epilepsy v0.874 SETD1A Zornitza Stark edited their review of gene: SETD1A: Added comment: PMID 32346159: Described 15 individuals with de novo SETD1A variants presenting with global developmental delay and/or intellectual disability, subtle facial dysmorphisms, behavioral and psychiatric problems. Examined cellular phenotypes in three patient-derived cell lines with three variants: p.Gly535Alafs*12, c.4582-2_4582delAG, and p.Tyr1499Asp and results suggested that that these variants behave as loss-of-function (LoF) alleles.; Changed publications: 31197650, 32346159; Changed phenotypes: Epilepsy, Intellectual disability
Mendeliome v0.4748 HPDL Zornitza Stark Phenotypes for gene: HPDL were changed from Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Progressive neurological disorder; Leigh-like syndrome to Spastic paraplegia-83 (SPG83), MIM#619027; Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Progressive neurological disorder; Leigh-like syndrome
Mendeliome v0.4747 HPDL Zornitza Stark edited their review of gene: HPDL: Added comment: Although two distinct distinct disease associations have been assigned by OMIM, these clinical presentations likely represent a continuum of severity for an underlying mitochondrial disorder.; Changed phenotypes: Spastic paraplegia-83 (SPG83), MIM#619027, Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026
Hereditary Spastic Paraplegia v0.152 HPDL Zornitza Stark changed review comment from: 17 individuals from 13 families, with a spectrum of neurologic impairment ranging from a severe congenital form without any neurological development (n = 2/17, 12%) to infantile-onset presentations (n = 10/17, 59%) with moderate to severe neurodevelopmental issues, partly with a pathology reminiscent of mitochondrial disease (Leigh-like syndrome), to juvenile-onset spastic paraplegia (n = 5/17, 29%).
Sources: Literature; to: 17 individuals from 13 families, with a spectrum of neurologic impairment ranging from a severe congenital form without any neurological development (n = 2/17, 12%) to infantile-onset presentations (n = 10/17, 59%) with moderate to severe neurodevelopmental issues, partly with a pathology reminiscent of mitochondrial disease (Leigh-like syndrome), to juvenile-onset spastic paraplegia (n = 5/17, 29%).

Although two distinct distinct disease associations have been assigned by OMIM, these clinical presentations likely represent a continuum of severity for an underlying mitochondrial disorder.
Sources: Literature
Hereditary Spastic Paraplegia v0.152 HPDL Zornitza Stark edited their review of gene: HPDL: Changed phenotypes: Spastic paraplegia-83 (SPG83), MIM# 619027, Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026, Progressive neurological disorder, Leigh-like syndrome
Genetic Epilepsy v0.874 HPDL Zornitza Stark Marked gene: HPDL as ready
Genetic Epilepsy v0.874 HPDL Zornitza Stark Gene: hpdl has been classified as Green List (High Evidence).
Genetic Epilepsy v0.874 HPDL Zornitza Stark Classified gene: HPDL as Green List (high evidence)
Genetic Epilepsy v0.874 HPDL Zornitza Stark Gene: hpdl has been classified as Green List (High Evidence).
Genetic Epilepsy v0.873 HPDL Zornitza Stark gene: HPDL was added
gene: HPDL was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPDL were set to 32707086
Phenotypes for gene: HPDL were set to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Progressive neurological disorder; Leigh-like syndrome
Review for gene: HPDL was set to GREEN
Added comment: 17 individuals from 13 families, with a spectrum of neurologic impairment ranging from a severe congenital form without any neurological development (n = 2/17, 12%) to infantile-onset presentations (n = 10/17, 59%) with moderate to severe neurodevelopmental issues, partly with a pathology reminiscent of mitochondrial disease (Leigh-like syndrome), to juvenile-onset spastic paraplegia (n = 5/17, 29%).

Seizures/epilepsy were reported in 9/17, 53%.

Frequently observed additional clinical findings included chronic progression of neurological signs (n = 16/17, 94%), motor developmental delay (n = 12/17, 71%), intellectual impairment (n = 11/17, 65%), microcephaly (n = 9/16, 56%) . Other relevant clinical findings were visual disturbances/strabismus (n = 9/17, 53%) and loss of developmental milestones (n = 6/17, 35%).

Acute central respiratory failure leading to life-threatening events requiring partly mechanically assisted ventilation occurred in half of individuals with infantile presentation (n = 5/10, 50%), respectively one third of all individuals (n = 5/17, 29%).

Demyelinating neuropathy was present in three individuals (n = 3/11, 27%), with reduced sensory nerve conduction velocity (NCV) in all and severely reduced motor NCV in one.
Sources: Literature
Regression v0.171 HPDL Zornitza Stark commented on gene: HPDL: 17 individuals from 13 families, with a spectrum of neurologic impairment ranging from a severe congenital form without any neurological development (n = 2/17, 12%) to infantile-onset presentations (n = 10/17, 59%) with moderate to severe neurodevelopmental issues, partly with a pathology reminiscent of mitochondrial disease (Leigh-like syndrome), to juvenile-onset spastic paraplegia (n = 5/17, 29%).

Frequently observed clinical findings included chronic progression of neurological signs (n = 16/17, 94%), motor developmental delay (n = 12/17, 71%), intellectual impairment (n = 11/17, 65%), microcephaly (n = 9/16, 56%), and seizures/epilepsy (n = 9/17, 53%). Other relevant clinical findings were visual disturbances/strabismus (n = 9/17, 53%) and loss of developmental milestones (n = 6/17, 35%).

Acute central respiratory failure leading to life-threatening events requiring partly mechanically assisted ventilation occurred in half of individuals with infantile presentation (n = 5/10, 50%), respectively one third of all individuals (n = 5/17, 29%).

Demyelinating neuropathy was present in three individuals (n = 3/11, 27%), with reduced sensory nerve conduction velocity (NCV) in all and severely reduced motor NCV in one.
Mitochondrial disease v0.508 HPDL Zornitza Stark edited their review of gene: HPDL: Added comment: 17 individuals from 13 families, with a spectrum of neurologic impairment ranging from a severe congenital form without any neurological development (n = 2/17, 12%) to infantile-onset presentations (n = 10/17, 59%) with moderate to severe neurodevelopmental issues, partly with a pathology reminiscent of mitochondrial disease (Leigh-like syndrome), to juvenile-onset spastic paraplegia (n = 5/17, 29%).

Frequently observed clinical findings included chronic progression of neurological signs (n = 16/17, 94%), motor developmental delay (n = 12/17, 71%), intellectual impairment (n = 11/17, 65%), microcephaly (n = 9/16, 56%), and seizures/epilepsy (n = 9/17, 53%). Other relevant clinical findings were visual disturbances/strabismus (n = 9/17, 53%) and loss of developmental milestones (n = 6/17, 35%).

Acute central respiratory failure leading to life-threatening events requiring partly mechanically assisted ventilation occurred in half of individuals with infantile presentation (n = 5/10, 50%), respectively one third of all individuals (n = 5/17, 29%).

Demyelinating neuropathy was present in three individuals (n = 3/11, 27%), with reduced sensory nerve conduction velocity (NCV) in all and severely reduced motor NCV in one.; Changed publications: 32707086; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v0.152 HPDL Zornitza Stark Marked gene: HPDL as ready
Hereditary Spastic Paraplegia v0.152 HPDL Zornitza Stark Gene: hpdl has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.152 HPDL Zornitza Stark Classified gene: HPDL as Green List (high evidence)
Hereditary Spastic Paraplegia v0.152 HPDL Zornitza Stark Gene: hpdl has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.151 HPDL Zornitza Stark gene: HPDL was added
gene: HPDL was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPDL were set to 32707086
Phenotypes for gene: HPDL were set to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Progressive neurological disorder; Leigh-like syndrome
Review for gene: HPDL was set to GREEN
Added comment: 17 individuals from 13 families, with a spectrum of neurologic impairment ranging from a severe congenital form without any neurological development (n = 2/17, 12%) to infantile-onset presentations (n = 10/17, 59%) with moderate to severe neurodevelopmental issues, partly with a pathology reminiscent of mitochondrial disease (Leigh-like syndrome), to juvenile-onset spastic paraplegia (n = 5/17, 29%).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3050 HPDL Zornitza Stark changed review comment from: Intellectual impairment is variable, ranging from poor visual contact with inability to walk or speak to milder intellectual disability with the ability to say some words.; to: 17 individuals from 13 families, with a spectrum of neurologic impairment ranging from a severe congenital form without any neurological development (n = 2/17, 12%) to infantile-onset presentations (n = 10/17, 59%) with moderate to severe neurodevelopmental issues, partly with a pathology reminiscent of mitochondrial disease (Leigh-like syndrome), to juvenile-onset spastic paraplegia (n = 5/17, 29%).

Intellectual impairment is variable, ranging from poor visual contact with inability to walk or speak to milder intellectual disability with the ability to say some words.

Frequently observed additional clinical findings included chronic progression of neurological signs (n = 16/17, 94%), microcephaly (n = 9/16, 56%), and seizures/epilepsy (n = 9/17, 53%). Other relevant clinical findings were visual disturbances/strabismus (n = 9/17, 53%) and loss of developmental milestones (n = 6/17, 35%).

Acute central respiratory failure leading to life-threatening events requiring partly mechanically assisted ventilation occurred in half of individuals with infantile presentation (n = 5/10, 50%), respectively one third of all individuals (n = 5/17, 29%).

Demyelinating neuropathy was present in three individuals (n = 3/11, 27%), with reduced sensory nerve conduction velocity (NCV) in all and severely reduced motor NCV in one.
Mendeliome v0.4747 HPDL Zornitza Stark commented on gene: HPDL: 17 individuals from 13 families, with a spectrum of neurologic impairment ranging from a severe congenital form without any neurological development (n = 2/17, 12%) to infantile-onset presentations (n = 10/17, 59%) with moderate to severe neurodevelopmental issues, partly with a pathology reminiscent of mitochondrial disease (Leigh-like syndrome), to juvenile-onset spastic paraplegia (n = 5/17, 29%).

Frequently observed clinical findings included chronic progression of neurological signs (n = 16/17, 94%), motor developmental delay (n = 12/17, 71%), intellectual impairment (n = 11/17, 65%), microcephaly (n = 9/16, 56%), and seizures/epilepsy (n = 9/17, 53%). Other relevant clinical findings were visual disturbances/strabismus (n = 9/17, 53%) and loss of developmental milestones (n = 6/17, 35%).

Acute central respiratory failure leading to life-threatening events requiring partly mechanically assisted ventilation occurred in half of individuals with infantile presentation (n = 5/10, 50%), respectively one third of all individuals (n = 5/17, 29%).

Demyelinating neuropathy was present in three individuals (n = 3/11, 27%), with reduced sensory nerve conduction velocity (NCV) in all and severely reduced motor NCV in one.
Leukodystrophy v0.205 HPDL Zornitza Stark Marked gene: HPDL as ready
Leukodystrophy v0.205 HPDL Zornitza Stark Gene: hpdl has been classified as Green List (High Evidence).
Leukodystrophy v0.205 HPDL Zornitza Stark Classified gene: HPDL as Green List (high evidence)
Leukodystrophy v0.205 HPDL Zornitza Stark Gene: hpdl has been classified as Green List (High Evidence).
Leukodystrophy v0.204 HPDL Zornitza Stark gene: HPDL was added
gene: HPDL was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPDL were set to 32707086
Phenotypes for gene: HPDL were set to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Progressive neurological disorder; Leigh-like syndrome
Review for gene: HPDL was set to GREEN
Added comment: Biallelic variants reported in 13 families with a neurodegenerative disease ranging from neonatal encephalopathy to adolescent-onset spastic paraplegia. Extensive MRI abnormalities described, primarily affecting white matter (white matter atrophy and deficient myelination), basal ganglia, thalamus and brainstem.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3050 HPDL Zornitza Stark Phenotypes for gene: HPDL were changed from Progressive neurological disorder; Leigh-like syndrome to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Progressive neurological disorder; Leigh-like syndrome
Intellectual disability syndromic and non-syndromic v0.3049 HPDL Zornitza Stark reviewed gene: HPDL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Mode of inheritance: None
Regression v0.171 HPDL Zornitza Stark Phenotypes for gene: HPDL were changed from Progressive neurological disorder; Leigh-like syndrome to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Progressive neurological disorder; Leigh-like syndrome
Regression v0.170 HPDL Zornitza Stark reviewed gene: HPDL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Mode of inheritance: None
Mitochondrial disease v0.508 HPDL Zornitza Stark Phenotypes for gene: HPDL were changed from Progressive neurological disorder; Leigh-like syndrome to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Progressive neurological disorder; Leigh-like syndrome
Mitochondrial disease v0.507 HPDL Zornitza Stark edited their review of gene: HPDL: Changed rating: GREEN; Changed phenotypes: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026
Mendeliome v0.4747 HPDL Zornitza Stark Phenotypes for gene: HPDL were changed from Progressive neurological disorder; Leigh-like syndrome to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Progressive neurological disorder; Leigh-like syndrome
Mendeliome v0.4746 HPDL Zornitza Stark edited their review of gene: HPDL: Changed rating: GREEN
Mendeliome v0.4746 HPDL Zornitza Stark reviewed gene: HPDL: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Mode of inheritance: None
Mendeliome v0.4746 SCN1A Zornitza Stark Publications for gene: SCN1A were set to 30368457; 12754708; 25754450; 32928894
Mendeliome v0.4745 SCN1A Zornitza Stark edited their review of gene: SCN1A: Changed publications: 29543227
Mendeliome v0.4745 SCN1A Zornitza Stark Phenotypes for gene: SCN1A were changed from Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208 to Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208; Genetic Epilepsy Febrile Seizures plus (GEFS+) Syndrome; Febrile seizures; Arthrogryposis multiplex congenita
Mendeliome v0.4744 SCN1A Zornitza Stark Publications for gene: SCN1A were set to 30368457; 12754708; 25754450
Mendeliome v0.4743 SCN1A Zornitza Stark edited their review of gene: SCN1A: Added comment: Note we have reported the association with AMC previously in PMID 29543227 (Supplementary info) in an infant presenting with AMC and severe EE, and de novo p.(Ile1347Asn) variant which at the time was thought to only partially explain the phenotype, but in light of this new report, likely fully explains the phenotype. Given the presence of severe seizure disorder in the two infants who were phenotyped in the newborn period, this likely represents the severe end of the spectrum of SCN1A-related disorders rather than a distinct association.; Changed phenotypes: Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208, Genetic Epilepsy Febrile Seizures plus (GEFS+) Syndrome, Febrile seizures, Arthrogryposis multiplex congenita
Mendeliome v0.4743 SCN1A Zornitza Stark Deleted their comment
Arthrogryposis v0.217 SCN1A Zornitza Stark edited their review of gene: SCN1A: Changed phenotypes: Dravet syndrome, MIM# 607208, Arthrogryposis multiplex congenita
Arthrogryposis v0.217 SCN1A Zornitza Stark edited their review of gene: SCN1A: Changed phenotypes: Dravet syndrome, MIM# 607208
Arthrogryposis v0.217 SCN1A Zornitza Stark Phenotypes for gene: SCN1A were changed from Arthrogryposis multiplex congenita to Arthrogryposis multiplex congenita; Dravet syndrome, MIM# 607208
Arthrogryposis v0.216 SCN1A Zornitza Stark Marked gene: SCN1A as ready
Arthrogryposis v0.216 SCN1A Zornitza Stark Gene: scn1a has been classified as Green List (High Evidence).
Arthrogryposis v0.216 SCN1A Zornitza Stark Classified gene: SCN1A as Green List (high evidence)
Arthrogryposis v0.216 SCN1A Zornitza Stark Gene: scn1a has been classified as Green List (High Evidence).
Arthrogryposis v0.215 SCN1A Zornitza Stark gene: SCN1A was added
gene: SCN1A was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: SCN1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN1A were set to 32928894; 29543227
Phenotypes for gene: SCN1A were set to Arthrogryposis multiplex congenita
Review for gene: SCN1A was set to GREEN
Added comment: Note SCN1A is a well-established cause of Dravet syndrome, MIM# 607208
-----
PMID: 32928894 (2020) - De novo missense variants in SCN1A (p.Leu893Phe, p.Ala989Thr, p.Ile236Thr) were identified in three unrelated patients with AMC which was diagnosed from the second trimester of pregnancy. One patient developed intractable epilepsy from birth and died at 21 days, while the other two pregnancies were terminated.

Note we have reported this association previously in PMID 29543227 (Supplementary info) in an infant presenting with AMC and severe EE, and de novo p.(Ile1347Asn) variant which at the time was thought to only partially explain the phenotype, but in light of this new report, likely fully explains the phenotype. Given the presence of severe seizure disorder in the two infants who were phenotype in the newborn period, this likely represents the severe end of the spectrum of SCN1A-related disorders rather than a distinct association.
Sources: Literature
Hereditary Haemorrhagic Telangiectasia v0.11 RASA1 Zornitza Stark Publications for gene: RASA1 were set to 27081547; 29891884; 30507091
Mendeliome v0.4743 PRKD1 Zornitza Stark changed review comment from: PMID: 32817298 (2020) - Two additional unrelated cases with de novo variants, c.1774G>C and c.1808G>A, and telangiectasia, ectodermal dysplasia, brachydactyly and congenital heart disease. Functional analysis using in vitro kinase assays with recombinant proteins showed that the c.1808G>A, p.(Arg603His) variant represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity. The c.1774G>C, p.(Gly592Arg) variant in contrast shows a defect in substrate phosphorylation representing a loss-of-function mutation.

c.1774G>C, p.(Gly592Arg) is recurrent, reported in 3/5 individuals.; to: PMID: 27479907 (2016): three individuals reported, two with the c.1774G>A variant and one with the c.896T>G variant. All had congenital heart disease, two had some developmental delay, and two had variable features of ectodermal dysplasia, including sparse hair, dry skin, thin skin, fragile nails, premature loss of primary teeth, and small widely spaced teeth; the third individuals had a 'disorganized eyebrow.'

PMID: 32817298 (2020) - Two additional unrelated cases with de novo variants, c.1774G>C and c.1808G>A, and telangiectasia, ectodermal dysplasia, brachydactyly and congenital heart disease. Functional analysis using in vitro kinase assays with recombinant proteins showed that the c.1808G>A, p.(Arg603His) variant represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity. The c.1774G>C, p.(Gly592Arg) variant in contrast shows a defect in substrate phosphorylation representing a loss-of-function mutation.

c.1774G>C, p.(Gly592Arg) is recurrent, reported in 3/5 individuals.
Congenital Heart Defect v0.70 PRKD1 Zornitza Stark changed review comment from: PMID: 32817298 (2020) - Two additional unrelated cases with de novo variants, c.1774G>C and c.1808G>A, and telangiectasia, ectodermal dysplasia, brachydactyly and congenital heart disease. Functional analysis using in vitro kinase assays with recombinant proteins showed that the c.1808G>A, p.(Arg603His) variant represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity. The c.1774G>C, p.(Gly592Arg) variant in contrast shows a defect in substrate phosphorylation representing a loss-of-function mutation.

c.1774G>C, p.(Gly592Arg) is recurrent, reported in 3/5 individuals.; to: PMID: 27479907 (2016): three individuals reported, two with the c.1774G>A variant and one with the c.896T>G variant. All had congenital heart disease, two had some developmental delay, and two had variable features of ectodermal dysplasia, including sparse hair, dry skin, thin skin, fragile nails, premature loss of primary teeth, and small widely spaced teeth; the third individuals had a 'disorganized eyebrow.'

PMID: 32817298 (2020) - Two additional unrelated cases with de novo variants, c.1774G>C and c.1808G>A, and telangiectasia, ectodermal dysplasia, brachydactyly and congenital heart disease. Functional analysis using in vitro kinase assays with recombinant proteins showed that the c.1808G>A, p.(Arg603His) variant represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity. The c.1774G>C, p.(Gly592Arg) variant in contrast shows a defect in substrate phosphorylation representing a loss-of-function mutation.

c.1774G>C, p.(Gly592Arg) is recurrent, reported in 3/5 individuals.
Ectodermal Dysplasia v0.24 PRKD1 Zornitza Stark reviewed gene: PRKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27479907, 32817298; Phenotypes: Congenital heart defects and ectodermal dysplasia, MIM# 617364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4743 PRKD1 Zornitza Stark Publications for gene: PRKD1 were set to 27479907
Mendeliome v0.4742 PRKD1 Zornitza Stark reviewed gene: PRKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27479907, 32817298; Phenotypes: Congenital heart defects and ectodermal dysplasia, 617364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.70 PRKD1 Zornitza Stark Publications for gene: PRKD1 were set to 27479907
Congenital Heart Defect v0.70 PRKD1 Zornitza Stark Mode of pathogenicity for gene: PRKD1 was changed from to Other
Congenital Heart Defect v0.69 PRKD1 Zornitza Stark edited their review of gene: PRKD1: Added comment: PMID: 32817298 (2020) - Two additional unrelated cases with de novo variants, c.1774G>C and c.1808G>A, and telangiectasia, ectodermal dysplasia, brachydactyly and congenital heart disease. Functional analysis using in vitro kinase assays with recombinant proteins showed that the c.1808G>A, p.(Arg603His) variant represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity. The c.1774G>C, p.(Gly592Arg) variant in contrast shows a defect in substrate phosphorylation representing a loss-of-function mutation.

c.1774G>C, p.(Gly592Arg) is recurrent, reported in 3/5 individuals.; Changed publications: 27479907, 32817298
Intellectual disability syndromic and non-syndromic v0.3049 PRKD1 Zornitza Stark Marked gene: PRKD1 as ready
Intellectual disability syndromic and non-syndromic v0.3049 PRKD1 Zornitza Stark Added comment: Comment when marking as ready: Literature reviewed again: ID/DD reported in 2/5 but unclear at present if this is part of the phenotype given low number of affected individuals.
Intellectual disability syndromic and non-syndromic v0.3049 PRKD1 Zornitza Stark Gene: prkd1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3049 PRKD1 Zornitza Stark Publications for gene: PRKD1 were set to 27479907
Intellectual disability syndromic and non-syndromic v0.3048 PRKD1 Zornitza Stark Classified gene: PRKD1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3048 PRKD1 Zornitza Stark Gene: prkd1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4742 SCN1A Arina Puzriakova reviewed gene: SCN1A: Rating: AMBER; Mode of pathogenicity: None; Publications: 32928894; Phenotypes: Arthrogryposis multiplex congenita; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary Haemorrhagic Telangiectasia v0.10 RASA1 Arina Puzriakova reviewed gene: RASA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32900839; Phenotypes: Capillary malformation-arteriovenous malformation 1, 608354; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.3047 PRKD1 Arina Puzriakova reviewed gene: PRKD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27479907, 32817298; Phenotypes: Congenital heart defects and ectodermal dysplasia, 617364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4742 SIX1 Zornitza Stark Marked gene: SIX1 as ready
Mendeliome v0.4742 SIX1 Zornitza Stark Gene: six1 has been classified as Green List (High Evidence).
Mendeliome v0.4742 SIX1 Zornitza Stark Phenotypes for gene: SIX1 were changed from to Deafness, autosomal dominant 23, MIM# 605192; Branchiootic syndrome 3, MIM# 608389
Mendeliome v0.4741 SIX1 Zornitza Stark Publications for gene: SIX1 were set to
Mendeliome v0.4740 SIX1 Zornitza Stark Mode of inheritance for gene: SIX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4739 SIX1 Zornitza Stark reviewed gene: SIX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15141091, 18330911, 21254961, 17637804, 29500469, 21700001, 24164807; Phenotypes: Deafness, autosomal dominant 23, MIM# 605192, Branchiootic syndrome 3, MIM# 608389; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.558 SIX1 Zornitza Stark Marked gene: SIX1 as ready
Deafness_IsolatedAndComplex v0.558 SIX1 Zornitza Stark Gene: six1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.558 SIX1 Zornitza Stark Phenotypes for gene: SIX1 were changed from to Deafness, autosomal dominant 23, MIM# 605192; Branchiootic syndrome 3, MIM# 608389
Deafness_IsolatedAndComplex v0.557 SIX1 Zornitza Stark Publications for gene: SIX1 were set to
Deafness_IsolatedAndComplex v0.556 SIX1 Zornitza Stark Mode of inheritance for gene: SIX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.555 SIX1 Zornitza Stark reviewed gene: SIX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15141091, 18330911, 21254961, 17637804, 29500469, 21700001, 24164807; Phenotypes: Deafness, autosomal dominant 23, MIM# 605192, Branchiootic syndrome 3, MIM# 608389; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4739 PTPRQ Zornitza Stark Marked gene: PTPRQ as ready
Mendeliome v0.4739 PTPRQ Zornitza Stark Gene: ptprq has been classified as Green List (High Evidence).
Mendeliome v0.4739 PTPRQ Zornitza Stark Phenotypes for gene: PTPRQ were changed from to Deafness, autosomal recessive 84A, MIM# 613391; Deafness, autosomal dominant 73, MIM# 617663
Mendeliome v0.4738 PTPRQ Zornitza Stark Publications for gene: PTPRQ were set to
Mendeliome v0.4737 PTPRQ Zornitza Stark Mode of inheritance for gene: PTPRQ was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4736 PTPRQ Zornitza Stark reviewed gene: PTPRQ: Rating: GREEN; Mode of pathogenicity: None; Publications: 20346435, 20472657, 25919374, 14534255, 22357859, 29849575, 29309402, 31655630; Phenotypes: Deafness, autosomal recessive 84A, MIM# 613391, Deafness, autosomal dominant 73, MIM# 617663; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.555 PTPRQ Zornitza Stark Phenotypes for gene: PTPRQ were changed from Deafness, autosomal recessive 84A, MIM# 613391 to Deafness, autosomal recessive 84A, MIM# 613391; Deafness, autosomal dominant 73, MIM# 617663
Deafness_IsolatedAndComplex v0.554 PTPRQ Zornitza Stark edited their review of gene: PTPRQ: Changed phenotypes: Deafness, autosomal recessive 84A, MIM# 613391, Deafness, autosomal dominant 73, MIM# 617663
Deafness_IsolatedAndComplex v0.554 PTPRQ Zornitza Stark Marked gene: PTPRQ as ready
Deafness_IsolatedAndComplex v0.554 PTPRQ Zornitza Stark Gene: ptprq has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.554 PTPRQ Zornitza Stark Phenotypes for gene: PTPRQ were changed from to Deafness, autosomal recessive 84A, MIM# 613391
Deafness_IsolatedAndComplex v0.553 PTPRQ Zornitza Stark Publications for gene: PTPRQ were set to
Deafness_IsolatedAndComplex v0.552 PTPRQ Zornitza Stark Mode of inheritance for gene: PTPRQ was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.551 PTPRQ Zornitza Stark reviewed gene: PTPRQ: Rating: GREEN; Mode of pathogenicity: None; Publications: 20346435, 20472657, 25919374, 14534255, 22357859, 29849575, 29309402, 31655630; Phenotypes: Deafness, autosomal recessive 84A, MIM# 613391; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.551 PRPS1 Zornitza Stark Marked gene: PRPS1 as ready
Deafness_IsolatedAndComplex v0.551 PRPS1 Zornitza Stark Gene: prps1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.551 PRPS1 Zornitza Stark Phenotypes for gene: PRPS1 were changed from to Deafness, X-linked 1, MIM# 304500; Charcot-Marie-Tooth disease, X-linked recessive, 5, MIM# 311070; Arts syndrome, MIM# 301835
Deafness_IsolatedAndComplex v0.550 PRPS1 Zornitza Stark Publications for gene: PRPS1 were set to
Deafness_IsolatedAndComplex v0.549 PRPS1 Zornitza Stark Mode of inheritance for gene: PRPS1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Deafness_IsolatedAndComplex v0.548 PRPS1 Zornitza Stark reviewed gene: PRPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24961627, 20021999, 27886419, 25785835, 25182139, 17701900, 25491489, 27256512; Phenotypes: Deafness, X-linked 1, MIM# 304500, Charcot-Marie-Tooth disease, X-linked recessive, 5, MIM# 311070, Arts syndrome, MIM# 301835; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Deafness_IsolatedAndComplex v0.548 POU4F3 Zornitza Stark changed review comment from: The hearing loss in DFNA15 individuals is progressive, with a highly variable age of onset between the second and fifth decades of life. The mechanism for disease is likely haploinsufficiency, due to the wide variant spectrum, however mice require only one copy of the functional gene to retain hearing. Over 80 affected individuals reported. Gene-disease association is supported by multiple lines of functional evidence.; to: The hearing loss in DFNA15 individuals is progressive, with a highly variable age of onset between the second and fifth decades of life. The mechanism for disease is likely haploinsufficiency, due to the wide variant spectrum, however mice require only one copy of the functional gene to retain hearing. Over 80 affected individuals reported. Gene-disease association is supported by multiple lines of functional evidence. DEFINITIVE by ClinGen.
Mendeliome v0.4736 POU4F3 Zornitza Stark Marked gene: POU4F3 as ready
Mendeliome v0.4736 POU4F3 Zornitza Stark Gene: pou4f3 has been classified as Green List (High Evidence).
Mendeliome v0.4736 POU4F3 Zornitza Stark Phenotypes for gene: POU4F3 were changed from to Deafness, autosomal dominant 15, MIM# 602459
Mendeliome v0.4735 POU4F3 Zornitza Stark Publications for gene: POU4F3 were set to
Mendeliome v0.4734 POU4F3 Zornitza Stark Mode of inheritance for gene: POU4F3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4733 POU4F3 Zornitza Stark reviewed gene: POU4F3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18228599, 9506947, 20434433, 28545070, 15254021, 8637595; Phenotypes: Deafness, autosomal dominant 15, MIM# 602459; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.548 POU4F3 Zornitza Stark Marked gene: POU4F3 as ready
Deafness_IsolatedAndComplex v0.548 POU4F3 Zornitza Stark Gene: pou4f3 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.548 POU4F3 Zornitza Stark Phenotypes for gene: POU4F3 were changed from to Deafness, autosomal dominant 15, MIM# 602459
Deafness_IsolatedAndComplex v0.547 POU4F3 Zornitza Stark Publications for gene: POU4F3 were set to
Deafness_IsolatedAndComplex v0.546 POU4F3 Zornitza Stark Mode of inheritance for gene: POU4F3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.545 POU4F3 Zornitza Stark reviewed gene: POU4F3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18228599, 9506947, 20434433, 28545070, 15254021, 8637595; Phenotypes: Deafness, autosomal dominant 15, MIM# 602459; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.545 PDZD7 Zornitza Stark Marked gene: PDZD7 as ready
Deafness_IsolatedAndComplex v0.545 PDZD7 Zornitza Stark Gene: pdzd7 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.545 PDZD7 Zornitza Stark Phenotypes for gene: PDZD7 were changed from to Deafness, autosomal recessive 57, MIM# 618003
Deafness_IsolatedAndComplex v0.544 PDZD7 Zornitza Stark Publications for gene: PDZD7 were set to
Deafness_IsolatedAndComplex v0.543 PDZD7 Zornitza Stark Mode of inheritance for gene: PDZD7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.542 PDZD7 Zornitza Stark reviewed gene: PDZD7: Rating: GREEN; Mode of pathogenicity: None; Publications: 19028668, 26416264, 26849169, 27068579, 26445815, 28173822, 24334608; Phenotypes: Deafness, autosomal recessive 57, MIM# 618003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.171 IGSF10 Zornitza Stark edited their review of gene: IGSF10: Changed rating: AMBER
Differences of Sex Development v0.171 IGSF10 Zornitza Stark Marked gene: IGSF10 as ready
Differences of Sex Development v0.171 IGSF10 Zornitza Stark Gene: igsf10 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.171 IGSF10 Zornitza Stark Classified gene: IGSF10 as Amber List (moderate evidence)
Differences of Sex Development v0.171 IGSF10 Zornitza Stark Gene: igsf10 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.170 IGSF10 Zornitza Stark gene: IGSF10 was added
gene: IGSF10 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: IGSF10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IGSF10 were set to 27137492; 31042289
Phenotypes for gene: IGSF10 were set to delayed puberty; hypogonadotropic hypogonadism; primary ovary insufficiency
Added comment: PMID: 27137492 - 4 Finnish families segregating p.Glu161Lys, but Finnish MAF in ExAC is 2%. Another six additional families with a possible missense, but variants are seen in ExAC suggesting incomplete penetrance. Supporting in vitro functional assays and zebrafish model. PMID: 31042289 - 2 unrelated consanguineous families with homozygous variants and family with a heterozygous frameshift and apparent incomplete penetrance.
Sources: Expert list
Macrocephaly_Megalencephaly v0.54 KPTN Zornitza Stark Marked gene: KPTN as ready
Macrocephaly_Megalencephaly v0.54 KPTN Zornitza Stark Gene: kptn has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.54 KPTN Zornitza Stark Classified gene: KPTN as Green List (high evidence)
Macrocephaly_Megalencephaly v0.54 KPTN Zornitza Stark Gene: kptn has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.53 KPTN Zornitza Stark gene: KPTN was added
gene: KPTN was added to Macrocephaly_Megalencephaly. Sources: Expert Review
Mode of inheritance for gene: KPTN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KPTN were set to 24239382; 32358097; 32808430
Phenotypes for gene: KPTN were set to Mental retardation, autosomal recessive 41 (MIM#615637)
Review for gene: KPTN was set to GREEN
Added comment: 15 patients (9 from Amish families) reported with macrocephaly and intellectual disability with hom or chet variants in KPTN (PMID: 32808430).
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.3047 KPTN Zornitza Stark Marked gene: KPTN as ready
Intellectual disability syndromic and non-syndromic v0.3047 KPTN Zornitza Stark Gene: kptn has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3047 KPTN Zornitza Stark Phenotypes for gene: KPTN were changed from to Mental retardation, autosomal recessive 41 (MIM#615637)
Intellectual disability syndromic and non-syndromic v0.3046 KPTN Zornitza Stark Publications for gene: KPTN were set to
Intellectual disability syndromic and non-syndromic v0.3045 KPTN Zornitza Stark Mode of inheritance for gene: KPTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3044 KPTN Zornitza Stark reviewed gene: KPTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 24239382, 32358097, 32808430; Phenotypes: Mental retardation, autosomal recessive 41 (MIM#615637); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.872 KPTN Zornitza Stark Publications for gene: KPTN were set to 25847626; 24239382; 32358097; 32808430
Genetic Epilepsy v0.871 KPTN Zornitza Stark Publications for gene: KPTN were set to 25847626; 24239382
Genetic Epilepsy v0.870 KPTN Zornitza Stark Classified gene: KPTN as Green List (high evidence)
Genetic Epilepsy v0.870 KPTN Zornitza Stark Gene: kptn has been classified as Green List (High Evidence).
Genetic Epilepsy v0.869 KPTN Zornitza Stark edited their review of gene: KPTN: Added comment: Two further publications (PMID 32358097; 32808430), more individuals reported with seizures, upgrade to Green.; Changed rating: GREEN; Changed publications: 25847626, 24239382, 32358097, 32808430
Mendeliome v0.4733 KPTN Zornitza Stark Marked gene: KPTN as ready
Mendeliome v0.4733 KPTN Zornitza Stark Gene: kptn has been classified as Green List (High Evidence).
Mendeliome v0.4733 KPTN Zornitza Stark Phenotypes for gene: KPTN were changed from to Mental retardation, autosomal recessive 41 (MIM#615637)
Mendeliome v0.4732 KPTN Zornitza Stark Publications for gene: KPTN were set to
Mendeliome v0.4731 KPTN Zornitza Stark Mode of inheritance for gene: KPTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Paroxysmal Dyskinesia v0.82 RHOBTB2 Zornitza Stark Marked gene: RHOBTB2 as ready
Paroxysmal Dyskinesia v0.82 RHOBTB2 Zornitza Stark Gene: rhobtb2 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.82 RHOBTB2 Zornitza Stark Phenotypes for gene: RHOBTB2 were changed from Paroxysmal movement disorder to Epileptic encephalopathy, early infantile, 64, MIM# 618004; Paroxysmal movement disorder
Paroxysmal Dyskinesia v0.81 RHOBTB2 Zornitza Stark Classified gene: RHOBTB2 as Green List (high evidence)
Paroxysmal Dyskinesia v0.81 RHOBTB2 Zornitza Stark Gene: rhobtb2 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.80 RHOBTB2 Zornitza Stark reviewed gene: RHOBTB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 64, MIM# 618004; Mode of inheritance: None
Dystonia and Chorea v0.144 RHOBTB2 Zornitza Stark Marked gene: RHOBTB2 as ready
Dystonia and Chorea v0.144 RHOBTB2 Zornitza Stark Gene: rhobtb2 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.144 RHOBTB2 Zornitza Stark Phenotypes for gene: RHOBTB2 were changed from Dystonia, hypertonia, movement disorder; truncal hypotonia; hemiparesis; developmental and epileptic encephalopathy to Epileptic encephalopathy, early infantile, 64, MIM# 618004; Dystonia, hypertonia, movement disorder; truncal hypotonia; hemiparesis; developmental and epileptic encephalopathy
Dystonia and Chorea v0.143 RHOBTB2 Zornitza Stark Classified gene: RHOBTB2 as Green List (high evidence)
Dystonia and Chorea v0.143 RHOBTB2 Zornitza Stark Gene: rhobtb2 has been classified as Green List (High Evidence).
Mendeliome v0.4730 NPHS1 Zornitza Stark Marked gene: NPHS1 as ready
Mendeliome v0.4730 NPHS1 Zornitza Stark Gene: nphs1 has been classified as Green List (High Evidence).
Mendeliome v0.4730 NPHS1 Zornitza Stark Phenotypes for gene: NPHS1 were changed from to Nephrotic syndrome, type 1, MIM# 256300
Mendeliome v0.4729 NPHS1 Zornitza Stark Mode of inheritance for gene: NPHS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4728 TTI2 Zornitza Stark Marked gene: TTI2 as ready
Mendeliome v0.4728 TTI2 Zornitza Stark Gene: tti2 has been classified as Green List (High Evidence).
Mendeliome v0.4728 TTI2 Zornitza Stark Phenotypes for gene: TTI2 were changed from to Mental retardation, autosomal recessive 39, MIM#615541
Mendeliome v0.4727 TTI2 Zornitza Stark Publications for gene: TTI2 were set to
Mendeliome v0.4726 TTI2 Zornitza Stark Mode of inheritance for gene: TTI2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4725 TTI2 Zornitza Stark reviewed gene: TTI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32061250, 23956177, 31737043; Phenotypes: Mental retardation, autosomal recessive 39, MIM#615541; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3044 TTI2 Zornitza Stark Marked gene: TTI2 as ready
Intellectual disability syndromic and non-syndromic v0.3044 TTI2 Zornitza Stark Gene: tti2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3044 TTI2 Zornitza Stark Phenotypes for gene: TTI2 were changed from to Mental retardation, autosomal recessive 39 (MIM#615541) AR
Intellectual disability syndromic and non-syndromic v0.3043 TTI2 Zornitza Stark Publications for gene: TTI2 were set to
Intellectual disability syndromic and non-syndromic v0.3042 TTI2 Zornitza Stark Mode of inheritance for gene: TTI2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.38 IGSF10 Bryony Thompson Marked gene: IGSF10 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.38 IGSF10 Bryony Thompson Gene: igsf10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4725 IGSF10 Bryony Thompson Marked gene: IGSF10 as ready
Mendeliome v0.4725 IGSF10 Bryony Thompson Gene: igsf10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4725 IGSF10 Bryony Thompson Classified gene: IGSF10 as Amber List (moderate evidence)
Mendeliome v0.4725 IGSF10 Bryony Thompson Gene: igsf10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4724 IGSF10 Bryony Thompson gene: IGSF10 was added
gene: IGSF10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IGSF10 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: IGSF10 were set to 27137492; 31042289
Phenotypes for gene: IGSF10 were set to delayed puberty; hypogonadotropic hypogonadism; primary ovary insufficiency
Review for gene: IGSF10 was set to AMBER
Added comment: PMID: 27137492 - 4 Finnish families segregating p.Glu161Lys, but Finnish MAF in ExAC is 2%. Another six additional families with a possible missense, but variants are seen in ExAC suggesting incomplete penetrance. Supporting in vitro functional assays and zebrafish model. PMID: 31042289 - 2 unrelated consanguineous families with homozygous variants and family with a heterozygous frameshift and apparent incomplete penetrance.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.38 IGSF10 Bryony Thompson Classified gene: IGSF10 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.38 IGSF10 Bryony Thompson Gene: igsf10 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.37 IGSF10 Bryony Thompson edited their review of gene: IGSF10: Changed phenotypes: delayed puberty, hypogonadotropic hypogonadism, primary ovary insufficiency
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.37 IGSF10 Bryony Thompson gene: IGSF10 was added
gene: IGSF10 was added to Amenorrhoea. Sources: Literature
Mode of inheritance for gene: IGSF10 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: IGSF10 were set to 27137492; 31042289
Phenotypes for gene: IGSF10 were set to delayed puberty; hypogonadotropic hypogonadism
Review for gene: IGSF10 was set to AMBER
Added comment: PMID: 27137492 - 4 Finnish families segregating p.Glu161Lys, but Finnish MAF in ExAC is 2%. Another six additional families with a possible missense, but variants are seen in ExAC suggesting incomplete penetrance. Supporting in vitro functional assays and zebrafish model. PMID: 31042289 - 2 unrelated consanguineous families with homozygous variants and family with a heterozygous frameshift and apparent incomplete penetrance.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.36 HNF1B Bryony Thompson Classified gene: HNF1B as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.36 HNF1B Bryony Thompson Gene: hnf1b has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.35 HNF1B Bryony Thompson reviewed gene: HNF1B: Rating: RED; Mode of pathogenicity: None; Publications: 23431465; Phenotypes: Mayer-rokitansky-kuster-hauser syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Proteinuria v0.137 MAFB Zornitza Stark Marked gene: MAFB as ready
Proteinuria v0.137 MAFB Zornitza Stark Gene: mafb has been classified as Green List (High Evidence).
Mendeliome v0.4723 KPTN Melanie Marty reviewed gene: KPTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 24239382, 32358097, 32808430; Phenotypes: Mental retardation, autosomal recessive 41 (MIM#615637); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paroxysmal Dyskinesia v0.80 RHOBTB2 Eunice Chan gene: RHOBTB2 was added
gene: RHOBTB2 was added to Paroxysmal Dyskinesia. Sources: Other
Mode of inheritance for gene: RHOBTB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RHOBTB2 were set to PMID 29276004
Phenotypes for gene: RHOBTB2 were set to Paroxysmal movement disorder
Added comment: At least 5/10 patients described had paroxysmal, or chorea-like movements
8/10 have a movement disorder
Sources: Other
Dystonia and Chorea v0.142 RHOBTB2 Eunice Chan gene: RHOBTB2 was added
gene: RHOBTB2 was added to Dystonia - complex. Sources: Other
Mode of inheritance for gene: RHOBTB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RHOBTB2 were set to PMID: 29276004
Phenotypes for gene: RHOBTB2 were set to Dystonia, hypertonia, movement disorder; truncal hypotonia; hemiparesis; developmental and epileptic encephalopathy
Added comment: 8/10 patients described had dystonic, paroxysmal, or chorea-like movements
Sources: Other
Mendeliome v0.4723 NPHS1 Elena Savva reviewed gene: NPHS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nephrotic syndrome, type 1 256300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3041 TTI2 Michelle Torres reviewed gene: TTI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32061250, 23956177, 31737043; Phenotypes: Mental retardation, autosomal recessive 39 (MIM#615541) AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuria v0.137 MAFB Chirag Patel Classified gene: MAFB as Green List (high evidence)
Proteinuria v0.137 MAFB Chirag Patel Gene: mafb has been classified as Green List (High Evidence).
Proteinuria v0.137 MAFB Chirag Patel Classified gene: MAFB as Green List (high evidence)
Proteinuria v0.137 MAFB Chirag Patel Gene: mafb has been classified as Green List (High Evidence).
Proteinuria v0.137 MAFB Chirag Patel Classified gene: MAFB as Green List (high evidence)
Proteinuria v0.137 MAFB Chirag Patel Gene: mafb has been classified as Green List (High Evidence).
Proteinuria v0.136 MAFB Chirag Patel gene: MAFB was added
gene: MAFB was added to Proteinuria. Sources: Literature
Mode of inheritance for gene: MAFB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAFB were set to PMID: 30208859; 29396697; 23956186
Phenotypes for gene: MAFB were set to Multicentric carpotarsal osteolysis syndrome, OMIM#166300
Review for gene: MAFB was set to GREEN
gene: MAFB was marked as current diagnostic
Added comment: Renal disease is documented in multiple patients with this skeletal dysplasia (MCTO). Mostly presenting with proteinuria, FSGS on biopsy, and progressive renal failure.
Sources: Literature
Hypertrichosis syndromes v0.21 ARID2 Zornitza Stark Marked gene: ARID2 as ready
Hypertrichosis syndromes v0.21 ARID2 Zornitza Stark Gene: arid2 has been classified as Green List (High Evidence).
Hypertrichosis syndromes v0.21 ARID2 Zornitza Stark Phenotypes for gene: ARID2 were changed from to Coffin-Siris syndrome 6, MIM# 617808
Hypertrichosis syndromes v0.20 ARID2 Zornitza Stark Publications for gene: ARID2 were set to
Hypertrichosis syndromes v0.19 ARID2 Zornitza Stark Mode of inheritance for gene: ARID2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrichosis syndromes v0.18 ARID2 Zornitza Stark reviewed gene: ARID2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26238514, 30838730, 29698805, 28884947, 28124119; Phenotypes: Coffin-Siris syndrome 6, MIM# 617808; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3041 ARID2 Zornitza Stark reviewed gene: ARID2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26238514, 30838730, 29698805, 28884947, 28124119; Phenotypes: Coffin-Siris syndrome 6, MIM# 617808; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3041 ARID2 Zornitza Stark Marked gene: ARID2 as ready
Intellectual disability syndromic and non-syndromic v0.3041 ARID2 Zornitza Stark Gene: arid2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3041 ARID2 Zornitza Stark Phenotypes for gene: ARID2 were changed from to Coffin-Siris syndrome 6, MIM# 617808
Intellectual disability syndromic and non-syndromic v0.3040 ARID2 Zornitza Stark Publications for gene: ARID2 were set to
Intellectual disability syndromic and non-syndromic v0.3039 ARID2 Zornitza Stark Mode of inheritance for gene: ARID2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4723 PFN1 Zornitza Stark Marked gene: PFN1 as ready
Mendeliome v0.4723 PFN1 Zornitza Stark Gene: pfn1 has been classified as Green List (High Evidence).
Mendeliome v0.4723 PFN1 Zornitza Stark Publications for gene: PFN1 were set to
Mendeliome v0.4722 PFN1 Zornitza Stark Phenotypes for gene: PFN1 were changed from to Amyotrophic lateral sclerosis 18 (MIM# 614808); Paget’s disease of bone
Mendeliome v0.4721 PFN1 Zornitza Stark Mode of inheritance for gene: PFN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4720 PFN1 Zornitza Stark reviewed gene: PFN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31802421, 31611772, 31401564, 30203378, 28040732, 22801503; Phenotypes: Amyotrophic lateral sclerosis 18, MIM# 614808; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4720 PCDH15 Zornitza Stark Marked gene: PCDH15 as ready
Mendeliome v0.4720 PCDH15 Zornitza Stark Gene: pcdh15 has been classified as Green List (High Evidence).
Mendeliome v0.4720 PCDH15 Zornitza Stark Phenotypes for gene: PCDH15 were changed from to Usher syndrome, type 1F, MIM# 602083; Deafness, autosomal recessive 23, MIM# 609533
Mendeliome v0.4719 PCDH15 Zornitza Stark Publications for gene: PCDH15 were set to
Mendeliome v0.4718 PCDH15 Zornitza Stark Mode of inheritance for gene: PCDH15 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4717 PCDH15 Zornitza Stark reviewed gene: PCDH15: Rating: GREEN; Mode of pathogenicity: None; Publications: 11398101, 11487575, 11138007, 12782354, 16260500, 14570705, 25930172, 28281779; Phenotypes: Usher syndrome, type 1F, MIM# 602083, Deafness, autosomal recessive 23, MIM# 609533; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.542 PCDH15 Zornitza Stark Marked gene: PCDH15 as ready
Deafness_IsolatedAndComplex v0.542 PCDH15 Zornitza Stark Gene: pcdh15 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.542 PCDH15 Zornitza Stark Phenotypes for gene: PCDH15 were changed from to Usher syndrome, type 1F, MIM# 602083; Deafness, autosomal recessive 23, MIM# 609533
Deafness_IsolatedAndComplex v0.541 PCDH15 Zornitza Stark Publications for gene: PCDH15 were set to
Deafness_IsolatedAndComplex v0.540 PCDH15 Zornitza Stark Mode of inheritance for gene: PCDH15 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.539 PCDH15 Zornitza Stark reviewed gene: PCDH15: Rating: GREEN; Mode of pathogenicity: None; Publications: 11398101, 11487575, 11138007, 12782354, 16260500, 14570705, 25930172, 28281779; Phenotypes: Usher syndrome, type 1F, MIM# 602083, Deafness, autosomal recessive 23, MIM# 609533; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.539 WFS1 Zornitza Stark Marked gene: WFS1 as ready
Deafness_IsolatedAndComplex v0.539 WFS1 Zornitza Stark Gene: wfs1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.539 WFS1 Zornitza Stark Phenotypes for gene: WFS1 were changed from to Deafness, autosomal dominant 6/14/38, MIM# 600965; Wolfram syndrome 1 222300; Wolfram-like syndrome, autosomal dominant, MIM# 614296
Deafness_IsolatedAndComplex v0.538 WFS1 Zornitza Stark Publications for gene: WFS1 were set to
Deafness_IsolatedAndComplex v0.537 WFS1 Zornitza Stark Mode of inheritance for gene: WFS1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.536 WFS1 Zornitza Stark edited their review of gene: WFS1: Changed publications: 11709537, 12073007, 16648378, 18544103, 20069065, 21538838, 25250959, 27395765, 28802351, 29529044, 12754709, 16151413, 21446023, 21602428
Deafness_IsolatedAndComplex v0.536 WFS1 Zornitza Stark reviewed gene: WFS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11709537, 12073007, 16648378, 18544103, 20069065, 21538838, 25250959, 27395765, 28802351, 29529044; Phenotypes: Deafness, autosomal dominant 6/14/38, MIM# 600965, Wolfram syndrome 1 222300, Wolfram-like syndrome, autosomal dominant, MIM# 614296; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4717 PFN1 Melanie Marty reviewed gene: PFN1: Rating: AMBER; Mode of pathogenicity: None; Publications: 32392277, 31991009, 31346562, 32589291, 22801503; Phenotypes: Paget’s disease of bone; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Usher Syndrome v0.17 WHRN Zornitza Stark Marked gene: WHRN as ready
Usher Syndrome v0.17 WHRN Zornitza Stark Gene: whrn has been classified as Green List (High Evidence).
Usher Syndrome v0.17 WHRN Zornitza Stark Publications for gene: WHRN were set to
Usher Syndrome v0.16 WHRN Zornitza Stark reviewed gene: WHRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 17171570, 21738389, 22147658, 26338283, 12833159, 20502675, 28254438, 27117407, 12833159, 29270100, 15841483; Phenotypes: Usher syndrome, type 2D, MIM# 611383, Deafness, autosomal recessive 31, MIM# 607084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.101 WHRN Zornitza Stark Marked gene: WHRN as ready
Additional findings_Paediatric v0.101 WHRN Zornitza Stark Gene: whrn has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.101 WHRN Zornitza Stark Phenotypes for gene: WHRN were changed from Hearing loss to Usher syndrome, type 2D, MIM# 611383; Deafness, autosomal recessive 31, MIM# 607084
Additional findings_Paediatric v0.100 WHRN Zornitza Stark Publications for gene: WHRN were set to
Additional findings_Paediatric v0.99 WHRN Zornitza Stark Classified gene: WHRN as Green List (high evidence)
Additional findings_Paediatric v0.99 WHRN Zornitza Stark Gene: whrn has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.98 WHRN Zornitza Stark reviewed gene: WHRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 17171570, 21738389, 22147658, 26338283, 12833159, 20502675, 28254438, 27117407, 12833159, 29270100, 15841483; Phenotypes: Usher syndrome, type 2D, MIM# 611383, Deafness, autosomal recessive 31, MIM# 607084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4717 WHRN Zornitza Stark Marked gene: WHRN as ready
Mendeliome v0.4717 WHRN Zornitza Stark Gene: whrn has been classified as Green List (High Evidence).
Mendeliome v0.4717 WHRN Zornitza Stark Phenotypes for gene: WHRN were changed from to Usher syndrome, type 2D, MIM# 611383; Deafness, autosomal recessive 31, MIM# 607084
Mendeliome v0.4716 WHRN Zornitza Stark Publications for gene: WHRN were set to
Mendeliome v0.4715 WHRN Zornitza Stark Mode of inheritance for gene: WHRN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4714 WHRN Zornitza Stark reviewed gene: WHRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 17171570, 21738389, 22147658, 26338283, 12833159, 20502675, 28254438, 27117407, 12833159, 29270100, 15841483; Phenotypes: Usher syndrome, type 2D, MIM# 611383, Deafness, autosomal recessive 31, MIM# 607084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.536 WHRN Zornitza Stark edited their review of gene: WHRN: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.536 WHRN Zornitza Stark Marked gene: WHRN as ready
Deafness_IsolatedAndComplex v0.536 WHRN Zornitza Stark Gene: whrn has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.536 WHRN Zornitza Stark Phenotypes for gene: WHRN were changed from to Usher syndrome, type 2D, MIM# 611383; Deafness, autosomal recessive 31, MIM# 607084
Deafness_IsolatedAndComplex v0.535 WHRN Zornitza Stark Mode of inheritance for gene: WHRN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.534 WHRN Zornitza Stark Publications for gene: WHRN were set to
Deafness_IsolatedAndComplex v0.533 WHRN Zornitza Stark edited their review of gene: WHRN: Changed phenotypes: Usher syndrome, type 2D, MIM# 611383, Deafness, autosomal recessive 31, MIM# 607084
Deafness_IsolatedAndComplex v0.533 WHRN Zornitza Stark changed review comment from: Association with Usher syndrome: DEFINITIVE by ClinGen, multiple families and animal models. Of note, the Whrn(neo/neo) mouse model, in which the N-terminal and long transcripts are ablated, leads to Usher syndrome (Mather et al. 2015, PMID: 26307081).

