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Mendeliome v0.13890 AR Elena Savva Phenotypes for gene: AR were changed from to Hypospadias 1, X-linked MIM#30063; Androgen insensitivity MIM#300068; Androgen insensitivity, partial, with or without breast cancer MIM#312300; Spinal and bulbar muscular atrophy of Kennedy MIM#313200
Mendeliome v0.13890 AR Elena Savva Publications for gene: AR were set to
Mendeliome v0.13889 AR Elena Savva Mode of inheritance for gene: AR was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.13888 AR Elena Savva reviewed gene: AR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22334387; Phenotypes: Hypospadias 1, X-linked MIM#30063, Androgen insensitivity MIM#300068, Androgen insensitivity, partial, with or without breast cancer MIM#312300, Spinal and bulbar muscular atrophy of Kennedy MIM#313200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.13888 DCLRE1C Zornitza Stark Marked gene: DCLRE1C as ready
Mendeliome v0.13885 ARCN1 Elena Savva Marked gene: ARCN1 as ready
Mendeliome v0.13885 ARCN1 Elena Savva Gene: arcn1 has been classified as Green List (High Evidence).
Mendeliome v0.13884 DCHS1 Zornitza Stark Marked gene: DCHS1 as ready
Mendeliome v0.13879 APPL1 Elena Savva Marked gene: APPL1 as ready
Mendeliome v0.13879 AQP1 Elena Savva Phenotypes for gene: AQP1 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension
Mendeliome v0.13878 APRT Elena Savva Marked gene: APRT as ready
Mendeliome v0.13878 AQP1 Elena Savva Phenotypes for gene: AQP1 were changed from to Pulmonary arterial hypertension
Mendeliome v0.13877 AQP1 Elena Savva Marked gene: AQP1 as ready
Mendeliome v0.13875 AQP1 Elena Savva reviewed gene: AQP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:22683574, 29650961; Phenotypes: Pulmonary arterial hypertension; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.13873 APOC4-APOC2 Elena Savva Marked gene: APOC4-APOC2 as ready
Mendeliome v0.13870 APOC2 Elena Savva Marked gene: APOC2 as ready
Mendeliome v0.13868 APOC3 Elena Savva Marked gene: APOC3 as ready
Mendeliome v0.13864 ACTL6B Zornitza Stark edited their review of gene: ACTL6B: Changed phenotypes: Epileptic encephalopathy, early infantile, 76, MIM# 618468, Intellectual developmental disorder with severe speech and ambulation defects, MIM# 618470; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13862 MAPKAPK5 Zornitza Stark Phenotypes for gene: MAPKAPK5 were changed from Developmental delay, variable brain anomalies, congenital heart defects, dysmorphic to Neurocardiofaciodigital syndrome, MIM# 619869
Mendeliome v0.13861 MAPKAPK5 Zornitza Stark edited their review of gene: MAPKAPK5: Changed phenotypes: Neurocardiofaciodigital syndrome, MIM# 619869
Mendeliome v0.13860 DCAF17 Zornitza Stark Marked gene: DCAF17 as ready
Mendeliome v0.13857 CYP2C19 Ain Roesley Marked gene: CYP2C19 as ready
Mendeliome v0.13856 CYP2B6 Ain Roesley Marked gene: CYP2B6 as ready
Mendeliome v0.13854 DAZ4 Zornitza Stark Marked gene: DAZ4 as ready
Mendeliome v0.13853 DAZ3 Zornitza Stark Marked gene: DAZ3 as ready
Mendeliome v0.13852 CYP2A6 Ain Roesley Marked gene: CYP2A6 as ready
Mendeliome v0.13852 CYP2A6 Ain Roesley Phenotypes for gene: CYP2A6 were changed from to Coumarin resistance MIM#122700
Mendeliome v0.13851 CYP2A6 Ain Roesley reviewed gene: CYP2A6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Coumarin resistance MIM#122700; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.13851 DAZ2 Zornitza Stark Marked gene: DAZ2 as ready
Mendeliome v0.13850 DAZ1 Zornitza Stark Marked gene: DAZ1 as ready
Mendeliome v0.13848 CYP27A1 Ain Roesley Marked gene: CYP27A1 as ready
Mendeliome v0.13846 DARS2 Zornitza Stark Marked gene: DARS2 as ready
Mendeliome v0.13846 DARS2 Zornitza Stark Gene: dars2 has been classified as Green List (High Evidence).
Mendeliome v0.13846 DARS2 Zornitza Stark Phenotypes for gene: DARS2 were changed from to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, MIM# 611105
Mendeliome v0.13845 CYP26C1 Ain Roesley Marked gene: CYP26C1 as ready
Mendeliome v0.13845 DARS2 Zornitza Stark Publications for gene: DARS2 were set to
Mendeliome v0.13844 DARS2 Zornitza Stark Mode of inheritance for gene: DARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13843 DARS2 Zornitza Stark changed review comment from: Slowly progressive disorder with variable age of onset, multiple families reported.; to: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is defined on the basis of a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy (Scheper et al., 2007). Affected individuals develop slowly progressive cerebellar ataxia, spasticity, and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline.
Mendeliome v0.13842 DARS2 Zornitza Stark reviewed gene: DARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 17384640, 15002045, 16788019; Phenotypes: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, MIM# 611105; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13842 D2HGDH Zornitza Stark Marked gene: D2HGDH as ready
Mendeliome v0.13842 D2HGDH Zornitza Stark Phenotypes for gene: D2HGDH were changed from to D-2-hydroxyglutaric aciduria MIM#600721
Mendeliome v0.13839 D2HGDH Zornitza Stark reviewed gene: D2HGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 25778941, 31349060, 15609246, 20020533; Phenotypes: D-2-hydroxyglutaric aciduria MIM#600721; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13839 CYP7B1 Zornitza Stark Marked gene: CYP7B1 as ready
Mendeliome v0.13839 CYP7B1 Zornitza Stark Phenotypes for gene: CYP7B1 were changed from to Bile acid synthesis defect, congenital, 3 MIM#613812; Spastic paraplegia 5A, autosomal recessive MIM#270800; Disorders of bile acid biosynthesis
Mendeliome v0.13836 CYP1A2 Ain Roesley Marked gene: CYP1A2 as ready
Mendeliome v0.13835 KLF4 Zornitza Stark Marked gene: KLF4 as ready
Mendeliome v0.13834 CYP19A1 Ain Roesley Marked gene: CYP19A1 as ready
Mendeliome v0.13834 CYP19A1 Ain Roesley Phenotypes for gene: CYP19A1 were changed from to Aromatase deficiency (MIM#613546), AR; Aromatase excess syndrome (MIM#139300), AD
Mendeliome v0.13832 CYP19A1 Ain Roesley reviewed gene: CYP19A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17164303, 25264451; Phenotypes: Aromatase deficiency (MIM#613546), AR, Aromatase excess syndrome (MIM#139300), AD; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13832 CYCS Ain Roesley Marked gene: CYCS as ready
Mendeliome v0.13828 CYC1 Ain Roesley Marked gene: CYC1 as ready
Mendeliome v0.13828 CYC1 Ain Roesley Phenotypes for gene: CYC1 were changed from to Mitochondrial complex III deficiency, nuclear type 6 MIM#615453
Mendeliome v0.13826 CYC1 Ain Roesley reviewed gene: CYC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23910460, 34252606; Phenotypes: Mitochondrial complex III deficiency, nuclear type 6 MIM#615453; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13825 HNRNPA2B1 Zornitza Stark Phenotypes for gene: HNRNPA2B1 were changed from Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 MIM#615422 to oculopharyngeal muscular dystrophy, MONDO:0008116; Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 MIM#615422
Mendeliome v0.13820 KCNH5 Zornitza Stark Marked gene: KCNH5 as ready
Mendeliome v0.13820 CREB1 Zornitza Stark Phenotypes for gene: CREB1 were changed from corpus callosum agenesis; thyroid follicular hypoplasia to Agenesis of corpus callosum, MONDO:0009022
Mendeliome v0.13819 SLC16A12 Zornitza Stark Marked gene: SLC16A12 as ready
Mendeliome v0.13819 SLC16A12 Zornitza Stark Phenotypes for gene: SLC16A12 were changed from to Cataract 47, juvenile, with microcornea, MIM# 612018
Mendeliome v0.13816 SLC14A1 Zornitza Stark Marked gene: SLC14A1 as ready
Mendeliome v0.13812 SLC12A5 Zornitza Stark Marked gene: SLC12A5 as ready
Mendeliome v0.13809 CORIN Zornitza Stark Marked gene: CORIN as ready
Mendeliome v0.13809 DUSP6 Zornitza Stark Marked gene: DUSP6 as ready
Mendeliome v0.13805 DYRK1B Zornitza Stark Marked gene: DYRK1B as ready
Mendeliome v0.13798 KLF4 Elena Savva gene: KLF4 was added
gene: KLF4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KLF4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KLF4 were set to PMID: 35168889; 10431239
Phenotypes for gene: KLF4 were set to Hereditary palmoplantar keratoderma MONDO:0019272, KFL4-related
Review for gene: KLF4 was set to GREEN
Added comment: PMID: 35168889 - 3 patients from 2 unrelated families with palmoplantar keratoderma. Two variants found, fs and a missense.
Functional studies on patient skin biopsy shows "slightly but significantly decreased" protein expression in both children.
Gene was shown to bind the DSG1 promoter and regulate expression. Transfected cells showed reduced DSG1 expression.

PMID: 10431239 - mouse K/O died shortly after birth due to loss of skin barrier function

gnomAD: single het fs in the population
Sources: Literature
Mendeliome v0.13797 CTR9 Zornitza Stark Marked gene: CTR9 as ready
Mendeliome v0.13797 HNRNPA2B1 Naomi Baker reviewed gene: HNRNPA2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:35484142; Phenotypes: oculopharyngeal muscular dystrophy, MONDO:0008116; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13796 P3H2 Daniel Flanagan reviewed gene: P3H2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35499085; Phenotypes: Myopia, high, with cataract and vitreoretinal degeneration (MIM# 614292); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13796 CDH4 Ain Roesley Marked gene: CDH4 as ready
Mendeliome v0.13796 DNAH14 Zornitza Stark Marked gene: DNAH14 as ready
Mendeliome v0.13796 CDH4 Ain Roesley gene: CDH4 was added
gene: CDH4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDH4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDH4 were set to 35034853
Phenotypes for gene: CDH4 were set to coloboma MONDO#0001476, CDH4-related
Review for gene: CDH4 was set to RED
gene: CDH4 was marked as current diagnostic
Added comment: 1x family with AD coloboma

Also presented with ID and post natal microcephaly

zebrafish KO model
Sources: Literature
Mendeliome v0.13793 CD164 Alison Yeung Marked gene: CD164 as ready
Mendeliome v0.13792 CD164 Alison Yeung gene: CD164 was added
gene: CD164 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CD164 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CD164 were set to 26197441; 35254497; 26197441
Phenotypes for gene: CD164 were set to Deafness, autosomal dominant 66, MIM# 616969
Review for gene: CD164 was set to GREEN
Added comment: p.(Arg192Ter), a truncating variant that results in loss of 6 amino acids, was detected in two families (one Polish and one Korean) with hearing loss. Four affected (heterozygous) and two unaffected (neg) were tested, however 14 members had been diagnosed with HL in a large multi generational family (gene panel 237 genes). The second family (WES) had two affected heterozygous and no unaffected were tested. This same variant had previously been reported in a Danish family (12 affected heterozygous and 13 unaffected negative, but one younger member unaffected are heterozygous) with hearing loss (PMID: 26197441), for which functional studies in HEK cells demonstrated that the truncated protein was almost completely retained on the plasma cell membrane in contrast to the wild-type protein, which targeted primarily to the endo-lysosomal compartments. The YHTL motif, deleted by the c.574C>T nonsense mutation, is a canonical sorting motif
known to be recognized by specific adaptor proteins in the cytosol, leading to subcellular trafficking of the transmembrane protein to endosomes and lysosomes.
Sources: Literature
Mendeliome v0.13791 CTR9 Dean Phelan gene: CTR9 was added
gene: CTR9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CTR9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTR9 were set to PMID: 35499524
Phenotypes for gene: CTR9 were set to Neurodevelopmental disorder (MONDO:0700092), CTR9 related; Intellectual disability (MONDO:0001071); hypotonia (HP:0001252); joint hyperlaxity (HP:0001388); speech delay; coordination problems; tremor (HP:0001337); autism spectrum disorder (MONDO:0005258)
Review for gene: CTR9 was set to GREEN
Added comment: PMID: 35499524 - Thirteen individuals with variables degrees of intellectual disability, hypotonia, joint hyperlaxity, speech delay, coordination problems, tremor, autism spectrum disorder. Mild dysmorphism and cardiac anomalies were less frequent. Eleven of the variants were shown to be de novo.
Sources: Literature
Mendeliome v0.13791 TULP3 Zornitza Stark Marked gene: TULP3 as ready
Mendeliome v0.13789 DNAH14 Chern Lim gene: DNAH14 was added
gene: DNAH14 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNAH14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH14 were set to PMID: 35438214
Phenotypes for gene: DNAH14 were set to Neurodevelopmental disorder, DNAH14-related (MONDO#0700092)
Review for gene: DNAH14 was set to GREEN
gene: DNAH14 was marked as current diagnostic
Added comment: PMID: 35438214:
- Three previously unreported patients with compound heterozygous DNAH14 variants, including one nonsense, one frameshift, and four missense variants. A spectrum of neurological and developmental phenotypes was observed, including seizures, global developmental delay, microcephaly, and hypotonia.
Sources: Literature
Mendeliome v0.13789 ANK3 Ain Roesley Phenotypes for gene: ANK3 were changed from Mental retardation, autosomal recessive, 37 615493; Intellectual disability, autosomal dominant; coloboma MONDO#0001476, ANK3-related to Mental retardation, autosomal recessive, 37 615493; Intellectual disability, autosomal dominant; coloboma MONDO#0001476, ANK3-related
Mendeliome v0.13788 PRDM13 Zornitza Stark Phenotypes for gene: PRDM13 were changed from Retinal dystrophy; Chorioretinal atrophy, progressive bifocal, MIM# 600790; intellectual disability, MONDO:0001071, PRDM13-associated; ataxia with cerebellar hypoplasia, MONDO:0016054, PRDM13-associated; congenital hypogonadotropic hypogonadism, MONDO:0015770 to Retinal dystrophy; Chorioretinal atrophy, progressive bifocal, MIM# 600790; intellectual disability, MONDO:0001071, PRDM13-associated; ataxia with cerebellar hypoplasia, MONDO:0016054, PRDM13-associated; congenital hypogonadotropic hypogonadism, MONDO:0015770
Mendeliome v0.13788 ANK3 Ain Roesley Phenotypes for gene: ANK3 were changed from Mental retardation, autosomal recessive, 37 615493; Intellectual disability, autosomal dominant to Mental retardation, autosomal recessive, 37 615493; Intellectual disability, autosomal dominant; coloboma MONDO#0001476, ANK3-related
Mendeliome v0.13787 TULP3 Anna Ritchie gene: TULP3 was added
gene: TULP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TULP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TULP3 were set to PMID: 35397207
Phenotypes for gene: TULP3 were set to progressive degenerative liver fibrosis with variable fibrocystic kidney disease; hypertrophic cardiomyopathy MONDO:0005045
Review for gene: TULP3 was set to GREEN
Added comment: 15 individuals from eight unrelated families with bi-allelic variants in TULP3 were detected. The affected individuals reported are mostly adults, in the 3rd through 7th decades of life, and presented with progressive degenerative liver fibrosis with variable fibrocystic kidney disease and hypertrophic cardiomyopathy.

The human phenotype was ecapitulated in adult zebrafish and confirmed disruption of critical ciliary cargo composition in several primary cell lines derived from affected individuals
Sources: Literature
Mendeliome v0.13786 DROSHA Zornitza Stark Marked gene: DROSHA as ready
Mendeliome v0.13784 PRDM13 Dean Phelan reviewed gene: PRDM13: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35390279; Phenotypes: Pontocerebellar hypoplasia (MONDO:0020135), PRDM13 related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13784 DROSHA Lucy Spencer gene: DROSHA was added
gene: DROSHA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DROSHA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DROSHA were set to 35405010
Phenotypes for gene: DROSHA were set to Neurodevelopmental disorder (MONDO#0700092), DROSHA-related
Review for gene: DROSHA was set to AMBER
Added comment: 2 individuals with profound intellectual disability, epilepsy, white matter atrophy, microcephaly, and dysmorphic features, who carry damaging de novo heterozygous variants in DROSHA. Both variants are missense, absent from gnomad. Both individuals noted to have Rett-like features.

Functional studies in patient fibroblasts showed one of the missense altered the expression of mature miRNA. Fruit fly models with homozygous LOF variants die during larval stages. introduction of the missense seen in the patients was able to partially rescue this phenotype suggesting LOF is not the mechanism.
Sources: Literature
Mendeliome v0.13784 KCNH5 Elena Savva gene: KCNH5 was added
gene: KCNH5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCNH5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNH5 were set to https://www.medrxiv.org/content/10.1101/2022.04.26.22274147v1
Phenotypes for gene: KCNH5 were set to Neurodevelopmental disorders
Mode of pathogenicity for gene: KCNH5 was set to Other
Review for gene: KCNH5 was set to GREEN
Added comment: Happ (2022), preprint: Screen of 893 patients with DEE found 17 patients with missense variants (16/17 de novo, 1/17 inherited). GOF mechanism suggested.
Patient phenotypes included focal/generalized seizures, Cognitive outcome for the ten individuals >5 years ranged from normal (3/10) to mild (3/10), moderate (2/10), severe (1/10) and profound (1/10) intellectual disability (ID)

p.Arg327His (7 probands), p.Arg333His (4 probands) were recurring
Sources: Literature
Mendeliome v0.13783 PPFIBP1 Zornitza Stark Marked gene: PPFIBP1 as ready
Mendeliome v0.13783 STX1A Ain Roesley Marked gene: STX1A as ready
Mendeliome v0.13782 STX1A Ain Roesley changed review comment from: Preprint:
8 individuals - 2x hom (related) and 6x hets (all de novo except 1x unknown)

7 unrelated since the 2 siblings share similar features:
7/7 ID, 7/7 motor delay, 4/7 epilepsy, 5/7 neonatal hypotonia 2/7 regression, 2/7 ASD excluding 1 with features but did not meet criteria
Sources: Literature; to: Preprint: https://www.medrxiv.org/content/10.1101/2022.04.20.22274073v1
8 individuals - 2x hom (related) and 6x hets (all de novo except 1x unknown)

7 unrelated since the 2 siblings share similar features:
7/7 ID, 7/7 motor delay, 4/7 epilepsy, 5/7 neonatal hypotonia 2/7 regression, 2/7 ASD excluding 1 with features but did not meet criteria
Sources: Literature
Mendeliome v0.13781 PPFIBP1 Zornitza Stark gene: PPFIBP1 was added
gene: PPFIBP1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: PPFIBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPFIBP1 were set to https://www.medrxiv.org/content/10.1101/2022.04.04.22273309v1
Phenotypes for gene: PPFIBP1 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: PPFIBP1 was set to GREEN
Added comment: 16 individuals from 10 unrelated families reported with moderate to profound developmental delay, often refractory early-onset epilepsy and progressive microcephaly. Drosophila model.
Sources: Expert Review
Mendeliome v0.13778 STX1A Ain Roesley gene: STX1A was added
gene: STX1A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: STX1A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Review for gene: STX1A was set to GREEN
gene: STX1A was marked as current diagnostic
Added comment: Preprint:
8 individuals - 2x hom (related) and 6x hets (all de novo except 1x unknown)

7 unrelated since the 2 siblings share similar features:
7/7 ID, 7/7 motor delay, 4/7 epilepsy, 5/7 neonatal hypotonia 2/7 regression, 2/7 ASD excluding 1 with features but did not meet criteria
Sources: Literature
Mendeliome v0.13777 HYDIN Zornitza Stark Marked gene: HYDIN as ready
Mendeliome v0.13777 HYDIN Zornitza Stark Phenotypes for gene: HYDIN were changed from to Ciliary dyskinesia, primary, 5 (MIM#608647)
Mendeliome v0.13774 HYDIN Zornitza Stark reviewed gene: HYDIN: Rating: GREEN; Mode of pathogenicity: None; Publications: 23022101, 23849777, 28441829, 31116566; Phenotypes: Ciliary dyskinesia, primary, 5 (MIM#608647); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13774 HTRA2 Zornitza Stark Marked gene: HTRA2 as ready
Mendeliome v0.13771 HTR1A Zornitza Stark Marked gene: HTR1A as ready
Mendeliome v0.13767 HSPD1 Zornitza Stark Marked gene: HSPD1 as ready
Mendeliome v0.13767 HSPD1 Zornitza Stark Phenotypes for gene: HSPD1 were changed from to Leukodystrophy, hypomyelinating, 4, MIM# 612233; Spastic paraplegia 13, autosomal dominant, MIM# 605280
Mendeliome v0.13764 HSPD1 Zornitza Stark reviewed gene: HSPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18571143, 27405012, 32532876, 28377887, 27405012, 11898127, 17420924; Phenotypes: Leukodystrophy, hypomyelinating, 4, MIM# 612233, Spastic paraplegia 13, autosomal dominant, MIM# 605280; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13764 HSD3B7 Zornitza Stark Marked gene: HSD3B7 as ready
Mendeliome v0.13761 HSD3B2 Zornitza Stark Marked gene: HSD3B2 as ready
Mendeliome v0.13758 CPN1 Ain Roesley changed review comment from: only 1 probed reported thus far; to: only 1 proband reported thus far
Mendeliome v0.13758 CUBN Ain Roesley Marked gene: CUBN as ready
Mendeliome v0.13758 CUBN Ain Roesley Phenotypes for gene: CUBN were changed from to Imerslund-Grasbeck syndrome 1 MIM#261100 AR; [Proteinuria, chronic benign] MIM#618884
Mendeliome v0.13755 CUBN Ain Roesley reviewed gene: CUBN: Rating: GREEN; Mode of pathogenicity: None; Publications: 31613795, 21903995, 31497480; Phenotypes: Imerslund-Grasbeck syndrome 1 MIM#261100 AR, [Proteinuria, chronic benign] MIM#618884; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13755 CTSF Ain Roesley Marked gene: CTSF as ready
Mendeliome v0.13753 CTSC Ain Roesley Marked gene: CTSC as ready
Mendeliome v0.13750 CTNS Ain Roesley Marked gene: CTNS as ready
Mendeliome v0.13750 CTNS Ain Roesley Phenotypes for gene: CTNS were changed from to Cystinosis, atypical nephropathic MIM#219800; Cystinosis, late-onset juvenile or adolescent nephropathic MIM#219900; Cystinosis, nephropathic MIM#219800; Cystinosis, ocular nonnephropathic MIM#219750
Mendeliome v0.13747 CTNS Ain Roesley reviewed gene: CTNS: Rating: ; Mode of pathogenicity: None; Publications: 20301574, 9537412, 31068690; Phenotypes: Cystinosis, atypical nephropathic MIM#219800, Cystinosis, late-onset juvenile or adolescent nephropathic MIM#219900, Cystinosis, nephropathic MIM#219800, Cystinosis, ocular nonnephropathic MIM#219750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13747 CTNNA1 Ain Roesley Marked gene: CTNNA1 as ready
Mendeliome v0.13747 CTNNA1 Ain Roesley Phenotypes for gene: CTNNA1 were changed from to Macular dystrophy, butterfly-shaped pigmentary, 2, MIM# 608970; Familial exudative vitreoretinopathy MONDO#0019516, CTNNA1-related
Mendeliome v0.13745 CTNNA1 Ain Roesley reviewed gene: CTNNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26691986, 33497368; Phenotypes: Macular dystrophy, butterfly-shaped pigmentary, 2, MIM# 608970, Familial exudative vitreoretinopathy MONDO#0019516, CTNNA1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13745 CTHRC1 Ain Roesley Marked gene: CTHRC1 as ready
Mendeliome v0.13745 CTHRC1 Ain Roesley Phenotypes for gene: CTHRC1 were changed from to Barrett esophagus/esophageal adenocarcinoma MIM#614266
Mendeliome v0.13743 CTHRC1 Ain Roesley reviewed gene: CTHRC1: Rating: RED; Mode of pathogenicity: None; Publications: 21791690; Phenotypes: Barrett esophagus/esophageal adenocarcinoma MIM#614266; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.13743 CSRP3 Ain Roesley Marked gene: CSRP3 as ready
Mendeliome v0.13743 CSRP3 Ain Roesley Phenotypes for gene: CSRP3 were changed from to hypertrophic cardiomyopathy12 MIM#612124; dilated cardiomyopathy 1M MIM#607482
Mendeliome v0.13741 CSRP3 Ain Roesley reviewed gene: CSRP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18505755, 30681346, 12507422, 14567970, 19412328; Phenotypes: hypertrophic cardiomyopathy12 MIM#612124, dilated cardiomyopathy 1M MIM#607482; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13741 CRYGS Ain Roesley Marked gene: CRYGS as ready
Mendeliome v0.13741 CRYGS Ain Roesley Phenotypes for gene: CRYGS were changed from to Cataract 20, multiple types MIM#116100
Mendeliome v0.13739 CRYGS Ain Roesley reviewed gene: CRYGS: Rating: GREEN; Mode of pathogenicity: None; Publications: 34014271, 16141006, 18587492, 19262743; Phenotypes: Cataract 20, multiple types MIM#116100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13739 CRYGB Ain Roesley Marked gene: CRYGB as ready
Mendeliome v0.13739 CRYGB Ain Roesley Phenotypes for gene: CRYGB were changed from to Cataract 39, multiple types, autosomal dominant MIM#615188
Mendeliome v0.13737 CRYGB Ain Roesley reviewed gene: CRYGB: Rating: RED; Mode of pathogenicity: None; Publications: 23288985; Phenotypes: Cataract 39, multiple types, autosomal dominant MIM#615188; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13737 CRYAB Ain Roesley Marked gene: CRYAB as ready
Mendeliome v0.13737 CRYAB Ain Roesley Phenotypes for gene: CRYAB were changed from to Cataract 16, multiple types MIM#613763 AD, AR; Myopathy, myofibrillar, 2 MIM#608810 AD; Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related MIM#613869 AR
Mendeliome v0.13735 CRYAB Ain Roesley reviewed gene: CRYAB: Rating: GREEN; Mode of pathogenicity: None; Publications: 31215171, 21337604, 21130652, 32420686, 33272090; Phenotypes: Cataract 16, multiple types MIM#613763 AD, AR, Myopathy, myofibrillar, 2 MIM#608810 AD, Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related MIM#613869 AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13735 CRX Ain Roesley Marked gene: CRX as ready
Mendeliome v0.13732 CREB1 Ain Roesley Marked gene: CREB1 as ready
Mendeliome v0.13732 CREB1 Ain Roesley Phenotypes for gene: CREB1 were changed from to corpus callosum agenesis; thyroid follicular hypoplasia
Mendeliome v0.13729 CREB1 Ain Roesley reviewed gene: CREB1: Rating: RED; Mode of pathogenicity: None; Publications: 22267179; Phenotypes: corpus callosum agenesis, thyroid follicular hypoplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13729 SLC16A12 Samantha Ayres reviewed gene: SLC16A12: Rating: GREEN; Mode of pathogenicity: None; Publications: 20181839, 21778275, 18304496, 29088427, 34126080; Phenotypes: Cataract 47, juvenile, with microcornea, MIM# 612018; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13729 CRBN Ain Roesley Marked gene: CRBN as ready
Mendeliome v0.13727 CRB1 Ain Roesley Marked gene: CRB1 as ready
Mendeliome v0.13727 CRB1 Ain Roesley Phenotypes for gene: CRB1 were changed from to Leber congenital amaurosis 8 MIM#613835; Pigmented paravenous chorioretinal atrophy MIM#172870; Retinitis pigmentosa-12 MIM#600105
Mendeliome v0.13725 CRB1 Ain Roesley reviewed gene: CRB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30285347, 32922261, 31884620, 15459956; Phenotypes: Leber congenital amaurosis 8 MIM#613835, Pigmented paravenous chorioretinal atrophy MIM#172870, Retinitis pigmentosa-12 MIM#600105; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13725 CPT1A Ain Roesley Marked gene: CPT1A as ready
Mendeliome v0.13723 CPS1 Ain Roesley Marked gene: CPS1 as ready
Mendeliome v0.13722 CPS1 Ain Roesley reviewed gene: CPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8486760, 17310273, 21120950, 31268178; Phenotypes: Carbamoylphosphate synthetase I deficiency MIM#237300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13722 CPOX Ain Roesley Marked gene: CPOX as ready
Mendeliome v0.13722 CPOX Ain Roesley Phenotypes for gene: CPOX were changed from to Coproporphyria, MIM#121300; Harderoporphyria, MIM#121300
Mendeliome v0.13720 CPOX Ain Roesley reviewed gene: CPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 30828546, 28349448, 23582006, 24156084; Phenotypes: Coproporphyria, MIM#121300, Harderoporphyria, MIM#121300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13720 CPN1 Ain Roesley Marked gene: CPN1 as ready
Mendeliome v0.13720 CPN1 Ain Roesley Phenotypes for gene: CPN1 were changed from to Carboxypeptidase N deficiency MIM#212070
Mendeliome v0.13717 CPN1 Ain Roesley reviewed gene: CPN1: Rating: RED; Mode of pathogenicity: None; Publications: 12560874, 7437116; Phenotypes: Carboxypeptidase N deficiency MIM#212070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13717 COMP Ain Roesley Marked gene: COMP as ready
Mendeliome v0.13717 HSD11B1 Zornitza Stark Marked gene: HSD11B1 as ready
Mendeliome v0.13713 HRG Zornitza Stark Marked gene: HRG as ready
Mendeliome v0.13710 HP Zornitza Stark Marked gene: HP as ready
Mendeliome v0.13708 HOXD13 Zornitza Stark Marked gene: HOXD13 as ready
Mendeliome v0.13705 HOXA13 Zornitza Stark Marked gene: HOXA13 as ready
Mendeliome v0.13702 HOXA1 Zornitza Stark Marked gene: HOXA1 as ready
Mendeliome v0.13699 HOXA1 Zornitza Stark changed review comment from: At least 10 families reported.

175-176insG is known as the Saudi Arabian variant, while 76C>T is known as the Native American variant.

Features include:
Conotruncal heart defects, Abnormalities of the internal carotid artery and other cerebral arteries, Abnormal skull base

Biallelic variants in this gene cause a syndrome affecting hindbrain development, with BSAS and ABDS allelic disorders.; to: Biallelic variants in this gene cause a syndrome affecting hindbrain development, with BSAS and ABDS allelic disorders.

At least 10 families reported.

175-176insG is known as the Saudi Arabian variant, while 76C>T is known as the Native American variant.

Features include:
Conotruncal heart defects, Abnormalities of the internal carotid artery and other cerebral arteries, Abnormal skull base
Mendeliome v0.13699 HNRNPA1 Zornitza Stark Marked gene: HNRNPA1 as ready
Mendeliome v0.13696 HNF4A Zornitza Stark Marked gene: HNF4A as ready
Mendeliome v0.13696 HNF4A Zornitza Stark Phenotypes for gene: HNF4A were changed from to Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young, OMIM #616026; MODY, type I, OMIM # 125850
Mendeliome v0.13693 HNF4A Zornitza Stark reviewed gene: HNF4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31875549, 24285859, 22802087, 30005691, 28458902; Phenotypes: Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young, OMIM #616026, MODY, type I, OMIM # 125850; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13693 HNF1A Zornitza Stark Marked gene: HNF1A as ready
Mendeliome v0.13690 HMX1 Zornitza Stark Marked gene: HMX1 as ready
Mendeliome v0.13690 HMX1 Zornitza Stark Phenotypes for gene: HMX1 were changed from to Oculoauricular syndrome, MIM#612109
Mendeliome v0.13687 HMX1 Zornitza Stark changed review comment from: Oculoauricular syndrome (OCACS) is characterized by complex ocular anomalies, including congenital cataract, anterior segment dysgenesis, iris coloboma, and early-onset retinal dystrophy, and dysplastic ears with abnormal external ear cartilage.

At least two families and two animal models. Also evidence that duplication of long-range enhancer causes microbial.; to: Oculoauricular syndrome (OCACS) is characterized by complex ocular anomalies, including congenital cataract, anterior segment dysgenesis, iris coloboma, and early-onset retinal dystrophy, and dysplastic ears with abnormal external ear cartilage.

At least two families and two animal models. Also evidence that duplication of long-range enhancer causes microtia.
Mendeliome v0.13687 HMX1 Zornitza Stark reviewed gene: HMX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18423520, 25574057, 33465110, 32552830, 31691317; Phenotypes: Oculoauricular syndrome, MIM#612109; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13687 COL9A1 Ain Roesley Marked gene: COL9A1 as ready
Mendeliome v0.13683 DUSP6 Krithika Murali changed review comment from: PMID: 23643382 Miraoui et al 2013 - - candidate gene study for genes in the FGFR1 pathway that may be associated with CHH, either as causative genes or disease modifiers. A cohort of 386 CHH individuals and 155 unaffected controls of European descent. A number of affected individuals included in this cohort already had known causative variants in CHH-associated genes. The coding exons and proximal introns (≥15 bp from splice sites) of FGF17, FGF18, IL17RD, DUSP6, SPRY2, SPRY4, and FLRT3 were amplified by PCR and determined by direct sequencing.

Summary of DUSP6 variants identified in this study
c.229 T>A p.(Phe77Ile) - absent gnomAD v2 and v3
c.545C>T p.(Ser182Phe) - 203 hets gnomad v2, 137 hets and 1 hom - v3 - identified in conjunction with FGFR1 variant in this individual
c.566A>G p.Asn189Ser - v2 57 hets, v3 29 hets (another individual identified with this variant and an SPRY4 variant)
c.1037C>T p.Thr346Met - 81 hets v2, 27 hets and 1 hom v3 (identified in conjunction with SPRY4 variant

No segregation information provided.

PMID: 23643382 - Dusp6 null mouse model reportedly has craniofacial defects and hearing defects, but no mention of hypogonadotropic hypogonadism. In 5 unrelated individuals with congenital hypogonadotropic hypogonadism 4 heterozygous missense were identified. In 3 of the probands, the DUSP6 mutation was accompanied by a heterozygous missense mutation in another HH-associated gene. 3 of the 4 variants have subpopulation allele frequencies in gnomAD v2.1 that are higher than expected for a dominant condition: p.Thr346Met (AJ AF 0.002797), p.Ser182Phe (NFE AF 0.001396), p.Asn189Ser (NFE AF 0.0003641). No functional assays were conducted.

PMID: 32389901 - 6 unrelated male Chinese Kallman syndrome cases with 4 DUSP6 missense variants. 2 of 4 variants have East Asian allele frequencies in gnomAD v2.1 that are higher than expected for a dominant condition: p.Pro188Leu (EAS AF 0.001203), p.Arg83Gln (EAS AF 0.001129). No functional assays conducted.; to: PMID: 23643382 Miraoui et al 2013 - - candidate gene study for genes in the FGFR1 pathway that may be associated with CHH, either as causative genes or disease modifiers. A cohort of 386 CHH individuals and 155 unaffected controls of European descent. A number of affected individuals included in this cohort already had known causative variants in CHH-associated genes. The coding exons and proximal introns (≥15 bp from splice sites) of FGF17, FGF18, IL17RD, DUSP6, SPRY2, SPRY4, and FLRT3 were amplified by PCR and determined by direct sequencing.

Summary of DUSP6 variants identified in this study
c.229 T>A p.(Phe77Ile) - absent gnomAD v2 and v3
c.545C>T p.(Ser182Phe) - 203 hets gnomad v2, 137 hets and 1 hom - v3 - identified in conjunction with FGFR1 variant in this individual
c.566A>G p.Asn189Ser - v2 57 hets, v3 29 hets (another individual identified with this variant and an SPRY4 variant)
c.1037C>T p.Thr346Met - 81 hets v2, 27 hets and 1 hom v3 (identified in conjunction with SPRY4 variant

No segregation information provided. Dusp6 null mouse model reportedly has craniofacial defects and hearing defects, but no mention of hypogonadotropic hypogonadism.

PMID: 32389901 - 6 unrelated male Chinese Kallman syndrome cases with 4 DUSP6 missense variants. 2 of 4 variants have East Asian allele frequencies in gnomAD v2.1 that are higher than expected for a dominant condition: p.Pro188Leu (EAS AF 0.001203), p.Arg83Gln (EAS AF 0.001129). No functional assays conducted.
Mendeliome v0.13683 DUSP6 Krithika Murali changed review comment from: 1 study cited by OMIM (Miraoui et al 2013) - heterozygous variants in 5 unrelated individuals with congenital hypogonadotrophic hypogonadism (CHH). 4/5 variants highly prevalent in healthy population and/or in conjunction with variants in other genes either known to be associated with CHH or possibly associated. No additional studies published since this paper.

PMID: 23643382 Miraoui et al 2013 - - candidate gene study for genes in the FGFR1 pathway that may be associated with CHH, either as causative genes or disease modifiers. A cohort of 386 CHH individuals and 155 unaffected controls of European descent. A number of affected individuals included in this cohort already had known causative variants in CHH-associated genes. The coding exons and proximal introns (≥15 bp from splice sites) of FGF17, FGF18, IL17RD, DUSP6, SPRY2, SPRY4, and FLRT3 were amplified by PCR and determined by direct sequencing.

Summary of DUSP6 variants identified in this study
c.229 T>A p.(Phe77Ile) - absent gnomAD v2 and v3
c.545C>T p.(Ser182Phe) - 203 hets gnomad v2, 137 hets and 1 hom - v3 - identified in conjunction with FGFR1 variant in this individual
c.566A>G p.Asn189Ser - v2 57 hets, v3 29 hets (another individual identified with this variant and an SPRY4 variant)
c.1037C>T p.Thr346Met - 81 hets v2, 27 hets and 1 hom v3 (identified in conjunction with SPRY4 variant

No segregation information provided.; to: PMID: 23643382 Miraoui et al 2013 - - candidate gene study for genes in the FGFR1 pathway that may be associated with CHH, either as causative genes or disease modifiers. A cohort of 386 CHH individuals and 155 unaffected controls of European descent. A number of affected individuals included in this cohort already had known causative variants in CHH-associated genes. The coding exons and proximal introns (≥15 bp from splice sites) of FGF17, FGF18, IL17RD, DUSP6, SPRY2, SPRY4, and FLRT3 were amplified by PCR and determined by direct sequencing.

Summary of DUSP6 variants identified in this study
c.229 T>A p.(Phe77Ile) - absent gnomAD v2 and v3
c.545C>T p.(Ser182Phe) - 203 hets gnomad v2, 137 hets and 1 hom - v3 - identified in conjunction with FGFR1 variant in this individual
c.566A>G p.Asn189Ser - v2 57 hets, v3 29 hets (another individual identified with this variant and an SPRY4 variant)
c.1037C>T p.Thr346Met - 81 hets v2, 27 hets and 1 hom v3 (identified in conjunction with SPRY4 variant

No segregation information provided.

PMID: 23643382 - Dusp6 null mouse model reportedly has craniofacial defects and hearing defects, but no mention of hypogonadotropic hypogonadism. In 5 unrelated individuals with congenital hypogonadotropic hypogonadism 4 heterozygous missense were identified. In 3 of the probands, the DUSP6 mutation was accompanied by a heterozygous missense mutation in another HH-associated gene. 3 of the 4 variants have subpopulation allele frequencies in gnomAD v2.1 that are higher than expected for a dominant condition: p.Thr346Met (AJ AF 0.002797), p.Ser182Phe (NFE AF 0.001396), p.Asn189Ser (NFE AF 0.0003641). No functional assays were conducted.

PMID: 32389901 - 6 unrelated male Chinese Kallman syndrome cases with 4 DUSP6 missense variants. 2 of 4 variants have East Asian allele frequencies in gnomAD v2.1 that are higher than expected for a dominant condition: p.Pro188Leu (EAS AF 0.001203), p.Arg83Gln (EAS AF 0.001129). No functional assays conducted.
Mendeliome v0.13683 COQ9 Ain Roesley Marked gene: COQ9 as ready
Mendeliome v0.13683 COQ9 Ain Roesley Phenotypes for gene: COQ9 were changed from to Coenzyme Q10 deficiency, primary, 5, MIM#614654
Mendeliome v0.13681 COQ9 Ain Roesley reviewed gene: COQ9: Rating: GREEN; Mode of pathogenicity: None; Publications: 19375058, 26081641, 23255162, 31821167; Phenotypes: Coenzyme Q10 deficiency, primary, 5, MIM#614654; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13681 COQ8B Ain Roesley Marked gene: COQ8B as ready
Mendeliome v0.13680 COQ8A Ain Roesley Marked gene: COQ8A as ready
Mendeliome v0.13680 COQ8A Ain Roesley Phenotypes for gene: COQ8A were changed from to Coenzyme Q10 deficiency, primary, 4 MIM#612016
Mendeliome v0.13679 COQ8A Ain Roesley reviewed gene: COQ8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32337771; Phenotypes: Coenzyme Q10 deficiency, primary, 4 MIM#612016; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13679 COQ7 Ain Roesley Marked gene: COQ7 as ready
Mendeliome v0.13679 COQ7 Ain Roesley Phenotypes for gene: COQ7 were changed from to Coenzyme Q10 deficiency, primary, 8 MIM#616733
Mendeliome v0.13678 COQ7 Ain Roesley reviewed gene: COQ7: Rating: GREEN; Mode of pathogenicity: None; Publications: 26084283, 31240163, 33215859, 28409910; Phenotypes: Coenzyme Q10 deficiency, primary, 8 MIM#616733; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13678 COQ6 Ain Roesley Marked gene: COQ6 as ready
Mendeliome v0.13678 COQ6 Ain Roesley Phenotypes for gene: COQ6 were changed from to Coenzyme Q10 deficiency, primary, 6 MIM#614650
Mendeliome v0.13677 COQ6 Ain Roesley reviewed gene: COQ6: Rating: GREEN; Mode of pathogenicity: None; Publications: 28125198; Phenotypes: Coenzyme Q10 deficiency, primary, 6 MIM#614650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13675 COL9A2 Ain Roesley Marked gene: COL9A2 as ready
Mendeliome v0.13674 COL6A3 Ain Roesley Marked gene: COL6A3 as ready
Mendeliome v0.13674 COL6A3 Ain Roesley Phenotypes for gene: COL6A3 were changed from to Bethlem myopathy 1 MIM#158810; Dystonia 27 MIM#616411; Ullrich congenital muscular dystrophy 1 MIM#254090
Mendeliome v0.13673 COL6A3 Ain Roesley reviewed gene: COL6A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301676; Phenotypes: Bethlem myopathy 1 MIM#158810, Dystonia 27 MIM#616411, Ullrich congenital muscular dystrophy 1 MIM#254090; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13673 COL6A2 Ain Roesley changed review comment from: GeneReviews PMID:20301676

AD variants typically occur near the N terminal of the triple helical (TH) domain, which contains a critical region of 10 to 15 Gly-X-Y triplets; in-frame exon-skipping variants and glycine substitutions in this region tend to result in more severe phenotypes

AR variants are usually nonsense or fs, or biallelic variants located near the C-terminal end of the TH domain, where they will be excluded from assembly

COL621 accounts for 44-46% of Collagen VI-Related Dystrophies cases; to: GeneReviews PMID:20301676

AD variants typically occur near the N terminal of the triple helical (TH) domain, which contains a critical region of 10 to 15 Gly-X-Y triplets; in-frame exon-skipping variants and glycine substitutions in this region tend to result in more severe phenotypes

AR variants are usually nonsense or fs, or biallelic variants located near the C-terminal end of the TH domain, where they will be excluded from assembly

COL6A2 accounts for 44-46% of Collagen VI-Related Dystrophies cases
Mendeliome v0.13673 COL6A2 Ain Roesley Marked gene: COL6A2 as ready
Mendeliome v0.13673 COL6A2 Ain Roesley Phenotypes for gene: COL6A2 were changed from to Bethlem myopathy 1 MIM#158810; Ullrich congenital muscular dystrophy 1 MIM#254090
Mendeliome v0.13671 COL6A2 Ain Roesley reviewed gene: COL6A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301676; Phenotypes: Bethlem myopathy 1 MIM#158810, Ullrich congenital muscular dystrophy 1 MIM#254090; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13671 COL6A1 Ain Roesley changed review comment from: Well established association

Genereviews PMID:20301676

AD variants typically occur near the N terminal of the triple helical (TH) domain, which contains a critical region of 10 to 15 Gly-X-Y triplets; in-frame exon-skipping variants and glycine substitutions in this region tend to result in more severe phenotypes

AR variants are usually nonsense or fs, or biallelic variants located near the C-terminal end of the TH domain, where they will be excluded from assembly; to: Well established association

Genereviews PMID:20301676

AD variants typically occur near the N terminal of the triple helical (TH) domain, which contains a critical region of 10 to 15 Gly-X-Y triplets; in-frame exon-skipping variants and glycine substitutions in this region tend to result in more severe phenotypes

AR variants are usually nonsense or fs, or biallelic variants located near the C-terminal end of the TH domain, where they will be excluded from assembly

COL6A1 accounts for 35-38% of Collagen VI-Related Dystrophies cases
Mendeliome v0.13671 COL6A1 Ain Roesley Marked gene: COL6A1 as ready
Mendeliome v0.13671 COL6A1 Ain Roesley Phenotypes for gene: COL6A1 were changed from to Bethlem myopathy MIM#158810; Ullrich congenital muscular dystrophy MIM#254090
Mendeliome v0.13669 COL6A1 Ain Roesley changed review comment from: Well established association

Both loss-of-function and dominant negative mechanism has been reported for this gene. Mutations result in a spectrum of disease, ranging from the milder Bethlem myopathy (monoallelic) to the more severe Ullrich congenital muscular dystrophy (biallelic) (PMID: 29277723; 24443028).
Sources: Literature; to: Well established association

Genereviews PMID:20301676

AD variants typically occur near the N terminal of the triple helical (TH) domain, which contains a critical region of 10 to 15 Gly-X-Y triplets; in-frame exon-skipping variants and glycine substitutions in this region tend to result in more severe phenotypes

AR variants are usually nonsense or fs, or biallelic variants located near the C-terminal end of the TH domain, where they will be excluded from assembly
Mendeliome v0.13669 COL6A1 Ain Roesley reviewed gene: COL6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25535305, 15955946, 23738969, 29277723, 24443028; Phenotypes: Bethlem myopathy MIM#158810, Ullrich congenital muscular dystrophy MIM#254090; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13669 COL5A2 Ain Roesley Marked gene: COL5A2 as ready
Mendeliome v0.13668 COL4A4 Ain Roesley Marked gene: COL4A4 as ready
Mendeliome v0.13666 COL4A3 Ain Roesley Marked gene: COL4A3 as ready
Mendeliome v0.13665 COL4A2 Ain Roesley Marked gene: COL4A2 as ready
Mendeliome v0.13664 COL4A1 Ain Roesley Marked gene: COL4A1 as ready
Mendeliome v0.13664 COL4A1 Ain Roesley Phenotypes for gene: COL4A1 were changed from to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps MIM#611773; Brain small vessel disease with or without ocular anomalies MIM#175780; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant MIM#618564
Mendeliome v0.13662 COL4A1 Ain Roesley reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24628545, 25719457, 21625620, 23225343, 23065703, 20818663, 20301768; Phenotypes: Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps MIM#611773, Brain small vessel disease with or without ocular anomalies MIM#175780, Microangiopathy and leukoencephalopathy, pontine, autosomal dominant MIM#618564; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13662 HMOX1 Zornitza Stark Marked gene: HMOX1 as ready
Mendeliome v0.13658 COL27A1 Ain Roesley Marked gene: COL27A1 as ready
Mendeliome v0.13656 COL1A2 Ain Roesley edited their review of gene: COL1A2: Changed phenotypes: Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2, MIM# 619120, Ehlers-Danlos syndrome, arthrochalasia type, 2, MIM# 617821, Ehlers-Danlos syndrome, cardiac valvular type, MIM# 225320, Osteogenesis imperfecta, type II, MIM# 166210, Osteogenesis imperfecta, type III, MIM# 259420, Osteogenesis imperfecta, type IV, MIM# 166220
Mendeliome v0.13656 COL1A2 Ain Roesley Marked gene: COL1A2 as ready
Mendeliome v0.13656 COL1A2 Ain Roesley Phenotypes for gene: COL1A2 were changed from to Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2, MIM# 619120; Ehlers-Danlos syndrome, arthrochalasia type, 2, MIM# 617821; Ehlers-Danlos syndrome, cardiac valvular type, MIM# 225320; Osteogenesis imperfecta, type II, MIM# 166210; Osteogenesis imperfecta, type III, MIM# 259420; Osteogenesis imperfecta, type IV, MIM# 166220
Mendeliome v0.13653 COL1A2 Ain Roesley reviewed gene: COL1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28306229, 32091183, 2993307, 30821104; Phenotypes: Ehlers-Danlos syndrome, arthrochalasia type, 2 MIM#617821, Ehlers-Danlos syndrome, cardiac valvular type MIM#225320; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13653 COL1A1 Ain Roesley changed review comment from: COL1A1 is mostly associated with osteogenesis imperfecta however, substitutions of arginine by cysteine in the triple helical domain) have been reported in individuals w/classic EDS & aneurysm & dissection of large vessels (PMID: 20301422;20301667)

The mild forms are usually caused by haploinsufficiency and result in a reduced amount of normal type I collagen, the severe and lethal forms result from dominant negative variants which produce structural defects in the collagen molecule (PMID:12362985).; to: COL1A1 is mostly associated with osteogenesis imperfecta however, substitutions of arginine by cysteine in the triple helical domain) have been reported in individuals w/classic EDS & aneurysm & dissection of large vessels (PMID: 20301422;20301667)

For skeletal phenotypes:
The mild forms are usually caused by haploinsufficiency and result in a reduced amount of normal type I collagen, the severe and lethal forms result from dominant negative variants which produce structural defects in the collagen molecule (PMID:12362985).
Mendeliome v0.13653 COL1A1 Ain Roesley changed review comment from: COL1A1 is mostly associated with osteogenesis imperfecta however, substitutions of arginine by cysteine in the triple helical domain) have been reported in individuals w/classic EDS & aneurysm & dissection of large vessels (PMID: 20301422;20301667); to: COL1A1 is mostly associated with osteogenesis imperfecta however, substitutions of arginine by cysteine in the triple helical domain) have been reported in individuals w/classic EDS & aneurysm & dissection of large vessels (PMID: 20301422;20301667)

The mild forms are usually caused by haploinsufficiency and result in a reduced amount of normal type I collagen, the severe and lethal forms result from dominant negative variants which produce structural defects in the collagen molecule (PMID:12362985).
Mendeliome v0.13653 COL1A1 Ain Roesley Marked gene: COL1A1 as ready
Mendeliome v0.13653 COL1A1 Ain Roesley Phenotypes for gene: COL1A1 were changed from to Caffey disease MIM#114000; Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 MIM#619115; Ehlers-Danlos syndrome, arthrochalasia type, 1 MIM#130060; Osteogenesis imperfecta, type I MIM#166200; Osteogenesis imperfecta, type II MIM#166210; Osteogenesis imperfecta, type III MIM#259420; Osteogenesis imperfecta, type IV MIM#166220
Mendeliome v0.13652 COL1A1 Ain Roesley reviewed gene: COL1A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301422, 20301667, 30071989, 28981071, 12362985, 28956891; Phenotypes: Caffey disease MIM#114000, Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 MIM#619115, Ehlers-Danlos syndrome, arthrochalasia type, 1 MIM#130060, Osteogenesis imperfecta, type I MIM#166200, Osteogenesis imperfecta, type II MIM#166210, Osteogenesis imperfecta, type III MIM#259420, Osteogenesis imperfecta, type IV MIM#166220; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13652 COL18A1 Ain Roesley Marked gene: COL18A1 as ready
Mendeliome v0.13650 COL17A1 Ain Roesley Marked gene: COL17A1 as ready
Mendeliome v0.13649 COL17A1 Ain Roesley commented on gene: COL17A1: For Epithelial recurrent erosion dystrophy, AD:
Multiple families reported, c.3156C>T is recurrent.

For EB, AR:
well established association (GeneReviews PMID:20301304)
Mendeliome v0.13649 COL12A1 Ain Roesley Marked gene: COL12A1 as ready
Mendeliome v0.13648 COL12A1 Ain Roesley Phenotypes for gene: COL12A1 were changed from to Myopathic EDS; Bethlem myopathy 2 MIM#616471; Ullrich congenital muscular dystrophy 2 MIM#616470
Mendeliome v0.13647 COL12A1 Ain Roesley reviewed gene: COL12A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28306229, 31273343, 24334604; Phenotypes: Myopathic EDS, Bethlem myopathy 2 MIM#616471, Ullrich congenital muscular dystrophy 2 MIM#616470; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13647 COL11A2 Ain Roesley Marked gene: COL11A2 as ready
Mendeliome v0.13645 COG7 Ain Roesley Marked gene: COG7 as ready
Mendeliome v0.13643 COASY Ain Roesley Marked gene: COASY as ready
Mendeliome v0.13643 COASY Ain Roesley Phenotypes for gene: COASY were changed from to Neurodegeneration with brain iron accumulation 6 MIM#615643; Pontocerebellar hypoplasia, type 12 MIM#v618266
Mendeliome v0.13642 COASY Ain Roesley changed review comment from: Green for both NBIA and PCH; to: Green for both NBIA and PCH

only 2 variants reported for PCH - a fs (c.1549_1550delAG) and c.1486-3C>G (Recurrent)
Mendeliome v0.13642 COASY Ain Roesley reviewed gene: COASY: Rating: GREEN; Mode of pathogenicity: None; Publications: 30089828, 28489334, 24360804, 35499143; Phenotypes: Neurodegeneration with brain iron accumulation 6 MIM#615643, Pontocerebellar hypoplasia, type 12 MIM#v618266; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13642 HMBS Zornitza Stark Marked gene: HMBS as ready
Mendeliome v0.13642 HMBS Zornitza Stark Phenotypes for gene: HMBS were changed from to Porphyria, acute intermittent, MIM#176000; Porphyria, acute intermittent, non-erythroid variant, MIM#176000
Mendeliome v0.13640 HMBS Zornitza Stark reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Porphyria, acute intermittent, MIM#176000, Porphyria, acute intermittent, non-erythroid variant, MIM#176000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13640 HK1 Zornitza Stark Marked gene: HK1 as ready
Mendeliome v0.13640 HK1 Zornitza Stark Phenotypes for gene: HK1 were changed from to Neuropathy, hereditary motor and sensory, Russe type , MIM#605285; Haemolytic anaemia due to hexokinase deficiency, MIM# 235700; Neurodevelopmental disorder with visual defects and brain anomalies, MIM# 618547; Retinitis pigmentosa 79, MIM# 617460
Mendeliome v0.13637 HK1 Zornitza Stark changed review comment from: HMSNR is an autosomal recessive progressive complex peripheral neuropathy characterized by onset in the first decade of distal lower limb weakness and muscle atrophy resulting in walking difficulties. Distal impairment of the upper limbs usually occurs later, as does proximal lower limb weakness. There is distal sensory impairment, with pes cavus and areflexia. Laboratory studies suggest that it is a myelinopathy resulting in reduced nerve conduction velocities in the demyelinating range as well as a length-dependent axonopathy.