Associated with isolated AR deafness: MODERATE by ClinGen. Of note, the Whrn(wi/wi) model, which disrupts only the long and C-terminal transcripts, results in a mouse with profound hearing loss and severe vestibular defect without a retinal phenotype (Ebrahim et al. 2016, PMID: 27117407). The Whrn(tm1b/tm1b) model disrupts the C-terminal transcripts, resulting in a mouse with mild-hearing loss and no vestibular or retinal defects (Ebrahim et al. 2016, PMID: 27117407). Several families reported with AR deafness, however, in many reports, there is insufficient phenotyping to be certain an eye phenotype is absent.; to: Multiple transcripts with differential tissue expression exist for WHRN which are thought to explain the basis for distinct phenotypes. The long transcript is expressed in the retina, vestibule and cochlea, whereas the C-terminal transcript is expressed exclusively in the cochlea and vestibule and the N-terminal transcript is expressed exclusively in the retina (Ebrahim et al. 2016, PMID: 27117407).

Association with Usher syndrome: DEFINITIVE by ClinGen, multiple families and animal models. Of note, the Whrn(neo/neo) mouse model, in which the N-terminal and long transcripts are ablated, leads to Usher syndrome (Mather et al. 2015, PMID: 26307081).

Associated with isolated AR deafness: MODERATE by ClinGen. Of note, the Whrn(wi/wi) model, which disrupts only the long and C-terminal transcripts, results in a mouse with profound hearing loss and severe vestibular defect without a retinal phenotype (Ebrahim et al. 2016, PMID: 27117407). The Whrn(tm1b/tm1b) model disrupts the C-terminal transcripts, resulting in a mouse with mild-hearing loss and no vestibular or retinal defects (Ebrahim et al. 2016, PMID: 27117407). Several families reported with AR deafness, however, in many reports, there is insufficient phenotyping to be certain an eye phenotype is absent.
Motor Neurone Disease v0.111 PFN1 Ain Roesley reviewed gene: PFN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23141414, 22801503, 25499087, 24309268, 22801503, 26908597; Phenotypes: Amyotrophic lateral sclerosis 18 (MIM# 614808); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4714 PFN1 Ain Roesley reviewed gene: PFN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23141414, 22801503, 25499087, 24309268, 22801503, 26908597; Phenotypes: Amyotrophic lateral sclerosis 18 (MIM# 614808); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.533 WHRN Zornitza Stark reviewed gene: WHRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 17171570, 21738389, 22147658, 26338283, 12833159, 20502675, 28254438, 27117407, 12833159, 29270100, 15841483; Phenotypes: Usher syndrome, type 2D, MIM# 611383; Mode of inheritance: None
Deafness_IsolatedAndComplex v0.533 PAX3 Zornitza Stark Marked gene: PAX3 as ready
Deafness_IsolatedAndComplex v0.533 PAX3 Zornitza Stark Gene: pax3 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.533 PAX3 Zornitza Stark Phenotypes for gene: PAX3 were changed from to Waardenburg syndrome, type 1, MIM# 193500
Deafness_IsolatedAndComplex v0.532 PAX3 Zornitza Stark Publications for gene: PAX3 were set to
Deafness_IsolatedAndComplex v0.531 PAX3 Zornitza Stark Mode of inheritance for gene: PAX3 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.530 PAX3 Zornitza Stark reviewed gene: PAX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27759048, 7897628, 28690861, 30314436, 25932447, 7726174, 12949970; Phenotypes: Waardenburg syndrome, type 1, MIM# 193500; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.4714 OTOGL Zornitza Stark Marked gene: OTOGL as ready
Mendeliome v0.4714 OTOGL Zornitza Stark Gene: otogl has been classified as Green List (High Evidence).
Mendeliome v0.4714 OTOGL Zornitza Stark Phenotypes for gene: OTOGL were changed from to Deafness, autosomal recessive 84B, MIM# 614944
Mendeliome v0.4713 OTOGL Zornitza Stark Publications for gene: OTOGL were set to
Mendeliome v0.4712 OTOGL Zornitza Stark Mode of inheritance for gene: OTOGL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4711 OTOGL Zornitza Stark reviewed gene: OTOGL: Rating: GREEN; Mode of pathogenicity: None; Publications: 23122586, 23850727, 25829320, ​25719458, 28426234; Phenotypes: Deafness, autosomal recessive 84B, MIM# 614944; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.530 OTOGL Zornitza Stark Marked gene: OTOGL as ready
Deafness_IsolatedAndComplex v0.530 OTOGL Zornitza Stark Gene: otogl has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.530 OTOGL Zornitza Stark Phenotypes for gene: OTOGL were changed from Deafness, autosomal recessive 84B, MIM# 614944 to Deafness, autosomal recessive 84B, MIM# 614944
Deafness_IsolatedAndComplex v0.530 OTOGL Zornitza Stark Phenotypes for gene: OTOGL were changed from to Deafness, autosomal recessive 84B, MIM# 614944
Deafness_IsolatedAndComplex v0.529 OTOGL Zornitza Stark Publications for gene: OTOGL were set to
Deafness_IsolatedAndComplex v0.528 OTOGL Zornitza Stark Mode of inheritance for gene: OTOGL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.527 OTOGL Zornitza Stark reviewed gene: OTOGL: Rating: GREEN; Mode of pathogenicity: None; Publications: 23122586, 23850727, 25829320, ​25719458, 28426234; Phenotypes: Deafness, autosomal recessive 84B, MIM# 614944; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.98 RDX Zornitza Stark Marked gene: RDX as ready
Additional findings_Paediatric v0.98 RDX Zornitza Stark Gene: rdx has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.98 RDX Zornitza Stark Phenotypes for gene: RDX were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 24, MIM# 611022
Additional findings_Paediatric v0.97 RDX Zornitza Stark Publications for gene: RDX were set to
Additional findings_Paediatric v0.96 RDX Zornitza Stark Classified gene: RDX as Green List (high evidence)
Additional findings_Paediatric v0.96 RDX Zornitza Stark Gene: rdx has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.95 RDX Zornitza Stark reviewed gene: RDX: Rating: GREEN; Mode of pathogenicity: None; Publications: 17226784, 19215054, 22567349, 26226137, 15314067; Phenotypes: Deafness, autosomal recessive 24, MIM# 611022; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4711 RDX Zornitza Stark Marked gene: RDX as ready
Mendeliome v0.4711 RDX Zornitza Stark Gene: rdx has been classified as Green List (High Evidence).
Mendeliome v0.4711 RDX Zornitza Stark Phenotypes for gene: RDX were changed from to Deafness, autosomal recessive 24, MIM# 611022
Mendeliome v0.4710 RDX Zornitza Stark Publications for gene: RDX were set to
Mendeliome v0.4709 RDX Zornitza Stark Mode of inheritance for gene: RDX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4708 RDX Zornitza Stark reviewed gene: RDX: Rating: GREEN; Mode of pathogenicity: None; Publications: 17226784, 19215054, 22567349, 26226137, 15314067; Phenotypes: Deafness, autosomal recessive 24, MIM# 611022; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.527 RDX Zornitza Stark Marked gene: RDX as ready
Deafness_IsolatedAndComplex v0.527 RDX Zornitza Stark Gene: rdx has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.527 RDX Zornitza Stark Phenotypes for gene: RDX were changed from to Deafness, autosomal recessive 24, MIM# 611022
Deafness_IsolatedAndComplex v0.526 RDX Zornitza Stark Publications for gene: RDX were set to
Deafness_IsolatedAndComplex v0.525 RDX Zornitza Stark Mode of inheritance for gene: RDX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.524 RDX Zornitza Stark reviewed gene: RDX: Rating: GREEN; Mode of pathogenicity: None; Publications: 17226784, 19215054, 22567349, 26226137, 15314067; Phenotypes: Deafness, autosomal recessive 24, MIM# 611022; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3038 ARID2 Ee Ming Wong reviewed gene: ARID2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26238514; Phenotypes: neurodevelopmental delay, global developmental delay, gross motor delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Progressive Neurological Conditions v0.1 Bryony Thompson Changed child panels to: Myopathy - paediatric onset; Ataxia - paediatric; Leukodystrophy - paediatric; Hereditary Spastic Paraplegia - paediatric; Dystonia - complex; Ataxia - adult onset; Early-onset Dementia; Motor Neuron Disease; Myopathy - adult onset; Early-onset Parkinson disease; Hereditary Neuropathy - complex; Leukodystrophy - adult onset; Limb Girdle Muscular Dystrophy; Hereditary Neuropathy_CMT - isolated; Brain Calcification; Hereditary Spastic Paraplegia - adult onset; Brain Channelopathies; Dystonia - isolated/combined
Mendeliome v0.4708 OTOA Zornitza Stark Marked gene: OTOA as ready
Mendeliome v0.4708 OTOA Zornitza Stark Gene: otoa has been classified as Green List (High Evidence).
Mendeliome v0.4708 OTOA Zornitza Stark Phenotypes for gene: OTOA were changed from to Deafness, autosomal recessive 22, MIM# 607039
Mendeliome v0.4707 OTOA Zornitza Stark Publications for gene: OTOA were set to
Mendeliome v0.4706 OTOA Zornitza Stark Mode of inheritance for gene: OTOA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4705 OTOA Zornitza Stark reviewed gene: OTOA: Rating: GREEN; Mode of pathogenicity: None; Publications: 11972037, 19888295, 23173898, 16460646, 26029705, 26969326, 23129639; Phenotypes: Deafness, autosomal recessive 22, MIM# 607039; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.524 OTOA Zornitza Stark Marked gene: OTOA as ready
Deafness_IsolatedAndComplex v0.524 OTOA Zornitza Stark Gene: otoa has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.524 OTOA Zornitza Stark Phenotypes for gene: OTOA were changed from to Deafness, autosomal recessive 22, MIM# 607039
Deafness_IsolatedAndComplex v0.523 OTOA Zornitza Stark Publications for gene: OTOA were set to
Deafness_IsolatedAndComplex v0.522 OTOA Zornitza Stark Mode of inheritance for gene: OTOA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.521 OTOA Zornitza Stark reviewed gene: OTOA: Rating: GREEN; Mode of pathogenicity: None; Publications: 11972037, 19888295, 23173898, 16460646, 26029705, 26969326, 23129639; Phenotypes: Deafness, autosomal recessive 22, MIM# 607039; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Usher Syndrome v0.16 MYO7A Zornitza Stark Marked gene: MYO7A as ready
Usher Syndrome v0.16 MYO7A Zornitza Stark Gene: myo7a has been classified as Green List (High Evidence).
Usher Syndrome v0.16 MYO7A Zornitza Stark Publications for gene: MYO7A were set to
Usher Syndrome v0.15 MYO7A Zornitza Stark reviewed gene: MYO7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 23559863, 18181211, 25211151, 11391666; Phenotypes: Usher syndrome, type 1B, MIM# 276900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4705 MYO7A Zornitza Stark Marked gene: MYO7A as ready
Mendeliome v0.4705 MYO7A Zornitza Stark Gene: myo7a has been classified as Green List (High Evidence).
Mendeliome v0.4705 MYO7A Zornitza Stark Phenotypes for gene: MYO7A were changed from to Deafness, autosomal dominant 11, MIM# 601317; Deafness, autosomal recessive 2, 600060; Usher syndrome, type 1B, MIM# 276900
Mendeliome v0.4704 MYO7A Zornitza Stark Publications for gene: MYO7A were set to
Mendeliome v0.4703 MYO7A Zornitza Stark Mode of inheritance for gene: MYO7A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4702 MYO7A Zornitza Stark reviewed gene: MYO7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 9354784, 15300860, 15121790, 15221449, 16449806, 21150918, 23451214, 23383098, 28802369, 29400105, 23559863, 18181211, 25211151; Phenotypes: Deafness, autosomal dominant 11, MIM# 601317, Deafness, autosomal recessive 2, 600060, Usher syndrome, type 1B, MIM# 276900; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.521 MYO7A Zornitza Stark Marked gene: MYO7A as ready
Deafness_IsolatedAndComplex v0.521 MYO7A Zornitza Stark Gene: myo7a has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.521 MYO7A Zornitza Stark Phenotypes for gene: MYO7A were changed from to Deafness, autosomal dominant 11, MIM# 601317; Deafness, autosomal recessive 2, 600060; Usher syndrome, type 1B, MIM# 276900
Deafness_IsolatedAndComplex v0.520 MYO7A Zornitza Stark Publications for gene: MYO7A were set to
Deafness_IsolatedAndComplex v0.519 MYO7A Zornitza Stark Mode of inheritance for gene: MYO7A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.518 MYO7A Zornitza Stark reviewed gene: MYO7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 9354784, 15300860, 15121790, 15221449, 16449806, 21150918, 23451214, 23383098, 28802369, 29400105, 23559863, 18181211, 25211151; Phenotypes: Deafness, autosomal dominant 11, MIM# 601317, Deafness, autosomal recessive 2, 600060, Usher syndrome, type 1B, MIM# 276900; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Progressive Neurological Conditions v0.0 Bryony Thompson Added Panel Progressive Neurological Conditions
Set child panels to: Myopathy - paediatric onset; Ataxia - paediatric; Leukodystrophy - paediatric; Hereditary Spastic Paraplegia - paediatric; Dystonia - complex; Ataxia - adult onset; Early-onset Dementia; Motor Neuron Disease; Myopathy - adult onset; Early-onset Parkinson disease; Hereditary Neuropathy - complex; Leukodystrophy - adult onset; Limb Girdle Muscular Dystrophy; Hereditary Neuropathy_CMT - isolated; Hereditary Spastic Paraplegia - adult onset; Dystonia - isolated/combined
Set panel types to: Royal Melbourne Hospital; Rare Disease
Deafness_IsolatedAndComplex v0.518 SMPX Zornitza Stark Marked gene: SMPX as ready
Deafness_IsolatedAndComplex v0.518 SMPX Zornitza Stark Gene: smpx has been classified as Green List (High Evidence).
Mendeliome v0.4702 SMPX Zornitza Stark Marked gene: SMPX as ready
Mendeliome v0.4702 SMPX Zornitza Stark Gene: smpx has been classified as Green List (High Evidence).
Mendeliome v0.4702 SMPX Zornitza Stark Phenotypes for gene: SMPX were changed from to Deafness, X-linked 4, MIM# 300066
Mendeliome v0.4701 SMPX Zornitza Stark Publications for gene: SMPX were set to
Mendeliome v0.4700 SMPX Zornitza Stark Mode of inheritance for gene: SMPX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.4699 SMPX Zornitza Stark reviewed gene: SMPX: Rating: GREEN; Mode of pathogenicity: None; Publications: 21549342, 21549336, 21893181, 22911656, 28542515; Phenotypes: Deafness, X-linked 4, MIM# 300066; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Deafness_IsolatedAndComplex v0.518 SMPX Zornitza Stark Phenotypes for gene: SMPX were changed from Deafness, X-linked 4, MIM# 300066 to Deafness, X-linked 4, MIM# 300066
Deafness_IsolatedAndComplex v0.517 SMPX Zornitza Stark Phenotypes for gene: SMPX were changed from to Deafness, X-linked 4, MIM# 300066
Deafness_IsolatedAndComplex v0.516 SMPX Zornitza Stark Publications for gene: SMPX were set to
Deafness_IsolatedAndComplex v0.515 SMPX Zornitza Stark Mode of inheritance for gene: SMPX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Deafness_IsolatedAndComplex v0.514 SMPX Zornitza Stark reviewed gene: SMPX: Rating: GREEN; Mode of pathogenicity: None; Publications: 21549342, 21549336, 21893181, 22911656, 28542515; Phenotypes: Deafness, X-linked 4, MIM# 300066; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.4699 MYO6 Zornitza Stark Marked gene: MYO6 as ready
Mendeliome v0.4699 MYO6 Zornitza Stark Gene: myo6 has been classified as Green List (High Evidence).
Mendeliome v0.4699 MYO6 Zornitza Stark Phenotypes for gene: MYO6 were changed from to Deafness, autosomal dominant 22, MIM# 606346; Deafness, autosomal recessive 37, MIM# 607821
Mendeliome v0.4698 MYO6 Zornitza Stark Publications for gene: MYO6 were set to
Mendeliome v0.4697 MYO6 Zornitza Stark Mode of inheritance for gene: MYO6 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.4696 MYO6 Zornitza Stark reviewed gene: MYO6: Rating: GREEN; Mode of pathogenicity: None; Publications: 24105371, 11468689, 25999546, 25227905, 18348273, 27171474; Phenotypes: Deafness, autosomal dominant 22, MIM# 606346, Deafness, autosomal recessive 37, MIM# 607821; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.514 MYO6 Zornitza Stark Marked gene: MYO6 as ready
Deafness_IsolatedAndComplex v0.514 MYO6 Zornitza Stark Gene: myo6 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.514 MYO6 Zornitza Stark Phenotypes for gene: MYO6 were changed from to Deafness, autosomal dominant 22, MIM# 606346; Deafness, autosomal recessive 37, MIM# 607821
Deafness_IsolatedAndComplex v0.513 MYO6 Zornitza Stark Publications for gene: MYO6 were set to
Deafness_IsolatedAndComplex v0.512 MYO6 Zornitza Stark Mode of inheritance for gene: MYO6 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.511 MYO6 Zornitza Stark reviewed gene: MYO6: Rating: GREEN; Mode of pathogenicity: None; Publications: 24105371, 11468689, 25999546, 25227905, 18348273, 27171474; Phenotypes: Deafness, autosomal dominant 22, MIM# 606346, Deafness, autosomal recessive 37, MIM# 607821; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.4696 MYO15A Zornitza Stark Marked gene: MYO15A as ready
Mendeliome v0.4696 MYO15A Zornitza Stark Gene: myo15a has been classified as Green List (High Evidence).
Mendeliome v0.4696 MYO15A Zornitza Stark Phenotypes for gene: MYO15A were changed from to Deafness, autosomal recessive 3, MIM# 600316
Mendeliome v0.4695 MYO15A Zornitza Stark Publications for gene: MYO15A were set to
Mendeliome v0.4694 MYO15A Zornitza Stark Mode of inheritance for gene: MYO15A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4693 MYO15A Zornitza Stark reviewed gene: MYO15A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27375115, 26226137, 23208854, 19309289, 9603735, 10915760; Phenotypes: Deafness, autosomal recessive 3, MIM# 600316; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.511 MYO15A Zornitza Stark Marked gene: MYO15A as ready
Deafness_IsolatedAndComplex v0.511 MYO15A Zornitza Stark Gene: myo15a has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.511 MYO15A Zornitza Stark Phenotypes for gene: MYO15A were changed from to Deafness, autosomal recessive 3, MIM# 600316
Deafness_IsolatedAndComplex v0.510 MYO15A Zornitza Stark Publications for gene: MYO15A were set to
Deafness_IsolatedAndComplex v0.509 MYO15A Zornitza Stark Mode of inheritance for gene: MYO15A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.508 MYO15A Zornitza Stark reviewed gene: MYO15A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27375115, 26226137, 23208854, 19309289, 9603735, 10915760; Phenotypes: Deafness, autosomal recessive 3, MIM# 600316; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4693 MYH9 Zornitza Stark Marked gene: MYH9 as ready
Mendeliome v0.4693 MYH9 Zornitza Stark Gene: myh9 has been classified as Green List (High Evidence).
Mendeliome v0.4693 MYH9 Zornitza Stark Phenotypes for gene: MYH9 were changed from to Deafness, autosomal dominant 17, MIM# 603622; Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, MIM# 155100; MYH9-related disorders
Mendeliome v0.4692 MYH9 Zornitza Stark Publications for gene: MYH9 were set to
Mendeliome v0.4691 MYH9 Zornitza Stark Mode of inheritance for gene: MYH9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4690 MYH9 Zornitza Stark reviewed gene: MYH9: Rating: GREEN; Mode of pathogenicity: None; Publications: 9390828, 24890873, 17146397, 25505834, 16630581, 16162639, 23976996, 21908426; Phenotypes: Deafness, autosomal dominant 17, MIM# 603622, Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, MIM# 155100, MYH9-related disorders; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.508 MYH9 Zornitza Stark Marked gene: MYH9 as ready
Deafness_IsolatedAndComplex v0.508 MYH9 Zornitza Stark Gene: myh9 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.508 MYH9 Zornitza Stark Phenotypes for gene: MYH9 were changed from to Deafness, autosomal dominant 17, MIM# 603622; Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, MIM# 155100; MYH9-related disorders
Deafness_IsolatedAndComplex v0.507 MYH9 Zornitza Stark Publications for gene: MYH9 were set to
Deafness_IsolatedAndComplex v0.506 MYH9 Zornitza Stark Mode of inheritance for gene: MYH9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.505 MYH9 Zornitza Stark edited their review of gene: MYH9: Changed phenotypes: Deafness, autosomal dominant 17, MIM# 603622, Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, MIM# 155100, MYH9-related disorders
Deafness_IsolatedAndComplex v0.505 MYH9 Zornitza Stark reviewed gene: MYH9: Rating: GREEN; Mode of pathogenicity: None; Publications: 9390828, 24890873, 17146397, 25505834, 16630581, 16162639, 23976996, 21908426; Phenotypes: Deafness, autosomal dominant 17, MIM# 603622, MYH9-related disorders; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.505 MITF Zornitza Stark Marked gene: MITF as ready
Deafness_IsolatedAndComplex v0.505 MITF Zornitza Stark Gene: mitf has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.505 MITF Zornitza Stark Phenotypes for gene: MITF were changed from to Waardenburg syndrome, type 2A, MIM# 193510
Deafness_IsolatedAndComplex v0.504 MITF Zornitza Stark Publications for gene: MITF were set to
Deafness_IsolatedAndComplex v0.503 MITF Zornitza Stark Mode of inheritance for gene: MITF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.502 MITF Zornitza Stark reviewed gene: MITF: Rating: GREEN; Mode of pathogenicity: None; Publications: 7874167, 23512835, 27759048, 28356565, 9499424, 27349893; Phenotypes: Waardenburg syndrome, type 2A, MIM# 193510; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4690 MARVELD2 Zornitza Stark Marked gene: MARVELD2 as ready
Mendeliome v0.4690 MARVELD2 Zornitza Stark Gene: marveld2 has been classified as Green List (High Evidence).
Mendeliome v0.4690 MARVELD2 Zornitza Stark Phenotypes for gene: MARVELD2 were changed from to Deafness, autosomal recessive 49, MIM# 610153
Mendeliome v0.4689 MARVELD2 Zornitza Stark Publications for gene: MARVELD2 were set to
Mendeliome v0.4688 MARVELD2 Zornitza Stark Mode of inheritance for gene: MARVELD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4687 MARVELD2 Zornitza Stark reviewed gene: MARVELD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 17186462, 18084694, 22903915, 27344577, 26677943, 23979167; Phenotypes: Deafness, autosomal recessive 49, MIM# 610153; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.502 MARVELD2 Zornitza Stark Marked gene: MARVELD2 as ready
Deafness_IsolatedAndComplex v0.502 MARVELD2 Zornitza Stark Gene: marveld2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.502 MARVELD2 Zornitza Stark Phenotypes for gene: MARVELD2 were changed from to Deafness, autosomal recessive 49, MIM# 610153
Deafness_IsolatedAndComplex v0.501 MARVELD2 Zornitza Stark Publications for gene: MARVELD2 were set to
Deafness_IsolatedAndComplex v0.500 MARVELD2 Zornitza Stark Mode of inheritance for gene: MARVELD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.499 MARVELD2 Zornitza Stark reviewed gene: MARVELD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 17186462, 18084694, 22903915, 27344577, 26677943, 23979167; Phenotypes: Deafness, autosomal recessive 49, MIM# 610153; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bone Marrow Failure v0.167 RPL9 Zornitza Stark Publications for gene: RPL9 were set to 29114930; 20116044
Bone Marrow Failure v0.166 RPL9 Zornitza Stark Classified gene: RPL9 as Amber List (moderate evidence)
Bone Marrow Failure v0.166 RPL9 Zornitza Stark Gene: rpl9 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v0.165 RPL9 Zornitza Stark edited their review of gene: RPL9: Added comment: New publication, second individual reported with same c.-2+1G>C variant in the 5′UTR of RPL9, deleterious effect demonstrated, functional data, upgrade to Amber:

PMID: 31799629 (2020) - Female infant diagnosed with Diamond-Blackfan anaemia carrying a de novo variant (c.-2+1G>C) in the 5′UTR of RPL9, predicted to affect the donor splice site of exon 1. Phenotypic overlap can be seen with the previously reported case with the same variant, including colitis, thumb anomaly, and microcephaly. Functional studies showed the variant impairs processing of pre-rRNA during ribosome biogenesis, stabilises TP53 and impairs the proliferation and differentiation of erythroid cells. Zebrafish models of RPL9 LoF recapitulate the anaemia phenotype.; Changed rating: AMBER; Changed publications: 29114930, 20116044, 31799629
Diamond Blackfan anaemia v0.36 RPL9 Zornitza Stark Publications for gene: RPL9 were set to 29114930; 20116044
Diamond Blackfan anaemia v0.35 RPL9 Zornitza Stark Classified gene: RPL9 as Amber List (moderate evidence)
Diamond Blackfan anaemia v0.35 RPL9 Zornitza Stark Gene: rpl9 has been classified as Amber List (Moderate Evidence).
Diamond Blackfan anaemia v0.34 RPL9 Zornitza Stark edited their review of gene: RPL9: Added comment: New publication, second individual reported with same c.-2+1G>C variant in the 5′UTR of RPL9, deleterious effect demonstrated, functional data, upgrade to Amber:

PMID: 31799629 (2020) - Female infant diagnosed with Diamond-Blackfan anaemia carrying a de novo variant (c.-2+1G>C) in the 5′UTR of RPL9, predicted to affect the donor splice site of exon 1. Phenotypic overlap can be seen with the previously reported case with the same variant, including colitis, thumb anomaly, and microcephaly. Functional studies showed the variant impairs processing of pre-rRNA during ribosome biogenesis, stabilises TP53 and impairs the proliferation and differentiation of erythroid cells. Zebrafish models of RPL9 LoF recapitulate the anaemia phenotype.; Changed rating: AMBER; Changed publications: 29114930, 20116044, 31799629
Mendeliome v0.4687 RPL9 Zornitza Stark Marked gene: RPL9 as ready
Mendeliome v0.4687 RPL9 Zornitza Stark Added comment: Comment when marking as ready: Second individual reported with same c.-2+1G>C variant in the 5′UTR of RPL9, deleterious effect demonstrated, functional data, upgrade to Amber.
Mendeliome v0.4687 RPL9 Zornitza Stark Gene: rpl9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4687 RPL9 Zornitza Stark Publications for gene: RPL9 were set to 29114930; 20116044
Mendeliome v0.4686 RPL9 Zornitza Stark Classified gene: RPL9 as Amber List (moderate evidence)
Mendeliome v0.4686 RPL9 Zornitza Stark Gene: rpl9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4685 RPL9 Arina Puzriakova changed review comment from: PMID: 31799629 (2020) - One individual diagnosed with Diamond Blackfan anaemia carrying a de novo variant (c.-2+1G>C) in the 5′UTR of RPL9, predicted to affect the donor splice site of exon 1. Functional studies showed the variant impairs processing of pre-rRNA during ribosome biogenesis, stabilises TP53 and impairs the proliferation and differentiation of erythroid cells. Zebrafish models of RPL9 LoF recapitulate the anaemia phenotype.; to: PMID: 31799629 (2020) - Female infant diagnosed with Diamond-Blackfan anaemia carrying a de novo variant (c.-2+1G>C) in the 5′UTR of RPL9, predicted to affect the donor splice site of exon 1. Phenotypic overlap can be seen with the previously reported case with the same variant, including colitis, thumb anomaly, and microcephaly. Functional studies showed the variant impairs processing of pre-rRNA during ribosome biogenesis, stabilises TP53 and impairs the proliferation and differentiation of erythroid cells. Zebrafish models of RPL9 LoF recapitulate the anaemia phenotype.
Mendeliome v0.4685 RPL9 Arina Puzriakova reviewed gene: RPL9: Rating: AMBER; Mode of pathogenicity: None; Publications: 31799629; Phenotypes: Diamond Blackfan anaemia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4685 LRTOMT Zornitza Stark Marked gene: LRTOMT as ready
Mendeliome v0.4685 LRTOMT Zornitza Stark Gene: lrtomt has been classified as Green List (High Evidence).
Mendeliome v0.4685 LRTOMT Zornitza Stark Phenotypes for gene: LRTOMT were changed from to Deafness, autosomal recessive 63, MIM# 611451
Mendeliome v0.4684 LRTOMT Zornitza Stark Publications for gene: LRTOMT were set to
Mendeliome v0.4683 LRTOMT Zornitza Stark Mode of inheritance for gene: LRTOMT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4682 LRTOMT Zornitza Stark reviewed gene: LRTOMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 18953341, 18794526, 21739586, 18794526; Phenotypes: Deafness, autosomal recessive 63, MIM# 611451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.499 LRTOMT Zornitza Stark Marked gene: LRTOMT as ready
Deafness_IsolatedAndComplex v0.499 LRTOMT Zornitza Stark Gene: lrtomt has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.499 LRTOMT Zornitza Stark Phenotypes for gene: LRTOMT were changed from to Deafness, autosomal recessive 63, MIM# 611451
Deafness_IsolatedAndComplex v0.498 LRTOMT Zornitza Stark Publications for gene: LRTOMT were set to
Deafness_IsolatedAndComplex v0.497 LRTOMT Zornitza Stark Mode of inheritance for gene: LRTOMT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.496 LRTOMT Zornitza Stark reviewed gene: LRTOMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 18953341, 18794526, 21739586, 18794526; Phenotypes: Deafness, autosomal recessive 63, MIM# 611451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.496 LHFPL5 Zornitza Stark Marked gene: LHFPL5 as ready
Deafness_IsolatedAndComplex v0.496 LHFPL5 Zornitza Stark Gene: lhfpl5 has been classified as Green List (High Evidence).
Mendeliome v0.4682 LHFPL5 Zornitza Stark Marked gene: LHFPL5 as ready
Mendeliome v0.4682 LHFPL5 Zornitza Stark Gene: lhfpl5 has been classified as Green List (High Evidence).
Mendeliome v0.4682 LHFPL5 Zornitza Stark Phenotypes for gene: LHFPL5 were changed from to Deafness, autosomal recessive 67, MIM# 610265
Deafness_IsolatedAndComplex v0.496 LHFPL5 Zornitza Stark Phenotypes for gene: LHFPL5 were changed from to Deafness, autosomal recessive 67, MIM# 610265
Mendeliome v0.4681 LHFPL5 Zornitza Stark Publications for gene: LHFPL5 were set to
Mendeliome v0.4680 LHFPL5 Zornitza Stark Mode of inheritance for gene: LHFPL5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4679 LHFPL5 Zornitza Stark reviewed gene: LHFPL5: Rating: GREEN; Mode of pathogenicity: None; Publications: 16459341, 16752389, 21816241, 19888295, 26437881, 26029705, 15905332, 19102128, 25550511; Phenotypes: Deafness, autosomal recessive 67, MIM# 610265; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.495 LHFPL5 Zornitza Stark Publications for gene: LHFPL5 were set to
Deafness_IsolatedAndComplex v0.494 LHFPL5 Zornitza Stark Mode of inheritance for gene: LHFPL5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.493 LHFPL5 Zornitza Stark reviewed gene: LHFPL5: Rating: GREEN; Mode of pathogenicity: None; Publications: 16459341, 16752389, 21816241, 19888295, 26437881, 26029705, 15905332, 19102128, 25550511; Phenotypes: Deafness, autosomal recessive 67, MIM# 610265; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.493 KCNQ1 Zornitza Stark Marked gene: KCNQ1 as ready
Deafness_IsolatedAndComplex v0.493 KCNQ1 Zornitza Stark Gene: kcnq1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.493 KCNQ1 Zornitza Stark Phenotypes for gene: KCNQ1 were changed from to Jervell and Lange-Nielsen syndrome, MIM# 220400
Deafness_IsolatedAndComplex v0.492 KCNQ1 Zornitza Stark Mode of inheritance for gene: KCNQ1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.491 KCNQ1 Zornitza Stark reviewed gene: KCNQ1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Jervell and Lange-Nielsen syndrome, MIM# 220400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dilated Cardiomyopathy v0.85 Zornitza Stark removed gene:PGM1 from the panel
Dilated Cardiomyopathy v0.84 PGM1 Zornitza Stark Marked gene: PGM1 as ready
Dilated Cardiomyopathy v0.84 PGM1 Zornitza Stark Gene: pgm1 has been removed from the panel.
Cardiomyopathy_Paediatric v0.16 PGM1 Zornitza Stark Marked gene: PGM1 as ready
Cardiomyopathy_Paediatric v0.16 PGM1 Zornitza Stark Added comment: Comment when marking as ready: Severe cardiomyopathy can be a feature.
Cardiomyopathy_Paediatric v0.16 PGM1 Zornitza Stark Gene: pgm1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.16 PGM1 Zornitza Stark Phenotypes for gene: PGM1 were changed from Dilated Cardiomyopathy; Cleft Palate; Bifid Uvula; Hypothyroidism; Hepatopathy; Elevated transaminases; Hypogonadotropic hypogonadism; Hypoglycaemia; Rhabdomyolysis; Skeletal myopathy; Malignant hypothermia; Abnormal Coagulation to Congenital disorder of glycosylation, type It, MIM# 614921; Dilated cardiomyopathy
Cardiomyopathy_Paediatric v0.15 PGM1 Zornitza Stark Publications for gene: PGM1 were set to PMID: 31563034; PMID: 26303607PMID: 24878975; PMID: 27206562; PMID: 29858906; PMID: 32681750
Cardiomyopathy_Paediatric v0.14 PGM1 Zornitza Stark Classified gene: PGM1 as Green List (high evidence)
Cardiomyopathy_Paediatric v0.14 PGM1 Zornitza Stark Gene: pgm1 has been classified as Green List (High Evidence).
Mendeliome v0.4679 GYS1 Zornitza Stark Marked gene: GYS1 as ready
Mendeliome v0.4679 GYS1 Zornitza Stark Gene: gys1 has been classified as Green List (High Evidence).
Mendeliome v0.4679 GYS1 Zornitza Stark Phenotypes for gene: GYS1 were changed from to Glycogen storage disease 0, muscle, MIM# 611556
Mendeliome v0.4678 GYS1 Zornitza Stark Publications for gene: GYS1 were set to
Mendeliome v0.4677 GYS1 Zornitza Stark Mode of inheritance for gene: GYS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4676 GYS1 Zornitza Stark reviewed gene: GYS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17928598, 19699667, 21958591; Phenotypes: Glycogen storage disease 0, muscle, MIM# 611556; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Glycogen Storage Diseases v0.26 GYS1 Zornitza Stark Marked gene: GYS1 as ready
Glycogen Storage Diseases v0.26 GYS1 Zornitza Stark Gene: gys1 has been classified as Green List (High Evidence).
Glycogen Storage Diseases v0.26 GYS1 Zornitza Stark Phenotypes for gene: GYS1 were changed from to Glycogen storage disease 0, muscle, MIM# 611556
Glycogen Storage Diseases v0.25 GYS1 Zornitza Stark Publications for gene: GYS1 were set to
Glycogen Storage Diseases v0.24 GYS1 Zornitza Stark Mode of inheritance for gene: GYS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3038 PIGT Zornitza Stark Marked gene: PIGT as ready
Intellectual disability syndromic and non-syndromic v0.3038 PIGT Zornitza Stark Gene: pigt has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3038 PIGT Zornitza Stark Phenotypes for gene: PIGT were changed from to Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398
Intellectual disability syndromic and non-syndromic v0.3037 PIGT Zornitza Stark Publications for gene: PIGT were set to
Intellectual disability syndromic and non-syndromic v0.3036 PIGT Zornitza Stark Mode of inheritance for gene: PIGT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3035 PIGT Zornitza Stark reviewed gene: PIGT: Rating: GREEN; Mode of pathogenicity: None; Publications: 30976099, 25943031, 24906948, 24906948, 24906948, 28728837, 28728837, 28728837; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.869 PIGT Zornitza Stark Marked gene: PIGT as ready
Genetic Epilepsy v0.869 PIGT Zornitza Stark Gene: pigt has been classified as Green List (High Evidence).
Genetic Epilepsy v0.869 PIGT Zornitza Stark Phenotypes for gene: PIGT were changed from to Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398
Genetic Epilepsy v0.868 PIGT Zornitza Stark Publications for gene: PIGT were set to
Genetic Epilepsy v0.867 PIGT Zornitza Stark Mode of inheritance for gene: PIGT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.866 PIGT Zornitza Stark reviewed gene: PIGT: Rating: GREEN; Mode of pathogenicity: None; Publications: 30976099, 25943031, 24906948, 24906948, 24906948, 28728837, 28728837, 28728837; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.169 PIGT Zornitza Stark Publications for gene: PIGT were set to
Mendeliome v0.4676 PIGT Zornitza Stark Marked gene: PIGT as ready
Mendeliome v0.4676 PIGT Zornitza Stark Gene: pigt has been classified as Green List (High Evidence).
Mendeliome v0.4676 PIGT Zornitza Stark Phenotypes for gene: PIGT were changed from Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398 to Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398
Mendeliome v0.4675 PIGT Zornitza Stark Phenotypes for gene: PIGT were changed from to Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398
Mendeliome v0.4674 PIGT Zornitza Stark Publications for gene: PIGT were set to
Mendeliome v0.4673 PIGT Zornitza Stark Mode of inheritance for gene: PIGT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4672 PIGT Zornitza Stark reviewed gene: PIGT: Rating: GREEN; Mode of pathogenicity: None; Publications: 30976099, 25943031, 24906948, 24906948, 24906948, 28728837, 28728837, 28728837; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.168 PIGT Zornitza Stark Phenotypes for gene: PIGT were changed from to Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398
Congenital Disorders of Glycosylation v0.167 PIGT Zornitza Stark Mode of inheritance for gene: PIGT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3035 ALG13 Zornitza Stark Marked gene: ALG13 as ready
Intellectual disability syndromic and non-syndromic v0.3035 ALG13 Zornitza Stark Gene: alg13 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3035 ALG13 Zornitza Stark Phenotypes for gene: ALG13 were changed from to Congenital disorder of glycosylation, type Is (MIM# 300884)
Intellectual disability syndromic and non-syndromic v0.3034 ALG13 Zornitza Stark Publications for gene: ALG13 were set to
Intellectual disability syndromic and non-syndromic v0.3033 ALG13 Zornitza Stark Mode of inheritance for gene: ALG13 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.3032 ALG13 Zornitza Stark reviewed gene: ALG13: Rating: GREEN; Mode of pathogenicity: None; Publications: 23033978, 23934111, 24781210, 24896178, 25732998, 26138355, 26482601, 28940310, 32238909; Phenotypes: Congenital disorder of glycosylation, type Is (MIM# 300884); 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 v0.866 ALG13 Zornitza Stark Marked gene: ALG13 as ready
Genetic Epilepsy v0.866 ALG13 Zornitza Stark Gene: alg13 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.866 ALG13 Zornitza Stark Phenotypes for gene: ALG13 were changed from to Congenital disorder of glycosylation, type Is (MIM# 300884)
Genetic Epilepsy v0.865 ALG13 Zornitza Stark Publications for gene: ALG13 were set to
Genetic Epilepsy v0.864 ALG13 Zornitza Stark Mode of inheritance for gene: ALG13 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.863 ALG13 Zornitza Stark reviewed gene: ALG13: Rating: GREEN; Mode of pathogenicity: None; Publications: 23033978, 23934111, 24781210, 24896178, 25732998, 26138355, 26482601, 28940310, 32238909; Phenotypes: Congenital disorder of glycosylation, type Is (MIM# 300884); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.4672 ALG13 Zornitza Stark Marked gene: ALG13 as ready
Mendeliome v0.4672 ALG13 Zornitza Stark Gene: alg13 has been classified as Green List (High Evidence).
Mendeliome v0.4672 ALG13 Zornitza Stark Phenotypes for gene: ALG13 were changed from to Congenital disorder of glycosylation, type Is (MIM# 300884)
Mendeliome v0.4671 ALG13 Zornitza Stark Publications for gene: ALG13 were set to
Mendeliome v0.4670 ALG13 Zornitza Stark Mode of inheritance for gene: ALG13 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.4669 ALG13 Zornitza Stark reviewed gene: ALG13: Rating: GREEN; Mode of pathogenicity: None; Publications: 23033978, 23934111, 24781210, 24896178, 25732998, 26138355, 26482601, 28940310, 32238909; Phenotypes: Congenital disorder of glycosylation, type Is (MIM# 300884); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Congenital Disorders of Glycosylation v0.166 ALG13 Zornitza Stark edited their review of gene: ALG13: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Congenital Disorders of Glycosylation v0.166 ALG13 Zornitza Stark Publications for gene: ALG13 were set to 22492991; 28887793; 26138355
Congenital Disorders of Glycosylation v0.165 ALG13 Zornitza Stark Classified gene: ALG13 as Green List (high evidence)
Congenital Disorders of Glycosylation v0.165 ALG13 Zornitza Stark Gene: alg13 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.164 ALG13 Zornitza Stark reviewed gene: ALG13: Rating: GREEN; Mode of pathogenicity: None; Publications: 23033978, 23934111, 24781210, 24896178, 25732998, 26138355, 26482601, 28940310, 32238909; Phenotypes: Congenital disorder of glycosylation, type Is (MIM# 300884); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.74 FOXC1 Zornitza Stark Marked gene: FOXC1 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.74 FOXC1 Zornitza Stark Added comment: Comment when marking as ready: Appears to be a distinct association but I agree, the pathogenicity of the variants is not firmly established.
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.74 FOXC1 Zornitza Stark Gene: foxc1 has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.74 FOXC1 Zornitza Stark Marked gene: FOXC1 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.74 FOXC1 Zornitza Stark Gene: foxc1 has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.74 FOXC1 Zornitza Stark Phenotypes for gene: FOXC1 were changed from to Congenital anomalies of the kidney and urinary tract (CAKUT)
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.73 FOXC1 Zornitza Stark Publications for gene: FOXC1 were set to 32475988
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.72 FOXC1 Zornitza Stark Publications for gene: FOXC1 were set to
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.71 FOXC1 Zornitza Stark Mode of inheritance for gene: FOXC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4669 BLOC1S5 Zornitza Stark Marked gene: BLOC1S5 as ready
Mendeliome v0.4669 BLOC1S5 Zornitza Stark Gene: bloc1s5 has been classified as Green List (High Evidence).
Mendeliome v0.4669 BLOC1S5 Zornitza Stark Classified gene: BLOC1S5 as Green List (high evidence)
Mendeliome v0.4669 BLOC1S5 Zornitza Stark Gene: bloc1s5 has been classified as Green List (High Evidence).
Mendeliome v0.4668 BLOC1S5 Zornitza Stark gene: BLOC1S5 was added
gene: BLOC1S5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BLOC1S5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BLOC1S5 were set to 32565547
Phenotypes for gene: BLOC1S5 were set to Hermansky–Pudlak syndrome
Review for gene: BLOC1S5 was set to GREEN
Added comment: 2 unrelated patients with mild oculocutaneous albinism, moderate bleeding diathesis, platelet aggregation deficit, and a dramatically decreased number of platelet dense granules, all signs compatible with HPS. Identified distinct homozygous variants in the BLOC1S5 gene (patient 1: deletion of exons 3 and 4, patient 2: 1-bp deletion in exon 4). Parental segregation confirmatory in patient 1, quantitative PCR analysis confirmatory in patient 2). Functional tests performed on platelets of one patient displayed an absence of the obligate multisubunit complex BLOC-1, showing that the variant disrupts BLOC1S5 function and impairs BLOC-1 assembly. Expression of the patient-derived BLOC1S5 deletion in nonpigmented murine Bloc1s5-/- melan-mu melanocytes failed to rescue pigmentation, the assembly of a functional BLOC-1 complex, and melanosome cargo trafficking, unlike the wild-type allele. Pathogenic variants in the genes encoding three other BLOC-1 subunits (DTNBP1, BLOC1S3, and BLOC1S6) underlie HPS types 7, 8, and 9 respectively.
Sources: Literature
Bleeding and Platelet Disorders v0.202 BLOC1S5 Zornitza Stark Marked gene: BLOC1S5 as ready
Bleeding and Platelet Disorders v0.202 BLOC1S5 Zornitza Stark Gene: bloc1s5 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v0.202 BLOC1S5 Zornitza Stark Classified gene: BLOC1S5 as Green List (high evidence)
Bleeding and Platelet Disorders v0.202 BLOC1S5 Zornitza Stark Gene: bloc1s5 has been classified as Green List (High Evidence).
Ocular and Oculocutaneous Albinism v0.14 BLOC1S5 Zornitza Stark Marked gene: BLOC1S5 as ready
Ocular and Oculocutaneous Albinism v0.14 BLOC1S5 Zornitza Stark Gene: bloc1s5 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v0.84 PGM1 Sarah Donoghue gene: PGM1 was added
gene: PGM1 was added to Dilated Cardiomyopathy. Sources: Expert Review
Mode of inheritance for gene: PGM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGM1 were set to PMID: 31563034; PMID: 26303607PMID: 24878975; PMID: 27206562; PMID: 29858906; PMID: 32681750
Phenotypes for gene: PGM1 were set to Dilated Cardiomyopathy; Cleft Palate; Bifid Uvula; Hypothyroidism; Hepatopathy; Elevated transaminases; Hypogonadotropic hypogonadism; Hypoglycaemia; Rhabdomyolysis; Skeletal myopathy; Malignant hypothermia; Abnormal Coagulation
Penetrance for gene: PGM1 were set to Complete
gene: PGM1 was marked as current diagnostic
Added comment: Mixed type disorder of glycosylation - may have type I/II pattern
Often glycosylation abnormalities less prominent in adulthood
May also normalise with high milk intake