Founder variant in the Roma, -3818-195G-C, AltT2 EXON in 5'UTR identified in multiple families.

Note gene is associated with other phenotypes.; to: Bi-allelic variants and neuropathy: HMSNR is an autosomal recessive progressive complex peripheral neuropathy characterized by onset in the first decade of distal lower limb weakness and muscle atrophy resulting in walking difficulties. Distal impairment of the upper limbs usually occurs later, as does proximal lower limb weakness. There is distal sensory impairment, with pes cavus and areflexia. Laboratory studies suggest that it is a myelinopathy resulting in reduced nerve conduction velocities in the demyelinating range as well as a length-dependent axonopathy.

Founder variant in the Roma, -3818-195G-C, AltT2 EXON in 5'UTR identified in multiple families.

Note gene is associated with other phenotypes.
Mendeliome v0.13637 HK1 Zornitza Stark edited their review of gene: HK1: Added comment: Mono-allelic variants and ID: PMID30778173, 7 patients from 6 unrelated families with denovo missense variants in the N-terminal half of HK1

Mono-allelic variants and RP: Seven families reported with the same heterozygous missense variant, p.Glu847Lys and RP from different ethnicities. Some supportive evidence. Variant is present in 3 hets in gnomad.

Bi-allelic variants and haemolytic anaemia: more than 10 families reported.; Changed publications: 19536174, 30778173, 25316723, 25190649, 31621442, 32814480, 7655856, 12393545, 33361148, 31119733, 27282571; Changed phenotypes: Neuropathy, hereditary motor and sensory, Russe type , MIM#605285, Haemolytic anaemia due to hexokinase deficiency, MIM# 235700, Neurodevelopmental disorder with visual defects and brain anomalies, MIM# 618547, Retinitis pigmentosa 79, MIM# 617460; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13636 RPE65 Zornitza Stark Marked gene: RPE65 as ready
Mendeliome v0.13633 SLC24A1 Zornitza Stark Marked gene: SLC24A1 as ready
Mendeliome v0.13633 SLC24A1 Zornitza Stark Phenotypes for gene: SLC24A1 were changed from to Night blindness, congenital stationary (complete), 1D, autosomal recessive, MIM#613830, MONDO:0013450
Mendeliome v0.13630 SLC25A1 Zornitza Stark Marked gene: SLC25A1 as ready
Mendeliome v0.13630 SLC25A1 Zornitza Stark Phenotypes for gene: SLC25A1 were changed from to Combined D-2- and L-2-hydroxyglutaric aciduria MIM#: 615182, MONDO:0014072; Myasthenic syndrome, congenital, 23, presynaptic, MIM#618197, MONDO:0032596
Mendeliome v0.13627 RRAS Zornitza Stark Marked gene: RRAS as ready
Mendeliome v0.13623 SLC11A1 Zornitza Stark Marked gene: SLC11A1 as ready
Mendeliome v0.13619 SIL1 Zornitza Stark Marked gene: SIL1 as ready
Mendeliome v0.13619 SIL1 Zornitza Stark Phenotypes for gene: SIL1 were changed from to Marinesco-Sjogren syndrome, MIM#248800; MONDO#0009567
Mendeliome v0.13616 SLC24A1 Manny Jacobs reviewed gene: SLC24A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35486108, 35446361, 20850105, 26822852; Phenotypes: Night blindness, congenital stationary (complete), 1D, autosomal recessive, MIM#613830, MONDO:0013450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13616 SIK1 Zornitza Stark Marked gene: SIK1 as ready
Mendeliome v0.13613 SLC25A1 Manny Jacobs reviewed gene: SLC25A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26870663, 31527857, 31808147, 23561848, 23393310; Phenotypes: Combined D-2- and L-2-hydroxyglutaric aciduria MIM#: 615182, MONDO:0014072, Myasthenic syndrome, congenital, 23, presynaptic, MIM#618197, MONDO:0032596; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13613 RRAS Belinda Chong changed review comment from: Catts et al (2021) identified a 7-year-old boy with a history of craniosynostosis, congenital heart defect, and mild dysmorphic features who was incidentally found to have pediatric MDS with monosomy 7 in the context of previously unrecognized germline RRAS mutation. A heterozygous c.116_118dup (NM_006270.5) variant resulting in p.G39dup was identified and excluded in an unaffected sibling, and both parents.

Two individuals reported. One de novo variant, the inheritance of the other variant uncertain. Some supportive functional data. Rated as LIMITED by ClinGen (reviewed 27/04/2018).; to: Catts et al (2021) identified a 7-year-old boy with a history of craniosynostosis, congenital heart defect, and mild dysmorphic features who was incidentally found to have pediatric MDS with monosomy 7 in the context of previously unrecognized germline RRAS mutation. A heterozygous c.116_118dup (NM_006270.5) variant resulting in p.G39dup was identified and excluded in an unaffected sibling, and both parents.

Two individuals reported. One de novo variant, the inheritance of the other variant uncertain. Some supportive functional data. Rated as LIMITED by ClinGen (reviewed 27/04/2018).
Mendeliome v0.13613 HIBCH Zornitza Stark Marked gene: HIBCH as ready
Mendeliome v0.13610 HGF Zornitza Stark Marked gene: HGF as ready
Mendeliome v0.13607 HGD Zornitza Stark Marked gene: HGD as ready
Mendeliome v0.13604 HFE Zornitza Stark Marked gene: HFE as ready
Mendeliome v0.13602 HESX1 Zornitza Stark Marked gene: HESX1 as ready
Mendeliome v0.13602 HESX1 Zornitza Stark Phenotypes for gene: HESX1 were changed from to Growth hormone deficiency with pituitary anomalies, MIM#182230; Pituitary hormone deficiency, combined, 5, MIM#182230; Septooptic dysplasia, MIM#182230
Mendeliome v0.13600 HESX1 Zornitza Stark reviewed gene: HESX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Growth hormone deficiency with pituitary anomalies, MIM#182230, Pituitary hormone deficiency, combined, 5, MIM#182230, Septooptic dysplasia, MIM#182230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13599 HERC1 Zornitza Stark Marked gene: HERC1 as ready
Mendeliome v0.13599 HERC1 Zornitza Stark Phenotypes for gene: HERC1 were changed from to Macrocephaly, dysmorphic facies, and psychomotor retardation, MIM# 617011
Mendeliome v0.13596 HERC1 Zornitza Stark reviewed gene: HERC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28323226, 27108999, 26153217, 26138117, 20041218; Phenotypes: Macrocephaly, dysmorphic facies, and psychomotor retardation, MIM# 617011; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13596 HEPACAM Zornitza Stark Marked gene: HEPACAM as ready
Mendeliome v0.13596 HEPACAM Zornitza Stark Phenotypes for gene: HEPACAM were changed from to Megalencephalic leukoencephalopathy with subcortical cysts 2A, MIM# 613925; Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation, MIM# 613926
Mendeliome v0.13593 HEPACAM Zornitza Stark reviewed gene: HEPACAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 21419380, 21419380; Phenotypes: Megalencephalic leukoencephalopathy with subcortical cysts 2A, MIM# 613925, Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation, MIM# 613926; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.13593 LIPT2 Alison Yeung Marked gene: LIPT2 as ready
Mendeliome v0.13592 SIL1 Samantha Ayres reviewed gene: SIL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24176978, 16282977, 20301371; Phenotypes: Marinesco-Sjogren syndrome, MIM#248800, MONDO#0009567; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13592 DNASE2 Zornitza Stark Phenotypes for gene: DNASE2 were changed from Auto-inflammatory disorder; splenomegaly; glomerulonephritis; liver fibrosis; arthritis; HLH to Autoinflammatory-pancytopaenia syndrome, MIM# 619858
Mendeliome v0.13589 LIPH Alison Yeung Marked gene: LIPH as ready
Mendeliome v0.13587 LIPC Alison Yeung Marked gene: LIPC as ready
Mendeliome v0.13585 LIPC Alison Yeung Added comment: Comment on mode of inheritance: PMID: 1671786, 12777476, 1883393, 22798447 - 7 cases from 3 unrelated families with hepatic lipase deficiency and biallelic variants.
PMID: 26423094 - null mouse had dyslipidemia on a high cholesterol and fat diet
PMID: 23219720, 22464213 - 2 cases with hyperalphalipoproteinemia and heterozygous variants, with supporting in vitro funcitonal assays
Mendeliome v0.13583 LINS1 Alison Yeung Marked gene: LINS1 as ready
Mendeliome v0.13581 HCRT Zornitza Stark Marked gene: HCRT as ready
Mendeliome v0.13581 HCRT Zornitza Stark Phenotypes for gene: HCRT were changed from to Narcolepsy 1 , MIM# 161400
Mendeliome v0.13577 LIM2 Alison Yeung Marked gene: LIM2 as ready
Mendeliome v0.13577 HCRT Zornitza Stark reviewed gene: HCRT: Rating: RED; Mode of pathogenicity: None; Publications: 10973318, 11148249, 11723284; Phenotypes: Narcolepsy 1 , MIM# 161400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13577 LIM2 Alison Yeung Phenotypes for gene: LIM2 were changed from to Cataract 19, multiple types, MIM# 615277
Mendeliome v0.13574 LIM2 Alison Yeung reviewed gene: LIM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27814360, 11917274, 18596884, 33708862, 32202185, 21617753; Phenotypes: Cataract 19, multiple types, MIM# 615277; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13574 HCN1 Zornitza Stark Marked gene: HCN1 as ready
Mendeliome v0.13571 HCCS Zornitza Stark Marked gene: HCCS as ready
Mendeliome v0.13571 HCCS Zornitza Stark Phenotypes for gene: HCCS were changed from to Linear skin defects with multiple congenital anomalies 1, MIM# 309801
Mendeliome v0.13568 HCCS Zornitza Stark reviewed gene: HCCS: Rating: GREEN; Mode of pathogenicity: None; Publications: 17033964, 30068298, 24735900; Phenotypes: Linear skin defects with multiple congenital anomalies 1, MIM# 309801; 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 v0.13568 HBA2 Zornitza Stark Marked gene: HBA2 as ready
Mendeliome v0.13565 HBA1 Zornitza Stark Marked gene: HBA1 as ready
Mendeliome v0.13563 HAO1 Zornitza Stark Marked gene: HAO1 as ready
Mendeliome v0.13562 HAMP Zornitza Stark Marked gene: HAMP as ready
Mendeliome v0.13559 HADHB Zornitza Stark Marked gene: HADHB as ready
Mendeliome v0.13556 HADHA Zornitza Stark Marked gene: HADHA as ready
Mendeliome v0.13554 HADH Zornitza Stark Marked gene: HADH as ready
Mendeliome v0.13552 HACD1 Zornitza Stark Marked gene: HACD1 as ready
Mendeliome v0.13549 HAAO Zornitza Stark Marked gene: HAAO as ready
Mendeliome v0.13549 HAAO Zornitza Stark Phenotypes for gene: HAAO were changed from to Vertebral, cardiac, renal, and limb defects syndrome 1 MIM#617660; NAD deficiency
Mendeliome v0.13546 H6PD Zornitza Stark Marked gene: H6PD as ready
Mendeliome v0.13543 BUD23 Zornitza Stark Marked gene: BUD23 as ready
Mendeliome v0.13542 BTNL2 Zornitza Stark Marked gene: BTNL2 as ready
Mendeliome v0.13542 BTNL2 Zornitza Stark Phenotypes for gene: BTNL2 were changed from to {Sarcoidosis, susceptibility to, 2} 612387
Mendeliome v0.13539 BTNL2 Zornitza Stark reviewed gene: BTNL2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Sarcoidosis, susceptibility to, 2} 612387; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13539 BTK Zornitza Stark Marked gene: BTK as ready
Mendeliome v0.13536 BRIP1 Zornitza Stark Marked gene: BRIP1 as ready
Mendeliome v0.13533 BRAF Zornitza Stark Marked gene: BRAF as ready
Mendeliome v0.13533 BRAF Zornitza Stark Phenotypes for gene: BRAF were changed from to Noonan syndrome 7, MIM# 613706; Cardiofaciocutaneous syndrome, MIM# 115150
Mendeliome v0.13531 BRAF Zornitza Stark Mode of pathogenicity for gene: BRAF was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v0.13529 BRAF Zornitza Stark reviewed gene: BRAF: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 19206169, 18042262; Phenotypes: Noonan syndrome 7, MIM# 613706, Cardiofaciocutaneous syndrome, MIM# 115150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13529 BPGM Zornitza Stark Marked gene: BPGM as ready
Mendeliome v0.13525 BMPR1A Zornitza Stark Marked gene: BMPR1A as ready
Mendeliome v0.13522 BLVRA Zornitza Stark Marked gene: BLVRA as ready
Mendeliome v0.13518 BLK Zornitza Stark Marked gene: BLK as ready
Mendeliome v0.13518 BLK Zornitza Stark Phenotypes for gene: BLK were changed from to Common variable immunodeficiency, MONDO:0015517
Mendeliome v0.13514 BLK Zornitza Stark reviewed gene: BLK: Rating: AMBER; Mode of pathogenicity: None; Publications: 25926555; Phenotypes: Common variable immunodeficiency, MONDO:0015517; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13514 BHLHE41 Zornitza Stark Marked gene: BHLHE41 as ready
Mendeliome v0.13511 BFSP1 Zornitza Stark Marked gene: BFSP1 as ready
Mendeliome v0.13511 BFSP1 Zornitza Stark Phenotypes for gene: BFSP1 were changed from to Cataract 33, multiple types, MIM# 611391
Mendeliome v0.13508 BFSP1 Zornitza Stark reviewed gene: BFSP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17225135, 26694549, 24379646, 28450710, 31842807, 26694549; Phenotypes: Cataract 33, multiple types, MIM# 611391; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13508 BCL2 Zornitza Stark Marked gene: BCL2 as ready
Mendeliome v0.13507 BCKDK Zornitza Stark Marked gene: BCKDK as ready
Mendeliome v0.13504 BCL10 Zornitza Stark Marked gene: BCL10 as ready
Mendeliome v0.13501 BCHE Zornitza Stark Marked gene: BCHE as ready
Mendeliome v0.13499 BBS2 Zornitza Stark Marked gene: BBS2 as ready
Mendeliome v0.13499 BBS2 Zornitza Stark Phenotypes for gene: BBS2 were changed from to Bardet-Biedl syndrome 2, MIM# 615981; Retinitis pigmentosa 74, MIM# 616562
Mendeliome v0.13496 BBS12 Zornitza Stark Marked gene: BBS12 as ready
Mendeliome v0.13496 BBS12 Zornitza Stark Phenotypes for gene: BBS12 were changed from to Bardet-Biedl syndrome 12, MIM# 615989
Mendeliome v0.13493 BBS10 Zornitza Stark Marked gene: BBS10 as ready
Mendeliome v0.13493 BBS10 Zornitza Stark Phenotypes for gene: BBS10 were changed from to Bardet-Biedl syndrome 10, MIM# 615987
Mendeliome v0.13490 BBS1 Zornitza Stark Marked gene: BBS1 as ready
Mendeliome v0.13490 BBS1 Zornitza Stark Phenotypes for gene: BBS1 were changed from to Bardet-Biedl syndrome 1, MIM# 209900
Mendeliome v0.13487 BAG3 Zornitza Stark Marked gene: BAG3 as ready
Mendeliome v0.13487 BAG3 Zornitza Stark Phenotypes for gene: BAG3 were changed from to Cardiomyopathy, dilated, 1HH, MIM# 613881; Myopathy, myofibrillar, 6, MIM# 612954
Mendeliome v0.13484 BAG3 Zornitza Stark reviewed gene: BAG3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21353195, 25008357, 25448463, 24623017, 27391596, 28211974, 30442290, 31983221, 28737513, 29323723, 33947203, 25208129, 32453099, 22734908; Phenotypes: Cardiomyopathy, dilated, 1HH, MIM# 613881, Myopathy, myofibrillar, 6, MIM# 612954; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13484 BACH2 Zornitza Stark Marked gene: BACH2 as ready
Mendeliome v0.13481 B4GALT1 Zornitza Stark Marked gene: B4GALT1 as ready
Mendeliome v0.13478 B4GALT1 Zornitza Stark changed review comment from: Intellectual disability is part of CDG, although non-neurological forms of this CDG have been described.
Sources: Expert list; to: At least 3 unrelated families.
Sources: Expert list
Mendeliome v0.13478 B4GALNT1 Zornitza Stark Marked gene: B4GALNT1 as ready
Mendeliome v0.13478 B4GALNT1 Zornitza Stark Phenotypes for gene: B4GALNT1 were changed from to Spastic paraplegia 26, autosomal recessive (MIM #609195)
Mendeliome v0.13474 B4GALNT1 Zornitza Stark reviewed gene: B4GALNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23746551 24103911; Phenotypes: Spastic paraplegia 26, autosomal recessive (MIM #609195); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13474 B3GLCT Zornitza Stark Marked gene: B3GLCT as ready
Mendeliome v0.13471 APOA5 Zornitza Stark Marked gene: APOA5 as ready
Mendeliome v0.13471 AP1S2 Zornitza Stark Phenotypes for gene: AP1S2 were changed from Mental retardation, X-linked syndromic 5, MIM#304340 to Pettigrew syndrome, MIM# 304340
Mendeliome v0.13469 APCDD1 Zornitza Stark Marked gene: APCDD1 as ready
Mendeliome v0.13466 ANO10 Zornitza Stark Phenotypes for gene: ANO10 were changed from Spinocerebellar ataxia, autosomal recessive 10 MIM#613728 to Spinocerebellar ataxia, autosomal recessive 10, MIM#613728
Mendeliome v0.13464 ANO10 Zornitza Stark reviewed gene: ANO10: Rating: GREEN; Mode of pathogenicity: None; Publications: 21092923, 25182700; Phenotypes: Spinocerebellar ataxia, autosomal recessive 10, MIM#613728; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13464 PHOX2B Zornitza Stark Marked gene: PHOX2B as ready
Mendeliome v0.13461 PEX26 Zornitza Stark Marked gene: PEX26 as ready
Mendeliome v0.13458 PEX2 Zornitza Stark Marked gene: PEX2 as ready
Mendeliome v0.13455 PEX19 Zornitza Stark Marked gene: PEX19 as ready
Mendeliome v0.13454 PEX16 Zornitza Stark Marked gene: PEX16 as ready
Mendeliome v0.13451 PEX14 Zornitza Stark Marked gene: PEX14 as ready
Mendeliome v0.13448 PEX13 Zornitza Stark Marked gene: PEX13 as ready
Mendeliome v0.13446 PEX12 Zornitza Stark Marked gene: PEX12 as ready
Mendeliome v0.13443 ENTPD1 Zornitza Stark commented on gene: ENTPD1: PMID 35471564: 27 individuals from 17 families published, expanding the phenotype to a complex neurodevelopmental disorder characterised by ID, white matter abnormalities and spastic paraplegia.
Mendeliome v0.13443 RSPH1 Zornitza Stark Marked gene: RSPH1 as ready
Mendeliome v0.13443 RSPH1 Zornitza Stark Phenotypes for gene: RSPH1 were changed from to Ciliary dyskinesia, primary, 24 MIM#615481
Mendeliome v0.13437 APOA2 Elena Savva Marked gene: APOA2 as ready
Mendeliome v0.13435 APOA1 Elena Savva Marked gene: APOA1 as ready
Mendeliome v0.13435 APOA1 Elena Savva Phenotypes for gene: APOA1 were changed from to Amyloidosis, 3 or more types MIM#105200; Hypoalphalipoproteinemia, primary, 2 MIM#618463; Hypoalphalipoproteinemia, primary, 2, intermediate MIM#619836
Mendeliome v0.13434 APOA1 Elena Savva reviewed gene: APOA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Amyloidosis, 3 or more types MIM#105200, Hypoalphalipoproteinemia, primary, 2 MIM#618463, Hypoalphalipoproteinemia, primary, 2, intermediate MIM#619836; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13434 AP1S2 Elena Savva Marked gene: AP1S2 as ready
Mendeliome v0.13434 AP1S2 Elena Savva Phenotypes for gene: AP1S2 were changed from to Mental retardation, X-linked syndromic 5, MIM#304340
Mendeliome v0.13432 ANO10 Elena Savva Phenotypes for gene: ANO10 were changed from Spinocerebellar ataxia, autosomal recessive 10 MIM#613728 to Spinocerebellar ataxia, autosomal recessive 10 MIM#613728
Mendeliome v0.13430 ANO10 Elena Savva Phenotypes for gene: ANO10 were changed from to Spinocerebellar ataxia, autosomal recessive 10 MIM#613728
Mendeliome v0.13430 ANO10 Elena Savva Marked gene: ANO10 as ready
Mendeliome v0.13429 DIO1 Zornitza Stark Marked gene: DIO1 as ready
Mendeliome v0.13422 TUBA8 Zornitza Stark changed review comment from: Two families reported initially (PMID 19896110). However, note that mouse model does not have a brain phenotype and WES in the original families identified homozygous, previously reported as pathogenic, LoF variant in SNAP29, which is much more likely to be causative (28388629).; to: Bi-allelic variants and cortical dysplasia: Two families reported initially (PMID 19896110). However, note that mouse model does not have a brain phenotype and WES in the original families identified homozygous, previously reported as pathogenic, LoF variant in SNAP29, which is much more likely to be causative (28388629).
Mendeliome v0.13422 TUBA8 Zornitza Stark edited their review of gene: TUBA8: Added comment: Mono-allelic variants and macrothrombocytopaenia: 6 unrelated individuals with missense variants found in a large cohort of blood donors, some functional data. Individuals were generally asymptomatic.; Changed rating: AMBER; Changed publications: 34704371; Changed phenotypes: Macrothrombocytopaenia, isolated, 2, autosomal dominant, MIM# 619840; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13422 NRCAM Zornitza Stark Phenotypes for gene: NRCAM were changed from neurodevelopmental disorder, NRCAM-related, MONDO:0700092 to Neurodevelopmental disorder with neuromuscular and skeletal abnormalities, MIM# 619833
Mendeliome v0.13421 NRCAM Zornitza Stark reviewed gene: NRCAM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with neuromuscular and skeletal abnormalities, MIM# 619833; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13420 PEX3 Zornitza Stark Marked gene: PEX3 as ready
Mendeliome v0.13417 PEX5 Zornitza Stark Marked gene: PEX5 as ready
Mendeliome v0.13414 PEX7 Zornitza Stark Marked gene: PEX7 as ready
Mendeliome v0.13411 PFKM Zornitza Stark Marked gene: PFKM as ready
Mendeliome v0.13408 PGAM2 Zornitza Stark Marked gene: PGAM2 as ready
Mendeliome v0.13405 PHF11 Zornitza Stark Marked gene: PHF11 as ready
Mendeliome v0.13404 PHIP Zornitza Stark Marked gene: PHIP as ready
Mendeliome v0.13401 PHIP Zornitza Stark changed review comment from: Chung-Jansen syndrome (CHUJANS) is characterized by global developmental delay apparent from infancy, impaired intellectual development or learning difficulties, behavioral abnormalities, dysmorphic features, and obesity.

More than 20 individuals reported.; to: Chung-Jansen syndrome (CHUJANS) is characterized by global developmental delay apparent from infancy, impaired intellectual development or learning difficulties, behavioural abnormalities, dysmorphic features, and obesity.

More than 20 individuals reported.
Mendeliome v0.13401 PHKA2 Zornitza Stark Marked gene: PHKA2 as ready
Mendeliome v0.13398 PIK3CA Zornitza Stark Marked gene: PIK3CA as ready
Mendeliome v0.13398 PIK3CA Zornitza Stark Phenotypes for gene: PIK3CA were changed from to Megalencephaly-capillary malformation (MCAP) syndrome , MIM#602501; CLAPO syndrome, somatic, MIM# 613089; CLOVE syndrome, somatic, MIM# 612918
Mendeliome v0.13396 PIK3CA Zornitza Stark reviewed gene: PIK3CA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalencephaly-capillary malformation (MCAP) syndrome , MIM#602501, CLAPO syndrome, somatic, MIM# 613089, CLOVE syndrome, somatic, MIM# 612918; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13396 PISD Zornitza Stark Phenotypes for gene: PISD were changed from to Liberfarb syndrome, MIM# 618889; Intellectual disability; cataracts; retinal degeneration; microcephaly; deafness; short stature; white matter abnormalities
Mendeliome v0.13393 PISD Zornitza Stark edited their review of gene: PISD: Changed phenotypes: Liberfarb syndrome, MIM# 618889, Intellectual disability, cataracts, retinal degeneration, microcephaly, deafness, short stature, white matter abnormalities
Mendeliome v0.13393 PHYH Zornitza Stark Marked gene: PHYH as ready
Mendeliome v0.13390 PHYH Zornitza Stark edited their review of gene: PHYH: Added comment: Refsum disease is an autosomal recessive inborn error of lipid metabolism classically characterized by a tetrad of clinical abnormalities: retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and elevated protein levels in the cerebrospinal fluid (CSF) without an increase in the number of cells.

Well established gene-disease association.; Changed publications: 9326939, 9326940
Mendeliome v0.13390 PIEZO2 Zornitza Stark Marked gene: PIEZO2 as ready
Mendeliome v0.13390 PIEZO2 Zornitza Stark Phenotypes for gene: PIEZO2 were changed from to Marden-Walker syndrome (MIM#248700); Arthrogryposis, distal, type 3 (MIM#114300); Arthrogryposis, distal, type 5 (MIM#108145); Arthrogryposis, distal, with impaired proprioception and touch, MIM# 617146
Mendeliome v0.13387 PIEZO2 Zornitza Stark changed review comment from: Bi-allelic variants: more than 5 unrelated families reported.

Mono-allelic variants:
DA5, more than 20 families reported.
DA3, more than 10 families reported, R2686H is recurrent.; to: Bi-allelic variants: more than 5 unrelated families reported.

Mono-allelic variants:
DA5, more than 20 families reported.
DA3, more than 10 families reported, R2686H is recurrent.
Marden-Walker: 2 families reported.
Mendeliome v0.13387 PIEZO2 Zornitza Stark edited their review of gene: PIEZO2: Changed phenotypes: Marden-Walker syndrome (MIM#248700), Arthrogryposis, distal, type 3 (MIM#114300), Arthrogryposis, distal, type 5 (MIM#108145), Arthrogryposis, distal, with impaired proprioception and touch, MIM# 617146
Mendeliome v0.13387 PIEZO2 Zornitza Stark changed review comment from: Bi-allelic variants: more than 5 unrelated families reported.

Mono-allelic variants:
DA5, more than 20 families reported.; to: Bi-allelic variants: more than 5 unrelated families reported.

Mono-allelic variants:
DA5, more than 20 families reported.
DA3, more than 10 families reported, R2686H is recurrent.
Mendeliome v0.13387 PIEZO2 Zornitza Stark changed review comment from: Bi-allelic variants: more than 5 unrelated families reported.

Mono-allelic variants:
DA3, more than 20 families reported.; to: Bi-allelic variants: more than 5 unrelated families reported.

Mono-allelic variants:
DA5, more than 20 families reported.
Mendeliome v0.13387 PIEZO2 Zornitza Stark changed review comment from: Bi-allelic variants: more than 5 unrelated families reported.; to: Bi-allelic variants: more than 5 unrelated families reported.

Mono-allelic variants:
DA3, more than 20 families reported.
Mendeliome v0.13387 RSPH1 Belinda Chong reviewed gene: RSPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23993197; Phenotypes: Ciliary dyskinesia, primary, 24 MIM#615481; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13387 PIEZO2 Zornitza Stark reviewed gene: PIEZO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27653382, 27607563, 27843126, 27974811; Phenotypes: Marden-Walker syndrome (MIM#248700), Arthrogryposis, distal, type 3 (MIM#114300), Arthrogryposis, distal, type 5 (MIM#108145); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13387 BSCL2 Zornitza Stark Marked gene: BSCL2 as ready
Mendeliome v0.13387 BSCL2 Zornitza Stark Phenotypes for gene: BSCL2 were changed from to Neuropathy, distal hereditary motor, type VC, MIM# 619112; Encephalopathy, progressive, with or without lipodystrophy, MIM#615924; Lipodystrophy, congenital generalized, type 2, MIM# 269700; Silver spastic paraplegia syndrome, MIM# 270685; Developmental and epileptic encephalopathy, BSCL2-related, dominant, MONDO:0100062
Mendeliome v0.13384 BSCL2 Zornitza Stark edited their review of gene: BSCL2: Added comment: Multiple families reported with bi-allelic variants and isolated or syndromic lipodystrophy.

Mono-allelic variants and DEE: Two families reported with de novo variants in PMIDs 31369919 and 35290466. We are aware of further three individuals identified as a result of clinical testing, so a total of 4 with a change at position p.Pro149; Changed publications: 14981520, 15732094, 11479539, 15181077, 15126564, 23564749, 31369919, 35290466
Mendeliome v0.13384 BSCL2 Zornitza Stark edited their review of gene: BSCL2: Changed phenotypes: Neuropathy, distal hereditary motor, type VC, MIM# 619112, Encephalopathy, progressive, with or without lipodystrophy, MIM#615924, Lipodystrophy, congenital generalized, type 2, MIM# 269700, Silver spastic paraplegia syndrome, MIM# 270685, Developmental and epileptic encephalopathy, BSCL2-related, dominant, MONDO:0100062; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13384 CNNM2 Ain Roesley Marked gene: CNNM2 as ready
Mendeliome v0.13384 CNNM2 Ain Roesley Phenotypes for gene: CNNM2 were changed from to Hypomagnesemia 6, renal MIM#613882; Hypomagnesemia, seizures, and mental retardation MIM#616418
Mendeliome v0.13382 CNNM2 Ain Roesley reviewed gene: CNNM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34604137, 35170241; Phenotypes: Hypomagnesemia 6, renal MIM#613882, Hypomagnesemia, seizures, and mental retardation MIM#616418; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13382 PIGC Zornitza Stark Marked gene: PIGC as ready
Mendeliome v0.13379 CNGB1 Ain Roesley Marked gene: CNGB1 as ready
Mendeliome v0.13377 CNGA1 Ain Roesley Marked gene: CNGA1 as ready
Mendeliome v0.13375 CLN8 Ain Roesley Marked gene: CLN8 as ready
Mendeliome v0.13375 CLN8 Ain Roesley Phenotypes for gene: CLN8 were changed from to Ceroid lipofuscinosis, neuronal, 8, MIM# 600143; Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, MIM# 610003
Mendeliome v0.13374 CLN8 Ain Roesley reviewed gene: CLN8: Rating: GREEN; Mode of pathogenicity: None; Publications: 10508524, 15024724, 16570191; Phenotypes: Ceroid lipofuscinosis, neuronal, 8, MIM# 600143, Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, MIM# 610003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13374 CLN6 Ain Roesley Marked gene: CLN6 as ready
Mendeliome v0.13372 CLEC7A Ain Roesley Marked gene: CLEC7A as ready
Mendeliome v0.13370 PIGW Zornitza Stark Marked gene: PIGW as ready
Mendeliome v0.13367 PIK3R2 Zornitza Stark Marked gene: PIK3R2 as ready
Mendeliome v0.13364 PITX2 Zornitza Stark Marked gene: PITX2 as ready
Mendeliome v0.13361 PITX3 Zornitza Stark Marked gene: PITX3 as ready
Mendeliome v0.13361 PITX3 Zornitza Stark Phenotypes for gene: PITX3 were changed from Anterior segment dysgenesis 1, multiple subtypes, MIM# 107250; Cataract 11, multiple types, MIM# 610623; Microphthalmia to Anterior segment dysgenesis 1, multiple subtypes, MIM# 107250; Cataract 11, multiple types, MIM# 610623; Microphthalmia MONDO:0021129
Mendeliome v0.13360 PITX3 Zornitza Stark Phenotypes for gene: PITX3 were changed from to Anterior segment dysgenesis 1, multiple subtypes, MIM# 107250; Cataract 11, multiple types, MIM# 610623; Microphthalmia
Mendeliome v0.13357 PITX3 Zornitza Stark reviewed gene: PITX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29405783; Phenotypes: Anterior segment dysgenesis 1, multiple subtypes, MIM# 107250, Cataract 11, multiple types, MIM# 610623, Microphthalmia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13357 CLDN19 Zornitza Stark Phenotypes for gene: CLDN19 were changed from Hypomagnesemia 5, renal, with ocular involvement, MIM#248190 to Hypomagnesaemia 5, renal, with ocular involvement, MIM#248190
Mendeliome v0.13356 PEX11B Zornitza Stark Marked gene: PEX11B as ready
Mendeliome v0.13356 PEX11B Zornitza Stark Added comment: Comment when marking as ready: Two published families and one International.
Mendeliome v0.13353 PER2 Zornitza Stark Marked gene: PER2 as ready
Mendeliome v0.13349 PDZD7 Zornitza Stark Marked gene: PDZD7 as ready
Mendeliome v0.13346 PDYN Zornitza Stark Marked gene: PDYN as ready
Mendeliome v0.13346 PDYN Zornitza Stark Added comment: Comment when marking as ready: The presence of some of these variants in the population is concerning. However, functional data also supports gene-disease association.
Mendeliome v0.13346 PDYN Zornitza Stark Phenotypes for gene: PDYN were changed from to Spinocerebellar ataxia 23 - MIM#610245
Mendeliome v0.13343 PDGFRA Zornitza Stark Marked gene: PDGFRA as ready
Mendeliome v0.13340 RSPH3 Zornitza Stark Marked gene: RSPH3 as ready
Mendeliome v0.13340 RSPH3 Zornitza Stark Phenotypes for gene: RSPH3 were changed from to Ciliary dyskinesia, primary, 32 MIM#616481
Mendeliome v0.13337 RSPH4A Zornitza Stark Marked gene: RSPH4A as ready
Mendeliome v0.13337 RSPH4A Zornitza Stark Phenotypes for gene: RSPH4A were changed from to Ciliary dyskinesia, primary, 11, OMIM#612649
Mendeliome v0.13334 RSPH9 Zornitza Stark Marked gene: RSPH9 as ready
Mendeliome v0.13334 RSPH9 Zornitza Stark Phenotypes for gene: RSPH9 were changed from to Ciliary dyskinesia, primary, 12, MIM#612650
Mendeliome v0.13331 BVES Zornitza Stark Marked gene: BVES as ready
Mendeliome v0.13331 BVES Zornitza Stark Phenotypes for gene: BVES were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 25, MIM# 616812
Mendeliome v0.13327 BVES Zornitza Stark changed review comment from: PMID: 26642364 - 1 family (3 affecteds) with cardiac arrhythmia and limb-girdle muscular dystrophy. Supported by functional studies. The proband showed lower limb girdle weakness at ~40 years old with muscle biopsy proving dystrophic changes. His 2 affected grandchildren had onset in teenage years.

PMID: 32528171 - 1 patient with limb girdle weakness.

PMID: 31119192 - 3 families (4 affecteds) with limb-girdle muscular weakness and cardiac abnormalities/arrhythmia. All had onset in adulthood, with exercise intolerance or proximal weakness.; to: PMID: 26642364 - 1 family (3 affecteds) with cardiac arrhythmia and limb-girdle muscular dystrophy. Supported by functional studies: zebrafish model. The proband showed lower limb girdle weakness at ~40 years old with muscle biopsy proving dystrophic changes. His 2 affected grandchildren had onset in teenage years.

PMID: 32528171 - 1 patient with limb girdle weakness.

PMID: 31119192 - 3 families (4 affecteds) with limb-girdle muscular weakness and cardiac abnormalities/arrhythmia. All had onset in adulthood, with exercise intolerance or proximal weakness.
Mendeliome v0.13327 BVES Zornitza Stark reviewed gene: BVES: Rating: GREEN; Mode of pathogenicity: None; Publications: 26642364, 32528171, 31119192; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 25, MIM# 616812; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13327 FLII Bryony Thompson Phenotypes for gene: FLII were changed from Dilated cardiomyopathy to Dilated cardiomyopathy MONDO:0005021
Mendeliome v0.13326 CLDN19 Ain Roesley Marked gene: CLDN19 as ready
Mendeliome v0.13326 CLDN19 Ain Roesley Phenotypes for gene: CLDN19 were changed from to Hypomagnesemia 5, renal, with ocular involvement, MIM#248190
Mendeliome v0.13324 CLDN19 Ain Roesley reviewed gene: CLDN19: Rating: GREEN; Mode of pathogenicity: None; Publications: 17033971, 22422540, 27530400]; Phenotypes: Hypomagnesemia 5, renal, with ocular involvement, MIM#248190; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13324 CLDN16 Ain Roesley Marked gene: CLDN16 as ready
Mendeliome v0.13323 CLDN1 Ain Roesley Marked gene: CLDN1 as ready
Mendeliome v0.13322 CLCNKB Ain Roesley Marked gene: CLCNKB as ready
Mendeliome v0.13322 CLCNKB Ain Roesley Phenotypes for gene: CLCNKB were changed from to Bartter syndrome, type 3, MIM# 607364; Bartter syndrome, type 4b, digenic, MIM# 613090
Mendeliome v0.13320 CLCNKB Ain Roesley reviewed gene: CLCNKB: Rating: GREEN; Mode of pathogenicity: None; Publications: 9326936, 15044642, 18310267; Phenotypes: Bartter syndrome, type 3, MIM# 607364, Bartter syndrome, type 4b, digenic, MIM# 613090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13320 CLCF1 Ain Roesley Marked gene: CLCF1 as ready
Mendeliome v0.13318 CIT Ain Roesley Marked gene: CIT as ready
Mendeliome v0.13317 CIT Ain Roesley Phenotypes for gene: CIT were changed from Microcephaly 17, primary, autosomal recessive (MIM#617090) to Microcephaly 17, primary, autosomal recessive (MIM#617090)
Mendeliome v0.13317 CIT Ain Roesley Phenotypes for gene: CIT were changed from to Microcephaly 17, primary, autosomal recessive (MIM#617090)
Mendeliome v0.13315 CIT Ain Roesley reviewed gene: CIT: Rating: GREEN; Mode of pathogenicity: None; Publications: 27453578, 27503289, 27453579; Phenotypes: Microcephaly 17, primary, autosomal recessive (MIM#617090); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13315 CISH Ain Roesley Marked gene: CISH as ready
Mendeliome v0.13314 CISD2 Ain Roesley Marked gene: CISD2 as ready
Mendeliome v0.13313 CILP Ain Roesley Marked gene: CILP as ready
Mendeliome v0.13312 PDYN Krithika Murali reviewed gene: PDYN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301317, 23471613, 23108490, 22243190, 22287014; Phenotypes: Spinocerebellar ataxia 23 - MIM#610245; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13312 CIC Ain Roesley Marked gene: CIC as ready
Mendeliome v0.13310 CHST14 Ain Roesley Marked gene: CHST14 as ready
Mendeliome v0.13308 CHRNA2 Ain Roesley Marked gene: CHRNA2 as ready
Mendeliome v0.13306 CHRM2 Ain Roesley Marked gene: CHRM2 as ready
Mendeliome v0.13306 CHRM2 Ain Roesley Phenotypes for gene: CHRM2 were changed from to Familial Dilated Cardiomyopathy MONDO#0016333, CHRM2-related
Mendeliome v0.13304 CHRM2 Ain Roesley reviewed gene: CHRM2: Rating: RED; Mode of pathogenicity: None; Publications: 23743182, 18451336; Phenotypes: Familial Dilated Cardiomyopathy MONDO#0016333, CHRM2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13304 CHN1 Ain Roesley Marked gene: CHN1 as ready
Mendeliome v0.13302 CHN1 Ain Roesley Mode of pathogenicity for gene: CHN1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v0.13301 CHN1 Ain Roesley reviewed gene: CHN1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 20301369; Phenotypes: Duane retraction syndrome 2,MIM#604356; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13301 CHMP4B Ain Roesley Marked gene: CHMP4B as ready
Mendeliome v0.13301 CHMP4B Ain Roesley Phenotypes for gene: CHMP4B were changed from to Cataract 31, multiple types MIM#605387
Mendeliome v0.13299 CHMP4B Ain Roesley reviewed gene: CHMP4B: Rating: GREEN; Mode of pathogenicity: None; Publications: 34722561, 17701905, 10682967, 30078984; Phenotypes: Cataract 31, multiple types MIM#605387; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13299 CHM Ain Roesley Marked gene: CHM as ready
Mendeliome v0.13297 CHIT1 Ain Roesley Marked gene: CHIT1 as ready
Mendeliome v0.13297 PDGFRA Krithika Murali changed review comment from: ?Suitability for Incidentalome versus Mendeliome based on adult age of diagnosis in reported cases.

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Six unrelated families reported with heterozygous germline variants associated with familial GIST and/or inflammatory fibroid polyps - IFP (benign lesions caused by excessive tissue proliferation and inflammatory cell infiltration into the lumen of the GI tract). Note that reported individuals diagnosed as adults. One individual reported with diagnosis of gastric mass/polyps age 22 (in 1977) raising the possibility of pre-symptomatic disease onset in adolescence. Green PanelApp England in the following panels: tumour predisposition - childhood onset; inherited predisposition to GIST; sarcoma cancer susceptibility.

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PMID 34107389 Hodan et al 2021 - report a 35 yo F with jejunal IFP and a heterozygous germline missense PDGFRA variant (c.1664A>G p.Y555C) . The variant segregated with 3 relatives with confirmed IFPs. Two obligate carriers were reported to have had a similar phenotype while at least one obligate male carrier had no reported history of IFPs. This variant was also reported in an unrelated family with multiple IFPs in 2006.

PMID 29486293 Manley et al 2018 - proband is a 50 yo M with multiple ileal intusussceptions and IFPs and GIST. Heterozygous D846V germline variant identified. Variant identified in daughter and 2 siblings. Coarser face, coarser skin, broader hands and feet, unexplained premature loss of teeth requiring dentures in their 40s described in relatives with the variant, no polyps or tumour identified in screened family members. Pdgfra +/K mutant mice recapitulated the human phenotype. Mice with the constitutively activated mutant PDGFRA shown to have diffuse expansion of the gastrointestinal submucosa, which exhibits an increased number of spindled fibroblast-like cells and marked collagen deposition. Mutant mice also develop intestinal polyps morphologically similar to IFPs. The Pdgfra +/K mice also exhibit thickened skin due to excess collagen deposition within the dermis and subcutaneous tissues.

PMID 25975287 Ricci et al 2015 - report a family with het germline P653L PDGFRA missense variant. The proband was a 67 yo M with multiple intra-abdominal GIST and gastric/colonic inflammatory fibroid polyps. Multiple adult relatives (youngest age 31) were diagnosed with IFPs/fibrous tumours with the variant segregating with disease.

PMID: 18670346 Carney et al 2008 and PMID: 17566086 Pasini et al 2007 - heterozygous germline PDGFRA mutation (V561D) in an individual with GIST and multiple polyps, diagnosed initially aged 22 with multiple GIST/polyps. No other relatives available for genotyping and no other significant family history reported.

PMID: 17087943 de Raedt et al 2006 - heterozygous PDGFRA(Y555C) variant reported in a family with multiple relatives affected by IFP, including one death from secondary bowel obstruction age 35.

PMID: 14699510 Chompret et al 2004 - Heterozygous c.2675G>T D846Y germline variant detected in a French family with 5 relatives developing adult-onset GIST, variant segregated with disease.

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Gain of function somatic variants associated with sporadic GIST. Somatic chromosomal rearrangements resulting in PDGFRA and FIP1L1 gene fusion associated with idiopathic hypereosinophilic syndrome.; to: Six unrelated families reported with heterozygous germline variants associated with familial GIST and/or inflammatory fibroid polyps - IFP (benign lesions caused by excessive tissue proliferation and inflammatory cell infiltration into the lumen of the GI tract). Note that reported individuals diagnosed as adults. One individual reported with diagnosis of gastric mass/polyps age 22 (in 1977) raising the possibility of pre-symptomatic disease onset in adolescence. Green PanelApp England in the following panels: tumour predisposition - childhood onset; inherited predisposition to GIST; sarcoma cancer susceptibility.

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PMID 34107389 Hodan et al 2021 - report a 35 yo F with jejunal IFP and a heterozygous germline missense PDGFRA variant (c.1664A>G p.Y555C) . The variant segregated with 3 relatives with confirmed IFPs. Two obligate carriers were reported to have had a similar phenotype while at least one obligate male carrier had no reported history of IFPs. This variant was also reported in an unrelated family with multiple IFPs in 2006.

PMID 29486293 Manley et al 2018 - proband is a 50 yo M with multiple ileal intusussceptions and IFPs and GIST. Heterozygous D846V germline variant identified. Variant identified in daughter and 2 siblings. Coarser face, coarser skin, broader hands and feet, unexplained premature loss of teeth requiring dentures in their 40s described in relatives with the variant, no polyps or tumour identified in screened family members. Pdgfra +/K mutant mice recapitulated the human phenotype. Mice with the constitutively activated mutant PDGFRA shown to have diffuse expansion of the gastrointestinal submucosa, which exhibits an increased number of spindled fibroblast-like cells and marked collagen deposition. Mutant mice also develop intestinal polyps morphologically similar to IFPs. The Pdgfra +/K mice also exhibit thickened skin due to excess collagen deposition within the dermis and subcutaneous tissues.

PMID 25975287 Ricci et al 2015 - report a family with het germline P653L PDGFRA missense variant. The proband was a 67 yo M with multiple intra-abdominal GIST and gastric/colonic inflammatory fibroid polyps. Multiple adult relatives (youngest age 31) were diagnosed with IFPs/fibrous tumours with the variant segregating with disease.

PMID: 18670346 Carney et al 2008 and PMID: 17566086 Pasini et al 2007 - heterozygous germline PDGFRA mutation (V561D) in an individual with GIST and multiple polyps, diagnosed initially aged 22 with multiple GIST/polyps. No other relatives available for genotyping and no other significant family history reported.

PMID: 17087943 de Raedt et al 2006 - heterozygous PDGFRA(Y555C) variant reported in a family with multiple relatives affected by IFP, including one death from secondary bowel obstruction age 35.

PMID: 14699510 Chompret et al 2004 - Heterozygous c.2675G>T D846Y germline variant detected in a French family with 5 relatives developing adult-onset GIST, variant segregated with disease.

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Gain of function somatic variants associated with sporadic GIST. Somatic chromosomal rearrangements resulting in PDGFRA and FIP1L1 gene fusion associated with idiopathic hypereosinophilic syndrome.
Mendeliome v0.13296 CHD1 Ain Roesley Marked gene: CHD1 as ready
Mendeliome v0.13296 CHD1 Ain Roesley Phenotypes for gene: CHD1 were changed from to Pilarowski-Bjornsson syndrome, MIM#617682
Mendeliome v0.13294 CHD1 Ain Roesley reviewed gene: CHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28866611; Phenotypes: Pilarowski-Bjornsson syndrome, MIM#617682; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13294 CFP Ain Roesley Marked gene: CFP as ready
Mendeliome v0.13292 CFI Ain Roesley Marked gene: CFI as ready
Mendeliome v0.13292 CFI Ain Roesley Marked gene: CFI as ready
Mendeliome v0.13289 RSPH3 Belinda Chong reviewed gene: RSPH3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26073779; Phenotypes: Ciliary dyskinesia, primary, 32 MIM#616481; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13289 HSPG2 Zornitza Stark changed review comment from: Allelic disorders with some phenotypic overlap.

Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive condition defined by the association of myotonia with chondrodysplasia; blepharophimosis is a key feature. More than 20 families reported.

Silverman-Handmaker dyssegmental dysplasia (DDSH) is a lethal autosomal recessive skeletal dysplasia with anisospondyly and micromelia. Individuals with DDSH also have a flat face, micrognathia, cleft palate and reduced joint mobility, and frequently have an encephalocele. The endochondral growth plate is short, the calcospherites (spherical calcium-phosphorus crystals produced by hypertrophic chondrocytes) are unfused, and there is mucoid degeneration of the resting cartilage. Two families reported.; to: Allelic disorders with some phenotypic overlap.

Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive condition defined by the association of myotonia with chondrodysplasia; blepharophimosis is a key feature. More than 20 families reported.

Silverman-Handmaker dyssegmental dysplasia (DDSH) is a lethal autosomal recessive skeletal dysplasia with anisospondyly and micromelia. Individuals with DDSH also have a flat face, micrognathia, cleft palate and reduced joint mobility, and frequently have an encephalocele. The endochondral growth plate is short, the calcospherites (spherical calcium-phosphorus crystals produced by hypertrophic chondrocytes) are unfused, and there is mucoid degeneration of the resting cartilage. Two families reported. Appears associated with null variants.
Mendeliome v0.13289 PKD1 Zornitza Stark Marked gene: PKD1 as ready
Mendeliome v0.13287 PKD2 Zornitza Stark Marked gene: PKD2 as ready
Mendeliome v0.13285 PKLR Zornitza Stark Marked gene: PKLR as ready
Mendeliome v0.13282 PKP1 Zornitza Stark Marked gene: PKP1 as ready
Mendeliome v0.13279 PLA2G5 Zornitza Stark Marked gene: PLA2G5 as ready
Mendeliome v0.13276 PLCE1 Zornitza Stark Marked gene: PLCE1 as ready
Mendeliome v0.13273 PLCG2 Zornitza Stark Marked gene: PLCG2 as ready
Mendeliome v0.13273 PLCG2 Zornitza Stark Phenotypes for gene: PLCG2 were changed from to Common variable immunodeficiency; Autoinflammation, antibody deficiency, and immune dysregulation syndrome MIM#614878
Mendeliome v0.13266 PLEKHM1 Zornitza Stark changed review comment from: Three individuals reported with mono allelic variants, and one with bi-allelic. Animal model.; to: Three individuals reported with mono allelic variants, and two with bi-allelic. Animal models.
Mendeliome v0.13266 PLEKHM1 Zornitza Stark Marked gene: PLEKHM1 as ready
Mendeliome v0.13263 RSPH4A Belinda Chong changed review comment from: Radial spokes are regularly spaced along cilia, sperm, and flagella axonemes and have a multisubunit 'stalk' and 'head' that form a signal transduction scaffold between the central microtubule pair and dynein arms. RSPH4A is predicted to be a component of the radial spoke head based on homology with proteins in the biflagellate alga Chlamydomonas reinhardtii and other ciliates (Castleman et al., 2009; PMID19200523)

9 families with primary ciliary dyskinesia without situs inversus (Kott et al. 2013 (PMID:23993197), Castleman et al., 2009 (PMID19200523) and Daniels et al. 2013; (PMID:23798057)):
- In affected members of 4 Pakistani families with CILD11, Castleman et al. (2009) identified a homozygous mutation in the RSPH4A gene.
- In affected members of a family of northern European descent with CILD11, Castleman et al. (2009) identified compound heterozygosity for 2 mutations in the RSPH4A gene
- Kott et al. (2013) identified pathogenic mutations in the RSPH4A gene in 7 (14%) of 48 families with a specific CILD.

Common founder mutation:
- Daniels et al. (2013) identified a common founder mutation in the RSPH4A gene in 9 patients with CILD11, all of whom had Puerto Rican ancestry.

Multiple individuals in ClinVar with primary ciliary dyskinesia; to: Radial spokes are regularly spaced along cilia, sperm, and flagella axonemes and have a multisubunit 'stalk' and 'head' that form a signal transduction scaffold between the central microtubule pair and dynein arms. RSPH4A is predicted to be a component of the radial spoke head based on homology with proteins in the biflagellate alga Chlamydomonas reinhardtii and other ciliates (Castleman et al., 2009; PMID19200523)

9 families with primary ciliary dyskinesia without situs inversus (Kott et al. 2013 (PMID:23993197), Castleman et al., 2009 (PMID19200523) and Daniels et al. 2013; (PMID:23798057)):
- In affected members of 4 Pakistani families with CILD11, Castleman et al. (2009) identified a homozygous mutation in the RSPH4A gene.
- In affected members of a family of northern European descent with CILD11, Castleman et al. (2009) identified compound heterozygosity for 2 mutations in the RSPH4A gene
- Kott et al. (2013) identified pathogenic mutations in the RSPH4A gene in 7 (14%) of 48 families with a specific CILD.

Common founder mutation:
- Daniels et al. (2013) identified a common founder mutation in the RSPH4A gene in 9 patients with CILD11, all of whom had Puerto Rican ancestry.

Multiple individuals in ClinVar with primary ciliary dyskinesia

PMID: 25789548; Frommer 2015: 8 PCD families reported, only 4 different variants identified. Functional studies performed.

PMID: 22448264; Ziętkiewicz 2012: 4 additional families/variants reported.
Mendeliome v0.13263 RSPH4A Belinda Chong reviewed gene: RSPH4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 23798057, 23798057, 23798057; Phenotypes: Ciliary dyskinesia, primary, 11 OMIM#612649; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13263 RSPH9 Belinda Chong reviewed gene: RSPH9: Rating: GREEN; Mode of pathogenicity: None; Publications: 25789548, 22384920, 23993197, 19200523, 27626380; Phenotypes: Ciliary dyskinesia, primary, 12 MIM#612650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13263 PLN Zornitza Stark Marked gene: PLN as ready
Mendeliome v0.13263 PLN Zornitza Stark Phenotypes for gene: PLN were changed from to Cardiomyopathy, dilated, 1P, MIM# 609909; Cardiomyopathy, hypertrophic, 18 (MIM #613874)
Mendeliome v0.13260 PLN Zornitza Stark reviewed gene: PLN: Rating: GREEN; Mode of pathogenicity: None; Publications: 33947203; Phenotypes: Cardiomyopathy, dilated, 1P, MIM# 609909, Cardiomyopathy, hypertrophic, 18 (MIM #613874); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13260 PLOD1 Zornitza Stark Marked gene: PLOD1 as ready
Mendeliome v0.13257 PLOD2 Zornitza Stark Marked gene: PLOD2 as ready
Mendeliome v0.13254 PMFBP1 Zornitza Stark Marked gene: PMFBP1 as ready
Mendeliome v0.13251 PMPCA Zornitza Stark Marked gene: PMPCA as ready
Mendeliome v0.13251 PMPCA Zornitza Stark Phenotypes for gene: PMPCA were changed from to Spinocerebellar ataxia, autosomal recessive 2, MIM# 213200
Mendeliome v0.13248 PMPCA Zornitza Stark reviewed gene: PMPCA: Rating: GREEN; Mode of pathogenicity: None; Publications: 25808372, 26657514, 33272776, 30617178; Phenotypes: Spinocerebellar ataxia, autosomal recessive 2, MIM# 213200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13248 PMPCB Zornitza Stark Marked gene: PMPCB as ready
Mendeliome v0.13245 PNPO Zornitza Stark Marked gene: PNPO as ready
Mendeliome v0.13242 PODXL Zornitza Stark Marked gene: PODXL as ready
Mendeliome v0.13239 POFUT1 Zornitza Stark Marked gene: POFUT1 as ready
Mendeliome v0.13236 POLG Zornitza Stark Marked gene: POLG as ready
Mendeliome v0.13233 POMGNT1 Zornitza Stark Marked gene: POMGNT1 as ready
Mendeliome v0.13233 POMGNT1 Zornitza Stark Phenotypes for gene: POMGNT1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 MIM#614830; Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8 MIM#618135; Retinitis pigmentosa 76 617123
Mendeliome v0.13230 POMGNT1 Zornitza Stark reviewed gene: POMGNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27391550, 26908613, 30961548, 30937090; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 MIM#614830, Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8 MIM#618135, Retinitis pigmentosa 76 617123; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13230 POMGNT2 Zornitza Stark Marked gene: POMGNT2 as ready
Mendeliome v0.13230 POMGNT2 Zornitza Stark Phenotypes for gene: POMGNT2 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8, MIM# 614830; Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8, MIM# 618135
Mendeliome v0.13227 POMGNT2 Zornitza Stark reviewed gene: POMGNT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34301702, 27066570, 26060116, 22958903; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8, MIM# 614830, Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8, MIM# 618135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13227 POMK Zornitza Stark Marked gene: POMK as ready
Mendeliome v0.13227 POMK Zornitza Stark Phenotypes for gene: POMK were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, MIM# 615249; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 12, MIM# 616094
Mendeliome v0.13224 POMK Zornitza Stark reviewed gene: POMK: Rating: GREEN; Mode of pathogenicity: None; Publications: 32907597, 31833209, 29910097, 28109637, 24925318, 24556084; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, MIM# 615249, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 12, MIM# 616094; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13224 RAX2 Zornitza Stark Marked gene: RAX2 as ready
Mendeliome v0.13221 RASA1 Zornitza Stark Marked gene: RASA1 as ready
Mendeliome v0.13220 PDX1 Zornitza Stark Marked gene: PDX1 as ready
Mendeliome v0.13220 PDX1 Zornitza Stark Phenotypes for gene: PDX1 were changed from to Pancreatic agenesis 1 - MIM#260370 (AR); MODY, type IV - MIM#606392(AD)
Mendeliome v0.13215 PDP1 Zornitza Stark Marked gene: PDP1 as ready
Mendeliome v0.13212 PDHB Zornitza Stark Marked gene: PDHB as ready
Mendeliome v0.13210 RSPO1 Zornitza Stark Marked gene: RSPO1 as ready
Mendeliome v0.13210 RSPO1 Zornitza Stark Phenotypes for gene: RSPO1 were changed from to Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal MIM#610644; Palmoplantar hyperkeratosis and true hermaphroditism MIM#610644
Mendeliome v0.13203 PDHA1 Zornitza Stark Marked gene: PDHA1 as ready
Mendeliome v0.13200 PDE6H Zornitza Stark Marked gene: PDE6H as ready
Mendeliome v0.13197 PDE6G Zornitza Stark Marked gene: PDE6G as ready
Mendeliome v0.13193 PDE6C Zornitza Stark Marked gene: PDE6C as ready
Mendeliome v0.13190 PDE6B Zornitza Stark Marked gene: PDE6B as ready
Mendeliome v0.13190 PDE6B Zornitza Stark Phenotypes for gene: PDE6B were changed from to Night blindness, congenital stationary, autosomal dominant 2 - MIM#163500; Retinitis pigmentosa-40 - MIM#613801
Mendeliome v0.13187 PDE6A Zornitza Stark Marked gene: PDE6A as ready
Mendeliome v0.13184 PDE4D Zornitza Stark Marked gene: PDE4D as ready
Mendeliome v0.13181 PDE3A Zornitza Stark Marked gene: PDE3A as ready
Mendeliome v0.13179 PDE11A Zornitza Stark Marked gene: PDE11A as ready
Mendeliome v0.13179 PDE11A Zornitza Stark Phenotypes for gene: PDE11A were changed from to Pigmented nodular adrenocortical disease, primary, 2 - MIM#610475
Mendeliome v0.13175 SHH Zornitza Stark Marked gene: SHH as ready
Mendeliome v0.13175 SHH Zornitza Stark Added comment: Comment when marking as ready: DISPUTED association with schizencephaly
Mendeliome v0.13175 SHH Zornitza Stark Phenotypes for gene: SHH were changed from to Holoprosencephaly 3, MIM#142945; Microphthalmia with coloboma 5, MIM#611638; Single median maxillary central incisor, MIM#147250
Mendeliome v0.13172 FAM111B Zornitza Stark reviewed gene: FAM111B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: hereditary sclerosing poikiloderma with tendon and pulmonary involvement MONDO:0014310; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13172 SH3BP2 Zornitza Stark commented on gene: SH3BP2: Cherubism is characterized by a loss of bone, restricted to the jaws, and by the replacement of this bone with fibrous tissues, leading to facial swelling. Involvement of the infraorbital rim and the orbital floor leads to the upward tilting of the eyeballs and consequent exposure of the inferior part of the sclerae, giving a 'cherubic' appearance. Submandibular lymph node enlargement is often reported. Functional impairment includes mastication and speech problems, tooth alterations, and loss of normal vision. Onset of the disease is usually between 14 months and 4 years of age. The disease progresses through puberty, then stabilizes, and in some cases regresses without treatment.
Mendeliome v0.13172 SH3BP2 Zornitza Stark Marked gene: SH3BP2 as ready
Mendeliome v0.13170 SH3BP2 Zornitza Stark Mode of pathogenicity for gene: SH3BP2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v0.13168 SH3BP2 Zornitza Stark reviewed gene: SH3BP2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: ; Phenotypes: Cherubism, MIM#118400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13167 TLR8 Zornitza Stark Phenotypes for gene: TLR8 were changed from Immunodeficiency; bone marrow failure; Autoinflammatory syndrome MONDO:0019751 to Immunodeficiency 98 with autoinflammation, X-linked, MIM# 301078
Mendeliome v0.13159 CDKN1B Zornitza Stark Marked gene: CDKN1B as ready
Mendeliome v0.13158 DNAJB11 Elena Savva reviewed gene: DNAJB11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34177435, 29706351, 29777155, 33129895; Phenotypes: Polycystic kidney disease 6 with or without polycystic liver disease, MIM#618061, Ivermark II syndrome, Prenatal Polycystic Kidney Disease; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.13157 SLC12A3 Zornitza Stark Marked gene: SLC12A3 as ready
Mendeliome v0.13153 PIDD1 Zornitza Stark Phenotypes for gene: PIDD1 were changed from Global developmental delay; Intellectual disability; Seizures; Autism; Behavioral abnormality; Psychosis; Pachygyria; Lissencephaly; Abnormality of the corpus callosum to Intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, MIM# 619827
Mendeliome v0.13152 PIDD1 Zornitza Stark edited their review of gene: PIDD1: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, MIM# 619827
Mendeliome v0.13152 SLC12A1 Zornitza Stark Marked gene: SLC12A1 as ready
Mendeliome v0.13152 SLC12A1 Zornitza Stark Phenotypes for gene: SLC12A1 were changed from to Bartter syndrome, type 1, MIM# 601678
Mendeliome v0.13149 SLC12A1 Zornitza Stark reviewed gene: SLC12A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8640224, 9355073, 28095294; Phenotypes: Bartter syndrome, type 1, MIM# 601678; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13149 FGF23 Bryony Thompson Marked gene: FGF23 as ready
Mendeliome v0.13147 PDX1 Krithika Murali reviewed gene: PDX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9326926, 10545531, 10720084, 12970316, 20009086, 19496967; Phenotypes: Pancreatic agenesis 1 - MIM#260370 (AR), MODY, type IV - MIM#606392(AD); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13144 FGF14 Bryony Thompson Phenotypes for gene: FGF14 were changed from Spinocerebellar ataspinocerebellar ataxia type 27 MONDO:0012247; hereditary episodic ataxia MONDO:0016227xia 27 MIM#609307 to Spinocerebellar ataspinocerebellar ataxia type 27 MONDO:0012247; hereditary episodic ataxia MONDO:0016227
Mendeliome v0.13142 FGF14 Bryony Thompson Phenotypes for gene: FGF14 were changed from Spinocerebellar ataxia 27 MIM#609307 to Spinocerebellar ataspinocerebellar ataxia type 27 MONDO:0012247; hereditary episodic ataxia MONDO:0016227xia 27 MIM#609307
Mendeliome v0.13141 FGF14 Bryony Thompson edited their review of gene: FGF14: Added comment: 4 families with spinocerebellar ataxia and 7 families with episodic ataxia. Supporting animal models for both SCA and EA.; Changed publications: 12123606, 12489043, 15470364, 29253853, 30017992, 32112487, 32162847; Changed phenotypes: spinocerebellar ataxia type 27 MONDO:0012247, hereditary episodic ataxia MONDO:0016227; Set current diagnostic: yes
Mendeliome v0.13141 FGF10 Bryony Thompson Marked gene: FGF10 as ready
Mendeliome v0.13141 FGF10 Bryony Thompson Phenotypes for gene: FGF10 were changed from to congenital alveolar dysplasia due to FGF10 MONDO:0100090; acinar dysplasia caused by mutation in FGF10 MONDO:0600017
Mendeliome v0.13138 FGF10 Bryony Thompson reviewed gene: FGF10: Rating: GREEN; Mode of pathogenicity: None; Publications: 9916808, 15654336, 16501574, 16630169, 17213838, 33967277, 30639323; Phenotypes: congenital alveolar dysplasia due to FGF10 MONDO:0100090, acinar dysplasia caused by mutation in FGF10 MONDO:0600017; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13138 FFAR4 Bryony Thompson Marked gene: FFAR4 as ready
Mendeliome v0.13138 FFAR4 Bryony Thompson Gene: ffar4 has been classified as Red List (Low Evidence).
Mendeliome v0.13138 FFAR4 Bryony Thompson Phenotypes for gene: FFAR4 were changed from to {Obesity, susceptibility to} MIM#607514
Mendeliome v0.13137 FFAR4 Bryony Thompson Publications for gene: FFAR4 were set to
Mendeliome v0.13136 FFAR4 Bryony Thompson Classified gene: FFAR4 as Red List (low evidence)
Mendeliome v0.13136 FFAR4 Bryony Thompson Gene: ffar4 has been classified as Red List (Low Evidence).
Mendeliome v0.13135 FFAR4 Bryony Thompson reviewed gene: FFAR4: Rating: RED; Mode of pathogenicity: None; Publications: 22343897, 34043793; Phenotypes: {Obesity, susceptibility to} MIM#607514; Mode of inheritance: Unknown
Mendeliome v0.13135 FDX2 Bryony Thompson Marked gene: FDX2 as ready
Mendeliome v0.13132 FDFT1 Bryony Thompson Marked gene: FDFT1 as ready
Mendeliome v0.13129 FBXO7 Bryony Thompson Marked gene: FBXO7 as ready
Mendeliome v0.13129 FBXO7 Bryony Thompson Phenotypes for gene: FBXO7 were changed from to parkinsonian-pyramidal syndrome MONDO:0009830
Mendeliome v0.13125 FBXO7 Bryony Thompson reviewed gene: FBXO7: Rating: GREEN; Mode of pathogenicity: None; Publications: 18513678, 19038853, 34781237; Phenotypes: parkinsonian-pyramidal syndrome MONDO:0009830; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13125 RSPO1 Belinda Chong reviewed gene: RSPO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17041600, 18085567, 18250098, 18250097; Phenotypes: Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal MIM#610644, Palmoplantar hyperkeratosis and true hermaphroditism MIM#610644; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13125 FBP1 Bryony Thompson Marked gene: FBP1 as ready
Mendeliome v0.13121 FBP1 Bryony Thompson changed review comment from: Well-established gene-disease association. Fructose-1,6-bisphosphatase (FBP1) deficiency is metabolic disorder characterised by episodic acute crises of lactic acidosis and ketotic hypoglycaemia, manifesting as hyperventilation, apneic spells, seizures, and/or coma. Both SNVs and CNVs have been reported.; to: Well-established gene-disease association. Fructose-1,6-bisphosphatase (FBP1) deficiency is a metabolic disorder characterised by episodic acute crises of lactic acidosis and ketotic hypoglycaemia, manifesting as hyperventilation, apneic spells, seizures, and/or coma. Both SNVs and CNVs have been reported.
Mendeliome v0.13121 CLPB Zornitza Stark Phenotypes for gene: CLPB were changed from 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271; Neutropenia, severe congenital, 9, autosomal dominant, MIM# 619813 to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271; 3-methylglutaconic aciduria, type VIIA, autosomal dominant, MIM# 619835; Neutropenia, severe congenital, 9, autosomal dominant, MIM# 619813
Mendeliome v0.13120 CLPB Zornitza Stark edited their review of gene: CLPB: Changed phenotypes: 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271, 3-methylglutaconic aciduria, type VIIA, autosomal dominant, MIM# 619835, Neutropenia, severe congenital, 9, autosomal dominant, MIM# 619813
Mendeliome v0.13120 GLRA2 Zornitza Stark Marked gene: GLRA2 as ready
Mendeliome v0.13119 GLRA2 Zornitza Stark gene: GLRA2 was added
gene: GLRA2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: GLRA2 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: GLRA2 were set to 26370147; 20479760; 35294868
Phenotypes for gene: GLRA2 were set to Intellectual developmental disorder, X-linked, syndromic, Pilorge type, MIM# 301076
Review for gene: GLRA2 was set to GREEN
Added comment: More than 10 unrelated families reported. Both males and females affected, though some mothers are asymptomatic or mild. Zebrafish model.
Sources: Expert list
Mendeliome v0.13117 FASTKD2 Bryony Thompson Marked gene: FASTKD2 as ready
Mendeliome v0.13115 FASLG Bryony Thompson Marked gene: FASLG as ready
Mendeliome v0.13112 FAS Bryony Thompson Marked gene: FAS as ready
Mendeliome v0.13109 FARSB Bryony Thompson Marked gene: FARSB as ready
Mendeliome v0.13109 FARSB Bryony Thompson Gene: farsb has been classified as Green List (High Evidence).
Mendeliome v0.13109 FARSB Bryony Thompson Phenotypes for gene: FARSB were changed from to Rajab interstitial lung disease with brain calcifications 1 MONDO:0100215
Mendeliome v0.13108 FARSB Bryony Thompson Publications for gene: FARSB were set to
Mendeliome v0.13107 FARSB Bryony Thompson Mode of inheritance for gene: FARSB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13106 FARSB Bryony Thompson reviewed gene: FARSB: Rating: GREEN; Mode of pathogenicity: None; Publications: 29573043, 30014610, 29979980; Phenotypes: Rajab interstitial lung disease with brain calcifications 1 MONDO:0100215; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13106 FARS2 Bryony Thompson Marked gene: FARS2 as ready
Mendeliome v0.13106 FARS2 Bryony Thompson Gene: fars2 has been classified as Green List (High Evidence).
Mendeliome v0.13106 FARS2 Bryony Thompson Phenotypes for gene: FARS2 were changed from to combined oxidative phosphorylation defect type 14 MONDO:0013986; hereditary spastic paraplegia 77 MONDO:0014882
Mendeliome v0.13105 FARS2 Bryony Thompson Publications for gene: FARS2 were set to
Mendeliome v0.13104 FARS2 Bryony Thompson Mode of inheritance for gene: FARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13103 FARS2 Bryony Thompson reviewed gene: FARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30250868, 30177229, 29126765, 28043061; Phenotypes: combined oxidative phosphorylation defect type 14 MONDO:0013986, hereditary spastic paraplegia 77 MONDO:0014882; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13103 FAM58A Bryony Thompson Marked gene: FAM58A as ready
Mendeliome v0.13100 PDE6B Krithika Murali reviewed gene: PDE6B: Rating: GREEN; Mode of pathogenicity: None; Publications: 8394174, 8075643, 17044014, 7599633, 18854872; Phenotypes: Night blindness, congenital stationary, autosomal dominant 2 - MIM#163500, Retinitis pigmentosa-40 - MIM#613801; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13100 FAM161A Bryony Thompson Marked gene: FAM161A as ready
Mendeliome v0.13100 PDE11A Krithika Murali reviewed gene: PDE11A: Rating: RED; Mode of pathogenicity: None; Publications: 16767104, 18559625, 21047926, 17178847; Phenotypes: Pigmented nodular adrenocortical disease, primary, 2 - MIM#610475; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13097 FAM126A Bryony Thompson Marked gene: FAM126A as ready
Mendeliome v0.13096 SHH Samantha Ayres reviewed gene: SHH: Rating: GREEN; Mode of pathogenicity: None; Publications: 21976454, 12503095, 22791840, 19057928, 19533790; Phenotypes: Holoprosencephaly 3, MIM#142945, Microphthalmia with coloboma 5, MIM#611638, Schizencephaly, MIM#269160, Single median maxillary central incisor, MIM#147250; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13094 FAM111B Bryony Thompson Marked gene: FAM111B as ready
Mendeliome v0.13094 FAM111B Bryony Thompson Phenotypes for gene: FAM111B were changed from to hereditary sclerosing poikiloderma with tendon and pulmonary involvement MONDO:0014310
Mendeliome v0.13090 FAM111B Bryony Thompson reviewed gene: FAM111B: Rating: ; Mode of pathogenicity: Other; Publications: 24268661, 26471370, 26495788, 27406236; Phenotypes: hereditary sclerosing poikiloderma with tendon and pulmonary involvement MONDO:0014310; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.13090 FAM111A Bryony Thompson Marked gene: FAM111A as ready
Mendeliome v0.13086 FADD Bryony Thompson Marked gene: FADD as ready
Mendeliome v0.13085 FAH Bryony Thompson Marked gene: FAH as ready
Mendeliome v0.13080 F12 Bryony Thompson Marked gene: F12 as ready
Mendeliome v0.13080 F12 Bryony Thompson Phenotypes for gene: F12 were changed from to Hereditary angioedema type 3 MONDO:0012526
Mendeliome v0.13078 POMP Zornitza Stark Marked gene: POMP as ready
Mendeliome v0.13078 POMP Zornitza Stark Phenotypes for gene: POMP were changed from to Keratosis linearis with ichthyosis congenita and sclerosing keratoderma MIM#601952; Proteasome-associated autoinflammatory syndrome 2, MIM# 618048
Mendeliome v0.13075 POMP Zornitza Stark reviewed gene: POMP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20226437, 27503413, 29805043; Phenotypes: Keratosis linearis with ichthyosis congenita and sclerosing keratoderma MIM#601952, Proteasome-associated autoinflammatory syndrome 2, MIM# 618048; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13075 POMT1 Zornitza Stark Marked gene: POMT1 as ready
Mendeliome v0.13075 POMT1 Zornitza Stark Phenotypes for gene: POMT1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 613155; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308
Mendeliome v0.13073 POMT1 Zornitza Stark reviewed gene: POMT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 613155, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13073 POMT2 Zornitza Stark Marked gene: POMT2 as ready
Mendeliome v0.13073 POMT2 Zornitza Stark Phenotypes for gene: POMT2 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 613156; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 613158
Mendeliome v0.13071 POMT2 Zornitza Stark edited their review of gene: POMT2: Changed phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 613156, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 613158
Mendeliome v0.13071 POMT2 Zornitza Stark reviewed gene: POMT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150 Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 613156 Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 613158; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13071 PPARA Zornitza Stark Marked gene: PPARA as ready
Mendeliome v0.13071 PPARA Zornitza Stark Gene: ppara has been classified as Red List (Low Evidence).
Mendeliome v0.13071 PPARA Zornitza Stark Phenotypes for gene: PPARA were changed from to {Hyperapobetalipoproteinemia, susceptibility to}
Mendeliome v0.13070 PPARA Zornitza Stark Mode of inheritance for gene: PPARA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13069 PPARA Zornitza Stark Classified gene: PPARA as Red List (low evidence)
Mendeliome v0.13069 PPARA Zornitza Stark Gene: ppara has been classified as Red List (Low Evidence).
Mendeliome v0.13068 PPARA Zornitza Stark reviewed gene: PPARA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Hyperapobetalipoproteinemia, susceptibility to}; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13068 PPM1K Zornitza Stark Marked gene: PPM1K as ready
Mendeliome v0.13068 PPM1K Zornitza Stark Phenotypes for gene: PPM1K were changed from to Maple syrup urine disease, mild variant, MIM#615135
Mendeliome v0.13064 PPM1K Zornitza Stark reviewed gene: PPM1K: Rating: RED; Mode of pathogenicity: None; Publications: 23086801; Phenotypes: Maple syrup urine disease, mild variant, MIM#615135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13064 PPOX Zornitza Stark Marked gene: PPOX as ready
Mendeliome v0.13064 PPOX Zornitza Stark Phenotypes for gene: PPOX were changed from to Porphyria variegata , MIM#176200
Mendeliome v0.13061 PPOX Zornitza Stark reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 12357337, 32247286, 23324528, 27982422; Phenotypes: Porphyria variegata , MIM#176200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13061 PPP1R15B Zornitza Stark Marked gene: PPP1R15B as ready
Mendeliome v0.13061 SGCG Samantha Ayres reviewed gene: SGCG: Rating: GREEN; Mode of pathogenicity: None; Publications: 18285821, 8923014, 7481775, 8968757, 27708273; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 5 MIM#253700, autosomal recessive limb-girdle muscular dystrophy MONDO:0015152; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13061 CFHR5 Ain Roesley Marked gene: CFHR5 as ready
Mendeliome v0.13059 CFH Ain Roesley Marked gene: CFH as ready
Mendeliome v0.13059 CFH Ain Roesley Phenotypes for gene: CFH were changed from to Basal laminar drusen MIM#126700; Complement factor H deficiency MIM#609814; {Hemolytic uremic syndrome, atypical, susceptibility to, 1} MIMI#235400
Mendeliome v0.13058 CFH Ain Roesley reviewed gene: CFH: Rating: GREEN; Mode of pathogenicity: None; Publications: 27572114, 25814826, 20301541, 9312129, 10803850, 29888403, 30905644; Phenotypes: Basal laminar drusen MIM#126700, Complement factor H deficiency MIM#609814, {Hemolytic uremic syndrome, atypical, susceptibility to, 1} MIMI#235400; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13054 PPP1R3A Zornitza Stark Marked gene: PPP1R3A as ready
Mendeliome v0.13050 PRCD Zornitza Stark Marked gene: PRCD as ready
Mendeliome v0.13047 PRDM16 Zornitza Stark Marked gene: PRDM16 as ready
Mendeliome v0.13047 PRDM16 Zornitza Stark Phenotypes for gene: PRDM16 were changed from to Cardiomyopathy, dilated, 1LL MIM#615373; Left ventricular noncompaction 8 MIM#615373
Mendeliome v0.13043 PRDM16 Zornitza Stark reviewed gene: PRDM16: Rating: AMBER; Mode of pathogenicity: None; Publications: 23768516, 29367541, 34915728, 31965688, 29367541; Phenotypes: Cardiomyopathy, dilated, 1LL MIM#615373, Left ventricular noncompaction 8 MIM#615373; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13043 CFD Ain Roesley Marked gene: CFD as ready
Mendeliome v0.13040 CEP78 Ain Roesley Marked gene: CEP78 as ready
Mendeliome v0.13040 CEP78 Ain Roesley Phenotypes for gene: CEP78 were changed from to Cone-rod dystrophy and hearing loss MIM#617236
Mendeliome v0.13038 CEP78 Ain Roesley reviewed gene: CEP78: Rating: GREEN; Mode of pathogenicity: None; Publications: 28005958, 27588451, 27588452, 27627988; Phenotypes: Cone-rod dystrophy and hearing loss MIM#617236; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13038 CEBPA Ain Roesley Marked gene: CEBPA as ready
Mendeliome v0.13037 CEACAM16 Ain Roesley Marked gene: CEACAM16 as ready
Mendeliome v0.13036 CDKN2A Ain Roesley Marked gene: CDKN2A as ready
Mendeliome v0.13033 CDK4 Ain Roesley Marked gene: CDK4 as ready
Mendeliome v0.13031 CDK10 Ain Roesley changed review comment from: >5 families; to: 6 families thus far
Mendeliome v0.13031 CDK10 Ain Roesley Marked gene: CDK10 as ready
Mendeliome v0.13030 CDHR1 Ain Roesley Marked gene: CDHR1 as ready
Mendeliome v0.13028 CDC73 Ain Roesley Marked gene: CDC73 as ready
Mendeliome v0.13028 CDC73 Ain Roesley Phenotypes for gene: CDC73 were changed from to Hyperparathyroidism-jaw tumour syndrome, MIM# 145001; Hyperparathyroidism, familial primary, MIM# 145000
Mendeliome v0.13027 CDC73 Ain Roesley reviewed gene: CDC73: Rating: GREEN; Mode of pathogenicity: None; Publications: 12434154; Phenotypes: Hyperparathyroidism-jaw tumour syndrome, MIM# 145001, Hyperparathyroidism, familial primary, MIM# 145000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.13025 CDC42 Ain Roesley Marked gene: CDC42 as ready
Mendeliome v0.13024 CDC14A Ain Roesley Marked gene: CDC14A as ready
Mendeliome v0.13022 CD79B Ain Roesley Marked gene: CD79B as ready
Mendeliome v0.13020 PRDM5 Zornitza Stark Marked gene: PRDM5 as ready
Mendeliome v0.13017 PREPL Zornitza Stark Marked gene: PREPL as ready
Mendeliome v0.13014 PRG4 Zornitza Stark Marked gene: PRG4 as ready
Mendeliome v0.13014 PRG4 Zornitza Stark Phenotypes for gene: PRG4 were changed from to Camptodactyly-arthropathy-coxa vara-pericarditis syndrome, MIM# 208250
Mendeliome v0.13011 PRG4 Zornitza Stark reviewed gene: PRG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 10545950, 29397575; Phenotypes: Camptodactyly-arthropathy-coxa vara-pericarditis syndrome, MIM# 208250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13010 PRICKLE1 Zornitza Stark Marked gene: PRICKLE1 as ready
Mendeliome v0.13007 PRKAR1A Zornitza Stark Marked gene: PRKAR1A as ready
Mendeliome v0.13007 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Green List (High Evidence).
Mendeliome v0.13007 PRKAR1A Zornitza Stark Phenotypes for gene: PRKAR1A were changed from to Acrodysostosis 1, with or without hormone resistance, MIM# 101800; Carney complex, type 1, MIM# 160980; Myxoma, intracardiac, MIM# 255960; Pigmented nodular adrenocortical disease, primary, 1, MIM# 610489
Mendeliome v0.13006 PRKAR1A Zornitza Stark Publications for gene: PRKAR1A were set to
Mendeliome v0.13005 PRKAR1A Zornitza Stark Mode of inheritance for gene: PRKAR1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13004 PRKAR1A Zornitza Stark reviewed gene: PRKAR1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 10973256, 11115848, 12424709, 21651393; Phenotypes: Acrodysostosis 1, with or without hormone resistance, MIM# 101800, Carney complex, type 1, MIM# 160980, Myxoma, intracardiac, MIM# 255960, Pigmented nodular adrenocortical disease, primary, 1, MIM# 610489; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13004 PRKCG Zornitza Stark Marked gene: PRKCG as ready
Mendeliome v0.13004 PRKCG Zornitza Stark Phenotypes for gene: PRKCG were changed from to Spinocerebellar ataxia 14, MIM# 605361
Mendeliome v0.13001 PRKCG Zornitza Stark reviewed gene: PRKCG: Rating: GREEN; Mode of pathogenicity: None; Publications: 12644968, 14676051, 14694043, 16193476, 33739604, 34292398; Phenotypes: Spinocerebellar ataxia 14, MIM# 605361; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13001 PRKG1 Zornitza Stark Marked gene: PRKG1 as ready
Mendeliome v0.12998 PRMT7 Zornitza Stark Marked gene: PRMT7 as ready
Mendeliome v0.12995 PRODH Zornitza Stark Marked gene: PRODH as ready
Mendeliome v0.12992 PROK2 Zornitza Stark Marked gene: PROK2 as ready
Mendeliome v0.12989 PROM1 Zornitza Stark Marked gene: PROM1 as ready
Mendeliome v0.12989 PROM1 Zornitza Stark Phenotypes for gene: PROM1 were changed from to Inherited retinal dystrophy, MONDO:0019118; Cone-rod dystrophy 12, MIM# 612657; Macular dystrophy, retinal, 2, MI# 608051; Retinitis pigmentosa 41, MIM# 612095; Stargardt disease 4, MIM# 603786
Mendeliome v0.12986 PROM1 Zornitza Stark reviewed gene: PROM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10587575, 17605048, 18654668, 29416601, 31576780, 34664634, 32820593; Phenotypes: Inherited retinal dystrophy, MONDO:0019118, Cone-rod dystrophy 12, MIM# 612657, Macular dystrophy, retinal, 2, MI# 608051, Retinitis pigmentosa 41, MIM# 612095, Stargardt disease 4, MIM# 603786; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12986 PROS1 Zornitza Stark Marked gene: PROS1 as ready
Mendeliome v0.12983 PRPF3 Zornitza Stark Marked gene: PRPF3 as ready
Mendeliome v0.12980 PRPF4 Zornitza Stark Marked gene: PRPF4 as ready
Mendeliome v0.12977 PRPF6 Zornitza Stark Marked gene: PRPF6 as ready
Mendeliome v0.12973 PRPH Zornitza Stark Marked gene: PRPH as ready
Mendeliome v0.12969 PRSS1 Zornitza Stark Marked gene: PRSS1 as ready
Mendeliome v0.12969 PRSS1 Zornitza Stark Phenotypes for gene: PRSS1 were changed from to Pancreatitis, hereditary, MIM# 167800
Mendeliome v0.12966 PRSS1 Zornitza Stark reviewed gene: PRSS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8841182, 10204851, 10529393, 11097832, 11702203, 15776435, 16791840, 18461367, 17072318; Phenotypes: Pancreatitis, hereditary, MIM# 167800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12966 PRSS12 Zornitza Stark Marked gene: PRSS12 as ready
Mendeliome v0.12962 PSMC2 Zornitza Stark Marked gene: PSMC2 as ready
Mendeliome v0.12961 PSMC3IP Zornitza Stark Marked gene: PSMC3IP as ready
Mendeliome v0.12961 PSMC3IP Zornitza Stark Phenotypes for gene: PSMC3IP were changed from to Ovarian dysgenesis 3, MIM# 614324
Mendeliome v0.12958 PSMC3IP Zornitza Stark reviewed gene: PSMC3IP: Rating: GREEN; Mode of pathogenicity: None; Publications: 21963259, 35352317, 34878148, 30406445, 29240891; Phenotypes: Ovarian dysgenesis 3, MIM# 614324; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12958 PSMD12 Zornitza Stark Marked gene: PSMD12 as ready
Mendeliome v0.12955 PSPH Zornitza Stark Marked gene: PSPH as ready
Mendeliome v0.12952 PSTPIP1 Zornitza Stark Marked gene: PSTPIP1 as ready
Mendeliome v0.12952 PSTPIP1 Zornitza Stark Phenotypes for gene: PSTPIP1 were changed from to Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416; PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome
Mendeliome v0.12949 PSTPIP1 Zornitza Stark reviewed gene: PSTPIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11971877, 34938582, 34778321, 34745107, 34492165, 34047005; Phenotypes: Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416, PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12949 PTGDR Zornitza Stark Marked gene: PTGDR as ready
Mendeliome v0.12946 PTH Zornitza Stark Marked gene: PTH as ready
Mendeliome v0.12946 PTH Zornitza Stark Phenotypes for gene: PTH were changed from to Hypoparathyroidism, familial isolated 1, MIM# 146200
Mendeliome v0.12943 PTH Zornitza Stark reviewed gene: PTH: Rating: GREEN; Mode of pathogenicity: None; Publications: 2212001, 1302009, 10523031, 35165722, 32421798; Phenotypes: Hypoparathyroidism, familial isolated 1, MIM# 146200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12943 PTH1R Zornitza Stark Marked gene: PTH1R as ready
Mendeliome v0.12943 PTH1R Zornitza Stark Phenotypes for gene: PTH1R were changed from to Failure of tooth eruption, primary MIM#125350; Eiken syndrome MIM#600002; Metaphyseal chondrodysplasia, Murk Jansen type MIM#156400; Chondrodysplasia, Blomstrand type MIM#215045
Mendeliome v0.12940 PTH1R Zornitza Stark reviewed gene: PTH1R: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Failure of tooth eruption, primary MIM#125350, Eiken syndrome MIM#600002, Metaphyseal chondrodysplasia, Murk Jansen type MIM#156400, Chondrodysplasia, Blomstrand type MIM#215045; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12940 PTHLH Zornitza Stark Marked gene: PTHLH as ready
Mendeliome v0.12937 PTPN14 Zornitza Stark Marked gene: PTPN14 as ready
Mendeliome v0.12934 CLPB Zornitza Stark Phenotypes for gene: CLPB were changed from 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271 to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271; Neutropenia, severe congenital, 9, autosomal dominant, MIM# 619813
Mendeliome v0.12933 CLPB Zornitza Stark edited their review of gene: CLPB: Changed phenotypes: 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271, Neutropenia, severe congenital, 9, autosomal dominant, MIM# 619813
Mendeliome v0.12933 GCNA Zornitza Stark Phenotypes for gene: GCNA were changed from primary spermatogenic failure to Spermatogenic failure, X-linked, 4, MIM# 301077
Mendeliome v0.12930 PTPN22 Zornitza Stark Marked gene: PTPN22 as ready
Mendeliome v0.12928 PTPRO Zornitza Stark Marked gene: PTPRO as ready
Mendeliome v0.12925 PTRH2 Zornitza Stark Marked gene: PTRH2 as ready
Mendeliome v0.12922 PTRH2 Zornitza Stark commented on gene: PTRH2: Infantile-onset multisystem neurologic, endocrine, and pancreatic disease-1 (IMNEPD1) is an autosomal recessive multisystemic disorder with variable expressivity. The core features usually include global developmental delay with impaired intellectual development and speech delay, ataxia, sensorineural hearing loss, and pancreatic insufficiency. Additional features may include peripheral neuropathy, postnatal microcephaly, dysmorphic facial features, and cerebellar atrophy.

More than 5 unrelated families reported. The Q85P missense variant is reported in several families, likely founder effect.
Mendeliome v0.12922 PTS Zornitza Stark Marked gene: PTS as ready
Mendeliome v0.12920 PUM1 Zornitza Stark Marked gene: PUM1 as ready
Mendeliome v0.12920 PUM1 Zornitza Stark Phenotypes for gene: PUM1 were changed from to Spinocerebellar ataxia 47, MIM# 617931; Neurodevelopmental disorder, MONDO:0700092, PUM1-related
Mendeliome v0.12917 PUM1 Zornitza Stark reviewed gene: PUM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29474920, 25768905, 30903679, 31859446; Phenotypes: Spinocerebellar ataxia 47, MIM# 617931, Neurodevelopmental disorder, MONDO:0700092, PUM1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12917 PYCR2 Zornitza Stark Marked gene: PYCR2 as ready
Mendeliome v0.12913 PYROXD1 Zornitza Stark Marked gene: PYROXD1 as ready
Mendeliome v0.12913 PYROXD1 Zornitza Stark Phenotypes for gene: PYROXD1 were changed from to Myopathy, myofibrillar, 8 , MIM#617258
Mendeliome v0.12910 F12 Bryony Thompson commented on gene: F12: Also associated with FXII deficiency - PMID: 29383625, 20022356, 18024408, 20386432, 26709783, 21264442, 28007010, 15205584, 30700128 - Biallalelic loss-of-function variants are a well-established cause of FXII deficiency. FXII deficiency is not associated with bleeding risk unlike other coagulation factors, it is either asymptomatic or characterized by a prolonged activated partial thromboplastin time. DEFINITIVE gene-disease validity classification by the ClinGen Hemostasis Thrombosis VCEP, Classification - 01/22/2020
Mendeliome v0.12910 PYROXD1 Zornitza Stark reviewed gene: PYROXD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27745833; Phenotypes: Myopathy, myofibrillar, 8 , MIM#617258; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12910 F12 Bryony Thompson reviewed gene: F12: Rating: GREEN; Mode of pathogenicity: Other; Publications: 26193639, 16638441, 17381464, 21849258, 17186468, 19178938, 30463937, 23994767; Phenotypes: Hereditary angioedema type 3 MONDO:0012526; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12910 SGCD Zornitza Stark Marked gene: SGCD as ready
Mendeliome v0.12910 SGCD Zornitza Stark Phenotypes for gene: SGCD were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 6, MIM# 601287; autosomal recessive limb-girdle muscular dystrophy MONDO:0015152
Mendeliome v0.12907 SGCD Zornitza Stark reviewed gene: SGCD: Rating: GREEN; Mode of pathogenicity: None; Publications: 8841194, 19259135, 20623375, 10838250, 10735275, 9832045, 30733730; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 6, MIM# 601287, autosomal recessive limb-girdle muscular dystrophy MONDO:0015152; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12907 SGCB Zornitza Stark Marked gene: SGCB as ready
Mendeliome v0.12907 SGCB Zornitza Stark Phenotypes for gene: SGCB were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 4 MIM#604286; autosomal recessive limb-girdle muscular dystrophy, MONDO:0015152
Mendeliome v0.12904 SGCA Zornitza Stark Marked gene: SGCA as ready
Mendeliome v0.12904 SGCA Zornitza Stark Phenotypes for gene: SGCA were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 3 MIM#608099; autosomal recessive limb-girdle muscular dystrophy, MONDO:0015152
Mendeliome v0.12901 SFXN4 Zornitza Stark Marked gene: SFXN4 as ready
Mendeliome v0.12898 SFRP4 Zornitza Stark Marked gene: SFRP4 as ready
Mendeliome v0.12895 RASGRP1 Zornitza Stark Marked gene: RASGRP1 as ready
Mendeliome v0.12892 PDCD1 Zornitza Stark Marked gene: PDCD1 as ready
Mendeliome v0.12887 PCK2 Zornitza Stark Marked gene: PCK2 as ready
Mendeliome v0.12883 PCCB Zornitza Stark Marked gene: PCCB as ready
Mendeliome v0.12880 PCCA Zornitza Stark Marked gene: PCCA as ready
Mendeliome v0.12874 PC Zornitza Stark Marked gene: PC as ready
Mendeliome v0.12874 PC Zornitza Stark Phenotypes for gene: PC were changed from to Pyruvate carboxylase deficiency - MIM#266150
Mendeliome v0.12871 PAX9 Zornitza Stark Marked gene: PAX9 as ready
Mendeliome v0.12866 SET Zornitza Stark Marked gene: SET as ready
Mendeliome v0.12863 SERPING1 Zornitza Stark Marked gene: SERPING1 as ready
Mendeliome v0.12863 SERPING1 Zornitza Stark Phenotypes for gene: SERPING1 were changed from to Angioedema, hereditary, 1 and 2, MIM#106100; Complement component 4, partial deficiency of, MIM#120790
Mendeliome v0.12859 SGCD Samantha Ayres edited their review of gene: SGCD: Added comment: Variants identified in multiple cases of cardiomyopathy, however most are too common in the general population to explain the disease.
First described in the literature with potential association to cardiomyopathy in 2000 (Tsubata et al 10974018).
Case-control study by Mazzarotto et al 2020, did not identify enrichment of SGCD in DCM cohort.

Animal models demonstrate mild cardiomyopathy phenotype.

Curated as 'limited' gene-disease association by ClinGen; Changed rating: RED; Changed publications: 10974018, 31983221, 23695275; Changed phenotypes: Cardiomyopathy, dilated, 1L, MIM#606685, dilated cardiomyopathy MONDO:0005021; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12859 SGCD Samantha Ayres reviewed gene: SGCD: Rating: GREEN; Mode of pathogenicity: None; Publications: 8841194, 30733730, 10838250; Phenotypes: autosomal recessive limb-girdle muscular dystrophy MONDO:0015152, Muscular dystrophy, limb-girdle, autosomal recessive 6, MIM#601287; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12859 SGCB Samantha Ayres reviewed gene: SGCB: Rating: GREEN; Mode of pathogenicity: None; Publications: 18285821; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 4 MIM#604286, autosomal recessive limb-girdle muscular dystrophy, MONDO:0015152; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12859 SGCA Samantha Ayres reviewed gene: SGCA: Rating: GREEN; Mode of pathogenicity: None; Publications: 30007747, 9192266, 34404573; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 3 MIM#608099, autosomal recessive limb-girdle muscular dystrophy, MONDO:0015152; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12859 SERPIND1 Zornitza Stark Marked gene: SERPIND1 as ready
Mendeliome v0.12859 SERPIND1 Zornitza Stark Phenotypes for gene: SERPIND1 were changed from to heparin cofactor 2 deficiency, MONDO:0012876; Thrombophilia 10 due to heparin cofactor II deficiency, MIM#612356
Mendeliome v0.12855 PDCD1 Krithika Murali changed review comment from: No OMIM gene disease association.

1 individual from a consanguineous family reported with PDCD1 deficiency.

PMID: 34183838 (Nat Medicine 2021) - proband is the son of consanguineous Turkish parents. He was diagnosed with type 1 diabetes (T1D), hypothyroidism, and juvenile idiopathic arthritis (JIA) at the age of three years. He developed abdominal TB age 10 and died from pulmonary alveolar haemorrhage age 11. WES identified homozygous intragenic PDCD1 gene duplication (c.105dupC p.T36Hfs*70). Absent from population databases and unaffected parents confirmed to be heterozygous. Supportive in vitro studies showing absent expression or function of PD-1 protein. Proband's older brother died at the age of 3 from unexplained pneumonitis and had a history of T1DM and juvenile idiopathic arthritis.; to: No OMIM gene disease association.

1 individual from a consanguineous family reported with PDCD1 deficiency.

PMID: 34183838 (Nat Medicine 2021) - proband is the son of consanguineous Turkish parents. He was diagnosed with type 1 diabetes (T1D), hypothyroidism, and juvenile idiopathic arthritis (JIA) at the age of three years. He developed abdominal TB age 10 and died from pulmonary alveolar haemorrhage age 11. WES identified homozygous intragenic PDCD1 gene duplication (c.105dupC p.T36Hfs*70). Absent from population databases and unaffected parents confirmed to be heterozygous. Supportive in vitro studies showing absent expression or function of PD-1 protein. Proband's older brother died at the age of 3 from unexplained pneumonitis and had a history of T1DM and juvenile idiopathic arthritis.
Mendeliome v0.12855 CD79A Ain Roesley Marked gene: CD79A as ready
Mendeliome v0.12853 CD70 Ain Roesley Marked gene: CD70 as ready
Mendeliome v0.12851 CD55 Ain Roesley Marked gene: CD55 as ready
Mendeliome v0.12849 CD46 Ain Roesley Marked gene: CD46 as ready
Mendeliome v0.12848 PC Krithika Murali reviewed gene: PC: Rating: GREEN; Mode of pathogenicity: None; Publications: 9585612, 12112657; Phenotypes: Pyruvate carboxylase deficiency - MIM#266150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12848 CD40 Ain Roesley Marked gene: CD40 as ready
Mendeliome v0.12846 CD36 Ain Roesley Marked gene: CD36 as ready
Mendeliome v0.12846 CD36 Ain Roesley Phenotypes for gene: CD36 were changed from to Platelet glycoprotein IV deficiency MIM#608404; {Malaria, cerebral, reduced risk of} MIM#611162; {Malaria, cerebral, susceptibility to} MIM#611162
Mendeliome v0.12844 CD36 Ain Roesley reviewed gene: CD36: Rating: GREEN; Mode of pathogenicity: None; Publications: 7686693, 11950861, 10890433, 24960640, 10890433; Phenotypes: Platelet glycoprotein IV deficiency MIM#608404, {Malaria, cerebral, reduced risk of} MIM#611162, {Malaria, cerebral, susceptibility to} MIM#611162; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12844 CD36 Ain Roesley reviewed gene: CD36: Rating: GREEN; Mode of pathogenicity: None; Publications: 7533783, 11950861, 10890433, 12506336; Phenotypes: {Malaria, cerebral, reduced risk of} MIM#611162, {Malaria, cerebral, susceptibility to} MIM#611162, Platelet glycoprotein IV deficiency MIM#608404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12844 CD209 Ain Roesley Marked gene: CD209 as ready
Mendeliome v0.12843 CD151 Ain Roesley Marked gene: CD151 as ready
Mendeliome v0.12841 CCR5 Ain Roesley Marked gene: CCR5 as ready
Mendeliome v0.12838 CCR2 Ain Roesley changed review comment from: Currently no mendelian gene-disease association; to: Vall64Ile has been associated with reduction in the progression to AIDS. Mutant results in normal expression levels of the CCR2 receptor and has no effect on the incidence of HIV infection. However, in contrast to normal CCR2 peptides, the mutant protein preferentially dimerizes with the CXCR4 polypeptide, isolating it in the endoplasmic reticulum. It is also thought that the inhibitory effect is dependent on the stages of HIV-1 infection and interactions with other genetic variants.
Mendeliome v0.12836 CCR2 Ain Roesley Marked gene: CCR2 as ready
Mendeliome v0.12836 SLC25A12 Zornitza Stark Marked gene: SLC25A12 as ready
Mendeliome v0.12833 SLC25A13 Zornitza Stark Marked gene: SLC25A13 as ready
Mendeliome v0.12830 SLC25A15 Zornitza Stark Marked gene: SLC25A15 as ready
Mendeliome v0.12827 SLC25A19 Zornitza Stark Marked gene: SLC25A19 as ready
Mendeliome v0.12824 SLC25A22 Zornitza Stark Marked gene: SLC25A22 as ready
Mendeliome v0.12821 TRPM1 Zornitza Stark Marked gene: TRPM1 as ready
Mendeliome v0.12821 TRPM1 Zornitza Stark Phenotypes for gene: TRPM1 were changed from to Night blindness, congenital stationary (complete), 1C, autosomal recessive, MIM# 613216
Mendeliome v0.12818 TRPM1 Zornitza Stark reviewed gene: TRPM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19878917, 19896113, 19896109; Phenotypes: Night blindness, congenital stationary (complete), 1C, autosomal recessive, MIM# 613216; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12818 TRPC6 Zornitza Stark Marked gene: TRPC6 as ready
Mendeliome v0.12815 TRAPPC2 Zornitza Stark Marked gene: TRAPPC2 as ready
Mendeliome v0.12815 TRAPPC2 Zornitza Stark Phenotypes for gene: TRAPPC2 were changed from to Spondyloepiphyseal dysplasia tarda, MIM# 313400
Mendeliome v0.12812 TRAPPC2 Zornitza Stark reviewed gene: TRAPPC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10431248, 14755465, 33726005, 20301324, 32953644; Phenotypes: Spondyloepiphyseal dysplasia tarda, MIM# 313400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.12812 TRAPPC12 Zornitza Stark Marked gene: TRAPPC12 as ready
Mendeliome v0.12812 TRAPPC11 Zornitza Stark Marked gene: TRAPPC11 as ready
Mendeliome v0.12812 TRAPPC11 Zornitza Stark Phenotypes for gene: TRAPPC11 were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 18, MIM# 615356
Mendeliome v0.12809 TRAPPC11 Zornitza Stark reviewed gene: TRAPPC11: Rating: GREEN; Mode of pathogenicity: None; Publications: 23830518, 26322222, 29855340, 30105108; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 18, MIM# 615356; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12809 TRAK1 Zornitza Stark Marked gene: TRAK1 as ready
Mendeliome v0.12806 TPMT Zornitza Stark Marked gene: TPMT as ready
Mendeliome v0.12804 TRNT1 Zornitza Stark Marked gene: TRNT1 as ready
Mendeliome v0.12801 TRMU Zornitza Stark Marked gene: TRMU as ready
Mendeliome v0.12798 TRMT5 Zornitza Stark Marked gene: TRMT5 as ready
Mendeliome v0.12793 ETV1 Bryony Thompson Marked gene: ETV1 as ready
Mendeliome v0.12793 EXT1 Bryony Thompson reviewed gene: EXT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7550340, 8981950, 20534475; Phenotypes: hereditary multiple osteochondromas MONDO:0005508, exostoses, multiple, type 1 MONDO:0007585; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.12790 EXOC3L2 Bryony Thompson Phenotypes for gene: EXOC3L2 were changed from Dandy-Walker malformation; renal dysplasia; bone marrow failure to Dandy-Walker malformation, MONDO:0009072; renal dysplasia; bone marrow failure
Mendeliome v0.12789 ETFDH Bryony Thompson Marked gene: ETFDH as ready
Mendeliome v0.12787 SERPING1 Samantha Ayres reviewed gene: SERPING1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35386643, 31517426, 29753808; Phenotypes: Angioedema, hereditary, 1 and 2, MIM#106100, Complement component 4, partial deficiency of, MIM#120790; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12787 SERPIND1 Samantha Ayres reviewed gene: SERPIND1: Rating: GREEN; Mode of pathogenicity: None; Publications: 2863444, 8902986, 2647747, 15337701, 31064749, 11204559, 8562924, 29296762; Phenotypes: heparin cofactor 2 deficiency, MONDO:0012876, Thrombophilia 10 due to heparin cofactor II deficiency, MIM#612356; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12787 TRMT10C Zornitza Stark Marked gene: TRMT10C as ready
Mendeliome v0.12784 PDHA2 Zornitza Stark Marked gene: PDHA2 as ready
Mendeliome v0.12784 PDHA2 Zornitza Stark gene: PDHA2 was added
gene: PDHA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDHA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDHA2 were set to 29581481; 35172124
Phenotypes for gene: PDHA2 were set to Spermatogenic failure-70, MIM#619828
Review for gene: PDHA2 was set to RED
Added comment: Three individuals reported from different families with same homozygous missense variant. Same ethnic background, likely founder effect.
Sources: Literature
Mendeliome v0.12783 TRDN Zornitza Stark Marked gene: TRDN as ready
Mendeliome v0.12783 TRDN Zornitza Stark Phenotypes for gene: TRDN were changed from to Cardiac arrhythmia syndrome, with or without skeletal muscle weakness, MIM# 615441
Mendeliome v0.12780 TRDN Zornitza Stark reviewed gene: TRDN: Rating: GREEN; Mode of pathogenicity: None; Publications: 31983240, 25922419, 30649896, 22422768; Phenotypes: Cardiac arrhythmia syndrome, with or without skeletal muscle weakness, MIM# 615441; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12780 TRHR Zornitza Stark Marked gene: TRHR as ready
Mendeliome v0.12777 TRIM37 Zornitza Stark Marked gene: TRIM37 as ready
Mendeliome v0.12774 TRIM32 Zornitza Stark Marked gene: TRIM32 as ready
Mendeliome v0.12774 TRIM32 Zornitza Stark Phenotypes for gene: TRIM32 were changed from to Bardet-Biedl syndrome 11, MIM# 615988; Muscular dystrophy, limb-girdle, autosomal recessive 8 MIM#254110
Mendeliome v0.12771 TRIM32 Zornitza Stark edited their review of gene: TRIM32: Added comment: >3 unrelated cases with myopathy, adult onset reported; Changed rating: GREEN; Changed publications: 16606853, 31309175, 11822024; Changed phenotypes: Bardet-Biedl syndrome 11, MIM# 615988, Muscular dystrophy, limb-girdle, autosomal recessive 8 MIM#254110
Mendeliome v0.12771 TRPM4 Zornitza Stark Marked gene: TRPM4 as ready
Mendeliome v0.12771 TRPM4 Zornitza Stark Phenotypes for gene: TRPM4 were changed from to Progressive familial heart block, type IB, MIM# 604559; Erythrokeratodermia variabilis et progressiva 6, MIM# 618531
Mendeliome v0.12767 TRPM4 Zornitza Stark reviewed gene: TRPM4: Rating: AMBER; Mode of pathogenicity: None; Publications: 19726882, 20562447, 21887725, 20562447, 35205305, 34897640, 30528822; Phenotypes: Progressive familial heart block, type IB, MIM# 604559, Erythrokeratodermia variabilis et progressiva 6 618531; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12767 TRPV4 Zornitza Stark Marked gene: TRPV4 as ready
Mendeliome v0.12767 TRPV4 Zornitza Stark Phenotypes for gene: TRPV4 were changed from to Hereditary motor and sensory neuropathy, type IIc, MIM# 606071; Neuronopathy, distal hereditary motor, type VIII, MIM# 600175
Mendeliome v0.12765 TTPA Zornitza Stark Marked gene: TTPA as ready
Mendeliome v0.12762 TTC19 Zornitza Stark Marked gene: TTC19 as ready
Mendeliome v0.12762 TTC19 Zornitza Stark Phenotypes for gene: TTC19 were changed from to Mitochondrial complex III deficiency, nuclear type 2, MIM#615157
Mendeliome v0.12759 TTC19 Zornitza Stark edited their review of gene: TTC19: Added comment: Mitochondrial complex III deficiency nuclear type 2 is an autosomal recessive severe neurodegenerative disorder that usually presents in childhood, but may show later onset, even in adulthood. Affected individuals have motor disability, with ataxia, apraxia, dystonia, and dysarthria, associated with necrotic lesions throughout the brain. Most patients also have cognitive impairment and axonal neuropathy and become severely disabled later in life. The disorder may present clinically as spinocerebellar ataxia or Leigh syndrome, or with psychiatric disturbances.