Abnormalities of coagulation, hypothyroidism, hypogonadotrophic hypogonadism, hypoglycaemia, can have abnormal IGF1, IGFB3

This condition is treatable with galactose - may correct glycosylation abnormalities
Sources: Expert Review
Cardiomyopathy_Paediatric v0.13 PGM1 Sarah Donoghue gene: PGM1 was added
gene: PGM1 was added to Cardiomyopathy_Paediatric. Sources: Expert Review
Mode of inheritance for gene: PGM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGM1 were set to PMID: 31563034; PMID: 26303607PMID: 24878975; PMID: 27206562; PMID: 29858906; PMID: 32681750
Phenotypes for gene: PGM1 were set to Dilated Cardiomyopathy; Cleft Palate; Bifid Uvula; Hypothyroidism; Hepatopathy; Elevated transaminases; Hypogonadotropic hypogonadism; Hypoglycaemia; Rhabdomyolysis; Skeletal myopathy; Malignant hypothermia; Abnormal Coagulation
Penetrance for gene: PGM1 were set to Complete
Review for gene: PGM1 was set to GREEN
gene: PGM1 was marked as current diagnostic
Added comment: Mixed type disorder of glycosylation - may have type I/II pattern
Often glycosylation abnormalities less prominent in adulthood
May also normalise with high milk intake

Abnormalities of coagulation, hypothyroidism, hypogonadotrophic hypogonadism, hypoglycaemia, can have abnormal IGF1, IGFB3

This condition is treatable with galactose - may correct glycosylation abnormalities
Sources: Expert Review
Ataxia v0.262 CAD Zornitza Stark Marked gene: CAD as ready
Ataxia v0.262 CAD Zornitza Stark Gene: cad has been classified as Green List (High Evidence).
Blepharophimosis v0.18 FOXL2 Zornitza Stark Marked gene: FOXL2 as ready
Blepharophimosis v0.18 FOXL2 Zornitza Stark Gene: foxl2 has been classified as Green List (High Evidence).
Blepharophimosis v0.18 FOXL2 Zornitza Stark Phenotypes for gene: FOXL2 were changed from to Blepharophimosis, epicanthus inversus, and ptosis, type 1 with premature ovarian insufficiency (POI) and type II without POI (MIM# 110100)
Blepharophimosis v0.17 FOXL2 Zornitza Stark Publications for gene: FOXL2 were set to
Blepharophimosis v0.16 FOXL2 Zornitza Stark Mode of inheritance for gene: FOXL2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4667 FOXL2 Zornitza Stark Marked gene: FOXL2 as ready
Mendeliome v0.4667 FOXL2 Zornitza Stark Gene: foxl2 has been classified as Green List (High Evidence).
Mendeliome v0.4667 FOXL2 Zornitza Stark Phenotypes for gene: FOXL2 were changed from to Blepharophimosis, epicanthus inversus, and ptosis, type 1 with premature ovarian insufficiency (POI) and type II without POI (MIM# 110100)
Mendeliome v0.4666 FOXL2 Zornitza Stark Publications for gene: FOXL2 were set to
Mendeliome v0.4665 FOXL2 Zornitza Stark Mode of inheritance for gene: FOXL2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Glycogen Storage Diseases v0.23 GYS1 Sarah Donoghue reviewed gene: GYS1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17928598, PMID: 19699667, PMID: 21958591; Phenotypes: Sudden cardiac death, skeletal myopathy, Syncope, Epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Congenital Disorders of Glycosylation v0.164 PIGT Sarah Donoghue reviewed gene: PIGT: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25943031, PMID: 24906948, PMID: 23636107, PMID: 30813157 PMID: 28728837, PMID: 27916860, PMID: 29868109, PMID: 30976099; Phenotypes: Intellectual disability, Hypotonia, Leukodystrophy, Cortical visual impairment, Strabismus, Hearing Loss, Patent Ductus Arteriosus, Cardiomyopathy, Gastroesophageal Reflux, Nephrocalcinosis, Ureteric dilatation, Slender long bones, Scoliosis, Brachycephaly, Short arms, Pectus excavated, joint hyper mobility, High forehead, bitemporal narrowing, broad nasal root, antevered nose, depressed nasal bridge, long philtrum with a deep groove, cupid bow lips; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Congenital Disorders of Glycosylation v0.164 ALG13 Sarah Donoghue reviewed gene: ALG13: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31444733; Phenotypes: Microcephaly, infantile spasms, developmental regression, hypotonia, epileptic encephalopathy, intellectual disability; Mode of inheritance: None
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.70 FOXC1 Chirag Patel Classified gene: FOXC1 as Amber List (moderate evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.70 FOXC1 Chirag Patel Gene: foxc1 has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.69 FOXC1 Chirag Patel edited their review of gene: FOXC1: Added comment: Seven FOXC1 'pathogenic' variants in 8 CAKUT families identified through WES. All individuals carrying the FOXC1 pathogenic variants are heterozygote. There was incomplete penetrance and variable expressivity in families. None of the 7 pathogenic variants were reported before in patients with Axenfeld–Rieger syndrome, anterior segment dysgenesis, or congenital glaucoma. Two of the seven pathogenic variants are novel, i.e., they were never observed in the population database before, including the gnomAD database that collects 141,456 control individuals.34 The other five pathogenic variants, though reported in the population database, are present in less than five individuals as a heterozygote. The locations of these pathogenic variants do not cluster in the forkhead domain (where variants causing Axenfeld–Rieger syndrome or anterior segment dysgenesis are located).
NB they call them pathogenic - but no documentation of ACMG criteria used.

Previous animal studies show CAKUT in homozygous and heterozygous mice.; Changed rating: AMBER; Changed publications: PMID: 32475988; Changed phenotypes: Congenital anomalies of the kidney and urinary tract (CAKUT); Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ocular and Oculocutaneous Albinism v0.14 BLOC1S5 Chirag Patel Classified gene: BLOC1S5 as Green List (high evidence)
Ocular and Oculocutaneous Albinism v0.14 BLOC1S5 Chirag Patel Gene: bloc1s5 has been classified as Green List (High Evidence).
Ocular and Oculocutaneous Albinism v0.14 BLOC1S5 Chirag Patel Classified gene: BLOC1S5 as Green List (high evidence)
Ocular and Oculocutaneous Albinism v0.14 BLOC1S5 Chirag Patel Gene: bloc1s5 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v0.201 BLOC1S5 Chirag Patel gene: BLOC1S5 was added
gene: BLOC1S5 was added to Bleeding Disorders. Sources: Literature
Mode of inheritance for gene: BLOC1S5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BLOC1S5 were set to PMID: 32565547
Phenotypes for gene: BLOC1S5 were set to Hermansky–Pudlak syndrome type 11, no OMIM#
Review for gene: BLOC1S5 was set to GREEN
gene: BLOC1S5 was marked as current diagnostic
Added comment: 2 unrelated patients with mild oculocutaneous albinism, moderate bleeding diathesis, platelet aggregation deficit, and a dramatically decreased number of platelet dense granules, all signs compatible with HPS. Identified distinct homozygous variants in the BLOC1S5 gene (patient 1: deletion of exons 3 and 4, patient 2: 1-bp deletion in exon 4). Parental segregation confirmatory in patient 1, quantitative PCR analysis confirmatory in patient 2).

Functional tests performed on platelets of one patient displayed an absence of the obligate multisubunit complex BLOC-1, showing that the variant disrupts BLOC1S5 function and impairs BLOC-1 assembly. Expression of the patient-derived BLOC1S5 deletion in nonpigmented murine Bloc1s5-/- melan-mu melanocytes failed to rescue pigmentation, the assembly of a functional BLOC-1 complex, and melanosome cargo trafficking, unlike the wild-type allele.

Pathogenic variants in the genes encoding three other BLOC-1 subunits (DTNBP1, BLOC1S3, and BLOC1S6) underlie HPS types 7, 8, and 9 respectively.
Sources: Literature
Bleeding and Platelet Disorders v0.201 BLOC1S5 Chirag Patel gene: BLOC1S5 was added
gene: BLOC1S5 was added to Bleeding Disorders. Sources: Literature
Mode of inheritance for gene: BLOC1S5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BLOC1S5 were set to PMID: 32565547
Phenotypes for gene: BLOC1S5 were set to Hermansky–Pudlak syndrome type 11, no OMIM#
Review for gene: BLOC1S5 was set to GREEN
gene: BLOC1S5 was marked as current diagnostic
Added comment: 2 unrelated patients with mild oculocutaneous albinism, moderate bleeding diathesis, platelet aggregation deficit, and a dramatically decreased number of platelet dense granules, all signs compatible with HPS. Identified distinct homozygous variants in the BLOC1S5 gene (patient 1: deletion of exons 3 and 4, patient 2: 1-bp deletion in exon 4). Parental segregation confirmatory in patient 1, quantitative PCR analysis confirmatory in patient 2).

Functional tests performed on platelets of one patient displayed an absence of the obligate multisubunit complex BLOC-1, showing that the variant disrupts BLOC1S5 function and impairs BLOC-1 assembly. Expression of the patient-derived BLOC1S5 deletion in nonpigmented murine Bloc1s5-/- melan-mu melanocytes failed to rescue pigmentation, the assembly of a functional BLOC-1 complex, and melanosome cargo trafficking, unlike the wild-type allele.

Pathogenic variants in the genes encoding three other BLOC-1 subunits (DTNBP1, BLOC1S3, and BLOC1S6) underlie HPS types 7, 8, and 9 respectively.
Sources: Literature
Ocular and Oculocutaneous Albinism v0.13 BLOC1S5 Chirag Patel gene: BLOC1S5 was added
gene: BLOC1S5 was added to Ocular and Oculocutaneous Albinism. Sources: Literature
Mode of inheritance for gene: BLOC1S5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BLOC1S5 were set to PMID: 32565547
Phenotypes for gene: BLOC1S5 were set to Hermansky–Pudlak syndrome type 11, no OMIM#
Review for gene: BLOC1S5 was set to GREEN
gene: BLOC1S5 was marked as current diagnostic
Added comment: 2 unrelated patients with mild oculocutaneous albinism, moderate bleeding diathesis, platelet aggregation deficit, and a dramatically decreased number of platelet dense granules, all signs compatible with HPS. Identified distinct homozygous variants in the BLOC1S5 gene (patient 1: deletion of exons 3 and 4, patient 2: 1-bp deletion in exon 4). Parental segregation confirmatory in patient 1, quantitative PCR analysis confirmatory in patient 2).

Functional tests performed on platelets of one patient displayed an absence of the obligate multisubunit complex BLOC-1, showing that the variant disrupts BLOC1S5 function and impairs BLOC-1 assembly. Expression of the patient-derived BLOC1S5 deletion in nonpigmented murine Bloc1s5-/- melan-mu melanocytes failed to rescue pigmentation, the assembly of a functional BLOC-1 complex, and melanosome cargo trafficking, unlike the wild-type allele.

Pathogenic variants in the genes encoding three other BLOC-1 subunits (DTNBP1, BLOC1S3, and BLOC1S6) underlie HPS types 7, 8, and 9 respectively.
Sources: Literature
Ataxia v0.262 CAD Chirag Patel Classified gene: CAD as Green List (high evidence)
Ataxia v0.262 CAD Chirag Patel Gene: cad has been classified as Green List (High Evidence).
Ataxia v0.261 CAD Chirag Patel gene: CAD was added
gene: CAD was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: CAD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAD were set to PMID: 32820246
Phenotypes for gene: CAD were set to Epileptic encephalopathy, early infantile, 50; OMIM # 616457
Review for gene: CAD was set to GREEN
gene: CAD was marked as current diagnostic
Added comment: 2020 series: 6/20 patients reported had ataxia relating to cerebellar atrophy, which is an expansion to the phenotype.
Sources: Literature
Early-onset Dementia v0.125 C9orf72 Bryony Thompson Classified gene: C9orf72 as No list
Early-onset Dementia v0.125 C9orf72 Bryony Thompson Gene: c9orf72 has been removed from the panel.
Early-onset Dementia v0.124 ATN1 Bryony Thompson Classified gene: ATN1 as No list
Early-onset Dementia v0.124 ATN1 Bryony Thompson Gene: atn1 has been removed from the panel.
Early-onset Dementia v0.123 DRPLA Bryony Thompson Marked STR: DRPLA as ready
Early-onset Dementia v0.123 DRPLA Bryony Thompson Str: drpla has been classified as Green List (High Evidence).
Early-onset Dementia v0.123 DRPLA Bryony Thompson Classified STR: DRPLA as Green List (high evidence)
Early-onset Dementia v0.123 DRPLA Bryony Thompson Str: drpla has been classified as Green List (High Evidence).
Early-onset Dementia v0.122 DRPLA Bryony Thompson STR: DRPLA was added
STR: DRPLA was added to Early-onset Dementia. Sources: Expert list
STR tags were added to STR: DRPLA.
Mode of inheritance for STR: DRPLA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: DRPLA were set to 29325606; 20301664
Phenotypes for STR: DRPLA were set to Dentatorubral-pallidoluysian atrophy MIM#125370
Review for STR: DRPLA was set to GREEN
STR: DRPLA was marked as clinically relevant
Added comment: NM_001007026​.1:c.1462_1464CAG[X] Toxic gain of function mechanism of disease Benign: ≤35 repeats Mutable normal: 20-35 repeats Pathogenic: ≥48 repeats Age <20 years: ≥63 repeats - ataxia, myoclonus, seizures, progressive intellectual deterioration Age 21-40 years 61-69 repeats, >40 years 48-67 repeats: ataxia, choreoathetosis, dementia, psychiatric disturbance
Sources: Expert list
Mendeliome v0.4664 FOXL2 Ain Roesley changed review comment from: PMID: 31077882; 19x probands reported, AD.

PMID: 18642388;
BPES type I : Mutations predicted to result in proteins with truncation before the poly-Ala tract
BPES type II: poly-Ala expansions (WT poly-Ala is between aa 221-234)
Exceptions: Truncated proteins with complete forkhead and poly-Ala domains, can be either Type I and II

NOTE: only 1 family reported for AR (PMID: 17089161); to: PMID: 31077882; >100 probands reported, AD.

PMID: 18642388;
BPES type I : Mutations predicted to result in proteins with truncation before the poly-Ala tract
BPES type II: poly-Ala expansions (WT poly-Ala is between aa 221-234)
Exceptions: Truncated proteins with complete forkhead and poly-Ala domains, can be either Type I and II

NOTE: only 1 family reported for AR (PMID: 17089161)
Blepharophimosis v0.15 FOXL2 Ain Roesley changed review comment from: PMID: 31077882; 19x probands reported, AD.

PMID: 18642388;
BPES type I : Mutations predicted to result in proteins with truncation before the poly-Ala tract
BPES type II: poly-Ala expansions (WT poly-Ala is between aa 221-234)
Exceptions: Truncated proteins with complete forkhead and poly-Ala domains, can be either Type I and II

NOTE: only 1 family reported for AR (PMID: 17089161); to: PMID: 31077882; >100 probands reported, AD.

PMID: 18642388;
BPES type I : Mutations predicted to result in proteins with truncation before the poly-Ala tract
BPES type II: poly-Ala expansions (WT poly-Ala is between aa 221-234)
Exceptions: Truncated proteins with complete forkhead and poly-Ala domains, can be either Type I and II

NOTE: only 1 family reported for AR (PMID: 17089161)
Mendeliome v0.4664 FOXL2 Ain Roesley reviewed gene: FOXL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31077882, 18642388, 17089161; Phenotypes: Blepharophimosis, epicanthus inversus, and ptosis, type 1 with premature ovarian insufficiency (POI) and type II without POI (MIM# 110100); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Blepharophimosis v0.15 FOXL2 Ain Roesley reviewed gene: FOXL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31077882, 18642388, 17089161; Phenotypes: Blepharophimosis, epicanthus inversus, and ptosis, type 1 with premature ovarian insufficiency (POI) and type II without POI (MIM# 110100); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4664 ILDR1 Zornitza Stark Marked gene: ILDR1 as ready
Mendeliome v0.4664 ILDR1 Zornitza Stark Gene: ildr1 has been classified as Green List (High Evidence).
Mendeliome v0.4664 ILDR1 Zornitza Stark Phenotypes for gene: ILDR1 were changed from to Deafness, autosomal recessive 42, MIM# 609646
Mendeliome v0.4663 ILDR1 Zornitza Stark Publications for gene: ILDR1 were set to
Mendeliome v0.4662 ILDR1 Zornitza Stark Mode of inheritance for gene: ILDR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4661 ILDR1 Zornitza Stark reviewed gene: ILDR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21255762, 23226338, 22903915, 27344577, 21255762, 23239027, 25822906, 25819842, 24990150; Phenotypes: Deafness, autosomal recessive 42, MIM# 609646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.491 ILDR1 Zornitza Stark Marked gene: ILDR1 as ready
Deafness_IsolatedAndComplex v0.491 ILDR1 Zornitza Stark Gene: ildr1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.491 ILDR1 Zornitza Stark Phenotypes for gene: ILDR1 were changed from to Deafness, autosomal recessive 42, MIM# 609646
Deafness_IsolatedAndComplex v0.490 ILDR1 Zornitza Stark Publications for gene: ILDR1 were set to
Deafness_IsolatedAndComplex v0.489 ILDR1 Zornitza Stark Mode of inheritance for gene: ILDR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.488 ILDR1 Zornitza Stark reviewed gene: ILDR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21255762, 23226338, 22903915, 27344577, 21255762, 23239027, 25822906, 25819842, 24990150; Phenotypes: Deafness, autosomal recessive 42, MIM# 609646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.488 HSD17B4 Zornitza Stark Marked gene: HSD17B4 as ready
Deafness_IsolatedAndComplex v0.488 HSD17B4 Zornitza Stark Gene: hsd17b4 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.488 HSD17B4 Zornitza Stark Phenotypes for gene: HSD17B4 were changed from to Perrault syndrome 1, MIM# 233400
Deafness_IsolatedAndComplex v0.487 HSD17B4 Zornitza Stark Publications for gene: HSD17B4 were set to
Deafness_IsolatedAndComplex v0.486 HSD17B4 Zornitza Stark Mode of inheritance for gene: HSD17B4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.485 HSD17B4 Zornitza Stark reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24553428, 23181892, 20673864; Phenotypes: Perrault syndrome 1, MIM# 233400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4661 HOXA2 Zornitza Stark Marked gene: HOXA2 as ready
Mendeliome v0.4661 HOXA2 Zornitza Stark Gene: hoxa2 has been classified as Green List (High Evidence).
Mendeliome v0.4661 HOXA2 Zornitza Stark Phenotypes for gene: HOXA2 were changed from to Microtia with or without hearing impairment, MIM# 612290
Mendeliome v0.4660 HOXA2 Zornitza Stark Publications for gene: HOXA2 were set to
Mendeliome v0.4659 HOXA2 Zornitza Stark Mode of inheritance for gene: HOXA2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4658 HOXA2 Zornitza Stark reviewed gene: HOXA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18394579, 23775976, 27503514, 32649979, 31567444; Phenotypes: Microtia with or without hearing impairment, MIM# 612290; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.485 HOXA2 Zornitza Stark edited their review of gene: HOXA2: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.485 HOXA2 Zornitza Stark Marked gene: HOXA2 as ready
Deafness_IsolatedAndComplex v0.485 HOXA2 Zornitza Stark Gene: hoxa2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.485 HOXA2 Zornitza Stark Phenotypes for gene: HOXA2 were changed from to Microtia with or without hearing impairment, MIM# 612290
Deafness_IsolatedAndComplex v0.484 HOXA2 Zornitza Stark Publications for gene: HOXA2 were set to
Deafness_IsolatedAndComplex v0.483 HOXA2 Zornitza Stark Mode of inheritance for gene: HOXA2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.482 HOXA2 Zornitza Stark reviewed gene: HOXA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18394579, 23775976, 27503514, 32649979, 31567444; Phenotypes: Microtia with or without hearing impairment, MIM# 612290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.95 GRXCR1 Zornitza Stark Marked gene: GRXCR1 as ready
Additional findings_Paediatric v0.95 GRXCR1 Zornitza Stark Gene: grxcr1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.95 GRXCR1 Zornitza Stark Phenotypes for gene: GRXCR1 were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 25, MIM# 613285
Additional findings_Paediatric v0.94 GRXCR1 Zornitza Stark Publications for gene: GRXCR1 were set to
Additional findings_Paediatric v0.93 GRXCR1 Zornitza Stark Classified gene: GRXCR1 as Green List (high evidence)
Additional findings_Paediatric v0.93 GRXCR1 Zornitza Stark Gene: grxcr1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.92 GRXCR1 Zornitza Stark reviewed gene: GRXCR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20137778, 25802247, 26226137, 26445815, 26969326, 20137774; Phenotypes: Deafness, autosomal recessive 25, MIM# 613285; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4658 GRXCR1 Zornitza Stark Marked gene: GRXCR1 as ready
Mendeliome v0.4658 GRXCR1 Zornitza Stark Gene: grxcr1 has been classified as Green List (High Evidence).
Mendeliome v0.4658 GRXCR1 Zornitza Stark Phenotypes for gene: GRXCR1 were changed from to Deafness, autosomal recessive 25, MIM# 613285
Mendeliome v0.4657 GRXCR1 Zornitza Stark Publications for gene: GRXCR1 were set to
Mendeliome v0.4656 GRXCR1 Zornitza Stark Mode of inheritance for gene: GRXCR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4655 GRXCR1 Zornitza Stark reviewed gene: GRXCR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20137778, 25802247, 26226137, 26445815, 26969326, 20137774; Phenotypes: Deafness, autosomal recessive 25, MIM# 613285; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.482 GRXCR1 Zornitza Stark Marked gene: GRXCR1 as ready
Deafness_IsolatedAndComplex v0.482 GRXCR1 Zornitza Stark Gene: grxcr1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.482 GRXCR1 Zornitza Stark Phenotypes for gene: GRXCR1 were changed from to Deafness, autosomal recessive 25, MIM# 613285
Deafness_IsolatedAndComplex v0.481 GRXCR1 Zornitza Stark Publications for gene: GRXCR1 were set to
Deafness_IsolatedAndComplex v0.480 GRXCR1 Zornitza Stark Mode of inheritance for gene: GRXCR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.479 GRXCR1 Zornitza Stark reviewed gene: GRXCR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20137778, 25802247, 26226137, 26445815, 26969326, 20137774; Phenotypes: Deafness, autosomal recessive 25, MIM# 613285; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3032 GPSM2 Zornitza Stark edited their review of gene: GPSM2: Changed publications: 20602914, 22578326, 28387217, 27180139, 27064331
Intellectual disability syndromic and non-syndromic v0.3032 GPSM2 Zornitza Stark Publications for gene: GPSM2 were set to
Intellectual disability syndromic and non-syndromic v0.3031 GPSM2 Zornitza Stark Mode of inheritance for gene: GPSM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v0.218 GPSM2 Zornitza Stark Marked gene: GPSM2 as ready
Callosome v0.218 GPSM2 Zornitza Stark Gene: gpsm2 has been classified as Green List (High Evidence).
Callosome v0.218 GPSM2 Zornitza Stark Phenotypes for gene: GPSM2 were changed from to Chudley-McCullough syndrome, MIM# 604213
Callosome v0.217 GPSM2 Zornitza Stark Publications for gene: GPSM2 were set to
Callosome v0.216 GPSM2 Zornitza Stark Mode of inheritance for gene: GPSM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v0.215 GPSM2 Zornitza Stark reviewed gene: GPSM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20602914, 22578326, 28387217, 27180139, 27064331; Phenotypes: Chudley-McCullough syndrome, MIM# 604213; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4655 GPSM2 Zornitza Stark Marked gene: GPSM2 as ready
Mendeliome v0.4655 GPSM2 Zornitza Stark Gene: gpsm2 has been classified as Green List (High Evidence).
Mendeliome v0.4655 GPSM2 Zornitza Stark Phenotypes for gene: GPSM2 were changed from to Chudley-McCullough syndrome, MIM# 604213
Mendeliome v0.4654 GPSM2 Zornitza Stark Publications for gene: GPSM2 were set to
Mendeliome v0.4653 GPSM2 Zornitza Stark Mode of inheritance for gene: GPSM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4652 GPSM2 Zornitza Stark reviewed gene: GPSM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20602914, 22578326, 28387217, 27180139, 27064331; Phenotypes: Chudley-McCullough syndrome, MIM# 604213; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hydrocephalus_Ventriculomegaly v0.59 GPSM2 Zornitza Stark Marked gene: GPSM2 as ready
Hydrocephalus_Ventriculomegaly v0.59 GPSM2 Zornitza Stark Gene: gpsm2 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.59 GPSM2 Zornitza Stark Phenotypes for gene: GPSM2 were changed from to Chudley-McCullough syndrome, MIM# 604213
Hydrocephalus_Ventriculomegaly v0.58 GPSM2 Zornitza Stark Publications for gene: GPSM2 were set to
Hydrocephalus_Ventriculomegaly v0.57 GPSM2 Zornitza Stark Mode of inheritance for gene: GPSM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Hydrocephalus_Ventriculomegaly v0.56 GPSM2 Zornitza Stark reviewed gene: GPSM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20602914, 22578326, 28387217, 27180139, 27064331; Phenotypes: Chudley-McCullough syndrome, MIM# 604213; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.479 GPSM2 Zornitza Stark Marked gene: GPSM2 as ready
Deafness_IsolatedAndComplex v0.479 GPSM2 Zornitza Stark Gene: gpsm2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.479 GPSM2 Zornitza Stark Phenotypes for gene: GPSM2 were changed from to Chudley-McCullough syndrome, MIM# 604213
Deafness_IsolatedAndComplex v0.478 GPSM2 Zornitza Stark Publications for gene: GPSM2 were set to
Deafness_IsolatedAndComplex v0.477 GPSM2 Zornitza Stark Mode of inheritance for gene: GPSM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.476 GPSM2 Zornitza Stark reviewed gene: GPSM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20602914, 22578326, 28387217, 27180139, 27064331; Phenotypes: Chudley-McCullough syndrome, MIM# 604213; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4652 GIPC3 Zornitza Stark Marked gene: GIPC3 as ready
Mendeliome v0.4652 GIPC3 Zornitza Stark Gene: gipc3 has been classified as Green List (High Evidence).
Mendeliome v0.4652 GIPC3 Zornitza Stark Phenotypes for gene: GIPC3 were changed from to Deafness, autosomal recessive 15, MIM# 601869
Mendeliome v0.4651 GIPC3 Zornitza Stark Publications for gene: GIPC3 were set to
Mendeliome v0.4650 GIPC3 Zornitza Stark Mode of inheritance for gene: GIPC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4649 GIPC3 Zornitza Stark reviewed gene: GIPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21326233, 21660509; Phenotypes: Deafness, autosomal recessive 15, MIM# 601869; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.476 GIPC3 Zornitza Stark Marked gene: GIPC3 as ready
Deafness_IsolatedAndComplex v0.476 GIPC3 Zornitza Stark Gene: gipc3 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.476 GIPC3 Zornitza Stark Phenotypes for gene: GIPC3 were changed from to Deafness, autosomal recessive 15, MIM# 601869
Deafness_IsolatedAndComplex v0.475 GIPC3 Zornitza Stark Publications for gene: GIPC3 were set to
Deafness_IsolatedAndComplex v0.474 GIPC3 Zornitza Stark Mode of inheritance for gene: GIPC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.473 GIPC3 Zornitza Stark reviewed gene: GIPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21326233, 21660509; Phenotypes: Deafness, autosomal recessive 15, MIM# 601869; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.92 COCH Zornitza Stark Marked gene: COCH as ready
Additional findings_Paediatric v0.92 COCH Zornitza Stark Gene: coch has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.92 COCH Zornitza Stark Phenotypes for gene: COCH were changed from Deafness, non-syndromic, autosomal dominant to Deafness, autosomal dominant 9, MIM# 601369; Deafness, autosomal recessive 110, MIM# 618094
Additional findings_Paediatric v0.91 COCH Zornitza Stark Publications for gene: COCH were set to
Additional findings_Paediatric v0.90 COCH Zornitza Stark Mode of inheritance for gene: COCH was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Additional findings_Paediatric v0.89 COCH Zornitza Stark reviewed gene: COCH: Rating: GREEN; Mode of pathogenicity: None; Publications: 16151338, 28116169, 28099493, 9806553, 17561763, 21046548, 26256111, 22931125, 22610276, 18312449, 28733840, 18697796, 29449721, 32939038, 32562050; Phenotypes: Deafness, autosomal dominant 9, MIM# 601369, Deafness, autosomal recessive 110, MIM# 618094; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4649 COCH Zornitza Stark Phenotypes for gene: COCH were changed from Deafness, autosomal dominant 9, MIM# 601369 to Deafness, autosomal dominant 9, MIM# 601369; Deafness, autosomal recessive 110, MIM# 618094
Mendeliome v0.4648 COCH Zornitza Stark Publications for gene: COCH were set to 16151338; 28116169; 28099493; 9806553; 17561763; 21046548; 26256111; 22931125; 22610276; 18312449; 28733840; 18697796; 29449721
Mendeliome v0.4647 COCH Zornitza Stark changed review comment from: Mono-allelic variants: Over 50 affected individuals from more than 10 families reported, mouse model. Dominant negative effect postulated.

Bi-allelic variants: three families reported with bi-allelic variants in this gene and deafness. All variants are LOF, some functional data. PMIDs 29449721, 32939038, 32562050.; to: Mono-allelic variants: Over 50 affected individuals from more than 10 families reported, mouse model. Dominant negative effect postulated.

Bi-allelic variants: three families reported with bi-allelic variants in this gene and deafness. All variants are LOF, some functional data. PMIDs 29449721, 32939038, 32562050.
Mendeliome v0.4647 COCH Zornitza Stark changed review comment from: Over 50 affected individuals from more than 10 families reported, mouse model. Single family with two siblings reported with bi-allelic variants in this gene and deafness (homozygous LOF) in PMID 29449721, evidence for bi-allelic disease is limited.; to: Mono-allelic variants: Over 50 affected individuals from more than 10 families reported, mouse model. Dominant negative effect postulated.

Bi-allelic variants: three families reported with bi-allelic variants in this gene and deafness. All variants are LOF, some functional data. PMIDs 29449721, 32939038, 32562050.
Mendeliome v0.4647 COCH Zornitza Stark edited their review of gene: COCH: Changed publications: 16151338, 28116169, 28099493, 9806553, 17561763, 21046548, 26256111, 22931125, 22610276, 18312449, 28733840, 18697796, 29449721, 32939038, 32562050
Deafness_IsolatedAndComplex v0.473 COCH Zornitza Stark Phenotypes for gene: COCH were changed from Deafness, autosomal dominant 9, MIM# 601369; Deafness, autosomal recessive 110, MIM# 618094Deafness, autosomal recessive 110, MIM# 618094 to Deafness, autosomal dominant 9, MIM# 601369; Deafness, autosomal recessive 110, MIM# 618094
Mendeliome v0.4647 COCH Zornitza Stark edited their review of gene: COCH: Changed phenotypes: Deafness, autosomal dominant 9, MIM# 601369, Deafness, autosomal recessive 110, MIM# 618094
Deafness_IsolatedAndComplex v0.472 COCH Zornitza Stark Phenotypes for gene: COCH were changed from Deafness, autosomal dominant 9, MIM# 601369 to Deafness, autosomal dominant 9, MIM# 601369; Deafness, autosomal recessive 110, MIM# 618094Deafness, autosomal recessive 110, MIM# 618094
Deafness_IsolatedAndComplex v0.471 COCH Zornitza Stark Publications for gene: COCH were set to 16151338; 28116169; 28099493; 9806553; 17561763; 21046548; 26256111; 22931125; 22610276; 18312449; 28733840; 18697796; 29449721
Deafness_IsolatedAndComplex v0.470 COCH Zornitza Stark changed review comment from: Over 50 affected individuals from more than 10 families reported, mouse model. Single family with two siblings reported with bi-allelic variants in this gene and deafness (homozygous LOF) in PMID 29449721, evidence for bi-allelic disease is limited.; to: Mono-allelic variants: Over 50 affected individuals from more than 10 families reported, mouse model. Dominant negative effect postulated.

Bi-allelic variants: three families reported with bi-allelic variants in this gene and deafness. All variants are LOF, some functional data. PMIDs 29449721, 32939038, 32562050.
Deafness_IsolatedAndComplex v0.470 COCH Zornitza Stark edited their review of gene: COCH: Changed publications: 16151338, 28116169, 28099493, 9806553, 17561763, 21046548, 26256111, 22931125, 22610276, 18312449, 28733840, 18697796, 29449721, 32939038, 32562050
Deafness_IsolatedAndComplex v0.470 COCH Zornitza Stark edited their review of gene: COCH: Changed phenotypes: Deafness, autosomal dominant 9, MIM# 601369, Deafness, autosomal recessive 110, MIM# 618094
Mendeliome v0.4647 CNOT1 Zornitza Stark Phenotypes for gene: CNOT1 were changed from Holoprosencephaly 12, with or without pancreatic agenesis; OMIM# 618500 to Vissers-Bodmer syndrome, MIM#619033; Holoprosencephaly 12, with or without pancreatic agenesis; OMIM# 618500
Mendeliome v0.4646 CNOT1 Zornitza Stark Publications for gene: CNOT1 were set to PMID: 31006513
Mendeliome v0.4645 CNOT1 Zornitza Stark Mode of inheritance for gene: CNOT1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4644 CNOT1 Zornitza Stark reviewed gene: CNOT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Vissers-Bodmer syndrome, MIM#619033; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3030 CNOT1 Zornitza Stark Phenotypes for gene: CNOT1 were changed from Holoprosencephaly 12, with or without pancreatic agenesis 618500 to Vissers-Bodmer syndrome, MIM#619033; Holoprosencephaly 12, with or without pancreatic agenesis 618500
Intellectual disability syndromic and non-syndromic v0.3029 CNOT1 Zornitza Stark Publications for gene: CNOT1 were set to 31006510; 21679367; 31006513
Intellectual disability syndromic and non-syndromic v0.3028 CNOT1 Zornitza Stark reviewed gene: CNOT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Vissers-Bodmer syndrome, MIM#619033; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia v0.260 COQ5 Zornitza Stark Phenotypes for gene: COQ5 were changed from Cerebellar ataxia; encephalopathy; generalized tonic-clonic seizures; intellectual disability to Coenzyme Q10 deficiency, primary 9, MIM#619028; Cerebellar ataxia; encephalopathy; generalized tonic-clonic seizures; intellectual disability
Ataxia v0.259 COQ5 Zornitza Stark edited their review of gene: COQ5: Changed phenotypes: Coenzyme Q10 deficiency, primary 9, MIM#619028, Cerebellar ataxia, encephalopathy, generalized tonic-clonic seizures, intellectual disability
Intellectual disability syndromic and non-syndromic v0.3028 COQ5 Zornitza Stark Phenotypes for gene: COQ5 were changed from Cerebellar ataxia; encephalopathy; generalized tonic-clonic seizures; intellectual disability to Coenzyme Q10 deficiency, primary 9, MIM#619028; Cerebellar ataxia; encephalopathy; generalized tonic-clonic seizures; intellectual disability
Intellectual disability syndromic and non-syndromic v0.3027 COQ5 Zornitza Stark edited their review of gene: COQ5: Changed phenotypes: Coenzyme Q10 deficiency, primary 9, MIM#619028, Cerebellar ataxia, encephalopathy, generalized tonic-clonic seizures, intellectual disability
Mitochondrial disease v0.507 COQ5 Zornitza Stark Phenotypes for gene: COQ5 were changed from Cerebellar ataxia; encephalopathy; generalized tonic-clonic seizures; intellectual disability to Coenzyme Q10 deficiency, primary 9, MIM#619028; Cerebellar ataxia; encephalopathy; generalized tonic-clonic seizures; intellectual disability
Mitochondrial disease v0.506 COQ5 Zornitza Stark edited their review of gene: COQ5: Changed phenotypes: Coenzyme Q10 deficiency, primary 9, MIM#619028, Cerebellar ataxia, encephalopathy, generalized tonic-clonic seizures, intellectual disability
Mendeliome v0.4644 COQ5 Zornitza Stark Phenotypes for gene: COQ5 were changed from Cerebellar ataxia; encephalopathy; generalized tonic-clonic seizures; intellectual disability to Coenzyme Q10 deficiency, primary 9, MIM#619028; Cerebellar ataxia; encephalopathy; generalized tonic-clonic seizures; intellectual disability
Mendeliome v0.4643 COQ5 Zornitza Stark edited their review of gene: COQ5: Changed phenotypes: Coenzyme Q10 deficiency, primary 9, MIM#619028, Cerebellar ataxia, encephalopathy, generalized tonic-clonic seizures, intellectual disability
Mendeliome v0.4643 GATA3 Zornitza Stark Marked gene: GATA3 as ready
Mendeliome v0.4643 GATA3 Zornitza Stark Gene: gata3 has been classified as Green List (High Evidence).
Mendeliome v0.4643 GATA3 Zornitza Stark Phenotypes for gene: GATA3 were changed from to Hypoparathyroidism, sensorineural deafness, and renal dysplasia, MIM# 146255
Mendeliome v0.4642 GATA3 Zornitza Stark Publications for gene: GATA3 were set to
Mendeliome v0.4641 GATA3 Zornitza Stark Mode of inheritance for gene: GATA3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4640 GATA3 Zornitza Stark reviewed gene: GATA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10935639, 11389161, 21120445, 26316437, 25771973, 27387476, 30396722; Phenotypes: Hypoparathyroidism, sensorineural deafness, and renal dysplasia, MIM# 146255; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.470 GATA3 Zornitza Stark Marked gene: GATA3 as ready
Deafness_IsolatedAndComplex v0.470 GATA3 Zornitza Stark Gene: gata3 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.470 GATA3 Zornitza Stark Phenotypes for gene: GATA3 were changed from to Hypoparathyroidism, sensorineural deafness, and renal dysplasia, MIM# 146255
Deafness_IsolatedAndComplex v0.469 GATA3 Zornitza Stark Publications for gene: GATA3 were set to
Deafness_IsolatedAndComplex v0.468 GATA3 Zornitza Stark Mode of inheritance for gene: GATA3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.467 GATA3 Zornitza Stark reviewed gene: GATA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10935639, 11389161, 21120445, 26316437, 25771973, 27387476, 30396722; Phenotypes: Hypoparathyroidism, sensorineural deafness, and renal dysplasia, MIM# 146255; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4640 FGF3 Zornitza Stark Publications for gene: FGF3 were set to
Mendeliome v0.4639 FGF3 Zornitza Stark reviewed gene: FGF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21480479, 21306635, 18435799, 17236138, 21306635, 18701883, 8223243, 26995070, 29902227, 30504125; Phenotypes: Deafness, congenital with inner ear agenesis, microtia, and microdontia, MIM# 610706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.467 FGF3 Zornitza Stark Marked gene: FGF3 as ready
Deafness_IsolatedAndComplex v0.467 FGF3 Zornitza Stark Gene: fgf3 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.467 FGF3 Zornitza Stark Phenotypes for gene: FGF3 were changed from to Deafness, congenital with inner ear agenesis, microtia, and microdontia, MIM# 610706
Deafness_IsolatedAndComplex v0.466 FGF3 Zornitza Stark Publications for gene: FGF3 were set to
Deafness_IsolatedAndComplex v0.465 FGF3 Zornitza Stark Mode of inheritance for gene: FGF3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.464 FGF3 Zornitza Stark reviewed gene: FGF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21480479, 21306635, 18435799, 17236138, 21306635, 18701883, 8223243, 26995070, 29902227, 30504125; Phenotypes: Deafness, congenital with inner ear agenesis, microtia, and microdontia, MIM# 610706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.13 EYA4 Zornitza Stark Marked gene: EYA4 as ready
Cardiomyopathy_Paediatric v0.13 EYA4 Zornitza Stark Gene: eya4 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.13 EYA4 Zornitza Stark Phenotypes for gene: EYA4 were changed from Cardiomyopathy, dilated, 1J to Cardiomyopathy, dilated, 1J, MIM# 605362
Cardiomyopathy_Paediatric v0.12 EYA4 Zornitza Stark Publications for gene: EYA4 were set to
Cardiomyopathy_Paediatric v0.11 EYA4 Zornitza Stark reviewed gene: EYA4: Rating: AMBER; Mode of pathogenicity: None; Publications: 10769282, 30155266; Phenotypes: Cardiomyopathy, dilated, 1J, MIM# 605362; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4639 EYA4 Zornitza Stark Phenotypes for gene: EYA4 were changed from to Deafness, autosomal dominant 10, MIM# 601316; Cardiomyopathy, dilated, 1J, MIM# 605362
Mendeliome v0.4638 EYA4 Zornitza Stark Publications for gene: EYA4 were set to
Mendeliome v0.4637 EYA4 Zornitza Stark Mode of inheritance for gene: EYA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4636 EYA4 Zornitza Stark reviewed gene: EYA4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11159937, ​17568404, 25681523, 25963406, 25242383, 26331839, 18219393, 27545760, 15735644, 10769282, 30155266; Phenotypes: Deafness, autosomal dominant 10, MIM# 601316, Cardiomyopathy, dilated, 1J, MIM# 605362; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.464 EYA4 Zornitza Stark Marked gene: EYA4 as ready
Deafness_IsolatedAndComplex v0.464 EYA4 Zornitza Stark Gene: eya4 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.464 EYA4 Zornitza Stark Phenotypes for gene: EYA4 were changed from to Deafness, autosomal dominant 10, MIM# 601316
Deafness_IsolatedAndComplex v0.463 EYA4 Zornitza Stark Publications for gene: EYA4 were set to
Deafness_IsolatedAndComplex v0.462 EYA4 Zornitza Stark Mode of inheritance for gene: EYA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.461 EYA4 Zornitza Stark reviewed gene: EYA4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11159937, ​17568404, 25681523, 25963406, 25242383, 26331839, 18219393, 27545760, 15735644; Phenotypes: Deafness, autosomal dominant 10, MIM# 601316; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.461 EYA1 Zornitza Stark Marked gene: EYA1 as ready
Deafness_IsolatedAndComplex v0.461 EYA1 Zornitza Stark Gene: eya1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.461 EYA1 Zornitza Stark Phenotypes for gene: EYA1 were changed from to Branchiootic syndrome 1, MIM# 602588
Deafness_IsolatedAndComplex v0.460 EYA1 Zornitza Stark Mode of inheritance for gene: EYA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.459 EYA1 Zornitza Stark reviewed gene: EYA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Branchiootic syndrome 1, MIM# 602588; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.89 ESPN Zornitza Stark Marked gene: ESPN as ready
Additional findings_Paediatric v0.89 ESPN Zornitza Stark Gene: espn has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.89 ESPN Zornitza Stark Phenotypes for gene: ESPN were changed from Hearing loss to Deafness, autosomal recessive 36, MIM# 609006
Additional findings_Paediatric v0.88 ESPN Zornitza Stark Publications for gene: ESPN were set to
Additional findings_Paediatric v0.87 ESPN Zornitza Stark Classified gene: ESPN as Green List (high evidence)
Additional findings_Paediatric v0.87 ESPN Zornitza Stark Gene: espn has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.86 ESPN Zornitza Stark reviewed gene: ESPN: Rating: GREEN; Mode of pathogenicity: None; Publications: 15286153, 18973245, 26445815, 28281779, 10975527, 15930085; Phenotypes: Deafness, autosomal recessive 36, MIM# 609006; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Usher Syndrome v0.15 ESPN Zornitza Stark Marked gene: ESPN as ready
Usher Syndrome v0.15 ESPN Zornitza Stark Gene: espn has been classified as Red List (Low Evidence).
Usher Syndrome v0.15 ESPN Zornitza Stark Phenotypes for gene: ESPN were changed from ?Usher syndrome, type 1M, 618632; Deafness, autosomal recessive 36, 609006 to Usher syndrome, type 1M, MIM#618632
Usher Syndrome v0.14 ESPN Zornitza Stark Publications for gene: ESPN were set to
Usher Syndrome v0.13 ESPN Zornitza Stark Classified gene: ESPN as Red List (low evidence)
Usher Syndrome v0.13 ESPN Zornitza Stark Gene: espn has been classified as Red List (Low Evidence).
Usher Syndrome v0.12 ESPN Zornitza Stark reviewed gene: ESPN: Rating: RED; Mode of pathogenicity: None; Publications: 29572253; Phenotypes: Usher syndrome, type 1M, MIM# 618632; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4636 ESPN Zornitza Stark Marked gene: ESPN as ready
Mendeliome v0.4636 ESPN Zornitza Stark Gene: espn has been classified as Green List (High Evidence).
Mendeliome v0.4636 ESPN Zornitza Stark Phenotypes for gene: ESPN were changed from to Deafness, autosomal recessive 36, MIM# 609006; Deafness, neurosensory, without vestibular involvement, autosomal dominant, MIM# 609006
Mendeliome v0.4635 ESPN Zornitza Stark Publications for gene: ESPN were set to
Mendeliome v0.4634 ESPN Zornitza Stark Mode of inheritance for gene: ESPN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4633 ESPN Zornitza Stark reviewed gene: ESPN: Rating: GREEN; Mode of pathogenicity: None; Publications: 15286153, 18973245, 26445815, 28281779, 10975527, 15930085; Phenotypes: Deafness, autosomal recessive 36, MIM# 609006, Deafness, neurosensory, without vestibular involvement, autosomal dominant, MIM# 609006; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.459 ESPN Zornitza Stark Marked gene: ESPN as ready
Deafness_IsolatedAndComplex v0.459 ESPN Zornitza Stark Gene: espn has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.459 ESPN Zornitza Stark Phenotypes for gene: ESPN were changed from to Deafness, autosomal recessive 36, MIM# 609006; Deafness, neurosensory, without vestibular involvement, autosomal dominant, MIM# 609006
Deafness_IsolatedAndComplex v0.458 ESPN Zornitza Stark Publications for gene: ESPN were set to
Deafness_IsolatedAndComplex v0.457 ESPN Zornitza Stark Mode of inheritance for gene: ESPN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.456 ESPN Zornitza Stark reviewed gene: ESPN: Rating: GREEN; Mode of pathogenicity: None; Publications: 15286153, 18973245, 26445815, 28281779, 10975527, 15930085; Phenotypes: Deafness, autosomal recessive 36, MIM# 609006, Deafness, neurosensory, without vestibular involvement, autosomal dominant, MIM# 609006; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.456 DIAPH1 Zornitza Stark Marked gene: DIAPH1 as ready
Deafness_IsolatedAndComplex v0.456 DIAPH1 Zornitza Stark Gene: diaph1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.456 DIAPH1 Zornitza Stark Phenotypes for gene: DIAPH1 were changed from to Deafness, autosomal dominant 1, with or without thrombocytopenia, MIM# 124900
Deafness_IsolatedAndComplex v0.455 DIAPH1 Zornitza Stark Publications for gene: DIAPH1 were set to
Deafness_IsolatedAndComplex v0.454 DIAPH1 Zornitza Stark Mode of pathogenicity for gene: DIAPH1 was changed from to None
Deafness_IsolatedAndComplex v0.453 DIAPH1 Zornitza Stark Mode of inheritance for gene: DIAPH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4633 PRIMPOL Zornitza Stark edited their review of gene: PRIMPOL: Changed rating: RED
Mendeliome v0.4633 PRIMPOL Seb Lunke commented on gene: PRIMPOL
Mendeliome v0.4633 DFNB59 Zornitza Stark Marked gene: DFNB59 as ready
Mendeliome v0.4633 DFNB59 Zornitza Stark Gene: dfnb59 has been classified as Green List (High Evidence).
Mendeliome v0.4633 DFNB59 Zornitza Stark Phenotypes for gene: DFNB59 were changed from to Deafness, autosomal recessive 59, MIM# 610220
Mendeliome v0.4632 DFNB59 Zornitza Stark Publications for gene: DFNB59 were set to
Mendeliome v0.4631 DFNB59 Zornitza Stark Mode of inheritance for gene: DFNB59 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4630 DFNB59 Zornitza Stark reviewed gene: DFNB59: Rating: GREEN; Mode of pathogenicity: None; Publications: 16804542, 26166082, 22617256, 28964305, 17373699, 25631766, 28209736; Phenotypes: Deafness, autosomal recessive 59, MIM# 610220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.452 DFNB59 Zornitza Stark Marked gene: DFNB59 as ready
Deafness_IsolatedAndComplex v0.452 DFNB59 Zornitza Stark Gene: dfnb59 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.452 DFNB59 Zornitza Stark Phenotypes for gene: DFNB59 were changed from to Deafness, autosomal recessive 59, MIM# 610220
Deafness_IsolatedAndComplex v0.451 DFNB59 Zornitza Stark Publications for gene: DFNB59 were set to
Deafness_IsolatedAndComplex v0.450 DFNB59 Zornitza Stark Mode of inheritance for gene: DFNB59 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.449 DFNB59 Zornitza Stark changed review comment from: DEFINITIVE by ClinGen, over 50 affected individuals from more than 10 families reported, supportive functional data including animal models.; to: DEFINITIVE by ClinGen, over 50 affected individuals from more than 10 families reported, supportive functional data including animal models.