At least 4 unrelated families reported.; Changed publications: 21278747, 23532514, 24368687, 24397319
Mendeliome v0.12759 TSFM Zornitza Stark Marked gene: TSFM as ready
Mendeliome v0.12756 TSFM Zornitza Stark changed review comment from: Ataxia is a reported feature of this mitochondrial disorder.; to: At least 5 families reported, however 3 had the same homozygous variant, ?founder.
Mendeliome v0.12756 TPK1 Zornitza Stark Marked gene: TPK1 as ready
Mendeliome v0.12753 TP63 Zornitza Stark Marked gene: TP63 as ready
Mendeliome v0.12753 TP63 Zornitza Stark Phenotypes for gene: TP63 were changed from to ADULT syndrome, OMIM #103285; Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, OMIM #604292; Hay-Wells syndrome, OMIM #106260; Limb-mammary syndrome, OMIM #603543; Orofacial cleft 8, OMIM #618149; Rapp-Hodgkin syndrome, OMIM #129400; Split-hand/foot malformation 4, OMIM #605289
Mendeliome v0.12750 TP63 Zornitza Stark reviewed gene: TP63: Rating: GREEN; Mode of pathogenicity: None; Publications: 20556892; Phenotypes: ADULT syndrome, OMIM #103285, Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, OMIM #604292, Hay-Wells syndrome, OMIM #106260, Limb-mammary syndrome, OMIM #603543, Orofacial cleft 8, OMIM #618149, Rapp-Hodgkin syndrome, OMIM #129400, Split-hand/foot malformation 4, OMIM #605289; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12750 TOR1A Zornitza Stark Marked gene: TOR1A as ready
Mendeliome v0.12750 TOR1A Zornitza Stark Phenotypes for gene: TOR1A were changed from to Arthrogryposis multiplex congenita, MIM#618947; Dystonia-1, torsion, MIM#128100
Mendeliome v0.12747 TOR1A Zornitza Stark reviewed gene: TOR1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 30244176, 9288096, 19955557, 18477710, 32243914, 31583275, 31347572; Phenotypes: Arthrogryposis multiplex congenita, MIM#618947, Dystonia-1, torsion, MIM#128100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12747 TNXB Zornitza Stark Marked gene: TNXB as ready
Mendeliome v0.12744 TNPO3 Zornitza Stark Marked gene: TNPO3 as ready
Mendeliome v0.12744 TNPO3 Zornitza Stark Phenotypes for gene: TNPO3 were changed from to Muscular dystrophy, limb-girdle, autosomal dominant 2, MIM# 608423
Mendeliome v0.12741 TNPO3 Zornitza Stark reviewed gene: TNPO3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23667635, 23543484, 31071488, 31192305; Phenotypes: Muscular dystrophy, limb-girdle, autosomal dominant 2, MIM# 608423; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12741 RSPO2 Zornitza Stark Marked gene: RSPO2 as ready
Mendeliome v0.12738 PIGA Zornitza Stark changed review comment from: PIGA 34875027: variants in PIGA causing a neurodevelopment disorder and a juvenile form of hereditary hemochromatosis reported in > three unrelated patients. All patients had increased serum iron, ferritin and transferrin saturation levels, high ALP and low hepcidin. All patients had generalised seizures and intellectual disability. A subpopulation of patient blood cells showed a slight reduction of GPI-anchored proteins, suggesting that the mutations were hypomorphic and retained some residual activity. CRISPR/Cas12a-mediated knockdown of PIGA in Hep3B liver cells eliminated the cell surface expression of GPI-anchored proteins CD59 and hemojuvelin (HJV; 608374), as well as caused decreased expression of hepcidin (606464) compared to controls. These hypomorphic alleles could explain the milder neurologic phenotype, which allowed for sufficiently long survival for the iron overload phenotype to manifest.; to: PMID 34875027: variants in PIGA causing a neurodevelopment disorder and a juvenile form of hereditary hemochromatosis reported in > three unrelated patients. All patients had increased serum iron, ferritin and transferrin saturation levels, high ALP and low hepcidin. All patients had generalised seizures and intellectual disability. A subpopulation of patient blood cells showed a slight reduction of GPI-anchored proteins, suggesting that the mutations were hypomorphic and retained some residual activity. CRISPR/Cas12a-mediated knockdown of PIGA in Hep3B liver cells eliminated the cell surface expression of GPI-anchored proteins CD59 and hemojuvelin (HJV; 608374), as well as caused decreased expression of hepcidin (606464) compared to controls. These hypomorphic alleles could explain the milder neurologic phenotype, which allowed for sufficiently long survival for the iron overload phenotype to manifest.
Mendeliome v0.12737 PIGA Zornitza Stark edited their review of gene: PIGA: Added comment: PIGA 34875027: variants in PIGA causing a neurodevelopment disorder and a juvenile form of hereditary hemochromatosis reported in > three unrelated patients. All patients had increased serum iron, ferritin and transferrin saturation levels, high ALP and low hepcidin. All patients had generalised seizures and intellectual disability. A subpopulation of patient blood cells showed a slight reduction of GPI-anchored proteins, suggesting that the mutations were hypomorphic and retained some residual activity. CRISPR/Cas12a-mediated knockdown of PIGA in Hep3B liver cells eliminated the cell surface expression of GPI-anchored proteins CD59 and hemojuvelin (HJV; 608374), as well as caused decreased expression of hepcidin (606464) compared to controls. These hypomorphic alleles could explain the milder neurologic phenotype, which allowed for sufficiently long survival for the iron overload phenotype to manifest.; Changed publications: 22305531, 24357517, 24706016, 26545172, 33333793, 32694024, 34875027; Changed phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM# 300868, MONDO:0010466, Neurodevelopmental disorder with epilepsy and haemochromatosis, MIM# 301072
Mendeliome v0.12733 TNNC1 Zornitza Stark Marked gene: TNNC1 as ready
Mendeliome v0.12733 CACNA2D1 Alison Yeung Marked gene: CACNA2D1 as ready
Mendeliome v0.12731 TTC21B Dean Phelan edited their review of gene: TTC21B: Added comment: Correcting typographical error; Changed phenotypes: Glomerular disorder (MONDO:0019722), TTC21B-related
Mendeliome v0.12731 CACNA2D1 Michelle Torres gene: CACNA2D1 was added
gene: CACNA2D1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CACNA2D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACNA2D1 were set to 35293990
Phenotypes for gene: CACNA2D1 were set to developmental and epileptic encephalopathy disorder MONDO:0100062 CACNA2D1-related
Review for gene: CACNA2D1 was set to GREEN
Added comment: PMID 35293990: WES of 2x unrelated individuals with early-onset developmental epileptic encephalopathy, microcephaly, severe hypotonia, absent speech, spasticity, choreiform movements, orofacial dyskinesia, and 2 cortical visual impairment, corpus callosum hypoplasia and progressive volume loss. Patient 2 also had a tiny patent foramen ovale.

Patient 1 is homozygous for p.(Ser275Asnfs*13). mRNA and protein expression were reduced to ~10% of WT in fibroblasts

Patient 2 is cHet for p.(Leu9Alafs*5) and p.(Gly209Asp). mRNA expression in patients fibroblasts was similar to controls, and protein expression reduced to 31-38%. Functional of the p.(Gly209Asp) showed impaired localization and mutagenesis showed complete loss of channel function.
Sources: Literature
Mendeliome v0.12731 TTC21B Dean Phelan edited their review of gene: TTC21B: Added comment: Updated to include additional publications linking glomerular disorder.; Changed rating: GREEN; Changed publications: PMID: 35289079, 26940125, 28124483, 31208513, 34805047; Changed phenotypes: Glomerular disorder (MONOD:0019722), TTC21B-related
Mendeliome v0.12731 TRAPPC10 Zornitza Stark Marked gene: TRAPPC10 as ready
Mendeliome v0.12730 TNNC1 Zornitza Stark Phenotypes for gene: TNNC1 were changed from to Cardiomyopathy, dilated, 1Z, MIM# 611879; Cardiomyopathy, hypertrophic, 13 (MIM# 613243)
Mendeliome v0.12729 TTC21B Zornitza Stark Phenotypes for gene: TTC21B were changed from Nephronophthisis 12, MIM# 613820; Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819; Joubert syndrome to Nephronophthisis 12, MIM# 613820; Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819; Joubert syndrome; Glomerular disorder MONDO:0019722, TTC21B-related
Mendeliome v0.12728 TRAPPC10 Naomi Baker gene: TRAPPC10 was added
gene: TRAPPC10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRAPPC10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC10 were set to PMID: 35298461; 30167849
Phenotypes for gene: TRAPPC10 were set to neurodevelopmental disorder (MONDO:0700092), TRAPPC10-related
Review for gene: TRAPPC10 was set to GREEN
Added comment: PMID: 35298461 – two Pakistani families reported with homozygous variants. Family 1 has frameshift variant in 8 affected individual and family 2 has missense variant in 2 affected individuals. Patients present with microcephaly, short stature, hypotonia, severe ID and behavioural abnormalities. Seizures also reported in 4/10 individuals. Paper also reported brain abnormalities in null mouse model and other functional in transfected cell lines.

PMID: 30167849 – initial report of family 2 above.
Sources: Literature
Mendeliome v0.12726 TNNI1 Zornitza Stark Marked gene: TNNI1 as ready
Mendeliome v0.12725 TNNI1 Zornitza Stark Phenotypes for gene: TNNI1 were changed from arthrogryposis; joint contractures to Arthrogryposis MONDO:0008779, TNNI1-related
Mendeliome v0.12724 SLC35B2 Alison Yeung Marked gene: SLC35B2 as ready
Mendeliome v0.12723 ATP2B1 Zornitza Stark Marked gene: ATP2B1 as ready
Mendeliome v0.12722 SLC35B2 Melanie Marty changed review comment from: 2 x individuals with homozygous variants (c.1218_1220del and c.1224_1225del) in SLC35B2. Phenotypes included pre- and postnatal growth retardation, scoliosis, severe motor and intellectual disabilities and hypomyelinating leukodystrophy.

Functional analysis on patient cells showed that the variants result in a decreased expression of mRNA and affect protein subcellular localization leading to functional impairment of the protein.
Sources: Literature; to: 2 x individuals with homozygous variants (c.1218_1220del and c.1224_1225del) in SLC35B2. Phenotypes included pre- and postnatal growth retardation, scoliosis, severe motor and intellectual disabilities and hypomyelinating leukodystrophy.

Functional analysis on patient cells showed that the variants result in a decreased expression of mRNA and affect protein subcellular localization leading to functional impairment of the protein.
Sources: Literature
Mendeliome v0.12721 ADAM22 Alison Yeung Phenotypes for gene: ADAM22 were changed from Epileptic encephalopathy, early infantile, 61, MIM# 617933 to Developmental and epileptic encephalopathy 61 (MIM#617933)
Mendeliome v0.12720 MDFIC Zornitza Stark Marked gene: MDFIC as ready
Mendeliome v0.12720 TTC21B Dean Phelan reviewed gene: TTC21B: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35289079; Phenotypes: early onset hypertension, proteinuria, progressive kidney disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12720 FUZ Anna Ritchie changed review comment from: Novel missense p.(Arg284Pro) mutation in FUZ identified in twins presenting with craniosynostosis. Loss of Fuz resulted in increased mineralisation in both in vitro embryonic primary osteoblast cultures and in fibroblasts undergoing an osteogenic challenge. No previous reports have implicated changes in human FUZ in craniosynostosis. However, variations in FUZ have been found in patients with neural tube defects.; to: Novel missense p.(Arg284Pro) mutation in FUZ identified in twins presenting with craniosynostosis. Loss of Fuz resulted in increased mineralisation in both in vitro embryonic primary osteoblast cultures and in fibroblasts undergoing an osteogenic challenge. No previous reports have implicated changes in human FUZ in craniosynostosis. However, variations in FUZ have been found in patients with neural tube defects.
Mendeliome v0.12714 TNNI1 Krithika Murali gene: TNNI1 was added
gene: TNNI1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TNNI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNNI1 were set to 34934811
Phenotypes for gene: TNNI1 were set to arthrogryposis; joint contractures
Review for gene: TNNI1 was set to AMBER
Added comment: No OMIM gene disease association reported

PMID 34934811 Nishimori et al report 2 individuals from a Japanese family with joint contractures, elevated CK and a novel heterozygous TNNI1 variant.

The proband was born with clasped thumbs (gestational age not stated) requiring surgical correction at 5 months of age. At age 14 was diagnosed with contractures of the neck, trunk, hip and knee with elevated serum CK (1689 IU/L). No muscle weakness noted. Muscle biopsy showed moth-eaten appearance of type I fibres and electron microscopy showed type 1 fibre Z disk streaming.

Trio exome sequencing identified a paternally heterozygous nonsense TNNI1 variant (c.523A>T p.K175*). The proband's father and paternal grandfather (not genotyped) also have a history of joint contractures with elevated CK.

The affected amino acid residue is in the tropomyosin binding site near the C-terminus and is highly conserved. The variant is absent from gnomAD. rt-PCR products of mRNA from the patient's muscle biopsy showed presence of both mutated and normal transcripts.
Sources: Literature
Mendeliome v0.12714 TNNC1 Zornitza Stark reviewed gene: TNNC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33947203, 31983221, 17977476, 19808376, 11385718, 8572189, 21262074, 22815480, 26779504; Phenotypes: Cardiomyopathy, dilated, 1Z, MIM# 611879, Cardiomyopathy, hypertrophic, 13 (MIM# 613243); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12714 SLC35B2 Melanie Marty gene: SLC35B2 was added
gene: SLC35B2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC35B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC35B2 were set to PMID: 35325049
Phenotypes for gene: SLC35B2 were set to chondrodysplasia with hypomyelinating leukodystrophy, intellectual disability
Review for gene: SLC35B2 was set to AMBER
Added comment: 2 x individuals with homozygous variants (c.1218_1220del and c.1224_1225del) in SLC35B2. Phenotypes included pre- and postnatal growth retardation, scoliosis, severe motor and intellectual disabilities and hypomyelinating leukodystrophy.

Functional analysis on patient cells showed that the variants result in a decreased expression of mRNA and affect protein subcellular localization leading to functional impairment of the protein.
Sources: Literature
Mendeliome v0.12714 AHSG Elena Savva gene: AHSG was added
gene: AHSG was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AHSG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AHSG were set to PMID: 28054173; 9395485; 31288248; 17389622
Phenotypes for gene: AHSG were set to ?Alopecia-intellectual disability syndrome 1 MIM#203650; infantile cortical hyperostosis
Review for gene: AHSG was set to RED
Added comment: PMID: 28054173 - 7 relatives within a large consanguinous fam w/ alopecia and ID, and a hom missense (p.Arg317His). Modelling predicts this variant to be a phosphorylation site, functional studies show a difference in protein size. Unclear biological significance.
Alt change with stronger GS (p.(Arg317Cys)) is a common poly with 19 homozygotes in gnomAD.

No hom PTCs in gnomAD

PMID: 9395485 - K/O mouse model shows no gross anatomical abnormalities, were fertile and "healthy". No mentioned of ID, alopecia
PMID: 17389622 - K/O mouse model on the calcification resistant genetic background C57BL/6, shows uraemia and phosphate challenge. No mentioned of ID, alopecia

PMID: 31288248 - 1 hom infant (p.K2*, within 5' NMD escape region) with infantile cortical hyperostosis, loss of enzyme in patient serum shown by ELISA. No mentioned of ID, alopecia
Sources: Literature
Mendeliome v0.12713 VPS16 Ain Roesley Phenotypes for gene: VPS16 were changed from Dystonia 30, MIM#619291 to Dystonia 30, MIM#619291; mucopolysaccharidosis-like disorder, VPS16-related MONDO#0100365
Mendeliome v0.12711 MDFIC Belinda Chong gene: MDFIC was added
gene: MDFIC was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MDFIC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDFIC were set to 35235341
Phenotypes for gene: MDFIC were set to Central conducting lymphatic anomaly with lymphedema
Review for gene: MDFIC was set to GREEN
Added comment: Central conducting lymphatic anomaly (CCLA), characterized by the dysfunction of core collecting lymphatic vessels including the thoracic duct and cisterna chyli, and presenting as chylothorax, pleural effusions, chylous ascites, and lymphedema, is a severe disorder often resulting in fetal or perinatal demise.

Seven individuals with CCLA from six independent families. Clinical manifestations of affected fetuses and children included nonimmune hydrops fetalis (NIHF), pleural and pericardial effusions, and lymphedema. Generation of a mouse model of human MDFIC truncation variants revealed that homozygous mutant mice died perinatally exhibiting chylothorax.
Sources: Literature
Mendeliome v0.12711 ATP2B1 Daniel Flanagan gene: ATP2B1 was added
gene: ATP2B1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ATP2B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP2B1 were set to PMID: 35358416
Phenotypes for gene: ATP2B1 were set to Neurodevelopmental delay; autism; seizures; distal limb abnormalities
Review for gene: ATP2B1 was set to GREEN
Added comment: 12 unrelated individuals with variants in ATP2B1 and an overlapping phenotype of mild to moderate global development delay. Additional common symptoms include autism (5), dissimilar forms of seizures (6), and distal limb abnormalities (4). 9 variants proven to be de novo, other 3 variants had unknown inheritance. 9 missense and 3 nonsense reported. Supporting functional analysis for missense.
Sources: Expert list
Mendeliome v0.12711 VPS16 Ain Roesley changed review comment from: for AR MPS:
3 unrelated families - 2x hom c.2272‐18C>A and 1x hom p.Trp180Cys

RNA and functional studies done on the splice variant

for AD
see review below; to: for AR MPS:
3 unrelated families - 2x hom c.2272‐18C>A and 1x hom p.Trp180Cys

RNA and functional studies done on the splice variant

for AD
see review below

PMID:34901436 suggests dystonia is transcript specific
Mendeliome v0.12711 VPS16 Ain Roesley changed review comment from: for AR MPS:
3 unrelated families - 2x hom c.2272‐18C>A and 1x het p.Trp180Cys

RNA and functional studies done on the splice variant

for AD
see review below; to: for AR MPS:
3 unrelated families - 2x hom c.2272‐18C>A and 1x hom p.Trp180Cys

RNA and functional studies done on the splice variant

for AD
see review below
Mendeliome v0.12711 TNFSF4 Zornitza Stark Marked gene: TNFSF4 as ready
Mendeliome v0.12711 TNFSF4 Zornitza Stark Phenotypes for gene: TNFSF4 were changed from to {Myocardial infarction, susceptibility to} 608446
Mendeliome v0.12709 VPS16 Ain Roesley reviewed gene: VPS16: Rating: GREEN; Mode of pathogenicity: None; Publications: 33938619, 34013567; Phenotypes: mucopolysaccharidosis-like disorder, VPS16-related MONDO#0100365; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12708 TNFSF4 Zornitza Stark reviewed gene: TNFSF4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Myocardial infarction, susceptibility to} 608446; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12708 TNFSF11 Zornitza Stark Marked gene: TNFSF11 as ready
Mendeliome v0.12705 TNFRSF11B Zornitza Stark Marked gene: TNFRSF11B as ready
Mendeliome v0.12702 TMEM240 Zornitza Stark Marked gene: TMEM240 as ready
Mendeliome v0.12702 TMEM240 Zornitza Stark Phenotypes for gene: TMEM240 were changed from to Spinocerebellar ataxia 21, MIM# 607454
Mendeliome v0.12699 TMEM127 Zornitza Stark Marked gene: TMEM127 as ready
Mendeliome v0.12697 TMEM126B Zornitza Stark Marked gene: TMEM126B as ready
Mendeliome v0.12697 TMEM126B Zornitza Stark Phenotypes for gene: TMEM126B were changed from to Mitochondrial complex I deficiency, nuclear type 29, MIM# 618250
Mendeliome v0.12694 TMEM126B Zornitza Stark reviewed gene: TMEM126B: Rating: GREEN; Mode of pathogenicity: None; Publications: 27374774, 27374773; Phenotypes: Mitochondrial complex I deficiency, nuclear type 29, MIM# 618250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12694 TMEM106B Zornitza Stark Marked gene: TMEM106B as ready
Mendeliome v0.12691 TMEM106B Zornitza Stark changed review comment from: Cerebellar signs including ataxia prominent.; to: Hypomyelinating leukodystrophy-16 is an autosomal dominant neurologic disorder characterized by onset of hypotonia, nystagmus, and mildly delayed motor development in infancy. Affected individuals have motor disabilities, including ataxic or broad-based gait, hyperreflexia, intention tremor, dysmetria, and a mild pyramidal syndrome. Some patients have cognitive impairment, whereas others may have normal cognition or mild intellectual disability with speech difficulties. Brain imaging typically shows hypomyelination, leukodystrophy, and thin corpus callosum.

At least 5 unrelated individuals reported.
Mendeliome v0.12691 RAPSN Zornitza Stark Marked gene: RAPSN as ready
Mendeliome v0.12688 RAD51C Zornitza Stark Marked gene: RAD51C as ready
Mendeliome v0.12686 LIG3 Zornitza Stark Phenotypes for gene: LIG3 were changed from gut dysmotility; spasticity; ataxia; repetitive behaviours; neurogenic bladder; macular degeneration; leukoencephalopathy; cerebellar atrophy to Mitochondrial DNA depletion syndrome 20 (MNGIE type), MIM# 619780
Mendeliome v0.12684 SLC25A26 Zornitza Stark Marked gene: SLC25A26 as ready
Mendeliome v0.12684 GGN Zornitza Stark Marked gene: GGN as ready
Mendeliome v0.12679 SLC25A3 Zornitza Stark Marked gene: SLC25A3 as ready
Mendeliome v0.12678 SLC25A3 Zornitza Stark Phenotypes for gene: SLC25A3 were changed from to Mitochondrial phosphate carrier deficiency, MIM# 610773
Mendeliome v0.12676 SLC25A3 Zornitza Stark reviewed gene: SLC25A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 17273968, 21763135, 25681081; Phenotypes: Mitochondrial phosphate carrier deficiency, MIM# 610773; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12676 SLC25A4 Zornitza Stark Marked gene: SLC25A4 as ready
Mendeliome v0.12676 SLC25A4 Zornitza Stark Phenotypes for gene: SLC25A4 were changed from to Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, MIM#617184; Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR, MIM#615418; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2, MIM#609283
Mendeliome v0.12673 SLC25A4 Zornitza Stark reviewed gene: SLC25A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 30046662, 30013777, 29654543, 28823815; Phenotypes: Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, MIM#617184, Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR, MIM#615418, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2, MIM#609283; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12673 SLC25A42 Zornitza Stark Marked gene: SLC25A42 as ready
Mendeliome v0.12673 SLC25A42 Zornitza Stark Phenotypes for gene: SLC25A42 were changed from to Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression , MIM#618416
Mendeliome v0.12670 SLC25A42 Zornitza Stark reviewed gene: SLC25A42: Rating: GREEN; Mode of pathogenicity: None; Publications: 26541337, 29327420, 29923093, 34258143; Phenotypes: Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression , MIM#618416; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12670 SLC2A10 Zornitza Stark Marked gene: SLC2A10 as ready
Mendeliome v0.12670 SLC2A10 Zornitza Stark Phenotypes for gene: SLC2A10 were changed from to Arterial tortuosity syndrome, MIM# 208050
Mendeliome v0.12667 SLC2A10 Zornitza Stark reviewed gene: SLC2A10: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 16550171, 17935213; Phenotypes: Arterial tortuosity syndrome, MIM# 208050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12667 SLC2A2 Zornitza Stark changed review comment from: Fanconi-Bickel syndrome is a rare but well-defined clinical entity, inherited in an autosomal recessive mode and characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, and impaired utilization of glucose and galactose.

> 5 patients previously reported with the associated condition, which is a glycogen storage disease. SLC2A2 encodes for the glucose transporter, GLUT2.; to: Fanconi-Bickel syndrome is characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, and impaired utilization of glucose and galactose.

> 5 patients previously reported with the associated condition, which is a glycogen storage disease. SLC2A2 encodes for the glucose transporter, GLUT2.
Mendeliome v0.12667 SLC2A2 Zornitza Stark Marked gene: SLC2A2 as ready
Mendeliome v0.12664 SLC2A3 Zornitza Stark Marked gene: SLC2A3 as ready
Mendeliome v0.12663 SLC2A4 Zornitza Stark Marked gene: SLC2A4 as ready
Mendeliome v0.12662 SORT1 Zornitza Stark Marked gene: SORT1 as ready
Mendeliome v0.12659 SOX10 Zornitza Stark Marked gene: SOX10 as ready
Mendeliome v0.12659 SOX10 Zornitza Stark Phenotypes for gene: SOX10 were changed from to Kallman syndrome; PCWH syndrome (MIM#609136); Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584); Waardenburg syndrome, type 4C (MIM#613266)
Mendeliome v0.12656 SOX10 Zornitza Stark reviewed gene: SOX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 23643381, 24845202; Phenotypes: Kallman syndrome, PCWH syndrome (MIM#609136), Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584), Waardenburg syndrome, type 4C (MIM#613266); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12656 SOX17 Zornitza Stark Marked gene: SOX17 as ready
Mendeliome v0.12656 SOX17 Zornitza Stark Phenotypes for gene: SOX17 were changed from to Vesicoureteral reflux 3 MIM#613674; Pulmonary arterial hypertension, MONDO:0015924
Mendeliome v0.12653 SOX17 Zornitza Stark reviewed gene: SOX17: Rating: GREEN; Mode of pathogenicity: None; Publications: 29650961, 31406341, 20960469; Phenotypes: Vesicoureteral reflux 3 MIM#613674, Pulmonary arterial hypertension, MONDO:0015924; Mode of inheritance: None
Mendeliome v0.12653 SOX18 Zornitza Stark Marked gene: SOX18 as ready
Mendeliome v0.12650 SOX5 Zornitza Stark Marked gene: SOX5 as ready
Mendeliome v0.12647 SOX9 Zornitza Stark Marked gene: SOX9 as ready
Mendeliome v0.12644 NKX2-1 Zornitza Stark reviewed gene: NKX2-1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978, Chorea, hereditary benign MIM#118700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12644 SP7 Zornitza Stark Marked gene: SP7 as ready
Mendeliome v0.12641 SPAG7 Zornitza Stark Marked gene: SPAG7 as ready
Mendeliome v0.12641 SPAG7 Zornitza Stark Phenotypes for gene: SPAG7 were changed from to Periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome, MONDO:0018540
Mendeliome v0.12637 SPAG7 Zornitza Stark reviewed gene: SPAG7: Rating: RED; Mode of pathogenicity: None; Publications: 24452265; Phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12637 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Mendeliome v0.12637 SPATA5 Zornitza Stark Phenotypes for gene: SPATA5 were changed from to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, MIM# 616577
Mendeliome v0.12634 SPATA5 Zornitza Stark reviewed gene: SPATA5: Rating: GREEN; Mode of pathogenicity: None; Publications: 30009132, 29343804; Phenotypes: Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, MIM# 616577; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12634 SPECC1L Zornitza Stark Marked gene: SPECC1L as ready
Mendeliome v0.12631 SSR4 Zornitza Stark Marked gene: SSR4 as ready
Mendeliome v0.12628 SRY Zornitza Stark Marked gene: SRY as ready
Mendeliome v0.12625 SRP54 Zornitza Stark Marked gene: SRP54 as ready
Mendeliome v0.12622 SRD5A2 Zornitza Stark Marked gene: SRD5A2 as ready
Mendeliome v0.12619 SPRY1 Zornitza Stark Marked gene: SPRY1 as ready
Mendeliome v0.12618 SPINK5 Zornitza Stark Marked gene: SPINK5 as ready
Mendeliome v0.12615 SPINK1 Zornitza Stark Marked gene: SPINK1 as ready
Mendeliome v0.12615 SPINK1 Zornitza Stark Phenotypes for gene: SPINK1 were changed from to Tropical calcific pancreatitis, MIM# 608189; Pancreatitis, hereditary, MIM# 167800
Mendeliome v0.12612 SPINK1 Zornitza Stark reviewed gene: SPINK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10835640, 11355022, 11938439, 16823394, 17274009, 27535533; Phenotypes: Tropical calcific pancreatitis, MIM# 608189, Pancreatitis, hereditary, MIM# 167800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12612 SPG7 Zornitza Stark Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, MIM# 607259 to Spastic paraplegia 7, autosomal recessive, MIM# 607259; Autosomal dominant optic atrophy, MONDO:0020250
Mendeliome v0.12610 SPG7 Zornitza Stark changed review comment from: SPG7 mutations most often lead to spastic paraparesis (HSP) and/or hereditary cerebellar ataxia (HCA), frequently with mixed phenotypes.

Well established for bi-allelic variants.

Enrichment of mono-allelic variants reported in a couple of cohorts, although a recent one suggests digenic inheritance.; to: SPG7 mutations most often lead to spastic paraparesis (HSP) and/or hereditary cerebellar ataxia (HCA), frequently with mixed phenotypes.

Well established for bi-allelic variants.

Enrichment of mono-allelic variants reported in a couple of cohorts, although a recent one suggests digenic inheritance.

Association with OA: 7 families reported for AD OA, including 5 missense and 2 frameshift variants, PMID 32548275
Mendeliome v0.12610 SPG7 Zornitza Stark edited their review of gene: SPG7: Changed publications: 9635427, 9635427, 16534102, 18799786, 22571692, 34500365, 33598982, 32548275; Changed phenotypes: Spastic paraplegia 7, autosomal recessive, MIM# 607259, Autosomal dominant optic atrophy, MONDO:0020250; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12610 SPG7 Zornitza Stark Marked gene: SPG7 as ready
Mendeliome v0.12610 SPG7 Zornitza Stark Phenotypes for gene: SPG7 were changed from to Spastic paraplegia 7, autosomal recessive, MIM# 607259
Mendeliome v0.12607 SPG7 Zornitza Stark reviewed gene: SPG7: Rating: GREEN; Mode of pathogenicity: None; Publications: 9635427, 9635427, 16534102, 18799786, 22571692, 34500365, 33598982; Phenotypes: Spastic paraplegia 7, autosomal recessive, MIM# 607259; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12607 RSPO4 Zornitza Stark Marked gene: RSPO4 as ready
Mendeliome v0.12604 RTN4IP1 Zornitza Stark Marked gene: RTN4IP1 as ready
Mendeliome v0.12604 RTN4IP1 Zornitza Stark Phenotypes for gene: RTN4IP1 were changed from to Optic atrophy 10 with or without ataxia, mental retardation, and seizures, MIM#616732
Mendeliome v0.12601 RUNX1 Zornitza Stark Marked gene: RUNX1 as ready
Mendeliome v0.12598 PAX6 Zornitza Stark Marked gene: PAX6 as ready
Mendeliome v0.12598 PAX6 Zornitza Stark Phenotypes for gene: PAX6 were changed from to Coloboma of optic nerve - MIM# 120430; Coloboma, ocular - MIM#120200; Morning glory disc anomaly - MIM#120430; Aniridia - MIM#106210; Anterior segment dysgenesis 5, multiple subtypes - MIM#604229; Cataract with late-onset corneal dystrophy - MIM#106210; Foveal hypoplasia 1- MIM#136520; Keratitis - MIM#148190; Optic nerve hypoplasia - MIM#165550
Mendeliome v0.12595 PAX2 Zornitza Stark Marked gene: PAX2 as ready
Mendeliome v0.12592 TSEN15 Zornitza Stark Marked gene: TSEN15 as ready
Mendeliome v0.12592 TSEN15 Zornitza Stark Phenotypes for gene: TSEN15 were changed from to Pontocerebellar hypoplasia, type 2F, MIM # 617026, MONDO:0014874
Mendeliome v0.12589 TSEN15 Zornitza Stark reviewed gene: TSEN15: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pontocerebellar hypoplasia, type 2F, MIM # 617026, MONDO:0014874; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12589 RAB33B Zornitza Stark Marked gene: RAB33B as ready
Mendeliome v0.12586 RAB28 Zornitza Stark Marked gene: RAB28 as ready
Mendeliome v0.12583 PAM16 Zornitza Stark Marked gene: PAM16 as ready
Mendeliome v0.12583 PAM16 Zornitza Stark Phenotypes for gene: PAM16 were changed from to Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type, OMIM # 613320
Mendeliome v0.12580 PALLD Zornitza Stark Marked gene: PALLD as ready
Mendeliome v0.12578 AMPD3 Zornitza Stark Marked gene: AMPD3 as ready
Mendeliome v0.12573 RTN4IP1 Belinda Chong reviewed gene: RTN4IP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26593267, 31077085; Phenotypes: Optic atrophy 10 with or without ataxia, mental retardation, and seizures, MIM#616732; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12573 PAX6 Krithika Murali reviewed gene: PAX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 31700164, 30986449, 29930474, 22171686; Phenotypes: ?Coloboma of optic nerve - MIM# 120430, ?Coloboma, ocular - MIM#120200, ?Morning glory disc anomaly - MIM#120430, Aniridia - MIM#106210, Anterior segment dysgenesis 5, multiple subtypes - MIM#604229, Cataract with late-onset corneal dystrophy - MIM#106210, Foveal hypoplasia 1- MIM#136520, Keratitis - MIM#148190, Optic nerve hypoplasia - MIM#165550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12573 TSEN15 Manny Jacobs reviewed gene: TSEN15: Rating: ; Mode of pathogenicity: None; Publications: PMID: 25558065, 27392077; Phenotypes: Pontocerebellar hypoplasia, type 2F, MIM # 617026, MONDO:0014874; Mode of inheritance: None
Mendeliome v0.12571 SERPINC1 Zornitza Stark Marked gene: SERPINC1 as ready
Mendeliome v0.12571 SERPINC1 Zornitza Stark Phenotypes for gene: SERPINC1 were changed from to hereditary antithrombin deficiency MONDO:0013144; Thrombophilia 7 due to antithrombin III deficiency, MIM#613118
Mendeliome v0.12568 SERPINB8 Zornitza Stark Marked gene: SERPINB8 as ready
Mendeliome v0.12565 SERPINB6 Zornitza Stark Marked gene: SERPINB6 as ready
Mendeliome v0.12561 PAM16 Krithika Murali reviewed gene: PAM16: Rating: GREEN; Mode of pathogenicity: None; Publications: 24786642, 27354339; Phenotypes: Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type, OMIM # 613320; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12561 CCM2 Ain Roesley Marked gene: CCM2 as ready
Mendeliome v0.12559 CCL2 Ain Roesley Marked gene: CCL2 as ready
Mendeliome v0.12557 CCDC88A Ain Roesley Marked gene: CCDC88A as ready
Mendeliome v0.12555 ANK1 Elena Savva Marked gene: ANK1 as ready
Mendeliome v0.12554 ANKH Elena Savva Marked gene: ANKH as ready
Mendeliome v0.12554 CCDC50 Ain Roesley Marked gene: CCDC50 as ready
Mendeliome v0.12553 ANKLE2 Elena Savva Phenotypes for gene: ANKLE2 were changed from Microcephaly 16, primary, autosomal recessive, MIM# 616681 to Microcephaly 16, primary, autosomal recessive, MIM# 616681
Mendeliome v0.12552 ANKLE2 Elena Savva Phenotypes for gene: ANKLE2 were changed from Microcephaly 16, primary, autosomal recessive, MIM# 616681 to Microcephaly 16, primary, autosomal recessive, MIM# 616681
Mendeliome v0.12548 ANKLE2 Elena Savva Phenotypes for gene: ANKLE2 were changed from to Microcephaly 16, primary, autosomal recessive, MIM# 616681
Mendeliome v0.12547 ANKLE2 Elena Savva Marked gene: ANKLE2 as ready
Mendeliome v0.12546 CAV3 Ain Roesley Marked gene: CAV3 as ready
Mendeliome v0.12542 CATSPER2 Ain Roesley Marked gene: CATSPER2 as ready
Mendeliome v0.12541 CATSPER2 Ain Roesley Phenotypes for gene: CATSPER2 were changed from to spermatogenic failure; non-syndromic hearing loss
Mendeliome v0.12539 CATSPER2 Ain Roesley reviewed gene: CATSPER2: Rating: AMBER; Mode of pathogenicity: None; Publications: 17098888, 30629171, 12825070; Phenotypes: spermatogenic failure, non-syndromic hearing loss; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12539 ANGPTL3 Elena Savva Marked gene: ANGPTL3 as ready
Mendeliome v0.12536 CATSPER1 Ain Roesley Marked gene: CATSPER1 as ready
Mendeliome v0.12534 ETFA Bryony Thompson Marked gene: ETFA as ready
Mendeliome v0.12533 ERLIN2 Bryony Thompson Marked gene: ERLIN2 as ready
Mendeliome v0.12532 TSHB Zornitza Stark Marked gene: TSHB as ready
Mendeliome v0.12531 ERLIN2 Bryony Thompson Phenotypes for gene: ERLIN2 were changed from to hereditary spastic paraplegia 18 MONDO:0012639
Mendeliome v0.12528 TSHR Zornitza Stark Marked gene: TSHR as ready
Mendeliome v0.12525 CAT Ain Roesley Marked gene: CAT as ready
Mendeliome v0.12523 TSPAN7 Zornitza Stark Marked gene: TSPAN7 as ready
Mendeliome v0.12519 TSPAN7 Zornitza Stark changed review comment from: The P172H missense, which is reported in two families, is present at a high frequency in gnomad, including 66 hemizygotes.; to: The P172H missense, which is reported in two families, is present at a high frequency in gnomad, including 66 hemizygotes.

Most variants in ClinVar are either VOUS or LB.
Mendeliome v0.12518 ERLIN2 Bryony Thompson reviewed gene: ERLIN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23109145, 21330303, 21796390, 29528531, 32094424, 34734492; Phenotypes: hereditary spastic paraplegia 18 MONDO:0012639; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12518 AMT Elena Savva Marked gene: AMT as ready
Mendeliome v0.12518 EPX Bryony Thompson Marked gene: EPX as ready
Mendeliome v0.12516 AMHR2 Elena Savva Marked gene: AMHR2 as ready
Mendeliome v0.12514 ALX4 Elena Savva Marked gene: ALX4 as ready
Mendeliome v0.12512 ALX4 Elena Savva Phenotypes for gene: ALX4 were changed from to Frontonasal dysplasia 2 MIM# 613451; Parietal foramina 2 MIM# 609597; {Craniosynostosis 5, susceptibility to} MIM#615529
Mendeliome v0.12510 ALX4 Elena Savva reviewed gene: ALX4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22829454, 34586326; Phenotypes: Frontonasal dysplasia 2 MIM# 613451, Parietal foramina 2 MIM# 609597, {Craniosynostosis 5, susceptibility to} MIM#615529; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12508 ALMS1 Elena Savva Marked gene: ALMS1 as ready
Mendeliome v0.12508 ALDH6A1 Elena Savva Marked gene: ALDH6A1 as ready
Mendeliome v0.12508 ALDH18A1 Elena Savva Phenotypes for gene: ALDH18A1 were changed from Cutis laxa, autosomal recessive, type IIIA MIM#219150; Spastic paraplegia 9A, autosomal dominant MIM#601162; Spastic paraplegia 9B, autosomal recessive MIM#616586; Cutis laxa, autosomal dominant 3 MIM#616603; disorders of ornithine or proline metabolism to Cutis laxa, autosomal recessive, type IIIA MIM#219150; Spastic paraplegia 9A, autosomal dominant MIM#601162; Spastic paraplegia 9B, autosomal recessive MIM#616586; Cutis laxa, autosomal dominant 3 MIM#616603; disorders of ornithine or proline metabolism
Mendeliome v0.12505 ALDH18A1 Elena Savva Phenotypes for gene: ALDH18A1 were changed from to Cutis laxa, autosomal recessive, type IIIA MIM#219150; Spastic paraplegia 9A, autosomal dominant MIM#601162; Spastic paraplegia 9B, autosomal recessive MIM#616586; Cutis laxa, autosomal dominant 3 MIM#616603; disorders of ornithine or proline metabolism
Mendeliome v0.12504 ALDH18A1 Elena Savva Marked gene: ALDH18A1 as ready
Mendeliome v0.12503 SERPINC1 Samantha Ayres reviewed gene: SERPINC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31359133, 30356112, 23910795, 28317092, 29747524, 11018075, 14590998; Phenotypes: hereditary antithrombin deficiency MONDO:0013144, Thrombophilia 7 due to antithrombin III deficiency, MIM#613118; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.12503 CASR Ain Roesley Marked gene: CASR as ready
Mendeliome v0.12503 CASR Ain Roesley Phenotypes for gene: CASR were changed from to Hyperparathyroidism, neonatal MIM#239200; Hypocalcemia, autosomal dominant MIM#601198; Hypocalcemia autosomal dominant, with Bartter syndrome MIM#601198; hypercalcemia, type I MIM#145980
Mendeliome v0.12501 CASR Ain Roesley reviewed gene: CASR: Rating: GREEN; Mode of pathogenicity: None; Publications: 7916660, 7726161, 8675635, 17698911, 22620673, 26646938, 22422767; Phenotypes: Hyperparathyroidism, neonatal MIM#239200, Hypocalcemia, autosomal dominant MIM#601198, Hypocalcemia autosomal dominant, with Bartter syndrome MIM#601198, hypercalcemia, type I MIM#145980; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12500 CASQ1 Ain Roesley Marked gene: CASQ1 as ready
Mendeliome v0.12500 CASQ1 Ain Roesley Phenotypes for gene: CASQ1 were changed from to Myopathy, vacuolar, with CASQ1 aggregates MIM#616231
Mendeliome v0.12498 CASQ1 Ain Roesley reviewed gene: CASQ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26136523, 30258016; Phenotypes: Myopathy, vacuolar, with CASQ1 aggregates MIM#616231; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.12498 TMEM98 Zornitza Stark Marked gene: TMEM98 as ready
Mendeliome v0.12495 TMEM70 Zornitza Stark Marked gene: TMEM70 as ready
Mendeliome v0.12495 TMEM70 Zornitza Stark Phenotypes for gene: TMEM70 were changed from to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, MIM# 614052
Mendeliome v0.12492 TMEM70 Zornitza Stark reviewed gene: TMEM70: Rating: GREEN; Mode of pathogenicity: None; Publications: 18953340, 21147908, 30950220; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, MIM# 614052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12492 TMEM38B Zornitza Stark Marked gene: TMEM38B as ready
Mendeliome v0.12489 TMEM199 Zornitza Stark Marked gene: TMEM199 as ready
Mendeliome v0.12486 TMEM173 Zornitza Stark Marked gene: TMEM173 as ready
Mendeliome v0.12483 TMC6 Zornitza Stark Marked gene: TMC6 as ready
Mendeliome v0.12480 TLR5 Zornitza Stark Marked gene: TLR5 as ready
Mendeliome v0.12479 TLR3 Zornitza Stark Marked gene: TLR3 as ready
Mendeliome v0.12476 TLR2 Zornitza Stark Marked gene: TLR2 as ready
Mendeliome v0.12475 FTCD Zornitza Stark Marked gene: FTCD as ready
Mendeliome v0.12472 FTCD Zornitza Stark Marked gene: FTCD as ready
Mendeliome v0.12469 FGF14 Zornitza Stark Marked gene: FGF14 as ready
Mendeliome v0.12469 FGF14 Zornitza Stark Phenotypes for gene: FGF14 were changed from to Spinocerebellar ataxia 27 MIM#609307
Mendeliome v0.12467 FAT4 Zornitza Stark Marked gene: FAT4 as ready
Mendeliome v0.12464 ERLIN1 Zornitza Stark Marked gene: ERLIN1 as ready
Mendeliome v0.12464 ERCC6 Zornitza Stark Marked gene: ERCC6 as ready
Mendeliome v0.12460 SLC30A2 Zornitza Stark Marked gene: SLC30A2 as ready
Mendeliome v0.12457 SLC2A9 Zornitza Stark Marked gene: SLC2A9 as ready
Mendeliome v0.12453 EPOR Bryony Thompson Phenotypes for gene: EPOR were changed from to primary familial polycythemia due to EPO receptor mutation MONDO:0007572
Mendeliome v0.12451 EPS8 Bryony Thompson reviewed gene: EPS8: Rating: GREEN; Mode of pathogenicity: None; Publications: 24741995, 27344577, 30303587, 34637946, 21526224; Phenotypes: Autosomal recessive nonsyndromic hearing loss 102 MONDO:0014428; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12449 EPOR Bryony Thompson reviewed gene: EPOR: Rating: GREEN; Mode of pathogenicity: Other; Publications: 8506290, 11559951, 17488692, 18492694, 30507031; Phenotypes: primary familial polycythemia due to EPO receptor mutation MONDO:0007572; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12449 SLC30A8 Zornitza Stark Marked gene: SLC30A8 as ready
Mendeliome v0.12445 SLC34A1 Zornitza Stark changed review comment from: Infantile hypercalcaemia and bi-allelic variants: More than 5 unrelated families reported.

Nephrolithiasis and mono-allelic variants: multiple families reported.; to: Infantile hypercalcaemia and bi-allelic variants: More than 5 unrelated families reported.

Nephrolithiasis and mono-allelic variants: multiple families reported.

Single family reported with renal Fanconi and homozygous variant.
Mendeliome v0.12445 SLC34A1 Zornitza Stark Marked gene: SLC34A1 as ready
Mendeliome v0.12442 SLC34A2 Zornitza Stark Marked gene: SLC34A2 as ready
Mendeliome v0.12442 SLC34A2 Zornitza Stark Phenotypes for gene: SLC34A2 were changed from to Pulmonary alveolar microlithiasis, MIM# 265100
Mendeliome v0.12439 SLC34A2 Zornitza Stark reviewed gene: SLC34A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16960801, 34581165, 33884208, 32328294, 31941744; Phenotypes: Pulmonary alveolar microlithiasis, MIM# 265100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12439 SLC35A1 Zornitza Stark Marked gene: SLC35A1 as ready
Mendeliome v0.12439 EPO Bryony Thompson Marked gene: EPO as ready
Mendeliome v0.12435 SLC39A13 Zornitza Stark Marked gene: SLC39A13 as ready
Mendeliome v0.12432 SLC39A5 Zornitza Stark Marked gene: SLC39A5 as ready
Mendeliome v0.12430 EPO Bryony Thompson changed review comment from: PMID: 27651169, 29514032, 25985138 - At least 4 families reported with heterozygous variants segregating with erythrocytosis. Mechanism of disease is gain-of-function. Frameshift variants identified (c.32delG, c.19delC) use of an alternative promoter (P2) in intron 1 causing the production of functional transcripts and increased amounts of biologically active EPO compared to controls, and 5’UTR conserved variant (c.‐136G>A) and expected to have a similar mechanism.

PMID: 28283061 - single proband from a consanguineous family with severe anaemia (Diamond-Blackfan anaemia phenotype) reported with a homozygous missense (R150Q) showing a mild reduction in its affinity for the EPO receptor; to: PMID: 27651169, 29514032, 25985138 - At least 4 families reported with heterozygous variants segregating with erythrocytosis. Mechanism of disease is gain-of-function. Frameshift variants identified (c.32delG, c.19delC) use of an alternative promoter (P2) in intron 1 causing the production of functional transcripts and increased amounts of biologically active EPO compared to controls, and 5’UTR conserved variant (c.‐136G>A) expected to have a similar mechanism.

PMID: 28283061 - single proband from a consanguineous family with severe anaemia (Diamond-Blackfan anaemia phenotype) reported with a homozygous missense (R150Q) showing a mild reduction in its affinity for the EPO receptor
Mendeliome v0.12426 EPM2A Bryony Thompson Marked gene: EPM2A as ready
Mendeliome v0.12422 EPHA3 Bryony Thompson Marked gene: EPHA3 as ready
Mendeliome v0.12421 EPHA2 Bryony Thompson Marked gene: EPHA2 as ready
Mendeliome v0.12421 EPHA2 Bryony Thompson Phenotypes for gene: EPHA2 were changed from to cataract 6 multiple types MONDO:0007288
Mendeliome v0.12420 SLC40A1 Zornitza Stark Marked gene: SLC40A1 as ready
Mendeliome v0.12415 EPHA2 Bryony Thompson reviewed gene: EPHA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19005574, 19649315, 19306328, 33671840; Phenotypes: cataract 6 multiple types MONDO:0007288; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12415 SLC4A11 Zornitza Stark Marked gene: SLC4A11 as ready
Mendeliome v0.12413 SLC4A4 Zornitza Stark Marked gene: SLC4A4 as ready
Mendeliome v0.12413 SLC4A4 Zornitza Stark Phenotypes for gene: SLC4A4 were changed from to Renal tubular acidosis, proximal, with ocular abnormalities, MIM# 604278; Hemiplegic migraine
Mendeliome v0.12410 SLC4A4 Zornitza Stark reviewed gene: SLC4A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 10545938, 11274232, 35260236, 33439394, 29914390; Phenotypes: Renal tubular acidosis, proximal, with ocular abnormalities, MIM# 604278, Hemiplegic migraine; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12410 ENO3 Bryony Thompson Marked gene: ENO3 as ready
Mendeliome v0.12407 ENG Bryony Thompson Marked gene: ENG as ready
Mendeliome v0.12407 ENG Bryony Thompson Phenotypes for gene: ENG were changed from to hereditary hemorrhagic telangiectasia MONDO:0019180
Mendeliome v0.12404 ENG Bryony Thompson reviewed gene: ENG: Rating: GREEN; Mode of pathogenicity: None; Publications: 34012068, 30336550, 7894484, 10751092, 20414677, 30763665, 17384219, 20364125; Phenotypes: hereditary hemorrhagic telangiectasia MONDO:0019180; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.12404 EMP2 Bryony Thompson Marked gene: EMP2 as ready
Mendeliome v0.12400 ELP2 Bryony Thompson Marked gene: ELP2 as ready
Mendeliome v0.12397 ELOVL4 Bryony Thompson Marked gene: ELOVL4 as ready
Mendeliome v0.12397 ELOVL5 Bryony Thompson Marked gene: ELOVL5 as ready
Mendeliome v0.12397 ELOVL5 Bryony Thompson Phenotypes for gene: ELOVL5 were changed from to spinocerebellar ataxia type 38 MONDO:0014417
Mendeliome v0.12396 ELOVL4 Bryony Thompson Phenotypes for gene: ELOVL4 were changed from to congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome MONDO:0013760; spinocerebellar ataxia type 34 MONDO:0007574; Stargardt disease MONDO:0019353
Mendeliome v0.12390 ELOVL4 Bryony Thompson reviewed gene: ELOVL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11138005, 15028284, 11726641, 17208947, 22100072, 24566826, 34227061, 24571530, 26010696; Phenotypes: congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome MONDO:0013760, spinocerebellar ataxia type 34 MONDO:0007574, Stargardt disease MONDO:0019353; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12390 ELN Bryony Thompson Marked gene: ELN as ready
Mendeliome v0.12390 ELN Bryony Thompson Phenotypes for gene: ELN were changed from to cutis laxa, autosomal dominant 1 MONDO:0007411; supravalvular aortic stenosis MONDO:0008504
Mendeliome v0.12387 ELN Bryony Thompson reviewed gene: ELN: Rating: GREEN; Mode of pathogenicity: None; Publications: 8132745, 9580666, 9873040, 10190324, 10190538, 22573328, 28383366; Phenotypes: cutis laxa, autosomal dominant 1 MONDO:0007411, supravalvular aortic stenosis MONDO:0008504; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.12387 ARPC4 Bryony Thompson Publications for gene: ARPC4 were set to DOI:https://doi.org/10.1016/j.xhgg.2021.100072
Mendeliome v0.12386 ARPC4 Bryony Thompson edited their review of gene: ARPC4: Changed publications: 35047857; Set current diagnostic: yes
Mendeliome v0.12386 SLC52A2 Zornitza Stark Marked gene: SLC52A2 as ready
Mendeliome v0.12384 SLC52A3 Zornitza Stark Marked gene: SLC52A3 as ready
Mendeliome v0.12382 DVL2 Bryony Thompson Marked gene: DVL2 as ready
Mendeliome v0.12381 SLC5A2 Zornitza Stark Marked gene: SLC5A2 as ready
Mendeliome v0.12381 DVL2 Bryony Thompson gene: DVL2 was added
gene: DVL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DVL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DVL2 were set to 35047859; 33599851; 30521570
Phenotypes for gene: DVL2 were set to Robinow syndrome MONDO:0019978
Review for gene: DVL2 was set to AMBER
Added comment: A single case with Robinow syndrome identified with a de novo frameshift variant in the last exon of the gene (c.2105dupC, p.Pro703Serfs*103). Also, a canine DVL2 frameshift variant has been associated with a Robinow-like syndrome in dogs, contributing to the brachycephalic phenotype and caudal vertebral anomalies.
Sources: Literature
Mendeliome v0.12379 SLC6A17 Zornitza Stark Marked gene: SLC6A17 as ready
Mendeliome v0.12379 TAMM41 Bryony Thompson Marked gene: TAMM41 as ready
Mendeliome v0.12378 TAMM41 Bryony Thompson gene: TAMM41 was added
gene: TAMM41 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TAMM41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAMM41 were set to 35321494; 29253589
Phenotypes for gene: TAMM41 were set to inborn mitochondrial metabolism disorder MONDO:0004069; hypotonia; developmental delay; myopathy; ptosis
Review for gene: TAMM41 was set to GREEN
Added comment: Three unrelated individuals with mitochondrial disease that share clinical features, including lethargy at birth, hypotonia, developmental delay, myopathy, and ptosis with biallelic variants. Tissue-specific observations on OXPHOS were identified, cardiolipin levels were unchanged in subject fibroblasts but significantly decreased in the skeletal muscle of affected individuals. The missense variants identified were defective in yeast models. In an in vitro cell model knockdown of TAMM41 resulted in decreased mitochondrial CDP diacylglycerol synthase activity, decreased cardiolipin levels and a decrease in oxygen consumption.
Sources: Literature
Mendeliome v0.12377 SLC6A17 Zornitza Stark Phenotypes for gene: SLC6A17 were changed from to Mental retardation, autosomal recessive 48, MIM# 616269
Mendeliome v0.12373 SLC6A17 Zornitza Stark reviewed gene: SLC6A17: Rating: AMBER; Mode of pathogenicity: None; Publications: 25704603, 23672601; Phenotypes: Mental retardation, autosomal recessive 48, MIM# 616269; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12373 SLC6A19 Zornitza Stark Marked gene: SLC6A19 as ready
Mendeliome v0.12373 SLC6A19 Zornitza Stark Phenotypes for gene: SLC6A19 were changed from to Hartnup disorder, MIM# 234500; Hyperglycinuria, MIM# 138500; Iminoglycinuria, MIM# 242600
Mendeliome v0.12371 BNIP1 Bryony Thompson Marked gene: BNIP1 as ready
Mendeliome v0.12370 BNIP1 Bryony Thompson gene: BNIP1 was added
gene: BNIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BNIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BNIP1 were set to 35266227; 31344970
Phenotypes for gene: BNIP1 were set to spondyloepiphyseal dysplasia MONDO:0016761
Review for gene: BNIP1 was set to AMBER
Added comment: Two apparently unrelated cases with spondyloepiphyseal dysplasia from India were identified with the same variant (c.84+3A>T). The kindred coefficient comparison of the 2 cases exome data suggested they were unrelated, however there was a stretch of shared homozygosity suggesting remote consanguinity. ~80% aberrantly spliced BNIP1 pre-mRNAs, reduced BNIP1 mRNA level to ~80%, and BNIP1 protein level reduction by ~50% were detected in one of the cases fibroblasts. A block at the terminal stage of autolysosome formation and/or clearance in patient fibroblasts was suggested based on the data. A drosophila model of the BNIP1 orthologue Sec20 also demonstrated defective autolysosome formation.
Sources: Literature
Mendeliome v0.12369 EIF4E Bryony Thompson Marked gene: EIF4E as ready
Mendeliome v0.12366 TLL1 Zornitza Stark Marked gene: TLL1 as ready
Mendeliome v0.12365 TK2 Zornitza Stark Marked gene: TK2 as ready
Mendeliome v0.12362 TJP2 Zornitza Stark Marked gene: TJP2 as ready
Mendeliome v0.12359 TIMP3 Zornitza Stark Marked gene: TIMP3 as ready
Mendeliome v0.12356 TIMM50 Zornitza Stark Marked gene: TIMM50 as ready
Mendeliome v0.12353 TIMM44 Zornitza Stark Marked gene: TIMM44 as ready
Mendeliome v0.12352 TICAM1 Zornitza Stark Marked gene: TICAM1 as ready
Mendeliome v0.12349 TTBK2 Zornitza Stark Marked gene: TTBK2 as ready
Mendeliome v0.12349 TTBK2 Zornitza Stark Phenotypes for gene: TTBK2 were changed from to Spinocerebellar ataxia 11, MIM# 604432, MONDO:0011464
Mendeliome v0.12346 TTBK2 Zornitza Stark reviewed gene: TTBK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301723; Phenotypes: Spinocerebellar ataxia 11, MIM# 604432, MONDO:0011464; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12346 TTLL5 Zornitza Stark Marked gene: TTLL5 as ready
Mendeliome v0.12343 TTR Zornitza Stark Marked gene: TTR as ready
Mendeliome v0.12343 TTR Zornitza Stark Phenotypes for gene: TTR were changed from to Amyloidosis, hereditary, transthyretin-related, MIM #105210; Carpal tunnel syndrome, familial, MIM# 115430
Mendeliome v0.12339 EIF2B4 Zornitza Stark Phenotypes for gene: EIF2B4 were changed from leukoencephalopathy with vanishing white matter MONDO:0011380; ataxia; spasticity; optic atrophy; primary ovarian failure to Leukoencephalopathy with vanishing white matter, MIM# 603896; leukoencephalopathy with vanishing white matter MONDO:0011380; ataxia; spasticity; optic atrophy; primary ovarian failure
Mendeliome v0.12338 PADI6 Zornitza Stark Marked gene: PADI6 as ready
Mendeliome v0.12335 PADI3 Zornitza Stark Marked gene: PADI3 as ready
Mendeliome v0.12332 PACS2 Zornitza Stark Marked gene: PACS2 as ready
Mendeliome v0.12329 PABPN1 Zornitza Stark Marked gene: PABPN1 as ready
Mendeliome v0.12329 PABPN1 Zornitza Stark Phenotypes for gene: PABPN1 were changed from to Oculopharyngeal muscular dystrophy - MIM#164300
Mendeliome v0.12326 AGK Zornitza Stark Marked gene: AGK as ready
Mendeliome v0.12326 AGK Zornitza Stark Phenotypes for gene: AGK were changed from to Sengers syndrome, MIM#212350; Cataract 38 MIM#614691
Mendeliome v0.12323 TTBK2 Manny Jacobs reviewed gene: TTBK2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 18037885, 31485862, 20667868, 27165044; Phenotypes: Spinocerebellar ataxia 11, MIM# 604432, MONDO:0011464; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12323 EIF2B5 Bryony Thompson Marked gene: EIF2B5 as ready
Mendeliome v0.12323 TTR Manny Jacobs reviewed gene: TTR: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:1570831, 1626570, 16115295, 16194874, 26537620; Phenotypes: Amyloidosis, hereditary, transthyretin-related, MIM #105210, Carpal tunnel syndrome, familial, MIM# 115430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12323 EIF2B5 Bryony Thompson Phenotypes for gene: EIF2B5 were changed from to leukoencephalopathy with vanishing white matter MONDO:0011380; ataxia; spasticity; optic atrophy; primary ovarian failure
Mendeliome v0.12321 P3H2 Zornitza Stark Marked gene: P3H2 as ready
Mendeliome v0.12321 P3H2 Zornitza Stark Phenotypes for gene: P3H2 were changed from to Myopia, high, with cataract and vitreoretinal degeneration - MIM#614292
Mendeliome v0.12316 AKT3 Elena Savva Marked gene: AKT3 as ready
Mendeliome v0.12316 EIF2B4 Bryony Thompson Marked gene: EIF2B4 as ready
Mendeliome v0.12314 EIF2B4 Bryony Thompson Phenotypes for gene: EIF2B4 were changed from to leukoencephalopathy with vanishing white matter MONDO:0011380; ataxia; spasticity; optic atrophy; primary ovarian failure
Mendeliome v0.12311 EIF2B3 Bryony Thompson Marked gene: EIF2B3 as ready
Mendeliome v0.12311 AFP Zornitza Stark Marked gene: AFP as ready
Mendeliome v0.12311 AFP Zornitza Stark Added comment: Comment when marking as ready: Raised or low levels of AFP are observed in some medical conditions, kept Amber due to possible phenotypic overlap.
Mendeliome v0.12311 AFP Zornitza Stark Phenotypes for gene: AFP were changed from to Alpha-fetoprotein deficiency MIM#615969; [Hereditary persistence of alpha-fetoprotein] MIM#615970
Mendeliome v0.12304 AHCY Elena Savva Marked gene: AHCY as ready
Mendeliome v0.12302 EIF2B1 Bryony Thompson Marked gene: EIF2B1 as ready
Mendeliome v0.12302 AGL Elena Savva Marked gene: AGL as ready
Mendeliome v0.12298 EIF2AK3 Bryony Thompson Marked gene: EIF2AK3 as ready
Mendeliome v0.12293 THSD1 Zornitza Stark Marked gene: THSD1 as ready
Mendeliome v0.12289 EFNA4 Bryony Thompson Marked gene: EFNA4 as ready
Mendeliome v0.12288 RBMX Zornitza Stark Marked gene: RBMX as ready
Mendeliome v0.12287 RBMX Zornitza Stark gene: RBMX was added
gene: RBMX was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: RBMX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RBMX were set to 25256757; 34260915
Phenotypes for gene: RBMX were set to Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238
Review for gene: RBMX was set to AMBER
Added comment: Hemizygous truncating variant reported segregating in multiple affected individuals in a single family. Some supportive functional data.
Sources: Expert Review
Mendeliome v0.12284 EHBP1 Bryony Thompson Marked gene: EHBP1 as ready
Mendeliome v0.12284 EHBP1 Bryony Thompson Phenotypes for gene: EHBP1 were changed from to {Prostate cancer, hereditary, 12} MIM#611868
Mendeliome v0.12282 EHBP1 Bryony Thompson reviewed gene: EHBP1: Rating: RED; Mode of pathogenicity: None; Publications: 18264098; Phenotypes: {Prostate cancer, hereditary, 12} MIM#611868; Mode of inheritance: None
Mendeliome v0.12282 PABPN1 Krithika Murali reviewed gene: PABPN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19080757, 33805441; Phenotypes: Oculopharyngeal muscular dystrophy - MIM#164300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12282 AGK Elena Savva reviewed gene: AGK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22415731, 25208612; Phenotypes: Sengers syndrome, MIM#212350, Cataract 38 MIM#614691; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12282 EDNRB Bryony Thompson Marked gene: EDNRB as ready
Mendeliome v0.12281 P3H2 Krithika Murali reviewed gene: P3H2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21885030, 24172257, 25469533; Phenotypes: Myopia, high, with cataract and vitreoretinal degeneration - MIM#614292; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12281 AFP Elena Savva reviewed gene: AFP: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 15280901, 18854864; Phenotypes: Alpha-fetoprotein deficiency MIM#615969, [Hereditary persistence of alpha-fetoprotein] MIM#615970; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12281 ADRB2 Elena Savva Marked gene: ADRB2 as ready
Mendeliome v0.12279 THRB Zornitza Stark Marked gene: THRB as ready
Mendeliome v0.12279 THRB Zornitza Stark Phenotypes for gene: THRB were changed from to Thyroid hormone resistance, MIM# 188570; Thyroid hormone resistance, autosomal recessive, MIM# 274300; Thyroid hormone resistance, selective pituitary, MIM# 145650
Mendeliome v0.12276 THRB Zornitza Stark reviewed gene: THRB: Rating: GREEN; Mode of pathogenicity: None; Publications: 25135573, 31590893; Phenotypes: Thyroid hormone resistance, MIM# 188570, Thyroid hormone resistance, autosomal recessive, MIM# 274300, Thyroid hormone resistance, selective pituitary, MIM# 145650; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.12276 SLC6A2 Zornitza Stark Marked gene: SLC6A2 as ready
Mendeliome v0.12272 SMARCAD1 Zornitza Stark Marked gene: SMARCAD1 as ready
Mendeliome v0.12272 SMARCAD1 Zornitza Stark Gene: smarcad1 has been classified as Green List (High Evidence).
Mendeliome v0.12272 SMARCAD1 Zornitza Stark Phenotypes for gene: SMARCAD1 were changed from Huriez syndrome, OMIM #181600; Basan syndrome, MIM# 129200; Adermatoglyphia, MIM# 136000 to Huriez syndrome, OMIM #181600; Basan syndrome, MIM# 129200; Adermatoglyphia, MIM# 136000
Mendeliome v0.12272 SMARCAD1 Zornitza Stark Phenotypes for gene: SMARCAD1 were changed from to Huriez syndrome, OMIM #181600; Basan syndrome, MIM# 129200; Adermatoglyphia, MIM# 136000
Mendeliome v0.12271 SMARCAD1 Zornitza Stark Publications for gene: SMARCAD1 were set to
Mendeliome v0.12270 SMARCAD1 Zornitza Stark Mode of inheritance for gene: SMARCAD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12269 SMARCAD1 Zornitza Stark Mode of inheritance for gene: SMARCAD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12268 SMARCAD1 Zornitza Stark reviewed gene: SMARCAD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29409814; Phenotypes: Huriez syndrome, OMIM #181600, Basan syndrome, MIM# 129200, Adermatoglyphia, MIM# 136000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12268 SMARCB1 Zornitza Stark Marked gene: SMARCB1 as ready
Mendeliome v0.12268 SMARCB1 Zornitza Stark Gene: smarcb1 has been classified as Green List (High Evidence).
Mendeliome v0.12268 SMARCB1 Zornitza Stark Phenotypes for gene: SMARCB1 were changed from to Coffin-Siris syndrome 3, MIM# 614608
Mendeliome v0.12267 SMARCB1 Zornitza Stark Publications for gene: SMARCB1 were set to
Mendeliome v0.12266 SMARCB1 Zornitza Stark Mode of inheritance for gene: SMARCB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12265 SMARCB1 Zornitza Stark reviewed gene: SMARCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34205270, 31530938, 25168959; Phenotypes: Coffin-Siris syndrome 3, MIM# 614608; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12265 SMN2 Zornitza Stark Marked gene: SMN2 as ready
Mendeliome v0.12265 SMN2 Zornitza Stark Phenotypes for gene: SMN2 were changed from to {Spinal muscular atrophy, type III, modifier of} 253400
Mendeliome v0.12262 SMN2 Zornitza Stark reviewed gene: SMN2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: {Spinal muscular atrophy, type III, modifier of} 253400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12262 OTOG Zornitza Stark Marked gene: OTOG as ready
Mendeliome v0.12261 EDNRB Bryony Thompson Phenotypes for gene: EDNRB were changed from to Waardenburg syndrome type 4A MONDO:0010192; sensorineural hearing loss; pigmentary abnormalities; Hirschsprung disease
Mendeliome v0.12258 EDNRB Bryony Thompson reviewed gene: EDNRB: Rating: GREEN; Mode of pathogenicity: None; Publications: 28502583, 25852447, 21373256, 16237557, 11773966, 11891690, 8001158, 10528251, 10528251, 19764031, 28236341; Phenotypes: Waardenburg syndrome type 4A (MONDO:0010192); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12255 OTC Zornitza Stark Marked gene: OTC as ready
Mendeliome v0.12255 OTC Zornitza Stark Phenotypes for gene: OTC were changed from to Ornithine transcarbamylase deficiency - MIM#311250
Mendeliome v0.12253 OSTM1 Zornitza Stark Marked gene: OSTM1 as ready
Mendeliome v0.12250 OSMR Zornitza Stark Marked gene: OSMR as ready
Mendeliome v0.12250 OSMR Zornitza Stark Phenotypes for gene: OSMR were changed from to Amyloidosis, primary localized cutaneous, 1 - MIM#105250
Mendeliome v0.12247 OSBPL2 Zornitza Stark Marked gene: OSBPL2 as ready
Mendeliome v0.12244 OR2J3 Zornitza Stark Marked gene: OR2J3 as ready
Mendeliome v0.12243 OPN1SW Zornitza Stark Marked gene: OPN1SW as ready
Mendeliome v0.12240 OPN1MW Zornitza Stark Marked gene: OPN1MW as ready
Mendeliome v0.12236 OPN1LW Zornitza Stark Marked gene: OPN1LW as ready
Mendeliome v0.12230 SERPINA6 Zornitza Stark Marked gene: SERPINA6 as ready
Mendeliome v0.12227 SERPINA1 Zornitza Stark Marked gene: SERPINA1 as ready
Mendeliome v0.12224 OTC Krithika Murali reviewed gene: OTC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ornithine transcarbamylase deficiency - MIM#311250; 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 v0.12224 OSMR Krithika Murali reviewed gene: OSMR: Rating: GREEN; Mode of pathogenicity: None; Publications: 19375894, 19528426, 25054142, 20507362, 19690585; Phenotypes: Amyloidosis, primary localized cutaneous, 1 - MIM#105250; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12224 SERPINA1 Samantha Ayres changed review comment from: Well established gene-disease relationship

Rated as C by babyseq due to low penetrance in childhood. Can cause hepatic dysfunction in infancy. Identification would prevent further investigation and potentially lead to optimising respiratory health due to adult onset respiratory involvement.; to: Well established gene-disease relationship

Rated as C by babyseq due to low penetrance in childhood. Can cause hepatic dysfunction in infancy. Identification would prevent further investigation and potentially lead to optimising respiratory health due to adult onset respiratory involvement.

MUTATIONAL & CLINICAL SPECTRUM
ZZ genotype: 2% have severe, neonatal/early-onset liver disease (potentially fatal/requiring liver transplantation), up to 6% have childhood onset liver disease. Also associated with adult-onset lung disease particularly emphysema (50%+ penetrance) - smoking is an important risk factor (close to 100% penetrance).

TREATMENT
There is no specific treatment for liver disease beyond transplant. There is treatment (AAT augmentation therapy) available to delay progression of lung disease phenotype.
Mendeliome v0.12224 THRA Zornitza Stark Marked gene: THRA as ready
Mendeliome v0.12221 TGM1 Zornitza Stark Marked gene: TGM1 as ready
Mendeliome v0.12218 TGM3 Zornitza Stark Marked gene: TGM3 as ready
Mendeliome v0.12214 OAT Zornitza Stark Marked gene: OAT as ready
Mendeliome v0.12211 NUP93 Zornitza Stark Marked gene: NUP93 as ready
Mendeliome v0.12208 NUP62 Zornitza Stark Marked gene: NUP62 as ready
Mendeliome v0.12204 ADH1B Zornitza Stark Marked gene: ADH1B as ready
Mendeliome v0.12203 CASP8 Zornitza Stark Marked gene: CASP8 as ready
Mendeliome v0.12203 CASP8 Zornitza Stark Added comment: Comment when marking as ready: Amber in view of the functional data.
Mendeliome v0.12198 ADCY3 Zornitza Stark Marked gene: ADCY3 as ready
Mendeliome v0.12194 TGFB3 Zornitza Stark Marked gene: TGFB3 as ready
Mendeliome v0.12191 TGFB2 Zornitza Stark Marked gene: TGFB2 as ready
Mendeliome v0.12189 TGFB1 Zornitza Stark Marked gene: TGFB1 as ready
Mendeliome v0.12186 TG Zornitza Stark Marked gene: TG as ready
Mendeliome v0.12183 OAT Krithika Murali edited their review of gene: OAT: Added comment: Biallelic variants associated with deficiency of mitochondrial enzyme ornithine aminotransferase and elevation of plasma ornithine levels without elevation of ammonia. Characterized by ocular anomalies; however, neurological and muscular features may also be present.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12183 ADRB1 Elena Savva Phenotypes for gene: ADRB1 were changed from [Resting heart rate] MIM#607276; [Short sleep, familial natural, 2] MIM#618591 to [Resting heart rate] MIM#607276; [Short sleep, familial natural, 2] MIM#618591
Mendeliome v0.12182 ADRB1 Elena Savva Phenotypes for gene: ADRB1 were changed from to [Resting heart rate] MIM#607276; [Short sleep, familial natural, 2] MIM#618591
Mendeliome v0.12181 ADRB1 Elena Savva Marked gene: ADRB1 as ready
Mendeliome v0.12180 ADRB1 Elena Savva reviewed gene: ADRB1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 31473062, 34716504; Phenotypes: [Resting heart rate] MIM#607276, [Short sleep, familial natural, 2] MIM#618591; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.12180 NTN1 Zornitza Stark Marked gene: NTN1 as ready
Mendeliome v0.12177 NSD1 Zornitza Stark Marked gene: NSD1 as ready
Mendeliome v0.12174 NRCAM Zornitza Stark Marked gene: NRCAM as ready
Mendeliome v0.12174 NR4A3 Zornitza Stark Marked gene: NR4A3 as ready
Mendeliome v0.12173 NKX2-5 Zornitza Stark Marked gene: NKX2-5 as ready
Mendeliome v0.12172 NKX2-5 Zornitza Stark reviewed gene: NKX2-5: Rating: GREEN; Mode of pathogenicity: None; Publications: 25742962, 26805889; Phenotypes: Ventricular septal defect 3 (MIM#614432), Tetralogy of Fallot (MIM#187500); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12172 NKX2-5 Zornitza Stark Phenotypes for gene: NKX2-5 were changed from to Atrial septal defect 7, with or without AV conduction defects, MIM# 108900; Ventricular septal defect 3 (MIM#614432); Tetralogy of Fallot (MIM#187500)
Mendeliome v0.12169 NKX2-1 Zornitza Stark Marked gene: NKX2-1 as ready
Mendeliome v0.12169 NKX2-1 Zornitza Stark Phenotypes for gene: NKX2-1 were changed from to Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700
Mendeliome v0.12166 NDUFAF5 Zornitza Stark Marked gene: NDUFAF5 as ready
Mendeliome v0.12166 NDUFAF5 Zornitza Stark Phenotypes for gene: NDUFAF5 were changed from to Mitochondrial complex I deficiency, nuclear type 3 MIM#618224
Mendeliome v0.12163 NDUFS4 Zornitza Stark Marked gene: NDUFS4 as ready
Mendeliome v0.12163 NDUFS4 Zornitza Stark Phenotypes for gene: NDUFS4 were changed from to Mitochondrial complex I deficiency, nuclear type 1 - MIM#252010
Mendeliome v0.12160 NDUFV2 Zornitza Stark Marked gene: NDUFV2 as ready
Mendeliome v0.12160 NDUFV2 Zornitza Stark Phenotypes for gene: NDUFV2 were changed from to Mitochondrial complex I deficiency, nuclear type 7 - MIM#618229
Mendeliome v0.12154 CA2 Zornitza Stark Phenotypes for gene: CA2 were changed from to Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM#259730
Mendeliome v0.12152 CASP8 Ain Roesley changed review comment from: Boderline red/amber

1 family (the 2nd family reported in PMID:25814141 was found to be distantly related to the one in PMID:12353035)

Mice with targeted T cell and B cell caspase-8 deficiency present normal thymocyte development but a marked decrease in peripheral blood T-cells. Besides, when challenged with the lymphocytic choriomeningitis virus (LCMV), these animals showed a significantly impaired immune response to the infection that included impaired CD8 cell expansion and an abrogated ability to generate virus-specific CD8+ cytotoxic T-cells.; to: Borderline red/amber

1 family (the 2nd family reported in PMID:25814141 was found to be distantly related to the one in PMID:12353035)

Mice with targeted T cell and B cell caspase-8 deficiency present normal thymocyte development but a marked decrease in peripheral blood T-cells. Besides, when challenged with the lymphocytic choriomeningitis virus (LCMV), these animals showed a significantly impaired immune response to the infection that included impaired CD8 cell expansion and an abrogated ability to generate virus-specific CD8+ cytotoxic T-cells.
Mendeliome v0.12151 ADGRV1 Elena Savva Marked gene: ADGRV1 as ready
Mendeliome v0.12149 CASP10 Ain Roesley Marked gene: CASP10 as ready
Mendeliome v0.12148 NUBPL Zornitza Stark Marked gene: NUBPL as ready
Mendeliome v0.12148 NUBPL Zornitza Stark Phenotypes for gene: NUBPL were changed from to Mitochondrial complex I deficiency, nuclear type 21 - MIM#618242
Mendeliome v0.12145 NTRK1 Zornitza Stark Marked gene: NTRK1 as ready
Mendeliome v0.12142 NTF4 Zornitza Stark Marked gene: NTF4 as ready
Mendeliome v0.12139 CASK Ain Roesley Phenotypes for gene: CASK were changed from FG syndrome 4 MIM#300422; Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749; Mental retardation, with or without nystagmus MIM#300422 to FG syndrome 4 MIM#300422; Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749; Mental retardation, with or without nystagmus MIM#300422
Mendeliome v0.12138 CASK Ain Roesley Phenotypes for gene: CASK were changed from to FG syndrome 4 MIM#300422; Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749; Mental retardation, with or without nystagmus MIM#300422
Mendeliome v0.12137 CASK Ain Roesley Marked gene: CASK as ready
Mendeliome v0.12137 CASK Ain Roesley Marked gene: CASK as ready
Mendeliome v0.12135 NSUN2 Zornitza Stark Marked gene: NSUN2 as ready
Mendeliome v0.12135 NSUN2 Zornitza Stark Phenotypes for gene: NSUN2 were changed from to Mental retardation, autosomal recessive 5 - MIM#611091
Mendeliome v0.12134 CASK Ain Roesley reviewed gene: CASK: Rating: GREEN; Mode of pathogenicity: None; Publications: 24278995; Phenotypes: FG syndrome 4 MIM#300422, Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749, Mental retardation, with or without nystagmus MIM#300422; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Mendeliome v0.12132 NSUN2 Zornitza Stark reviewed gene: NSUN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22541559, 22541562, 21063731, 22577224, 35126837; Phenotypes: Mental retardation, autosomal recessive 5 - MIM#611091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12132 NRXN1 Zornitza Stark Marked gene: NRXN1 as ready
Mendeliome v0.12129 CARD11 Ain Roesley Phenotypes for gene: CARD11 were changed from Immunodeficiency 11A, autosomal recessive, MIM# 615206; Immunodeficiency 11B with atopic dermatitis, autosomal dominant, MIM# 617638 to Immunodeficiency 11A, autosomal recessive, MIM# 615206; Immunodeficiency 11B with atopic dermatitis, autosomal dominant, MIM# 617638
Mendeliome v0.12128 CARD11 Ain Roesley Phenotypes for gene: CARD11 were changed from to Immunodeficiency 11A, autosomal recessive, MIM# 615206; Immunodeficiency 11B with atopic dermatitis, autosomal dominant, MIM# 617638
Mendeliome v0.12128 CARD11 Ain Roesley Marked gene: CARD11 as ready
Mendeliome v0.12128 CARD11 Ain Roesley Gene: card11 has been classified as Green List (High Evidence).
Mendeliome v0.12128 CARD11 Ain Roesley Publications for gene: CARD11 were set to
Mendeliome v0.12128 CARD11 Ain Roesley Mode of inheritance for gene: CARD11 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12127 CARD11 Ain Roesley reviewed gene: CARD11: Rating: GREEN; Mode of pathogenicity: None; Publications: 23561803, 12818158, 23374270, 28628108; Phenotypes: Immunodeficiency 11A, autosomal recessive, MIM# 615206, Immunodeficiency 11B with atopic dermatitis, autosomal dominant, MIM# 617638; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12127 CALM3 Ain Roesley Marked gene: CALM3 as ready
Mendeliome v0.12126 CALM2 Ain Roesley Marked gene: CALM2 as ready
Mendeliome v0.12124 CALM1 Ain Roesley Marked gene: CALM1 as ready
Mendeliome v0.12124 CALM1 Ain Roesley Phenotypes for gene: CALM1 were changed from to Long QT syndrome 14 MIM#616247; Ventricular tachycardia, catecholaminergic polymorphic, 4 MIM#614916
Mendeliome v0.12122 CALM1 Ain Roesley reviewed gene: CALM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31170290; Phenotypes: Long QT syndrome 14 MIM#616247, Ventricular tachycardia, catecholaminergic polymorphic, 4 MIM#614916; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.12122 NRL Zornitza Stark Marked gene: NRL as ready
Mendeliome v0.12118 CACNA2D4 Ain Roesley Marked gene: CACNA2D4 as ready
Mendeliome v0.12117 NR2F2 Zornitza Stark Marked gene: NR2F2 as ready
Mendeliome v0.12117 NR2F2 Zornitza Stark Phenotypes for gene: NR2F2 were changed from to 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779
Mendeliome v0.12115 SERAC1 Zornitza Stark Marked gene: SERAC1 as ready
Mendeliome v0.12112 SEMA3A Zornitza Stark Marked gene: SEMA3A as ready
Mendeliome v0.12112 SEMA3A Zornitza Stark Phenotypes for gene: SEMA3A were changed from to Hypogonadotropic hypogonadism 16 with or without anosmia - MIM#614897; congenital heart disease; short stature
Mendeliome v0.12109 SCP2 Zornitza Stark Marked gene: SCP2 as ready
Mendeliome v0.12107 CACNA2D2 Ain Roesley Phenotypes for gene: CACNA2D2 were changed from Cerebellar atrophy with seizures and variable developmental delay MIM#618501 to Cerebellar atrophy with seizures and variable developmental delay MIM#618501
Mendeliome v0.12105 CACNA2D2 Ain Roesley Phenotypes for gene: CACNA2D2 were changed from Cerebellar atrophy with seizures and variable developmental delay MIM#618501 to Cerebellar atrophy with seizures and variable developmental delay MIM#618501
Mendeliome v0.12104 CACNA2D2 Ain Roesley Phenotypes for gene: CACNA2D2 were changed from to Cerebellar atrophy with seizures and variable developmental delay MIM#618501
Mendeliome v0.12103 CACNA2D2 Ain Roesley Marked gene: CACNA2D2 as ready
Mendeliome v0.12101 CACNA2D2 Ain Roesley edited their review of gene: CACNA2D2: Changed publications: 23339110, 24358150, 30410802, 29997391, 31402629, 11487633, 11756448, 4177347, 14660671, 15331424; Changed phenotypes: Cerebellar atrophy with seizures and variable developmental delay MIM#618501
Mendeliome v0.12100 CACNA2D2 Ain Roesley reviewed gene: CACNA2D2: Rating: GREEN; Mode of pathogenicity: None; Publications: Cerebellar atrophy with seizures and variable developmental delay MIM#618501; Phenotypes: 23339110, 24358150, 30410802, 29997391, 31402629, 11487633, 11756448, 4177347, 14660671, 15331424; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12099 CACNA1F Ain Roesley Marked gene: CACNA1F as ready
Mendeliome v0.12099 TUBB1 Zornitza Stark Marked gene: TUBB1 as ready
Mendeliome v0.12099 CACNA1F Ain Roesley Phenotypes for gene: CACNA1F were changed from to Aland Island eye disease MIM#300600; Cone-rod dystrophy, X-linked, 3 MIM#300476; Night blindness, congenital stationary (incomplete), 2A, X-linked MIM#300071
Mendeliome v0.12097 CACNA1F Ain Roesley reviewed gene: CACNA1F: Rating: GREEN; Mode of pathogenicity: None; Publications: 17525176, 16505158, 23776498, 24124559, 26075273, 25999675; Phenotypes: Aland Island eye disease MIM#300600, Cone-rod dystrophy, X-linked, 3 MIM#300476, Night blindness, congenital stationary (incomplete), 2A, X-linked MIM#300071; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.12096 SCARB2 Zornitza Stark Marked gene: SCARB2 as ready
Mendeliome v0.12096 SCARB2 Zornitza Stark Gene: scarb2 has been classified as Green List (High Evidence).
Mendeliome v0.12096 SCARB2 Zornitza Stark Phenotypes for gene: SCARB2 were changed from to Progressive Myoclonus Epilepsy, MONDO:0020074; Epilepsy, progressive myoclonic 4, with or without renal failure, MIM #254900
Mendeliome v0.12095 SCARB2 Zornitza Stark Publications for gene: SCARB2 were set to
Mendeliome v0.12094 SCARB2 Zornitza Stark Mode of inheritance for gene: SCARB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12093 SASH1 Zornitza Stark Marked gene: SASH1 as ready
Mendeliome v0.12093 SASH1 Zornitza Stark Phenotypes for gene: SASH1 were changed from to Dyschromatosis universalis hereditaria 1, MIM #127500; familial generalized lentiginosis MONDO:007891
Mendeliome v0.12090 SASH1 Zornitza Stark reviewed gene: SASH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dyschromatosis universalis hereditaria 1, MIM# 127500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12090 CABP2 Ain Roesley Marked gene: CABP2 as ready
Mendeliome v0.12090 TUBB4B Zornitza Stark Marked gene: TUBB4B as ready
Mendeliome v0.12090 TUBB4B Zornitza Stark Phenotypes for gene: TUBB4B were changed from to Leber congenital amaurosis with early onset deafness, LCAEOD, OMIM #617879; MONDO:0060650
Mendeliome v0.12088 TUBB4B Zornitza Stark reviewed gene: TUBB4B: Rating: GREEN; Mode of pathogenicity: None; Publications: 35240325; Phenotypes: Leber congenital amaurosis with early onset deafness, LCAEOD, OMIM #617879, MONDO:0060650; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12086 TUFM Zornitza Stark Marked gene: TUFM as ready
Mendeliome v0.12083 CA2 Ain Roesley Marked gene: CA2 as ready
Mendeliome v0.12083 CA2 Ain Roesley reviewed gene: CA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34624559, 33555497, 12566520, 7627193; Phenotypes: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM#259730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12082 CA12 Ain Roesley Marked gene: CA12 as ready
Mendeliome v0.12080 NR2E3 Zornitza Stark Marked gene: NR2E3 as ready
Mendeliome v0.12077 NR0B2 Zornitza Stark Marked gene: NR0B2 as ready
Mendeliome v0.12076 NR0B2 Zornitza Stark Phenotypes for gene: NR0B2 were changed from to Obesity, mild, early-onset, MIM# 601665
Mendeliome v0.12074 NPSR1 Zornitza Stark Marked gene: NPSR1 as ready
Mendeliome v0.12071 ACER3 Zornitza Stark edited their review of gene: ACER3: Added comment: Additional publication (Dehvani et al., 2021; PMID: 34281620) detailing three further unrelated cases, each with novel homozygous variants in the ACER3 gene. All individuals displayed features of progressive leukoencephalopathy, developmental delay, hypotonia, appendicular spasticity, and dystonia. Early development is apparently normal followed by symptoms of stagnation and neurologic regression (onset within first year of life).; Changed rating: GREEN; Changed publications: 32816236, 26792856, 34281620; Changed phenotypes: Leukodystrophy, progressive, early childhood-onset, MIM:617762
Mendeliome v0.12071 LIAS Alison Yeung Marked gene: LIAS as ready
Mendeliome v0.12068 LHX4 Alison Yeung Phenotypes for gene: LHX4 were changed from to Pituitary hormone deficiency, combined, 4, MIM# 262700
Mendeliome v0.12067 LHX4 Alison Yeung Marked gene: LHX4 as ready
Mendeliome v0.12066 LHX4 Alison Yeung reviewed gene: LHX4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined, 4, MIM# 262700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.12066 SEMA3A Samantha Ayres reviewed gene: SEMA3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 28075028, 33369061, 20301509, 21059704, 24124006, 22927827; Phenotypes: Hypogonadotropic hypogonadism 16 with or without anosmia - MIM#614897, congenital heart disease, short stature; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.12066 LHX3 Alison Yeung Marked gene: LHX3 as ready
Mendeliome v0.12066 LHX3 Alison Yeung Phenotypes for gene: LHX3 were changed from to Pituitary hormone deficiency, combined, 3, MIM# 221750
Mendeliome v0.12064 LHX3 Alison Yeung reviewed gene: LHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined, 3, MIM# 221750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12064 LHB Alison Yeung Marked gene: LHB as ready
Mendeliome v0.12062 SCARB2 Samantha Ayres reviewed gene: SCARB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18308289, 18424452, 23659519, 19847901, 18022370, 19933215; Phenotypes: Progressive Myoclonus Epilepsy, MONDO:0020074, Epilepsy, progressive myoclonic 4, with or without renal failure, MIM #254900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12062 SASH1 Samantha Ayres reviewed gene: SASH1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23333244, 27885802, 32981204; Phenotypes: Dyschromatosis universalis hereditaria 1, MIM #127500, familial generalized lentiginosis MONDO:007891; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.12062 NUBPL Krithika Murali reviewed gene: NUBPL: Rating: GREEN; Mode of pathogenicity: None; Publications: 20818383, 32518176, 23553477, 31917109, 32518176, 31787496, 30897263, 22826544; Phenotypes: Mitochondrial complex I deficiency, nuclear type 21 - MIM#618242; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12062 TUBB4B Manny Jacobs reviewed gene: TUBB4B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29198720; Phenotypes: Leber congenital amaurosis with early onset deafness, LCAEOD, OMIM #617879, MONDO:0060650; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12062 LGI1 Alison Yeung Marked gene: LGI1 as ready
Mendeliome v0.12059 LEMD3 Alison Yeung Marked gene: LEMD3 as ready
Mendeliome v0.12056 LDLRAP1 Alison Yeung Marked gene: LDLRAP1 as ready
Mendeliome v0.12053 LDHB Alison Yeung Marked gene: LDHB as ready
Mendeliome v0.12049 LCAT Alison Yeung Marked gene: LCAT as ready
Mendeliome v0.12046 LCA5 Alison Yeung Marked gene: LCA5 as ready
Mendeliome v0.12043 NR2F2 Krithika Murali reviewed gene: NR2F2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24702954, 29478779, 31687637, 27363585, 29222010, 29663647; Phenotypes: 46,XX sex reversal 5 - MIM#618901, Congenital heart defects, multiple types, 4 - MIM#615779; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12043 MSMB Zornitza Stark Marked gene: MSMB as ready
Mendeliome v0.12043 MSMB Zornitza Stark Phenotypes for gene: MSMB were changed from to {Prostate cancer, hereditary, 13} 611928
Mendeliome v0.12040 MSMB Zornitza Stark reviewed gene: MSMB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Prostate cancer, hereditary, 13} 611928; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12040 SON Zornitza Stark Marked gene: SON as ready
Mendeliome v0.12037 SNX3 Zornitza Stark Marked gene: SNX3 as ready
Mendeliome v0.12036 SMARCE1 Zornitza Stark Phenotypes for gene: SMARCE1 were changed from Coffin-Siris syndrome 5, MIM# 616938 to Coffin-Siris syndrome 5, MIM# 616938; {Meningioma, familial, susceptibility to} 607174
Mendeliome v0.12035 SMARCE1 Zornitza Stark changed review comment from: Coffin-Siris syndrome is a rare congenital disorder characterized by delayed psychomotor development, intellectual disability, coarse facial features, and hypoplasia of the distal phalanges, particularly the fifth digit. Other features may also be observed, including congenital heart defects, hypoplasia of the corpus callosum, and poor overall growth with short stature and microcephaly.

Accounts for ~2% of Coffin Siris syndrome.; to: Coffin-Siris syndrome is a rare congenital disorder characterized by delayed psychomotor development, intellectual disability, coarse facial features, and hypoplasia of the distal phalanges, particularly the fifth digit. Other features may also be observed, including congenital heart defects, hypoplasia of the corpus callosum, and poor overall growth with short stature and microcephaly.

Accounts for ~2% of Coffin Siris syndrome.

Germline LoF variants also linked to familial meningioma.
Mendeliome v0.12035 SMARCE1 Zornitza Stark edited their review of gene: SMARCE1: Changed publications: 23377182, 22426308, 23906836, 23929686, 32732226, 32436246, 32410215, 34205270; Changed phenotypes: Coffin-Siris syndrome 5, MIM# 616938, {Meningioma, familial, susceptibility to} 607174
Mendeliome v0.12035 SMARCE1 Zornitza Stark Publications for gene: SMARCE1 were set to 22426308; 23906836; 23929686; 32732226; 32436246; 32410215; 34205270
Mendeliome v0.12034 SMARCE1 Zornitza Stark Marked gene: SMARCE1 as ready
Mendeliome v0.12034 SMARCE1 Zornitza Stark Gene: smarce1 has been classified as Green List (High Evidence).
Mendeliome v0.12034 SMARCE1 Zornitza Stark Phenotypes for gene: SMARCE1 were changed from to Coffin-Siris syndrome 5, MIM# 616938
Mendeliome v0.12033 SMARCE1 Zornitza Stark Publications for gene: SMARCE1 were set to
Mendeliome v0.12032 SMARCE1 Zornitza Stark Mode of inheritance for gene: SMARCE1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12031 SMARCE1 Zornitza Stark reviewed gene: SMARCE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22426308, 23906836, 23929686, 32732226, 32436246, 32410215, 34205270; Phenotypes: Coffin-Siris syndrome 5, MIM# 616938; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12031 MAX Zornitza Stark Marked gene: MAX as ready
Mendeliome v0.12028 MAT1A Zornitza Stark Marked gene: MAT1A as ready
Mendeliome v0.12025 SNX14 Zornitza Stark Marked gene: SNX14 as ready
Mendeliome v0.12025 SNX14 Zornitza Stark Phenotypes for gene: SNX14 were changed from to Spinocerebellar ataxia, autosomal recessive 20 (MIM#616354)
Mendeliome v0.12022 SNX14 Zornitza Stark reviewed gene: SNX14: Rating: GREEN; Mode of pathogenicity: None; Publications: 25439728, 25848753, 27913285; Phenotypes: Spinocerebellar ataxia, autosomal recessive 20 (MIM#616354); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12022 SNORD118 Zornitza Stark Marked gene: SNORD118 as ready
Mendeliome v0.12019 SNAP29 Zornitza Stark Marked gene: SNAP29 as ready
Mendeliome v0.12019 SNAP29 Zornitza Stark Phenotypes for gene: SNAP29 were changed from to Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome, MIM#609528
Mendeliome v0.12016 SNAP29 Zornitza Stark reviewed gene: SNAP29: Rating: GREEN; Mode of pathogenicity: None; Publications: 29051910, 21073448, 30793783; Phenotypes: Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome, MIM#609528; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12016 SNAP25 Zornitza Stark Marked gene: SNAP25 as ready
Mendeliome v0.12013 SNAI2 Zornitza Stark Marked gene: SNAI2 as ready
Mendeliome v0.12013 SNAI2 Zornitza Stark Phenotypes for gene: SNAI2 were changed from to Waardenburg syndrome, type 2D, MIM# 608890; Piebaldism, MIM# 172800
Mendeliome v0.12009 SNAI2 Zornitza Stark reviewed gene: SNAI2: Rating: AMBER; Mode of pathogenicity: None; Publications: 12444107, 30936914, 12955764, 24443330; Phenotypes: Waardenburg syndrome, type 2D, MIM# 608890, Piebaldism, MIM# 172800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12009 SMS Zornitza Stark Marked gene: SMS as ready
Mendeliome v0.12005 RPS10 Zornitza Stark Marked gene: RPS10 as ready
Mendeliome v0.12002 ROBO3 Zornitza Stark Marked gene: ROBO3 as ready
Mendeliome v0.11999 ROBO2 Zornitza Stark Marked gene: ROBO2 as ready
Mendeliome v0.11996 RNF216 Zornitza Stark Marked gene: RNF216 as ready
Mendeliome v0.11996 RNF216 Zornitza Stark Phenotypes for gene: RNF216 were changed from to Cerebellar ataxia and hypogonadotropic hypogonadism MIM#212840
Mendeliome v0.11993 ATP2B2 Zornitza Stark Marked gene: ATP2B2 as ready
Mendeliome v0.11991 TFAP2B Zornitza Stark Marked gene: TFAP2B as ready
Mendeliome v0.11990 TFAP2B Zornitza Stark changed review comment from: Well established association with syndromic and non-syndromic PDA.; to: Well established association with syndromic and non-syndromic PDA.

Four individuals reported in PMID: 31292255 (Correction in PMID: 31405973) as part of a craniosynostosis cohort: 2 de novo and 2 inherited. There is evidence for reduced penetrance as in one case the variant was inherited from an unaffected parent (affected parent for the other inherited variant).
Mendeliome v0.11990 TFAP2B Zornitza Stark edited their review of gene: TFAP2B: Changed publications: 31292255, 11505339, 15684060, 18752453, 21643846; Changed phenotypes: Char syndrome, MIM# 169100, Patent ductus arteriosus 2, MIM# 617035, Syndromic craniosynostosis
Mendeliome v0.11990 TFAP2B Zornitza Stark Phenotypes for gene: TFAP2B were changed from Char syndrome, MIM# 169100; Patent ductus arteriosus 2, MIM# 617035 to Char syndrome, MIM# 169100; Patent ductus arteriosus 2, MIM# 617035; Syndromic craniosynostosis
Mendeliome v0.11989 TFAP2B Zornitza Stark Phenotypes for gene: TFAP2B were changed from to Char syndrome, MIM# 169100; Patent ductus arteriosus 2, MIM# 617035
Mendeliome v0.11986 TFAP2B Zornitza Stark reviewed gene: TFAP2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 11505339, 15684060, 18752453, 21643846; Phenotypes: Char syndrome, MIM# 169100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11986 TERT Zornitza Stark Marked gene: TERT as ready
Mendeliome v0.11986 TERT Zornitza Stark Phenotypes for gene: TERT were changed from to Dyskeratosis congenita, MIM# 613989; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, MIM# 614742
Mendeliome v0.11983 TERT Zornitza Stark reviewed gene: TERT: Rating: GREEN; Mode of pathogenicity: None; Publications: 16247010, 15814878; Phenotypes: Dyskeratosis congenita, MIM# 613989, Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, MIM# 614742; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11983 TERC Zornitza Stark Marked gene: TERC as ready
Mendeliome v0.11980 TEK Zornitza Stark Marked gene: TEK as ready
Mendeliome v0.11980 TEK Zornitza Stark Phenotypes for gene: TEK were changed from to Glaucoma 3, primary congenital, E, MIM# 617272; Venous malformations, multiple cutaneous and mucosal, MIM# 600195
Mendeliome v0.11977 TEK Zornitza Stark reviewed gene: TEK: Rating: GREEN; Mode of pathogenicity: None; Publications: 27270174, 19888299; Phenotypes: Glaucoma 3, primary congenital, E, MIM# 617272, Venous malformations, multiple cutaneous and mucosal, MIM# 600195; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11977 TEAD1 Zornitza Stark Marked gene: TEAD1 as ready
Mendeliome v0.11975 TEAD1 Zornitza Stark changed review comment from: Sveinsson chorioretinal atrophy (SCRA) is characterized by bilateral, well-defined, tongue-shaped strips of atrophic retina and choroid that extend from the optic nerve into the peripheral ocular fundus. The lesions may be evident at birth and usually progress at a variable rate, sometimes leading to central visual loss. Separate small distinct circular atrophic lesions are observed in the peripheral ocular fundus in some patients. Congenital anterior polar cataracts are found in approximately 25% of affected individuals.

The vast majority of reported cases were of Icelandic origin but the characteristic clinical picture of SCRA is also described in patients of non-Icelandic descent. The variant reported in the Icelanding population is (c.1261T>C, p.Tyr421His), another variant at same position c.1261T>A, p.Tyr421Asn also reported in non-Icelandic family.

Functional data supports gene-disease association.; to: Sveinsson chorioretinal atrophy (SCRA) is characterized by bilateral, well-defined, tongue-shaped strips of atrophic retina and choroid that extend from the optic nerve into the peripheral ocular fundus. The lesions may be evident at birth and usually progress at a variable rate, sometimes leading to central visual loss. Separate small distinct circular atrophic lesions are observed in the peripheral ocular fundus in some patients. Congenital anterior polar cataracts are found in approximately 25% of affected individuals.

The vast majority of reported cases were of Icelandic origin but the characteristic clinical picture of SCRA is also described in patients of non-Icelandic descent. The variant reported in the Icelanding population is (c.1261T>C, p.Tyr421His), another variant at same position c.1261T>A, p.Tyr421Asn also reported in non-Icelandic family.

A de novo nonsense variant has also been reported in a case with Aicardi syndrome with infantile spasms, agenesis of the corpus callosum, and chorioretinal lacunae.
Mendeliome v0.11973 TDP1 Zornitza Stark Phenotypes for gene: TDP1 were changed from to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 , MIM# 607250
Mendeliome v0.11969 TDP1 Zornitza Stark reviewed gene: TDP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31182267, 12244316; Phenotypes: Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 , MIM# 607250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11969 TCIRG1 Zornitza Stark Marked gene: TCIRG1 as ready
Mendeliome v0.11966 TCF4 Zornitza Stark Marked gene: TCF4 as ready
Mendeliome v0.11963 TCAP Zornitza Stark Marked gene: TCAP as ready
Mendeliome v0.11963 TCAP Zornitza Stark Phenotypes for gene: TCAP were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 7, MIM# 601954
Mendeliome v0.11961 TCAP Zornitza Stark reviewed gene: TCAP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 7, MIM# 601954; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11961 TBX5 Zornitza Stark Marked gene: TBX5 as ready
Mendeliome v0.11958 TBX20 Zornitza Stark Marked gene: TBX20 as ready
Mendeliome v0.11955 TBL1XR1 Zornitza Stark Marked gene: TBL1XR1 as ready
Mendeliome v0.11955 TBL1XR1 Zornitza Stark Phenotypes for gene: TBL1XR1 were changed from to Mental retardation, autosomal dominant 41, MIM# 616944; Pierpont syndrome, MIM# 602342
Mendeliome v0.11952 TBL1XR1 Zornitza Stark reviewed gene: TBL1XR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26769062, 30365874, 25425123, 9450851, 23160955, 28687524, 23176139, 16007632; Phenotypes: Mental retardation, autosomal dominant 41, MIM# 616944, Pierpont syndrome, MIM# 602342; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11952 TBCK Zornitza Stark Marked gene: TBCK as ready
Mendeliome v0.11952 TBCK Zornitza Stark Phenotypes for gene: TBCK were changed from to Hypotonia, infantile, with psychomotor retardation and characteristic facies 3, MIM# 616900
Mendeliome v0.11949 TBCK Zornitza Stark reviewed gene: TBCK: Rating: GREEN; Mode of pathogenicity: None; Publications: 27040692, 30103036, 27040691; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 3, MIM# 616900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11949 TBC1D23 Zornitza Stark Marked gene: TBC1D23 as ready
Mendeliome v0.11949 TBC1D23 Zornitza Stark Phenotypes for gene: TBC1D23 were changed from to Pontocerebellar hypoplasia, type 11, MIM# 617695
Mendeliome v0.11946 TBC1D1 Zornitza Stark Marked gene: TBC1D1 as ready
Mendeliome v0.11946 TBC1D1 Zornitza Stark Phenotypes for gene: TBC1D1 were changed from to CAKUT; Non-syndromic renal or urinary tract malformation, MONDO:0019720
Mendeliome v0.11943 TBC1D1 Zornitza Stark reviewed gene: TBC1D1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26572137; Phenotypes: CAKUT, Non-syndromic renal or urinary tract malformation, MONDO:0019720; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11943 TAZ Zornitza Stark Marked gene: TAZ as ready
Mendeliome v0.11943 TAZ Zornitza Stark Phenotypes for gene: TAZ were changed from to Barth syndrome, MIM# 302060
Mendeliome v0.11941 TAZ Zornitza Stark reviewed gene: TAZ: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Barth syndrome, MIM# 302060; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.11940 TAT Zornitza Stark Marked gene: TAT as ready
Mendeliome v0.11938 TAS2R38 Zornitza Stark Marked gene: TAS2R38 as ready
Mendeliome v0.11938 TAS2R38 Zornitza Stark Phenotypes for gene: TAS2R38 were changed from to [Phenylthiocarbamide tasting] 171200
Mendeliome v0.11935 TAS2R38 Zornitza Stark reviewed gene: TAS2R38: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: [Phenylthiocarbamide tasting] 171200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11935 TAS2R16 Zornitza Stark Marked gene: TAS2R16 as ready
Mendeliome v0.11932 TANGO2 Zornitza Stark Marked gene: TANGO2 as ready
Mendeliome v0.11932 TANGO2 Zornitza Stark Phenotypes for gene: TANGO2 were changed from to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878
Mendeliome v0.11929 TANGO2 Zornitza Stark reviewed gene: TANGO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26805782, 30245509; Phenotypes: Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11929 TACR3 Zornitza Stark Marked gene: TACR3 as ready
Mendeliome v0.11926 TAC3 Zornitza Stark Marked gene: TAC3 as ready
Mendeliome v0.11923 T Zornitza Stark Marked gene: T as ready
Mendeliome v0.11916 LARGE1 Zornitza Stark Publications for gene: LARGE1 were set to
Mendeliome v0.11915 LARGE1 Zornitza Stark Mode of inheritance for gene: LARGE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11910 LBR Alison Yeung Marked gene: LBR as ready
Mendeliome v0.11908 LAT Alison Yeung Marked gene: LAT as ready
Mendeliome v0.11906 LAMB2 Zornitza Stark Phenotypes for gene: LAMB2 were changed from to Pierson syndrome, MIM# 609049; Nephrotic syndrome, type 5, with or without ocular abnormalities, MIM# 614199
Mendeliome v0.11903 L1CAM Zornitza Stark Phenotypes for gene: L1CAM were changed from Hydrocephalus due to aqueductal stenosis, MIM# 307000; MASA syndrome, MIM# 303350; L1 syndrome, MONDO:0017140 to Hydrocephalus due to aqueductal stenosis, MIM# 307000; MASA syndrome, MIM# 303350; L1 syndrome, MONDO:0017140; Corpus callosum, partial agenesis of, MIM# 304100
Mendeliome v0.11902 L1CAM Zornitza Stark reviewed gene: L1CAM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hydrocephalus due to aqueductal stenosis, MIM# 307000, Corpus callosum, partial agenesis of, MIM# 304100; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.11900 NPRL3 Zornitza Stark Marked gene: NPRL3 as ready
Mendeliome v0.11900 NPRL3 Zornitza Stark Phenotypes for gene: NPRL3 were changed from to Epilepsy, familial focal, with variable foci 3- MIM#617118
Mendeliome v0.11897 NPPC Zornitza Stark Marked gene: NPPC as ready
Mendeliome v0.11893 NOTCH2 Zornitza Stark Marked gene: NOTCH2 as ready
Mendeliome v0.11890 NOTCH1 Zornitza Stark Marked gene: NOTCH1 as ready
Mendeliome v0.11887 NONO Zornitza Stark Marked gene: NONO as ready
Mendeliome v0.11884 NOL3 Zornitza Stark Marked gene: NOL3 as ready
Mendeliome v0.11880 NOG Zornitza Stark Marked gene: NOG as ready
Mendeliome v0.11880 NOG Zornitza Stark Phenotypes for gene: NOG were changed from to Brachydactyly, type B2 - MIM#611377; Multiple synostoses syndrome 1 (MIM#186500); Stapes ankylosis with broad thumbs and toes (MIM#184460); Symphalangism, proximal, 1A (MIM#185800); Tarsal-carpal coalition syndrome (MIM#186570)
Mendeliome v0.11877 NNT Zornitza Stark Marked gene: NNT as ready
Mendeliome v0.11874 NLRP7 Zornitza Stark Marked gene: NLRP7 as ready
Mendeliome v0.11871 NLRP12 Zornitza Stark Marked gene: NLRP12 as ready
Mendeliome v0.11868 TCF20 Elena Savva reviewed gene: TCF20: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 34904221, 30739909, 30819258, 25228304; Phenotypes: Developmental delay with variable intellectual impairment and behavioral abnormalities MIM#618430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.11868 LAS1L Alison Yeung Marked gene: LAS1L as ready
Mendeliome v0.11865 LARGE1 Alison Yeung Phenotypes for gene: LARGE1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A6, MIM# 613154; Muscular dystrophy-dystroglycanopathy type B6, MIM# 608840
Mendeliome v0.11864 LARGE1 Alison Yeung Marked gene: LARGE1 as ready
Mendeliome v0.11864 LARGE1 Alison Yeung Gene: large1 has been classified as Green List (High Evidence).
Mendeliome v0.11864 LARGE1 Alison Yeung reviewed gene: LARGE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12966029, 19067344, 17436019, 21248746; Phenotypes: Muscular dystrophy-dystroglycanopathy type A6, MIM# 613154, Muscular dystrophy-dystroglycanopathy type B6, MIM# 608840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11864 LAMC3 Alison Yeung Marked gene: LAMC3 as ready
Mendeliome v0.11864 LAMB2 Alison Yeung Marked gene: LAMB2 as ready
Mendeliome v0.11864 LAMB2 Alison Yeung changed review comment from: Pierson syndrome (PIERS) is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss.

Nephrotic syndrome type 5 is an autosomal recessive disorder characterized by very early onset of progressive renal failure manifest as proteinuria with consecutive edema starting in utero or within the first 3 months of life. A subset of patients may develop mild ocular anomalies, such as myopia, nystagmus, and strabismus.

The two disorders are likely part of a spectrum. More than 5 unrelated families reported. ; to: Pierson syndrome (PIERS) is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss.

Nephrotic syndrome type 5 is an autosomal recessive disorder characterized by very early onset of progressive renal failure manifest as proteinuria with consecutive edema starting in utero or within the first 3 months of life. A subset of patients may develop mild ocular anomalies, such as myopia, nystagmus, and strabismus.

More than 5 unrelated families reported.
Mendeliome v0.11864 LAMB2 Alison Yeung changed review comment from: Pierson syndrome (PIERS) is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss.

Nephrotic syndrome type 5 is an autosomal recessive disorder characterized by very early onset of progressive renal failure manifest as proteinuria with consecutive edema starting in utero or within the first 3 months of life. A subset of patients may develop mild ocular anomalies, such as myopia, nystagmus, and strabismus.; to: Pierson syndrome (PIERS) is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss.

Nephrotic syndrome type 5 is an autosomal recessive disorder characterized by very early onset of progressive renal failure manifest as proteinuria with consecutive edema starting in utero or within the first 3 months of life. A subset of patients may develop mild ocular anomalies, such as myopia, nystagmus, and strabismus.