New HGNC name is PJVK.
Deafness_IsolatedAndComplex v0.449 DFNB59 Zornitza Stark reviewed gene: DFNB59: Rating: GREEN; Mode of pathogenicity: None; Publications: 16804542, 26166082, 22617256, 28964305, 17373699, 25631766, 28209736; Phenotypes: Deafness, autosomal recessive 59, MIM# 610220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.449 DFNB59 Zornitza Stark Tag new gene name tag was added to gene: DFNB59.
Mendeliome v0.4630 DFNA5 Zornitza Stark Marked gene: DFNA5 as ready
Mendeliome v0.4630 DFNA5 Zornitza Stark Gene: dfna5 has been classified as Green List (High Evidence).
Mendeliome v0.4630 DFNA5 Zornitza Stark Phenotypes for gene: DFNA5 were changed from to Deafness, autosomal dominant 5, MIM# 600994
Mendeliome v0.4629 DFNA5 Zornitza Stark Publications for gene: DFNA5 were set to
Mendeliome v0.4628 DFNA5 Zornitza Stark Mode of inheritance for gene: DFNA5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4627 DFNA5 Zornitza Stark Tag new gene name tag was added to gene: DFNA5.
Mendeliome v0.4627 DFNA5 Zornitza Stark reviewed gene: DFNA5: Rating: GREEN; Mode of pathogenicity: None; Publications: 9771715, 14676472, ​14559215, 24933359, 17868390, 24506266, 12853124, 14736743, 22848872; Phenotypes: Deafness, autosomal dominant 5, MIM# 600994; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.449 DFNA5 Zornitza Stark Marked gene: DFNA5 as ready
Deafness_IsolatedAndComplex v0.449 DFNA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is GSDME
Deafness_IsolatedAndComplex v0.449 DFNA5 Zornitza Stark Gene: dfna5 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.449 DFNA5 Zornitza Stark Phenotypes for gene: DFNA5 were changed from to Deafness, autosomal dominant 5, MIM# 600994
Deafness_IsolatedAndComplex v0.448 DFNA5 Zornitza Stark Publications for gene: DFNA5 were set to
Deafness_IsolatedAndComplex v0.447 DFNA5 Zornitza Stark Mode of inheritance for gene: DFNA5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.446 DFNA5 Zornitza Stark Tag new gene name tag was added to gene: DFNA5.
Deafness_IsolatedAndComplex v0.446 DFNA5 Zornitza Stark reviewed gene: DFNA5: Rating: GREEN; Mode of pathogenicity: None; Publications: 9771715, 14676472, ​14559215, 24933359, 17868390, 24506266, 12853124, 14736743, 22848872; Phenotypes: Deafness, autosomal dominant 5, MIM# 600994; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.446 COL9A3 Zornitza Stark Marked gene: COL9A3 as ready
Deafness_IsolatedAndComplex v0.446 COL9A3 Zornitza Stark Gene: col9a3 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.446 COL9A3 Zornitza Stark Phenotypes for gene: COL9A3 were changed from to Stickler syndrome
Deafness_IsolatedAndComplex v0.445 COL9A3 Zornitza Stark Publications for gene: COL9A3 were set to
Deafness_IsolatedAndComplex v0.444 COL9A3 Zornitza Stark Mode of inheritance for gene: COL9A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.443 COL9A3 Zornitza Stark reviewed gene: COL9A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30450842, 31090205, 24273071; Phenotypes: Stickler syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.89 C9orf72 Bryony Thompson Marked STR: C9orf72 as ready
Early-onset Parkinson disease v0.89 C9orf72 Bryony Thompson Str: c9orf72 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.89 C9orf72 Bryony Thompson Classified STR: C9orf72 as Green List (high evidence)
Early-onset Parkinson disease v0.89 C9orf72 Bryony Thompson Str: c9orf72 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.88 C9orf72 Bryony Thompson STR: C9orf72 was added
STR: C9orf72 was added to Early-onset Parkinson disease. Sources: Expert list
STR tags were added to STR: C9orf72.
Mode of inheritance for STR: C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: C9orf72 were set to 25577942; 31779815
Phenotypes for STR: C9orf72 were set to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 MIM#105550
Review for STR: C9orf72 was set to GREEN
STR: C9orf72 was marked as clinically relevant
Added comment: NG_031977​.1:g.5321GGGGCC[X] Repeat expansion affects the protein degradation pathways and may contribute to TDP‐43 accumulation Normal alleles: ≤25 G4C2 hexanucleotide repeat units generally considered normal Pathogenic high-penetrance alleles: ≥60 G4C2 hexanucleotide repeat units are considered pathogenic Note: The minimal size of a G4C2 pathogenic repeat is under debate: some studies consider repeats of >30 G4C2 hexanucleotide repeat units as pathogenic, whereas others use a cutoff of 60 G4C2 hexanucleotide repeat units.
Sources: Expert list
Early-onset Parkinson disease v0.87 C9orf72 Bryony Thompson Classified gene: C9orf72 as No list
Early-onset Parkinson disease v0.87 C9orf72 Bryony Thompson Gene: c9orf72 has been removed from the panel.
Early-onset Parkinson disease v0.86 HTT Bryony Thompson Classified gene: HTT as No list
Early-onset Parkinson disease v0.86 HTT Bryony Thompson Gene: htt has been removed from the panel.
Early-onset Parkinson disease v0.85 RIC3 Bryony Thompson Marked gene: RIC3 as ready
Early-onset Parkinson disease v0.85 RIC3 Bryony Thompson Gene: ric3 has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.85 RIC3 Bryony Thompson gene: RIC3 was added
gene: RIC3 was added to Early-onset Parkinson disease. Sources: Other
Mode of inheritance for gene: RIC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RIC3 were set to 27055476; 28153381; 28606768; 32794657
Phenotypes for gene: RIC3 were set to Parkinson disease
Review for gene: RIC3 was set to RED
Added comment: Segregation reported in a single Indian family (PMID: 27055476), with limited in vitro functional assays. The variant is present in the South Asian population in gnomAD v2.1 14/30,596 alleles. The association has not been replicated in any additional studies.
Sources: Other
Mendeliome v0.4627 RIC3 Bryony Thompson Marked gene: RIC3 as ready
Mendeliome v0.4627 RIC3 Bryony Thompson Gene: ric3 has been classified as Red List (Low Evidence).
Mendeliome v0.4627 RIC3 Bryony Thompson Classified gene: RIC3 as Red List (low evidence)
Mendeliome v0.4627 RIC3 Bryony Thompson Gene: ric3 has been classified as Red List (Low Evidence).
Mendeliome v0.4626 RIC3 Bryony Thompson reviewed gene: RIC3: Rating: RED; Mode of pathogenicity: None; Publications: 27055476, 28153381, 28606768, 32794657; Phenotypes: Parkinson disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4626 PRIMPOL Zornitza Stark Tag disputed tag was added to gene: PRIMPOL.
Mendeliome v0.4626 PRIMPOL Zornitza Stark Classified gene: PRIMPOL as Red List (low evidence)
Mendeliome v0.4626 PRIMPOL Zornitza Stark Gene: primpol has been classified as Red List (Low Evidence).
Mitochondrial disease v0.506 MIEF2 Zornitza Stark Phenotypes for gene: MIEF2 were changed from Progressive muscle weakness; Exercise intolerance; Ragged red and COX negative fibres; Complex I and IV deficiency to Combined oxidative phosphorylation deficiency 49, MIM# 619024; Progressive muscle weakness; Exercise intolerance; Ragged red and COX negative fibres; Complex I and IV deficiency
Mendeliome v0.4625 MIEF2 Zornitza Stark Phenotypes for gene: MIEF2 were changed from Progressive muscle weakness; Exercise intolerance; Ragged red and COX negative fibres; Complex I and IV deficiency to Combined oxidative phosphorylation deficiency 49, MIM# 619024; Progressive muscle weakness; Exercise intolerance; Ragged red and COX negative fibres; Complex I and IV deficiency
Mendeliome v0.4624 MRPS25 Zornitza Stark Phenotypes for gene: MRPS25 were changed from Dyskinetic cerebral palsy; Mitochondrial myopathy; Partial agenesis of the corpus callosum to Combined oxidative phosphorylation deficiency 50, MIM# 619025; Dyskinetic cerebral palsy; Mitochondrial myopathy; Partial agenesis of the corpus callosum
Mendeliome v0.4623 MRPS25 Zornitza Stark edited their review of gene: MRPS25: Changed phenotypes: Combined oxidative phosphorylation deficiency 50, MIM# 619025, Dyskinetic cerebral palsy, Mitochondrial myopathy, Partial agenesis of the corpus callosum
Mitochondrial disease v0.505 MRPS25 Zornitza Stark Phenotypes for gene: MRPS25 were changed from Dyskinetic cerebral palsy; Mitochondrial myopathy; Partial agenesis of the corpus callosum to Combined oxidative phosphorylation deficiency 50, MIM# 619025; Dyskinetic cerebral palsy; Mitochondrial myopathy; Partial agenesis of the corpus callosum
Mitochondrial disease v0.504 MRPS25 Zornitza Stark edited their review of gene: MRPS25: Changed phenotypes: Combined oxidative phosphorylation deficiency 50, MIM# 619025, Dyskinetic cerebral palsy, Mitochondrial myopathy, Partial agenesis of the corpus callosum
Mendeliome v0.4623 MIEF2 Zornitza Stark edited their review of gene: MIEF2: Changed phenotypes: Combined oxidative phosphorylation deficiency 49, MIM# 619024, Progressive muscle weakness, Exercise intolerance, Ragged red and COX negative fibres, Complex I and IV deficiency
Mitochondrial disease v0.504 MIEF2 Zornitza Stark edited their review of gene: MIEF2: Changed phenotypes: Combined oxidative phosphorylation deficiency 49, MIM# 619024, Progressive muscle weakness, Exercise intolerance, Ragged red and COX negative fibres, Complex I and IV deficiency
Mendeliome v0.4623 PRIMPOL Sebastian Lunke reviewed gene: PRIMPOL: Rating: RED; Mode of pathogenicity: None; Publications: 23579484, 32375772, 25262353, 27230014, 25680975, 31560770; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.443 COL9A2 Zornitza Stark Marked gene: COL9A2 as ready
Deafness_IsolatedAndComplex v0.443 COL9A2 Zornitza Stark Gene: col9a2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.443 COL9A2 Zornitza Stark Phenotypes for gene: COL9A2 were changed from to Stickler syndrome, type V, MIM# 614284
Deafness_IsolatedAndComplex v0.442 COL9A2 Zornitza Stark Publications for gene: COL9A2 were set to
Deafness_IsolatedAndComplex v0.441 COL9A2 Zornitza Stark Mode of inheritance for gene: COL9A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.440 COL9A2 Zornitza Stark reviewed gene: COL9A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31090205, 21671392, 20686772, 27666725, 15802199, 15710493; Phenotypes: Stickler syndrome, type V, MIM# 614284; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuria v0.135 COL4A5 Zornitza Stark Marked gene: COL4A5 as ready
Proteinuria v0.135 COL4A5 Zornitza Stark Gene: col4a5 has been classified as Green List (High Evidence).
Proteinuria v0.135 COL4A5 Zornitza Stark Phenotypes for gene: COL4A5 were changed from to Alport syndrome 1, X-linked, MIM# 301050
Proteinuria v0.134 COL4A5 Zornitza Stark Mode of inheritance for gene: COL4A5 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Proteinuria v0.133 COL4A5 Zornitza Stark reviewed gene: COL4A5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alport syndrome 1, X-linked, MIM# 301050; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Haematuria_Alport v0.37 COL4A5 Zornitza Stark Marked gene: COL4A5 as ready
Haematuria_Alport v0.37 COL4A5 Zornitza Stark Gene: col4a5 has been classified as Green List (High Evidence).
Haematuria_Alport v0.37 COL4A5 Zornitza Stark Phenotypes for gene: COL4A5 were changed from to Alport syndrome 1, X-linked, MIM# 301050
Haematuria_Alport v0.36 COL4A5 Zornitza Stark Mode of inheritance for gene: COL4A5 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Haematuria_Alport v0.35 COL4A5 Zornitza Stark reviewed gene: COL4A5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alport syndrome 1, X-linked, MIM# 301050; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.4623 COL4A5 Zornitza Stark Marked gene: COL4A5 as ready
Mendeliome v0.4623 COL4A5 Zornitza Stark Gene: col4a5 has been classified as Green List (High Evidence).
Mendeliome v0.4623 COL4A5 Zornitza Stark Phenotypes for gene: COL4A5 were changed from to Alport syndrome 1, X-linked, MIM# 301050
Mendeliome v0.4622 COL4A5 Zornitza Stark Mode of inheritance for gene: COL4A5 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.4621 COL4A5 Zornitza Stark reviewed gene: COL4A5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alport syndrome 1, X-linked, MIM# 301050; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Deafness_IsolatedAndComplex v0.440 COL4A5 Zornitza Stark Marked gene: COL4A5 as ready
Deafness_IsolatedAndComplex v0.440 COL4A5 Zornitza Stark Gene: col4a5 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.440 COL4A5 Zornitza Stark Phenotypes for gene: COL4A5 were changed from to Alport syndrome 1, X-linked, MIM# 301050
Deafness_IsolatedAndComplex v0.439 COL4A5 Zornitza Stark Mode of inheritance for gene: COL4A5 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Deafness_IsolatedAndComplex v0.438 COL4A5 Zornitza Stark reviewed gene: COL4A5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alport syndrome 1, X-linked, MIM# 301050; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Deafness_IsolatedAndComplex v0.438 COL11A2 Zornitza Stark Marked gene: COL11A2 as ready
Deafness_IsolatedAndComplex v0.438 COL11A2 Zornitza Stark Gene: col11a2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.438 COL11A2 Zornitza Stark Phenotypes for gene: COL11A2 were changed from to Deafness, autosomal dominant 13, MIM# 601868; Deafness, autosomal recessive 53, MIM# 609706; Otospondylomegaepiphyseal dysplasia, autosomal dominant, MIM# 184840; Otospondylomegaepiphyseal dysplasia, autosomal recessive, MIM# 215150
Deafness_IsolatedAndComplex v0.437 COL11A2 Zornitza Stark Publications for gene: COL11A2 were set to 10581026; 25633957; 16033917
Deafness_IsolatedAndComplex v0.437 COL11A2 Zornitza Stark Publications for gene: COL11A2 were set to
Deafness_IsolatedAndComplex v0.436 COL11A2 Zornitza Stark Mode of inheritance for gene: COL11A2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.435 COL11A2 Zornitza Stark reviewed gene: COL11A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10581026, 25633957, 16033917; Phenotypes: Deafness, autosomal dominant 13, MIM# 601868, Deafness, autosomal recessive 53, MIM# 609706, Otospondylomegaepiphyseal dysplasia, autosomal dominant, MIM# 184840, Otospondylomegaepiphyseal dysplasia, autosomal recessive, MIM# 215150; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.435 COL11A1 Zornitza Stark Marked gene: COL11A1 as ready
Deafness_IsolatedAndComplex v0.435 COL11A1 Zornitza Stark Gene: col11a1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.435 COL11A1 Zornitza Stark Phenotypes for gene: COL11A1 were changed from to Stickler syndrome, type II, MIM# 604841; Marshall syndrome, MIM# 154780
Deafness_IsolatedAndComplex v0.434 COL11A1 Zornitza Stark Mode of inheritance for gene: COL11A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.433 COL11A1 Zornitza Stark reviewed gene: COL11A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Stickler syndrome, type II, MIM# 604841, Marshall syndrome, MIM# 154780; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.433 COCH Zornitza Stark Marked gene: COCH as ready
Deafness_IsolatedAndComplex v0.433 COCH Zornitza Stark Gene: coch has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.433 COCH Zornitza Stark edited their review of gene: COCH: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4621 COCH Zornitza Stark Marked gene: COCH as ready
Mendeliome v0.4621 COCH Zornitza Stark Gene: coch has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.433 COCH Zornitza Stark Mode of inheritance for gene: COCH was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4621 COCH Zornitza Stark Phenotypes for gene: COCH were changed from to Deafness, autosomal dominant 9, MIM# 601369
Mendeliome v0.4620 COCH Zornitza Stark Publications for gene: COCH were set to
Mendeliome v0.4619 COCH Zornitza Stark Mode of inheritance for gene: COCH was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4618 COCH Zornitza Stark reviewed gene: COCH: Rating: GREEN; Mode of pathogenicity: None; Publications: 16151338, 28116169, 28099493, 9806553, 17561763, 21046548, 26256111, 22931125, 22610276, 18312449, 28733840, 18697796, 29449721; Phenotypes: Deafness, autosomal dominant 9, MIM# 601369; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.432 COCH Zornitza Stark Phenotypes for gene: COCH were changed from to Deafness, autosomal dominant 9, MIM# 601369
Deafness_IsolatedAndComplex v0.431 COCH Zornitza Stark Publications for gene: COCH were set to
Deafness_IsolatedAndComplex v0.430 COCH Zornitza Stark Mode of inheritance for gene: COCH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.429 COCH Zornitza Stark reviewed gene: COCH: Rating: GREEN; Mode of pathogenicity: None; Publications: 16151338, 28116169, 28099493, 9806553, 17561763, 21046548, 26256111, 22931125, 22610276, 18312449, 28733840, 18697796, 29449721; Phenotypes: Deafness, autosomal dominant 9, MIM# 601369; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Usher Syndrome v0.12 CLRN1 Zornitza Stark Marked gene: CLRN1 as ready
Usher Syndrome v0.12 CLRN1 Zornitza Stark Gene: clrn1 has been classified as Green List (High Evidence).
Usher Syndrome v0.12 CLRN1 Zornitza Stark Phenotypes for gene: CLRN1 were changed from ?Usher syndrome, type 3A, 276902Retinitis pigmentosa 61, 614180 to Usher syndrome, type 3A, 276902; Retinitis pigmentosa 61, 614180
Usher Syndrome v0.11 CLRN1 Zornitza Stark Publications for gene: CLRN1 were set to
Usher Syndrome v0.10 CLRN1 Zornitza Stark reviewed gene: CLRN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11524702, 24596593, 22135276, 21675857, 19753315, 27110679, 26943149, 22787034; Phenotypes: Usher syndrome, type 3A, MIM# 276902; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4618 CLRN1 Zornitza Stark Marked gene: CLRN1 as ready
Mendeliome v0.4618 CLRN1 Zornitza Stark Gene: clrn1 has been classified as Green List (High Evidence).
Mendeliome v0.4618 CLRN1 Zornitza Stark Phenotypes for gene: CLRN1 were changed from to Usher syndrome, type 3A, MIM# 276902
Mendeliome v0.4617 CLRN1 Zornitza Stark Publications for gene: CLRN1 were set to
Mendeliome v0.4616 CLRN1 Zornitza Stark Mode of inheritance for gene: CLRN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4615 CLRN1 Zornitza Stark reviewed gene: CLRN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11524702, 24596593, 22135276, 21675857, 19753315, 27110679, 26943149, 22787034; Phenotypes: Usher syndrome, type 3A, MIM# 276902; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.429 CLRN1 Zornitza Stark Marked gene: CLRN1 as ready
Deafness_IsolatedAndComplex v0.429 CLRN1 Zornitza Stark Gene: clrn1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.429 CLRN1 Zornitza Stark Phenotypes for gene: CLRN1 were changed from to Usher syndrome, type 3A, MIM# 276902
Deafness_IsolatedAndComplex v0.428 CLRN1 Zornitza Stark Publications for gene: CLRN1 were set to 11524702; 24596593; 22135276; 21675857; 19753315; 27110679; 26943149; 22787034
Deafness_IsolatedAndComplex v0.428 CLRN1 Zornitza Stark Publications for gene: CLRN1 were set to
Deafness_IsolatedAndComplex v0.427 CLRN1 Zornitza Stark Mode of inheritance for gene: CLRN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.426 CLRN1 Zornitza Stark reviewed gene: CLRN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11524702, 24596593, 22135276, 21675857, 19753315, 27110679, 26943149, 22787034; Phenotypes: Usher syndrome, type 3A, MIM# 276902; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.86 CLPP Zornitza Stark Marked gene: CLPP as ready
Additional findings_Paediatric v0.86 CLPP Zornitza Stark Gene: clpp has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.86 CLPP Zornitza Stark Phenotypes for gene: CLPP were changed from Perrault syndrome to Perrault syndrome 3, MIM# 614129
Additional findings_Paediatric v0.85 CLPP Zornitza Stark Publications for gene: CLPP were set to
Additional findings_Paediatric v0.84 CLPP Zornitza Stark Classified gene: CLPP as Green List (high evidence)
Additional findings_Paediatric v0.84 CLPP Zornitza Stark Gene: clpp has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.83 CLPP Zornitza Stark reviewed gene: CLPP: Rating: GREEN; Mode of pathogenicity: None; Publications: 23541340, 27087618, 27899912, 25254289; Phenotypes: Perrault syndrome 3, MIM# 614129; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.426 CLPP Zornitza Stark Publications for gene: CLPP were set to 23541340; 27087618; 27899912; 25254289
Deafness_IsolatedAndComplex v0.425 CLPP Zornitza Stark edited their review of gene: CLPP: Changed publications: 23541340, 27087618, 27899912, 25254289, 23851121
Deafness_IsolatedAndComplex v0.425 CLPP Zornitza Stark changed review comment from: Perrault syndrome (PRLTS) is an autosomal recessive disorder characterized by sensorineural hearing loss (SNHL) and premature ovarian failure (POF) secondary to ovarian dysgenesis. Affected males have SNHL but show normal pubertal development. A spectrum of additional clinical features, including cerebellar ataxia, learning disability, and peripheral neuropathy, have been described in some affected individuals. More than 5 unrelated families reported.; to: Perrault syndrome (PRLTS) is an autosomal recessive disorder characterized by sensorineural hearing loss (SNHL) and premature ovarian failure (POF) secondary to ovarian dysgenesis. Affected males have SNHL but show normal pubertal development. A spectrum of additional clinical features, including cerebellar ataxia, learning disability, and peripheral neuropathy, have been described in some affected individuals. More than 5 unrelated families (11 probands) reported, mouse model.
Mendeliome v0.4615 CLPP Zornitza Stark Marked gene: CLPP as ready
Mendeliome v0.4615 CLPP Zornitza Stark Gene: clpp has been classified as Green List (High Evidence).
Mendeliome v0.4615 CLPP Zornitza Stark Phenotypes for gene: CLPP were changed from to Perrault syndrome 3, MIM# 614129
Mendeliome v0.4614 CLPP Zornitza Stark Publications for gene: CLPP were set to
Mendeliome v0.4613 CLPP Zornitza Stark Mode of inheritance for gene: CLPP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4612 CLPP Zornitza Stark reviewed gene: CLPP: Rating: GREEN; Mode of pathogenicity: None; Publications: 23541340, 27087618, 27899912, 25254289; Phenotypes: Perrault syndrome 3, MIM# 614129; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.425 CLPP Zornitza Stark Marked gene: CLPP as ready
Deafness_IsolatedAndComplex v0.425 CLPP Zornitza Stark Gene: clpp has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.425 CLPP Zornitza Stark Phenotypes for gene: CLPP were changed from to Perrault syndrome 3, MIM# 614129
Deafness_IsolatedAndComplex v0.424 CLPP Zornitza Stark Publications for gene: CLPP were set to
Deafness_IsolatedAndComplex v0.423 CLPP Zornitza Stark Mode of inheritance for gene: CLPP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.422 CLPP Zornitza Stark reviewed gene: CLPP: Rating: GREEN; Mode of pathogenicity: None; Publications: 23541340, 27087618, 27899912, 25254289; Phenotypes: Perrault syndrome 3, MIM# 614129; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.422 CIB2 Zornitza Stark Marked gene: CIB2 as ready
Deafness_IsolatedAndComplex v0.422 CIB2 Zornitza Stark Gene: cib2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.422 CIB2 Zornitza Stark Phenotypes for gene: CIB2 were changed from to Deafness, autosomal recessive 48, MIM# 609439
Additional findings_Paediatric v0.83 CIB2 Zornitza Stark Marked gene: CIB2 as ready
Additional findings_Paediatric v0.83 CIB2 Zornitza Stark Gene: cib2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.83 CIB2 Zornitza Stark Classified gene: CIB2 as Green List (high evidence)
Additional findings_Paediatric v0.83 CIB2 Zornitza Stark Gene: cib2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.82 CIB2 Zornitza Stark gene: CIB2 was added
gene: CIB2 was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: CIB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CIB2 were set to 23023331; 23023331; 26173970; 26473954; 27344577; 26226137; 26445815
Phenotypes for gene: CIB2 were set to Deafness, autosomal recessive 48, MIM# 609439
Review for gene: CIB2 was set to GREEN
Added comment: DEFINITIVE association with isolated deafness, REFUTED association with Usher syndrome by ClinGen. Multiple families, mouse and zebrafish animal models, all families but one with isolated deafness.
Sources: Expert list
Mendeliome v0.4612 CLDN14 Zornitza Stark Marked gene: CLDN14 as ready
Mendeliome v0.4612 CLDN14 Zornitza Stark Gene: cldn14 has been classified as Green List (High Evidence).
Mendeliome v0.4612 CLDN14 Zornitza Stark Phenotypes for gene: CLDN14 were changed from to Deafness, autosomal recessive 29, MIM# 614035
Mendeliome v0.4611 CLDN14 Zornitza Stark Publications for gene: CLDN14 were set to
Mendeliome v0.4610 CLDN14 Zornitza Stark Mode of inheritance for gene: CLDN14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4609 CLDN14 Zornitza Stark reviewed gene: CLDN14: Rating: GREEN; Mode of pathogenicity: None; Publications: 11163249, 20811388, 22246673, 23235333, 27870113, 27838790, 12913076; Phenotypes: Deafness, autosomal recessive 29, MIM# 614035; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.421 CLDN14 Zornitza Stark Marked gene: CLDN14 as ready
Deafness_IsolatedAndComplex v0.421 CLDN14 Zornitza Stark Gene: cldn14 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.421 CLDN14 Zornitza Stark Phenotypes for gene: CLDN14 were changed from to Deafness, autosomal recessive 29, MIM# 614035
Deafness_IsolatedAndComplex v0.420 CLDN14 Zornitza Stark Publications for gene: CLDN14 were set to
Deafness_IsolatedAndComplex v0.419 CLDN14 Zornitza Stark Mode of inheritance for gene: CLDN14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.418 CLDN14 Zornitza Stark reviewed gene: CLDN14: Rating: GREEN; Mode of pathogenicity: None; Publications: 11163249, 20811388, 22246673, 23235333, 27870113, 27838790, 12913076; Phenotypes: Deafness, autosomal recessive 29, MIM# 614035; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4609 CIB2 Zornitza Stark Marked gene: CIB2 as ready
Mendeliome v0.4609 CIB2 Zornitza Stark Gene: cib2 has been classified as Green List (High Evidence).
Mendeliome v0.4609 CIB2 Zornitza Stark Phenotypes for gene: CIB2 were changed from to Deafness, autosomal recessive 48, MIM# 609439
Mendeliome v0.4608 CIB2 Zornitza Stark Publications for gene: CIB2 were set to
Mendeliome v0.4607 CIB2 Zornitza Stark Mode of inheritance for gene: CIB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4606 CIB2 Zornitza Stark reviewed gene: CIB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23023331, 23023331, 26173970, 26473954, 27344577, 26226137, 26445815; Phenotypes: Deafness, autosomal recessive 48, MIM# 609439; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.23 CIB2 Zornitza Stark reviewed gene: CIB2: Rating: RED; Mode of pathogenicity: None; Publications: 23023331, 23023331, 26173970, 26473954, 27344577, 26226137, 26445815; Phenotypes: Usher syndrome, type IJ 614869; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Usher Syndrome v0.10 CIB2 Zornitza Stark Marked gene: CIB2 as ready
Usher Syndrome v0.10 CIB2 Zornitza Stark Gene: cib2 has been classified as Red List (Low Evidence).
Usher Syndrome v0.10 CIB2 Zornitza Stark Publications for gene: CIB2 were set to
Usher Syndrome v0.9 CIB2 Zornitza Stark Classified gene: CIB2 as Red List (low evidence)
Usher Syndrome v0.9 CIB2 Zornitza Stark Gene: cib2 has been classified as Red List (Low Evidence).
Usher Syndrome v0.8 CIB2 Zornitza Stark Tag refuted tag was added to gene: CIB2.
Usher Syndrome v0.8 CIB2 Zornitza Stark reviewed gene: CIB2: Rating: RED; Mode of pathogenicity: None; Publications: 23023331, 23023331, 26173970, 26473954, 27344577, 26226137, 26445815; Phenotypes: Usher syndrome, type IJ 614869; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.418 CIB2 Zornitza Stark Publications for gene: CIB2 were set to
Deafness_IsolatedAndComplex v0.417 CIB2 Zornitza Stark Mode of inheritance for gene: CIB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.416 CIB2 Zornitza Stark reviewed gene: CIB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23023331, 23023331, 26173970, 26473954, 27344577, 26226137, 26445815; Phenotypes: Deafness, autosomal recessive 48, MIM# 609439; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.416 CHD7 Zornitza Stark Marked gene: CHD7 as ready
Deafness_IsolatedAndComplex v0.416 CHD7 Zornitza Stark Gene: chd7 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.416 CHD7 Zornitza Stark Phenotypes for gene: CHD7 were changed from to CHARGE syndrome, MIM# 214800
Deafness_IsolatedAndComplex v0.415 CHD7 Zornitza Stark Mode of inheritance for gene: CHD7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.414 CHD7 Zornitza Stark reviewed gene: CHD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: CHARGE syndrome, MIM# 214800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.414 BSND Zornitza Stark Marked gene: BSND as ready
Deafness_IsolatedAndComplex v0.414 BSND Zornitza Stark Gene: bsnd has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.414 BSND Zornitza Stark Phenotypes for gene: BSND were changed from to Sensorineural deafness with mild renal dysfunction, MIM# 602522; Bartter syndrome, type 4a, MIM# 602522
Deafness_IsolatedAndComplex v0.413 BSND Zornitza Stark Publications for gene: BSND were set to
Deafness_IsolatedAndComplex v0.412 BSND Zornitza Stark Mode of inheritance for gene: BSND was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.411 BSND Zornitza Stark reviewed gene: BSND: Rating: GREEN; Mode of pathogenicity: None; Publications: 19646679; Phenotypes: Sensorineural deafness with mild renal dysfunction, MIM# 602522, Bartter syndrome, type 4a, MIM# 602522; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.411 BCS1L Zornitza Stark Marked gene: BCS1L as ready
Deafness_IsolatedAndComplex v0.411 BCS1L Zornitza Stark Gene: bcs1l has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.411 BCS1L Zornitza Stark Phenotypes for gene: BCS1L were changed from to Bjornstad syndrome, MIM# 262000; Leigh syndrome, MIM# 256000; BCS1L-related mitochondrial disease
Deafness_IsolatedAndComplex v0.410 BCS1L Zornitza Stark Publications for gene: BCS1L were set to
Deafness_IsolatedAndComplex v0.409 BCS1L Zornitza Stark Mode of inheritance for gene: BCS1L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.408 BCS1L Zornitza Stark reviewed gene: BCS1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 26563427, 24172246, 17314340; Phenotypes: Bjornstad syndrome, MIM# 262000, Leigh syndrome, MIM# 256000, BCS1L-related mitochondrial disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypercalcaemia v0.13 GCM2 Zornitza Stark Mode of pathogenicity for gene: GCM2 was changed from None to Other
Hypercalcaemia v0.12 CDKN1B Alison Yeung Marked gene: CDKN1B as ready
Hypercalcaemia v0.12 CDKN1B Alison Yeung Gene: cdkn1b has been classified as Green List (High Evidence).
Hypercalcaemia v0.12 CDKN1B Alison Yeung Classified gene: CDKN1B as Green List (high evidence)
Hypercalcaemia v0.12 CDKN1B Alison Yeung Gene: cdkn1b has been classified as Green List (High Evidence).
Hypercalcaemia v0.12 CDKN1B Alison Yeung Classified gene: CDKN1B as Green List (high evidence)
Hypercalcaemia v0.12 CDKN1B Alison Yeung Gene: cdkn1b has been classified as Green List (High Evidence).
Hypercalcaemia v0.11 CDKN1B Alison Yeung gene: CDKN1B was added
gene: CDKN1B was added to Hypercalcaemia. Sources: Literature
Mode of inheritance for gene: CDKN1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CDKN1B were set to 24819502; 17030811; 23555276
Phenotypes for gene: CDKN1B were set to Multiple endocrine neoplasia type 4, MEN4, OMIM #610755
Review for gene: CDKN1B was set to GREEN
gene: CDKN1B was marked as current diagnostic
Added comment: More than 3 unrelated individuals reported.
Sources: Literature
Mendeliome v0.4606 GCM2 Zornitza Stark Marked gene: GCM2 as ready
Mendeliome v0.4606 GCM2 Zornitza Stark Gene: gcm2 has been classified as Green List (High Evidence).
Mendeliome v0.4606 GCM2 Zornitza Stark Phenotypes for gene: GCM2 were changed from to Hyperparathyroidism 4, OMIM #617343
Mendeliome v0.4605 GCM2 Zornitza Stark Publications for gene: GCM2 were set to
Mendeliome v0.4604 GCM2 Zornitza Stark Mode of pathogenicity for gene: GCM2 was changed from to Other
Mendeliome v0.4603 GCM2 Zornitza Stark Mode of inheritance for gene: GCM2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4602 GCM2 Zornitza Stark edited their review of gene: GCM2: Changed mode of pathogenicity: Other
Mendeliome v0.4602 GCM2 Zornitza Stark reviewed gene: GCM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27745835; Phenotypes: Hyperparathyroidism 4, OMIM #617343; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.81 F13A1 Zornitza Stark Marked gene: F13A1 as ready
Additional findings_Paediatric v0.81 F13A1 Zornitza Stark Gene: f13a1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.81 F13A1 Zornitza Stark Classified gene: F13A1 as Green List (high evidence)
Additional findings_Paediatric v0.81 F13A1 Zornitza Stark Gene: f13a1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.80 F13A1 Zornitza Stark gene: F13A1 was added
gene: F13A1 was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: F13A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: F13A1 were set to Factor XIIIA deficiency, MIM# 613225
Review for gene: F13A1 was set to GREEN
Added comment: Congenital disorder, treatable.
Sources: Expert list
Hypercalcaemia v0.10 GCM2 Alison Yeung Marked gene: GCM2 as ready
Hypercalcaemia v0.10 GCM2 Alison Yeung Gene: gcm2 has been classified as Green List (High Evidence).
Hypercalcaemia v0.10 GCM2 Alison Yeung Classified gene: GCM2 as Green List (high evidence)
Hypercalcaemia v0.10 GCM2 Alison Yeung Gene: gcm2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.79 F10 Zornitza Stark Marked gene: F10 as ready
Additional findings_Paediatric v0.79 F10 Zornitza Stark Gene: f10 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.79 F10 Zornitza Stark Classified gene: F10 as Green List (high evidence)
Additional findings_Paediatric v0.79 F10 Zornitza Stark Gene: f10 has been classified as Green List (High Evidence).
Hypercalcaemia v0.9 GCM2 Alison Yeung gene: GCM2 was added
gene: GCM2 was added to Hypercalcaemia. Sources: Literature
Mode of inheritance for gene: GCM2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GCM2 were set to 27745835
Phenotypes for gene: GCM2 were set to Hyperparathyroidism 4, OMIM #617343
Penetrance for gene: GCM2 were set to unknown
Review for gene: GCM2 was set to GREEN
Added comment: 7 unrelated kindreds with causative variants identified. Functional studies demonstrated gain-of-function/activating mutations
Sources: Literature
Additional findings_Paediatric v0.78 F10 Zornitza Stark gene: F10 was added
gene: F10 was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: F10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: F10 were set to Factor X deficiency, MIM# 227600
Review for gene: F10 was set to GREEN
Added comment: Established gene-disease association, congenital disorder which is treatable.
Sources: Expert list
Additional findings_Paediatric v0.77 DUOXA2 Zornitza Stark Marked gene: DUOXA2 as ready
Additional findings_Paediatric v0.77 DUOXA2 Zornitza Stark Gene: duoxa2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.77 DUOXA2 Zornitza Stark Phenotypes for gene: DUOXA2 were changed from Thyroid dyshormonogenesis to Thyroid dyshormonogenesis 5, MIM# 274900
Additional findings_Paediatric v0.76 DUOXA2 Zornitza Stark Classified gene: DUOXA2 as Green List (high evidence)
Additional findings_Paediatric v0.76 DUOXA2 Zornitza Stark Gene: duoxa2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.75 DUOXA2 Zornitza Stark changed review comment from: Evidence for gene-disease association assessed as moderate.; to: Evidence for gene-disease association assessed as moderate. However, treatment available.
Additional findings_Paediatric v0.75 DUOXA2 Zornitza Stark edited their review of gene: DUOXA2: Changed rating: GREEN
Hyperthyroidism v0.14 THRA Zornitza Stark Marked gene: THRA as ready
Hyperthyroidism v0.14 THRA Zornitza Stark Added comment: Comment when marking as ready: Included in this panel as TFTs potentially suggestive of hyperthyroidism – elevated T3, non-suppressed TSH, even though the associated condition is hypothyroidism.
Hyperthyroidism v0.14 THRA Zornitza Stark Gene: thra has been classified as Green List (High Evidence).
Hyperthyroidism v0.14 SLC16A2 Zornitza Stark Marked gene: SLC16A2 as ready
Hyperthyroidism v0.14 SLC16A2 Zornitza Stark Gene: slc16a2 has been classified as Green List (High Evidence).
Hyperthyroidism v0.14 SLC16A2 Zornitza Stark Phenotypes for gene: SLC16A2 were changed from MENTAL RETARDATION, X-LINKED, WITH HYPOTONIA; mental retardation, X-linked, with hypotonia; Allan-Herndon-Dudley syndrome; ALLAN-HERNDON SYNDROME; T3 RESISTANCE; AHDS; ALLAN-HERNDON-DUDLEY SYNDROME; MENTAL RETARDATION AND MUSCULAR ATROPHY; Monocarboxylate transporter 8 (MCT8) defect; MCT8 (SLC16A2)-specific thyroid hormone cell transporter deficiency; TRIIODOTHYRONINE RESISTANCE; Allan-Herndon-Dudley syndrome, 300523; monocarboxylate transporter 8 (MCT8) deficiency; Allan-Herndon-Dudley Syndrome; 300523; MONOCARBOXYLATE TRANSPORTER 8 DEFICIENCY; Allan_Herndon_Dudley Syndrome to Allan-Herndon-Dudley syndrome, MIM# 300523
Hyperthyroidism v0.13 SLC16A2 Zornitza Stark Publications for gene: SLC16A2 were set to 24847459
Hyperthyroidism v0.12 THRA Zornitza Stark Marked gene: THRA as ready
Hyperthyroidism v0.12 THRA Zornitza Stark Gene: thra has been classified as Green List (High Evidence).
Hyperthyroidism v0.12 THRA Zornitza Stark Phenotypes for gene: THRA were changed from Resistance to Thyroid Hormone due to defective thyroid receptor alpha (RTHa); Hypothyroidism, congenital, nongoitrous, 6, 614450; congenital nongoitrous hypothyroidism 6; RTH alpha; HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 6; Resistance to thyroid hormone alpha; CHNG6 to Hypothyroidism, congenital, nongoitrous, 6 614450
Hyperthyroidism v0.11 THRA Zornitza Stark Mode of pathogenicity for gene: THRA was changed from to Other
Mendeliome v0.4602 SECISBP2 Zornitza Stark Marked gene: SECISBP2 as ready
Mendeliome v0.4602 SECISBP2 Zornitza Stark Gene: secisbp2 has been classified as Green List (High Evidence).
Mendeliome v0.4602 SECISBP2 Zornitza Stark Phenotypes for gene: SECISBP2 were changed from to Thyroid hormone metabolism, abnormal, MIM# 609698
Mendeliome v0.4601 SECISBP2 Zornitza Stark Publications for gene: SECISBP2 were set to
Mendeliome v0.4600 SECISBP2 Zornitza Stark Mode of inheritance for gene: SECISBP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4599 SECISBP2 Zornitza Stark reviewed gene: SECISBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16228000, 19602558, 21084748, 22247018; Phenotypes: Thyroid hormone metabolism, abnormal, MIM# 609698; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hyperthyroidism v0.10 SECISBP2 Zornitza Stark Marked gene: SECISBP2 as ready
Hyperthyroidism v0.10 SECISBP2 Zornitza Stark Gene: secisbp2 has been classified as Green List (High Evidence).
Hyperthyroidism v0.10 SECISBP2 Zornitza Stark Phenotypes for gene: SECISBP2 were changed from Selenocysteine insertion sequence binding protein 2 (SBP2) defect; Thyroid hormone metabolism, abnormal, 609698; Short stature-delayed bone age due to thyroid hormone metabolism deficiency; THYROID HORMONE METABOLISM, ABNORMAL; Abnormal thyroid hormone metabolism to Thyroid hormone metabolism, abnormal, MIM# 609698
Hyperthyroidism v0.9 SECISBP2 Zornitza Stark Publications for gene: SECISBP2 were set to 22986150; 24629861; 19602558; 22247018; 20501692; 16228000; Diversity Selenium Functions in Health and Disease, Edited by Regina Brigelius-Flohe and Helmut Sies, Chapter 16. Mutations in SECISBP2. Erik Schoenmakers, Carla Moran, Nadia Schoenmakers and Krishna Chatterjee. CRC Press 2015. Pages 343 376. Print ISBN: 978-1-4822-5126-5. eBook ISBN: 978-1-4822-5127-2. DOI: 10.1201/b18810-23; 21084748
Intellectual disability syndromic and non-syndromic v0.3027 SECISBP2 Zornitza Stark Marked gene: SECISBP2 as ready
Intellectual disability syndromic and non-syndromic v0.3027 SECISBP2 Zornitza Stark Gene: secisbp2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3027 SECISBP2 Zornitza Stark Classified gene: SECISBP2 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.3027 SECISBP2 Zornitza Stark Gene: secisbp2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3026 SECISBP2 Anna Le Fevre gene: SECISBP2 was added
gene: SECISBP2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SECISBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SECISBP2 were set to 16228000; 19602558; 21084748; 22247018
Phenotypes for gene: SECISBP2 were set to #609698 THYROID HORMONE METABOLISM, ABNORMAL
Penetrance for gene: SECISBP2 were set to unknown
Review for gene: SECISBP2 was set to RED
Added comment: Multiple families with biallelic loss of function variants have been reported with a disorder of thyroid hormone metabolism involving synthesis of selenoproteins. Features include short stature with delayed bone age, muscle weakness with fatty infiltration of skeletal muscle, azoospermia, and mild developmental delay. Photosensitivity and high frequency SNHL have been reported. Thyroid function tests show elevated FT4 and rT3, low FT3 and normal or mildly elevated TSH. Incomplete loss of SECISBP2 function has been hypothesized to cause a milder phenotype.