The two disorders are likely part of a spectrum. More than 5 unrelated families reported.
Mendeliome v0.11864 LAMB2 Alison Yeung reviewed gene: LAMB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 14136829, 15372515, 17256789; Phenotypes: Pierson syndrome, MIM# 609049, Nephrotic syndrome, type 5, with or without ocular abnormalities, MIM# 614199; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11864 L1CAM Alison Yeung Marked gene: L1CAM as ready
Mendeliome v0.11863 TRIM63 Zornitza Stark Phenotypes for gene: TRIM63 were changed from Hypertrophic cardiomyopathy to Hypertrophic cardiomyopathy, MONDO:0005045
Mendeliome v0.11862 TRIM63 Zornitza Stark edited their review of gene: TRIM63: Changed rating: GREEN; Changed phenotypes: Hypertrophic cardiomyopathy, MONDO:0005045; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11862 MYOM1 Zornitza Stark Phenotypes for gene: MYOM1 were changed from Hypertrophic cardiomyopathy to Hypertrophic cardiomyopathy, MONDO:0005045
Mendeliome v0.11860 MYOM1 Zornitza Stark edited their review of gene: MYOM1: Changed rating: RED; Changed phenotypes: Hypertrophic cardiomyopathy, MONDO:0005045
Mendeliome v0.11860 NPRL3 Krithika Murali reviewed gene: NPRL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27173016, 26285051, 33461085; Phenotypes: Epilepsy, familial focal, with variable foci 3- MIM#617118; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11860 NOG Krithika Murali reviewed gene: NOG: Rating: GREEN; Mode of pathogenicity: None; Publications: 11846737, 18440889, 12089654, 10080184, 15066478, 22088931, 17381491; Phenotypes: Brachydactyly, type B2 - MIM#611377, Multiple synostoses syndrome 1 (MIM#186500), Stapes ankylosis with broad thumbs and toes (MIM#184460), Symphalangism, proximal, 1A (MIM#185800), Tarsal-carpal coalition syndrome (MIM#186570); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11860 STAG1 Zornitza Stark Marked gene: STAG1 as ready
Mendeliome v0.11860 STAG1 Zornitza Stark Phenotypes for gene: STAG1 were changed from to Mental retardation, autosomal dominant 47, MIM# 617635
Mendeliome v0.11857 STAG1 Zornitza Stark reviewed gene: STAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28119487, 34440290; Phenotypes: Mental retardation, autosomal dominant 47, MIM# 617635; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11857 STAR Zornitza Stark Marked gene: STAR as ready
Mendeliome v0.11857 STAR Zornitza Stark Gene: star has been classified as Green List (High Evidence).
Mendeliome v0.11857 STAR Zornitza Stark Phenotypes for gene: STAR were changed from to Lipoid adrenal hyperplasia (MIM#201710)
Mendeliome v0.11856 STAR Zornitza Stark Publications for gene: STAR were set to
Mendeliome v0.11855 STAR Zornitza Stark Mode of inheritance for gene: STAR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11854 STAR Zornitza Stark reviewed gene: STAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 7892608, 8634702; Phenotypes: Lipoid adrenal hyperplasia (MIM#201710); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11854 STAT1 Zornitza Stark Marked gene: STAT1 as ready
Mendeliome v0.11851 STAT2 Zornitza Stark Marked gene: STAT2 as ready
Mendeliome v0.11848 STS Zornitza Stark Marked gene: STS as ready
Mendeliome v0.11846 STUB1 Zornitza Stark Marked gene: STUB1 as ready
Mendeliome v0.11846 STUB1 Zornitza Stark Phenotypes for gene: STUB1 were changed from to Spinocerebellar ataxia, autosomal recessive 16, MIM# 615768; Spinocerebellar ataxia 48, MIM#618093
Mendeliome v0.11843 STUB1 Zornitza Stark changed review comment from: Onset is typically in adolescence but onset in childhood also reported.
Sources: Expert list; to: Multiple families reported with mono-allelic and bi-allelic disease, variable age of onset.
Sources: Expert list
Mendeliome v0.11843 STUB1 Zornitza Stark edited their review of gene: STUB1: Changed publications: 25258038, 24742043, 32337344, 30381368, 31126790; Changed phenotypes: Spinocerebellar ataxia, autosomal recessive 16, MIM# 615768, Spinocerebellar ataxia 48, MIM#618093; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11843 STX11 Zornitza Stark Marked gene: STX11 as ready
Mendeliome v0.11840 NLRC4 Zornitza Stark Marked gene: NLRC4 as ready
Mendeliome v0.11836 NLGN3 Zornitza Stark Marked gene: NLGN3 as ready
Mendeliome v0.11834 NKX3-2 Zornitza Stark Marked gene: NKX3-2 as ready
Mendeliome v0.11831 NIPAL4 Zornitza Stark Marked gene: NIPAL4 as ready
Mendeliome v0.11828 NHS Zornitza Stark Marked gene: NHS as ready
Mendeliome v0.11828 NHS Zornitza Stark Phenotypes for gene: NHS were changed from to Nance-Horan syndrome - MIM#302350; Cataract 40, X-linked - MIM#302200
Mendeliome v0.11825 NFKBIL1 Zornitza Stark Marked gene: NFKBIL1 as ready
Mendeliome v0.11825 NFKBIL1 Zornitza Stark Phenotypes for gene: NFKBIL1 were changed from to {Rheumatoid arthritis, susceptibility to} - MIM#180300
Mendeliome v0.11823 NFIA Zornitza Stark Marked gene: NFIA as ready
Mendeliome v0.11823 NFIA Zornitza Stark Phenotypes for gene: NFIA were changed from to Brain malformations with or without urinary tract defects - MIM#613735
Mendeliome v0.11819 NEXN Zornitza Stark Marked gene: NEXN as ready
Mendeliome v0.11819 NEXN Zornitza Stark Phenotypes for gene: NEXN were changed from to Lethal fetal cardiomyopathy; Hydrops fetalis; Cardiomyopathy, dilated 1CC - MIM#613122
Mendeliome v0.11816 STX1B Zornitza Stark Marked gene: STX1B as ready
Mendeliome v0.11813 STX2 Zornitza Stark Marked gene: STX2 as ready
Mendeliome v0.11812 STX4 Zornitza Stark Marked gene: STX4 as ready
Mendeliome v0.11811 STXBP2 Zornitza Stark Marked gene: STXBP2 as ready
Mendeliome v0.11808 SULT2B1 Zornitza Stark Marked gene: SULT2B1 as ready
Mendeliome v0.11805 SUMF1 Zornitza Stark Marked gene: SUMF1 as ready
Mendeliome v0.11802 SUMO4 Zornitza Stark Marked gene: SUMO4 as ready
Mendeliome v0.11798 SURF1 Zornitza Stark Marked gene: SURF1 as ready
Mendeliome v0.11798 SURF1 Zornitza Stark Phenotypes for gene: SURF1 were changed from to Charcot-Marie-Tooth disease, type 4K MIM#616684; Mitochondrial complex IV deficiency, nuclear type 1 MIM#220110
Mendeliome v0.11795 SURF1 Zornitza Stark reviewed gene: SURF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843204, 9837813; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 1, MIM# 220110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11795 SUZ12 Zornitza Stark Marked gene: SUZ12 as ready
Mendeliome v0.11792 NHS Krithika Murali reviewed gene: NHS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31755796, 25266737; Phenotypes: Nance-Horan syndrome - MIM#302350, Cataract 40, X-linked - MIM#302200; 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 v0.11792 NFKBIL1 Krithika Murali reviewed gene: NFKBIL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Rheumatoid arthritis, susceptibility to} - MIM#180300; Mode of inheritance: None
Mendeliome v0.11792 NFIA Krithika Murali reviewed gene: NFIA: Rating: GREEN; Mode of pathogenicity: None; Publications: 35018717, 33973697, 32926563; Phenotypes: Brain malformations with or without urinary tract defects - MIM#613735; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11792 NEXN Krithika Murali reviewed gene: NEXN: Rating: GREEN; Mode of pathogenicity: None; Publications: 33947203, 33949776, 35166435, 32058062; Phenotypes: Lethal fetal cardiomyopathy, Hydrops fetalis, Cardiomyopathy, dilated 1CC - MIM#613122; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.11792 NEK2 Zornitza Stark Marked gene: NEK2 as ready
Mendeliome v0.11788 SYCP3 Zornitza Stark Marked gene: SYCP3 as ready
Mendeliome v0.11784 SYNE4 Zornitza Stark Marked gene: SYNE4 as ready
Mendeliome v0.11781 SYNGAP1 Zornitza Stark Phenotypes for gene: SYNGAP1 were changed from Mental retardation, autosomal dominant 5, MIM# 612621 to Intellectual disability, autosomal dominant 5 (MIM # 612621)
Mendeliome v0.11780 SYNGAP1 Zornitza Stark Marked gene: SYNGAP1 as ready
Mendeliome v0.11780 SYNGAP1 Zornitza Stark Phenotypes for gene: SYNGAP1 were changed from to Mental retardation, autosomal dominant 5, MIM# 612621
Mendeliome v0.11777 SYNGAP1 Zornitza Stark changed review comment from: Unsteady gait and ataxia mentioned in this cohort, but appears to be a rare feature. Presentation is typically with ID/seizures/hypotonia.; to: Well established gene-disease association.
Mendeliome v0.11777 SYNJ1 Zornitza Stark Marked gene: SYNJ1 as ready
Mendeliome v0.11777 SYNJ1 Zornitza Stark Phenotypes for gene: SYNJ1 were changed from to Developmental and epileptic encephalopathy 53, MIM# 617389; Parkinson disease 20, early-onset, MIM# 615530
Mendeliome v0.11774 SYNJ1 Zornitza Stark reviewed gene: SYNJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32435303, 27435091, 23804563, 23804577, 27496670, 33841314; Phenotypes: Developmental and epileptic encephalopathy 53, MIM# 617389, Parkinson disease 20, early-onset, MIM# 615530; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11774 ADCY10 Elena Savva Marked gene: ADCY10 as ready
Mendeliome v0.11774 SZT2 Zornitza Stark Marked gene: SZT2 as ready
Mendeliome v0.11771 C2CD6 Zornitza Stark Marked gene: C2CD6 as ready
Mendeliome v0.11769 CCDC62 Zornitza Stark Marked gene: CCDC62 as ready
Mendeliome v0.11768 NDUFV2 Krithika Murali reviewed gene: NDUFV2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33811136, 34405929, 12754703, 26008862, 30770271, 19167255; Phenotypes: Mitochondrial complex I deficiency, nuclear type 7 - MIM#618229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11768 TXNRD2 Zornitza Stark Marked gene: TXNRD2 as ready
Mendeliome v0.11764 TXNRD2 Zornitza Stark changed review comment from: Further cases reported in this large cohort of paediatric primary adrenal insufficiency.; to: Further cases reported in this large cohort of paediatric primary adrenal insufficiency.

Evidence for association with DCM is limited, considering pop frequency of variants reported.
Mendeliome v0.11764 ADCY10 Zornitza Stark Marked gene: ADCY10 as ready
Mendeliome v0.11762 TALDO1 Zornitza Stark Marked gene: TALDO1 as ready
Mendeliome v0.11759 USP9Y Zornitza Stark Marked gene: USP9Y as ready
Mendeliome v0.11754 ADAMTS10 Zornitza Stark changed review comment from: Weill-Marchesani syndrome is a rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, eye anomalies, including microspherophakia, ectopia of the lenses, severe myopia, and glaucoma, and, occasionally, heart defects
Sources: Expert list; to: Weill-Marchesani syndrome is a rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, eye anomalies, including microspherophakia, ectopia of the lenses, severe myopia, and glaucoma, and, occasionally, heart defects.

Multiple families reported.

Sources: Expert list
Mendeliome v0.11754 ADAMTS10 Zornitza Stark changed review comment from: Mild intellectual disability is described in around 10% of affected individuals.
Sources: Expert list; to: Weill-Marchesani syndrome is a rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, eye anomalies, including microspherophakia, ectopia of the lenses, severe myopia, and glaucoma, and, occasionally, heart defects
Sources: Expert list
Mendeliome v0.11753 SARS2 Zornitza Stark Marked gene: SARS2 as ready
Mendeliome v0.11753 SARS2 Zornitza Stark Gene: sars2 has been classified as Green List (High Evidence).
Mendeliome v0.11753 SARS2 Zornitza Stark Phenotypes for gene: SARS2 were changed from to Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, MIM#613845
Mendeliome v0.11752 SARS2 Zornitza Stark Publications for gene: SARS2 were set to
Mendeliome v0.11751 SARS2 Zornitza Stark Mode of inheritance for gene: SARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11750 SARS2 Zornitza Stark reviewed gene: SARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33751860; Phenotypes: Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, MIM#613845; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11748 ACTN2 Zornitza Stark reviewed gene: ACTN2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, hypertrophic, 23, with or without LVNC, MIM# 612158; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11748 USH2A Zornitza Stark Marked gene: USH2A as ready
Mendeliome v0.11745 NDUFS6 Zornitza Stark Marked gene: NDUFS6 as ready
Mendeliome v0.11745 NDUFS6 Zornitza Stark Phenotypes for gene: NDUFS6 were changed from to Mitochondrial complex I deficiency, nuclear type 9 - MIM#618232
Mendeliome v0.11742 USH1G Zornitza Stark Marked gene: USH1G as ready
Mendeliome v0.11739 USH1C Zornitza Stark Marked gene: USH1C as ready
Mendeliome v0.11736 UROS Zornitza Stark Marked gene: UROS as ready
Mendeliome v0.11733 NDUFS5 Zornitza Stark Marked gene: NDUFS5 as ready
Mendeliome v0.11730 ADAT3 Elena Savva Marked gene: ADAT3 as ready
Mendeliome v0.11730 ADAT3 Elena Savva Phenotypes for gene: ADAT3 were changed from to Mental retardation, autosomal recessive 36, MIM#615286
Mendeliome v0.11729 ADAMTS10 Elena Savva Phenotypes for gene: ADAMTS10 were changed from Weill-Marchesani syndrome 1, recessive, MIM#277600 to Weill-Marchesani syndrome 1, recessive, MIM#277600
Mendeliome v0.11728 ADAMTS10 Elena Savva Phenotypes for gene: ADAMTS10 were changed from to Weill-Marchesani syndrome 1, recessive, MIM#277600
Mendeliome v0.11727 ADAMTS10 Elena Savva Marked gene: ADAMTS10 as ready
Mendeliome v0.11723 ADAM9 Elena Savva Marked gene: ADAM9 as ready
Mendeliome v0.11723 ACVRL1 Elena Savva Phenotypes for gene: ACVRL1 were changed from Telangiectasia, hereditary hemorrhagic, type 2 MIM#600376 to Telangiectasia, hereditary hemorrhagic, type 2 MIM#600376
Mendeliome v0.11723 ACVRL1 Elena Savva Phenotypes for gene: ACVRL1 were changed from Telangiectasia, hereditary hemorrhagic, type 2 MIM#600376 to Telangiectasia, hereditary hemorrhagic, type 2 MIM#600376
Mendeliome v0.11722 ACVRL1 Elena Savva Phenotypes for gene: ACVRL1 were changed from to Telangiectasia, hereditary hemorrhagic, type 2 MIM#600376
Mendeliome v0.11721 ACVRL1 Elena Savva Marked gene: ACVRL1 as ready
Mendeliome v0.11720 ACVRL1 Elena Savva reviewed gene: ACVRL1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16542389; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 2 MIM#600376; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.11720 ACTN2 Elena Savva Phenotypes for gene: ACTN2 were changed from Myopathy, distal, 6, adult onset MIM#618655; Cardiomyopathy, hypertrophic, 23, with or without LVNC MIM#612158; Cardiomyopathy, dilated, 1AA, with or without LVNC MIM#612158; Myopathy, congenital with structured cores and Z-line abnormalities MIM#618654 to Myopathy, distal, 6, adult onset MIM#618655; Cardiomyopathy, hypertrophic, 23, with or without LVNC MIM#612158; Cardiomyopathy, dilated, 1AA, with or without LVNC MIM#612158; Myopathy, congenital with structured cores and Z-line abnormalities MIM#618654
Mendeliome v0.11719 SARS2 Samantha Ayres reviewed gene: SARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24034276, 21255763; Phenotypes: Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, MIM#613845; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11719 ACTN2 Elena Savva Phenotypes for gene: ACTN2 were changed from to Myopathy, distal, 6, adult onset MIM#618655; Cardiomyopathy, hypertrophic, 23, with or without LVNC MIM#612158; Cardiomyopathy, dilated, 1AA, with or without LVNC MIM#612158; Myopathy, congenital with structured cores and Z-line abnormalities MIM#618654
Mendeliome v0.11718 ACTN2 Elena Savva Marked gene: ACTN2 as ready
Mendeliome v0.11717 ACTN2 Elena Savva reviewed gene: ACTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34802252, 27287556; Phenotypes: Myopathy, distal, 6, adult onset MIM#618655, Cardiomyopathy, hypertrophic, 23, with or without LVNC MIM#612158, Cardiomyopathy, dilated, 1AA, with or without LVNC MIM#612158, Myopathy, congenital with structured cores and Z-line abnormalities MIM#618654; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.11717 ACADSB Elena Savva Marked gene: ACADSB as ready
Mendeliome v0.11718 ACTG1 Elena Savva Phenotypes for gene: ACTG1 were changed from to Baraitser-Winter syndrome 2 MIM#614583; Deafness, autosomal dominant 20/26 MIM#604717
Mendeliome v0.11717 ACTG1 Elena Savva Marked gene: ACTG1 as ready
Mendeliome v0.11716 ACTG1 Elena Savva reviewed gene: ACTG1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 29620237; Phenotypes: Baraitser-Winter syndrome 2MIM#614583, Deafness, autosomal dominant 20/26 MIM#604717; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11716 ACHE Elena Savva Marked gene: ACHE as ready
Mendeliome v0.11714 ACP4 Elena Savva Marked gene: ACP4 as ready
Mendeliome v0.11708 WAS Zornitza Stark Marked gene: WAS as ready
Mendeliome v0.11702 C8A Zornitza Stark Marked gene: C8A as ready
Mendeliome v0.11698 SAMHD1 Zornitza Stark Marked gene: SAMHD1 as ready
Mendeliome v0.11698 SAMHD1 Zornitza Stark Phenotypes for gene: SAMHD1 were changed from to Aicardi-Goutieres syndrome 5, MIM# 612952
Mendeliome v0.11695 UNC119 Zornitza Stark Marked gene: UNC119 as ready
Mendeliome v0.11691 UNC119 Zornitza Stark changed review comment from: Immunodeficiency 13: Single case reported with the missense Gly22Val. The allele frequency of this variant is >2% in the African/African American subpopulation in gnomAD v2.1, including 6 homozygotes. RED for this association.

Amber for association with cone-rod dystrophy.; to: Immunodeficiency 13: Single case reported with the missense Gly22Val. The allele frequency of this variant is >2% in the African/African American subpopulation in gnomAD v2.1, including 6 homozygotes. RED for this association.

Borderline Green for association with cone-rod dystrophy.
Mendeliome v0.11690 SAMD9 Zornitza Stark Marked gene: SAMD9 as ready
Mendeliome v0.11687 UCP3 Zornitza Stark Marked gene: UCP3 as ready
Mendeliome v0.11683 NDUFS3 Zornitza Stark Marked gene: NDUFS3 as ready
Mendeliome v0.11683 NDUFS3 Zornitza Stark Phenotypes for gene: NDUFS3 were changed from to Mitochondrial complex I deficiency, nuclear type 8 - MIM#618230
Mendeliome v0.11680 USH2A Belinda Chong edited their review of gene: USH2A: Added comment: Well established gene-disease association - Usher syndrome, DEFINITIVE by ClinGen.

PMID 20507924: Screened the long isoform of USH2A in 80 patients with nonsyndromic autosomal recessive RP and identified at least 1 deleterious mutation in 19% of cases. The authors stated that their findings supported USH2A as the most common known cause of RP in the United States.

https://www.ncbi.nlm.nih.gov/books/NBK1341/, PMID 17296898, ClinVar
Reports of cosegregation of Usher Syndrome and Retinitis Pigmentosa; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11680 C4A Zornitza Stark Marked gene: C4A as ready
Mendeliome v0.11680 NDUFS6 Krithika Murali reviewed gene: NDUFS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 15372108, 19259137, 30948790; Phenotypes: Mitochondrial complex I deficiency, nuclear type 9 - MIM#618232; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11680 NDUFS2 Zornitza Stark Marked gene: NDUFS2 as ready
Mendeliome v0.11680 NDUFS2 Zornitza Stark Phenotypes for gene: NDUFS2 were changed from to Mitochondrial complex I deficiency, nuclear type 6 - MIM#618228
Mendeliome v0.11674 C4A Ain Roesley changed review comment from: Associated with increased risk for systemic lupus erythematosus (SLE).
This is mostly involving haplotypes, gene copy number, gene conversions with/without C4B; to: Associated with increased risk for systemic lupus erythematosus (SLE).
This is mostly involving haplotypes, gene copy number, gene conversions with/without C4B

There are no LP/P SNV in clinvar

PMID: 32048120; 2019 Update of the IUIS Phenotypical Classification indicates that complete C4 deficiency requires both C4A+C4B and C4A alone leads to partial deficiency
Mendeliome v0.11674 USH1C Belinda Chong reviewed gene: USH1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 31858762, 10973247, 10973248, 11239869, 21203349, 12107438; Phenotypes: Usher syndrome, type 1C, MIM# 276904, Deafness, autosomal recessive 18A, MIM# 602092, ?Non-syndromic hearing loss; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11674 C4B Ain Roesley Marked gene: C4B as ready
Mendeliome v0.11674 C4B Zornitza Stark Marked gene: C4B as ready
Mendeliome v0.11668 C4B Ain Roesley changed review comment from: Associated with increased risk for systemic lupus erythematosus (SLE).
This is mostly involving haplotypes, gene copy number, gene conversions with/without C4A; to: Associated with increased risk for systemic lupus erythematosus (SLE).
This is mostly involving haplotypes, gene copy number, gene conversions with/without C4A

no LP/P SNVs in clinvar. (1 LP but evidence provided indicates that it was classified as a VUS)

PMID: 32048120;
2019 Update of the IUIS Phenotypical Classification indicates that complete C4 deficiency requires both C4A+C4B and C4A alone leads to partial deficiency
Mendeliome v0.11668 NDUFS1 Zornitza Stark Marked gene: NDUFS1 as ready
Mendeliome v0.11668 NDUFS1 Zornitza Stark Phenotypes for gene: NDUFS1 were changed from to Mitochondrial complex I deficiency, nuclear type 5 - MIM#618226
Mendeliome v0.11665 UCP3 Belinda Chong changed review comment from: Inheritance: Autosomal dominant, autosomal recessive and multifactorial

PMID: 21544083
Identified four novel mutations in the UCP3 gene (V56M, A111V, V192I and Q252X) in 200 children with severe, early-onset obesity (body mass index-standard deviation score >2.5; onset: <4 years) living in Southern Italy. Indicated that protein UCP3 affects long-chain fatty acid metabolism and can prevent cytosolic triglyceride storage. Also suggested that telmisartan, which increases fatty acid oxidation in rat skeletal muscle, also improves UCP3 wt and mutant protein activity, including the dominant-negative UCP3 mutants (V56M & Q252X).

All variants are present in GnomAD there are 56 - V56M, 325 - A111V, 9 - V192I and 2 - A252X; to: Inheritance: Autosomal dominant, autosomal recessive and multifactorial

PMID: 21544083
Identified four novel mutations in the UCP3 gene (V56M, A111V, V192I and Q252X) in 200 children with severe, early-onset obesity (body mass index-standard deviation score >2.5; onset: <4 years) living in Southern Italy. Indicated that protein UCP3 affects long-chain fatty acid metabolism and can prevent cytosolic triglyceride storage. Also suggested that telmisartan, which increases fatty acid oxidation in rat skeletal muscle, also improves UCP3 wt and mutant protein activity, including the dominant-negative UCP3 mutants (V56M & Q252X). Single pathogenic variant in ClinVar

All variants are present in GnomAD there are 56 - V56M, 325 - A111V, 9 - V192I and 2 - A252X
Mendeliome v0.11665 NDUFS4 Krithika Murali reviewed gene: NDUFS4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11181577, 11165261, 16478720, 10944442, 24295889, 22326555, 27079373, 15975579, 19364667, 27671926, 33093004, 29264396, 34484776; Phenotypes: Mitochondrial complex I deficiency, nuclear type 1 - MIM#252010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11665 UROD Belinda Chong reviewed gene: UROD: Rating: GREEN; Mode of pathogenicity: None; Publications: 23545314, 30514647, 9792863; Phenotypes: Porphyria cutanea tarda, Porphyria, hepatoerythropoietic (MIM#176100); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11665 UQCRB Belinda Chong commented on gene: UQCRB: Three families, two had the same variant. Functional data.
Mendeliome v0.11665 UQCRB Belinda Chong reviewed gene: UQCRB: Rating: GREEN; Mode of pathogenicity: None; Publications: 23281071, 28275242, 12709789, 25446085, 23454382; Phenotypes: Mitochondrial complex III deficiency, nuclear type 3, MIM# 615158; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11665 UQCC2 Belinda Chong reviewed gene: UQCC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24385928, 28804536; Phenotypes: Mitochondrial complex III deficiency, nuclear type 7 - MIM#615824; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11665 C9 Ain Roesley Marked gene: C9 as ready
Mendeliome v0.11662 C8B Ain Roesley Marked gene: C8B as ready
Mendeliome v0.11659 C8A Ain Roesley changed review comment from: 6 unrelated (2 japanese and 4 africans) with 3 different variants between them (2 splice - 1 with aberrant splicing proven on cDNA and 1 nonsense)

PMID: 8098723; 3 families hom for a nonsense and 2 families 3rd het for the same nonsense and unknown 2nd allele

Amber because no other reports apart from these papers and comprehensive sequencing was not done even in the 2020 paper.; to: 6 unrelated (2 japanese and 4 africans) with 3 different variants between them (2 splice - 1 with aberrant splicing proven on cDNA and 1 nonsense)


Amber because no other reports apart from these papers and comprehensive sequencing was not done even in the 2020 paper.
Mendeliome v0.11659 SAMHD1 Samantha Ayres reviewed gene: SAMHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19525956, 21102625, 33307271, 20301648; Phenotypes: Aicardi-Goutieres syndrome 5, MIM# 612952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11659 C7 Ain Roesley Marked gene: C7 as ready
Mendeliome v0.11652 C6 Ain Roesley Marked gene: C6 as ready
Mendeliome v0.11652 NDUFS3 Krithika Murali reviewed gene: NDUFS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22499348, 30140060, 14729820, 33097395; Phenotypes: Mitochondrial complex I deficiency, nuclear type 8 - MIM#618230; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11652 C5 Ain Roesley Marked gene: C5 as ready
Mendeliome v0.11649 NDUFS2 Krithika Murali reviewed gene: NDUFS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28031252, 31411514, 22036843, 20819849, 11220739, 23266820, 31411514; Phenotypes: Mitochondrial complex I deficiency, nuclear type 6 - MIM#618228; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11649 NDUFS1 Krithika Murali reviewed gene: NDUFS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33751534, 24952175, 20382551, 21203893, 20797884, 15824269, 25615419, 11349233, 22399432; Phenotypes: Mitochondrial complex I deficiency, nuclear type 5 - MIM#618226; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11649 C3 Ain Roesley Marked gene: C3 as ready
Mendeliome v0.11645 SMARCA4 Zornitza Stark Marked gene: SMARCA4 as ready
Mendeliome v0.11645 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Green List (High Evidence).
Mendeliome v0.11645 SMARCA4 Zornitza Stark Phenotypes for gene: SMARCA4 were changed from to Coffin-Siris syndrome 4, MIM# 614609
Mendeliome v0.11644 SMARCA4 Zornitza Stark Publications for gene: SMARCA4 were set to
Mendeliome v0.11643 SMARCA4 Zornitza Stark Mode of inheritance for gene: SMARCA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11642 SMARCA4 Zornitza Stark reviewed gene: SMARCA4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22426308; Phenotypes: Coffin-Siris syndrome 4, MIM# 614609; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11642 SMAD9 Zornitza Stark Marked gene: SMAD9 as ready
Mendeliome v0.11642 SMAD9 Zornitza Stark Phenotypes for gene: SMAD9 were changed from to Pulmonary hypertension, primary, 2 MIM#615342
Mendeliome v0.11639 SMAD9 Zornitza Stark reviewed gene: SMAD9: Rating: GREEN; Mode of pathogenicity: None; Publications: 29844917, 21920918, 19211612, 21898662; Phenotypes: Pulmonary hypertension, primary, 2 MIM#615342; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11639 SMAD7 Zornitza Stark Marked gene: SMAD7 as ready
Mendeliome v0.11636 SMAD4 Zornitza Stark Marked gene: SMAD4 as ready
Mendeliome v0.11636 SMAD4 Zornitza Stark Phenotypes for gene: SMAD4 were changed from to Juvenile polyposis/hereditary haemorrhagic telangiectasia syndrome, MIM# 175050; Polyposis, juvenile intestinal, MIM# 174900; Myhre syndrome, MIM# 139210
Mendeliome v0.11633 SMAD4 Zornitza Stark reviewed gene: SMAD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 30809044, 15235019, 16613914, 20101697, 22158539, 22243968; Phenotypes: Juvenile polyposis/hereditary haemorrhagic telangiectasia syndrome, MIM# 175050, Polyposis, juvenile intestinal, MIM# 174900, Myhre syndrome, MIM# 139210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11633 SLITRK6 Zornitza Stark Marked gene: SLITRK6 as ready
Mendeliome v0.11630 SLITRK1 Zornitza Stark Marked gene: SLITRK1 as ready
Mendeliome v0.11626 SLCO1B3 Zornitza Stark Marked gene: SLCO1B3 as ready
Mendeliome v0.11621 SLCO1B1 Zornitza Stark edited their review of gene: SLCO1B1: Added comment: Digenic inheritance proposed, with variants in SLCO1B3 also required.; Changed rating: AMBER; Changed publications: 33860121; Changed phenotypes: Hyperbilirubinemia, Rotor type, digenic 237450; Changed mode of inheritance: Other
Mendeliome v0.11619 SLC9A9 Zornitza Stark Marked gene: SLC9A9 as ready
Mendeliome v0.11615 SLC7A9 Zornitza Stark Marked gene: SLC7A9 as ready
Mendeliome v0.11612 SLC6A9 Zornitza Stark Marked gene: SLC6A9 as ready
Mendeliome v0.11609 SLC6A8 Zornitza Stark Marked gene: SLC6A8 as ready
Mendeliome v0.11606 ENPP1 Zornitza Stark Phenotypes for gene: ENPP1 were changed from to Arterial calcification, generalized, of infancy, 1, MIM# 208000; Cole disease, MIM# 615522; Hypophosphatemic rickets, autosomal recessive, 2, MIM# 613312
Mendeliome v0.11603 ENPP1 Zornitza Stark reviewed gene: ENPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24075184, 26617416, 28964717, 32598042, 35220637, 12881724, 15605415, 33005041, 20016754, 20137773, 20137772; Phenotypes: Arterial calcification, generalized, of infancy, 1, MIM# 208000, Cole disease, MIM# 615522, Hypophosphatemic rickets, autosomal recessive, 2, MIM# 613312; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11603 VMA21 Zornitza Stark Marked gene: VMA21 as ready
Mendeliome v0.11600 VPS33B Zornitza Stark Marked gene: VPS33B as ready
Mendeliome v0.11600 VPS33B Zornitza Stark Phenotypes for gene: VPS33B were changed from to Arthrogryposis, renal dysfunction, and cholestasis 1 (MIM#208085)
Mendeliome v0.11597 VPS33B Zornitza Stark reviewed gene: VPS33B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31240160, 31777725, 24415890, 15052268; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 1 (MIM#208085); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11597 VPS35 Zornitza Stark Marked gene: VPS35 as ready
Mendeliome v0.11597 VPS35 Zornitza Stark Phenotypes for gene: VPS35 were changed from to Parkinson disease 17, MIM# 614203
Mendeliome v0.11594 VPS35 Zornitza Stark reviewed gene: VPS35: Rating: ; Mode of pathogenicity: None; Publications: 21763482, 21763483, 22801713, 34704029; Phenotypes: Parkinson disease 17, MIM# 614203; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11594 VSX1 Zornitza Stark Marked gene: VSX1 as ready
Mendeliome v0.11590 VWF Zornitza Stark Marked gene: VWF as ready
Mendeliome v0.11588 VKORC1 Zornitza Stark Marked gene: VKORC1 as ready
Mendeliome v0.11588 VKORC1 Zornitza Stark Phenotypes for gene: VKORC1 were changed from to Vitamin K-dependent clotting factors, combined deficiency of, 2, MIM# 607473; Warfarin resistance, MIM# 122700
Mendeliome v0.11586 VIPAS39 Zornitza Stark Marked gene: VIPAS39 as ready
Mendeliome v0.11586 VIPAS39 Zornitza Stark Phenotypes for gene: VIPAS39 were changed from to Arthrogryposis, renal dysfunction, and cholestasis 2, MIM#613404
Mendeliome v0.11583 VIPAS39 Zornitza Stark reviewed gene: VIPAS39: Rating: GREEN; Mode of pathogenicity: None; Publications: 20190753, 35151346; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 2, MIM#613404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11583 VEGFA Zornitza Stark Marked gene: VEGFA as ready
Mendeliome v0.11583 VEGFA Zornitza Stark Phenotypes for gene: VEGFA were changed from to {Microvascular complications of diabetes 1} 603933
Mendeliome v0.11581 VEGFA Zornitza Stark reviewed gene: VEGFA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Microvascular complications of diabetes 1} 603933; Mode of inheritance: None
Mendeliome v0.11581 VDR Zornitza Stark Marked gene: VDR as ready
Mendeliome v0.11578 VCL Zornitza Stark Marked gene: VCL as ready
Mendeliome v0.11578 VCL Zornitza Stark Phenotypes for gene: VCL were changed from to Cardiomyopathy, dilated, 1W, MIM# 611407
Mendeliome v0.11575 VCL Zornitza Stark reviewed gene: VCL: Rating: GREEN; Mode of pathogenicity: None; Publications: 31983221, 32516855, 26406308, 26458567, 24062880, 11815424, 17785437, 17097056; Phenotypes: Cardiomyopathy, dilated, 1W, MIM# 611407; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11575 VANGL2 Zornitza Stark Marked gene: VANGL2 as ready
Mendeliome v0.11571 VANGL1 Zornitza Stark Marked gene: VANGL1 as ready
Mendeliome v0.11567 VAMP1 Zornitza Stark Marked gene: VAMP1 as ready
Mendeliome v0.11564 NDUFB8 Zornitza Stark Marked gene: NDUFB8 as ready
Mendeliome v0.11564 NDUFB8 Zornitza Stark Phenotypes for gene: NDUFB8 were changed from to Mitochondrial complex I deficiency, nuclear type 32 - MIM#618252
Mendeliome v0.11561 NDUFAF7 Zornitza Stark Marked gene: NDUFAF7 as ready
Mendeliome v0.11554 NDUFAF4 Zornitza Stark Marked gene: NDUFAF4 as ready
Mendeliome v0.11554 NDUFAF4 Zornitza Stark Phenotypes for gene: NDUFAF4 were changed from to Mitochondrial complex I deficiency, nuclear type 15 - MIM#618237
Mendeliome v0.11551 EDARADD Bryony Thompson Marked gene: EDARADD as ready
Mendeliome v0.11551 EDARADD Bryony Thompson Gene: edaradd has been classified as Green List (High Evidence).
Mendeliome v0.11551 EDARADD Bryony Thompson Mode of inheritance for gene: EDARADD was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.11550 EDARADD Bryony Thompson reviewed gene: EDARADD: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301291, 34219261, 11780064, 26991760, 34573371, 20979233, 17354266, 26440664; Phenotypes: autosomal dominant hypohidrotic ectodermal dysplasia MONDO:0015884, autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11550 EDAR Bryony Thompson Marked gene: EDAR as ready
Mendeliome v0.11550 EDAR Bryony Thompson Gene: edar has been classified as Green List (High Evidence).
Mendeliome v0.11550 EDAR Bryony Thompson Phenotypes for gene: EDAR were changed from to autosomal dominant hypohidrotic ectodermal dysplasia MONDO:0015884; autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619
Mendeliome v0.11549 EDAR Bryony Thompson Publications for gene: EDAR were set to
Mendeliome v0.11548 EDAR Bryony Thompson Mode of inheritance for gene: EDAR was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.11547 EDAR Bryony Thompson reviewed gene: EDAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 10431241, 20301291, 16435307, 20979233, 23401279, 18384562; Phenotypes: autosomal dominant hypohidrotic ectodermal dysplasia MONDO:0015884, autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11547 NDUFAF3 Zornitza Stark Marked gene: NDUFAF3 as ready
Mendeliome v0.11547 NDUFAF3 Zornitza Stark Phenotypes for gene: NDUFAF3 were changed from to Mitochondrial complex I deficiency, nuclear type 18 - MIM#618240
Mendeliome v0.11544 NDUFA2 Zornitza Stark Marked gene: NDUFA2 as ready
Mendeliome v0.11544 NDUFA2 Zornitza Stark Phenotypes for gene: NDUFA2 were changed from to Mitochondrial complex I deficiency, nuclear type 13 - MIM#618235
Mendeliome v0.11541 NDUFB8 Krithika Murali reviewed gene: NDUFB8: Rating: GREEN; Mode of pathogenicity: None; Publications: 29429571; Phenotypes: Mitochondrial complex I deficiency, nuclear type 32 - MIM#618252; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11540 NDUFAF4 Krithika Murali edited their review of gene: NDUFAF4: Added comment: 3 unrelated families reported with patient-specific functional evidence provided for each.

PMID: 32949790 - report two siblings with facial dysmorphism and lactic acidosis diagnosed neonatally with subsequent fatal early encephalopathy with apneic episodes, irritability, central hypoventilation, liver involvement and hyperammonemia. Cerebral white matter anomalies reported in one patient and cardiomyopathy in the other. WES identified homozygous nonsense NDUFAF4 variants with absent NDUFAF4 expression in patient fibroblasts. OXPHOS assembly studies demonstrated almost undetectable levels of fully assembled complex I and complex I–containing supercomplexes and an abnormal accumulation of SCIII2IV1 supercomplexes. Morphologically, fibroblasts showed rounder mitochondria and a diminished degree of branching of the mitochondrial network.

PMID: 28853723 - report one patient born at 38 weeks after IOL for IUGR. Presented age 7 months with developmental regression, growth failure and central hypotonia. Brain MRI revealed diffuse bilateral signal alterations in the basal ganglia and thalami and an EEG showed generalized slowing with multifocal spikes consistent with an epileptogenic focus. Homozygous missense NDUFAF4 variants identified. Lentiviral complementation of patient fibroblasts with wild-type NDUFAF4 rescued complex I deficiency and assembly defect

PMID 18179882 - report multiple affected individuals from one family. Most presented soon after birth with severe metabolic acidosis and high plasma lactate levels. Patients who survived longer were repeatedly admitted because of exacerbation of the acidosis during intercurrent infections. One long-term survivor had profound ID.; Changed publications: 32949790, 28853723, 18179882
Mendeliome v0.11540 NDUFAF4 Krithika Murali reviewed gene: NDUFAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 32949790, 28853723; Phenotypes: Mitochondrial complex I deficiency, nuclear type 15 - MIM#618237; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11540 NDUFAF3 Krithika Murali reviewed gene: NDUFAF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27986404, 29344937, 19463981; Phenotypes: Mitochondrial complex I deficiency, nuclear type 18 - MIM#618240; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11540 UBA5 Zornitza Stark Marked gene: UBA5 as ready
Mendeliome v0.11540 UBA5 Zornitza Stark Phenotypes for gene: UBA5 were changed from to Spinocerebellar ataxia, autosomal recessive 24, MIM# 617133; Epileptic encephalopathy, early infantile, 44 617132; Hypomyelinating neuropathy
Mendeliome v0.11537 UBA5 Zornitza Stark changed review comment from: Bi-allelic variants in UBA5 cause a range of neurological phenotypes. Ataxia has been specifically described only in one sibling pair. Multiple individuals reported with a more severe EE/ID phenotype, and non-specific movement disorders.; to: Bi-allelic variants in UBA5 cause a range of neurological phenotypes. Ataxia has been specifically described only in one sibling pair. Multiple individuals reported with a more severe EE/ID phenotype, and non-specific movement disorders.

Also note these two reports of demyelinating peripheral neuropathy: 26872069 pair of sibs with mild ataxia, one with neuropathy; 32179706 five individuals from a consanguineous family presenting in infancy with severe fatal neuropathy. Some functional data. Due to early mortality, uncertain at present whether additional features would have developed.
Mendeliome v0.11537 UBA5 Zornitza Stark edited their review of gene: UBA5: Changed rating: GREEN; Changed publications: 26872069, 27545681, 27545674, 32179706, 26872069; Changed phenotypes: Spinocerebellar ataxia, autosomal recessive 24, MIM# 617133, Epileptic encephalopathy, early infantile, 44 617132, Hypomyelinating neuropathy
Mendeliome v0.11537 NDUFA2 Krithika Murali reviewed gene: NDUFA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28857146, 32154054, 18513682; Phenotypes: Mitochondrial complex I deficiency, nuclear type 13 - MIM#618235; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11537 KANSL1 Zornitza Stark Marked gene: KANSL1 as ready
Mendeliome v0.11537 IKBKG Zornitza Stark Marked gene: IKBKG as ready
Mendeliome v0.11535 IKBKB Zornitza Stark Marked gene: IKBKB as ready
Mendeliome v0.11532 IL10RB Zornitza Stark Marked gene: IL10RB as ready
Mendeliome v0.11532 IL10RB Zornitza Stark Phenotypes for gene: IL10RB were changed from to Inflammatory bowel disease 25, early onset, autosomal recessive, MIM# 612567
Mendeliome v0.11529 IL12B Zornitza Stark Marked gene: IL12B as ready
Mendeliome v0.11526 IL10RB Zornitza Stark reviewed gene: IL10RB: Rating: GREEN; Mode of pathogenicity: None; Publications: 19890111, 21519361, 35187668, 31096038; Phenotypes: Inflammatory bowel disease 25, early onset, autosomal recessive, MIM# 612567; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11526 IL10RA Zornitza Stark Marked gene: IL10RA as ready
Mendeliome v0.11526 IL10RA Zornitza Stark Phenotypes for gene: IL10RA were changed from to Inflammatory bowel disease 28, early onset, autosomal recessive, MIM# 613148
Mendeliome v0.11523 IL10RA Zornitza Stark reviewed gene: IL10RA: Rating: GREEN; Mode of pathogenicity: None; Publications: 19890111, 21519361, 22476154; Phenotypes: Inflammatory bowel disease 28, early onset, autosomal recessive, MIM# 613148; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11523 IL10 Zornitza Stark changed review comment from: At least two families and a mouse model.

Rare variants in this gene are also associated with susceptibility to a range of immune-related complex disorder.; to: At least two families and a mouse model.

Rare variants in this gene are also associated with susceptibility to a range of immune-related complex disorders.
Mendeliome v0.11523 IL10 Zornitza Stark Marked gene: IL10 as ready
Mendeliome v0.11523 IL10 Zornitza Stark Phenotypes for gene: IL10 were changed from to Diseases of Immune Dysregulation; Early-onset inflammatory bowel disease
Mendeliome v0.11520 IL10 Zornitza Stark reviewed gene: IL10: Rating: GREEN; Mode of pathogenicity: None; Publications: 22236434, 20951137, 19890111; Phenotypes: Diseases of Immune Dysregulation, Early-onset inflammatory bowel disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11520 IGLL1 Zornitza Stark Marked gene: IGLL1 as ready
Mendeliome v0.11517 IGHMBP2 Zornitza Stark Marked gene: IGHMBP2 as ready
Mendeliome v0.11517 IGHMBP2 Zornitza Stark Phenotypes for gene: IGHMBP2 were changed from to Neuronopathy, distal hereditary motor, type VI, MIM# 604320; Charcot-Marie-Tooth disease, axonal, type 2S, MIM# 616155
Mendeliome v0.11514 IGHMBP2 Zornitza Stark reviewed gene: IGHMBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuronopathy, distal hereditary motor, type VI, MIM# 604320, Charcot-Marie-Tooth disease, axonal, type 2S, MIM# 616155; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11514 CCDC134 Zornitza Stark Marked gene: CCDC134 as ready
Mendeliome v0.11512 RACGAP1 Zornitza Stark Marked gene: RACGAP1 as ready
Mendeliome v0.11508 KIF23 Zornitza Stark edited their review of gene: KIF23: Added comment: Second individual reported, elongation variant.; Changed rating: AMBER; Changed publications: 23570799, 33159567; Changed phenotypes: Anaemia, congenital dyserythropoietic, type IIIA 105600
Mendeliome v0.11508 IL12RB1 Zornitza Stark Marked gene: IL12RB1 as ready
Mendeliome v0.11505 IL13 Zornitza Stark Marked gene: IL13 as ready
Mendeliome v0.11503 NDUFAF2 Zornitza Stark Marked gene: NDUFAF2 as ready
Mendeliome v0.11503 NDUFAF2 Zornitza Stark Phenotypes for gene: NDUFAF2 were changed from to Mitochondrial complex I deficiency, nuclear type 10 - MIM#618233
Mendeliome v0.11500 NDUFAF1 Zornitza Stark Marked gene: NDUFAF1 as ready
Mendeliome v0.11500 NDUFAF1 Zornitza Stark Phenotypes for gene: NDUFAF1 were changed from to Mitochondrial complex I deficiency, nuclear type 11 - MIM#618234
Mendeliome v0.11497 NDUFA9 Zornitza Stark Marked gene: NDUFA9 as ready
Mendeliome v0.11497 NDUFA9 Zornitza Stark Phenotypes for gene: NDUFA9 were changed from to Mitochondrial complex I deficiency, nuclear type 26 - MIM#618247
Mendeliome v0.11494 NDUFA7 Zornitza Stark Marked gene: NDUFA7 as ready
Mendeliome v0.11493 TPTE2P5 Zornitza Stark Marked gene: TPTE2P5 as ready
Mendeliome v0.11492 IL6 Zornitza Stark Marked gene: IL6 as ready
Mendeliome v0.11492 IL6 Zornitza Stark Phenotypes for gene: IL6 were changed from to {Crohn disease-associated growth failure} 266600; {Intracranial hemorrhage in brain cerebrovascular malformations, susceptibility to} 108010; {Rheumatoid arthritis, systemic juvenile} 604302; {Kaposi sarcoma, susceptibility to} 148000; {Type 1 diabetes mellitus} 222100; {Type 2 diabetes mellitus} 125853
Mendeliome v0.11490 IL6 Zornitza Stark reviewed gene: IL6: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: {Crohn disease-associated growth failure} 266600, {Intracranial hemorrhage in brain cerebrovascular malformations, susceptibility to} 108010, {Rheumatoid arthritis, systemic juvenile} 604302, {Kaposi sarcoma, susceptibility to} 148000, {Type 1 diabetes mellitus} 222100, {Type 2 diabetes mellitus} 125853; Mode of inheritance: None
Mendeliome v0.11490 IL4 Zornitza Stark Marked gene: IL4 as ready
Mendeliome v0.11489 IL36RN Zornitza Stark Marked gene: IL36RN as ready
Mendeliome v0.11489 IL36RN Zornitza Stark Phenotypes for gene: IL36RN were changed from to Psoriasis 14, pustular, MIM# 614204
Mendeliome v0.11486 IL36RN Zornitza Stark reviewed gene: IL36RN: Rating: GREEN; Mode of pathogenicity: None; Publications: 21848462, 21839423, 22903787, 23648549; Phenotypes: Psoriasis 14, pustular, MIM# 614204; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11486 IL31RA Zornitza Stark Marked gene: IL31RA as ready
Mendeliome v0.11486 IL31RA Zornitza Stark Phenotypes for gene: IL31RA were changed from to Amyloidosis, primary localized cutaneous, 2, MIM# 613955
Mendeliome v0.11483 IL31RA Zornitza Stark reviewed gene: IL31RA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Amyloidosis, primary localized cutaneous, 2, MIM# 613955; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11483 NDUFAF2 Krithika Murali reviewed gene: NDUFAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528536, 34364746, 16200211, 19384974, 20571988; Phenotypes: Mitochondrial complex I deficiency, nuclear type 10 - MIM#618233; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11483 NDUFAF1 Krithika Murali reviewed gene: NDUFAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17557076, 21931170, 16218961, 24963768, 34975718; Phenotypes: Mitochondrial complex I deficiency, nuclear type 11 - MIM#618234; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11483 NDUFA9 Krithika Murali reviewed gene: NDUFA9: Rating: GREEN; Mode of pathogenicity: None; Publications: 26425749, 28671271, 22114105; Phenotypes: Mitochondrial complex I deficiency, nuclear type 26 - MIM#618247; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11483 IL2RA Zornitza Stark Marked gene: IL2RA as ready
Mendeliome v0.11480 IL1RN Zornitza Stark Marked gene: IL1RN as ready
Mendeliome v0.11477 IREB2 Zornitza Stark Marked gene: IREB2 as ready
Mendeliome v0.11477 IREB2 Zornitza Stark Phenotypes for gene: IREB2 were changed from to Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia, MIM#618451
Mendeliome v0.11474 ISG15 Zornitza Stark Marked gene: ISG15 as ready
Mendeliome v0.11471 ISCU Zornitza Stark Marked gene: ISCU as ready
Mendeliome v0.11471 ISCU Zornitza Stark Phenotypes for gene: ISCU were changed from to Myopathy with lactic acidosis, hereditary, MIM# 255125
Mendeliome v0.11468 ISCU Zornitza Stark reviewed gene: ISCU: Rating: GREEN; Mode of pathogenicity: None; Publications: 29079705, 18304497, 18296749, 19567699; Phenotypes: Myopathy with lactic acidosis, hereditary, MIM# 255125; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11468 IRS1 Zornitza Stark Marked gene: IRS1 as ready
Mendeliome v0.11468 IRS1 Zornitza Stark Phenotypes for gene: IRS1 were changed from to {Coronary artery disease, susceptibility to}; {Type 2 diabetes mellitus, susceptibility to}, MIM# 125853
Mendeliome v0.11466 IRS1 Zornitza Stark reviewed gene: IRS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Coronary artery disease, susceptibility to}, {Type 2 diabetes mellitus, susceptibility to}, MIM# 125853; Mode of inheritance: None
Mendeliome v0.11466 IRF8 Zornitza Stark Marked gene: IRF8 as ready
Mendeliome v0.11463 IRF5 Zornitza Stark Marked gene: IRF5 as ready
Mendeliome v0.11461 IRF1 Zornitza Stark Marked gene: IRF1 as ready
Mendeliome v0.11460 IREB2 Zornitza Stark reviewed gene: IREB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30915432, 31243445, 11175792; Phenotypes: Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia, MIM#618451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11459 NDUFA10 Zornitza Stark reviewed gene: NDUFA10: Rating: GREEN; Mode of pathogenicity: None; Publications: 21150889, 26741492, 28247337; Phenotypes: Mitochondrial complex I deficiency, nuclear type 22 - MIM#618243; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11459 NDUFA10 Zornitza Stark Marked gene: NDUFA10 as ready
Mendeliome v0.11459 NDUFA10 Zornitza Stark Phenotypes for gene: NDUFA10 were changed from to Mitochondrial complex I deficiency, nuclear type 22 - MIM#618243
Mendeliome v0.11456 NDST1 Zornitza Stark Marked gene: NDST1 as ready
Mendeliome v0.11456 NDST1 Zornitza Stark Phenotypes for gene: NDST1 were changed from to Mental retardation, autosomal recessive 46 - MIM#616116
Mendeliome v0.11453 NCR3 Zornitza Stark Marked gene: NCR3 as ready
Mendeliome v0.11452 NCOA4 Zornitza Stark Marked gene: NCOA4 as ready
Mendeliome v0.11451 NCF4 Zornitza Stark Marked gene: NCF4 as ready
Mendeliome v0.11448 NCF2 Zornitza Stark Marked gene: NCF2 as ready
Mendeliome v0.11445 SALL4 Zornitza Stark Marked gene: SALL4 as ready
Mendeliome v0.11442 TYROBP Zornitza Stark Marked gene: TYROBP as ready
Mendeliome v0.11439 IRAK4 Zornitza Stark Marked gene: IRAK4 as ready
Mendeliome v0.11436 INSR Zornitza Stark Marked gene: INSR as ready
Mendeliome v0.11433 INS Zornitza Stark Marked gene: INS as ready
Mendeliome v0.11430 INO80 Zornitza Stark Marked gene: INO80 as ready
Mendeliome v0.11430 INO80 Zornitza Stark Phenotypes for gene: INO80 were changed from to Primary immunodeficiency, MONDO:0003778
Mendeliome v0.11426 INO80 Zornitza Stark reviewed gene: INO80: Rating: AMBER; Mode of pathogenicity: None; Publications: 25312759; Phenotypes: Primary immunodeficiency, MONDO:0003778; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11426 IMPAD1 Zornitza Stark Marked gene: IMPAD1 as ready
Mendeliome v0.11423 ILF2 Zornitza Stark changed review comment from: Cannot find evidence for association with Mendelian disease.; to: Limited data to support association with autism: two variants in a large ASD cohort and other supportive evidence. Assessed as 'strong candidate' by SFARI.
Mendeliome v0.11423 ILF2 Zornitza Stark Marked gene: ILF2 as ready
Mendeliome v0.11422 NDUFA10 Krithika Murali reviewed gene: NDUFA10: Rating: GREEN; Mode of pathogenicity: None; Publications: 26741492, 21150889; Phenotypes: Mitochondrial complex I deficiency, nuclear type 22 - MIM#618243; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11422 NDST1 Krithika Murali reviewed gene: NDST1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25125150, 21937992, 32878022, 28211985; Phenotypes: Mental retardation, autosomal recessive 46 - MIM#616116; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11422 IFNGR2 Zornitza Stark Marked gene: IFNGR2 as ready
Mendeliome v0.11419 IFNGR1 Zornitza Stark Marked gene: IFNGR1 as ready
Mendeliome v0.11419 IFNGR1 Zornitza Stark Phenotypes for gene: IFNGR1 were changed from to Immunodeficiency 27A, mycobacteriosis, AR, MIM# 209950; Immunodeficiency 27B, mycobacteriosis, AD, MIM# 615978
Mendeliome v0.11416 IFNGR1 Zornitza Stark reviewed gene: IFNGR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7815885, 8960475, 9389728, 10811850, 10192386, 12244188, 15589309; Phenotypes: Immunodeficiency 27A, mycobacteriosis, AR, MIM# 209950, Immunodeficiency 27B, mycobacteriosis, AD, MIM# 615978; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11416 IFITM3 Zornitza Stark Marked gene: IFITM3 as ready
Mendeliome v0.11414 IDH3B Zornitza Stark Marked gene: IDH3B as ready
Mendeliome v0.11411 IDH2 Zornitza Stark Marked gene: IDH2 as ready
Mendeliome v0.11411 IDH2 Zornitza Stark Phenotypes for gene: IDH2 were changed from to D-2-hydroxyglutaric aciduria 2, MIM# 613657
Mendeliome v0.11408 IDH2 Zornitza Stark reviewed gene: IDH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25778941, 27142242, 20847235, 24049096; Phenotypes: D-2-hydroxyglutaric aciduria 2, MIM# 613657; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11408 ICOS Zornitza Stark Marked gene: ICOS as ready
Mendeliome v0.11408 ICOS Zornitza Stark Phenotypes for gene: ICOS were changed from to Immunodeficiency, common variable, 1 MIM# 607594
Mendeliome v0.11405 ICOS Zornitza Stark reviewed gene: ICOS: Rating: GREEN; Mode of pathogenicity: None; Publications: 12577056, 15507387, 19380800, 28861081, 31858365, 11343122, 16982935; Phenotypes: Immunodeficiency, common variable, 1 MIM# 607594; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11405 ICAM4 Zornitza Stark Marked gene: ICAM4 as ready
Mendeliome v0.11403 ACACA Zornitza Stark Marked gene: ACACA as ready
Mendeliome v0.11403 ACACA Zornitza Stark Phenotypes for gene: ACACA were changed from to Acetyl-CoA carboxylase deficiency MIM#613933
Mendeliome v0.11399 ABL1 Zornitza Stark Marked gene: ABL1 as ready
Mendeliome v0.11399 ABCG8 Zornitza Stark Marked gene: ABCG8 as ready
Mendeliome v0.11394 ACACA Elena Savva reviewed gene: ACACA: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34552920, 10677481, 16717184; Phenotypes: Acetyl-CoA carboxylase deficiency MIM#613933; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11394 ACAD8 Elena Savva Marked gene: ACAD8 as ready
Mendeliome v0.11391 C2 Ain Roesley Marked gene: C2 as ready
Mendeliome v0.11390 ABL1 Elena Savva Phenotypes for gene: ABL1 were changed from to Congenital heart defects and skeletal malformations syndrome MIM#617602
Mendeliome v0.11388 ABL1 Elena Savva reviewed gene: ABL1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 28288113, 30855488, 32643838; Phenotypes: Congenital heart defects and skeletal malformations syndrome MIM#617602; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.11387 C1S Ain Roesley Marked gene: C1S as ready
Mendeliome v0.11386 ABCC8 Elena Savva Marked gene: ABCC8 as ready
Mendeliome v0.11384 C1R Ain Roesley Marked gene: C1R as ready
Mendeliome v0.11382 ITCH Zornitza Stark Marked gene: ITCH as ready
Mendeliome v0.11379 C1QTNF5 Ain Roesley Marked gene: C1QTNF5 as ready
Mendeliome v0.11378 C1QTNF5 Ain Roesley Mode of pathogenicity for gene: C1QTNF5 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v0.11377 C1QTNF5 Ain Roesley reviewed gene: C1QTNF5: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 33949280, 12944416, 30451557, 28939808, : 32036094; Phenotypes: Retinal degeneration, late-onset, autosomal dominant MIM#605670; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.11377 ITGA7 Zornitza Stark Marked gene: ITGA7 as ready
Mendeliome v0.11377 ITGA7 Zornitza Stark Phenotypes for gene: ITGA7 were changed from to Muscular dystrophy, congenital, due to ITGA7 deficiency, MIM# 613204
Mendeliome v0.11374 ITGA7 Zornitza Stark reviewed gene: ITGA7: Rating: GREEN; Mode of pathogenicity: None; Publications: 34552617, 9590299; Phenotypes: Muscular dystrophy, congenital, due to ITGA7 deficiency, MIM# 613204; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11373 C1QC Ain Roesley Marked gene: C1QC as ready
Mendeliome v0.11372 ITPA Zornitza Stark Marked gene: ITPA as ready
Mendeliome v0.11369 IVD Zornitza Stark Marked gene: IVD as ready
Mendeliome v0.11365 C1QB Ain Roesley Marked gene: C1QB as ready
Mendeliome v0.11365 IYD Zornitza Stark Marked gene: IYD as ready
Mendeliome v0.11364 C12orf57 Ain Roesley Marked gene: C12orf57 as ready
Mendeliome v0.11364 C12orf4 Ain Roesley Marked gene: C12orf4 as ready
Mendeliome v0.11362 C1GALT1C1 Ain Roesley Marked gene: C1GALT1C1 as ready
Mendeliome v0.11354 IARS2 Zornitza Stark Marked gene: IARS2 as ready
Mendeliome v0.11354 IARS2 Zornitza Stark Gene: iars2 has been classified as Green List (High Evidence).
Mendeliome v0.11354 IARS2 Zornitza Stark Phenotypes for gene: IARS2 were changed from to Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, MIM# 616007
Mendeliome v0.11353 IARS2 Zornitza Stark Publications for gene: IARS2 were set to
Mendeliome v0.11352 IARS2 Zornitza Stark Mode of inheritance for gene: IARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11351 IARS2 Zornitza Stark reviewed gene: IARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28328135, 30419932, 25130867, 30041933; Phenotypes: Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, MIM# 616007; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11351 KAAG1 Zornitza Stark Marked gene: KAAG1 as ready
Mendeliome v0.11350 KATNAL2 Zornitza Stark Marked gene: KATNAL2 as ready
Mendeliome v0.11346 KCNA1 Zornitza Stark Marked gene: KCNA1 as ready
Mendeliome v0.11342 KCNA5 Zornitza Stark Marked gene: KCNA5 as ready
Mendeliome v0.11339 KCND3 Zornitza Stark Marked gene: KCND3 as ready
Mendeliome v0.11339 KCND3 Zornitza Stark Phenotypes for gene: KCND3 were changed from Spinocerebellar ataxia 19, MIM# 607346 to Spinocerebellar ataxia 19, MIM# 607346
Mendeliome v0.11338 KCND3 Zornitza Stark Phenotypes for gene: KCND3 were changed from to Spinocerebellar ataxia 19, MIM# 607346
Mendeliome v0.11335 KCND3 Zornitza Stark reviewed gene: KCND3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23280837, 23280838, 34361012, 34067185, 33575485, 32823520; Phenotypes: Spinocerebellar ataxia 19, MIM# 607346; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11335 KCNE5 Zornitza Stark Marked gene: KCNE5 as ready
Mendeliome v0.11331 KCNE5 Zornitza Stark changed review comment from: Associated with Brugada is DISPUTED.

Rare variants in KCNE5 reported in AF cohorts with some supportive functional data.; to: Association with Brugada is DISPUTED.

Rare variants in KCNE5 reported in AF cohorts with some supportive functional data.
Mendeliome v0.11331 KCNJ10 Zornitza Stark Marked gene: KCNJ10 as ready
Mendeliome v0.11328 KCNK18 Zornitza Stark Marked gene: KCNK18 as ready
Mendeliome v0.11325 KCNK3 Zornitza Stark Marked gene: KCNK3 as ready
Mendeliome v0.11324 KCNK3 Zornitza Stark Phenotypes for gene: KCNK3 were changed from Pulmonary hypertension, primary, 4 MIM#615344 to Pulmonary hypertension, primary, 4 MIM#615344; Neurodevelopmental disorder, MONDO:0700092, KCNK3-related
Mendeliome v0.11323 KCNMA1 Zornitza Stark Marked gene: KCNMA1 as ready
Mendeliome v0.11323 KCNMA1 Zornitza Stark Phenotypes for gene: KCNMA1 were changed from to Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, MIM# 609446; Cerebellar atrophy, developmental delay, and seizures, MIM# 617643; Liang-Wang syndrome, MIM# 618729
Mendeliome v0.11320 KCNMA1 Zornitza Stark changed review comment from: Multiple individuals with KCNMA1-related channelopathy described, both mono allelic and bi-allelic disease reported; a variety of neurologic symptoms, including ID; some variants are LoF and some are gain of function, some correlation between mechanism of pathogenicity and phenotype.; to: Multiple individuals with KCNMA1-related channelopathy described, both mono allelic and bi-allelic disease reported; a variety of neurologic symptoms, including ID; some variants are LoF and some are gain of function, some correlation between mechanism of pathogenicity and phenotype.

Liang-Wang syndrome is a polymalformation syndrome with neurological involvement.
Mendeliome v0.11320 KCNMA1 Zornitza Stark reviewed gene: KCNMA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15937479, 26195193, 27567911, 29545233, 31427379, 31152168; Phenotypes: Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, MIM# 609446, Cerebellar atrophy, developmental delay, and seizures, MIM# 617643, Liang-Wang syndrome, MIM# 618729; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11320 NAT8L Zornitza Stark Marked gene: NAT8L as ready
Mendeliome v0.11320 KCNMB1 Zornitza Stark Marked gene: KCNMB1 as ready
Mendeliome v0.11318 ECHS1 Zornitza Stark Marked gene: ECHS1 as ready
Mendeliome v0.11318 NAT8L Zornitza Stark Phenotypes for gene: NAT8L were changed from to N-acetylaspartate deficiency - MIM#614063
Mendeliome v0.11314 NAT8L Zornitza Stark reviewed gene: NAT8L: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: N-acetylaspartate deficiency - MIM#614063; Mode of inheritance: None
Mendeliome v0.11314 NAT2 Zornitza Stark Marked gene: NAT2 as ready
Mendeliome v0.11310 EDA Bryony Thompson Marked gene: EDA as ready
Mendeliome v0.11307 ECHS1 Bryony Thompson Phenotypes for gene: ECHS1 were changed from to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, MIM# 616277; Leigh syndrome MONDO:0009723; cerebral palsy MONDO:0006497; paroxysmal dystonia MONDO:0016058
Mendeliome v0.11304 ECHS1 Bryony Thompson reviewed gene: ECHS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528536, 34364746, 32858208, 31399326, 25125611, 25393721, 32677093; Phenotypes: Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, MIM# 616277, Leigh syndrome MONDO:0009723, cerebral palsy MONDO:0006497, paroxysmal dystonia MONDO:0016058; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11304 ARHGAP35 Ain Roesley Phenotypes for gene: ARHGAP35 were changed from Developmental disorder to neurodevelopmental disorder, ARHGAP35-related MONDO#0700092
Mendeliome v0.11303 ARHGAP35 Ain Roesley Classified gene: ARHGAP35 as Green List (high evidence)
Mendeliome v0.11303 ARHGAP35 Ain Roesley Gene: arhgap35 has been classified as Green List (High Evidence).
Mendeliome v0.11302 ARHGAP35 Ain Roesley Classified gene: ARHGAP35 as Green List (high evidence)
Mendeliome v0.11302 ARHGAP35 Ain Roesley Gene: arhgap35 has been classified as Green List (High Evidence).
Mendeliome v0.11301 ARHGAP35 Ain Roesley reviewed gene: ARHGAP35: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder, ARHGAP35-related MONDO#0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.11301 KCNV2 Zornitza Stark Marked gene: KCNV2 as ready
Mendeliome v0.11298 KHDC3L Zornitza Stark Marked gene: KHDC3L as ready
Mendeliome v0.11295 KIAA1109 Zornitza Stark changed review comment from: ALKKUCS is an autosomal recessive severe neurodevelopmental disorder characterized by arthrogryposis, brain abnormalities associated with cerebral parenchymal underdevelopment, and global developmental delay. Most affected individuals die in utero or soon after birth. Additional abnormalities may include hypotonia, dysmorphic facial features, and involvement of other organ systems, such as cardiac or renal. The few patients who survive have variable intellectual disability and may have seizures.; to: ALKKUCS is an autosomal recessive severe neurodevelopmental disorder characterized by arthrogryposis, brain abnormalities associated with cerebral parenchymal underdevelopment, and global developmental delay. Most affected individuals die in utero or soon after birth. Additional abnormalities may include hypotonia, dysmorphic facial features, and involvement of other organ systems, such as cardiac or renal. The few patients who survive have variable intellectual disability and may have seizures.

More than 10 families reported.
Mendeliome v0.11295 KIAA1109 Zornitza Stark Marked gene: KIAA1109 as ready
Mendeliome v0.11292 KIF1A Zornitza Stark Marked gene: KIF1A as ready
Mendeliome v0.11292 KIF1A Zornitza Stark Phenotypes for gene: KIF1A were changed from to Neuropathy, hereditary sensory, type IIC, MIM# 614213; NESCAV syndrome, MIM# 614255; Spastic paraplegia 30, MIM# 610357
Mendeliome v0.11289 KIF1A Zornitza Stark edited their review of gene: KIF1A: Changed phenotypes: Neuropathy, hereditary sensory, type IIC, MIM# 614213, NESCAV syndrome, MIM# 614255, Spastic paraplegia 30, MIM# 610357; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11289 KIF5A Zornitza Stark Marked gene: KIF5A as ready
Mendeliome v0.11289 KIF5A Zornitza Stark Phenotypes for gene: KIF5A were changed from to Neuropathy; Spastic paraplegia 10, autosomal dominant, MIM# 604187; Myoclonus, intractable, neonatal, MIM# 617235
Mendeliome v0.11286 KIF5A Zornitza Stark edited their review of gene: KIF5A: Added comment: Neonatal intractable myoclonus is a severe neurologic disorder characterized by the onset of intractable myoclonic seizures soon after birth. Affected infants have intermittent apnea, abnormal eye movements, pallor of the optic nerve, and lack of developmental progress. Brain imaging shows a progressive leukoencephalopathy. At least 3 unrelated individuals with de novo LoF variants.

SPG10/CMT: variants are generally in the motor domain.; Changed publications: 30057544, 29892902, 28902413, 26403765, 25695920, 25008398, 27463701, 27414745; Changed phenotypes: Neuropathy, Spastic paraplegia 10, autosomal dominant, MIM# 604187, Myoclonus, intractable, neonatal, MIM# 617235
Mendeliome v0.11286 KIT Zornitza Stark Marked gene: KIT as ready
Mendeliome v0.11284 KIZ Zornitza Stark Marked gene: KIZ as ready
Mendeliome v0.11281 KLF11 Zornitza Stark Marked gene: KLF11 as ready
Mendeliome v0.11277 KLF6 Zornitza Stark Marked gene: KLF6 as ready
Mendeliome v0.11276 KLHDC8B Zornitza Stark Marked gene: KLHDC8B as ready
Mendeliome v0.11274 KLHL10 Zornitza Stark Marked gene: KLHL10 as ready
Mendeliome v0.11269 TLN1 Bryony Thompson Marked gene: TLN1 as ready
Mendeliome v0.11268 TLN1 Bryony Thompson gene: TLN1 was added
gene: TLN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TLN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TLN1 were set to 30888838
Phenotypes for gene: TLN1 were set to idiopathic spontaneous coronary artery dissection MONDO:0007385
Review for gene: TLN1 was set to AMBER
Added comment: 10 unique rare heterozygous missense variants in 11 individuals were identified in a 2 generation SCAD family and 56 unrelated individuals with sporadic SCAD. All variants had a MAF of less than 0.06% and occurred within highly conserved β-integrin, F-actin, or vinculin binding domains. Incomplete penetrance was evident in the familial case and five individuals with sporadic SCAD from whom parental DNA was available. No functional assays were conducted.
Sources: Literature
Mendeliome v0.11267 NAT8L Krithika Murali reviewed gene: NAT8L: Rating: AMBER; Mode of pathogenicity: None; Publications: 11310630, 19807691, 32275776; Phenotypes: ?N-acetylaspartate deficiency - MIM#614063; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11267 KLK1 Zornitza Stark Marked gene: KLK1 as ready
Mendeliome v0.11267 KLK1 Zornitza Stark Phenotypes for gene: KLK1 were changed from to [Kallikrein, decreased urinary activity of] 615953
Mendeliome v0.11265 KLK1 Zornitza Stark reviewed gene: KLK1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: [Kallikrein, decreased urinary activity of] 615953; Mode of inheritance: None
Mendeliome v0.11265 KLKB1 Zornitza Stark Marked gene: KLKB1 as ready
Mendeliome v0.11261 KRT1 Zornitza Stark Marked gene: KRT1 as ready
Mendeliome v0.11261 KRT1 Zornitza Stark Phenotypes for gene: KRT1 were changed from to Epidermolytic hyperkeratosis, MIM#113800; Ichthyosis, cyclic, with epidermolytic hyperkeratosis, MIM# 607602; Ichthyosis histrix, Curth-Macklin type, MIM# 146590; Palmoplantar keratoderma, epidermolytic, MIM# 144200; Palmoplantar keratoderma, nonepidermolytic, MIM# 600962
Mendeliome v0.11258 KRT1 Zornitza Stark reviewed gene: KRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7511022, 21271994, 11286630; Phenotypes: Epidermolytic hyperkeratosis, MIM#113800, Ichthyosis, cyclic, with epidermolytic hyperkeratosis, MIM# 607602, Ichthyosis histrix, Curth-Macklin type, MIM# 146590, Palmoplantar keratoderma, epidermolytic, MIM# 144200, Palmoplantar keratoderma, nonepidermolytic, MIM# 600962; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11258 KRT12 Zornitza Stark Marked gene: KRT12 as ready
Mendeliome v0.11255 TSR1 Bryony Thompson Marked gene: TSR1 as ready
Mendeliome v0.11255 TSR1 Bryony Thompson gene: TSR1 was added
gene: TSR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TSR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TSR1 were set to 31296288; 31296287
Phenotypes for gene: TSR1 were set to idiopathic spontaneous coronary artery dissection MONDO:0007385
Review for gene: TSR1 was set to RED
Added comment: A single case-control study with 85 SCAD cases and 296 non-SCAD controls from the Chinese Han population that underwent exome sequencing. TSR1 was the top hit in association analyses (p < 5.41 × 10-5 in both the optimal sequence kernel association and mixed effects score tests), with 5 variants identified in 8 SCAD cases.
Sources: Literature
Mendeliome v0.11254 TMEM151A Bryony Thompson Marked gene: TMEM151A as ready
Mendeliome v0.11253 TMEM151A Bryony Thompson gene: TMEM151A was added
gene: TMEM151A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM151A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM151A were set to 34820915; 34518509
Phenotypes for gene: TMEM151A were set to episodic kinesigenic dyskinesia MONDO:0044202
Review for gene: TMEM151A was set to GREEN
Added comment: PMID: 34820915 - 24 heterozygous TMEM151A variants detected in 29 PRRT2-negative patients from 25 families
PMID: 34518509 - TMEM151A variants identified in 3 AD families and 8 isolated PKD patients with incomplete penetrance identified in 3 of the isolated cases. Also, supporting mouse model and in vitro functional assays suggesting loss of function as the mechanism of disease.
Sources: Literature
Mendeliome v0.11252 KRT13 Zornitza Stark Marked gene: KRT13 as ready
Mendeliome v0.11249 KRT16 Zornitza Stark Marked gene: KRT16 as ready
Mendeliome v0.11249 KRT16 Zornitza Stark Phenotypes for gene: KRT16 were changed from to Palmoplantar keratoderma, nonepidermolytic, focal (MIM#613000); Pachyonychia congenita 1 (MIM#167200)
Mendeliome v0.11246 KRT16 Zornitza Stark reviewed gene: KRT16: Rating: GREEN; Mode of pathogenicity: None; Publications: 8595410, 10839714; Phenotypes: Palmoplantar keratoderma, nonepidermolytic, focal (MIM#613000), Pachyonychia congenita 1 (MIM#167200); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11246 KRT18 Zornitza Stark Marked gene: KRT18 as ready
Mendeliome v0.11243 KRT25 Zornitza Stark Marked gene: KRT25 as ready
Mendeliome v0.11240 KRT4 Zornitza Stark Marked gene: KRT4 as ready
Mendeliome v0.11237 KRT74 Zornitza Stark Marked gene: KRT74 as ready
Mendeliome v0.11233 KRT75 Zornitza Stark Marked gene: KRT75 as ready
Mendeliome v0.11233 KRT75 Zornitza Stark Phenotypes for gene: KRT75 were changed from to {Pseudofolliculitis barbae, susceptibility to} 612318
Mendeliome v0.11231 KRT75 Zornitza Stark reviewed gene: KRT75: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Pseudofolliculitis barbae, susceptibility to} 612318; Mode of inheritance: None
Mendeliome v0.11231 KRT81 Zornitza Stark Marked gene: KRT81 as ready
Mendeliome v0.11228 NARS2 Zornitza Stark Marked gene: NARS2 as ready
Mendeliome v0.11228 NARS2 Zornitza Stark Gene: nars2 has been classified as Green List (High Evidence).
Mendeliome v0.11228 NARS2 Zornitza Stark Phenotypes for gene: NARS2 were changed from to Combined oxidative phosphorylation deficiency 24 - MIM#616239; Deafness, autosomal recessive 94 - MIM#618434
Mendeliome v0.11227 NARS2 Zornitza Stark Publications for gene: NARS2 were set to
Mendeliome v0.11226 NARS2 Zornitza Stark Mode of inheritance for gene: NARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11225 PNPLA3 Zornitza Stark Marked gene: PNPLA3 as ready
Mendeliome v0.11221 NANS Zornitza Stark Marked gene: NANS as ready
Mendeliome v0.11218 S1PR2 Zornitza Stark Marked gene: S1PR2 as ready
Mendeliome v0.11215 NALCN Zornitza Stark Marked gene: NALCN as ready
Mendeliome v0.11215 NALCN Zornitza Stark Phenotypes for gene: NALCN were changed from to Congenital contractures of the limbs and face, hypotonia, and developmental delay - MIM#616266; Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 - MIM#615419
Mendeliome v0.11212 NAGS Zornitza Stark Marked gene: NAGS as ready
Mendeliome v0.11209 NACC1 Zornitza Stark Marked gene: NACC1 as ready
Mendeliome v0.11209 NACC1 Zornitza Stark Phenotypes for gene: NACC1 were changed from to Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination - MIM#617393
Mendeliome v0.11206 NAA15 Zornitza Stark Marked gene: NAA15 as ready
Mendeliome v0.11203 NARS2 Krithika Murali reviewed gene: NARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25385316, 25807530, 30327238, 28077841; Phenotypes: Combined oxidative phosphorylation deficiency 24 - MIM#616239, ?Deafness, autosomal recessive 94 - MIM#618434; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11203 KRT83 Zornitza Stark Marked gene: KRT83 as ready
Mendeliome v0.11203 KRT83 Zornitza Stark Phenotypes for gene: KRT83 were changed from to Erythrokeratodermia variabilis et progressiva 5, MIM# 617756; Monilethrix , MIM#158000
Mendeliome v0.11199 KRT83 Zornitza Stark reviewed gene: KRT83: Rating: AMBER; Mode of pathogenicity: None; Publications: 27965375, 15744029, 25557232; Phenotypes: Erythrokeratodermia variabilis et progressiva 5, MIM# 617756, Monilethrix , MIM#158000; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11199 KRT10 Zornitza Stark Marked gene: KRT10 as ready
Mendeliome v0.11194 ERLEC1 Bryony Thompson Marked gene: ERLEC1 as ready
Mendeliome v0.11192 NALCN Krithika Murali reviewed gene: NALCN: Rating: GREEN; Mode of pathogenicity: None; Publications: 25683120, 23749988, 24075186, 30167850; Phenotypes: Congenital contractures of the limbs and face, hypotonia, and developmental delay - MIM#616266, Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 - MIM#615419; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11189 IRX5 Zornitza Stark edited their review of gene: IRX5: Added comment: Third family with Hamamy syndrome and homozygous missense variant reported, p.Arg168His. Two cousins, >4 meioses, good segregation data.

4th family as part of large heterogenous cohort of consanguineous families also reported with homozygous frameshift (last exon), but limited phenotypic data.; Changed rating: GREEN; Changed publications: 22581230, 27453922, 34899143
Mendeliome v0.11189 NACC1 Krithika Murali reviewed gene: NACC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28132692; Phenotypes: Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination - MIM#617393; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11189 EARS2 Bryony Thompson Marked gene: EARS2 as ready
Mendeliome v0.11189 EARS2 Bryony Thompson Gene: ears2 has been classified as Green List (High Evidence).
Mendeliome v0.11189 EARS2 Bryony Thompson Phenotypes for gene: EARS2 were changed from to Leigh syndrome MONDO:0009723; Combined oxidative phosphorylation deficiency 12 MIM#614924; leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome MONDO:0013971
Mendeliome v0.11188 EARS2 Bryony Thompson Publications for gene: EARS2 were set to
Mendeliome v0.11187 EARS2 Bryony Thompson Mode of inheritance for gene: EARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11186 EARS2 Bryony Thompson reviewed gene: EARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22492562, 23008233, 25854774, 26619324, 26893310, 27206875, 27571996, 27117034; Phenotypes: Leigh syndrome MONDO:0009723, Combined oxidative phosphorylation deficiency 12 MIM#614924, leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome MONDO:0013971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11185 KRT8 Zornitza Stark Marked gene: KRT8 as ready
Mendeliome v0.11181 KRT85 Zornitza Stark Marked gene: KRT85 as ready
Mendeliome v0.11178 KRT86 Zornitza Stark Marked gene: KRT86 as ready
Mendeliome v0.11175 KRT9 Zornitza Stark Marked gene: KRT9 as ready
Mendeliome v0.11175 KRT9 Zornitza Stark Phenotypes for gene: KRT9 were changed from to Palmoplantar keratoderma, epidermolytic (MIM#144200)
Mendeliome v0.11172 KRT9 Zornitza Stark reviewed gene: KRT9: Rating: GREEN; Mode of pathogenicity: None; Publications: 31525823, 29044727, 7512862; Phenotypes: Palmoplantar keratoderma, epidermolytic (MIM#144200); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11172 KY Zornitza Stark Marked gene: KY as ready
Mendeliome v0.11172 KY Zornitza Stark Phenotypes for gene: KY were changed from to Myopathy, myofibrillar, 7, MIM#617114
Mendeliome v0.11169 KY Zornitza Stark reviewed gene: KY: Rating: GREEN; Mode of pathogenicity: None; Publications: 11136708, 27485408, 27484770, 30591934; Phenotypes: Myopathy, myofibrillar, 7, MIM#617114; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11169 KYNU Zornitza Stark Marked gene: KYNU as ready
Mendeliome v0.11169 KYNU Zornitza Stark Phenotypes for gene: KYNU were changed from to Hydroxykynureninuria MIM#236800; Vertebral, cardiac, renal, and limb defects syndrome 2 MIM#617661; Disorders of histidine, tryptophan or lysine metabolism
Mendeliome v0.11166 JAG1 Zornitza Stark Marked gene: JAG1 as ready
Mendeliome v0.11166 JAG1 Zornitza Stark Phenotypes for gene: JAG1 were changed from to Alagille syndrome 1, MIM# 118450; Charcot-Marie-Tooth disease, axonal, type 2HH, MIM# 619574
Mendeliome v0.11163 JAG1 Zornitza Stark changed review comment from: Two unrelated families reported with CMT type 2. Affected individuals in both families exhibited severe vocal fold paresis, a rare feature of peripheral nerve disease that can be life-threatening. Studies of mutant protein posttranslational modification and localization indicated that the mutations (p.Ser577Arg, p.Ser650Pro) impair protein glycosylation and reduce JAG1 cell surface expression. Mice harboring heterozygous CMT2-associated mutations exhibited mild peripheral neuropathy, and homozygous expression resulted in embryonic lethality by midgestation. Pre-existing rat model.
Sources: Literature; to: Association with Alagille is very well established.

Two unrelated families reported with CMT type 2. Affected individuals in both families exhibited severe vocal fold paresis, a rare feature of peripheral nerve disease that can be life-threatening. Studies of mutant protein posttranslational modification and localization indicated that the mutations (p.Ser577Arg, p.Ser650Pro) impair protein glycosylation and reduce JAG1 cell surface expression. Mice harboring heterozygous CMT2-associated mutations exhibited mild peripheral neuropathy, and homozygous expression resulted in embryonic lethality by midgestation. Pre-existing rat model.
Sources: Literature
Mendeliome v0.11163 JAG1 Zornitza Stark edited their review of gene: JAG1: Changed phenotypes: Alagille syndrome 1, MIM# 118450, Charcot-Marie-Tooth disease, axonal, type 2HH, MIM# 619574
Mendeliome v0.11163 JUP Zornitza Stark Marked gene: JUP as ready
Mendeliome v0.11163 JUP Zornitza Stark Phenotypes for gene: JUP were changed from to Arrhythmogenic right ventricular dysplasia 12, MIM# 611528; Naxos disease, MIM# 601214
Mendeliome v0.11160 JUP Zornitza Stark edited their review of gene: JUP: Changed phenotypes: Arrhythmogenic right ventricular dysplasia 12, MIM# 611528, Naxos disease, MIM# 601214
Mendeliome v0.11160 JUP Zornitza Stark reviewed gene: JUP: Rating: GREEN; Mode of pathogenicity: None; Publications: 2945574, 21668431, 2945574, 9610536, 18937352, 10902626, 15851108, 27170944, 11691526, 16893920, 29802319, 31275992, 25820315, 25820315, 25765472, 25705887, 25087486, 21668431, 20130592, 17924338, 20031617, 10902626, 20130592, 21320868, 32212272; Phenotypes: Arrhythmogenic right ventricular dysplasia 12, MIM# 611528; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11160 JPT1 Zornitza Stark Marked gene: JPT1 as ready
Mendeliome v0.11159 JAK2 Zornitza Stark Marked gene: JAK2 as ready
Mendeliome v0.11155 ZNF644 Zornitza Stark Marked gene: ZNF644 as ready
Mendeliome v0.11152 ZNF513 Zornitza Stark Marked gene: ZNF513 as ready
Mendeliome v0.11148 ZNF408 Zornitza Stark Marked gene: ZNF408 as ready
Mendeliome v0.11145 ZNF335 Zornitza Stark Marked gene: ZNF335 as ready
Mendeliome v0.11145 ZNF335 Zornitza Stark Phenotypes for gene: ZNF335 were changed from to Microcephaly 10, primary, autosomal recessive (MIM#615095)
Mendeliome v0.11142 ZNF335 Zornitza Stark reviewed gene: ZNF335: Rating: GREEN; Mode of pathogenicity: None; Publications: 23178126, 27540107, 29652087; Phenotypes: Microcephaly 10, primary, autosomal recessive (MIM#615095); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11142 ZMYND11 Zornitza Stark Marked gene: ZMYND11 as ready
Mendeliome v0.11142 ZMYND11 Zornitza Stark Phenotypes for gene: ZMYND11 were changed from to Mental retardation, autosomal dominant 30, MIM# 616083
Mendeliome v0.11139 ZMYND11 Zornitza Stark reviewed gene: ZMYND11: Rating: GREEN; Mode of pathogenicity: None; Publications: 32097528, 34216016; Phenotypes: Mental retardation, autosomal dominant 30 MIM# 616083; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11139 ZFPM2 Zornitza Stark Marked gene: ZFPM2 as ready
Mendeliome v0.11135 RPA1 Zornitza Stark Phenotypes for gene: RPA1 were changed from Bone marrow failure; T- and B-cell lymphopaenia; pulmonary fibrosis; skin manifestations; short telomeres to Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, MIM# 619767; Bone marrow failure; T- and B-cell lymphopaenia; pulmonary fibrosis; skin manifestations; short telomeres
Mendeliome v0.11134 RPA1 Zornitza Stark edited their review of gene: RPA1: Changed phenotypes: Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, MIM# 619767, Bone marrow failure, T- and B-cell lymphopaenia, pulmonary fibrosis, skin manifestations, short telomeres
Mendeliome v0.11134 OPCML Zornitza Stark Marked gene: OPCML as ready
Mendeliome v0.11134 OPCML Zornitza Stark Phenotypes for gene: OPCML were changed from to Ovarian cancer, somatic, MIM#167000
Mendeliome v0.11132 OPCML Naomi Baker reviewed gene: OPCML: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ovarian cancer, somatic, MIM#167000; Mode of inheritance: Other
Mendeliome v0.11132 NFE2L1 Bryony Thompson Marked gene: NFE2L1 as ready
Mendeliome v0.11132 NFE2L1 Bryony Thompson gene: NFE2L1 was added
gene: NFE2L1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NFE2L1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFE2L1 were set to 35112409
Phenotypes for gene: NFE2L1 were set to Syndromic disease, MONDO:0002254
Review for gene: NFE2L1 was set to RED
Added comment: A single patient with developmental delay, hypotonia, hypospadias, bifid scrotum, and failure to thrive, with a heterozygous nonsense variant in the last exon. In vitro functional assays suggest a dominant-negative effect.
Sources: Literature
Mendeliome v0.11131 ZFP57 Zornitza Stark Marked gene: ZFP57 as ready
Mendeliome v0.11128 XYLT2 Zornitza Stark Marked gene: XYLT2 as ready
Mendeliome v0.11128 XYLT2 Zornitza Stark Phenotypes for gene: XYLT2 were changed from to Spondyloocular syndrome MIM# 605822
Mendeliome v0.11125 XYLT2 Zornitza Stark reviewed gene: XYLT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26027496, 26987875, 30891060, 28484880; Phenotypes: Spondyloocular syndrome MIM# 605822; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11125 XRCC3 Zornitza Stark Marked gene: XRCC3 as ready
Mendeliome v0.11124 XIAP Zornitza Stark Marked gene: XIAP as ready
Mendeliome v0.11121 XG Zornitza Stark Marked gene: XG as ready
Mendeliome v0.11115 OPDM4 Bryony Thompson Marked STR: OPDM4 as ready
Mendeliome v0.11114 OPDM4 Bryony Thompson STR: OPDM4 was added
STR: OPDM4 was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: OPDM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: OPDM4 were set to 35148830
Phenotypes for STR: OPDM4 were set to Oculopharyngodistal myopathy MONDO:0025193
Review for STR: OPDM4 was set to GREEN
STR: OPDM4 was marked as clinically relevant
Added comment: 5'UTR repeat upstream of RILPL1. Analyses suggest that toxic RNA gain-of-function is the mechanism of disease for the repeat expansion. Distribution of CGG repeat units in RILPL1 ranged from 9 to 16 among 200 normal controls. The size of the CGG repeat ranged from 139 to 197 (169.91 ± 21.82) repeats in 11 unrelated individuals with OPDM. Segregation evidence from 1 family, with 2 affected individuals with the repeat expansion and 1 individual with essential tremor but not OPDM and 86 repeats (intermediate).
Sources: Literature
Mendeliome v0.11113 RECQL Alison Yeung Marked gene: RECQL as ready
Mendeliome v0.11112 HIST1H4E Alison Yeung Marked gene: HIST1H4E as ready
Mendeliome v0.11111 HIST1H4D Zornitza Stark Marked gene: HIST1H4D as ready
Mendeliome v0.11110 RECQL Dean Phelan gene: RECQL was added
gene: RECQL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RECQL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RECQL were set to PMID: 35025765
Phenotypes for gene: RECQL were set to Photosensitivity; facial dysmorphism; xeropthalmia; skeletal abnormalities
Review for gene: RECQL was set to AMBER
Added comment: PMID: 35025765
- Homozygous missense variants identified in two seemingly unrelated families with a genome instability disorder. Both families had the same missense variant. Phenotype was progeroid facial features, skin photosensitivity, xeroderma, and slender elongated thumbs.
Sources: Literature
Mendeliome v0.11109 HIST1H4E Paul De Fazio changed review comment from: 17 patients identified with de novo missense variants affecting Lys31, Pro32, Arg35, Leu37, Arg40 (recurrent), Arg45 (recurrent), Tyr98 (recurrent). All individuals had ID/dev delay. Additional phenotypes in some but not all individuals included epilepsy, hypotonia, facial dysmorphism. Most had reduced birth length, OFC, weight (-1 to -3SD).
A zebrafish model has developmental defects.
Sources: Literature; to: HGNC recognised gene: H4C5
17 patients identified with de novo missense variants affecting Lys31, Pro32, Arg35, Leu37, Arg40 (recurrent), Arg45 (recurrent), Tyr98 (recurrent). All individuals had ID/dev delay. Additional phenotypes in some but not all individuals included epilepsy, hypotonia, facial dysmorphism. Most had reduced birth length, OFC, weight (-1 to -3SD).
A zebrafish model has developmental defects.
Sources: Literature
Mendeliome v0.11107 HIST1H4C Paul De Fazio changed review comment from: 6 additional individuals with ID and dev delay. All variants were de novo. Lys92 (Lys91 in H4 nomenclature) and Pro33 (Pro32) were the only variants identified. Additional phenotypes in some but not all patients included hypotonia, facial dysmorphisms, conductive hearing loss. Most had reduced birth length, OFC, weight (-1 to -2.5SD).
A zebrafish model has developmental defects.; to: HGNC recognised gene: H4C3
6 additional individuals with ID and dev delay. All variants were de novo. Lys92 (Lys91 in H4 nomenclature) and Pro33 (Pro32) were the only variants identified. Additional phenotypes in some but not all patients included hypotonia, facial dysmorphisms, conductive hearing loss. Most had reduced birth length, OFC, weight (-1 to -2.5SD).
A zebrafish model has developmental defects.
Mendeliome v0.11107 CPSF3 Alison Yeung Marked gene: CPSF3 as ready
Mendeliome v0.11107 AL117258.1 Zornitza Stark Marked gene: AL117258.1 as ready
Mendeliome v0.11107 AL117258.1 Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name is CIROP. Previous alias LMLN2.
Mendeliome v0.11107 AL117258.1 Melanie Marty changed review comment from: Gene also known as CIROP

Homozygous or compound heterozygous CIROP variants identified in 12 families with congenital heart defects associated with heterotaxy.

Functional tests performed on Xenopus and zebrafish embryos showed that CIROP was essential for left side symmetry and is expressed in ciliated left–right organisers.
Sources: Literature; to: Gene also known as CIROP and LMLN2

Homozygous or compound heterozygous CIROP variants identified in 12 families with congenital heart defects associated with heterotaxy.

Functional tests performed on Xenopus and zebrafish embryos showed that CIROP was essential for left side symmetry and is expressed in ciliated left–right organisers.
Sources: Literature
Mendeliome v0.11107 AL117258.1 Zornitza Stark Phenotypes for gene: AL117258.1 were changed from Heterotaxy, congenital heart defects to Heterotaxy MONDO:0018677, congenital heart defects
Mendeliome v0.11103 HIST1H4F Zornitza Stark Marked gene: HIST1H4F as ready
Mendeliome v0.11103 HIST1H4E Paul De Fazio gene: HIST1H4E was added
gene: HIST1H4E was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIST1H4E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H4E were set to 35202563
Phenotypes for gene: HIST1H4E were set to Neurodevelopmental disorder, HIST1H4E-related MONDO:0700092
Review for gene: HIST1H4E was set to GREEN
gene: HIST1H4E was marked as current diagnostic
Added comment: 17 patients identified with de novo missense variants affecting Lys31, Pro32, Arg35, Leu37, Arg40 (recurrent), Arg45 (recurrent), Tyr98 (recurrent). All individuals had ID/dev delay. Additional phenotypes in some but not all individuals included epilepsy, hypotonia, facial dysmorphism. Most had reduced birth length, OFC, weight (-1 to -3SD).
A zebrafish model has developmental defects.
Sources: Literature
Mendeliome v0.11103 HIST1H4D Paul De Fazio gene: HIST1H4D was added
gene: HIST1H4D was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIST1H4D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H4D were set to 35202563
Phenotypes for gene: HIST1H4D were set to Neurodevelopmental disorder, HIST1H4D-related MONDO:0700092
Review for gene: HIST1H4D was set to AMBER
gene: HIST1H4D was marked as current diagnostic
Added comment: Single individual described with a de novo missense variant Arg41His (Arg40 in H4 nomenclature). Apart from language delay and moderate ID, phenotypes included facial dysmorphisms and cochlear abnormalities and arhinencephaly on MRI. Hearing was normal. Birth length, OFC, weight were all reduced (-2 to -2.5SD).
A zebrafish model has developmental defects.
Sources: Literature
Mendeliome v0.11099 CPSF3 Belinda Chong gene: CPSF3 was added
gene: CPSF3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CPSF3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPSF3 were set to 35121750
Phenotypes for gene: CPSF3 were set to Intellectual disability syndrome
Review for gene: CPSF3 was set to GREEN
Added comment: study of a deficit of observed homozygous carriers of missense variants, versus an expected number in a set of 153,054 chip-genotyped Icelanders, to identify potentially pathogenic genotypes

Six homozygous carriers of missense variants in CPSF3 show severe intellectual disability, seizures, microcephaly, and abnormal muscle tone.

- Four identified through Icelandic geneology (p.Gly468Glu), three carrier couples total of four children who had died prematurely. Tested archival samples for two of these children, and confirm a homozygous genotype.
- Two of Mexican descent (p.Ile354Thr), first-degree cousins
Sources: Literature
Mendeliome v0.11099 ZBTB11 Chern Lim reviewed gene: ZBTB11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:35104841; Phenotypes: Intellectual developmental disorder, autosomal recessive 69 (MIM#618383), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11098 CRLS1 Zornitza Stark Marked gene: CRLS1 as ready
Mendeliome v0.11097 AL117258.1 Melanie Marty gene: AL117258.1 was added
gene: AL117258.1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AL117258.1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AL117258.1 were set to 34903892
Phenotypes for gene: AL117258.1 were set to Heterotaxy, congenital heart defects
Review for gene: AL117258.1 was set to GREEN
Added comment: Gene also known as CIROP

Homozygous or compound heterozygous CIROP variants identified in 12 families with congenital heart defects associated with heterotaxy.

Functional tests performed on Xenopus and zebrafish embryos showed that CIROP was essential for left side symmetry and is expressed in ciliated left–right organisers.
Sources: Literature
Mendeliome v0.11097 NAV2 Alison Yeung Marked gene: NAV2 as ready
Mendeliome v0.11097 NAV2 Alison Yeung Added comment: Comment when marking as ready: Single reported individual. Functional studies and mouse model supportive evidence.
Mendeliome v0.11096 HIST1H4I Zornitza Stark Marked gene: HIST1H4I as ready
Mendeliome v0.11095 NRCAM Ee Ming Wong gene: NRCAM was added
gene: NRCAM was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NRCAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRCAM were set to PMID: 35108495
Phenotypes for gene: NRCAM were set to neurodevelopmental disorder, MONDO:0700092
Penetrance for gene: NRCAM were set to unknown
Review for gene: NRCAM was set to GREEN
gene: NRCAM was marked as current diagnostic
Added comment: -Ten individuals from 8 families with developmental delay/intellectual disability, hypotonia, peripheral neuropathy, and/or spasticity.
- Affected individuals are biallelic for missense and/or LoF variants which are mainly in the fibronectin type III (Fn-III) domain
- Zebrafish mutants lacking the third Fn-III domain displayed significantly altered swimming behavior compared to wild-type larvae (p < 0.03) and a trend toward increased amounts of alpha-tubulin fibers in the dorsal telencephalon, demonstrating an alteration in white matter tracts and projections
Sources: Literature
Mendeliome v0.11093 ZBTB7A Zornitza Stark Marked gene: ZBTB7A as ready
Mendeliome v0.11092 CRLS1 Michelle Torres gene: CRLS1 was added
gene: CRLS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CRLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRLS1 were set to 35147173
Phenotypes for gene: CRLS1 were set to Mitochondrial disease MONDO:0044970 CRLS1-related
Added comment: - Three families (4 individuals) with cardiolipin deficiency.
- Two families (one consanguineous with 2 affected siblings) with homozygous the p.(Ile109Asn) had infantile progressive encephalopathy, bull’s eye maculopathy, auditory neuropathy, diabetes insipidus, autonomic instability, cardiac defects and early death.
- The fourth individual cHet p.(Ala172Asp) and p.(Leu217Phe) presented with chronic encephalopathy with neurodevelopmental regression, congenital nystagmus with decreased vision, sensorineural hearing loss, failure to thrive and acquired microcephaly.
- Functional studies on patient cells showed increased levels of the substrate of CRLS1 and impaired mitochondrial morphology and biogenesis
Sources: Literature
Mendeliome v0.11092 HIST1H4I Elena Savva gene: HIST1H4I was added
gene: HIST1H4I was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIST1H4I was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H4I were set to PMID: 35202563
Phenotypes for gene: HIST1H4I were set to Neurodevelopmental syndrome
Review for gene: HIST1H4I was set to GREEN
Added comment: PMID: 35202563
- 3 unrelated de novo patients, p.His75Arg was recurring and observed in 2/3 probands.
- Zebrafish study shows both variants resulted in a significant increases in developmental issues such as in mild dev delay, necrosis and defective organogenesis.
- All patients had intellectual disability and motor and/or gross developmental delay and dysmorphisms.
- 2/3 patients showed bilateral conductive hearing loss
Sources: Literature
Mendeliome v0.11092 NAV2 Dean Phelan gene: NAV2 was added
gene: NAV2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NAV2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAV2 were set to PMID:35218524
Phenotypes for gene: NAV2 were set to Developmental delay; cerebellar hypoplasia; cerebellar dysplasia
Review for gene: NAV2 was set to AMBER
Added comment: PMID:35218524
- Two compound heterozygous LOF variants identified in one female with developmental delay and a diagnosis of cerebellar hypoplasia and dysplasia. Functional studies showed cellular migration deficits. Hypomorphic mouse model revealed developmental anomalies including cerebellar hypoplasia and dysplasia, corpus callosum hypo-dysgenesis, and agenesis of the olfactory bulbs.
Sources: Literature
Mendeliome v0.11092 ZBTB7A Daniel Flanagan gene: ZBTB7A was added
gene: ZBTB7A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ZBTB7A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZBTB7A were set to 34515416; 31645653
Phenotypes for gene: ZBTB7A were set to Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin (MIM#619769)
Review for gene: ZBTB7A was set to GREEN
Added comment: PMID: 34515416. Monoallelic ZBTB7A variants identified in 12 individuals from 11 families, with macrocephaly (11/12), some degree of ID (12/12), autistic features (7/12) and hypertrophy of pharyngeal lymphoid tissue (12/12). Variants included LoF variants and missense, 8 variants were de novo.

PMID: 31645653. De novo ZBTB7A missense identified in a boy with macrocephaly, intellectual disability, and sleep apnea.
Sources: Expert list
Mendeliome v0.11092 TIAM1 Alison Yeung Marked gene: TIAM1 as ready
Mendeliome v0.11091 TIAM1 Alison Yeung gene: TIAM1 was added
gene: TIAM1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TIAM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TIAM1 were set to https://doi.org/10.1016/j.ajhg.2022.01.020
Phenotypes for gene: TIAM1 were set to Neurodevelopmental disorder, TIAM1-related, MONDO:0700092
Review for gene: TIAM1 was set to GREEN
Added comment: Reported in 4 unrelated individuals. Phenotype of developmental delay/intellectual disability and seizures. Loss of ortholog in Drosophila reduces the survival rate, and the surviving adults exhibit climbing defects, are prone to severe seizures, and have a short lifespan. Functional studies in 3 variants from two probands showed loss of function.
Sources: Literature
Mendeliome v0.11090 EHD1 Zornitza Stark Marked gene: EHD1 as ready
Mendeliome v0.11089 EHD1 Zornitza Stark gene: EHD1 was added
gene: EHD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EHD1 were set to 35149593
Phenotypes for gene: EHD1 were set to Inherited renal tubular disease, MONDO:0015962, EHD1-related
Review for gene: EHD1 was set to AMBER
Added comment: Six individuals (5-33 years) with proteinuria and a high-frequency hearing deficit reported with the homozygous missense variant c.1192C>T (p.R398W) in EHD1. Proteinuria (0.7-2.1 g/d) consisted predominantly of low molecular weight proteins, reflecting impaired renal proximal tubular endocytosis of filtered proteins. Ehd1 knockout and Ehd1R398W/R398W knockin mice also showed a high-frequency hearing deficit and impaired receptor-mediated endocytosis in proximal tubules, and a zebrafish model showed impaired ability to reabsorb low molecular weight dextran. Single founder variant but two animal models, hence Amber
Sources: Literature
Mendeliome v0.11086 PTCH1 Seb Lunke Marked gene: PTCH1 as ready
Mendeliome v0.11083 RECQL4 Seb Lunke Marked gene: RECQL4 as ready
Mendeliome v0.11078 AP3D1 Zornitza Stark edited their review of gene: AP3D1: Added comment: Now four affected individuals from two unrelated families, with a mouse model that recapitulates the human phenotype.; Changed rating: GREEN; Changed publications: 26744459, 9697856, 30472485; Changed phenotypes: Hermansky-Pudlak syndrome 10, MIM# 617050, Oculocutaneous albinism, Severe neutropaenia, Recurrent infections, Seizures, Hearing loss, Neurodevelopmental delay
Mendeliome v0.11077 PPP2R3C Zornitza Stark Marked gene: PPP2R3C as ready
Mendeliome v0.11076 PPP2R3C Zornitza Stark gene: PPP2R3C was added
gene: PPP2R3C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPP2R3C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP2R3C were set to 30893644; 34714774; 34750818
Phenotypes for gene: PPP2R3C were set to Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy, OMIM # 618419
Review for gene: PPP2R3C was set to GREEN
Added comment: Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (GDRM) is characterized by 46,XY complete gonadal dysgenesis in association with extragonadal anomalies, low birth weight, typical facial gestalt, rod and cone dystrophy, sensorineural hearing loss, omphalocele, anal atresia, renal agenesis, skeletal abnormalities, dry and scaly skin, severe myopathy, and neuromotor delay. 11 unrelated families with syndromic complete gonadal dysgenesis. 9 families had 46,XY females with complete gonadal dysgenesis, but 2 families had 46,XX patients with hypergonadotropic hypogonadism, nonvisualized gonads, primary amenorrhea, and absence of secondary sexual characteristics. Variants segregated with disease in each family and were not found in ethnically matched controls or in public variant databases. The heterozygous fathers exhibited morphologic abnormalities of spermatozoa and reduced fertility.
Sources: Literature
Mendeliome v0.11074 CHKA Zornitza Stark Marked gene: CHKA as ready
Mendeliome v0.11071 CDX2 Chirag Patel edited their review of gene: CDX2: Added comment: 9 families, with heterozygous variants identified with WES, presenting with congenital abnormalities affecting the development of the anus, the renal and urogenital system, the vertebrae and/or the limbs in varying sequences and severity (incl. sirenomelia and persistent cloaca). A recurrent pathogenic missense variant in the HOX domain of the protein p.(Arg237His) was found in 3 unrelated families. In the mouse cdx2 is essential for anteroposterior patterning of embryonal axis and morphogenesis of cloacal structures. Cdx2 heterozygous conditional mutant mice show a variable phenotype (including imperforate anus, sirenomelia, posterior vertebral truncations, and bladder anomalies).; Changed rating: GREEN; Changed publications: PMID: 29177441, 34671974; Changed phenotypes: Congenital abnormalities of anus, renal and urogenital system, vertebrae and/or the limbs; Set current diagnostic: yes
Mendeliome v0.11071 CHKA Konstantinos Varvagiannis gene: CHKA was added
gene: CHKA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CHKA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHKA were set to 35202461
Phenotypes for gene: CHKA were set to Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Penetrance for gene: CHKA were set to Complete
Review for gene: CHKA was set to GREEN
Added comment: Klöckner (2022 - PMID: 35202461) describe the phenotype of 6 individuals (from 5 unrelated families) harboring biallelic CHKA variants.

Shared features incl. abnormal muscle tone(6/6 - hypertonia or hypotonia, 3/6 each), DD/ID (6/6,severe in 4, severe/profound in 2), epilepsy (6/6 - onset: infancy - 3y2m | epileptic spasms or GS at onset), microcephaly (6/6), movement disorders (3/6 - incl. dyskinesia, rigidity, choreoatetotic movements). 2/5 individuals exhibited MRI abnormalities, notably hypomyelination. Short stature was observed in 4/6.

Eventual previous genetic testing was not discussed.

Exome sequencing (quattro ES for 2 sibs, trio ES for 1 individual, singleton for 3 probands) revealed biallelic CHKA variants in all affected individuals. Sanger sequencing was performed for confirmation and segregation studies.

Other variants (in suppl.) were not deemed to be causative for the neurodevelopmental phenotype.

3 different missense, 1 start-loss and 1 truncating variant were identified, namely (NM_0012772.2):
- c.421C>T/p.(Arg141Trp) [3 hmz subjects from 2 consanguineous families],
- c.580C>T/p.Pro194Ser [1 hmz individual born to consanguineous parents],
- c.2T>C/p.(Met1?) [1 hmz individual born to related parents],
- c.14dup/p.(Cys6Leufs*19) in trans with c.1021T>C/p.(Phe341Leu) in 1 individual.

CHKA encodes choline kinase alpha, an enzyme catalyzing the first step of phospholipid synthesis in the Kennedy pathway. The pathway is involved in de novo synthesis of glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine being the most abundant in eukaryotic membranes.

CHKA with its paralog (CHKB) phosphorylates either choline or ethanolamine to phosphocholine or phosphoethanolamine respectively with conversion of ATP to ADP.

As the authors comment, biallelic pathogenic variants in CHKB cause a NDD with muscular dystrophy, hypotonia, ID, microcephaly and structural mitochondrial anomalies (MIM 602541). [Prominent mitochondrial patterning was observed in a single muscle biopsy available from an individual with biallelic CHKA variants].

Other disorders of the Kennedy pathway (due to biallelic PCYT2, SELENOI, PCYT1A variants) present with overlapping features incl. variable DD/ID (no-severe), microcephaly, seizures, visual impairment etc.

CHKA variants were either absent or observed once in gnomAD, affected highly conserved AAs with multiple in silico predictions in favor of a deleterious effect.

In silico modeling suggests structural effects for several of the missense variants (Arg141Trp, Pro194Ser presumably affect ADP binding, Phe341 lying close to the binding site of phosphocholine).

Each of the missense variants was expressed in yeast cells and W. Blot suggested expression at the expected molecular weight at comparative levels. The 3 aforementioned variants exhibited reduced catalytic activity (20%, 15%, 50% respectively).

NMD is thought to underly the deleterious effect of the frameshift one (not studied).

The start-loss variant is expected to result in significantly impaired expression and protein function as eventual utilization of the next possible start codon - occurring at position 123 - would remove 26% of the protein.

Chka(-/-) is embryonically lethal in mice, suggesting that complete loss is not compatible with life. Reduction of choline kinase activity by 30% in heterozygous mice did not appear to result in behavioral abnormalities although this was not studied in detail (PMID cited: 18029352). Finally, screening of 1566 mouse lines identified 198 genes whose disruption yields neuroanatomical phenotypes, Chka(+/-) mice being among these (PMID cited: 31371714).

There is no associated phenotype in OMIM, Gene2Phenotype or SysID.