At least two reports of children with delayed milestones.
One report of an affected adult with mild ID.
Further reports may clarify if this phenotype typically includes ID.
Sources: Literature
Hyperthyroidism v0.8 SECISBP2 Anna Le Fevre reviewed gene: SECISBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16228000, 19602558, 21084748, 22247018; Phenotypes: #609698 THYROID HORMONE METABOLISM, ABNORMAL; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.111 SBMA Zornitza Stark Marked STR: SBMA as ready
Motor Neurone Disease v0.111 SBMA Zornitza Stark Str: sbma has been classified as Green List (High Evidence).
Motor Neurone Disease v0.110 DNAJB2 Zornitza Stark Marked gene: DNAJB2 as ready
Motor Neurone Disease v0.110 DNAJB2 Zornitza Stark Gene: dnajb2 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.110 DNAJB2 Zornitza Stark Phenotypes for gene: DNAJB2 were changed from to Spinal muscular atrophy, distal, autosomal recessive, 5, 614881
Motor Neurone Disease v0.109 DNAJB2 Zornitza Stark Mode of inheritance for gene: DNAJB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.75 IYD Zornitza Stark Marked gene: IYD as ready
Additional findings_Paediatric v0.75 IYD Zornitza Stark Added comment: Comment when marking as ready: More than 4 families reported, treatable disorder.
Additional findings_Paediatric v0.75 IYD Zornitza Stark Gene: iyd has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.75 IYD Zornitza Stark Phenotypes for gene: IYD were changed from Thyroid dyshormonogenesis to Thyroid dyshormonogenesis 4, MIM# 274800
Additional findings_Paediatric v0.74 IYD Zornitza Stark Publications for gene: IYD were set to
Additional findings_Paediatric v0.73 IYD Zornitza Stark Classified gene: IYD as Green List (high evidence)
Additional findings_Paediatric v0.73 IYD Zornitza Stark Gene: iyd has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.72 IRF6 Zornitza Stark Marked gene: IRF6 as ready
Additional findings_Paediatric v0.72 IRF6 Zornitza Stark Gene: irf6 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.72 IRF6 Zornitza Stark Phenotypes for gene: IRF6 were changed from van der Woude syndrome; Popliteal pterygium syndrome to van der Woude syndrome MIM# 119300
Additional findings_Paediatric v0.71 IRF6 Zornitza Stark Classified gene: IRF6 as Green List (high evidence)
Additional findings_Paediatric v0.71 IRF6 Zornitza Stark Gene: irf6 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.70 INS Zornitza Stark Marked gene: INS as ready
Additional findings_Paediatric v0.70 INS Zornitza Stark Gene: ins has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.70 INS Zornitza Stark Classified gene: INS as Green List (high evidence)
Additional findings_Paediatric v0.70 INS Zornitza Stark Gene: ins has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.55 CAPN3 Zornitza Stark Publications for gene: CAPN3 were set to 31937337; 28881388
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.54 CAPN3 Zornitza Stark Mode of inheritance for gene: CAPN3 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
Motor Neurone Disease v0.107 IGHMBP2 Zornitza Stark Classified gene: IGHMBP2 as Red List (low evidence)
Motor Neurone Disease v0.107 IGHMBP2 Zornitza Stark Gene: ighmbp2 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.106 IGHMBP2 Zornitza Stark changed review comment from: SMA-like disorder with prominent diaphragmatic involvement but onset is in infancy.; to: SMA-like disorder with prominent diaphragmatic involvement but onset is in infancy. Included in Hereditary Neuropathy_Isolated panel.
Motor Neurone Disease v0.106 IGHMBP2 Zornitza Stark edited their review of gene: IGHMBP2: Changed rating: RED
Motor Neurone Disease v0.106 EXOSC8 Zornitza Stark Marked gene: EXOSC8 as ready
Motor Neurone Disease v0.106 EXOSC8 Zornitza Stark Gene: exosc8 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.106 EXOSC8 Zornitza Stark Phenotypes for gene: EXOSC8 were changed from to Pontocerebellar hypoplasia, type 1C, MIM# 616081
Motor Neurone Disease v0.105 EXOSC8 Zornitza Stark Publications for gene: EXOSC8 were set to
Motor Neurone Disease v0.104 EXOSC8 Zornitza Stark Mode of inheritance for gene: EXOSC8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.103 EXOSC8 Zornitza Stark Classified gene: EXOSC8 as Red List (low evidence)
Motor Neurone Disease v0.103 EXOSC8 Zornitza Stark Gene: exosc8 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.102 EXOSC8 Zornitza Stark changed review comment from: This disorder includes a spinal muscular atrophy component in addition to the PCH, but onset is typically in infancy.; to: This disorder includes a spinal muscular atrophy component in addition to the PCH, but onset is typically in infancy. Gene is included in Hereditary Neuropathy_Complex panel.
Motor Neurone Disease v0.102 EXOSC8 Zornitza Stark edited their review of gene: EXOSC8: Changed rating: RED
Motor Neurone Disease v0.102 DYNC1H1 Zornitza Stark Marked gene: DYNC1H1 as ready
Motor Neurone Disease v0.102 DYNC1H1 Zornitza Stark Gene: dync1h1 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.102 DYNC1H1 Zornitza Stark Phenotypes for gene: DYNC1H1 were changed from to Spinal muscular atrophy, lower extremity-predominant 1, AD, MIM# 158600
Motor Neurone Disease v0.101 DYNC1H1 Zornitza Stark Mode of inheritance for gene: DYNC1H1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.100 DYNC1H1 Zornitza Stark Classified gene: DYNC1H1 as Red List (low evidence)
Motor Neurone Disease v0.100 DYNC1H1 Zornitza Stark Gene: dync1h1 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.99 DYNC1H1 Zornitza Stark reviewed gene: DYNC1H1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy, lower extremity-predominant 1, AD, MIM# 158600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.99 BSCL2 Zornitza Stark reviewed gene: BSCL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Motor Neurone Disease v0.99 BICD2 Zornitza Stark Marked gene: BICD2 as ready
Motor Neurone Disease v0.99 BICD2 Zornitza Stark Gene: bicd2 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.99 BICD2 Zornitza Stark Phenotypes for gene: BICD2 were changed from to Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, 615290; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291
Motor Neurone Disease v0.98 BICD2 Zornitza Stark Mode of inheritance for gene: BICD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.97 BICD2 Zornitza Stark Classified gene: BICD2 as Red List (low evidence)
Motor Neurone Disease v0.97 BICD2 Zornitza Stark Gene: bicd2 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.96 BICD2 Zornitza Stark reviewed gene: BICD2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, 615290, Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.96 ATP7A Zornitza Stark Marked gene: ATP7A as ready
Motor Neurone Disease v0.96 ATP7A Zornitza Stark Gene: atp7a has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.96 ATP7A Zornitza Stark Phenotypes for gene: ATP7A were changed from to Spinal muscular atrophy, distal, X-linked 3, 300489
Motor Neurone Disease v0.95 ATP7A Zornitza Stark Mode of inheritance for gene: ATP7A was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Motor Neurone Disease v0.94 ATP7A Zornitza Stark Classified gene: ATP7A as Red List (low evidence)
Motor Neurone Disease v0.94 ATP7A Zornitza Stark Gene: atp7a has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.93 ATP7A Zornitza Stark reviewed gene: ATP7A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy, distal, X-linked 3, 300489; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Motor Neurone Disease v0.93 ASAH1 Zornitza Stark Marked gene: ASAH1 as ready
Motor Neurone Disease v0.93 ASAH1 Zornitza Stark Gene: asah1 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.93 ASAH1 Zornitza Stark Phenotypes for gene: ASAH1 were changed from to Spinal muscular atrophy with progressive myoclonic epilepsy, 159950
Motor Neurone Disease v0.92 ASAH1 Zornitza Stark Mode of inheritance for gene: ASAH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.91 ASAH1 Zornitza Stark Classified gene: ASAH1 as Red List (low evidence)
Motor Neurone Disease v0.91 ASAH1 Zornitza Stark Gene: asah1 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.90 ASAH1 Zornitza Stark changed review comment from: Early childhood onset, included in Peripheral Neuropathy panels.; to: Early childhood onset, included in Hereditary Neuropathy panels.
Motor Neurone Disease v0.90 ASAH1 Zornitza Stark reviewed gene: ASAH1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy with progressive myoclonic epilepsy, 159950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hyperthyroidism v0.8 SLC16A2 Anna Le Fevre reviewed gene: SLC16A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25517855, 21098685, 31410843; Phenotypes: #300523 ALLAN-HERNDON-DUDLEY SYNDROME; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Motor Neurone Disease v0.90 VRK1 Zornitza Stark Marked gene: VRK1 as ready
Motor Neurone Disease v0.90 VRK1 Zornitza Stark Gene: vrk1 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.90 VRK1 Zornitza Stark Phenotypes for gene: VRK1 were changed from to Distal hereditary motor neuropathy; dHMN/dSMA
Motor Neurone Disease v0.89 VRK1 Zornitza Stark Publications for gene: VRK1 were set to
Motor Neurone Disease v0.88 VRK1 Zornitza Stark Mode of inheritance for gene: VRK1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.87 VRK1 Zornitza Stark Classified gene: VRK1 as Red List (low evidence)
Motor Neurone Disease v0.87 VRK1 Zornitza Stark Gene: vrk1 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.86 VRK1 Zornitza Stark reviewed gene: VRK1: Rating: RED; Mode of pathogenicity: None; Publications: 31560180, 32242460, 31178479, 31837156, 30847374; Phenotypes: Distal hereditary motor neuropathy, dHMN/dSMA; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4599 UBA1 Zornitza Stark Marked gene: UBA1 as ready
Mendeliome v0.4599 UBA1 Zornitza Stark Gene: uba1 has been classified as Green List (High Evidence).
Mendeliome v0.4599 UBA1 Zornitza Stark Phenotypes for gene: UBA1 were changed from to Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830
Mendeliome v0.4598 UBA1 Zornitza Stark Publications for gene: UBA1 were set to
Mendeliome v0.4597 UBA1 Zornitza Stark Mode of inheritance for gene: UBA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4596 UBA1 Zornitza Stark reviewed gene: UBA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18179898, 32181232, 31932168, 29034082, 27699224, 26028276, 23518311; Phenotypes: Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.214 UBA1 Zornitza Stark Marked gene: UBA1 as ready
Arthrogryposis v0.214 UBA1 Zornitza Stark Gene: uba1 has been classified as Green List (High Evidence).
Arthrogryposis v0.214 UBA1 Zornitza Stark Phenotypes for gene: UBA1 were changed from to Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830
Arthrogryposis v0.213 UBA1 Zornitza Stark Publications for gene: UBA1 were set to
Arthrogryposis v0.212 UBA1 Zornitza Stark Mode of inheritance for gene: UBA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.211 UBA1 Zornitza Stark reviewed gene: UBA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18179898, 32181232, 31932168, 29034082, 27699224, 26028276, 23518311; Phenotypes: Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Motor Neurone Disease v0.85 UBA1 Zornitza Stark Marked gene: UBA1 as ready
Motor Neurone Disease v0.85 UBA1 Zornitza Stark Gene: uba1 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.85 UBA1 Zornitza Stark Phenotypes for gene: UBA1 were changed from to Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830
Motor Neurone Disease v0.84 UBA1 Zornitza Stark Publications for gene: UBA1 were set to
Motor Neurone Disease v0.83 UBA1 Zornitza Stark Mode of inheritance for gene: UBA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Motor Neurone Disease v0.82 UBA1 Zornitza Stark Classified gene: UBA1 as Red List (low evidence)
Motor Neurone Disease v0.82 UBA1 Zornitza Stark Gene: uba1 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.81 UBA1 Zornitza Stark reviewed gene: UBA1: Rating: RED; Mode of pathogenicity: None; Publications: 18179898, 32181232, 31932168, 29034082, 27699224, 26028276, 23518311; Phenotypes: Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Motor Neurone Disease v0.81 TRPV4 Zornitza Stark Marked gene: TRPV4 as ready
Motor Neurone Disease v0.81 TRPV4 Zornitza Stark Gene: trpv4 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.81 TRPV4 Zornitza Stark Phenotypes for gene: TRPV4 were changed from to Spinal muscular atrophy, distal, congenital nonprogressive, 600175
Motor Neurone Disease v0.80 TRPV4 Zornitza Stark Mode of inheritance for gene: TRPV4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.79 TRPV4 Zornitza Stark Classified gene: TRPV4 as Red List (low evidence)
Motor Neurone Disease v0.79 TRPV4 Zornitza Stark Gene: trpv4 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.78 TRPV4 Zornitza Stark reviewed gene: TRPV4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary Neuropathy v0.86 TRIP4 Zornitza Stark Marked gene: TRIP4 as ready
Hereditary Neuropathy v0.86 TRIP4 Zornitza Stark Gene: trip4 has been classified as Green List (High Evidence).
Hereditary Neuropathy v0.86 TRIP4 Zornitza Stark Phenotypes for gene: TRIP4 were changed from Spinal muscular atrophy with congenital bone fractures 1 to Spinal muscular atrophy with congenital bone fractures 1, MIM# 616866
Hereditary Neuropathy v0.85 TRIP4 Zornitza Stark Publications for gene: TRIP4 were set to
Hereditary Neuropathy v0.84 TRIP4 Zornitza Stark reviewed gene: TRIP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26924529; Phenotypes: Spinal muscular atrophy with congenital bone fractures 1, MIM# 616866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4596 TRIP4 Zornitza Stark Marked gene: TRIP4 as ready
Mendeliome v0.4596 TRIP4 Zornitza Stark Gene: trip4 has been classified as Green List (High Evidence).
Mendeliome v0.4596 TRIP4 Zornitza Stark Phenotypes for gene: TRIP4 were changed from to Spinal muscular atrophy with congenital bone fractures 1, MIM# 616866; Muscular dystrophy, congenital, Davignon-Chauveau type 617066
Mendeliome v0.4595 TRIP4 Zornitza Stark Publications for gene: TRIP4 were set to
Mendeliome v0.4594 TRIP4 Zornitza Stark Mode of inheritance for gene: TRIP4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4593 TRIP4 Zornitza Stark reviewed gene: TRIP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26924529, 31794073; Phenotypes: Spinal muscular atrophy with congenital bone fractures 1, MIM# 616866, Muscular dystrophy, congenital, Davignon-Chauveau type 617066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.78 TRIP4 Zornitza Stark Marked gene: TRIP4 as ready
Motor Neurone Disease v0.78 TRIP4 Zornitza Stark Gene: trip4 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.78 TRIP4 Zornitza Stark Phenotypes for gene: TRIP4 were changed from to Spinal muscular atrophy with congenital bone fractures 1, MIM# 616866
Motor Neurone Disease v0.77 TRIP4 Zornitza Stark Publications for gene: TRIP4 were set to
Motor Neurone Disease v0.76 TRIP4 Zornitza Stark Mode of inheritance for gene: TRIP4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.75 TRIP4 Zornitza Stark Classified gene: TRIP4 as Red List (low evidence)
Motor Neurone Disease v0.75 TRIP4 Zornitza Stark Gene: trip4 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.74 TRIP4 Zornitza Stark reviewed gene: TRIP4: Rating: RED; Mode of pathogenicity: None; Publications: 26924529; Phenotypes: Spinal muscular atrophy with congenital bone fractures 1, MIM# 616866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.74 SPG11 Zornitza Stark Marked gene: SPG11 as ready
Motor Neurone Disease v0.74 SPG11 Zornitza Stark Gene: spg11 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.74 SPG11 Zornitza Stark Phenotypes for gene: SPG11 were changed from to Amyotrophic lateral sclerosis 5, juvenile, MIM# 602099
Motor Neurone Disease v0.73 SPG11 Zornitza Stark Publications for gene: SPG11 were set to
Motor Neurone Disease v0.72 C9orf72 Bryony Thompson Marked STR: C9orf72 as ready
Motor Neurone Disease v0.72 C9orf72 Bryony Thompson Str: c9orf72 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.72 C9orf72 Bryony Thompson Tag STR tag was added to STR: C9orf72.
Motor Neurone Disease v0.72 C9orf72 Bryony Thompson Classified STR: C9orf72 as Green List (high evidence)
Motor Neurone Disease v0.72 C9orf72 Bryony Thompson Str: c9orf72 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.71 C9orf72 Bryony Thompson STR: C9orf72 was added
STR: C9orf72 was added to Motor Neuron Disease. Sources: Expert list
Mode of inheritance for STR: C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: C9orf72 were set to 25577942
Phenotypes for STR: C9orf72 were set to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 MIM#105550
Review for STR: C9orf72 was set to GREEN
STR: C9orf72 was marked as clinically relevant
Added comment: NG_031977​.1:g.5321GGGGCC[X]
Repeat expansion affects the protein degradation pathways and may contribute to TDP‐43 accumulation
Normal alleles: ≤25 G4C2 hexanucleotide repeat units generally considered normal
Pathogenic high-penetrance alleles: ≥60 G4C2 hexanucleotide repeat units are considered pathogenic
Note: The minimal size of a G4C2 pathogenic repeat is under debate: some studies consider repeats of >30 G4C2 hexanucleotide repeat units as pathogenic, whereas others use a cutoff of 60 G4C2 hexanucleotide repeat units.
Sources: Expert list
Motor Neurone Disease v0.70 SPG11 Zornitza Stark Mode of inheritance for gene: SPG11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.69 SPG11 Zornitza Stark reviewed gene: SPG11: Rating: GREEN; Mode of pathogenicity: None; Publications: 20110243; Phenotypes: Amyotrophic lateral sclerosis 5, juvenile, MIM# 602099; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.69 PLEKHG5 Zornitza Stark Marked gene: PLEKHG5 as ready
Motor Neurone Disease v0.69 PLEKHG5 Zornitza Stark Gene: plekhg5 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.69 PLEKHG5 Zornitza Stark Phenotypes for gene: PLEKHG5 were changed from to Spinal muscular atrophy, distal, autosomal recessive, 4, MIM# 611067
Motor Neurone Disease v0.68 PLEKHG5 Zornitza Stark Publications for gene: PLEKHG5 were set to
Motor Neurone Disease v0.67 PLEKHG5 Zornitza Stark Mode of inheritance for gene: PLEKHG5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.66 PLEKHG5 Zornitza Stark Classified gene: PLEKHG5 as Red List (low evidence)
Motor Neurone Disease v0.66 PLEKHG5 Zornitza Stark Gene: plekhg5 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.65 PLEKHG5 Zornitza Stark reviewed gene: PLEKHG5: Rating: RED; Mode of pathogenicity: None; Publications: 17564964; Phenotypes: Spinal muscular atrophy, distal, autosomal recessive, 4, MIM# 611067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.65 LAS1L Zornitza Stark Phenotypes for gene: LAS1L were changed from Wilson-Turner syndrome, MIM# 309585 to congenital lethal motor neuron disease
Motor Neurone Disease v0.64 LAS1L Zornitza Stark edited their review of gene: LAS1L: Changed phenotypes: congenital lethal motor neuron disease
Intellectual disability syndromic and non-syndromic v0.3026 LAS1L Zornitza Stark Mode of inheritance for gene: LAS1L was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.3025 LAS1L Zornitza Stark edited their review of gene: LAS1L: Changed rating: GREEN; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Motor Neurone Disease v0.64 LAS1L Zornitza Stark Marked gene: LAS1L as ready
Motor Neurone Disease v0.64 LAS1L Zornitza Stark Gene: las1l has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.64 LAS1L Zornitza Stark Phenotypes for gene: LAS1L were changed from to Wilson-Turner syndrome, MIM# 309585
Motor Neurone Disease v0.63 LAS1L Zornitza Stark Publications for gene: LAS1L were set to
Motor Neurone Disease v0.62 LAS1L Zornitza Stark Mode of inheritance for gene: LAS1L was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Motor Neurone Disease v0.61 LAS1L Zornitza Stark Classified gene: LAS1L as Red List (low evidence)
Motor Neurone Disease v0.61 LAS1L Zornitza Stark Gene: las1l has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.60 LAS1L Zornitza Stark reviewed gene: LAS1L: Rating: RED; Mode of pathogenicity: None; Publications: 24647030; Phenotypes: Wilson-Turner syndrome, MIM# 309585; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.53 CAPN3 Kristin Rigbye reviewed gene: CAPN3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32342993; Phenotypes: Autosomal recessive limb-girdle muscular dystrophy 1 (MIM#253600), Autosomal dominant limb-girdle muscular dystrophy 4 (MIM#618129); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Motor Neurone Disease v0.60 IGHMBP2 Zornitza Stark Marked gene: IGHMBP2 as ready
Motor Neurone Disease v0.60 IGHMBP2 Zornitza Stark Gene: ighmbp2 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.60 IGHMBP2 Zornitza Stark Phenotypes for gene: IGHMBP2 were changed from to Neuronopathy, distal hereditary motor, type VI 604320
Motor Neurone Disease v0.59 IGHMBP2 Zornitza Stark Mode of inheritance for gene: IGHMBP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.58 IGHMBP2 Zornitza Stark reviewed gene: IGHMBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuronopathy, distal hereditary motor, type VI 604320; Mode of inheritance: None
Hereditary Neuropathy v0.84 EXOSC9 Zornitza Stark Marked gene: EXOSC9 as ready
Hereditary Neuropathy v0.84 EXOSC9 Zornitza Stark Gene: exosc9 has been classified as Green List (High Evidence).
Hereditary Neuropathy v0.84 EXOSC9 Zornitza Stark Classified gene: EXOSC9 as Green List (high evidence)
Hereditary Neuropathy v0.84 EXOSC9 Zornitza Stark Gene: exosc9 has been classified as Green List (High Evidence).
Hereditary Neuropathy v0.83 EXOSC9 Zornitza Stark gene: EXOSC9 was added
gene: EXOSC9 was added to Hereditary Neuropathy - complex. Sources: Expert Review
Mode of inheritance for gene: EXOSC9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC9 were set to 30690203; 29727687
Phenotypes for gene: EXOSC9 were set to Pontocerebellar hypoplasia, type 1D, MIM# 618065
Review for gene: EXOSC9 was set to GREEN
Added comment: Six unrelated families reported, p.Leu14Pro variant is recurrent, disorder combines cerebellar atrophy and spinal motoneuronopathy.
Sources: Expert Review
Hereditary Neuropathy v0.82 EXOSC8 Zornitza Stark Phenotypes for gene: EXOSC8 were changed from dHMN/dSMA; Pontocerebellar hypoplasia, type 1c to dHMN/dSMA; Pontocerebellar hypoplasia, type 1c, MIM# 616081
Hereditary Neuropathy v0.81 EXOSC8 Zornitza Stark Publications for gene: EXOSC8 were set to
Hereditary Neuropathy v0.80 EXOSC8 Zornitza Stark Classified gene: EXOSC8 as Green List (high evidence)
Hereditary Neuropathy v0.80 EXOSC8 Zornitza Stark Gene: exosc8 has been classified as Green List (High Evidence).
Hereditary Neuropathy v0.79 EXOSC8 Zornitza Stark Deleted their comment
Hereditary Neuropathy v0.79 EXOSC8 Zornitza Stark commented on gene: EXOSC8: Panel is both paediatric and adult, condition has an SMA component in addition to the PCH.
Hereditary Neuropathy v0.79 EXOSC8 Zornitza Stark reviewed gene: EXOSC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 24989451; Phenotypes: Pontocerebellar hypoplasia, type 1C, MIM# 616081; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.58 EXOSC8 Zornitza Stark reviewed gene: EXOSC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 24989451; Phenotypes: Pontocerebellar hypoplasia, type 1C, MIM# 616081; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4593 EXOSC9 Zornitza Stark Marked gene: EXOSC9 as ready
Mendeliome v0.4593 EXOSC9 Zornitza Stark Gene: exosc9 has been classified as Green List (High Evidence).
Mendeliome v0.4593 EXOSC9 Zornitza Stark Phenotypes for gene: EXOSC9 were changed from to Pontocerebellar hypoplasia, type 1D, MIM# 618065
Mendeliome v0.4592 EXOSC9 Zornitza Stark Publications for gene: EXOSC9 were set to
Mendeliome v0.4591 EXOSC9 Zornitza Stark Mode of inheritance for gene: EXOSC9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4590 EXOSC9 Zornitza Stark reviewed gene: EXOSC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 30690203, 29727687; Phenotypes: Pontocerebellar hypoplasia, type 1D, MIM# 618065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.69 INS Lilian Downie gene: INS was added
gene: INS was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: INS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: INS were set to Diabetes mellitus, permanent neonatal MIM# 618858Permanent neonatal diabetes mellitus-4 (PNDM4) is characterized by chronic hyperglycemia due to severe nonautoimmune insulin deficiency diagnosed in the first months of life
Review for gene: INS was set to GREEN
Added comment: Permanent neonatal diabetes mellitus-4 (PNDM4) is characterized by chronic hyperglycemia due to severe nonautoimmune insulin deficiency diagnosed in the first months of life. Not assessed by Babyseq, included in NC NEXUS list.
Sources: Expert list
Motor Neurone Disease v0.58 DNAJB2 Zornitza Stark reviewed gene: DNAJB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Additional findings_Paediatric v0.69 IRF6 Lilian Downie reviewed gene: IRF6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: van der Woude syndrome MIM# 119300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.69 IYD Lilian Downie reviewed gene: IYD: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18434651, 18765512, 30240412; Phenotypes: Thyroid dyshormonogenesis 4 MIM# 274800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4590 SLC7A14 Zornitza Stark Marked gene: SLC7A14 as ready
Mendeliome v0.4590 SLC7A14 Zornitza Stark Gene: slc7a14 has been classified as Red List (Low Evidence).
Mendeliome v0.4590 SLC7A14 Zornitza Stark Phenotypes for gene: SLC7A14 were changed from to Retinitis pigmentosa 68, MIM# MIM#615725
Mendeliome v0.4589 SLC7A14 Zornitza Stark Publications for gene: SLC7A14 were set to
Mendeliome v0.4588 SLC7A14 Zornitza Stark Mode of inheritance for gene: SLC7A14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4587 SLC7A14 Zornitza Stark Classified gene: SLC7A14 as Red List (low evidence)
Mendeliome v0.4587 SLC7A14 Zornitza Stark Gene: slc7a14 has been classified as Red List (Low Evidence).
Mendeliome v0.4586 SLC7A14 Zornitza Stark Tag disputed tag was added to gene: SLC7A14.
Mendeliome v0.4586 SLC7A14 Zornitza Stark reviewed gene: SLC7A14: Rating: RED; Mode of pathogenicity: None; Publications: 31921845, 30924391, 24670872; Phenotypes: Retinitis pigmentosa 68, MIM# MIM#615725; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa v0.65 SLC7A14 Zornitza Stark Tag disputed tag was added to gene: SLC7A14.
Retinitis pigmentosa v0.65 SLC7A14 Zornitza Stark Marked gene: SLC7A14 as ready
Retinitis pigmentosa v0.65 SLC7A14 Zornitza Stark Gene: slc7a14 has been classified as Red List (Low Evidence).
Retinitis pigmentosa v0.65 ADIPOR1 Zornitza Stark Marked gene: ADIPOR1 as ready
Retinitis pigmentosa v0.65 ADIPOR1 Zornitza Stark Gene: adipor1 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa v0.65 Zornitza Stark Panel name changed from Autosomal Recessive/X-Linked Retinitis Pigmentosa to Retinitis pigmentosa_Autosomal Recessive/X-linked
Hyperthyroidism v0.8 THRB Zornitza Stark Marked gene: THRB as ready
Hyperthyroidism v0.8 THRB Zornitza Stark Gene: thrb has been classified as Green List (High Evidence).
Hyperthyroidism v0.8 THRB Zornitza Stark Phenotypes for gene: THRB were changed from Thyroid Hormone Resistance, Selective Pituitary; 145650; THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL RECESSIVE; thyroid hormone unresponsiveness, generalized RTH, RTH beta; THYROID HORMONE UNRESPONSIVENESS; REFETOFF SYNDROME; Refetoff syndrome; THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL DOMINANT; PRTH; Thyroid hormone resistance, selective pituitary, 145650; GRTH; THYROID HORMONE RESISTANCE, SELECTIVE PITUITARY; Resistance to thyroid hormone (RTH); Thyroid hormone resistance, 188570; Thyroid hormone resistance, autosomal recessive, 274300; Thyroid Hormone Resistance (monoallelic); HYPERTHYROIDISM, FAMILIAL, DUE TO INAPPROPRIATE THYROTROPIN SECRETION; THYROID HORMONE UNRESPONSIVENESS HYPERTHYROXINEMIA, FAMILIAL EUTHYROID, SECONDARY TO PITUITARY AND PERIPHERAL RESISTANCE TO THYROID HORMONES to Thyroid hormone resistance, MIM# 188570; Thyroid hormone resistance, autosomal recessive, MIM# 274300; Thyroid hormone resistance, selective pituitary, MIM# 145650
Hyperthyroidism v0.7 THRB Zornitza Stark Publications for gene: THRB were set to 24847459
Hyperthyroidism v0.6 THRB Zornitza Stark Mode of pathogenicity for gene: THRB was changed from to Other
Hyperthyroidism v0.5 THRB Zornitza Stark Mode of inheritance for gene: THRB 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
Hyperthyroidism v0.4 THRA Anna Le Fevre reviewed gene: THRA: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 25135573, 27381958, 24847459, 27144938; Phenotypes: #190120 THYROID HORMONE RECEPTOR, ALPHA-1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hyperthyroidism v0.4 THRB Anna Le Fevre changed review comment from: Monoallelic variants in THRB can cause a dominant negative effect as the altered receptor inhibits the function of the wild-type thyroid hormone receptor (THR) β. This can lead to elevated thyroid hormone signaling through THRα
receptors.

Diagnosis of this familial euthyroid hyperthyroxinemia is important to avoid unnecessary medical or surgical treatment and may impact on pregnancy management.

Different variants can have varying effects on THRβ function and THRβ expression varies among organs, which is thought to make the genotype and phenotype relationship unclear. There is overlap between the previously subcategorised peripheral, isolated pituitary and generalised phenotypes.

Biallelic variants cause a more severe phenotype including hearing impairment (consider adding THRB to hearing loss panel). A speculated mechanism in this condition is dominant-negative effect of mutant THRβ on wild-type THRα.; to: Monoallelic variants in THRB can cause a dominant negative effect due to an altered thyroid hormone receptor (THR) β inhibiting the function of the wild-type THRβ. This can lead to elevated thyroid hormone signaling through THRα receptors.

Diagnosis of this familial euthyroid hyperthyroxinemia is important to avoid unnecessary medical or surgical treatment and may impact on pregnancy management.

Different variants can have varying effects on THRβ function and THRβ expression varies among organs, which is thought to make the genotype and phenotype relationship unclear. There is overlap between the previously subcategorised peripheral, isolated pituitary and generalised phenotypes.

Biallelic variants cause a more severe phenotype including hearing impairment (consider adding THRB to hearing loss panel). A speculated mechanism in this condition is dominant-negative effect of mutant THRβ on wild-type THRα.
Hyperthyroidism v0.4 THRB Anna Le Fevre reviewed gene: THRB: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 25135573, 31590893; Phenotypes: #188570 THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL DOMINANT, #274300 THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL RECESSIVE, #145650 THYROID HORMONE RESISTANCE, SELECTIVE PITUITARY; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hyperthyroidism v0.4 TTR Zornitza Stark Marked gene: TTR as ready
Hyperthyroidism v0.4 TTR Zornitza Stark Gene: ttr has been classified as Green List (High Evidence).
Hyperthyroidism v0.4 TTR Zornitza Stark Publications for gene: TTR were set to 31590893; 26522458
Hyperthyroidism v0.3 ALB Anna Le Fevre edited their review of gene: ALB: Added comment: Gain of function mechanism.
Specific variants in ALB cause increased binding affinity for thyroid hormones. Immunoassay methods may show variably elevated free thyroid hormone levels. Individuals are euthyroid and identification is important to avoid unnecessary medical or surgical treatment.

Allelic conditions:
#616000 ANALBUMINEMIA; ANALBA
Biallelic loss of function variants cause very low amounts of circulating serum albumin.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hyperthyroidism v0.3 ALB Zornitza Stark reviewed gene: ALB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Familial dysalbuminaemic hyperthyroxinaemia, [Dysalbuminemic hyperthyroxinemia], 615999; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hyperthyroidism v0.3 TTR Anna Le Fevre reviewed gene: TTR: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 31590893, 26522458, 8784093; Phenotypes: # 145680 HYPERTHYROXINEMIA, DYSTRANSTHYRETINEMIC, DTTRH; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hyperthyroidism v0.3 ALB Anna Le Fevre Deleted their comment
Hyperthyroidism v0.3 ALB Anna Le Fevre changed review comment from: Gain-of-function mechanism.
Individuals with FDH-T4 or FDH-T3 present with altered thyroid function tests, but they are clinically euthyroid. Therefore, early identification of the syndromes is important to avoid unnecessary medical or surgical treatment. Both are dominantly inherited conditions caused by missense variants of ALB with increased affinity for thyroid hormones.

The allelic condition Analbuminemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin and is caused by biallelic loss of function variants.; to: Gain-of-function mechanism.
Individuals with FDH-T4 or FDH-T3 present with altered thyroid function tests, but they are clinically euthyroid. Therefore, early identification of the syndromes is important to avoid unnecessary medical or surgical treatment. Both are dominantly inherited conditions caused by missense variants of ALB with increased affinity for thyroid hormones.

The allelic condition Analbuminemia (ANALBUMINEMIA; ANALBA OMIM#616000) is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin and is caused by biallelic loss of function variants.
Retinitis pigmentosa v0.63 SCAPER Zornitza Stark Marked gene: SCAPER as ready
Retinitis pigmentosa v0.63 SCAPER Zornitza Stark Gene: scaper has been classified as Red List (Low Evidence).
Retinitis pigmentosa v0.63 SCAPER Zornitza Stark Publications for gene: SCAPER were set to 28794130; 31069901; 31192531; 30723319
Retinitis pigmentosa v0.62 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mendeliome v0.4586 ATP6V1B1 Zornitza Stark Marked gene: ATP6V1B1 as ready
Mendeliome v0.4586 ATP6V1B1 Zornitza Stark Gene: atp6v1b1 has been classified as Green List (High Evidence).
Mendeliome v0.4586 ATP6V1B1 Zornitza Stark Phenotypes for gene: ATP6V1B1 were changed from to Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM# 267300
Mendeliome v0.4585 ATP6V1B1 Zornitza Stark Publications for gene: ATP6V1B1 were set to
Mendeliome v0.4584 ATP6V1B1 Zornitza Stark Mode of inheritance for gene: ATP6V1B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4583 ATP6V1B1 Zornitza Stark reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9916796, 12414817, 16611712, 18798332; Phenotypes: Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM# 267300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.408 ATP6V1B1 Zornitza Stark Marked gene: ATP6V1B1 as ready
Deafness_IsolatedAndComplex v0.408 ATP6V1B1 Zornitza Stark Gene: atp6v1b1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.408 ATP6V1B1 Zornitza Stark Phenotypes for gene: ATP6V1B1 were changed from to Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM# 267300
Deafness_IsolatedAndComplex v0.407 ATP6V1B1 Zornitza Stark Publications for gene: ATP6V1B1 were set to
Deafness_IsolatedAndComplex v0.406 ATP6V1B1 Zornitza Stark Mode of inheritance for gene: ATP6V1B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.405 ATP6V1B1 Zornitza Stark reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9916796, 12414817, 16611712, 18798332; Phenotypes: Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM# 267300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.405 ATP2B2 Zornitza Stark Phenotypes for gene: ATP2B2 were changed from progressive sensorineural deafness to Dominant progressive sensorineural deafness; {Deafness, autosomal recessive 12, modifier of}, MIM# 601386
Mendeliome v0.4583 ATP2B2 Zornitza Stark reviewed gene: ATP2B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30535804, 15829536; Phenotypes: Dominant progressive sensorineural deafness, {Deafness, autosomal recessive 12, modifier of}, MIM# 601386; Mode of inheritance: None
Deafness_IsolatedAndComplex v0.404 ATP2B2 Zornitza Stark reviewed gene: ATP2B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30535804, 15829536; Phenotypes: Dominant deafness, {Deafness, autosomal recessive 12, modifier of}, MIM# 601386; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.404 ALMS1 Zornitza Stark Marked gene: ALMS1 as ready
Deafness_IsolatedAndComplex v0.404 ALMS1 Zornitza Stark Gene: alms1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.404 ALMS1 Zornitza Stark Phenotypes for gene: ALMS1 were changed from to Alstrom syndrome, MIM# 203800
Deafness_IsolatedAndComplex v0.403 ALMS1 Zornitza Stark Publications for gene: ALMS1 were set to
Deafness_IsolatedAndComplex v0.402 ALMS1 Zornitza Stark Mode of inheritance for gene: ALMS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.401 ALMS1 Zornitza Stark reviewed gene: ALMS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11941369, 17594715; Phenotypes: Alstrom syndrome, MIM# 203800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.401 ADGRV1 Zornitza Stark Marked gene: ADGRV1 as ready
Deafness_IsolatedAndComplex v0.401 ADGRV1 Zornitza Stark Gene: adgrv1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.401 ADGRV1 Zornitza Stark Phenotypes for gene: ADGRV1 were changed from to Usher syndrome, type 2C, MIM# 605472
Deafness_IsolatedAndComplex v0.400 ADGRV1 Zornitza Stark Publications for gene: ADGRV1 were set to
Deafness_IsolatedAndComplex v0.399 ADGRV1 Zornitza Stark Mode of inheritance for gene: ADGRV1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.398 ADGRV1 Zornitza Stark reviewed gene: ADGRV1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22147658, 25572244, 14740321; Phenotypes: Usher syndrome, type 2C, MIM# 605472; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.69 KRIT1 Zornitza Stark Marked gene: KRIT1 as ready
Additional findings_Paediatric v0.69 KRIT1 Zornitza Stark Added comment: Comment when marking as ready: Agree, potentially actionable in childhood.
Additional findings_Paediatric v0.69 KRIT1 Zornitza Stark Gene: krit1 has been classified as Amber List (Moderate Evidence).
Additional findings_Paediatric v0.69 KRIT1 Zornitza Stark Classified gene: KRIT1 as Amber List (moderate evidence)
Additional findings_Paediatric v0.69 KRIT1 Zornitza Stark Gene: krit1 has been classified as Amber List (Moderate Evidence).
Additional findings_Paediatric v0.68 MYH7 Zornitza Stark Marked gene: MYH7 as ready
Additional findings_Paediatric v0.68 MYH7 Zornitza Stark Gene: myh7 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.68 MYH7 Zornitza Stark Phenotypes for gene: MYH7 were changed from Left ventricular noncompaction; Cardiomyopathy, familial hypertrophic; Cardiomyopathy, dilated; Congenital fiber type disproportion; Myopathy, myosin storage; Laing distal myopathy; Scapuloperoneal syndrome, myopathic type to Myopathy and cardiomyopathy MIM#160760
Additional findings_Paediatric v0.67 MYH7 Zornitza Stark Classified gene: MYH7 as Green List (high evidence)
Additional findings_Paediatric v0.67 MYH7 Zornitza Stark Gene: myh7 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.66 NTRK1 Zornitza Stark Marked gene: NTRK1 as ready
Additional findings_Paediatric v0.66 NTRK1 Zornitza Stark Gene: ntrk1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.66 NTRK1 Zornitza Stark Phenotypes for gene: NTRK1 were changed from Medullary thyroid carcinoma, familial; Congenital insensitivity to pain with anhidrosis to Congenital insensitivity to pain with anhidrosis MIM#256800
Additional findings_Paediatric v0.65 NTRK1 Zornitza Stark Mode of inheritance for gene: NTRK1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.64 NTRK1 Zornitza Stark Classified gene: NTRK1 as Green List (high evidence)
Additional findings_Paediatric v0.64 NTRK1 Zornitza Stark Gene: ntrk1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.63 DUOXA2 Zornitza Stark edited their review of gene: DUOXA2: Changed phenotypes: Thyroid dyshormonogenesis 5, MIM# 274900
Additional findings_Paediatric v0.63 DUOXA2 Zornitza Stark reviewed gene: DUOXA2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.63 DCX Zornitza Stark Marked gene: DCX as ready
Additional findings_Paediatric v0.63 DCX Zornitza Stark Gene: dcx has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.63 DCX Zornitza Stark Phenotypes for gene: DCX were changed from Lennox-Gastaut syndrome; Lissencephaly, X-linked to Lissencephaly, X-linked, MIM# 300067
Additional findings_Paediatric v0.62 DCX Zornitza Stark Classified gene: DCX as Green List (high evidence)
Additional findings_Paediatric v0.62 DCX Zornitza Stark Gene: dcx has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.61 DCX Zornitza Stark reviewed gene: DCX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly, X-linked, MIM# 300067; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Additional findings_Paediatric v0.61 COL1A1 Zornitza Stark Marked gene: COL1A1 as ready
Additional findings_Paediatric v0.61 COL1A1 Zornitza Stark Gene: col1a1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.61 COL1A1 Zornitza Stark Phenotypes for gene: COL1A1 were changed from Caffey disease; Osteogenesis imperfecta, type I to Osteogenesis imperfecta, type I
Additional findings_Paediatric v0.60 COL1A1 Zornitza Stark Classified gene: COL1A1 as Green List (high evidence)
Additional findings_Paediatric v0.60 COL1A1 Zornitza Stark Gene: col1a1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.59 COL1A1 Zornitza Stark reviewed gene: COL1A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteogenesis imperfecta, type I; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.59 CLCN7 Zornitza Stark Marked gene: CLCN7 as ready
Additional findings_Paediatric v0.59 CLCN7 Zornitza Stark Gene: clcn7 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.59 CLCN7 Zornitza Stark Phenotypes for gene: CLCN7 were changed from Osteopetrosis to Osteopetrosis, autosomal recessive 4, MIM# 611490
Additional findings_Paediatric v0.58 CLCN7 Zornitza Stark Mode of inheritance for gene: CLCN7 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.57 CLCN7 Zornitza Stark Classified gene: CLCN7 as Green List (high evidence)
Additional findings_Paediatric v0.57 CLCN7 Zornitza Stark Gene: clcn7 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.56 CLCN7 Zornitza Stark reviewed gene: CLCN7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteopetrosis, autosomal recessive 4, MIM# 611490; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.56 CLCN1 Zornitza Stark Marked gene: CLCN1 as ready
Additional findings_Paediatric v0.56 CLCN1 Zornitza Stark Gene: clcn1 has been classified as Red List (Low Evidence).
Additional findings_Paediatric v0.56 CLCN1 Zornitza Stark Phenotypes for gene: CLCN1 were changed from Myotonia congenita to Myotonia congenita, dominant, MIM# 160800; Myotonia congenita, recessive, MIM# 255700
Additional findings_Paediatric v0.55 CLCN1 Zornitza Stark Mode of inheritance for gene: CLCN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Additional findings_Paediatric v0.54 CLCN1 Zornitza Stark reviewed gene: CLCN1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Myotonia congenita, dominant, MIM# 160800, Myotonia congenita, recessive, MIM# 255700; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Additional findings_Paediatric v0.54 CD3D Zornitza Stark Marked gene: CD3D as ready
Additional findings_Paediatric v0.54 CD3D Zornitza Stark Gene: cd3d has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.54 CD3D Zornitza Stark Classified gene: CD3D as Green List (high evidence)
Additional findings_Paediatric v0.54 CD3D Zornitza Stark Gene: cd3d has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.53 CD3D Zornitza Stark gene: CD3D was added
gene: CD3D was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: CD3D was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CD3D were set to Immunodeficiency 19, MIM# 615617
Review for gene: CD3D was set to GREEN
Added comment: SCID phenotype, treatable by BMT. Included in NC Nexus panel.
Sources: Expert list
Additional findings_Paediatric v0.52 CAV3 Zornitza Stark Marked gene: CAV3 as ready
Additional findings_Paediatric v0.52 CAV3 Zornitza Stark Gene: cav3 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.52 CAV3 Zornitza Stark Phenotypes for gene: CAV3 were changed from Cardiomyopathy, familial hypertrophic; Rippling muscle disease; Long QT syndrome-9; Caveolinopathy; Muscular dystrophy, limb-girdle, type IC, to Muscular dystrophy, limb-girdle, type IC; Caveolinopathy
Additional findings_Paediatric v0.51 CAV3 Zornitza Stark Mode of inheritance for gene: CAV3 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.50 CAV3 Zornitza Stark Classified gene: CAV3 as Green List (high evidence)
Additional findings_Paediatric v0.50 CAV3 Zornitza Stark Gene: cav3 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.49 CAV3 Zornitza Stark reviewed gene: CAV3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, type IC, Caveolinopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.49 CARD11 Zornitza Stark Marked gene: CARD11 as ready
Additional findings_Paediatric v0.49 CARD11 Zornitza Stark Gene: card11 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.49 CARD11 Zornitza Stark Classified gene: CARD11 as Green List (high evidence)
Additional findings_Paediatric v0.49 CARD11 Zornitza Stark Gene: card11 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.48 CARD11 Zornitza Stark gene: CARD11 was added
gene: CARD11 was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: CARD11 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CARD11 were set to 23561803; 12818158; 23374270; 28628108
Phenotypes for gene: CARD11 were set to Immunodeficiency 11A, MIM# 615206
Review for gene: CARD11 was set to GREEN
Added comment: At least two individuals with bi-allelic, and four with mono-allelic variants, animal model. Included in NC NEXUS panel.
Sources: Expert list
Additional findings_Paediatric v0.47 KRIT1 Lilian Downie gene: KRIT1 was added
gene: KRIT1 was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: KRIT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRIT1 were set to PMID: 30061145, 20301470, 27561926
Phenotypes for gene: KRIT1 were set to Cerebral cavernous malformations-1 MIM# 116860
Review for gene: KRIT1 was set to AMBER
Added comment: Not evaluated by Babyseq, included in NC NEXUS list. Cerebral cavernous angiomas are relatively rare vascular malformations that may involve any part of the central nervous system. Complications of rupture/bleeding can cause seizures, stroke, neurological deficits. Screening and management is available. Rare but can be paediatric onset: see PMID's.
Sources: Expert list
Additional findings_Paediatric v0.47 MYH7 Lilian Downie reviewed gene: MYH7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy and cardiomyopathy MIM#160760; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.47 NTRK1 Lilian Downie reviewed gene: NTRK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Insensitivity to pain, congenital, with anhidrosis MIM#256800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4583 C1orf194 Zornitza Stark Phenotypes for gene: C1orf194 were changed from Charcot-Marie-Tooth to Charcot-Marie-Tooth disease, intermediate or demyelinating
Mendeliome v0.4582 C1orf194 Zornitza Stark Publications for gene: C1orf194 were set to PMID: 31199454
Mendeliome v0.4581 ALB Zornitza Stark Marked gene: ALB as ready
Mendeliome v0.4581 ALB Zornitza Stark Gene: alb has been classified as Green List (High Evidence).
Mendeliome v0.4581 ALB Zornitza Stark Phenotypes for gene: ALB were changed from to Familial dysalbuminaemic hyperthyroxinaemia; [Dysalbuminemic hyperthyroxinemia], 615999; Analbuminemia, MIM# 616000
Mendeliome v0.4580 ALB Zornitza Stark Publications for gene: ALB were set to
Mendeliome v0.4579 ALB Zornitza Stark Mode of inheritance for gene: ALB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4578 ALB Zornitza Stark reviewed gene: ALB: Rating: GREEN; Mode of pathogenicity: None; Publications: 29163366, 24646103, 8064810, 27834068, 32635414; Phenotypes: Familial dysalbuminaemic hyperthyroxinaemia, [Dysalbuminemic hyperthyroxinemia], 615999, Analbuminemia, MIM# 616000; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hyperthyroidism v0.3 ALB Zornitza Stark Marked gene: ALB as ready
Hyperthyroidism v0.3 ALB Zornitza Stark Gene: alb has been classified as Green List (High Evidence).
Hyperthyroidism v0.3 ALB Zornitza Stark Publications for gene: ALB were set to 29163366; 24646103; 8064810; 27834068
Hyperthyroidism v0.2 ALB Zornitza Stark Mode of pathogenicity for gene: ALB was changed from to Other
Early-onset Dementia v0.121 TUBA4A Zornitza Stark Marked gene: TUBA4A as ready
Early-onset Dementia v0.121 TUBA4A Zornitza Stark Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Incidentalome v0.43 TUBA4A Zornitza Stark Marked gene: TUBA4A as ready
Incidentalome v0.43 TUBA4A Zornitza Stark Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Incidentalome v0.43 TUBA4A Zornitza Stark Phenotypes for gene: TUBA4A were changed from to Amyotrophic lateral sclerosis 22 with or without frontotemporal dementia, MIM# 616208
Incidentalome v0.42 TUBA4A Zornitza Stark Publications for gene: TUBA4A were set to
Incidentalome v0.41 TUBA4A Zornitza Stark Mode of inheritance for gene: TUBA4A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.40 TUBA4A Zornitza Stark Classified gene: TUBA4A as Amber List (moderate evidence)
Incidentalome v0.40 TUBA4A Zornitza Stark Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.121 TUBA4A Zornitza Stark Phenotypes for gene: TUBA4A were changed from to Amyotrophic lateral sclerosis 22 with or without frontotemporal dementia, MIM# 616208
Incidentalome v0.39 TUBA4A Zornitza Stark reviewed gene: TUBA4A: Rating: AMBER; Mode of pathogenicity: None; Publications: 28069311, 25374358, 26675813; Phenotypes: Amyotrophic lateral sclerosis 22 with or without frontotemporal dementia, MIM# 616208; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.58 TUBA4A Zornitza Stark Marked gene: TUBA4A as ready
Motor Neurone Disease v0.58 TUBA4A Zornitza Stark Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.58 TUBA4A Zornitza Stark Phenotypes for gene: TUBA4A were changed from to Amyotrophic lateral sclerosis 22 with or without frontotemporal dementia, MIM# 616208
Motor Neurone Disease v0.57 TUBA4A Zornitza Stark Publications for gene: TUBA4A were set to
Motor Neurone Disease v0.56 TUBA4A Zornitza Stark Mode of inheritance for gene: TUBA4A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.55 TUBA4A Zornitza Stark Classified gene: TUBA4A as Amber List (moderate evidence)
Motor Neurone Disease v0.55 TUBA4A Zornitza Stark Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.54 TUBA4A Zornitza Stark reviewed gene: TUBA4A: Rating: AMBER; Mode of pathogenicity: None; Publications: 28069311, 25374358, 26675813; Phenotypes: Amyotrophic lateral sclerosis 22 with or without frontotemporal dementia, MIM# 616208; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.120 TUBA4A Zornitza Stark Publications for gene: TUBA4A were set to
Early-onset Dementia v0.119 TUBA4A Zornitza Stark Mode of inheritance for gene: TUBA4A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.118 TUBA4A Zornitza Stark Classified gene: TUBA4A as Amber List (moderate evidence)
Early-onset Dementia v0.118 TUBA4A Zornitza Stark Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.117 TUBA4A Zornitza Stark reviewed gene: TUBA4A: Rating: AMBER; Mode of pathogenicity: None; Publications: 28069311, 25374358, 26675813; Phenotypes: Amyotrophic lateral sclerosis 22 with or without frontotemporal dementia, MIM# 616208; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.117 CHCHD10 Zornitza Stark Publications for gene: CHCHD10 were set to 24934289; 31690696; 30877432; 32369233
Early-onset Dementia v0.116 CHCHD10 Zornitza Stark changed review comment from: CHCHD10 is a small protein of the mitochondrial intermembrane space that is enriched at cristae junctions. It is predicted to be involved in oxidative phosphorylation or in maintenance of cristae morphology. Variants have been associated with a broad spectrum of neurological/neuromuscular phenotypes. Several large multiplex families described segregating different neurological disorders, ranging from dementia, to SMA, to myopathy. GOF mechanism has been proposed for FTD/ALS association based on a mouse model.

Two families reported with p.Ser59Leu variant and predominantly a dementia phenotype. Variant segregated with disease in 8 family members in one of the families. No variants in this gene identified in an Australian cohort study, PMID 31690696; however, good functional data including from mouse model supports gene-disease association.; to: CHCHD10 is a small protein of the mitochondrial intermembrane space that is enriched at cristae junctions. It is predicted to be involved in oxidative phosphorylation or in maintenance of cristae morphology. Variants have been associated with a broad spectrum of neurological/neuromuscular phenotypes. Several large multiplex families described segregating different neurological disorders, ranging from dementia, to SMA, to myopathy. GOF mechanism has been proposed for FTD/ALS association based on a mouse model.

Two families reported with p.Ser59Leu variant, and one with a truncating variant and predominantly a dementia phenotype. Variant segregated with disease in 8 family members in one of the families. No variants in this gene identified in an Australian cohort study, PMID 31690696; however, good functional data including from mouse model supports gene-disease association.
Early-onset Dementia v0.116 CHCHD10 Zornitza Stark edited their review of gene: CHCHD10: Changed publications: 24934289, 31690696, 30877432, 32369233, 28069311
Early-onset Dementia v0.116 TTR Zornitza Stark Marked gene: TTR as ready
Early-onset Dementia v0.116 TTR Zornitza Stark Gene: ttr has been classified as Green List (High Evidence).
Early-onset Dementia v0.116 TTR Zornitza Stark Phenotypes for gene: TTR were changed from to Amyloidosis, hereditary, transthyretin-related, MIM# 105210
Early-onset Dementia v0.115 TTR Zornitza Stark Publications for gene: TTR were set to
Early-onset Dementia v0.114 TTR Zornitza Stark Mode of inheritance for gene: TTR was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.113 TTR Zornitza Stark reviewed gene: TTR: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301373; Phenotypes: Amyloidosis, hereditary, transthyretin-related, MIM# 105210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4578 TREM2 Zornitza Stark Marked gene: TREM2 as ready
Mendeliome v0.4578 TREM2 Zornitza Stark Gene: trem2 has been classified as Green List (High Evidence).
Mendeliome v0.4578 TREM2 Zornitza Stark Phenotypes for gene: TREM2 were changed from to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM# 618193
Mendeliome v0.4577 TREM2 Zornitza Stark Publications for gene: TREM2 were set to
Mendeliome v0.4576 TREM2 Zornitza Stark Mode of inheritance for gene: TREM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4575 TREM2 Zornitza Stark reviewed gene: TREM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12080485, 15883308; Phenotypes: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM# 618193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.170 TREM2 Zornitza Stark Marked gene: TREM2 as ready
Regression v0.170 TREM2 Zornitza Stark Gene: trem2 has been classified as Red List (Low Evidence).
Regression v0.170 TREM2 Zornitza Stark Phenotypes for gene: TREM2 were changed from to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM# 618193
Regression v0.169 TREM2 Zornitza Stark Publications for gene: TREM2 were set to
Regression v0.168 TREM2 Zornitza Stark Mode of inheritance for gene: TREM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.167 TREM2 Zornitza Stark Classified gene: TREM2 as Red List (low evidence)
Regression v0.167 TREM2 Zornitza Stark Gene: trem2 has been classified as Red List (Low Evidence).
Regression v0.166 TREM2 Zornitza Stark reviewed gene: TREM2: Rating: RED; Mode of pathogenicity: None; Publications: 12080485, 15883308; Phenotypes: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM# 618193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.113 TREM2 Zornitza Stark Marked gene: TREM2 as ready
Early-onset Dementia v0.113 TREM2 Zornitza Stark Gene: trem2 has been classified as Green List (High Evidence).
Early-onset Dementia v0.113 TREM2 Zornitza Stark Phenotypes for gene: TREM2 were changed from to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM# 618193
Early-onset Dementia v0.112 TREM2 Zornitza Stark Publications for gene: TREM2 were set to
Early-onset Dementia v0.111 TREM2 Zornitza Stark Mode of inheritance for gene: TREM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.110 TREM2 Zornitza Stark reviewed gene: TREM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12080485, 15883308; Phenotypes: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM# 618193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4575 SPG21 Zornitza Stark Marked gene: SPG21 as ready
Mendeliome v0.4575 SPG21 Zornitza Stark Gene: spg21 has been classified as Green List (High Evidence).
Mendeliome v0.4575 SPG21 Zornitza Stark Phenotypes for gene: SPG21 were changed from to Mast syndrome, MIM# 248900
Mendeliome v0.4574 SPG21 Zornitza Stark Publications for gene: SPG21 were set to
Mendeliome v0.4573 SPG21 Zornitza Stark Mode of inheritance for gene: SPG21 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4572 SPG21 Zornitza Stark Tag new gene name tag was added to gene: SPG21.
Mendeliome v0.4572 SPG21 Zornitza Stark reviewed gene: SPG21: Rating: GREEN; Mode of pathogenicity: None; Publications: 14564668, 24451228, 28752238, 26978163; Phenotypes: Mast syndrome, MIM# 248900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.110 SPG21 Zornitza Stark changed review comment from: Mast syndrome is an autosomal recessive complicated form of hereditary spastic paraplegia in which progressive spastic paraparesis is associated in more advanced cases with cognitive decline, dementia, and other neurologic abnormalities. Symptom onset usually occurs in adulthood, and the disorder is progressive with variable severity. Brain imaging shows thinning of the corpus callosum. The disorder occurs with high frequency in the Old Order Amish. Founder variant in Amish, two additional families and a mouse model.; to: Mast syndrome is an autosomal recessive complicated form of hereditary spastic paraplegia in which progressive spastic paraparesis is associated in more advanced cases with cognitive decline, dementia, and other neurologic abnormalities. Symptom onset usually occurs in adulthood, and the disorder is progressive with variable severity. Brain imaging shows thinning of the corpus callosum. The disorder occurs with high frequency in the Old Order Amish. Founder variant in Amish, two additional families and a mouse model.

New HGNC approved gene name is ACP33
Early-onset Dementia v0.110 SPG21 Zornitza Stark Tag new gene name tag was added to gene: SPG21.
Early-onset Dementia v0.110 SPG21 Zornitza Stark Marked gene: SPG21 as ready
Early-onset Dementia v0.110 SPG21 Zornitza Stark Gene: spg21 has been classified as Green List (High Evidence).
Early-onset Dementia v0.110 SPG21 Zornitza Stark Phenotypes for gene: SPG21 were changed from to Mast syndrome, MIM# 248900
Early-onset Dementia v0.109 SPG21 Zornitza Stark Publications for gene: SPG21 were set to
Early-onset Dementia v0.108 SPG21 Zornitza Stark Mode of inheritance for gene: SPG21 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.107 SPG21 Zornitza Stark edited their review of gene: SPG21: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.107 SPG21 Zornitza Stark edited their review of gene: SPG21: Changed rating: GREEN
Early-onset Dementia v0.107 SPG21 Zornitza Stark reviewed gene: SPG21: Rating: ; Mode of pathogenicity: None; Publications: 14564668, 24451228, 28752238, 26978163; Phenotypes: Mast syndrome, MIM# 248900; Mode of inheritance: None
Incidentalome v0.39 SNCB Zornitza Stark Marked gene: SNCB as ready
Incidentalome v0.39 SNCB Zornitza Stark Gene: sncb has been classified as Red List (Low Evidence).
Incidentalome v0.39 SNCB Zornitza Stark Tag disputed tag was added to gene: SNCB.
Incidentalome v0.39 SNCB Zornitza Stark Phenotypes for gene: SNCB were changed from to Dementia, Lewy body, MIM#127750
Early-onset Dementia v0.107 SNCB Zornitza Stark Tag disputed tag was added to gene: SNCB.
Incidentalome v0.38 SNCB Zornitza Stark Publications for gene: SNCB were set to
Incidentalome v0.37 SNCB Zornitza Stark Mode of inheritance for gene: SNCB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.36 SNCB Zornitza Stark Classified gene: SNCB as Red List (low evidence)
Incidentalome v0.36 SNCB Zornitza Stark Gene: sncb has been classified as Red List (Low Evidence).
Incidentalome v0.35 SNCB Zornitza Stark reviewed gene: SNCB: Rating: RED; Mode of pathogenicity: None; Publications: 15365127, 20697047; Phenotypes: Dementia, Lewy body, MIM#127750; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.107 SNCB Zornitza Stark Marked gene: SNCB as ready
Early-onset Dementia v0.107 SNCB Zornitza Stark Gene: sncb has been classified as Red List (Low Evidence).
Early-onset Dementia v0.107 SNCB Zornitza Stark Phenotypes for gene: SNCB were changed from to Dementia, Lewy body, MIM#127750
Early-onset Dementia v0.106 SNCB Zornitza Stark Publications for gene: SNCB were set to
Early-onset Dementia v0.105 SNCB Zornitza Stark Mode of inheritance for gene: SNCB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.104 SNCB Zornitza Stark Classified gene: SNCB as Red List (low evidence)
Early-onset Dementia v0.104 SNCB Zornitza Stark Gene: sncb has been classified as Red List (Low Evidence).
Early-onset Dementia v0.103 SNCB Zornitza Stark reviewed gene: SNCB: Rating: RED; Mode of pathogenicity: None; Publications: 15365127, 20697047; Phenotypes: Dementia, Lewy body, 127750; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hyperthyroidism v0.1 ALB Anna Le Fevre edited their review of gene: ALB: Changed publications: PMID: 29163366, 32635414
Hyperthyroidism v0.1 ALB Anna Le Fevre reviewed gene: ALB: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 29163366; Phenotypes: HYPERTHYROXINEMIA, FAMILIAL DYSALBUMINEMIC, FDAH (OMIM#615999); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Regression v0.166 FUS Zornitza Stark Marked gene: FUS as ready
Regression v0.166 FUS Zornitza Stark Gene: fus has been classified as Red List (Low Evidence).
Regression v0.166 FUS Zornitza Stark Phenotypes for gene: FUS were changed from to Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia, MIM# 608030
Regression v0.165 FUS Zornitza Stark Mode of inheritance for gene: FUS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Regression v0.164 FUS Zornitza Stark Classified gene: FUS as Red List (low evidence)
Regression v0.164 FUS Zornitza Stark Gene: fus has been classified as Red List (Low Evidence).
Regression v0.163 FUS Zornitza Stark reviewed gene: FUS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia, MIM# 608030; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.103 FUS Zornitza Stark Marked gene: FUS as ready
Early-onset Dementia v0.103 FUS Zornitza Stark Gene: fus has been classified as Green List (High Evidence).
Early-onset Dementia v0.103 FUS Zornitza Stark Phenotypes for gene: FUS were changed from to Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia, MIM# 608030
Early-onset Dementia v0.102 FUS Zornitza Stark Publications for gene: FUS were set to
Early-onset Dementia v0.101 FUS Zornitza Stark Mode of inheritance for gene: FUS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.100 FUS Zornitza Stark reviewed gene: FUS: Rating: GREEN; Mode of pathogenicity: None; Publications: 32941707, 32770214; Phenotypes: Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia, MIM# 608030; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.100 FTL Zornitza Stark Marked gene: FTL as ready
Early-onset Dementia v0.100 FTL Zornitza Stark Gene: ftl has been classified as Green List (High Evidence).
Early-onset Dementia v0.100 FTL Zornitza Stark Phenotypes for gene: FTL were changed from to Neurodegeneration with brain iron accumulation 3, MIM# 606159
Early-onset Dementia v0.99 FTL Zornitza Stark Publications for gene: FTL were set to
Early-onset Dementia v0.98 FTL Zornitza Stark Mode of inheritance for gene: FTL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.97 FTL Zornitza Stark reviewed gene: FTL: Rating: GREEN; Mode of pathogenicity: None; Publications: 11438811, 18854324, 15099026, 15173247; Phenotypes: Neurodegeneration with brain iron accumulation 3, MIM# 606159; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.97 FA2H Zornitza Stark Marked gene: FA2H as ready
Early-onset Dementia v0.97 FA2H Zornitza Stark Gene: fa2h has been classified as Red List (Low Evidence).
Early-onset Dementia v0.97 FA2H Zornitza Stark Phenotypes for gene: FA2H were changed from to Spastic paraplegia 35, autosomal recessive, MIM# 612319
Early-onset Dementia v0.96 FA2H Zornitza Stark Mode of inheritance for gene: FA2H was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.95 FA2H Zornitza Stark Classified gene: FA2H as Red List (low evidence)
Early-onset Dementia v0.95 FA2H Zornitza Stark Gene: fa2h has been classified as Red List (Low Evidence).
Early-onset Dementia v0.94 FA2H Zornitza Stark reviewed gene: FA2H: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 35, autosomal recessive, MIM# 612319; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.94 DCTN1 Zornitza Stark Marked gene: DCTN1 as ready
Early-onset Dementia v0.94 DCTN1 Zornitza Stark Gene: dctn1 has been classified as Green List (High Evidence).
Early-onset Dementia v0.94 DCTN1 Zornitza Stark Phenotypes for gene: DCTN1 were changed from to Perry syndrome, MIM# 168605
Early-onset Dementia v0.93 DCTN1 Zornitza Stark Publications for gene: DCTN1 were set to
Early-onset Dementia v0.92 DCTN1 Zornitza Stark Mode of inheritance for gene: DCTN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.91 DCTN1 Zornitza Stark reviewed gene: DCTN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19136952; Phenotypes: Perry syndrome, MIM# 168605; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.91 CYP27A1 Zornitza Stark Marked gene: CYP27A1 as ready
Early-onset Dementia v0.91 CYP27A1 Zornitza Stark Gene: cyp27a1 has been classified as Green List (High Evidence).
Early-onset Dementia v0.91 CYP27A1 Zornitza Stark Phenotypes for gene: CYP27A1 were changed from to Cerebrotendinous xanthomatosis, MIM# 213700
Early-onset Dementia v0.90 CYP27A1 Zornitza Stark Mode of inheritance for gene: CYP27A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.89 CYP27A1 Zornitza Stark reviewed gene: CYP27A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebrotendinous xanthomatosis, MIM# 213700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.89 CHCHD10 Zornitza Stark Marked gene: CHCHD10 as ready
Early-onset Dementia v0.89 CHCHD10 Zornitza Stark Gene: chchd10 has been classified as Green List (High Evidence).
Early-onset Dementia v0.89 CHCHD10 Zornitza Stark Phenotypes for gene: CHCHD10 were changed from to Frontotemporal dementia and/or amyotrophic lateral sclerosis 2, MIM# 615911
Early-onset Dementia v0.88 CHCHD10 Zornitza Stark Publications for gene: CHCHD10 were set to
Early-onset Dementia v0.87 CHCHD10 Zornitza Stark Mode of inheritance for gene: CHCHD10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.86 CHCHD10 Zornitza Stark reviewed gene: CHCHD10: Rating: GREEN; Mode of pathogenicity: None; Publications: 24934289, 31690696, 30877432, 32369233; Phenotypes: Frontotemporal dementia and/or amyotrophic lateral sclerosis 2, MIM# 615911; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurodegenerative disease - adult onset v0.2 Bryony Thompson Panel status changed from internal to public
Neurodegenerative disease - adult onset v0.1 Bryony Thompson Panel name changed from Neurology and neurodevelopmental disorders to Neurodegenerative disease - adult onset
Neurodegenerative disease - adult onset v0.0 Bryony Thompson Added Panel Neurology and neurodevelopmental disorders
Set child panels to: Ataxia - adult onset; Early-onset Dementia; Early-onset Parkinson disease; Motor Neuron Disease; Hereditary Spastic Paraplegia - adult onset
Set panel types to: Superpanel; Royal Melbourne Hospital; Rare Disease
Early-onset Dementia v0.86 C19orf12 Zornitza Stark Marked gene: C19orf12 as ready
Early-onset Dementia v0.86 C19orf12 Zornitza Stark Gene: c19orf12 has been classified as Green List (High Evidence).
Early-onset Dementia v0.86 C19orf12 Zornitza Stark Phenotypes for gene: C19orf12 were changed from to Neurodegeneration with brain iron accumulation 4, MIM# 614298
Early-onset Dementia v0.85 C19orf12 Zornitza Stark Publications for gene: C19orf12 were set to
Early-onset Dementia v0.84 C19orf12 Zornitza Stark Mode of inheritance for gene: C19orf12 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Dementia v0.83 C19orf12 Zornitza Stark reviewed gene: C19orf12: Rating: GREEN; Mode of pathogenicity: None; Publications: 23278385, 21981780, 23269600; Phenotypes: Neurodegeneration with brain iron accumulation 4, MIM# 614298; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Dementia v0.83 ATP13A2 Zornitza Stark Marked gene: ATP13A2 as ready
Early-onset Dementia v0.83 ATP13A2 Zornitza Stark Gene: atp13a2 has been classified as Green List (High Evidence).
Early-onset Dementia v0.83 ATP13A2 Zornitza Stark Phenotypes for gene: ATP13A2 were changed from to Kufor-Rakeb syndrome, MIM# 606693
Early-onset Dementia v0.82 ATP13A2 Zornitza Stark Mode of inheritance for gene: ATP13A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.81 ATP13A2 Zornitza Stark reviewed gene: ATP13A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Kufor-Rakeb syndrome, MIM# 606693; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.81 ARSA Zornitza Stark Marked gene: ARSA as ready
Early-onset Dementia v0.81 ARSA Zornitza Stark Gene: arsa has been classified as Green List (High Evidence).
Early-onset Dementia v0.81 ARSA Zornitza Stark Phenotypes for gene: ARSA were changed from to Metachromatic leukodystrophy, MIM# 250100, adult-onset
Early-onset Dementia v0.80 ARSA Zornitza Stark Publications for gene: ARSA were set to
Early-onset Dementia v0.79 ARSA Zornitza Stark Mode of inheritance for gene: ARSA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.78 ARSA Zornitza Stark reviewed gene: ARSA: Rating: GREEN; Mode of pathogenicity: None; Publications: 29486463, 26890752, 15710861; Phenotypes: Metachromatic leukodystrophy, MIM# 250100, adult-onset; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.78 APOE Zornitza Stark Marked gene: APOE as ready
Early-onset Dementia v0.78 APOE Zornitza Stark Gene: apoe has been classified as Green List (High Evidence).
Early-onset Dementia v0.78 APOE Zornitza Stark Phenotypes for gene: APOE were changed from to Alzheimer disease 2, MIM# 104310
Early-onset Dementia v0.77 APOE Zornitza Stark Mode of inheritance for gene: APOE was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.76 APOE Zornitza Stark reviewed gene: APOE: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alzheimer disease 2, MIM# 104310; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bone Marrow Failure v0.165 RPS20 Zornitza Stark Marked gene: RPS20 as ready
Bone Marrow Failure v0.165 RPS20 Zornitza Stark Gene: rps20 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v0.165 RPS20 Zornitza Stark Classified gene: RPS20 as Amber List (moderate evidence)
Bone Marrow Failure v0.165 RPS20 Zornitza Stark Gene: rps20 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v0.164 RPS20 Zornitza Stark gene: RPS20 was added
gene: RPS20 was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: RPS20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS20 were set to 32790018
Phenotypes for gene: RPS20 were set to Diamond Blackfan anaemia
Review for gene: RPS20 was set to AMBER
Added comment: Two unrelated cases where a de novo variant involving Ile84 (Ile84Ser and Ile84Asn), and reduce the RPS20 protein level in patient cells. Yeast models with mutation of the cognate residue resulted in defects in growth, ribosome biogenesis, and polysome formation. Loss of function may not be the mechanism of disease, because loss of function variants appear to be exclusively associated with familial colorectal cancer without the DBA phenotype.
Sources: Literature
Mendeliome v0.4572 LMX1A Zornitza Stark Marked gene: LMX1A as ready
Mendeliome v0.4572 LMX1A Zornitza Stark Gene: lmx1a has been classified as Green List (High Evidence).
Mendeliome v0.4572 LMX1A Zornitza Stark Phenotypes for gene: LMX1A were changed from to Deafness, autosomal dominant 7 MIM#601412; non-syndromic hearing loss
Mendeliome v0.4571 LMX1A Zornitza Stark Publications for gene: LMX1A were set to
Mendeliome v0.4570 LMX1A Zornitza Stark Mode of inheritance for gene: LMX1A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4569 LMX1A Zornitza Stark reviewed gene: LMX1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29754270, 32840933, 29971487; Phenotypes: Deafness, autosomal dominant 7 MIM#601412, non-syndromic hearing loss; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4569 RPS20 Bryony Thompson Marked gene: RPS20 as ready
Mendeliome v0.4569 RPS20 Bryony Thompson Gene: rps20 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4569 RPS20 Bryony Thompson Classified gene: RPS20 as Amber List (moderate evidence)
Mendeliome v0.4569 RPS20 Bryony Thompson Gene: rps20 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4568 RPS20 Bryony Thompson gene: RPS20 was added
gene: RPS20 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPS20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS20 were set to 32790018
Phenotypes for gene: RPS20 were set to Diamond Blackfan anaemia
Mode of pathogenicity for gene: RPS20 was set to Other
Review for gene: RPS20 was set to AMBER
Added comment: Two unrelated cases where a de novo variant involving Ile84 (Ile84Ser and Ile84Asn), and reduce the RPS20 protein level in patient cells. Yeast models with mutation of the cognate residue resulted in defects in growth, ribosome biogenesis, and polysome formation. Loss of function may not be the mechanism of disease, because loss of function variants appear to be exclusively associated with familial colorectal cancer without the DBA phenotype.
Sources: Literature
Diamond Blackfan anaemia v0.34 RPS20 Bryony Thompson Marked gene: RPS20 as ready
Diamond Blackfan anaemia v0.34 RPS20 Bryony Thompson Gene: rps20 has been classified as Amber List (Moderate Evidence).
Diamond Blackfan anaemia v0.34 RPS20 Bryony Thompson Classified gene: RPS20 as Amber List (moderate evidence)
Diamond Blackfan anaemia v0.34 RPS20 Bryony Thompson Gene: rps20 has been classified as Amber List (Moderate Evidence).
Diamond Blackfan anaemia v0.33 RPS20 Bryony Thompson gene: RPS20 was added
gene: RPS20 was added to Diamond Blackfan anaemia. Sources: Literature
Mode of inheritance for gene: RPS20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS20 were set to 32790018
Phenotypes for gene: RPS20 were set to Diamond Blackfan anaemia
Mode of pathogenicity for gene: RPS20 was set to Other
Review for gene: RPS20 was set to AMBER
Added comment: Two unrelated cases where a de novo variant involving Ile84 (Ile84Ser and Ile84Asn), and reduce the RPS20 protein level in patient cells. Yeast models with mutation of the cognate residue resulted in defects in growth, ribosome biogenesis, and polysome formation. Loss of function may not be the mechanism of disease, because loss of function variants appear to be exclusively associated with familial colorectal cancer without the DBA phenotype.
Sources: Literature
Deafness_IsolatedAndComplex v0.398 LMX1A Bryony Thompson Publications for gene: LMX1A were set to 29754270; 29971487
Deafness_IsolatedAndComplex v0.397 LMX1A Bryony Thompson Classified gene: LMX1A as Green List (high evidence)
Deafness_IsolatedAndComplex v0.397 LMX1A Bryony Thompson Gene: lmx1a has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.396 LMX1A Bryony Thompson reviewed gene: LMX1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29754270, 32840933, 29971487; Phenotypes: Deafness, autosomal dominant 7 MIM#601412, non-syndromic hearing loss; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.396 ACTG1 Zornitza Stark Mode of pathogenicity for gene: ACTG1 was changed from to Other
Deafness_IsolatedAndComplex v0.395 ACTG1 Zornitza Stark Marked gene: ACTG1 as ready
Deafness_IsolatedAndComplex v0.395 ACTG1 Zornitza Stark Gene: actg1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.395 ACTG1 Zornitza Stark Phenotypes for gene: ACTG1 were changed from to Deafness, autosomal dominant 20/26, MIM# 604717
Deafness_IsolatedAndComplex v0.394 ACTG1 Zornitza Stark Publications for gene: ACTG1 were set to
Deafness_IsolatedAndComplex v0.393 ACTG1 Zornitza Stark Mode of inheritance for gene: ACTG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.392 ACTG1 Zornitza Stark reviewed gene: ACTG1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 13680526, 14684684, 16773128, 19477959, 19497859; Phenotypes: Deafness, autosomal dominant 20/26, MIM# 604717; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4567 ABHD12 Zornitza Stark Publications for gene: ABHD12 were set to
Mendeliome v0.4566 ABHD12 Zornitza Stark reviewed gene: ABHD12: Rating: GREEN; Mode of pathogenicity: None; Publications: 20797687, 24697911; Phenotypes: Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract, MIM# 612674; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.392 ABHD12 Zornitza Stark Marked gene: ABHD12 as ready
Deafness_IsolatedAndComplex v0.392 ABHD12 Zornitza Stark Gene: abhd12 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.392 ABHD12 Zornitza Stark Phenotypes for gene: ABHD12 were changed from to Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract, MIM# 612674
Deafness_IsolatedAndComplex v0.391 ABHD12 Zornitza Stark Publications for gene: ABHD12 were set to
Deafness_IsolatedAndComplex v0.390 ABHD12 Zornitza Stark Mode of inheritance for gene: ABHD12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.389 ABHD12 Zornitza Stark reviewed gene: ABHD12: Rating: GREEN; Mode of pathogenicity: None; Publications: 20797687, 24697911; Phenotypes: Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract, MIM# 612674; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Alagille syndrome v1.0 Zornitza Stark promoted panel to version 1.0
Mendeliome v0.4566 SPAST Zornitza Stark Marked gene: SPAST as ready
Mendeliome v0.4566 SPAST Zornitza Stark Gene: spast has been classified as Green List (High Evidence).
Mendeliome v0.4566 SPAST Zornitza Stark Phenotypes for gene: SPAST were changed from to Spastic paraplegia 4, autosomal dominant (MIM#182601), AD
Mendeliome v0.4565 SPAST Zornitza Stark Publications for gene: SPAST were set to
Mendeliome v0.4564 SPAST Zornitza Stark Mode of inheritance for gene: SPAST was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4563 TRRAP Zornitza Stark Marked gene: TRRAP as ready
Mendeliome v0.4563 TRRAP Zornitza Stark Gene: trrap has been classified as Green List (High Evidence).
Mendeliome v0.4563 TRRAP Zornitza Stark Publications for gene: TRRAP were set to
Mendeliome v0.4562 TRRAP Zornitza Stark Phenotypes for gene: TRRAP were changed from to Developmental delay with or without dysmorphic facies and autism (MIM#618454)
Mendeliome v0.4561 TRRAP Zornitza Stark Mode of inheritance for gene: TRRAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mitochondrial disease v0.504 NDUFV2 Zornitza Stark Marked gene: NDUFV2 as ready
Mitochondrial disease v0.504 NDUFV2 Zornitza Stark Gene: ndufv2 has been classified as Green List (High Evidence).
Mitochondrial disease v0.504 NDUFV2 Zornitza Stark Tag deep intronic tag was added to gene: NDUFV2.
Tag founder tag was added to gene: NDUFV2.
Mitochondrial disease v0.504 NDUFV2 Zornitza Stark Mode of inheritance for gene: NDUFV2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.503 NDUFV2 Zornitza Stark Phenotypes for gene: NDUFV2 were changed from to Mitochondrial complex I deficiency, nuclear type 7 (MIM#618229)
Mitochondrial disease v0.502 NDUFV2 Zornitza Stark Publications for gene: NDUFV2 were set to
Mitochondrial disease v0.502 NDUFV2 Zornitza Stark Mode of inheritance for gene: NDUFV2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.501 NDUFV2 Zornitza Stark reviewed gene: NDUFV2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 7 (MIM#618229); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4560 TRRAP Chern Lim reviewed gene: TRRAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 30827496, 31231791; Phenotypes: Developmental delay with or without dysmorphic facies and autism (MIM#618454), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.4560 TRRAP Chern Lim Deleted their review
Mendeliome v0.4560 SPAST Chern Lim reviewed gene: SPAST: Rating: GREEN; Mode of pathogenicity: None; Publications: 30476002, 30006150; Phenotypes: Spastic paraplegia 4, autosomal dominant (MIM#182601), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.4560 TRRAP Chern Lim reviewed gene: TRRAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 30827496; Phenotypes: Developmental delay with or without dysmorphic facies and autism (MIM#618454), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Additional findings_Paediatric v0.47 BSCL2 Zornitza Stark Marked gene: BSCL2 as ready
Additional findings_Paediatric v0.47 BSCL2 Zornitza Stark Gene: bscl2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.47 BSCL2 Zornitza Stark Phenotypes for gene: BSCL2 were changed from Silver spastic paraplegia syndrome; Berardinelli-Seip lipodystrophy to Berardinelli-Seip lipodystrophy; Lipodystrophy, congenital generalized, type 2, MIM# 269700
Additional findings_Paediatric v0.46 BSCL2 Zornitza Stark Mode of inheritance for gene: BSCL2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.45 BSCL2 Zornitza Stark Classified gene: BSCL2 as Green List (high evidence)
Additional findings_Paediatric v0.45 BSCL2 Zornitza Stark Gene: bscl2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.44 BSCL2 Zornitza Stark reviewed gene: BSCL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lipodystrophy, congenital generalized, type 2, MIM# 269700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.44 PALB2 Zornitza Stark Marked gene: PALB2 as ready
Additional findings_Paediatric v0.44 PALB2 Zornitza Stark Gene: palb2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.44 PALB2 Zornitza Stark Phenotypes for gene: PALB2 were changed from Breast cancer to Fanconi anemia, complementation group N, MIM# 610832
Additional findings_Paediatric v0.43 PALB2 Zornitza Stark Publications for gene: PALB2 were set to
Additional findings_Paediatric v0.42 PALB2 Zornitza Stark Mode of inheritance for gene: PALB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.41 PALB2 Zornitza Stark Classified gene: PALB2 as Green List (high evidence)
Additional findings_Paediatric v0.41 PALB2 Zornitza Stark Gene: palb2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.40 P2RY12 Zornitza Stark Marked gene: P2RY12 as ready
Additional findings_Paediatric v0.40 P2RY12 Zornitza Stark Gene: p2ry12 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.40 P2RY12 Zornitza Stark Classified gene: P2RY12 as Green List (high evidence)
Additional findings_Paediatric v0.40 P2RY12 Zornitza Stark Gene: p2ry12 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.39 PDX1 Zornitza Stark Marked gene: PDX1 as ready
Additional findings_Paediatric v0.39 PDX1 Zornitza Stark Gene: pdx1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.39 PDX1 Zornitza Stark Classified gene: PDX1 as Green List (high evidence)
Additional findings_Paediatric v0.39 PDX1 Zornitza Stark Gene: pdx1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.38 PIK3CD Zornitza Stark Marked gene: PIK3CD as ready
Additional findings_Paediatric v0.38 PIK3CD Zornitza Stark Gene: pik3cd has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.38 PIK3CD Zornitza Stark Classified gene: PIK3CD as Green List (high evidence)
Additional findings_Paediatric v0.38 PIK3CD Zornitza Stark Gene: pik3cd has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.37 PTPRC Zornitza Stark Marked gene: PTPRC as ready
Additional findings_Paediatric v0.37 PTPRC Zornitza Stark Gene: ptprc has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.37 PTPRC Zornitza Stark Classified gene: PTPRC as Green List (high evidence)
Additional findings_Paediatric v0.37 PTPRC Zornitza Stark Gene: ptprc has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.36 RYR1 Zornitza Stark Marked gene: RYR1 as ready
Additional findings_Paediatric v0.36 RYR1 Zornitza Stark Gene: ryr1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.36 RYR1 Zornitza Stark Phenotypes for gene: RYR1 were changed from Centronuclear myopathy; Congenital fiber type disproportion; Multiminicore disease; Central core disease; Malignant hyperthermia to Malignant hyperthermia, multiminicore disease MIM#180901
Additional findings_Paediatric v0.35 RYR1 Zornitza Stark Mode of inheritance for gene: RYR1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Additional findings_Paediatric v0.34 RYR1 Zornitza Stark Classified gene: RYR1 as Green List (high evidence)
Additional findings_Paediatric v0.34 RYR1 Zornitza Stark Gene: ryr1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.33 SCNN1B Zornitza Stark Marked gene: SCNN1B as ready
Additional findings_Paediatric v0.33 SCNN1B Zornitza Stark Gene: scnn1b has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.33 SCNN1B Zornitza Stark Phenotypes for gene: SCNN1B were changed from Pseudohypoaldosteronism; Liddle syndrome to Pseudohypoaldosteronism, type I MIM# 264350
Additional findings_Paediatric v0.32 PALB2 Lilian Downie reviewed gene: PALB2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17200671; Phenotypes: Fanconi anemia, complementation group N MIM# 610832; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.32 SCNN1B Zornitza Stark Mode of inheritance for gene: SCNN1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.31 SCNN1B Zornitza Stark Classified gene: SCNN1B as Green List (high evidence)
Additional findings_Paediatric v0.31 SCNN1B Zornitza Stark Gene: scnn1b has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.30 SERPINA1 Zornitza Stark Marked gene: SERPINA1 as ready
Additional findings_Paediatric v0.30 SERPINA1 Zornitza Stark Gene: serpina1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.30 SERPINA1 Zornitza Stark Phenotypes for gene: SERPINA1 were changed from Antitrypsin alpha 1 deficiency to Antitrypsin alpha 1 deficiency; Emphysema due to AAT deficiency, OMIM #107400
Additional findings_Paediatric v0.29 SERPINA1 Zornitza Stark Classified gene: SERPINA1 as Green List (high evidence)
Additional findings_Paediatric v0.29 SERPINA1 Zornitza Stark Gene: serpina1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.28 SFTPC Zornitza Stark Marked gene: SFTPC as ready
Additional findings_Paediatric v0.28 SFTPC Zornitza Stark Gene: sftpc has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.28 SFTPC Zornitza Stark Phenotypes for gene: SFTPC were changed from Interstitial lung disease to Surfactant metabolism dysfunction, pulmonary, 2 MIM# 178620; Interstitial lung disease
Additional findings_Paediatric v0.27 SFTPC Zornitza Stark Classified gene: SFTPC as Green List (high evidence)
Additional findings_Paediatric v0.27 SFTPC Zornitza Stark Gene: sftpc has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.26 SGCD Zornitza Stark Marked gene: SGCD as ready
Additional findings_Paediatric v0.26 SGCD Zornitza Stark Gene: sgcd has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.26 SGCD Zornitza Stark Phenotypes for gene: SGCD were changed from Cardiomyopathy, dilated; Muscular dystrophy, limb-girdle, type 2F to Muscular dystrophy, limb-girdle, autosomal recessive 6, MIM# 601287
Additional findings_Paediatric v0.25 SGCD Zornitza Stark Classified gene: SGCD as Green List (high evidence)
Additional findings_Paediatric v0.25 SGCD Zornitza Stark Gene: sgcd has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.24 SLC6A19 Zornitza Stark Marked gene: SLC6A19 as ready
Additional findings_Paediatric v0.24 SLC6A19 Zornitza Stark Gene: slc6a19 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.24 SLC6A19 Zornitza Stark Phenotypes for gene: SLC6A19 were changed from Hartnup disorder to Hartnup disorder, MIM # 234500
Additional findings_Paediatric v0.23 SLC6A19 Zornitza Stark Classified gene: SLC6A19 as Green List (high evidence)
Additional findings_Paediatric v0.23 SLC6A19 Zornitza Stark Gene: slc6a19 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.22 PYGM Zornitza Stark Marked gene: PYGM as ready
Additional findings_Paediatric v0.22 PYGM Zornitza Stark Gene: pygm has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.22 PYGM Zornitza Stark Classified gene: PYGM as Green List (high evidence)
Additional findings_Paediatric v0.22 PYGM Zornitza Stark Gene: pygm has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.21 Zornitza Stark removed gene:P2RY1 from the panel
Additional findings_Paediatric v0.20 P2RY12 Lilian Downie gene: P2RY12 was added
gene: P2RY12 was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: P2RY12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: P2RY12 were set to Bleeding disorder, platelet-type, 8 MIM# 609821
Added comment: Characterized by mild to moderate mucocutaneous bleeding and excessive bleeding after surgery or trauma. The defect is due to the inability of ADP to induce platelet aggregation. Onset childhood. Treatable with FFP for procedures. Not reviewed by Babyseq, in the NC NEXUS list.
Sources: Expert list
Sources: Expert list
Additional findings_Paediatric v0.20 P2RY1 Lilian Downie gene: P2RY1 was added
gene: P2RY1 was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: P2RY1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: P2RY1 were set to Bleeding disorder, platelet-type, 8, MIM# 609821
Review for gene: P2RY1 was set to GREEN
Added comment: Characterized by mild to moderate mucocutaneous bleeding and excessive bleeding after surgery or trauma. The defect is due to the inability of ADP to induce platelet aggregation. Onset childhood. Treatable with FFP for procedures. Not reviewed by Babyseq, in the NC NEXUS list.
Sources: Expert list
Additional findings_Paediatric v0.20 PDX1 Lilian Downie gene: PDX1 was added
gene: PDX1 was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: PDX1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PDX1 were set to Pancreatic agenesis, MIM# # 260370
Review for gene: PDX1 was set to GREEN
Added comment: Neonatal onset IDDM, treatable. Not evaluated by Babyseq, included in NC NEXUS.
Sources: Expert list
Additional findings_Paediatric v0.20 PIK3CD Lilian Downie gene: PIK3CD was added
gene: PIK3CD was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: PIK3CD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PIK3CD were set to Immunodeficiency 14, MIM # 615513
Review for gene: PIK3CD was set to GREEN
Added comment: Primary immunodeficiency, characterized by onset of recurrent sinopulmonary and other infections in early childhood. Laboratory studies show defects in both B- and T-cell populations, with an inability to control infection with Epstein Barr-virus (EBV) and cytomegalovirus (CMV). Patient CD8+ T cells are skewed toward differentiation and senescence. Many patients develop lymphadenopathy, mucosal lymphoid aggregates, and/or increased serum IgM. There is also an increased susceptibility to B-cell lymphomas .
Not reviewed by Babyseq, included in NCNEXUS list. Treatable
Sources: Expert list
Additional findings_Paediatric v0.20 PTPRC Lilian Downie gene: PTPRC was added
gene: PTPRC was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: PTPRC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PTPRC were set to Severe combined immunodeficiency, T cell-negative, B-cell/natural killer-cell positive MIM# 151460
Review for gene: PTPRC was set to GREEN
Added comment: Not reviewed by Babyseq, paediatric onset disease that is actionable with BMT (included in NCNEXUS list).
Sources: Expert list
Additional findings_Paediatric v0.20 PYGM Lilian Downie gene: PYGM was added
gene: PYGM was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: PYGM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PYGM were set to McCardle disease MIM# 608455
Review for gene: PYGM was set to GREEN
Added comment: McCardle disease: glycogen storage disease type V (GSD5), characterized by onset of exercise intolerance and muscle cramps in childhood or adolescence. Transient myoglobinuria may occur after exercise, due to rhabdomyolysis. Severe myoglobinuria may lead to acute renal failure. Patients may report muscle weakness, myalgia, and lack of endurance since childhood or adolescence. Later in adult life, there is persistent and progressive muscle weakness and atrophy with fatty replacement. McArdle disease is a relatively benign disorder, except for possible renal failure as a complication of myoglobinuria
Not reviewed by Babyseq, included in NCNEXUS newborn screening list.
Actionable by controlled physical activity and programmed glucose intake.
Sources: Expert list
Additional findings_Paediatric v0.20 RYR1 Lilian Downie reviewed gene: RYR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: malignant hyperthermia, multiminicore disease MIM#180901; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Additional findings_Paediatric v0.20 SCNN1B Lilian Downie reviewed gene: SCNN1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pseudohypoaldosteronism, type I MIM# 264350; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.20 SERPINA1 Lilian Downie reviewed gene: SERPINA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Emphysema due to AAT deficiency, OMIM #107400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.20 SFTPC Lilian Downie reviewed gene: SFTPC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Surfactant metabolism dysfunction, pulmonary, 2 MIM# 178620; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.20 SGCD Lilian Downie reviewed gene: SGCD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 6, MIM# 601287; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.20 SLC6A19 Lilian Downie reviewed gene: SLC6A19: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hartnup disorder MIM # 234500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.20 BRAF Zornitza Stark Marked gene: BRAF as ready
Additional findings_Paediatric v0.20 BRAF Zornitza Stark Gene: braf has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.20 BRAF Zornitza Stark Phenotypes for gene: BRAF were changed from LEOPARD syndrome; Cardiofaciocutaneous syndrome to Noonan syndrome 7, MIM# 613706; Cardiofaciocutaneous syndrome, MIM# 115150
Additional findings_Paediatric v0.19 BRAF Zornitza Stark Classified gene: BRAF as Green List (high evidence)
Additional findings_Paediatric v0.19 BRAF Zornitza Stark Gene: braf has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.18 BRAF Zornitza Stark reviewed gene: BRAF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome 7, MIM# 613706, Cardiofaciocutaneous syndrome, MIM# 115150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.18 BMPR1A Zornitza Stark Marked gene: BMPR1A as ready
Additional findings_Paediatric v0.18 BMPR1A Zornitza Stark Gene: bmpr1a has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.18 BMPR1A Zornitza Stark Phenotypes for gene: BMPR1A were changed from Tetralogy of Fallot; Juvenile polyposis syndrome to Polyposis, juvenile intestinal, MIM# 174900
Additional findings_Paediatric v0.17 BMPR1A Zornitza Stark Classified gene: BMPR1A as Green List (high evidence)
Additional findings_Paediatric v0.17 BMPR1A Zornitza Stark Gene: bmpr1a has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.16 BMPR1A Zornitza Stark reviewed gene: BMPR1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polyposis, juvenile intestinal, MIM# 174900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.16 BCHE Zornitza Stark Marked gene: BCHE as ready
Additional findings_Paediatric v0.16 BCHE Zornitza Stark Gene: bche has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.16 BCHE Zornitza Stark Classified gene: BCHE as Green List (high evidence)
Additional findings_Paediatric v0.16 BCHE Zornitza Stark Gene: bche has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.15 BCHE Zornitza Stark gene: BCHE was added
gene: BCHE was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: BCHE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BCHE were set to Butyrylcholinesterase deficiency, MIM# 617936
Review for gene: BCHE was set to GREEN
Added comment: Individuals deficient in butyrylcholinesterase (BCHE) appear asymptomatic, apart from a heightened sensitivity to muscle relaxants such as suxamethonium (succinylcholine) and mivacurium, 2 BCHE carboxylester substrates. In individuals with usual BCHE levels, these drugs are rapidly hydrolyzed in plasma and their duration of action is short (less than 10 minutes). BCHE deficiency results in slower hydrolysis of these drugs and, consequently, a prolonged neuromuscular block, leading to apnea. Prolonged neuromuscular block occurs with BCHE deficiencies of marked severity (impairment over 70%).
Sources: Expert list
Additional findings_Paediatric v0.14 ATP7A Zornitza Stark Marked gene: ATP7A as ready
Additional findings_Paediatric v0.14 ATP7A Zornitza Stark Gene: atp7a has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.14 ATP7A Zornitza Stark Phenotypes for gene: ATP7A were changed from Occipital horn syndrome; Spinal muscular atrophy, distal, X-linked 3; Menkes syndrome to Menkes disease, MIM# 309400
Additional findings_Paediatric v0.13 ATP7A Zornitza Stark Classified gene: ATP7A as Green List (high evidence)
Additional findings_Paediatric v0.13 ATP7A Zornitza Stark Gene: atp7a has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.12 ATP7A Zornitza Stark reviewed gene: ATP7A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Menkes disease, MIM# 309400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Additional findings_Paediatric v0.12 AR Zornitza Stark edited their review of gene: AR: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Additional findings_Paediatric v0.12 AR Zornitza Stark Marked gene: AR as ready
Additional findings_Paediatric v0.12 AR Zornitza Stark Gene: ar has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.12 AR Zornitza Stark Phenotypes for gene: AR were changed from Spinal and bulbar muscular atrophy of Kennedy; Androgen insensitivity to Androgen insensitivity, MIM# 300068
Additional findings_Paediatric v0.11 AR Zornitza Stark Classified gene: AR as Green List (high evidence)
Additional findings_Paediatric v0.11 AR Zornitza Stark Gene: ar has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.10 AR Zornitza Stark reviewed gene: AR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Androgen insensitivity, MIM# 300068; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.10 APRT Zornitza Stark Marked gene: APRT as ready
Additional findings_Paediatric v0.10 APRT Zornitza Stark Gene: aprt has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.10 APRT Zornitza Stark Phenotypes for gene: APRT were changed from Adenine phosphoribosyltransferase deficiency to Adenine phosphoribosyltransferase deficiency, MIM# 614723
Additional findings_Paediatric v0.9 APRT Zornitza Stark Classified gene: APRT as Green List (high evidence)
Additional findings_Paediatric v0.9 APRT Zornitza Stark Gene: aprt has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.8 APRT Zornitza Stark reviewed gene: APRT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Adenine phosphoribosyltransferase deficiency, MIM# 614723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.8 ALDH7A1 Zornitza Stark Marked gene: ALDH7A1 as ready
Additional findings_Paediatric v0.8 ALDH7A1 Zornitza Stark Gene: aldh7a1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.8 ALDH7A1 Zornitza Stark Classified gene: ALDH7A1 as Green List (high evidence)
Additional findings_Paediatric v0.8 ALDH7A1 Zornitza Stark Gene: aldh7a1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.7 ALDH7A1 Zornitza Stark gene: ALDH7A1 was added
gene: ALDH7A1 was added to Newborn Screening_BabySeq. Sources: Expert list
Mode of inheritance for gene: ALDH7A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ALDH7A1 were set to Epilepsy, pyridoxine-dependent, MIM# 266100
Review for gene: ALDH7A1 was set to GREEN
Added comment: Highly penetrant childhood-onset disorder, well established gene-disease association. Treatable.
Sources: Expert list
Additional findings_Paediatric v0.6 ACADS Zornitza Stark Marked gene: ACADS as ready
Additional findings_Paediatric v0.6 ACADS Zornitza Stark Gene: acads has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.6 ACADS Zornitza Stark Classified gene: ACADS as Green List (high evidence)
Additional findings_Paediatric v0.6 ACADS Zornitza Stark Gene: acads has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.5 ACADS Zornitza Stark reviewed gene: ACADS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Acyl-CoA dehydrogenase, short-chain, deficiency of 201470; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.5 ABCC2 Zornitza Stark Marked gene: ABCC2 as ready
Additional findings_Paediatric v0.5 ABCC2 Zornitza Stark Gene: abcc2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.5 ABCC2 Zornitza Stark Phenotypes for gene: ABCC2 were changed from Dubin-Johnson syndrome to Dubin-Johnson syndrome, MIM# 237500
Additional findings_Paediatric v0.4 ABCC2 Zornitza Stark Publications for gene: ABCC2 were set to
Additional findings_Paediatric v0.3 ABCC2 Zornitza Stark Classified gene: ABCC2 as Green List (high evidence)
Additional findings_Paediatric v0.3 ABCC2 Zornitza Stark Gene: abcc2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.2 ABCC2 Zornitza Stark reviewed gene: ABCC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30344695, 11477083; Phenotypes: Dubin-Johnson syndrome, MIM# 237500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4560 UPF3B Zornitza Stark Marked gene: UPF3B as ready
Mendeliome v0.4560 UPF3B Zornitza Stark Gene: upf3b has been classified as Green List (High Evidence).
Mendeliome v0.4560 UPF3B Zornitza Stark Phenotypes for gene: UPF3B were changed from to Mental retardation, X-linked, syndromic 14, MIM# 300676
Mendeliome v0.4559 UPF3B Zornitza Stark Publications for gene: UPF3B were set to
Mendeliome v0.4558 UPF3B Zornitza Stark Mode of inheritance for gene: UPF3B was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4557 UPF3B Zornitza Stark reviewed gene: UPF3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 19377476, 17704778, 31737052, 28948974, 32667670; Phenotypes: Mental retardation, X-linked, syndromic 14, MIM# 300676; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.3025 UPF3B Zornitza Stark Marked gene: UPF3B as ready
Intellectual disability syndromic and non-syndromic v0.3025 UPF3B Zornitza Stark Gene: upf3b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3025 UPF3B Zornitza Stark Phenotypes for gene: UPF3B were changed from to Mental retardation, X-linked, syndromic 14, MIM# 300676
Intellectual disability syndromic and non-syndromic v0.3024 UPF3B Zornitza Stark Publications for gene: UPF3B were set to
Intellectual disability syndromic and non-syndromic v0.3023 UPF3B Zornitza Stark Mode of inheritance for gene: UPF3B was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.3022 UPF3B Zornitza Stark reviewed gene: UPF3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 19377476, 17704778, 31737052, 28948974; Phenotypes: Mental retardation, X-linked, syndromic 14, MIM# 300676; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Renal Ciliopathies and Nephronophthisis v0.116 NPHP1 Zornitza Stark Marked gene: NPHP1 as ready
Renal Ciliopathies and Nephronophthisis v0.116 NPHP1 Zornitza Stark Gene: nphp1 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.116 NPHP1 Zornitza Stark Phenotypes for gene: NPHP1 were changed from to Nephronophthisis 1, juvenile, MIM# 256100
Renal Ciliopathies and Nephronophthisis v0.115 NPHP1 Zornitza Stark Publications for gene: NPHP1 were set to
Renal Ciliopathies and Nephronophthisis v0.114 NPHP1 Zornitza Stark Mode of inheritance for gene: NPHP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.113 NPHP1 Zornitza Stark Tag SV/CNV tag was added to gene: NPHP1.
Renal Ciliopathies and Nephronophthisis v0.113 NPHP1 Zornitza Stark reviewed gene: NPHP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23559409; Phenotypes: Nephronophthisis 1, juvenile, MIM# 256100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4557 C1orf194 Arina Puzriakova changed review comment from: PMID: 32592472 (2020) - Another knockout mouse model by same research group, demonstrating defects in motor and sensory functions, myelination abnormalities, peripheral nerve loss and muscle atrophy.; to: PMID: 32592472 (2020) - An additional knockout mouse model by same research group, demonstrating defects in motor and sensory functions, myelination abnormalities, peripheral nerve loss and muscle atrophy.
Mendeliome v0.4557 C1orf194 Arina Puzriakova reviewed gene: C1orf194: Rating: ; Mode of pathogenicity: None; Publications: 32592472; Phenotypes: Charcot-Marie-Tooth; Mode of inheritance: None
Mendeliome v0.4557 MECP2 Arina Puzriakova reviewed gene: MECP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32469049; Phenotypes: Rett syndrome, 312750; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.3022 UPF3B Arina Puzriakova reviewed gene: UPF3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32667670; Phenotypes: Mental retardation, X-linked, syndromic 14, 300676; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4557 XPR1 Zornitza Stark Marked gene: XPR1 as ready
Mendeliome v0.4557 XPR1 Zornitza Stark Gene: xpr1 has been classified as Green List (High Evidence).
Mendeliome v0.4557 XPR1 Zornitza Stark Phenotypes for gene: XPR1 were changed from to Basal ganglia calcification, idiopathic, 6, MIM# 616413
Mendeliome v0.4556 XPR1 Zornitza Stark Publications for gene: XPR1 were set to
Mendeliome v0.4555 XPR1 Zornitza Stark Mode of inheritance for gene: XPR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4554 XPR1 Zornitza Stark reviewed gene: XPR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25938945; Phenotypes: Basal ganglia calcification, idiopathic, 6, MIM# 616413; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.44 XPR1 Zornitza Stark Marked gene: XPR1 as ready
Brain Calcification v0.44 XPR1 Zornitza Stark Gene: xpr1 has been classified as Green List (High Evidence).
Brain Calcification v0.44 XPR1 Zornitza Stark Phenotypes for gene: XPR1 were changed from to Basal ganglia calcification, idiopathic, 6, MIM# 616413
Brain Calcification v0.43 XPR1 Zornitza Stark Publications for gene: XPR1 were set to
Brain Calcification v0.42 XPR1 Zornitza Stark Mode of inheritance for gene: XPR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.41 XPR1 Zornitza Stark reviewed gene: XPR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25938945; Phenotypes: Basal ganglia calcification, idiopathic, 6, MIM# 616413; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.84 XPR1 Zornitza Stark Marked gene: XPR1 as ready
Early-onset Parkinson disease v0.84 XPR1 Zornitza Stark Gene: xpr1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.84 XPR1 Zornitza Stark Phenotypes for gene: XPR1 were changed from to Basal ganglia calcification, idiopathic, 6, MIM# 616413
Early-onset Parkinson disease v0.83 XPR1 Zornitza Stark Publications for gene: XPR1 were set to
Early-onset Parkinson disease v0.82 XPR1 Zornitza Stark Mode of inheritance for gene: XPR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.81 XPR1 Zornitza Stark reviewed gene: XPR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25938945; Phenotypes: Basal ganglia calcification, idiopathic, 6, MIM# 616413; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4554 VPS13C Zornitza Stark Marked gene: VPS13C as ready
Mendeliome v0.4554 VPS13C Zornitza Stark Gene: vps13c has been classified as Green List (High Evidence).
Mendeliome v0.4554 VPS13C Zornitza Stark Phenotypes for gene: VPS13C were changed from to Early-onset Parkinson disease-23, MIM# 616840
Mendeliome v0.4553 VPS13C Zornitza Stark Publications for gene: VPS13C were set to
Mendeliome v0.4552 VPS13C Zornitza Stark Mode of inheritance for gene: VPS13C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4551 VPS13C Zornitza Stark reviewed gene: VPS13C: Rating: GREEN; Mode of pathogenicity: None; Publications: 26942284 30452786 28862745; Phenotypes: Early-onset Parkinson disease-23, MIM# 616840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.81 TWNK Zornitza Stark Publications for gene: TWNK were set to
Early-onset Parkinson disease v0.80 TWNK Zornitza Stark Phenotypes for gene: TWNK were changed from to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 MIM#609286
Early-onset Parkinson disease v0.79 TAF1 Zornitza Stark Marked gene: TAF1 as ready
Early-onset Parkinson disease v0.79 TAF1 Zornitza Stark Gene: taf1 has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.79 TAF1 Zornitza Stark Phenotypes for gene: TAF1 were changed from to Dystonia-Parkinsonism, X-linked, MIM# 314250
Early-onset Parkinson disease v0.78 TAF1 Zornitza Stark Publications for gene: TAF1 were set to
Early-onset Parkinson disease v0.77 TAF1 Zornitza Stark Mode of inheritance for gene: TAF1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early-onset Parkinson disease v0.76 TAF1 Zornitza Stark Classified gene: TAF1 as Amber List (moderate evidence)
Early-onset Parkinson disease v0.76 TAF1 Zornitza Stark Gene: taf1 has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.75 TAF1 Zornitza Stark Tag deep intronic tag was added to gene: TAF1.
Tag founder tag was added to gene: TAF1.
Early-onset Parkinson disease v0.75 TAF1 Zornitza Stark reviewed gene: TAF1: Rating: AMBER; Mode of pathogenicity: None; Publications: 17273961; Phenotypes: Dystonia-Parkinsonism, X-linked, MIM# 314250; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4551 KIAA1161 Zornitza Stark Phenotypes for gene: KIAA1161 were changed from Basal ganglia calcification, idiopathic, 7, autosomal recessive; OMIM #618317; primary familial brain calcifications (PFBC); ataxia; dysarthria; cerebellar atrophy; akinetic-hypertonic syndrome to Basal ganglia calcification, idiopathic, 7, MIM #618317; primary familial brain calcifications (PFBC); ataxia; dysarthria; cerebellar atrophy; akinetic-hypertonic syndrome
Mendeliome v0.4550 KIAA1161 Zornitza Stark Publications for gene: KIAA1161 were set to 30656188; 30649222; 30460687; 29910000; 31009047
Mendeliome v0.4549 KIAA1161 Zornitza Stark Mode of inheritance for gene: KIAA1161 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4548 KIAA1161 Zornitza Stark Tag new gene name tag was added to gene: KIAA1161.
Mendeliome v0.4548 KIAA1161 Zornitza Stark edited their review of gene: KIAA1161: Added comment: In a cohort study comprising 435 individuals with primary brain calcification, 38 individuals identified with mono-allelic variants in this gene, in addition to 14 with bi-allelic variants. Clinical and imaging penetrance of individuals with bi-allelic variants were 100%, whereas among individuals with heterozygous variants, penetrance of imaging phenotype was reduced to 73.7% (28 of 38) and clinical penetrance was much lower. Most (34 of 38) remained asymptomatic whereas 4 had symptoms of uncertain clinical significance (nonspecific depression, epilepsy and late-onset parkinsonism). Compared with individuals with biallelic MYORG variants, individuals with heterozygous variants had brain calcifications with much lower calcification scores (P < 2e-16). HGNC approved name is MYORG.; Changed publications: 30656188, 30649222, 30460687, 29910000, 31951047; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Brain Calcification v0.41 KIAA1161 Zornitza Stark Phenotypes for gene: KIAA1161 were changed from Basal ganglia calcification, idiopathic, 7, autosomal recessive; OMIM #618317 to Basal ganglia calcification, idiopathic, 7, MIM#618317
Brain Calcification v0.40 KIAA1161 Zornitza Stark Publications for gene: KIAA1161 were set to PubMed: 30656188, 30649222, 30460687, 29910000
Brain Calcification v0.39 KIAA1161 Zornitza Stark Mode of inheritance for gene: KIAA1161 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Brain Calcification v0.38 KIAA1161 Zornitza Stark Tag new gene name tag was added to gene: KIAA1161.
Brain Calcification v0.38 KIAA1161 Zornitza Stark changed review comment from: In a cohort study comprising 435 individuals with primary brain calcification, 38 individuals identified with mono-allelic variants in this gene, in addition to 14 with bi-allelic variants. Clinical and imaging penetrance of individuals with bi-allelic variants were 100%, whereas among individuals with heterozygous variants, penetrance of imaging phenotype was reduced to 73.7% (28 of 38) and clinical penetrance was much lower. Most (34 of 38) remained asymptomatic whereas 4 had symptoms of uncertain clinical significance (nonspecific depression, epilepsy and late-onset parkinsonism). Compared with individuals with biallelic MYORG variants, individuals with heterozygous variants had brain calcifications with much lower calcification scores (P < 2e-16).; to: In a cohort study comprising 435 individuals with primary brain calcification, 38 individuals identified with mono-allelic variants in this gene, in addition to 14 with bi-allelic variants. Clinical and imaging penetrance of individuals with bi-allelic variants were 100%, whereas among individuals with heterozygous variants, penetrance of imaging phenotype was reduced to 73.7% (28 of 38) and clinical penetrance was much lower. Most (34 of 38) remained asymptomatic whereas 4 had symptoms of uncertain clinical significance (nonspecific depression, epilepsy and late-onset parkinsonism). Compared with individuals with biallelic MYORG variants, individuals with heterozygous variants had brain calcifications with much lower calcification scores (P < 2e-16).

HGNC approved name is MYORG.
Brain Calcification v0.38 KIAA1161 Zornitza Stark reviewed gene: KIAA1161: Rating: GREEN; Mode of pathogenicity: None; Publications: 31951047; Phenotypes: Basal ganglia calcification, idiopathic, 7, MIM#618317; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.75 PDGFRB Zornitza Stark Marked gene: PDGFRB as ready
Early-onset Parkinson disease v0.75 PDGFRB Zornitza Stark Gene: pdgfrb has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.75 PDGFRB Zornitza Stark Phenotypes for gene: PDGFRB were changed from to Basal ganglia calcification, idiopathic, 4, MIM# 615007
Early-onset Parkinson disease v0.74 PDGFRB Zornitza Stark Publications for gene: PDGFRB were set to
Early-onset Parkinson disease v0.73 PDGFRB Zornitza Stark Mode of inheritance for gene: PDGFRB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.72 PDGFRB Zornitza Stark reviewed gene: PDGFRB: Rating: GREEN; Mode of pathogenicity: None; Publications: 23255827, 30979360; Phenotypes: Basal ganglia calcification, idiopathic, 4 615007; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.72 PDGFB Zornitza Stark Marked gene: PDGFB as ready
Early-onset Parkinson disease v0.72 PDGFB Zornitza Stark Gene: pdgfb has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.72 PDGFB Zornitza Stark Phenotypes for gene: PDGFB were changed from to Basal ganglia calcification, idiopathic, 5, MIM# 615483
Early-onset Parkinson disease v0.71 PDGFB Zornitza Stark Publications for gene: PDGFB were set to
Early-onset Parkinson disease v0.70 PDGFB Zornitza Stark Mode of inheritance for gene: PDGFB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.69 PDGFB Zornitza Stark reviewed gene: PDGFB: Rating: GREEN; Mode of pathogenicity: None; Publications: 23913003; Phenotypes: Basal ganglia calcification, idiopathic, 5, MIM# 615483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.69 MECP2 Zornitza Stark Marked gene: MECP2 as ready
Early-onset Parkinson disease v0.69 MECP2 Zornitza Stark Gene: mecp2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.69 MECP2 Zornitza Stark Phenotypes for gene: MECP2 were changed from to MECP2-related disorders; Rett syndrome, MIM# 312750; Mental retardation, X-linked, syndromic 13, MIM# 300055
Early-onset Parkinson disease v0.68 MECP2 Zornitza Stark Publications for gene: MECP2 were set to
Early-onset Parkinson disease v0.67 MECP2 Zornitza Stark Mode of inheritance for gene: MECP2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early-onset Parkinson disease v0.66 MECP2 Zornitza Stark reviewed gene: MECP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31970230, 27050783; Phenotypes: MECP2-related disorders, Rett syndrome, MIM# 312750, Mental retardation, X-linked, syndromic 13, MIM# 300055; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early-onset Parkinson disease v0.66 GRN Zornitza Stark Phenotypes for gene: GRN were changed from to Frontotemporal lobar degeneration with ubiquitin-positive inclusions, MIM# 607485
Early-onset Parkinson disease v0.65 GRN Zornitza Stark Publications for gene: GRN were set to
Early-onset Parkinson disease v0.64 GRN Zornitza Stark Mode of inheritance for gene: GRN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.63 GRN Zornitza Stark reviewed gene: GRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 17923627, 20301545; Phenotypes: Frontotemporal lobar degeneration with ubiquitin-positive inclusions, MIM# 607485; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4548 ALG14 Zornitza Stark Marked gene: ALG14 as ready
Mendeliome v0.4548 ALG14 Zornitza Stark Gene: alg14 has been classified as Green List (High Evidence).
Mendeliome v0.4548 ALG14 Zornitza Stark Phenotypes for gene: ALG14 were changed from to Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Disorder of N-glycosylation
Mendeliome v0.4547 ALG14 Zornitza Stark Publications for gene: ALG14 were set to
Mendeliome v0.4546 ALG14 Zornitza Stark Mode of inheritance for gene: ALG14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4545 ALG14 Zornitza Stark reviewed gene: ALG14: Rating: GREEN; Mode of pathogenicity: None; Publications: 30221345, 23404334, 28733338; Phenotypes: Myasthenic syndrome, congenital, 15, without tubular aggregates 616227, Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031, Disorder of N-glycosylation; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.164 ALG14 Zornitza Stark Phenotypes for gene: ALG14 were changed from Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual disability; Disorder of N-glycosylation to Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Disorder of N-glycosylation
Congenital Disorders of Glycosylation v0.163 ALG14 Zornitza Stark edited their review of gene: ALG14: Changed phenotypes: Myasthenic syndrome, congenital, 15, without tubular aggregates 616227, Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031, Disorder of N-glycosylation
Intellectual disability syndromic and non-syndromic v0.3022 ALG14 Zornitza Stark Phenotypes for gene: ALG14 were changed from Myasthenic syndrome, congenital, 15, without tubular aggregates, MIM#616227; Intellectual disability to Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031
Intellectual disability syndromic and non-syndromic v0.3021 ALG14 Zornitza Stark edited their review of gene: ALG14: Changed phenotypes: intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031
Craniosynostosis v0.150 TCF12 Zornitza Stark Marked gene: TCF12 as ready
Craniosynostosis v0.150 TCF12 Zornitza Stark Gene: tcf12 has been classified as Green List (High Evidence).
Craniosynostosis v0.150 TCF12 Zornitza Stark Phenotypes for gene: TCF12 were changed from to Craniosynostosis 3, MIM# 615314
Craniosynostosis v0.149 TCF12 Zornitza Stark Publications for gene: TCF12 were set to
Craniosynostosis v0.148 TCF12 Zornitza Stark Mode of inheritance for gene: TCF12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.147 TCF12 Zornitza Stark reviewed gene: TCF12: Rating: GREEN; Mode of pathogenicity: None; Publications: 23354436; Phenotypes: Craniosynostosis 3, MIM# 615314; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4545 TCF12 Zornitza Stark Marked gene: TCF12 as ready
Mendeliome v0.4545 TCF12 Zornitza Stark Gene: tcf12 has been classified as Green List (High Evidence).
Mendeliome v0.4545 TCF12 Zornitza Stark Phenotypes for gene: TCF12 were changed from to Craniosynostosis 3, MIM# 615314; Kallman syndrome
Mendeliome v0.4544 TCF12 Zornitza Stark Publications for gene: TCF12 were set to
Mendeliome v0.4543 TCF12 Zornitza Stark Mode of inheritance for gene: TCF12 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4542 TCF12 Zornitza Stark reviewed gene: TCF12: Rating: GREEN; Mode of pathogenicity: None; Publications: 23354436, 32620954; Phenotypes: Craniosynostosis 3, MIM# 615314, Kallman syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.169 TCF12 Zornitza Stark Marked gene: TCF12 as ready
Differences of Sex Development v0.169 TCF12 Zornitza Stark Gene: tcf12 has been classified as Green List (High Evidence).
Differences of Sex Development v0.169 TCF12 Zornitza Stark Classified gene: TCF12 as Green List (high evidence)
Differences of Sex Development v0.169 TCF12 Zornitza Stark Gene: tcf12 has been classified as Green List (High Evidence).
Differences of Sex Development v0.168 TCF12 Zornitza Stark gene: TCF12 was added
gene: TCF12 was added to Disorders of Sex Differentiation. Sources: Literature
Mode of inheritance for gene: TCF12 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TCF12 were set to 32620954
Phenotypes for gene: TCF12 were set to Kallmann syndrome
Review for gene: TCF12 was set to GREEN
Added comment: Note monoallelic variants in this gene are a well-established cause of craniosynostosis.
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- PMID: 32620954 (2020) - 13 unrelated kindreds (11 de novo, 1 AD and 1 AR) comprising 14 affected individuals with an anosmic form of isolated GnRH deficiency (IGD) (Kallman syndrome) due to different LoF variants in TCF12.

Clinical manifestation included anosmia and pubertal failure (with reproductive phenotypes such as micropenis, bilateral cryptorchidism, hypospadias). Two unrelated individuals within the cohort additionally exhibited craniosynostosis, and a further two pedigrees had a family history of craniosynostosis (that did not affect the index case). Multiplex cases typically presented incomplete penetrance.

Loss of tcf12 in a mutant zebrafish model perturbed GnRH neuronal patterning, with concomitant expression attenuation of tcf3a/b and stub1 (latter mutated in other syndromic forms of IGD). Furthermore, restored STUB1 expression rescued loss of tcf12 in vivo.

Green for mono-allelic variants, caution with bi-allelic variants.
Sources: Literature
Incidentalome v0.35 PTEN Arina Puzriakova reviewed gene: PTEN: Rating: ; Mode of pathogenicity: None; Publications: 32588888; Phenotypes: Skewed immune repertoire composition; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4542 TCF12 Arina Puzriakova reviewed gene: TCF12: Rating: AMBER; Mode of pathogenicity: None; Publications: 32620954; Phenotypes: Kallmann syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.63 GCH1 Zornitza Stark Marked gene: GCH1 as ready
Early-onset Parkinson disease v0.63 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.63 GCH1 Zornitza Stark Phenotypes for gene: GCH1 were changed from to Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230
Early-onset Parkinson disease v0.62 GCH1 Zornitza Stark Publications for gene: GCH1 were set to
Early-onset Parkinson disease v0.61 GCH1 Zornitza Stark Mode of inheritance for gene: GCH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.60 GCH1 Zornitza Stark reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32170445, 32278297, 32746945, 30314816; Phenotypes: Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.60 DNAJC5 Zornitza Stark Marked gene: DNAJC5 as ready
Early-onset Parkinson disease v0.60 DNAJC5 Zornitza Stark Gene: dnajc5 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.60 DNAJC5 Zornitza Stark Phenotypes for gene: DNAJC5 were changed from to Ceroid lipofuscinosis, neuronal, 4, Parry type, MIM# 162350
Early-onset Parkinson disease v0.59 DNAJC5 Zornitza Stark Publications for gene: DNAJC5 were set to
Early-onset Parkinson disease v0.58 DNAJC5 Zornitza Stark Mode of inheritance for gene: DNAJC5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.57 DNAJC5 Zornitza Stark reviewed gene: DNAJC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22978711, 21820099, 22235333; Phenotypes: Ceroid lipofuscinosis, neuronal, 4, Parry type, MIM# 162350; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.57 CLN3 Zornitza Stark reviewed gene: CLN3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 3 MIM#204200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia and Chorea v0.142 VAMP1 Zornitza Stark Classified gene: VAMP1 as Amber List (moderate evidence)
Dystonia and Chorea v0.142 VAMP1 Zornitza Stark Gene: vamp1 has been classified as Amber List (Moderate Evidence).
Dystonia and Chorea v0.141 VAMP1 Zornitza Stark Tag founder tag was added to gene: VAMP1.
Dystonia and Chorea v0.141 VAMP1 Zornitza Stark edited their review of gene: VAMP1: Added comment: Single variant reported in four Newfoundland families, founder effect.; Changed rating: AMBER; Changed phenotypes: Spastic ataxia 1, autosomal dominant, MIM# 108600
Mendeliome v0.4542 RP1L1 Zornitza Stark Marked gene: RP1L1 as ready
Mendeliome v0.4542 RP1L1 Zornitza Stark Gene: rp1l1 has been classified as Green List (High Evidence).
Mendeliome v0.4542 RP1L1 Zornitza Stark Phenotypes for gene: RP1L1 were changed from to Occult macular dystrophy (MIM#613587) AD; Retinitis pigmentosa 88 (MIM#618826) AR
Mendeliome v0.4541 RP1L1 Zornitza Stark Publications for gene: RP1L1 were set to
Mendeliome v0.4540 RP1L1 Zornitza Stark Mode of inheritance for gene: RP1L1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hypertension and Aldosterone disorders v0.18 CYP11B2 Zornitza Stark Marked gene: CYP11B2 as ready
Hypertension and Aldosterone disorders v0.18 CYP11B2 Zornitza Stark Gene: cyp11b2 has been classified as Green List (High Evidence).
Hypertension and Aldosterone disorders v0.18 CYP11B2 Zornitza Stark Phenotypes for gene: CYP11B2 were changed from to Hypoaldosteronism, congenital, due to CMO I deficiency (MIM#203400) or due to CMO II deficiency (MIM#610600)
Hypertension and Aldosterone disorders v0.17 CYP11B2 Zornitza Stark Publications for gene: CYP11B2 were set to
Hypertension and Aldosterone disorders v0.16 CYP11B2 Zornitza Stark Mode of inheritance for gene: CYP11B2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4539 CYP11B2 Zornitza Stark Marked gene: CYP11B2 as ready
Mendeliome v0.4539 CYP11B2 Zornitza Stark Gene: cyp11b2 has been classified as Green List (High Evidence).
Mendeliome v0.4539 CYP11B2 Zornitza Stark Phenotypes for gene: CYP11B2 were changed from to Hypoaldosteronism, congenital, due to CMO I deficiency (MIM#203400) or due to CMO II deficiency (MIM#610600).
Mendeliome v0.4538 CYP11B2 Zornitza Stark Publications for gene: CYP11B2 were set to
Mendeliome v0.4537 CYP11B2 Zornitza Stark Mode of inheritance for gene: CYP11B2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v0.200 HPS5 Zornitza Stark Marked gene: HPS5 as ready
Bleeding and Platelet Disorders v0.200 HPS5 Zornitza Stark Gene: hps5 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v0.200 HPS5 Zornitza Stark Phenotypes for gene: HPS5 were changed from to Hermansky-Pudlak syndrome 5 (MIM#614074)
Bleeding and Platelet Disorders v0.199 HPS5 Zornitza Stark Publications for gene: HPS5 were set to
Bleeding and Platelet Disorders v0.198 HPS5 Zornitza Stark Mode of inheritance for gene: HPS5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v0.197 HPS5 Zornitza Stark reviewed gene: HPS5: Rating: GREEN; Mode of pathogenicity: None; Publications: 28296950, 32725903; Phenotypes: Hermansky-Pudlak syndrome 5 (MIM#614074); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4536 HPS5 Zornitza Stark Marked gene: HPS5 as ready
Mendeliome v0.4536 HPS5 Zornitza Stark Gene: hps5 has been classified as Green List (High Evidence).
Mendeliome v0.4536 HPS5 Zornitza Stark Phenotypes for gene: HPS5 were changed from to Hermansky-Pudlak syndrome 5 (MIM#614074)
Mendeliome v0.4535 HPS5 Zornitza Stark Publications for gene: HPS5 were set to
Mendeliome v0.4534 HPS5 Zornitza Stark Mode of inheritance for gene: HPS5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4533 HPS5 Zornitza Stark reviewed gene: HPS5: Rating: GREEN; Mode of pathogenicity: None; Publications: 28296950, 32725903; Phenotypes: Hermansky-Pudlak syndrome 5 (MIM#614074); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ocular and Oculocutaneous Albinism v0.12 HPS5 Zornitza Stark Marked gene: HPS5 as ready
Ocular and Oculocutaneous Albinism v0.12 HPS5 Zornitza Stark Gene: hps5 has been classified as Green List (High Evidence).
Ocular and Oculocutaneous Albinism v0.12 HPS5 Zornitza Stark Phenotypes for gene: HPS5 were changed from to Hermansky-Pudlak syndrome 5 (MIM#614074)
Ocular and Oculocutaneous Albinism v0.11 HPS5 Zornitza Stark Publications for gene: HPS5 were set to
Ocular and Oculocutaneous Albinism v0.10 HPS5 Zornitza Stark Mode of inheritance for gene: HPS5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4533 IBA57 Zornitza Stark Phenotypes for gene: IBA57 were changed from Multiple mitochondrial dysfunctions syndrome 3, MIM#615330 to Multiple mitochondrial dysfunctions syndrome 3, MIM#615330; Spastic paraplegia 74, autosomal recessive MIM#616451
Mendeliome v0.4532 IBA57 Zornitza Stark Publications for gene: IBA57 were set to 23462291; 25971455; 27785568; 28671726; 28913435
Mendeliome v0.4531 IBA57 Zornitza Stark changed review comment from: More than 15 families reported with bi-allelic variants in this gene and a severe neurodegenerative disorder characterised by loss of previously acquired developmental milestones in the first months or years of life. Some affected individuals have normal development in early infancy before the onset of symptoms, whereas others show delays from birth. Features included loss of motor function, spasticity, pyramidal signs, loss of speech, and cognitive impairment. The disease course is highly variable: some individuals die of respiratory failure early in childhood, whereas some survive but may be bedridden with a feeding tube. Less commonly, some individuals may survive and have a stable course with motor deficits and mild or even absent cognitive impairment, although there may be fluctuating symptoms, often in response to infection. Other variable features include visual problems and seizures. Brain imaging shows diffuse leukodystrophy in the subcortical region, brainstem, cerebellum, and spinal cord. Laboratory studies tend to show increased lactate and CSF glycine, and decreased activity of mitochondrial complexes I and II, although these findings are also variable.; to: MMDS3: More than 15 families reported with bi-allelic variants in this gene and a severe neurodegenerative disorder characterised by loss of previously acquired developmental milestones in the first months or years of life. Some affected individuals have normal development in early infancy before the onset of symptoms, whereas others show delays from birth. Features included loss of motor function, spasticity, pyramidal signs, loss of speech, and cognitive impairment. The disease course is highly variable: some individuals die of respiratory failure early in childhood, whereas some survive but may be bedridden with a feeding tube. Less commonly, some individuals may survive and have a stable course with motor deficits and mild or even absent cognitive impairment, although there may be fluctuating symptoms, often in response to infection. Other variable features include visual problems and seizures. Brain imaging shows diffuse leukodystrophy in the subcortical region, brainstem, cerebellum, and spinal cord. Laboratory studies tend to show increased lactate and CSF glycine, and decreased activity of mitochondrial complexes I and II, although these findings are also variable.

SPG74: Three families with spastic paraparesis as a feature of the condition.
Mendeliome v0.4531 IBA57 Zornitza Stark edited their review of gene: IBA57: Changed phenotypes: Multiple mitochondrial dysfunctions syndrome 3, MIM#615330, Spastic paraplegia 74, autosomal recessive MIM#616451
Mendeliome v0.4531 IBA57 Zornitza Stark edited their review of gene: IBA57: Changed publications: 23462291, 25971455, 27785568, 28671726, 28913435, 25609768 30258207
Mitochondrial disease v0.501 IBA57 Zornitza Stark Marked gene: IBA57 as ready
Mitochondrial disease v0.501 IBA57 Zornitza Stark Gene: iba57 has been classified as Green List (High Evidence).
Mitochondrial disease v0.501 IBA57 Zornitza Stark Phenotypes for gene: IBA57 were changed from to Multiple mitochondrial dysfunctions syndrome 3, MIM# 615330
Mitochondrial disease v0.500 IBA57 Zornitza Stark Publications for gene: IBA57 were set to
Mitochondrial disease v0.499 IBA57 Zornitza Stark Mode of inheritance for gene: IBA57 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.498 IBA57 Zornitza Stark reviewed gene: IBA57: Rating: GREEN; Mode of pathogenicity: None; Publications: 23462291, 25971455, 27785568, 28671726, 28913435; Phenotypes: Multiple mitochondrial dysfunctions syndrome 3, MIM# 615330; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4531 IBA57 Zornitza Stark Marked gene: IBA57 as ready
Mendeliome v0.4531 IBA57 Zornitza Stark Gene: iba57 has been classified as Green List (High Evidence).
Mendeliome v0.4531 IBA57 Zornitza Stark Phenotypes for gene: IBA57 were changed from to Multiple mitochondrial dysfunctions syndrome 3, MIM#615330
Mendeliome v0.4530 IBA57 Zornitza Stark Publications for gene: IBA57 were set to
Mendeliome v0.4529 IBA57 Zornitza Stark Mode of inheritance for gene: IBA57 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4528 IBA57 Zornitza Stark reviewed gene: IBA57: Rating: GREEN; Mode of pathogenicity: None; Publications: 23462291, 25971455, 27785568, 28671726, 28913435; Phenotypes: Multiple mitochondrial dysfunctions syndrome 3, MIM#615330; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy v0.203 IBA57 Zornitza Stark Marked gene: IBA57 as ready
Leukodystrophy v0.203 IBA57 Zornitza Stark Gene: iba57 has been classified as Green List (High Evidence).
Leukodystrophy v0.203 IBA57 Zornitza Stark Phenotypes for gene: IBA57 were changed from Multiple mitochondrial dysfunctions syndrome 3, 615330 to Multiple mitochondrial dysfunctions syndrome 3, MIM#615330
Leukodystrophy v0.202 IBA57 Zornitza Stark Publications for gene: IBA57 were set to
Leukodystrophy v0.201 IBA57 Zornitza Stark reviewed gene: IBA57: Rating: GREEN; Mode of pathogenicity: None; Publications: 23462291, 25971455, 27785568, 28671726, 28913435; Phenotypes: Multiple mitochondrial dysfunctions syndrome 3, MIM# 615330; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4528 RP1L1 Teresa Zhao reviewed gene: RP1L1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23281133, 30025130, 32360662; Phenotypes: Occult macular dystrophy (MIM#613587) AD, Retinitis pigmentosa 88 (MIM#618826) AR; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hypertension and Aldosterone disorders v0.15 CYP11B2 Paul De Fazio reviewed gene: CYP11B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 8439335, 9360501, 15240589, 9814506, 12788848, 8772616; Phenotypes: Hypoaldosteronism, congenital, due to CMO I deficiency (MIM#203400) or due to CMO II deficiency (MIM#610600).; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.4528 CYP11B2 Paul De Fazio reviewed gene: CYP11B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 8439335, 9360501, 15240589, 9814506, 12788848, 8772616; Phenotypes: Hypoaldosteronism, congenital, due to CMO I deficiency (MIM#203400) or due to CMO II deficiency (MIM#610600).; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Ocular and Oculocutaneous Albinism v0.9 HPS5 Ain Roesley edited their review of gene: HPS5: Changed rating: GREEN
Ocular and Oculocutaneous Albinism v0.9 HPS5 Ain Roesley reviewed gene: HPS5: Rating: ; Mode of pathogenicity: None; Publications: 28296950, 32725903; Phenotypes: Hermansky-Pudlak syndrome 5 (MIM#614074),; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy v0.201 IBA57 Teresa Zhao reviewed gene: IBA57: Rating: GREEN; Mode of pathogenicity: None; Publications: 27785568, 28671726; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pharmacogenomics_Paediatric v0.50 UGT1A1 David Metz gene: UGT1A1 was added
gene: UGT1A1 was added to Pharmacogenomics_Paediatric. Sources: Other
Mode of inheritance for gene: UGT1A1 was set to Other
Publications for gene: UGT1A1 were set to 21412232; 25817555; 26417955
Phenotypes for gene: UGT1A1 were set to Irinotecan metabolism, increased toxicities with reduced metaboliser status; Atazanavir metabolism, increased risk jaundice and discontinuation with reduced metaboliser status
Mode of pathogenicity for gene: UGT1A1 was set to Other
Review for gene: UGT1A1 was set to GREEN
Added comment: Sources: Other
Pharmacogenomics_Paediatric v0.50 SLCO1B1 David Metz reviewed gene: SLCO1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22617227; Phenotypes: Risk for simvastatin-induced myopathy; Mode of inheritance: None
Hyperthyroidism v0.1 Zornitza Stark Panel types changed to Rare Disease
Hyperthyroidism v0.0 TTR Zornitza Stark gene: TTR was added
gene: TTR was added to Hyperthyroidism. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: TTR was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TTR were set to 31590893; 26522458
Phenotypes for gene: TTR were set to DTTRH; [Dystransthyretinemic hyperthyroxinemia], 145680
Mode of pathogenicity for gene: TTR was set to Other
Hyperthyroidism v0.0 TSHR Zornitza Stark gene: TSHR was added
gene: TSHR was added to Hyperthyroidism. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: TSHR was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TSHR were set to Hyperthyroidism, nonautoimmune, 609152; Congenital, nonautoimmune hyperthyroidism
Hyperthyroidism v0.0 THRB Zornitza Stark gene: THRB was added
gene: THRB was added to Hyperthyroidism. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: THRB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: THRB were set to 24847459
Phenotypes for gene: THRB were set to Thyroid Hormone Resistance, Selective Pituitary; 145650; THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL RECESSIVE; thyroid hormone unresponsiveness, generalized RTH, RTH beta; THYROID HORMONE UNRESPONSIVENESS; REFETOFF SYNDROME; Refetoff syndrome; THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL DOMINANT; PRTH; Thyroid hormone resistance, selective pituitary, 145650; GRTH; THYROID HORMONE RESISTANCE, SELECTIVE PITUITARY; Resistance to thyroid hormone (RTH); Thyroid hormone resistance, 188570; Thyroid hormone resistance, autosomal recessive, 274300; Thyroid Hormone Resistance (monoallelic); HYPERTHYROIDISM, FAMILIAL, DUE TO INAPPROPRIATE THYROTROPIN SECRETION; THYROID HORMONE UNRESPONSIVENESS HYPERTHYROXINEMIA, FAMILIAL EUTHYROID, SECONDARY TO PITUITARY AND PERIPHERAL RESISTANCE TO THYROID HORMONES
Hyperthyroidism v0.0 THRA Zornitza Stark gene: THRA was added
gene: THRA was added to Hyperthyroidism. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: THRA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: THRA were set to 24847459; 27144938; 22168587; 23940126; 2567082; 22494134; 27381958
Phenotypes for gene: THRA were set to Resistance to Thyroid Hormone due to defective thyroid receptor alpha (RTHa); Hypothyroidism, congenital, nongoitrous, 6, 614450; congenital nongoitrous hypothyroidism 6; RTH alpha; HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 6; Resistance to thyroid hormone alpha; CHNG6
Hyperthyroidism v0.0 SLC16A2 Zornitza Stark gene: SLC16A2 was added
gene: SLC16A2 was added to Hyperthyroidism. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: SLC16A2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SLC16A2 were set to 24847459
Phenotypes for gene: SLC16A2 were set to MENTAL RETARDATION, X-LINKED, WITH HYPOTONIA; mental retardation, X-linked, with hypotonia; Allan-Herndon-Dudley syndrome; ALLAN-HERNDON SYNDROME; T3 RESISTANCE; AHDS; ALLAN-HERNDON-DUDLEY SYNDROME; MENTAL RETARDATION AND MUSCULAR ATROPHY; Monocarboxylate transporter 8 (MCT8) defect; MCT8 (SLC16A2)-specific thyroid hormone cell transporter deficiency; TRIIODOTHYRONINE RESISTANCE; Allan-Herndon-Dudley syndrome, 300523; monocarboxylate transporter 8 (MCT8) deficiency; Allan-Herndon-Dudley Syndrome; 300523; MONOCARBOXYLATE TRANSPORTER 8 DEFICIENCY; Allan_Herndon_Dudley Syndrome
Hyperthyroidism v0.0 SECISBP2 Zornitza Stark gene: SECISBP2 was added
gene: SECISBP2 was added to Hyperthyroidism. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: SECISBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SECISBP2 were set to 22986150; 24629861; 19602558; 22247018; 20501692; 16228000; Diversity Selenium Functions in Health and Disease, Edited by Regina Brigelius-Flohe and Helmut Sies, Chapter 16. Mutations in SECISBP2. Erik Schoenmakers, Carla Moran, Nadia Schoenmakers and Krishna Chatterjee. CRC Press 2015. Pages 343 376. Print ISBN: 978-1-4822-5126-5. eBook ISBN: 978-1-4822-5127-2. DOI: 10.1201/b18810-23; 21084748
Phenotypes for gene: SECISBP2 were set to Selenocysteine insertion sequence binding protein 2 (SBP2) defect; Thyroid hormone metabolism, abnormal, 609698; Short stature-delayed bone age due to thyroid hormone metabolism deficiency; THYROID HORMONE METABOLISM, ABNORMAL; Abnormal thyroid hormone metabolism
Hyperthyroidism v0.0 ALB Zornitza Stark gene: ALB was added
gene: ALB was added to Hyperthyroidism. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: ALB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ALB were set to 29163366; 24646103; 8064810; 27834068
Phenotypes for gene: ALB were set to Familial dysalbuminaemic hyperthyroxinaemia; [Dysalbuminemic hyperthyroxinemia], 615999
Hyperthyroidism v0.0 Zornitza Stark Added panel Hyperthyroidism
Pharmacogenomics_Paediatric v0.50 CYP2C9 David Metz edited their review of gene: CYP2C9: Changed phenotypes: Phenytoin metabolism - increased risk toxicities
Pharmacogenomics_Paediatric v0.50 CYP2C9 David Metz changed review comment from: 25099164
Reduced phenytoin metabolism, increased risk phenytoin-induced SJS/TEN
If CYP2C9 IM or PM and phenytoin naive, avoid phenytoin.; to: 25099164
If CYP2C9 IM, consider 25% reduction starting dose (moderate recommendation).
If CYP2C9 PM, consider 50% reduction starting dose phenytoin (strong recommendation).
Pharmacogenomics_Paediatric v0.50 HLA-B David Metz changed review comment from:
HLA-B*15:02:
Increased carbamazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increase oxcarbazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increased lamotrogine-induced SJS/TEN (meta-analysis, 25428396).
Increased phenytoin-induced SJS/TEN (moderate association, 23692434).

PMID 26094938
HLA-B*58:01 and allopurinol-induced SJS/TEN

PMID: 23232549
Carrier of HLA-B*5801 (HLA-B*5801/*X,b HLA-B*5801/HLA-B*5801), significant increase in risk of allopurinol induced SCAR (severe cutaneous adverse reaction).

HLA-B*5701 and Abacavir hypersensitivity.
25934581, 22378157

HLA-B*5701-positive patients have an 80-fold elevated risk of flucloxacillin-induced liver injury. However, the incidence is low (1-2 per 1000 individuals).
https://www.pharmgkb.org/chemical/PA164781042/guidelineAnnotation/PA166182810

PMID 32714190 (review article)
HLA-B*57:01, carbamazepine and SJS/TEN.
HLA-B*15:11, carbamazepine and SJS/TEN.

HLA-B*13:01, dapsone and DRESS (29458119); to:
HLA-B*15:02:
Increased carbamazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increase oxcarbazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increased lamotrogine-induced SJS/TEN (meta-analysis, 25428396).
Increased phenytoin-induced SJS/TEN (25099164).

PMID 26094938
HLA-B*58:01 and allopurinol-induced SJS/TEN

PMID: 23232549
Carrier of HLA-B*5801 (HLA-B*5801/*X,b HLA-B*5801/HLA-B*5801), significant increase in risk of allopurinol induced SCAR (severe cutaneous adverse reaction).

HLA-B*5701 and Abacavir hypersensitivity.
25934581, 22378157

HLA-B*5701-positive patients have an 80-fold elevated risk of flucloxacillin-induced liver injury. However, the incidence is low (1-2 per 1000 individuals).
https://www.pharmgkb.org/chemical/PA164781042/guidelineAnnotation/PA166182810

PMID 32714190 (review article)
HLA-B*57:01, carbamazepine and SJS/TEN.
HLA-B*15:11, carbamazepine and SJS/TEN.

HLA-B*13:01, dapsone and DRESS (29458119)
Pharmacogenomics_Paediatric v0.50 CYP2C9 David Metz edited their review of gene: CYP2C9: Added comment: 25099164
Reduced phenytoin metabolism, increased risk phenytoin-induced SJS/TEN
If CYP2C9 IM or PM and phenytoin naive, avoid phenytoin.; Changed publications: 18406467, 25099164; Changed phenotypes: Increased risk phenytoin-induced SJS/TEN
Pharmacogenomics_Paediatric v0.50 HLA-B David Metz changed review comment from:
HLA-B*15:02:
Increased carbamazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increase oxcarbazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increased lamotrogine-induced SJS/TEN (meta-analysis, 25428396).
Increased phenytoin-induced SJS/TEN (moderate association, 23692434).

PMID 26094938
HLA-B*58:01 and allopurinol-induced SJS/TEN

PMID: 23232549
Carrier of HLA-B*5801 (HLA-B*5801/*X,b HLA-B*5801/HLA-B*5801), significant increase in risk of allopurinol induced SCAR (severe cutaneous adverse reaction).

HLA-B*5701 and Abacavir hypersensitivity.
25934581, 22378157

HLA-B*5701-positive patients have an 80-fold elevated risk of flucloxacillin-induced liver injury. However, the incidence is low (1-2 per 1000 individuals).
https://www.pharmgkb.org/chemical/PA164781042/guidelineAnnotation/PA166182810

PMID 32714190 (review article)
HLA-B*57:01, carbamazepine and SJS/TEN.
HLA-B*15:11, carbamazepine and SJS/TEN.

HLA-B*13:01, dapsone and DRESS (29458119); to:
HLA-B*15:02:
Increased carbamazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increase oxcarbazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increased lamotrogine-induced SJS/TEN (meta-analysis, 25428396).
Increased phenytoin-induced SJS/TEN (moderate association, 23692434).

PMID 26094938
HLA-B*58:01 and allopurinol-induced SJS/TEN

PMID: 23232549
Carrier of HLA-B*5801 (HLA-B*5801/*X,b HLA-B*5801/HLA-B*5801), significant increase in risk of allopurinol induced SCAR (severe cutaneous adverse reaction).

HLA-B*5701 and Abacavir hypersensitivity.
25934581, 22378157

HLA-B*5701-positive patients have an 80-fold elevated risk of flucloxacillin-induced liver injury. However, the incidence is low (1-2 per 1000 individuals).
https://www.pharmgkb.org/chemical/PA164781042/guidelineAnnotation/PA166182810

PMID 32714190 (review article)
HLA-B*57:01, carbamazepine and SJS/TEN.
HLA-B*15:11, carbamazepine and SJS/TEN.

HLA-B*13:01, dapsone and DRESS (29458119)
Pharmacogenomics_Paediatric v0.50 SLCO1B1 David Metz gene: SLCO1B1 was added
gene: SLCO1B1 was added to Pharmacogenomics_Paediatric. Sources: Other
Mode of inheritance for gene: SLCO1B1 was set to Other
Publications for gene: SLCO1B1 were set to 22617227
Phenotypes for gene: SLCO1B1 were set to Risk for simvastatin-induced myopathy
Mode of pathogenicity for gene: SLCO1B1 was set to Other
Pharmacogenomics_Paediatric v0.50 DPYD David Metz changed review comment from: Fluoropyrimidine Dosing
Sources: Other; to: Fluoropyrimidine (5-FU) Dosing
Capecitabine
Tegafur

Sources:
31038729
28262261
https://www.pharmgkb.org/guidelineAnnotation/PA166202721
Mitochondrial disease v0.498 NDUFV2 Ain Roesley reviewed gene: NDUFV2: Rating: AMBER; Mode of pathogenicity: None; Publications: 12754703, 19167255, 26008862; Phenotypes: Mitochondrial complex I deficiency, nuclear type 7 (MIM#618229); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4528 NSUN3 Zornitza Stark Phenotypes for gene: NSUN3 were changed from combined mitochondrial respiratory chain complex deficiency to Combined oxidative phosphorylation deficiency 48, MIM# 619012
Mendeliome v0.4527 NSUN3 Zornitza Stark Publications for gene: NSUN3 were set to 27356879
Mendeliome v0.4526 NSUN3 Zornitza Stark edited their review of gene: NSUN3: Added comment: Second family reported with early-onset mitochondrial encephalomyopathy and seizures.; Changed publications: 27356879, 32488845; Changed phenotypes: Combined oxidative phosphorylation deficiency 48, MIM# 619012
Mitochondrial disease v0.498 NSUN3 Zornitza Stark Phenotypes for gene: NSUN3 were changed from combined mitochondrial respiratory chain complex deficiency to Combined oxidative phosphorylation deficiency 48, MIM# 619012
Mitochondrial disease v0.497 NSUN3 Zornitza Stark Publications for gene: NSUN3 were set to 27356879
Mitochondrial disease v0.496 NSUN3 Zornitza Stark reviewed gene: NSUN3: Rating: AMBER; Mode of pathogenicity: None; Publications: 27356879, 32488845; Phenotypes: Combined oxidative phosphorylation deficiency 48, MIM# 619012; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4526 LIFR Zornitza Stark Publications for gene: LIFR were set to 28334964
Mendeliome v0.4525 LIFR Zornitza Stark edited their review of gene: LIFR: Added comment: Bi-allelic variants: At least 28 unique variants (nonsense, frameshift, splicing, missense, gross deletions) have been reported in individuals with Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome, 22 of which are predicted to cause LOF, suggesting homozygous LOF is the mechanism of disease for this gene. Variants in this gene have been reported in at least 22 probands in four publications.

Mono-allelic variants: associated with CAKUT in 4 individuals, mouse model recapitulates phenotype.; Changed rating: GREEN; Changed publications: 14740318, 20447141, 24988918, 29620724, 28334964; Changed phenotypes: Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome, MIM# 601559, CAKUT; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4525 PAX7 Zornitza Stark Marked gene: PAX7 as ready
Mendeliome v0.4525 PAX7 Zornitza Stark Gene: pax7 has been classified as Green List (High Evidence).
Mendeliome v0.4525 PAX7 Zornitza Stark Phenotypes for gene: PAX7 were changed from to Myopathy, congenital, progressive, with scoliosis, MIM# 618578
Mendeliome v0.4524 PAX7 Zornitza Stark Publications for gene: PAX7 were set to
Mendeliome v0.4523 PAX7 Zornitza Stark Mode of inheritance for gene: PAX7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4522 PAX7 Zornitza Stark reviewed gene: PAX7: Rating: GREEN; Mode of pathogenicity: None; Publications: 31092906, 11030621, 24065826, 31092906, 8631261, 11030621, 24065826; Phenotypes: Myopathy, congenital, progressive, with scoliosis, MIM# 618578; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3021 MADD Zornitza Stark Phenotypes for gene: MADD were changed from intellectual disability to DEEAH syndrome, MIM#619004 (Developmental Delay With Endocrine, Exocrine, Autonomic, and Hematologic Abnormalities); Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia (NEDDISH), MIM# 619005
Intellectual disability syndromic and non-syndromic v0.3020 MADD Zornitza Stark Publications for gene: MADD were set to 28940097
Intellectual disability syndromic and non-syndromic v0.3019 MADD Zornitza Stark reviewed gene: MADD: Rating: GREEN; Mode of pathogenicity: None; Publications: 28940097, 29302074, 32761064; Phenotypes: DEEAH syndrome, MIM#619004 (Developmental Delay With Endocrine, Exocrine, Autonomic, and Hematologic Abnormalities), Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia (NEDDISH), MIM# 619005; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4522 MADD Zornitza Stark Phenotypes for gene: MADD were changed from Intellectual disability; seizures; autonomic dysfunction; endocrine dysfunction to DEEAH syndrome, MIM#619004 (Developmental Delay With Endocrine, Exocrine, Autonomic, and Hematologic Abnormalities); Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia (NEDDISH), MIM# 619005
Mendeliome v0.4521 MADD Zornitza Stark edited their review of gene: MADD: Added comment: OMIM have assigned two disease entities to this gene.

DEEAH syndrome: 12 families.
NEDDISH syndrome: 8 families.; Changed phenotypes: DEEAH syndrome, MIM#619004 (Developmental Delay With Endocrine, Exocrine, Autonomic, and Hematologic Abnormalities), Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia (NEDDISH), MIM# 619005
Genetic Epilepsy v0.863 MADD Zornitza Stark Phenotypes for gene: MADD were changed from Global developmental delay / Intellectual disability / Seizures; Global developmental delay / Intellectual disability / Seizures / Abnormality of the endocrine system / Exocrine pancreatic insufficiency / Constipation / Diarrhea / Anemia / Thrombocytopenia / Abnormality of the autonomic nervous system to DEEAH syndrome, MIM#619004 (Developmental Delay With Endocrine, Exocrine, Autonomic, and Hematologic Abnormalities); Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia (NEDDISH), MIM# 619005
Genetic Epilepsy v0.862 MADD Zornitza Stark reviewed gene: MADD: Rating: GREEN; Mode of pathogenicity: None; Publications: 28940097, 29302074, 32761064; Phenotypes: DEEAH syndrome, MIM#619004 (Developmental Delay With Endocrine, Exocrine, Autonomic, and Hematologic Abnormalities), Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia (NEDDISH), MIM# 619005; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4521 SLC12A2 Zornitza Stark Publications for gene: SLC12A2 were set to 30740830; 32294086
Mendeliome v0.4520 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Added comment: Monoallelic :
DD/ID was a feature in >= 6 individuals with monoallelic de novo SLC12A2. An individual with an exon 22 truncating variant was reported to have normal milestones and cognitive function. Exon 21 variants have been described in individuals with rather isolated hearing impairment (possibly some associated motor delay, but normal cognition). Hearing impairment was also reported in 2/6 patients with variants in other exons (1 missense / 1 frameshift).

Biallelic :
DD/ID was reported in at least 3 individuals in literature. Hearing impairment has been reported on 2 occasions (although this was not probably evaluated in all subjects).

---

Monoallelic SLC12A2 mutations :

► Individuals with de novo mutations and developmental disorder were first identified by the DDD study (2017 - PMID: 28135719). 5 of them have been reported in detail by McNeill et al (below).

► McNeill et al (2020 - PMID: 32658972) report on 6 individuals with neurodevelopmental disorder due to de novo SLC12A2 mutation. All presented DD or ID ranging from mild to severe. ASD was reported in 3/6. Sensorineural hearing loss was a feature in 2/6 with the remaining having normal formal evaluations. Brain, cardiac and/or additional malformations were reported in a single individual. Following non-diagnostic prior work-up (CMA, FMR1 or other investigations) trio exome sequencing revealed missense (4/6) or truncating variants (2/6).

Three additional individuals (incl. a father and his son) with missense variants in exon 21 (NM_001046.3 / p.Glu979Lys and p.Glu980Lys) presented with bilateral sensorineural hearing loss. Speech and/or motor delay reported in these cases were attributed to the hearing impairment/vestibular arreflexia (cognitive abilities not tested).

SLC12A2 encodes sodium-potassium-chloride transporter 1 (also NKCC1).

The GTEx project has identified 8 isoforms. In brain both exon 21-containing/deleted isoforms are expressed (cited Morita et al 2014 - PMID: 24695712). As the authors discuss, RNA-seq of the developing mouse cochlea suggests that the exon 21 containing isoform is the single transcript expressed. Evidence from RNA-seq data (BrainSpan project) and literature suggests that the significant amounts of exon 21 lacking isoforms in fetal brain compensate for the deleterious effects of exon 21 variants and explain the lack of NDD in relevant patients.

Slc12a2 (NKCC1) null mouse model has demonstrated that the transporter plays a role in accumulation of the potassium rich endolymph in the inner ear, with NKCC1 absence causing sensorineural deafness and imbalance. Slc12a2 display cochlear malformations, loss of hair cells and hearing impairment (cited Delpire et al 1999 - PMID: 10369265). The brain phenotype has not been studied extensively, although loss of Slc12a2 has been shown to inhibit neurogenesis (cited: Magalhães and Rivera et al. - PMID: 27582690).

Slc12a2 null zebrafish display a collapse of the otic vesicle and reduced endolymph (Abbas and Whitfield, 2009 - PMID: 19633174) relevant to the human hearing disorder.

In vitro assessment of NKCC1 ion transporter function in Xenopus laevis, supported the deleterious effect of the identified variants (significant reduction in K+ influx). Using available single cell RNA-seq data the authors further demonstrated that SLC12A2 expressing cells display transcriptomic profiles reflective of active neurogenesis.

► Delpire et al (2016 - PMID: 27900370 - not reviewed in detail) described a 13 y.o. girl harboring a de novo 11-bp deletion in SLC12A2 exon 22. This individual reached developmental milestones on time and had a NORMAL cognitive function. Hearing was seemingly normal. Features included orthostatic intolerance, respiratory weakness, multiple endocrine abnormalities, pancreatic insufficiency and multiorgan failure incl. gut and bladder. Exome in the proband, parents and 3 unaffected sibs suggested SLC12A2 as the only candidate for her phenotype. Functional analyses in Xenopus laevis oocytes suggested that a non functional transporter was expressed and trafficked to the membrane as the wt. Detection of the truncated protein at higher molecular sizes suggested either enhanced dimerization or misfolded aggregate. There was no dominant-negative effect of mutant NKCC1. In patient fibroblasts a reduced total and NKCC1-mediated K+ influx.

► Mutai et al (2020 - PMID: 32294086) report on several individuals from 4 families, harboring variants within exon 21 or - in one case - at it's 3' splice-site (leading to skipping oe this exon at the mRNA level). All subjects were investigated for severe/profound hearing loss (in line with the role of exon 21-included isoforms in cochlea. The variant segregated with hearing impairment in 3 generations of a family while in all other subjects the variant had occured as de novo event. Despite motor delays (e.g. the subject from fam2 could not hold head or sit at the age of 10m / the proband in Fam3 was able to hold his head and walk at 6 and 20 m respectively) behavior and cognition were commented to be within normal range.


-----

Biallelic SLC12A2 mutations:

► Anazi et al (2017 - PMID: 29288388) briefly reported on a 3 y.o. boy (17DG0776) with central hypotonia, neonatal respiratory distress, failure to thrive, global DD and microcephaly and a skeletal survey suggestive of osteopenia. After non-diagnostic prior investigations (CMA revealing a 1p duplication classified as VUS, extensive metabolic workup), WES revealed a homozygous SLC12A2 splicing variant [NM_001046.2:c.2617-2A>G].

► Macnamara et al (2019 - PMID: 30740830) described a 5.5 y.o. male with sensorineural hearing loss, profound delays in all developmental areas among several other features (choanal atresia, failure to thrive, respiratory problems, absent sweat and tear production or salivation, GI abnormalities). Genetic testing for several disorders considered (cystic fibrosis, spinal muscular atrophy, sequencing and del/dup analysis of mtDNA) was normal. CMA revealed paternal uniparental isodisomy for chr. 5 and WGS a homozygous 22kb deletion in SLC12A2. This was followed by confirmation of homozygosity in the proband, heterozygosity of the unaffected father, delineation of breakpoints (chr5:127441491-127471419). mRNA studies in patient fibroblasts confirmed deletion of ex2-7, splicing of ex1 directly to ex8 and introduction of a premature stop codon in ex9. qRT-PCR confirmed that mRNA is likely subjected to NMD (expression ~80% of control). Western blot confirmed absence of the protein in the patient's fibroblasts. Again mouse models are thought to recapitulate the hearing defect but also the deficient saliva production (cited Evans et al 2000 - PMID: 10831596). Again the authors speculate a role of SLC12A2 in brain development based on evidence from murine models (migration, dendritic growth, increse in neuron density through regulation of GABAergic signalling (Young et al 2012 - PMID: 23015452). Hypotheses are also made on a regulatory relationship between NKCC1 and CFTR based on mRNA data from the ko mouse model.

► Stödberg et al (2020 - PMID: 32754646) reported 2 sibs with a complex neurodevelopmental disorder due to compound heterozygosity for a frameshift SLC12A2 variant and a splicing one (NM_001046:c.1431delT and c.2006-1G>A). Both presented hypotonia, neonatal S. aureus parotitis and respiratory problems (incl. apneas). While the older sib died at the age of 22 days, the younger one had persistent respiratory issues incl. a dry respiratory mucosa motivating metabolic, immunology investigations and testing for CF. She displayed microcephaly (OFC -2.5 SD, H was also -3.5SD), severe intellectual disability. MRI was suggestive of white matter and basal ganglia abnormalities. Other features incl. hearing impairment, and lack of tears,saliva and sweat, constipation and intestinal malrotation. There was facial dysmorphism. The variants were the only retained following WGS of the 2 affected sisters, parents and an unaffected brother. The splicing variant was shown to result in skipping of exon 13, while the indel in NMD. Again the authors discuss that the deficient saliva production, impaired hearing and GI problems are recapitulated in the mouse model (several refs provided).; Changed rating: GREEN; Changed publications: 28135719, 32658972, 27900370, 32294086, 29288388, 30740830, 32754646; Changed phenotypes: Kilquist syndrome, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3019 SLC12A2 Zornitza Stark Publications for gene: SLC12A2 were set to 30740830
Intellectual disability syndromic and non-syndromic v0.3018 SLC12A2 Zornitza Stark Mode of inheritance for gene: SLC12A2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3017 SLC12A2 Konstantinos Varvagiannis reviewed gene: SLC12A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28135719, 32658972, 27900370, 32294086, 29288388, 30740830, 32754646; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pharmacogenomics_Paediatric v0.50 HLA-B David Metz changed review comment from:
HLA-B*15:02:
Increased carbamazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increase oxcarbazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increased lamotrogine-induced SJS/TEN (meta-analysis, 25428396).
Increased phenytoin-induced SJS/TEN (moderate association, 23692434).

PMID 26094938
HLA-B*58:01 and allopurinol-induced SJS/TEN

PMID: 23232549
Carrier of HLA-B*5801 (HLA-B*5801/*X,b HLA-B*5801/HLA-B*5801), significant increase in risk of allopurinol induced SCAR (severe cutaneous adverse reaction).

HLA-B*5701 and Abacavir hypersensitivity.
25934581, 22378157

HLA-B*5701-positive patients have an 80-fold elevated risk of flucloxacillin-induced liver injury. However, the incidence is low (1-2 per 1000 individuals).
https://www.pharmgkb.org/chemical/PA164781042/guidelineAnnotation/PA166182810

PMID 32714190 (review article)
HLA-B*57:01, carbamazepine and SJS/TEN.
HLA-B*15:11, carbamazepine and SJS/TEN.
HLA-B*31:01, carbamazepine and DRESS.

HLA-B*13:01, dapsone and DRESS (29458119)

PMID 32714190 (review article)
Phenytoin and B*15:02, B*13:01, B*51:01 (? strength)
Others (beta-lactams, fluclox, augmentin, nevirapine).; to:
HLA-B*15:02:
Increased carbamazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increase oxcarbazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increased lamotrogine-induced SJS/TEN (meta-analysis, 25428396).
Increased phenytoin-induced SJS/TEN (moderate association, 23692434).

PMID 26094938
HLA-B*58:01 and allopurinol-induced SJS/TEN

PMID: 23232549
Carrier of HLA-B*5801 (HLA-B*5801/*X,b HLA-B*5801/HLA-B*5801), significant increase in risk of allopurinol induced SCAR (severe cutaneous adverse reaction).

HLA-B*5701 and Abacavir hypersensitivity.
25934581, 22378157

HLA-B*5701-positive patients have an 80-fold elevated risk of flucloxacillin-induced liver injury. However, the incidence is low (1-2 per 1000 individuals).
https://www.pharmgkb.org/chemical/PA164781042/guidelineAnnotation/PA166182810

PMID 32714190 (review article)
HLA-B*57:01, carbamazepine and SJS/TEN.
HLA-B*15:11, carbamazepine and SJS/TEN.

HLA-B*13:01, dapsone and DRESS (29458119)
Pharmacogenomics_Paediatric v0.50 HLA-B David Metz changed review comment from:
HLA-B*15:02:
Increased carbamazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increase oxcarbazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increased lamotrogine-induced SJS/TEN (meta-analysis, 25428396).
Increased phenytoin-induced SJS/TEN (moderate association, 23692434).

PMID 26094938
HLA-B*58:01 and allopurinol-induced SJS/TEN

PMID: 23232549
Carrier of HLA-B*5801 (HLA-B*5801/*X,b HLA-B*5801/HLA-B*5801), significant increase in risk of allopurinol induced SCAR (severe cutaneous adverse reaction).

HLA-B*5701 and Abacavir hypersensitivity.
25934581, 22378157
HLA-B*5701-positive patients have an 80-fold elevated risk of flucloxacillin-induced liver injury. However, the incidence is low (1-2 per 1000 individuals).
https://www.pharmgkb.org/chemical/PA164781042/guidelineAnnotation/PA166182810

PMID 32714190 (review article)
HLA-B*57:01, carbamazepine and SJS/TEN.
HLA-B*15:11, carbamazepine and SJS/TEN.
HLA-B*31:01, carbamazepine and DRESS.

HLA-B*13:01, dapsone and DRESS (29458119)

PMID 32714190 (review article)
Phenytoin and B*15:02, B*13:01, B*51:01 (? strength)
Others (beta-lactams, fluclox, augmentin, nevirapine).; to:
HLA-B*15:02:
Increased carbamazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increase oxcarbazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increased lamotrogine-induced SJS/TEN (meta-analysis, 25428396).
Increased phenytoin-induced SJS/TEN (moderate association, 23692434).

PMID 26094938
HLA-B*58:01 and allopurinol-induced SJS/TEN

PMID: 23232549
Carrier of HLA-B*5801 (HLA-B*5801/*X,b HLA-B*5801/HLA-B*5801), significant increase in risk of allopurinol induced SCAR (severe cutaneous adverse reaction).

HLA-B*5701 and Abacavir hypersensitivity.
25934581, 22378157

HLA-B*5701-positive patients have an 80-fold elevated risk of flucloxacillin-induced liver injury. However, the incidence is low (1-2 per 1000 individuals).
https://www.pharmgkb.org/chemical/PA164781042/guidelineAnnotation/PA166182810

PMID 32714190 (review article)
HLA-B*57:01, carbamazepine and SJS/TEN.
HLA-B*15:11, carbamazepine and SJS/TEN.
HLA-B*31:01, carbamazepine and DRESS.

HLA-B*13:01, dapsone and DRESS (29458119)

PMID 32714190 (review article)
Phenytoin and B*15:02, B*13:01, B*51:01 (? strength)
Others (beta-lactams, fluclox, augmentin, nevirapine).
Pharmacogenomics_Paediatric v0.50 HLA-B David Metz changed review comment from:
HLA-B*15:02 positive:
Increased carbamazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increase oxcarbazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increased lamotrogine-induced SJS/TEN (meta-analysis, 25428396).

PMID 26094938
Strong association between HLA-B*58:01 and allopurinol-induced SJS/TEN

PMID: 23232549
Carrier of HLA-B*5801 (HLA-B*5801/*X,b HLA-B*5801/HLA-B*5801), significant increase in risk of allopurinol induced SCAR (severe cutaneous adverse reaction).

HLA-B*5701 and Abacavir hypersensitivity.
PMID: 25934581
PMID: 22378157

HLA-B*5701-positive patients have an 80-fold elevated risk of flucloxacillin-induced liver injury. However, the incidence is low (1-2 per 1000 individuals).
https://www.pharmgkb.org/chemical/PA164781042/guidelineAnnotation/PA166182810; to:
HLA-B*15:02:
Increased carbamazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increase oxcarbazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increased lamotrogine-induced SJS/TEN (meta-analysis, 25428396).
Increased phenytoin-induced SJS/TEN (moderate association, 23692434).

PMID 26094938
HLA-B*58:01 and allopurinol-induced SJS/TEN

PMID: 23232549
Carrier of HLA-B*5801 (HLA-B*5801/*X,b HLA-B*5801/HLA-B*5801), significant increase in risk of allopurinol induced SCAR (severe cutaneous adverse reaction).

HLA-B*5701 and Abacavir hypersensitivity.
25934581, 22378157
HLA-B*5701-positive patients have an 80-fold elevated risk of flucloxacillin-induced liver injury. However, the incidence is low (1-2 per 1000 individuals).
https://www.pharmgkb.org/chemical/PA164781042/guidelineAnnotation/PA166182810

PMID 32714190 (review article)
HLA-B*57:01, carbamazepine and SJS/TEN.
HLA-B*15:11, carbamazepine and SJS/TEN.
HLA-B*31:01, carbamazepine and DRESS.

HLA-B*13:01, dapsone and DRESS (29458119)

PMID 32714190 (review article)
Phenytoin and B*15:02, B*13:01, B*51:01 (? strength)
Others (beta-lactams, fluclox, augmentin, nevirapine).
Pharmacogenomics_Paediatric v0.50 HLA-B David Metz changed review comment from: PMID 29392710
HLA-B*15:02 positive:
Greater risk of carbamazepine-induced SJS/TEN.
Greater risk of oxcarbazepine induced SJS/TEN

PMID 26094938
Strong association between HLA-B*58:01 and allopurinol-induced SJS/TEN

PMID: 23232549
Carrier of HLA-B*5801 (HLA-B*5801/*X,b HLA-B*5801/HLA-B*5801), significant increase in risk of allopurinol induced SCAR (severe cutaneous adverse reaction).

HLA-B*5701 and Abacavir hypersensitivity.

HLA-B*5701-positive patients have an 80-fold elevated risk of flucloxacillin-induced liver injury. However, the incidence is low (1-2 per 1000 individuals).
https://www.pharmgkb.org/chemical/PA164781042/guidelineAnnotation/PA166182810; to:
HLA-B*15:02 positive:
Increased carbamazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increase oxcarbazepine-induced SJS/TEN (CPIC guideline, 29392710).
Increased lamotrogine-induced SJS/TEN (meta-analysis, 25428396).

PMID 26094938
Strong association between HLA-B*58:01 and allopurinol-induced SJS/TEN

PMID: 23232549
Carrier of HLA-B*5801 (HLA-B*5801/*X,b HLA-B*5801/HLA-B*5801), significant increase in risk of allopurinol induced SCAR (severe cutaneous adverse reaction).

HLA-B*5701 and Abacavir hypersensitivity.
PMID: 25934581
PMID: 22378157

HLA-B*5701-positive patients have an 80-fold elevated risk of flucloxacillin-induced liver injury. However, the incidence is low (1-2 per 1000 individuals).
https://www.pharmgkb.org/chemical/PA164781042/guidelineAnnotation/PA166182810
Mackenzie's Mission_Reproductive Carrier Screening v0.23 VPS37A Zornitza Stark reviewed gene: VPS37A: Rating: AMBER; Mode of pathogenicity: None; Publications: 22717650; Phenotypes: Spastic paraplegia 53, autosomal recessive, MIM# 614898; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4520 VPS37A Zornitza Stark Marked gene: VPS37A as ready
Mendeliome v0.4520 VPS37A Zornitza Stark Gene: vps37a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4520 VPS37A Zornitza Stark Phenotypes for gene: VPS37A were changed from to Spastic paraplegia 53, autosomal recessive, MIM# 614898
Mendeliome v0.4519 VPS37A Zornitza Stark Publications for gene: VPS37A were set to
Mendeliome v0.4518 VPS37A Zornitza Stark Mode of inheritance for gene: VPS37A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4517 VPS37A Zornitza Stark Classified gene: VPS37A as Amber List (moderate evidence)
Mendeliome v0.4517 VPS37A Zornitza Stark Gene: vps37a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4516 VPS37A Zornitza Stark reviewed gene: VPS37A: Rating: AMBER; Mode of pathogenicity: None; Publications: 22717650; Phenotypes: Spastic paraplegia 53, autosomal recessive, MIM# 614898; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v0.150 VPS37A Zornitza Stark Marked gene: VPS37A as ready
Hereditary Spastic Paraplegia v0.150 VPS37A Zornitza Stark Gene: vps37a has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v0.150 VPS37A Zornitza Stark Phenotypes for gene: VPS37A were changed from Spastic paraplegia 53, autosomal recessive; Spastic paraplegia 53, autosomal recessive, 614898, AR to Spastic paraplegia 53, autosomal recessive, MIM# 614898, AR
Hereditary Spastic Paraplegia v0.149 VPS37A Zornitza Stark Classified gene: VPS37A as Amber List (moderate evidence)
Hereditary Spastic Paraplegia v0.149 VPS37A Zornitza Stark Gene: vps37a has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v0.148 VPS37A Zornitza Stark reviewed gene: VPS37A: Rating: AMBER; Mode of pathogenicity: None; Publications: 22717650; Phenotypes: Spastic paraplegia 53, autosomal recessive, MIM# 614898; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v0.148 VAMP1 Zornitza Stark changed review comment from: Spasticity is a prominent feature of this condition. Single founder variant in multiple families from Newfoundland.
Sources: Expert list; to: Spasticity is a prominent feature of this condition. Single founder variant in multiple families from Newfoundland. Bi-allelic variants cause a myasthenic syndrome.
Sources: Expert list
Hereditary Spastic Paraplegia v0.148 VAMP1 Zornitza Stark Publications for gene: VAMP1 were set to
Hereditary Spastic Paraplegia v0.147 VAMP1 Zornitza Stark Classified gene: VAMP1 as Amber List (moderate evidence)
Hereditary Spastic Paraplegia v0.147 VAMP1 Zornitza Stark Gene: vamp1 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v0.146 VAMP1 Zornitza Stark Tag founder tag was added to gene: VAMP1.
Hereditary Spastic Paraplegia v0.146 VAMP1 Zornitza Stark changed review comment from: Spasticity is a prominent feature of this condition.
Sources: Expert list; to: Spasticity is a prominent feature of this condition. Single founder variant in multiple families from Newfoundland.
Sources: Expert list
Hereditary Spastic Paraplegia v0.146 VAMP1 Zornitza Stark edited their review of gene: VAMP1: Changed rating: AMBER
Hereditary Spastic Paraplegia v0.146 VAMP1 Zornitza Stark edited their review of gene: VAMP1: Changed publications: 22958904; Changed phenotypes: Spastic ataxia 1, autosomal dominant, MIM# 108600
Hereditary Spastic Paraplegia v0.146 UNC80 Zornitza Stark Marked gene: UNC80 as ready
Hereditary Spastic Paraplegia v0.146 UNC80 Zornitza Stark Gene: unc80 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v0.146 UNC80 Zornitza Stark Publications for gene: UNC80 were set to
Hereditary Spastic Paraplegia v0.145 UNC80 Zornitza Stark Classified gene: UNC80 as Amber List (moderate evidence)
Hereditary Spastic Paraplegia v0.145 UNC80 Zornitza Stark Gene: unc80 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v0.144 UNC80 Zornitza Stark reviewed gene: UNC80: Rating: AMBER; Mode of pathogenicity: None; Publications: 27513830; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v0.144 TTR Zornitza Stark Marked gene: TTR as ready
Hereditary Spastic Paraplegia v0.144 TTR Zornitza Stark Gene: ttr has been classified as Red List (Low Evidence).
Hereditary Spastic Paraplegia v0.144 TTR Zornitza Stark Phenotypes for gene: TTR were changed from Amyloidogenic transthyretin amyloidosis to Amyloidosis, hereditary, transthyretin-related, MIM# 105210
Hereditary Spastic Paraplegia v0.143 TTR Zornitza Stark Classified gene: TTR as Red List (low evidence)
Hereditary Spastic Paraplegia v0.143 TTR Zornitza Stark Gene: ttr has been classified as Red List (Low Evidence).
Hereditary Spastic Paraplegia v0.142 TTR Zornitza Stark reviewed gene: TTR: Rating: RED; Mode of pathogenicity: None; Publications: 8960746; Phenotypes: Amyloidosis, hereditary, transthyretin-related, MIM# 105210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3017 TECPR2 Zornitza Stark Marked gene: TECPR2 as ready
Intellectual disability syndromic and non-syndromic v0.3017 TECPR2 Zornitza Stark Gene: tecpr2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3017 TECPR2 Zornitza Stark Phenotypes for gene: TECPR2 were changed from to Spastic paraplegia 49, autosomal recessive, 615031; Autonomic-sensory neuropathy; Intellectual disability
Intellectual disability syndromic and non-syndromic v0.3016 TECPR2 Zornitza Stark Publications for gene: TECPR2 were set to
Intellectual disability syndromic and non-syndromic v0.3015 TECPR2 Zornitza Stark Mode of inheritance for gene: TECPR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3014 TECPR2 Zornitza Stark reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23176824, 26542466; Phenotypes: Spastic paraplegia 49, autosomal recessive, 615031, Autonomic-sensory neuropathy, Intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4516 TECPR2 Zornitza Stark Marked gene: TECPR2 as ready
Mendeliome v0.4516 TECPR2 Zornitza Stark Gene: tecpr2 has been classified as Green List (High Evidence).
Mendeliome v0.4516 TECPR2 Zornitza Stark Phenotypes for gene: TECPR2 were changed from to Spastic paraplegia 49, autosomal recessive, MIM# 615031; Autonomic-sensory neuropathy
Mendeliome v0.4515 TECPR2 Zornitza Stark Publications for gene: TECPR2 were set to
Mendeliome v0.4514 TECPR2 Zornitza Stark Mode of inheritance for gene: TECPR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4513 TECPR2 Zornitza Stark reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23176824, 26542466; Phenotypes: Spastic paraplegia 49, autosomal recessive, MIM# 615031, Autonomic-sensory neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v0.142 TECPR2 Zornitza Stark Marked gene: TECPR2 as ready
Hereditary Spastic Paraplegia v0.142 TECPR2 Zornitza Stark Gene: tecpr2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.142 TECPR2 Zornitza Stark Phenotypes for gene: TECPR2 were changed from Spastic paraplegia 49, autosomal recessive, 615031; Spastic paraplegia 49, autosomal recessive,615031, AR to Spastic paraplegia 49, autosomal recessive, 615031; Autonomic-sensory neuropathy
Hereditary Spastic Paraplegia v0.141 TECPR2 Zornitza Stark Publications for gene: TECPR2 were set to
Hereditary Spastic Paraplegia v0.140 TECPR2 Zornitza Stark reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23176824, 26542466; Phenotypes: Spastic paraplegia 49, autosomal recessive, MIM# 615031; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v0.140 STXBP1 Zornitza Stark Classified gene: STXBP1 as Red List (low evidence)
Hereditary Spastic Paraplegia v0.140 STXBP1 Zornitza Stark Gene: stxbp1 has been classified as Red List (Low Evidence).
Hereditary Spastic Paraplegia v0.139 STXBP1 Zornitza Stark edited their review of gene: STXBP1: Changed rating: RED
Hereditary Spastic Paraplegia v0.139 STXBP1 Zornitza Stark Marked gene: STXBP1 as ready
Hereditary Spastic Paraplegia v0.139 STXBP1 Zornitza Stark Gene: stxbp1 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v0.139 STXBP1 Zornitza Stark Phenotypes for gene: STXBP1 were changed from Early infantile epileptic encephalopathy 4 to Spasticity; Early infantile epileptic encephalopathy 4
Hereditary Spastic Paraplegia v0.138 STXBP1 Zornitza Stark Publications for gene: STXBP1 were set to
Hereditary Spastic Paraplegia v0.137 STXBP1 Zornitza Stark Classified gene: STXBP1 as Amber List (moderate evidence)
Hereditary Spastic Paraplegia v0.137 STXBP1 Zornitza Stark Gene: stxbp1 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v0.136 STXBP1 Zornitza Stark reviewed gene: STXBP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 32815282; Phenotypes: Spasticity; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Spastic Paraplegia v0.136 SOX10 Zornitza Stark Marked gene: SOX10 as ready
Hereditary Spastic Paraplegia v0.136 SOX10 Zornitza Stark Gene: sox10 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v0.136 SOX10 Zornitza Stark Mode of inheritance for gene: SOX10 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Spastic Paraplegia v0.135 SOX10 Zornitza Stark Classified gene: SOX10 as Amber List (moderate evidence)
Hereditary Spastic Paraplegia v0.135 SOX10 Zornitza Stark Gene: sox10 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v0.134 SOX10 Zornitza Stark reviewed gene: SOX10: Rating: AMBER; Mode of pathogenicity: None; Publications: 28534044; Phenotypes: PCWH syndrome, MIM# 609136; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Spastic Paraplegia v0.134 SARS2 Zornitza Stark Marked gene: SARS2 as ready
Hereditary Spastic Paraplegia v0.134 SARS2 Zornitza Stark Gene: sars2 has been classified as Red List (Low Evidence).
Hereditary Spastic Paraplegia v0.134 SARS2 Zornitza Stark gene: SARS2 was added
gene: SARS2 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: SARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARS2 were set to 27279129
Phenotypes for gene: SARS2 were set to Progressive spastic paraplegia
Review for gene: SARS2 was set to RED
Added comment: Single individual reported with homozygous splicing mutation in SARS2 and with progressive spastic paresis rather than HUPRA syndrome (hyperuricemia, pulmonary hypertension, renal failure in infancy, and alkalosis) which is generally associated with missense variants in this gene.
Sources: Literature
Hereditary Spastic Paraplegia v0.133 SAMHD1 Zornitza Stark Marked gene: SAMHD1 as ready
Hereditary Spastic Paraplegia v0.133 SAMHD1 Zornitza Stark Gene: samhd1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.133 SAMHD1 Zornitza Stark Phenotypes for gene: SAMHD1 were changed from Aicardi Goutieres syndrome 5 to Aicardi Goutieres syndrome 5, MIM# 612952
Hereditary Spastic Paraplegia v0.132 SAMHD1 Zornitza Stark reviewed gene: SAMHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 5, MIM# 612952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v0.132 RNASEH2B Zornitza Stark Marked gene: RNASEH2B as ready
Hereditary Spastic Paraplegia v0.132 RNASEH2B Zornitza Stark Gene: rnaseh2b has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.132 RNASEH2B Zornitza Stark Phenotypes for gene: RNASEH2B were changed from Aicardi Goutieres syndrome 2 to Aicardi Goutieres syndrome 2, MIM# 610181
Hereditary Spastic Paraplegia v0.131 RNASEH2B Zornitza Stark Publications for gene: RNASEH2B were set to
Hereditary Spastic Paraplegia v0.130 RNASEH2B Zornitza Stark reviewed gene: RNASEH2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 29691679, 30223285, 29239743, 28762473; Phenotypes: Aicardi-Goutieres syndrome 2, MIM# 610181; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4513 SMOC2 Zornitza Stark Marked gene: SMOC2 as ready
Mendeliome v0.4513 SMOC2 Zornitza Stark Gene: smoc2 has been classified as Green List (High Evidence).
Mendeliome v0.4513 SMOC2 Zornitza Stark Phenotypes for gene: SMOC2 were changed from to Dentin dysplasia, type I, with microdontia and misshapen teeth, MIM# 125400
Mendeliome v0.4512 SMOC2 Zornitza Stark Publications for gene: SMOC2 were set to
Mendeliome v0.4511 SMOC2 Zornitza Stark Mode of inheritance for gene: SMOC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4510 SMOC2 Zornitza Stark reviewed gene: SMOC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22152679, 23317772, 32908163; Phenotypes: Dentin dysplasia, type I, with microdontia and misshapen teeth, MIM# 125400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v0.130 PCYT2 Zornitza Stark Marked gene: PCYT2 as ready
Hereditary Spastic Paraplegia v0.130 PCYT2 Zornitza Stark Gene: pcyt2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.130 PCYT2 Zornitza Stark Classified gene: PCYT2 as Green List (high evidence)
Hereditary Spastic Paraplegia v0.130 PCYT2 Zornitza Stark Gene: pcyt2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.129 PCYT2 Zornitza Stark gene: PCYT2 was added
gene: PCYT2 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: PCYT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCYT2 were set to 31637422
Phenotypes for gene: PCYT2 were set to global developmental delay; regression; spastic parapesis or tetraparesis; epilepsy; progressive cerebral and cerebellar atrophy
Review for gene: PCYT2 was set to GREEN
Added comment: Biallelic hypomorph variants in 5 affected cases from 4 families with complicated hereditary spastic paraplegia, onset between 2 and 16 years of age. Zebrafish model similar to previous HSP zebrafish models.
Sources: Expert list
Ataxia v0.259 MAG Zornitza Stark Marked gene: MAG as ready
Ataxia v0.259 MAG Zornitza Stark Gene: mag has been classified as Green List (High Evidence).
Ataxia v0.259 MAG Zornitza Stark Classified gene: MAG as Green List (high evidence)
Ataxia v0.259 MAG Zornitza Stark Gene: mag has been classified as Green List (High Evidence).
Ataxia v0.258 MAG Zornitza Stark gene: MAG was added
gene: MAG was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: MAG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAG were set to 32629324; 32340215
Phenotypes for gene: MAG were set to Spastic paraplegia 75, autosomal recessive, MIM# 616680; Cerebellar ataxia; Oculomotor apraxia
Review for gene: MAG was set to GREEN
Added comment: At least 5 families reported where ataxia was a prominent feature.
Sources: Literature
Mendeliome v0.4510 MAG Zornitza Stark Marked gene: MAG as ready
Mendeliome v0.4510 MAG Zornitza Stark Gene: mag has been classified as Green List (High Evidence).
Mendeliome v0.4510 MAG Zornitza Stark Phenotypes for gene: MAG were changed from to Spastic paraplegia 75, autosomal recessive, MIM# 616680
Mendeliome v0.4509 MAG Zornitza Stark Publications for gene: MAG were set to
Mendeliome v0.4508 MAG Zornitza Stark Mode of inheritance for gene: MAG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4507 MAG Zornitza Stark reviewed gene: MAG: Rating: GREEN; Mode of pathogenicity: None; Publications: 24482476, 26179919, 31402626, 32629324; Phenotypes: Spastic paraplegia 75, autosomal recessive, MIM# 616680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v0.128 MAG Zornitza Stark Marked gene: MAG as ready
Hereditary Spastic Paraplegia v0.128 MAG Zornitza Stark Gene: mag has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.128 MAG Zornitza Stark Publications for gene: MAG were set to 31402626; 24482476; 26179919
Hereditary Spastic Paraplegia v0.127 MAG Zornitza Stark reviewed gene: MAG: Rating: GREEN; Mode of pathogenicity: None; Publications: 24482476, 26179919, 31402626, 32629324; Phenotypes: Spastic paraplegia 75, autosomal recessive, MIM# 616680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v0.127 GAN Zornitza Stark Marked gene: GAN as ready
Hereditary Spastic Paraplegia v0.127 GAN Zornitza Stark Gene: gan has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.127 GAN Zornitza Stark Phenotypes for gene: GAN were changed from Giant axonal neuropathy to Giant axonal neuropathy-1, MIM# 256850
Hereditary Spastic Paraplegia v0.126 GAN Zornitza Stark Publications for gene: GAN were set to 26381321
Hereditary Spastic Paraplegia v0.125 GAN Zornitza Stark reviewed gene: GAN: Rating: GREEN; Mode of pathogenicity: None; Publications: 11062483; Phenotypes: Giant axonal neuropathy-1, MIM# 256850; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v0.125 EXOSC3 Zornitza Stark Marked gene: EXOSC3 as ready
Hereditary Spastic Paraplegia v0.125 EXOSC3 Zornitza Stark Gene: exosc3 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v0.125 EXOSC3 Zornitza Stark Phenotypes for gene: EXOSC3 were changed from Pontocerebellar hypoplasia, type 1b to Pontocerebellar hypoplasia, type 1b; Complicated hereditary spastic paraplegia
Mendeliome v0.4507 DSTYK Zornitza Stark Tag SV/CNV tag was added to gene: DSTYK.
Mendeliome v0.4507 DSTYK Zornitza Stark Marked gene: DSTYK as ready
Mendeliome v0.4507 DSTYK Zornitza Stark Gene: dstyk has been classified as Green List (High Evidence).
Mendeliome v0.4507 DSTYK Zornitza Stark Phenotypes for gene: DSTYK were changed from to Congenital anomalies of kidney and urinary tract 1, MIM# 610805; Spastic paraplegia 23, MIM# 270750
Mendeliome v0.4506 DSTYK Zornitza Stark Publications for gene: DSTYK were set to
Mendeliome v0.4505 DSTYK Zornitza Stark Mode of inheritance for gene: DSTYK was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4504 DSTYK Zornitza Stark reviewed gene: DSTYK: Rating: GREEN; Mode of pathogenicity: None; Publications: 23862974, 23862974, 28618409, 28157540, 23862974; Phenotypes: Congenital anomalies of kidney and urinary tract 1, MIM# 610805, Spastic paraplegia 23, MIM# 270750; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4504 ZMYM2 Zornitza Stark Marked gene: ZMYM2 as ready
Mendeliome v0.4504 ZMYM2 Zornitza Stark Gene: zmym2 has been classified as Green List (High Evidence).
Mendeliome v0.4504 ZMYM2 Zornitza Stark Classified gene: ZMYM2 as Green List (high evidence)
Mendeliome v0.4504 ZMYM2 Zornitza Stark Gene: zmym2 has been classified as Green List (High Evidence).
Mendeliome v0.4503 ZMYM2 Zornitza Stark gene: ZMYM2 was added
gene: ZMYM2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZMYM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYM2 were set to 32891193
Phenotypes for gene: ZMYM2 were set to Congenital anomalies of kidney and urinary tract; Neurodevelopmental disorder
Review for gene: ZMYM2 was set to GREEN
Added comment: Heterozygous pathogenic (pLoF) ZMYM2 variants have been reported in individuals with syndromic presentation including CAKUT (in several cases) and variable neurological manifestations among extra-renal features.

--

Connaughton et al (2020 - PMID: 32891193) report on 19 individuals (from 15 unrelated families) with heterozygous pathogenic ZMYM2 variants.

Affected individuals from 7 families presented with CAKUT while all of them displayed extra-renal features. Neurological manifestations were reported in 16 individuals from 14 families (data not available for 1 fam), among others hypotonia (3/14 fam), speech delay (4/14 fam), global DD (9/14 fam), ID (4/14 fam), microcephaly (4/14 fam). ASD was reported in 4 fam (4 indiv). Seizures were reported in 2 fam (2 indiv). Variable other features included cardiac defects, facial dysmorphisms, small hands and feet with dys-/hypo-plastic nails and clinodactyly.

14 pLoF variants were identified, in most cases as de novo events (8 fam). In 2 families the variant was inherited from an affected parent. Germline mosaicism occurred in 1 family.

The human disease features were recapitulated in a X. tropicalis morpholino knockdown, with expression of truncating variants failing to rescue renal and craniofacial defects. Heterozygous Zmym2-deficient mice also recapitulated the features of CAKUT.

ZMYM2 (previously ZNF198) encodes a nuclear zinc finger protein localizing to the nucleus (and PML nuclear body).

It has previously been identified as transcriptional corepressor interacting with nuclear receptors and the LSD1-CoREST-HDAC1 complex. It has also been shown to interact with FOXP transcription factors.

The authors provide evidence for loss of interaction of the truncated ZMYM2 with FOXP1 (mutations in the latter having recently been reported in syndromic CAKUT).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3014 ZMYM2 Zornitza Stark edited their review of gene: ZMYM2: Changed rating: GREEN; Changed publications: 32891193; Changed phenotypes: Congenital anomalies of kidney and urinary tract, Neurodevelopmental disorder; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3014 ZMYM2 Zornitza Stark Marked gene: ZMYM2 as ready
Intellectual disability syndromic and non-syndromic v0.3014 ZMYM2 Zornitza Stark Added comment: Comment when marking as ready: Syndromic CAKUT, variable extra-renal phenotype but sufficient families with ID for Green rating.
Intellectual disability syndromic and non-syndromic v0.3014 ZMYM2 Zornitza Stark Gene: zmym2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3014 ZMYM2 Zornitza Stark Classified gene: ZMYM2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3014 ZMYM2 Zornitza Stark Gene: zmym2 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.69 ZMYM2 Zornitza Stark Marked gene: ZMYM2 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.69 ZMYM2 Zornitza Stark Gene: zmym2 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.69 ZMYM2 Zornitza Stark Classified gene: ZMYM2 as Green List (high evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.69 ZMYM2 Zornitza Stark Gene: zmym2 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.16 MTX2 Zornitza Stark Marked gene: MTX2 as ready
Mandibulofacial Acrofacial dysostosis v0.16 MTX2 Zornitza Stark Gene: mtx2 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.16 MTX2 Zornitza Stark Classified gene: MTX2 as Green List (high evidence)
Mandibulofacial Acrofacial dysostosis v0.16 MTX2 Zornitza Stark Gene: mtx2 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.15 MTX2 Zornitza Stark gene: MTX2 was added
gene: MTX2 was added to Mandibulofacial Acrofacial dysostosis. Sources: Literature
Mode of inheritance for gene: MTX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTX2 were set to 32917887
Phenotypes for gene: MTX2 were set to Mandibuloacral dysplasia; lipodystrophy; arterial calcification
Review for gene: MTX2 was set to GREEN
Added comment: Seven individuals from 5 unrelated families reported with severe progeroid form of MAD with growth retardation, small viscerocranium with mandibular underdevelopment, distal acro-osteolyses, lipodystrophy, altered skin pigmentation, renal focal glomerulosclerosis, and extremely severe hypertension in most cases, eventually associated with disseminated arterial calcification. Loss of MTX2 in patients' primary fibroblasts led to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients' fibroblasts were resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation.
Sources: Literature
Skeletal dysplasia v0.46 MTX2 Zornitza Stark Marked gene: MTX2 as ready
Skeletal dysplasia v0.46 MTX2 Zornitza Stark Gene: mtx2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.46 MTX2 Zornitza Stark Classified gene: MTX2 as Green List (high evidence)
Skeletal dysplasia v0.46 MTX2 Zornitza Stark Gene: mtx2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.45 MTX2 Zornitza Stark gene: MTX2 was added
gene: MTX2 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: MTX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTX2 were set to 32917887
Phenotypes for gene: MTX2 were set to Mandibuloacral dysplasia; lipodystrophy; arterial calcification
Review for gene: MTX2 was set to GREEN
Added comment: Seven individuals from 5 unrelated families reported with severe progeroid form of MAD with growth retardation, small viscerocranium with mandibular underdevelopment, distal acro-osteolyses, lipodystrophy, altered skin pigmentation, renal focal glomerulosclerosis, and extremely severe hypertension in most cases, eventually associated with disseminated arterial calcification. Loss of MTX2 in patients' primary fibroblasts led to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients' fibroblasts were resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation.
Sources: Literature
Lipodystrophy_Lipoatrophy v0.6 MTX2 Zornitza Stark Marked gene: MTX2 as ready
Lipodystrophy_Lipoatrophy v0.6 MTX2 Zornitza Stark Gene: mtx2 has been classified as Green List (High Evidence).
Lipodystrophy_Lipoatrophy v0.6 MTX2 Zornitza Stark Classified gene: MTX2 as Green List (high evidence)
Lipodystrophy_Lipoatrophy v0.6 MTX2 Zornitza Stark Gene: mtx2 has been classified as Green List (High Evidence).
Lipodystrophy_Lipoatrophy v0.5 MTX2 Zornitza Stark gene: MTX2 was added
gene: MTX2 was added to Lipodystrophy_Lipoatrophy. Sources: Literature
Mode of inheritance for gene: MTX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTX2 were set to 32917887
Phenotypes for gene: MTX2 were set to Mandibuloacral dysplasia; lipodystrophy; arterial calcification
Review for gene: MTX2 was set to GREEN
Added comment: Seven individuals from 5 unrelated families reported with severe progeroid form of MAD with growth retardation, small viscerocranium with mandibular underdevelopment, distal acro-osteolyses, lipodystrophy, altered skin pigmentation, renal focal glomerulosclerosis, and extremely severe hypertension in most cases, eventually associated with disseminated arterial calcification. Loss of MTX2 in patients' primary fibroblasts led to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients' fibroblasts were resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation.
Sources: Literature
Mendeliome v0.4502 MTX2 Zornitza Stark Marked gene: MTX2 as ready
Mendeliome v0.4502 MTX2 Zornitza Stark Gene: mtx2 has been classified as Green List (High Evidence).
Mendeliome v0.4502 MTX2 Zornitza Stark Classified gene: MTX2 as Green List (high evidence)
Mendeliome v0.4502 MTX2 Zornitza Stark Gene: mtx2 has been classified as Green List (High Evidence).
Mendeliome v0.4501 MTX2 Zornitza Stark gene: MTX2 was added
gene: MTX2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MTX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTX2 were set to 32917887
Phenotypes for gene: MTX2 were set to Mandibuloacral dysplasia; lipodystrophy; arterial calcification
Review for gene: MTX2 was set to GREEN
Added comment: Seven individuals from 5 unrelated families reported with severe progeroid form of MAD with growth retardation, small viscerocranium with mandibular underdevelopment, distal acro-osteolyses, lipodystrophy, altered skin pigmentation, renal focal glomerulosclerosis, and extremely severe hypertension in most cases, eventually associated with disseminated arterial calcification. Loss of MTX2 in patients' primary fibroblasts led to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients' fibroblasts were resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation.
Sources: Literature
Rasopathy v0.87 RREB1 Zornitza Stark Marked gene: RREB1 as ready
Rasopathy v0.87 RREB1 Zornitza Stark Gene: rreb1 has been classified as Red List (Low Evidence).
Rasopathy v0.87 RREB1 Zornitza Stark Tag SV/CNV tag was added to gene: RREB1.
Rasopathy v0.87 RREB1 Zornitza Stark gene: RREB1 was added
gene: RREB1 was added to Rasopathy. Sources: Literature
Mode of inheritance for gene: RREB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RREB1 were set to 32938917
Phenotypes for gene: RREB1 were set to Noonan syndrome-like disorder
Review for gene: RREB1 was set to RED
Added comment: Single individual reported with Noonan syndrome-like features and a deletion encompassing RREB1. Overlapping deletions in publicly reported databases examined, and RREB1 postulated to be the key gene. Rreb1 hemizygous mice display orbital hypertelorism and age dependent cardiac hypertrophy. RREB1 recruits SIN3A and KDM1A to an RRE in target promoters in human and murine cells to control histone H3K4 methylation of MAPK pathway genes. In summary, single well phenotyped individual with a CNV and experimental data to support gene-disease association.
Sources: Literature
Mendeliome v0.4500 RREB1 Zornitza Stark Marked gene: RREB1 as ready