Overall this gene can be considered for inclusion in the ID and epilepsy panes with green or amber rating (>3 individuals, >3 variants, variant studies, overlapping phenotype of disorders belonging to the same pathway, etc). Consider also inclusion in the microcephaly panel (where available this seemed to be of postnatal onset).
Sources: Literature
Mendeliome v0.11070 SOST Seb Lunke Marked gene: SOST as ready
Mendeliome v0.11066 PTDSS1 Zornitza Stark Marked gene: PTDSS1 as ready
Mendeliome v0.11066 PTDSS1 Zornitza Stark Phenotypes for gene: PTDSS1 were changed from to Lenz-Majewski hyperostotic dwarfism MIM#151050
Mendeliome v0.11063 PTDSS1 Zornitza Stark reviewed gene: PTDSS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24241535, 29341480, 31403251; Phenotypes: Lenz-Majewski hyperostotic dwarfism MIM#151050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11063 SLC22A4 Zornitza Stark Marked gene: SLC22A4 as ready
Mendeliome v0.11063 SLC22A4 Zornitza Stark Phenotypes for gene: SLC22A4 were changed from to susceptibility to rheumatoid arthritis MIM#180300
Mendeliome v0.11058 HSF2BP Zornitza Stark edited their review of gene: HSF2BP: Added comment: An additional two patients are described with homozygous missense variants, with supportive in vitro functional assay. PMID: 35174157 Now there are 5 affected patients from three independent families and three different biallelic missense variants associated with the condition.; Changed rating: GREEN; Changed publications: 32845237, 35174157
Mendeliome v0.11058 SLC22A4 Ain Roesley reviewed gene: SLC22A4: Rating: RED; Mode of pathogenicity: None; Publications: 15184985, 24972750; Phenotypes: susceptibility to rheumatoid arthritis MIM#180300; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.11056 TBC1D24 Zornitza Stark Marked gene: TBC1D24 as ready
Mendeliome v0.11053 SUCLG1 Zornitza Stark Marked gene: SUCLG1 as ready
Mendeliome v0.11050 RUNX2 Zornitza Stark Marked gene: RUNX2 as ready
Mendeliome v0.11050 RUNX2 Zornitza Stark Phenotypes for gene: RUNX2 were changed from to Cleidocranial dysplasia MIM#119600; Cleidocranial dysplasia, forme fruste, dental anomalies only MIM#119600; Cleidocranial dysplasia, forme fruste, with brachydactyly MIM#119600; Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly MIM#156510
Mendeliome v0.11047 RRM2B Zornitza Stark Marked gene: RRM2B as ready
Mendeliome v0.11044 RNASET2 Zornitza Stark Marked gene: RNASET2 as ready
Mendeliome v0.11041 C17orf53 Zornitza Stark Marked gene: C17orf53 as ready
Mendeliome v0.11040 C17orf53 Zornitza Stark gene: C17orf53 was added
gene: C17orf53 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: C17orf53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf53 were set to 34707299; 31467087
Phenotypes for gene: C17orf53 were set to Primary ovarian insufficiency
Review for gene: C17orf53 was set to AMBER
Added comment: PMID: 34707299. Homozygous LOF variant in individual with primary ovarian insufficiency PMID: 31467087. Mice with targeted mutations in Hrob are infertile due to depletion of germ cells.
Sources: Expert Review
Mendeliome v0.11036 TFAM Zornitza Stark edited their review of gene: TFAM: Added comment: PMID: 32399598. Homozygous missense variant predicted pathogenic in patient presenting with Perrault syndrome and intellectual disability

PMID: 34647195. Same homozygous missense variant in two sisters with premature ovarian insufficiency +/- seizures and their brother with seizures + intellectual disability. Patient fibroblasts have mtDNA depletion

PMID: 34647195. Zebrafish model with in-frame deletion has ovarian dysgenesis and mtDNA depletion; Changed rating: GREEN; Changed publications: 27448789, 29021295, 9500544, 32399598, 34647195, 34647195; Changed phenotypes: Mitochondrial DNA depletion syndrome 15 (hepatocerebral type) MIM#617156, Perrault syndrome
Mendeliome v0.11036 SPATA16 Zornitza Stark Marked gene: SPATA16 as ready
Mendeliome v0.11032 TNFRSF10B Zornitza Stark Marked gene: TNFRSF10B as ready
Mendeliome v0.11032 TNFRSF10B Zornitza Stark Phenotypes for gene: TNFRSF10B were changed from to Squamous cell carcinoma, head and neck MIM#275355
Mendeliome v0.11028 MAPK8IP1 Zornitza Stark Marked gene: MAPK8IP1 as ready
Mendeliome v0.11024 SMIM1 Zornitza Stark Marked gene: SMIM1 as ready
Mendeliome v0.11022 ACKR1 Zornitza Stark Marked gene: ACKR1 as ready
Mendeliome v0.11020 OGG1 Zornitza Stark Marked gene: OGG1 as ready
Mendeliome v0.11020 OGG1 Zornitza Stark Phenotypes for gene: OGG1 were changed from to Renal cell carcinoma, clear cell, somatic MIM#144700
Mendeliome v0.11016 B3GALNT1 Zornitza Stark Marked gene: B3GALNT1 as ready
Mendeliome v0.11014 SERPINA7 Zornitza Stark Marked gene: SERPINA7 as ready
Mendeliome v0.11011 RUNX2 Ain Roesley reviewed gene: RUNX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301686; Phenotypes: Cleidocranial dysplasia MIM#119600, Cleidocranial dysplasia, forme fruste, dental anomalies only MIM#119600, Cleidocranial dysplasia, forme fruste, with brachydactyly MIM#119600, Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly MIM#156510; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.11011 DLC1 Bryony Thompson Marked gene: DLC1 as ready
Mendeliome v0.11010 DLC1 Bryony Thompson gene: DLC1 was added
gene: DLC1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DLC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLC1 were set to 29773874
Phenotypes for gene: DLC1 were set to Nephrotic syndrome MONDO:0005377
Review for gene: DLC1 was set to GREEN
Added comment: Biallelic variants in 4 families, and knockdown of DLC1 in cultured podocytes reduces migration rate and treatment with dexamethasone abolishes RhoA activation.
Sources: Expert list
Mendeliome v0.11009 RNASEH2A Ain Roesley reviewed gene: RNASEH2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 15870678, 25604658, 23592335, 20301648; Phenotypes: Aicardi-Goutieres syndrome 4 MIM#610333; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11008 WARS2 Zornitza Stark Marked gene: WARS2 as ready
Mendeliome v0.11008 WARS2 Zornitza Stark Gene: wars2 has been classified as Green List (High Evidence).
Mendeliome v0.11008 WARS2 Zornitza Stark Phenotypes for gene: WARS2 were changed from to Parkinsonism-dystonia 3, childhood-onset, MIM# 619738; Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, MIM# 617710
Mendeliome v0.11007 WARS2 Zornitza Stark Publications for gene: WARS2 were set to
Mendeliome v0.11006 WARS2 Zornitza Stark Mode of inheritance for gene: WARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11005 WARS2 Zornitza Stark reviewed gene: WARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29120065, 31970218, 34890876, 28236339, 28650581, 28905505, 30920170; Phenotypes: Parkinsonism-dystonia 3, childhood-onset, MIM# 619738, Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, MIM# 617710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11005 NHLH2 Zornitza Stark Marked gene: NHLH2 as ready
Mendeliome v0.11005 NHLH2 Zornitza Stark gene: NHLH2 was added
gene: NHLH2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NHLH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHLH2 were set to 35066646
Phenotypes for gene: NHLH2 were set to Hypogonadotropic hypogonadism 27 without anosmia , MIM# 619755
Review for gene: NHLH2 was set to RED
Added comment: Single individual reported homozygous for a missense variant in this gene. Two other individuals heterozygous for missense variants identified as part of this cohort; however, had alternative diagnoses.
Sources: Literature
Mendeliome v0.11004 TNFRSF10B Paul De Fazio reviewed gene: TNFRSF10B: Rating: RED; Mode of pathogenicity: None; Publications: 9721851; Phenotypes: Squamous cell carcinoma, head and neck MIM#275355; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11004 OGG1 Paul De Fazio reviewed gene: OGG1: Rating: RED; Mode of pathogenicity: None; Publications: 10987279, 29305130; Phenotypes: Renal cell carcinoma, clear cell, somatic MIM#144700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.11003 NDUFA11 Zornitza Stark Marked gene: NDUFA11 as ready
Mendeliome v0.11003 NDUFA11 Zornitza Stark Phenotypes for gene: NDUFA11 were changed from to Mitochondrial complex I deficiency, nuclear type 14, MIM#618236
Mendeliome v0.10999 NDUFA11 Zornitza Stark reviewed gene: NDUFA11: Rating: AMBER; Mode of pathogenicity: None; Publications: 18306244, 31074871; Phenotypes: Mitochondrial complex I deficiency, nuclear type 14, MIM#618236; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10999 RIN2 Zornitza Stark Marked gene: RIN2 as ready
Mendeliome v0.10996 DLD Zornitza Stark Marked gene: DLD as ready
Mendeliome v0.10993 KIAA0391 Zornitza Stark changed review comment from: Comment when marking as ready: Note gene is referred to as PRORP in the manuscript, but HGNC approved name is KIAA0391.; to: HGNC approved name is now PRORP.
Mendeliome v0.10992 POLR3B Zornitza Stark Phenotypes for gene: POLR3B were changed from Ataxia, spasticity, and demyelinating neuropathy; Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism MIM#614381 to Charcot-Marie-Tooth disease, demyelinating, type 1I, MIM# 619742; Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 614381
Mendeliome v0.10991 POLR3B Zornitza Stark edited their review of gene: POLR3B: Changed phenotypes: Charcot-Marie-Tooth disease, demyelinating, type 1I, MIM# 619742, Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 614381; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10991 TBX15 Zornitza Stark Marked gene: TBX15 as ready
Mendeliome v0.10988 TBX18 Zornitza Stark Marked gene: TBX18 as ready
Mendeliome v0.10988 TBX18 Zornitza Stark Phenotypes for gene: TBX18 were changed from to Congenital anomalies of kidney and urinary tract 2, MIM# 143400
Mendeliome v0.10985 TBX18 Zornitza Stark reviewed gene: TBX18: Rating: GREEN; Mode of pathogenicity: None; Publications: 26235987; Phenotypes: Congenital anomalies of kidney and urinary tract 2, MIM# 143400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10985 TBX4 Zornitza Stark Phenotypes for gene: TBX4 were changed from Posterior amelia with pelvis and pulmonary hypoplasia; small patella syndrome to Amelia, posterior, with pelvic and pulmonary hypoplasia syndrome, MIM# 601360; Ischiocoxopodopatellar syndrome with or without pulmonary arterial hypertension, MIM# 147891
Mendeliome v0.10983 TGDS Zornitza Stark Marked gene: TGDS as ready
Mendeliome v0.10980 THOC6 Zornitza Stark Marked gene: THOC6 as ready
Mendeliome v0.10977 DRC1 Zornitza Stark Phenotypes for gene: DRC1 were changed from Ciliary dyskinesia, primary, 21, MIM# 615294 to Ciliary dyskinesia, primary, 21, MIM# 615294; Male infertility
Mendeliome v0.10975 DRC1 Zornitza Stark edited their review of gene: DRC1: Added comment: PMID 34169321: two individuals reported with homozygous variants and morphological abnormalities of sperm/male infertility.; Changed publications: 31960620, 34169321; Changed phenotypes: Ciliary dyskinesia, primary, 21, MIM# 615294, Male infertility
Mendeliome v0.10973 FUZ Zornitza Stark Marked gene: FUZ as ready
Mendeliome v0.10972 FTSJ1 Zornitza Stark Marked gene: FTSJ1 as ready
Mendeliome v0.10969 FLAD1 Zornitza Stark Marked gene: FLAD1 as ready
Mendeliome v0.10966 FGF17 Zornitza Stark Marked gene: FGF17 as ready
Mendeliome v0.10963 SYP Zornitza Stark Marked gene: SYP as ready
Mendeliome v0.10963 SYP Zornitza Stark Phenotypes for gene: SYP were changed from to Mental retardation, X-linked 96 MIM#300802
Mendeliome v0.10959 ZFYVE26 Zornitza Stark Marked gene: ZFYVE26 as ready
Mendeliome v0.10959 ZFYVE26 Zornitza Stark Phenotypes for gene: ZFYVE26 were changed from to Spastic paraplegia 15, autosomal recessive MIM#270700
Mendeliome v0.10956 ZDHHC9 Zornitza Stark Marked gene: ZDHHC9 as ready
Mendeliome v0.10956 ZDHHC9 Zornitza Stark Phenotypes for gene: ZDHHC9 were changed from to Mental retardation, X-linked syndromic, Raymond type MIM# 300799
Mendeliome v0.10953 FUZ Ain Roesley gene: FUZ was added
gene: FUZ was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FUZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FUZ were set to 21840926
Phenotypes for gene: FUZ were set to {Neural tube defects, susceptibility to} MIM#182940
Penetrance for gene: FUZ were set to unknown
Review for gene: FUZ was set to RED
gene: FUZ was marked as current diagnostic
Added comment: Spina bifida cohort. Negative for VANGL1 and VANGL2, only FUZ was sequenced.
Variants identified in 5 individuals.
Arg404Gln (39 hets in gnomAD) and Asp354Tyr (6 hets in gnomAD). These variants are listed as risk factor in ClinVar
Pro39Ser (absent in gnomAD) was de novo by parental sanger and showed reduced cell mobility on scratch assays.

2 other variants Gly140Glu and Ser142Thr were deemed non-causative due to poor in silicos and conservation

Finally, hom KO mouse models were done to prove neural tube defects
Sources: Literature
Mendeliome v0.10953 FGF17 Ain Roesley changed review comment from: 31200363;
1x individual

31748124
3x unrelated individuals. 1 has p.48_52del and another variant in OTUD4 (no current mendelian disease association), 1x with Pro120Leu (5 hets in gnomAD) and 1x with Lys191Arg (55 hets in gnomad)

23643382
3x unrelated individuals, including 1 large consanguineous 10-generation French Canadian family.
In this large family, 3 other variants in FGFR1, HS6ST1, and FLRT3 were identified. None of the other affecteds carried the FGF17 variant

Summary: 3x individuals with convincing evidence; to: PMID:31200363;
1x individual

PMID:31748124
3x unrelated individuals. 1 has p.48_52del and another variant in OTUD4 (no current mendelian disease association), 1x with Pro120Leu (5 hets in gnomAD) and 1x with Lys191Arg (55 hets in gnomad)

PMID:23643382
3x unrelated individuals, including 1 large consanguineous 10-generation French Canadian family.
In this large family, 3 other variants in FGFR1, HS6ST1, and FLRT3 were identified. None of the other affecteds carried the FGF17 variant

Summary: 3x individuals with convincing evidence
Mendeliome v0.10953 ZFYVE26 Ain Roesley changed review comment from: Genereviews:
>70 individuals reported; to: Genereviews:
>70 individuals reported.

While onset of spasticity is typically in mid- to late childhood or adolescence (i.e., between ages 5 and 18 years), other manifestations, such as developmental delay or learning disability, may be present earlier, often preceding motor involvement. Individuals with adult onset have also been reported.
Mendeliome v0.10953 ZFYVE26 Ain Roesley reviewed gene: ZFYVE26: Rating: GREEN; Mode of pathogenicity: None; Publications: 34057829; Phenotypes: Spastic paraplegia 15, autosomal recessive MIM#270700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10953 ZDHHC9 Ain Roesley reviewed gene: ZDHHC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 26000327, 29681091; Phenotypes: Mental retardation, X-linked syndromic, Raymond typeMIM# 300799; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.10953 SPRED2 Zornitza Stark Phenotypes for gene: SPRED2 were changed from Rasopathy; developmental delay; intellectual disability; cardiac defects; short stature; skeletal anomalies; a typical facial gestalt to Noonan syndrome 14, MIM# 619745
Mendeliome v0.10951 BAG5 Zornitza Stark Marked gene: BAG5 as ready
Mendeliome v0.10950 BAG5 Zornitza Stark gene: BAG5 was added
gene: BAG5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BAG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BAG5 were set to 35044787
Phenotypes for gene: BAG5 were set to Cardiomyopathy, dilated, 2F, MIM# 619747
Review for gene: BAG5 was set to GREEN
Added comment: 5 individuals from four unrelated families reported. All had early-onset disease, with the diagnosis being made in the second decade of life in 4 patients (families 1, 3, and 4) and at age 34 in 1 (family 2). Refractory ventricular arrhythmias (tachycardia or fibrillation), severely reduced left ventricular ejection fractions, elevated left ventricular diastolic dimensions, and elevated brain natriuretic peptide (BNP) levels reported. All developed severe heart failure requiring placement of a left ventricular assist device for circulatory support, and at least 1 underwent cardiac transplantation.
Sources: Literature
Mendeliome v0.10949 BCO1 Zornitza Stark Marked gene: BCO1 as ready
Mendeliome v0.10948 PRKCH Zornitza Stark Marked gene: PRKCH as ready
Mendeliome v0.10947 ALDH2 Zornitza Stark Marked gene: ALDH2 as ready
Mendeliome v0.10945 ABHD16A Zornitza Stark Marked gene: ABHD16A as ready
Mendeliome v0.10945 ABHD16A Zornitza Stark Phenotypes for gene: ABHD16A were changed from Spastic paraplegia; Intellectual Disability; Callosome to Spastic paraplegia 86, autosomal recessive, MIM# 619735; Intellectual Disability; Corpus callosum abnormalities
Mendeliome v0.10944 ABHD16A Zornitza Stark reviewed gene: ABHD16A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 86, autosomal recessive, MIM# 619735; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10944 GSPT2 Zornitza Stark Marked gene: GSPT2 as ready
Mendeliome v0.10943 SUMO1 Zornitza Stark Marked gene: SUMO1 as ready
Mendeliome v0.10940 CPS1 Belinda Chong reviewed gene: CPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8486760, 17310273, 21120950; Phenotypes: Carbamoylphosphate synthetase I deficiency MIM#237300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10940 THUMPD1 Zornitza Stark Marked gene: THUMPD1 as ready
Mendeliome v0.10940 THUMPD1 Zornitza Stark Phenotypes for gene: THUMPD1 were changed from Syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss and facial dysmorphism, AR to Syndromic disease, MONDO:0002254, THUMPD1-related
Mendeliome v0.10938 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, biallelic loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Mendeliome v0.10938 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022):
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Mendeliome v0.10938 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022) manuscript accepted in AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022):
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Mendeliome v0.10938 THUMPD1 Chern Lim gene: THUMPD1 was added
gene: THUMPD1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: THUMPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: THUMPD1 were set to Syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss and facial dysmorphism, AR
Review for gene: THUMPD1 was set to GREEN
gene: THUMPD1 was marked as current diagnostic
Added comment: Broly, M. et al. (2022) manuscript accepted in AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Mendeliome v0.10938 RAB39B Zornitza Stark Marked gene: RAB39B as ready
Mendeliome v0.10935 PTCHD1 Zornitza Stark Marked gene: PTCHD1 as ready
Mendeliome v0.10932 PPP3CA Zornitza Stark Marked gene: PPP3CA as ready
Mendeliome v0.10932 PPP3CA Zornitza Stark Phenotypes for gene: PPP3CA were changed from to Developmental and epileptic encephalopathy 91, MIM#617711; Arthrogryposis, cleft palate, craniosynostosis and impaired intellectual development, MIM#618265
Mendeliome v0.10929 PLP1 Zornitza Stark Marked gene: PLP1 as ready
Mendeliome v0.10929 PLP1 Zornitza Stark Phenotypes for gene: PLP1 were changed from to Pelizaeus-Merzbacher disease MIM#312080; Spastic paraplegia 2, X-linked MIM#312920
Mendeliome v0.10926 LDB3 Zornitza Stark Marked gene: LDB3 as ready
Mendeliome v0.10926 LDB3 Zornitza Stark Phenotypes for gene: LDB3 were changed from to Cardiomyopathy, dilated, 1C, with or without LVNC MIM#601493; Cardiomyopathy, hypertrophic, 24 MIM#601493; Left ventricular noncompaction 3 MIM#601493; Myopathy, myofibrillar, 4 MIM#609452
Mendeliome v0.10923 PPP3CA Chern Lim changed review comment from: PMID: 29432562:
- Overexpression studies using yeast showed missense variants in the autoinhibitory domain resulted in gain of function, missense variants in the catalytic domain resulted in loss of function (however dom-neg has not been ruled out).
- Loss-of-function and gain-of-function mutations of PPP3CA lead to early onset epileptic encephalopathy and multiple congenital abnormalities, respectively.

PMID: 32593294:
- Reported a patient with PTV in the C-term predicted to escape NMD, clinical features consistent with MIM#617711.
- Summarised that missense variants in catalytic domain and those upstream of autoinhibitory domain, PTVs in C-term predicted to escape NMD: LoF, MIM#617711. Missense in autoinhibitory domain: GoF, MIM#618265.; to: PMID: 29432562:
- Overexpression studies using yeast showed missense variants in the autoinhibitory domain resulted in gain of function, missense variants in the catalytic domain resulted in loss of function (however dom-neg has not been ruled out).
- Loss-of-function and gain-of-function mutations of PPP3CA lead to early onset epileptic encephalopathy and multiple congenital abnormalities, respectively.

PMID: 32593294:
- Reported a patient with PTV in the C-term predicted to escape NMD, clinical features consistent with MIM#617711.
- 15 variants have been reported. Summarised that missense variants in catalytic domain and those upstream of autoinhibitory domain, PTVs in C-term predicted to escape NMD: LoF, MIM#617711; missense in autoinhibitory domain: GoF, MIM#618265.
Mendeliome v0.10923 PPP3CA Chern Lim reviewed gene: PPP3CA: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 29432562, 32593294; Phenotypes: Developmental and epileptic encephalopathy 91, MIM#617711, Arthrogryposis, cleft palate, craniosynostosis and impaired intellectual development, MIM#618265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.10923 PLP1 Ain Roesley reviewed gene: PLP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301361; Phenotypes: Pelizaeus-Merzbacher disease MIM#312080, Spastic paraplegia 2, X-linked MIM#312920; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.10923 LDB3 Ain Roesley reviewed gene: LDB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26419279, 16427346, 14660611, 14662268, 27546599, 25911362; Phenotypes: Cardiomyopathy, dilated, 1C, with or without LVNC MIM#601493, Cardiomyopathy, hypertrophic, 24 MIM#601493, Left ventricular noncompaction 3 MIM#601493, Myopathy, myofibrillar, 4 MIM#609452; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.10921 PAX5 Zornitza Stark Marked gene: PAX5 as ready
Mendeliome v0.10920 COL25A1 Bryony Thompson Phenotypes for gene: COL25A1 were changed from Fibrosis of extraocular muscles, congenital, 5, MIM# 616219 to Fibrosis of extraocular muscles, congenital, 5, MIM# 616219; arthrogryposis multiplex congenita MONDO:0015168
Mendeliome v0.10918 COL25A1 Bryony Thompson reviewed gene: COL25A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35077597, 26437029; Phenotypes: arthrogryposis multiplex congenita MONDO:0015168; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10918 RPL8 Bryony Thompson Marked gene: RPL8 as ready
Mendeliome v0.10917 HYAL2 Krithika Murali reviewed gene: HYAL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34906488, 28081210, 23172227, 26515055; Phenotypes: Cleft lip and palate, cor triatriatum, congenital cardiac malformations; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10914 RPL8 Bryony Thompson gene: RPL8 was added
gene: RPL8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPL8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL8 were set to 25424902; 34961992
Phenotypes for gene: RPL8 were set to Diamond-Blackfan anemia MONDO:0015253
Review for gene: RPL8 was set to AMBER
Added comment: 2 unrelated DBA cases with de novo missense variants, and functional studies in lymphoblastoid cells and yeast models demonstrate the 2 missense variants are functionally deficient proteins that affect ribosome production.
Sources: Literature
Mendeliome v0.10908 ARR3 Bryony Thompson Marked gene: ARR3 as ready
Mendeliome v0.10908 ARR3 Bryony Thompson Gene: arr3 has been classified as Green List (High Evidence).
Mendeliome v0.10908 ARR3 Bryony Thompson Classified gene: ARR3 as Green List (high evidence)
Mendeliome v0.10908 ARR3 Bryony Thompson Gene: arr3 has been classified as Green List (High Evidence).
Mendeliome v0.10907 ARR3 Bryony Thompson gene: ARR3 was added
gene: ARR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARR3 was set to Other
Publications for gene: ARR3 were set to 27829781; 35001458
Phenotypes for gene: ARR3 were set to Myopia 26, X-linked, female-limited MIM#301010
Review for gene: ARR3 was set to GREEN
Added comment: At least 6 multi-generational families with female-limited early-onset high myopia. Only female carriers are affected and hemizygous males are unaffected. Authors hypothesise the mode of inheritance might be explained by metabolic interference due to X-inactivation.
Sources: Literature
Mendeliome v0.10906 SLC26A8 Bryony Thompson Marked gene: SLC26A8 as ready
Mendeliome v0.10903 PYROXD2 Zornitza Stark Marked gene: PYROXD2 as ready
Mendeliome v0.10900 OBSCN Zornitza Stark Phenotypes for gene: OBSCN were changed from Hypertrophic cardiomyopathy to Rhabdomyolysis MONDO:0005290, OBSCN-related
Mendeliome v0.10896 HAND2 Zornitza Stark Marked gene: HAND2 as ready
Mendeliome v0.10896 HAND2 Zornitza Stark Phenotypes for gene: HAND2 were changed from to Congenital heart disease
Mendeliome v0.10892 POP1 Zornitza Stark Marked gene: POP1 as ready
Mendeliome v0.10888 MVD Zornitza Stark Phenotypes for gene: MVD were changed from Porokeratosis 7, multiple types, MIM# 614714 to Porokeratosis 7, multiple types, MIM# 614714; Nonsyndromic genetic hearing loss MONDO:0019497, MVD-related, AR
Mendeliome v0.10886 PLCD1 Zornitza Stark Marked gene: PLCD1 as ready
Mendeliome v0.10883 AKAP10 Zornitza Stark Marked gene: AKAP10 as ready
Mendeliome v0.10883 AKAP10 Zornitza Stark Phenotypes for gene: AKAP10 were changed from to {Cardiac conduction defect, susceptibility to} MIM#115080; sudden cardiac arrest MONDO:0007264
Mendeliome v0.10880 HMCN1 Zornitza Stark Marked gene: HMCN1 as ready
Mendeliome v0.10880 HMCN1 Zornitza Stark Phenotypes for gene: HMCN1 were changed from to {Macular degeneration, age-related, 1} MIM#603075; age related macular degeneration 1 MONDO:0011285
Mendeliome v0.10876 CCND1 Zornitza Stark Marked gene: CCND1 as ready
Mendeliome v0.10873 PADI4 Zornitza Stark Marked gene: PADI4 as ready
Mendeliome v0.10873 PADI4 Zornitza Stark Phenotypes for gene: PADI4 were changed from to Susceptibility to rheumatoid arthritis
Mendeliome v0.10869 PDSS2 Zornitza Stark Marked gene: PDSS2 as ready
Mendeliome v0.10869 PDSS2 Zornitza Stark Phenotypes for gene: PDSS2 were changed from to Coenzyme Q10 deficiency, primary, 3 MIM#614652
Mendeliome v0.10866 PDHX Zornitza Stark Marked gene: PDHX as ready
Mendeliome v0.10863 MVD Paul De Fazio reviewed gene: MVD: Rating: RED; Mode of pathogenicity: None; Publications: 34135477; Phenotypes: Nonsyndromic genetic hearing loss MONDO:0019497, MVD-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10863 NDUFS8 Zornitza Stark Marked gene: NDUFS8 as ready
Mendeliome v0.10863 NDUFS8 Zornitza Stark Phenotypes for gene: NDUFS8 were changed from to Mitochondrial complex I deficiency, nuclear type 2 MIM#618222
Mendeliome v0.10860 NDUFV1 Zornitza Stark Marked gene: NDUFV1 as ready
Mendeliome v0.10860 NDUFV1 Zornitza Stark Phenotypes for gene: NDUFV1 were changed from to Mitochondrial complex I deficiency, nuclear type 4 MIM#618225
Mendeliome v0.10857 FZR1 Alison Yeung Marked gene: FZR1 as ready
Mendeliome v0.10855 SEZ6 Alison Yeung Marked gene: SEZ6 as ready
Mendeliome v0.10854 ADAMTS1 Zornitza Stark Marked gene: ADAMTS1 as ready
Mendeliome v0.10853 MPDZ Paul De Fazio reviewed gene: MPDZ: Rating: AMBER; Mode of pathogenicity: None; Publications: 34135477, 29026089; Phenotypes: Nonsyndromic genetic hearing loss MONDO:0019497, MPDZ-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10850 ATP5O Alison Yeung Marked gene: ATP5O as ready
Mendeliome v0.10849 SEZ6 Paul De Fazio gene: SEZ6 was added
gene: SEZ6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEZ6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEZ6 were set to 34135477
Phenotypes for gene: SEZ6 were set to Nonsyndromic genetic hearing loss MONDO:0019497, SEZ6-related
Review for gene: SEZ6 was set to RED
gene: SEZ6 was marked as current diagnostic
Added comment: Homozygous missense variant p.(Val698Ile) identified in 4 affected individuals from a single consanguineous Pakistani family by WES. 5 other genotyped unaffected individuals were heterozygous or homozygous wild-type. Variant is in gnomad (36 hets, 0 hom).

RNA expression studies show the gene is expressed in the mouse inner ear, but no functional studies were performed on the variant (in silico analysis only).
Sources: Literature
Mendeliome v0.10849 COL4A6 Lucy Spencer reviewed gene: COL4A6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33840813; Phenotypes: Hearing loss; 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 v0.10846 ADAMTS1 Paul De Fazio gene: ADAMTS1 was added
gene: ADAMTS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADAMTS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS1 were set to 34135477
Phenotypes for gene: ADAMTS1 were set to Nonsyndromic genetic hearing loss MONDO:0019497, ADAMTS1-related
Review for gene: ADAMTS1 was set to RED
gene: ADAMTS1 was marked as current diagnostic
Added comment: Homozygous missense variant p.(Ser135Ala) identified in 3 affected siblings from a single consanguineous Pakistani family by WES. A fourth unaffected sibling was homozygous wild type. Variant is in gnomad (26 hets, 1 hom).

RNA expression studies show the gene is expressed in the mouse inner ear, but no functional studies were performed on the variant (in silico analysis only).
Sources: Literature
Mendeliome v0.10844 ATP5O Ain Roesley gene: ATP5O was added
gene: ATP5O was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP5O was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP5O were set to 34954817
Phenotypes for gene: ATP5O were set to mitochondrial disease, ATP5F1E-related MONDO:0044970
Penetrance for gene: ATP5O were set to Complete
Review for gene: ATP5O was set to RED
gene: ATP5O was marked as current diagnostic
Added comment: Now known as ATP5PO (HGNC)

1 compound het individual with dev delay, muscular hypotonia, ID, dystonia, seizures and neurologic regression
Sources: Literature
Mendeliome v0.10844 BAP1 Anna Ritchie changed review comment from: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. All affected individuals harboring a de novo BAP1 variant had DD or ID (11/11) characterized notably by speech (11/ 11) and motor delay (6/11). Most of them had hypotonia (7/11), seizures (6/11), and abnormal behavior (8/10), including autism spectrum disorder, attention deficit hyperactivity disorder, and hypersensitivity. Almost all individuals showed dysmorphic facial features (10/11), and more than half (6/11) had skeletal mal- formations (involving the hands [4/11], feet [3/11], or spine [2/11],). Most of the individuals had growth failure (9/11), including four individuals with a very short stature.
Sources: Literature; to: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. All affected individuals harboring a de novo BAP1 variant had DD or ID (11/11) characterized notably by speech (11/ 11) and motor delay (6/11). Most of them had hypotonia (7/11), seizures (6/11), and abnormal behavior (8/10), including autism spectrum disorder, attention deficit hyperactivity disorder, and hypersensitivity. Almost all individuals showed dysmorphic facial features (10/11), and more than half (6/11) had skeletal malformations (involving the hands [4/11], feet [3/11], or spine [2/11]). Most of the individuals had growth failure (9/11), including four individuals with a very short stature.
Sources: Literature
Mendeliome v0.10844 ATP5E Ain Roesley reviewed gene: ATP5E: Rating: GREEN; Mode of pathogenicity: None; Publications: 34954817; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 MIM#614053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10844 BAP1 Anna Ritchie changed review comment from: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. Patients phenotypes also included developmental delay, speech and motor delay, seizures, hypotonia, abnormal behaviour, autism, attention deficit hyperactivity disorder, and hypersensitivity.
Sources: Literature; to: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. All affected individuals harboring a de novo BAP1 variant had DD or ID (11/11) characterized notably by speech (11/ 11) and motor delay (6/11). Most of them had hypotonia (7/11), seizures (6/11), and abnormal behavior (8/10), including autism spectrum disorder, attention deficit hyperactivity disorder, and hypersensitivity. Almost all individuals showed dysmorphic facial features (10/11), and more than half (6/11) had skeletal mal- formations (involving the hands [4/11], feet [3/11], or spine [2/11],). Most of the individuals had growth failure (9/11), including four individuals with a very short stature.
Sources: Literature
Mendeliome v0.10844 TMEM53 Zornitza Stark Marked gene: TMEM53 as ready
Mendeliome v0.10843 TMEM53 Zornitza Stark Phenotypes for gene: TMEM53 were changed from Sclerosing bone disorder, macrocephaly, impaired vision, short stature to Primary bone dysplasia MONDO:0018230, TMEM53-related; Sclerosing bone disorder, macrocephaly, impaired vision, short stature
Mendeliome v0.10842 MAN2C1 Alison Yeung Marked gene: MAN2C1 as ready
Mendeliome v0.10840 SLC38A3 Zornitza Stark Marked gene: SLC38A3 as ready
Mendeliome v0.10838 BAP1 Anna Ritchie gene: BAP1 was added
gene: BAP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAP1 were set to PMID: 35051358
Phenotypes for gene: BAP1 were set to syndromic intellectual disability MONDO:0000508
Penetrance for gene: BAP1 were set to unknown
Review for gene: BAP1 was set to GREEN
Added comment: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. Patients phenotypes also included developmental delay, speech and motor delay, seizures, hypotonia, abnormal behaviour, autism, attention deficit hyperactivity disorder, and hypersensitivity.
Sources: Literature
Mendeliome v0.10838 ARSK Zornitza Stark Marked gene: ARSK as ready
Mendeliome v0.10838 ARSK Zornitza Stark Gene: arsk has been classified as Green List (High Evidence).
Mendeliome v0.10838 ARSK Zornitza Stark Phenotypes for gene: ARSK were changed from Mucopolysaccharidosis to Mucopolysaccharidosis MONDO:0019249, ARSK-related
Mendeliome v0.10837 ARSK Zornitza Stark Classified gene: ARSK as Green List (high evidence)
Mendeliome v0.10837 ARSK Zornitza Stark Gene: arsk has been classified as Green List (High Evidence).
Mendeliome v0.10836 SLC38A3 Ain Roesley changed review comment from: 7 families 6 of whom are consanguineous but unique variants in all of them

Acquired microcephaly noted (8/10 with <-2 SD, 5/10 <-3 SD)

10/10 with axial hopotonia, absent speech, GDD/ID
9/10 with visual impairment
8/10 with seizures
8/10 with peripheral hypertonia
Sources: Literature; to: 7 families 6 of whom are consanguineous but unique variants in all of them

Acquired microcephaly noted (8/10 with >-2 SD, 5/10 >-3 SD)

10/10 with axial hopotonia, absent speech, GDD/ID
9/10 with visual impairment
8/10 with seizures
8/10 with peripheral hypertonia
Sources: Literature
Mendeliome v0.10836 TMEM53 Lucy Spencer gene: TMEM53 was added
gene: TMEM53 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM53 were set to PMID: 33824347
Phenotypes for gene: TMEM53 were set to Sclerosing bone disorder, macrocephaly, impaired vision, short stature
Review for gene: TMEM53 was set to GREEN
Added comment: PMID: 33824347- Previously unknown type of sclerosing bone disorder in 4 independent families, bi-allelic LOF variants in TMEM53. 5 individuals from 4 families, all have proportional or short limbed stature, not identifiable at birth. Head deformities (macrocephaly, dolichocephaly, prominent forehead), epicanthic folds, thick vermilion of upper and lower lips. Vision diminished after early childhood due to optic nerve compression.

3 of 4 families confirmed consanguineous, and all affected members from all 4 families have homozygous variants inherited from heterozygous parents. 3 families have the same splicing variant proven to cause exon 2 skipping and an NMD frameshift by RT-PCR. The other family has a an NMD frameshift variant. So 4 families but only 2 variants.
Sources: Literature
Mendeliome v0.10836 SLC38A3 Ain Roesley gene: SLC38A3 was added
gene: SLC38A3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC38A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC38A3 were set to 34605855
Phenotypes for gene: SLC38A3 were set to developmental epileptic encephalopathy, SLC38A3-related MONDO:0100062
Review for gene: SLC38A3 was set to GREEN
gene: SLC38A3 was marked as current diagnostic
Added comment: 7 families 6 of whom are consanguineous but unique variants in all of them

Acquired microcephaly noted (8/10 with <-2 SD, 5/10 <-3 SD)

10/10 with axial hopotonia, absent speech, GDD/ID
9/10 with visual impairment
8/10 with seizures
8/10 with peripheral hypertonia
Sources: Literature
Mendeliome v0.10836 FZR1 Alison Yeung gene: FZR1 was added
gene: FZR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FZR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FZR1 were set to 34788397
Phenotypes for gene: FZR1 were set to Developmental and epileptic encephalopathy, FZR1-related, MONDO:0100062
Review for gene: FZR1 was set to GREEN
Added comment: >3 unrelated individuals reported with de novo missense variants. Functional studies in Drosophila demonstrate missense variants cause LOF.
Sources: Literature
Mendeliome v0.10835 MAN2C1 Michelle Torres gene: MAN2C1 was added
gene: MAN2C1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAN2C1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2C1 were set to 35045343
Phenotypes for gene: MAN2C1 were set to neurodevelopmental disorder MONDO:0700092 MAN2C1-related
Review for gene: MAN2C1 was set to GREEN
Added comment: Six individuals from four different families, including two fetuses, exhibiting dysmorphic facial features, congenital anomalies such as tongue hamartoma, variable degrees of intellectual disability, and brain anomalies including polymicrogyria, interhemispheric cysts, hypothalamic hamartoma, callosal anomalies, and hypoplasia of brainstem and cerebellar vermis. Variants include PTC and missense.
Sources: Literature
Mendeliome v0.10835 ARSK Paul De Fazio gene: ARSK was added
gene: ARSK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARSK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARSK were set to 34916232; 32856704
Phenotypes for gene: ARSK were set to Mucopolysaccharidosis
Review for gene: ARSK was set to GREEN
gene: ARSK was marked as current diagnostic
Added comment: 4 individuals from 2 unrelated consanguineous families (Turkish and Indian) reported with a homozygous missense and an NMD-predicted nonsense variant. Affected individuals had features of mucopolysaccharidosis such as short stature, coarse facial features and dysostosis multiplex. Urinary GAG excretion was normal by conventional methods, but LC-MS/MS in 2 individuals revealed an increase in specific dermatan sulfate-derived disaccharides. Functional studies showed reduced protein levels and reduced enzyme activity for the nonsense and missense variant respectively.

A mouse model also shows a mucopolysaccharidosis phenotype, albeit milder.

Rated green (2 families, functional evidence, mouse model).
Sources: Literature
Mendeliome v0.10835 FRA10AC1 Zornitza Stark edited their review of gene: FRA10AC1: Added comment: PMID 34694367: 5 individuals from 3 unrelated families reported.

Variable ID, possibly related to variant type with LoF variants associated with more severe ID. All individuals had microcephaly, hypoplasia or agenesis of the corpus callosum, growth retardation, and craniofacial dysmorphism.; Changed rating: GREEN; Changed publications: 15203205, 34694367; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, FRA10AC1-related; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10835 NDUFS7 Zornitza Stark Marked gene: NDUFS7 as ready
Mendeliome v0.10835 NDUFS7 Zornitza Stark Phenotypes for gene: NDUFS7 were changed from to Mitochondrial complex I deficiency, nuclear type 3 MIM#618224
Mendeliome v0.10832 NDUFA1 Zornitza Stark Marked gene: NDUFA1 as ready
Mendeliome v0.10832 NDUFA1 Zornitza Stark Phenotypes for gene: NDUFA1 were changed from to Mitochondrial complex I deficiency, nuclear type 12 MIM#301020
Mendeliome v0.10829 MYO5A Zornitza Stark Marked gene: MYO5A as ready
Mendeliome v0.10826 LRPPRC Zornitza Stark Marked gene: LRPPRC as ready
Mendeliome v0.10826 LRPPRC Zornitza Stark Phenotypes for gene: LRPPRC were changed from to Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) MIM#220111
Mendeliome v0.10823 LRPPRC Zornitza Stark reviewed gene: LRPPRC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) MIM#220111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10823 AKAP10 Paul De Fazio reviewed gene: AKAP10: Rating: RED; Mode of pathogenicity: None; Publications: 12646697, 17485678; Phenotypes: {Cardiac conduction defect, susceptibility to} MIM#115080, sudden cardiac arrest MONDO:0007264; Mode of inheritance: Unknown; Current diagnostic: yes
Mendeliome v0.10823 HMCN1 Paul De Fazio reviewed gene: HMCN1: Rating: RED; Mode of pathogenicity: None; Publications: 25986072, 16020313, 14570714, 27007659; Phenotypes: {Macular degeneration, age-related, 1} MIM#603075, age related macular degeneration 1 MONDO:0011285; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.10823 PADI4 Paul De Fazio reviewed gene: PADI4: Rating: RED; Mode of pathogenicity: None; Publications: 16449362, 19470526, 26474773; Phenotypes: Susceptibility to rheumatoid arthritis; Mode of inheritance: Unknown; Current diagnostic: yes
Mendeliome v0.10823 PLCB1 Zornitza Stark Marked gene: PLCB1 as ready
Mendeliome v0.10823 PLCB1 Zornitza Stark Phenotypes for gene: PLCB1 were changed from to Epileptic encephalopathy, early infantile, 12 (MIM#613722)
Mendeliome v0.10820 PLCB1 Zornitza Stark reviewed gene: PLCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24684524, 20833646, 22690784, 26818157; Phenotypes: Epileptic encephalopathy, early infantile, 12 (MIM#613722); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10820 PLAA Zornitza Stark Marked gene: PLAA as ready
Mendeliome v0.10817 PGAP1 Zornitza Stark Marked gene: PGAP1 as ready
Mendeliome v0.10814 KCNN2 Zornitza Stark Phenotypes for gene: KCNN2 were changed from Neurodevelopmental movement disorders; Developmental Delay; Seizures to Neurodevelopmental disorder with or without variable movement or behavioural abnormalities, MIM#619725
Mendeliome v0.10813 KCNN2 Zornitza Stark edited their review of gene: KCNN2: Changed phenotypes: Neurodevelopmental disorder with or without variable movement or behavioural abnormalities, MIM#619725
Mendeliome v0.10813 KCNN2 Zornitza Stark reviewed gene: KCNN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with or without variable movement or behavioral abnormalities, MIM#619725; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10813 PDSS2 Ain Roesley reviewed gene: PDSS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29032433, 25349199, 17186472, 21723727, 10972372; Phenotypes: Coenzyme Q10 deficiency, primary, 3 MIM#614652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10812 PDHX Ain Roesley changed review comment from: >10 unrelated probands reported

PDHX c.1336C>T (p.Arg446Ter) is a Roma founder variant; c.1182+2T>C (p.Ile386SerfsTer13) is a Moroccan founder variant.; to: established gene-disease association

PDHX c.1336C>T (p.Arg446Ter) is a Roma founder variant; c.1182+2T>C (p.Ile386SerfsTer13) is a Moroccan founder variant.
Mendeliome v0.10812 NDUFV1 Ain Roesley reviewed gene: NDUFV1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34807224; Phenotypes: Mitochondrial complex I deficiency, nuclear type 4 MIM#618225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10812 NDUFS8 Ain Roesley reviewed gene: NDUFS8: Rating: GREEN; Mode of pathogenicity: None; Publications: 23430795, 9837812, 15159508, 22499348, 20818383, 20819849; Phenotypes: Mitochondrial complex I deficiency, nuclear type 2 MIM#618222; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10812 NDUFS7 Ain Roesley reviewed gene: NDUFS7: Rating: GREEN; Mode of pathogenicity: None; Publications: 17604671, 17275378, 10360771; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3 MIM#618224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10812 NDUFAF5 Ain Roesley reviewed gene: NDUFAF5: Rating: GREEN; Mode of pathogenicity: None; Publications: 34797029; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3 MIM#618224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10812 NDUFS7 Ain Roesley reviewed gene: NDUFS7: Rating: GREEN; Mode of pathogenicity: None; Publications: 34797029; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3 MIM#618224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10812 NDUFA1 Ain Roesley reviewed gene: NDUFA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29506883, 19185523, 17262856, 21596602; Phenotypes: Mitochondrial complex I deficiency, nuclear type 12 MIM#301020; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.10812 LRPPRC Ain Roesley changed review comment from: Established gene-disease association; to: Established gene-disease association

Onset in infancy and death usually occurs by age 2 years
Mendeliome v0.10812 LRPPRC Ain Roesley reviewed gene: LRPPRC: Rating: GREEN; Mode of pathogenicity: None; Publications: 32972427, 26510951, 21266382; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) MIM#220111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10812 MGP Zornitza Stark Marked gene: MGP as ready
Mendeliome v0.10808 ABCC9 Zornitza Stark Phenotypes for gene: ABCC9 were changed from Hypertrichotic osteochondrodysplasia, MIM# 239850; Cantu syndrome; mild ID, similar facies, myopathy, cerebral white matter hyperintensities; cardiac systolic dysfunction to Hypertrichotic osteochondrodysplasia, MIM# 239850; Cantu syndrome; Intellectual disability and myopathy syndrome, MIM# 619719
Mendeliome v0.10800 PIK3R5 Zornitza Stark Marked gene: PIK3R5 as ready
Mendeliome v0.10796 KIF26B Zornitza Stark Marked gene: KIF26B as ready
Mendeliome v0.10796 KIF26B Zornitza Stark gene: KIF26B was added
gene: KIF26B was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KIF26B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF26B were set to 30151950
Phenotypes for gene: KIF26B were set to Progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis
Review for gene: KIF26B was set to RED
Added comment: 1 report only of infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. Whole exome sequencing on the trio identified a de novo KIF26B missense variant (p.Gly546Ser). Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity.
Sources: Expert Review
Mendeliome v0.10795 ACP5 Alison Yeung Marked gene: ACP5 as ready
Mendeliome v0.10795 ACP2 Alison Yeung Marked gene: ACP2 as ready
Mendeliome v0.10794 CHP1 Zornitza Stark Marked gene: CHP1 as ready
Mendeliome v0.10793 CHP1 Zornitza Stark gene: CHP1 was added
gene: CHP1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CHP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHP1 were set to 29379881; 32787936
Phenotypes for gene: CHP1 were set to Spastic ataxia 9, autosomal recessive, MIM #618438
Review for gene: CHP1 was set to GREEN
Added comment: 2 different consanguineous families with 2 affected siblings with ataxia (1 paediatric onset, 1 adult onset). 3 of the patients had cerebellar atrophy. WES identified homozygous variants in CHP1 gene in both families (K19del and Arg91Cys), which segregated with the disorder in the family.

Decreased CHP1 protein on IHC of cerebellar tissue in family with Arg91Cys variant. In vitro functional expression studies in HEK293 cells showed that the K19del mutation resulted in decreased protein expression, with normal levels of transcript, suggesting defects in protein stability. The mutant protein formed massive protein aggregates in transfected neuronal cell bodies and neurite-like projections, whereas the wildtype protein showed a more uniform distribution. The mutant protein altered CHP1 association into functional complexes and impaired membrane localization of the Na+/H+ transporter NHE1. The findings indicated that the CHP1 mutation likely causes ataxia in an NHE1-dependent manner, resembling the mechanism observed in the Chp1 vacillator mutant mouse.
Sources: Expert Review
Mendeliome v0.10792 PI4KA Zornitza Stark Phenotypes for gene: PI4KA were changed from Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531; Neurodevelopmental syndrome with hypomyelinating leukodystrophy; Spastic paraplegia 84, autosomal recessive, MIM# 619621 to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531; Neurodevelopmental syndrome with hypomyelinating leukodystrophy; Spastic paraplegia 84, autosomal recessive, MIM# 619621; Gastrointestinal defects and immunodeficiency syndrome 2, MIM# 619708
Mendeliome v0.10791 PI4KA Zornitza Stark edited their review of gene: PI4KA: Changed phenotypes: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531, Neurodevelopmental syndrome with hypomyelinating leukodystrophy, Spastic paraplegia 84, autosomal recessive, MIM# 619621, Gastrointestinal defects and immunodeficiency syndrome 2, MIM# 619708
Mendeliome v0.10791 FNIP1 Zornitza Stark Phenotypes for gene: FNIP1 were changed from Hypertrophic Cardiomyopathy; Primary Immunodeficiency; Agammaglobulinemia; Neutropenia to Immunodeficiency 93 and hypertrophic cardiomyopathy, MIM# 619705
Mendeliome v0.10790 FNIP1 Zornitza Stark reviewed gene: FNIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 93 and hypertrophic cardiomyopathy, MIM# 619705; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10788 CYS1 Zornitza Stark Marked gene: CYS1 as ready
Mendeliome v0.10785 CAMK2G Zornitza Stark Marked gene: CAMK2G as ready
Mendeliome v0.10784 CAMK2G Zornitza Stark gene: CAMK2G was added
gene: CAMK2G was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CAMK2G was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMK2G were set to 30184290; 23033978
Phenotypes for gene: CAMK2G were set to Mental retardation, autosomal dominant 59, MIM# 618522
Review for gene: CAMK2G was set to AMBER
Added comment: Two unrelated individuals reported with de novo (p.Arg292Pro) variant. Functional data suggests GoF.
Sources: Expert Review
Mendeliome v0.10783 CSNK2B Zornitza Stark Marked gene: CSNK2B as ready
Mendeliome v0.10780 NCAPD3 Zornitza Stark Marked gene: NCAPD3 as ready
Mendeliome v0.10780 NCAPD3 Zornitza Stark Phenotypes for gene: NCAPD3 were changed from to Microcephaly 22, primary, autosomal recessive, MIM# 617984
Mendeliome v0.10776 NCAPD3 Zornitza Stark reviewed gene: NCAPD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 27737959; Phenotypes: Microcephaly 22, primary, autosomal recessive, MIM# 617984; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10776 CYP2C8 Zornitza Stark Marked gene: CYP2C8 as ready
Mendeliome v0.10774 HPGD Zornitza Stark Marked gene: HPGD as ready
Mendeliome v0.10774 HPGD Zornitza Stark Phenotypes for gene: HPGD were changed from to Hypertrophic osteoarthropathy, primary, autosomal recessive 1 MIM#259100; Cranioosteoarthropathy MIM#259100
Mendeliome v0.10771 GLMN Zornitza Stark Marked gene: GLMN as ready
Mendeliome v0.10768 GDI1 Zornitza Stark Marked gene: GDI1 as ready
Mendeliome v0.10764 NECTIN1 Zornitza Stark Marked gene: NECTIN1 as ready
Mendeliome v0.10761 AGR2 Zornitza Stark Marked gene: AGR2 as ready
Mendeliome v0.10760 AGR2 Zornitza Stark gene: AGR2 was added
gene: AGR2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AGR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGR2 were set to 34952832
Phenotypes for gene: AGR2 were set to CF-like disorder
Review for gene: AGR2 was set to GREEN
Added comment: 13 patients from 9 families with a CF-like phenotype consisting of recurrent lower respiratory infections (13/13), failure to thrive (13/13) and chronic diarrhoea (8/13), with high morbidity and mortality. All patients had biallelic variants in AGR2, (1) two splice-site variants, (2) gene deletion and (3) three missense variants.
Sources: Literature
Mendeliome v0.10759 HPGD Ain Roesley reviewed gene: HPGD: Rating: GREEN; Mode of pathogenicity: None; Publications: 20406614, 32282352, 31878983, 29282707; Phenotypes: Hypertrophic osteoarthropathy, primary, autosomal recessive 1 MIM#259100, Cranioosteoarthropathy MIM#259100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10759 IKZF2 Zornitza Stark Marked gene: IKZF2 as ready
Mendeliome v0.10758 IKZF2 Zornitza Stark gene: IKZF2 was added
gene: IKZF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IKZF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKZF2 were set to 34920454
Phenotypes for gene: IKZF2 were set to Immune dysregulation
Review for gene: IKZF2 was set to GREEN
Added comment: Six individuals with systemic lupus erythematosus, immune thrombocytopenia or EBV-associated haemophagocytic lymphohistiocytosis reported with variants in this gene. Patients exhibited hypogammaglobulinaemia, decreased number of T-follicular helper and NK-cells.
Sources: Literature
Mendeliome v0.10757 RHBDF2 Zornitza Stark Marked gene: RHBDF2 as ready
Mendeliome v0.10754 ANGPT2 Zornitza Stark Phenotypes for gene: ANGPT2 were changed from Lymphatic malformation-10, MIM#619369; Primary lymphoedema to Lymphatic malformation-10, MIM#619369; Primary lymphoedema; Hydrops
Mendeliome v0.10751 ANGPT2 Zornitza Stark edited their review of gene: ANGPT2: Added comment: Bi-allelic disease PMID 34876502: single family reported with four fetuses with hydrops fetalis homozygous for ANGPT2 NM_001147.2:c.557A>G. The consanguineous parents and surviving sibblings (a girl and a boy), were heterozygous for this variant. This variant is predicted to create a cryptic exonic splice site, resulting in a r.557_566del and nonsense-mediated mRNA decay. This prediction was supported by the lack of a transcript from this allele in the parents.; Changed publications: 32908006, 34876502; Changed phenotypes: Lymphatic malformation-10, MIM#619369, Primary lymphoedema, Hydrops; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.10751 BET1 Zornitza Stark Marked gene: BET1 as ready
Mendeliome v0.10750 BET1 Zornitza Stark gene: BET1 was added
gene: BET1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BET1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BET1 were set to 34779586
Phenotypes for gene: BET1 were set to Muscular dystrophy; Epilepsy
Review for gene: BET1 was set to AMBER
Added comment: Three individuals from 2 unrelated families reported.
Sources: Literature
Mendeliome v0.10749 PAX8 Zornitza Stark Marked gene: PAX8 as ready
Mendeliome v0.10746 PAPSS2 Zornitza Stark Marked gene: PAPSS2 as ready
Mendeliome v0.10741 UQCRC2 Zornitza Stark edited their review of gene: UQCRC2: Added comment: Third family with different variant reported, together with functional data.; Changed rating: GREEN; Changed publications: 28275242, 23281071, 33865955
Mendeliome v0.10740 STT3A Zornitza Stark Phenotypes for gene: STT3A were changed from Congenital disorder of glycosylation, type Iw MIM#615596 to Congenital disorder of glycosylation, type Iw, AR, OMIM #615596; Congenital disorder of glycosylation, type Iw, autosomal dominant, MIM# 619714
Mendeliome v0.10739 FMN2 Zornitza Stark Marked gene: FMN2 as ready
Mendeliome v0.10736 HAND1 Zornitza Stark Marked gene: HAND1 as ready
Mendeliome v0.10733 HAND1 Zornitza Stark Phenotypes for gene: HAND1 were changed from to Congenital heart disease, MONDO:0005453
Mendeliome v0.10732 ILK Zornitza Stark Marked gene: ILK as ready
Mendeliome v0.10732 ILK Zornitza Stark Phenotypes for gene: ILK were changed from to Dilated cardiomyopathy
Mendeliome v0.10728 ILK Zornitza Stark reviewed gene: ILK: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dilated cardiomyopathy; Mode of inheritance: None
Mendeliome v0.10728 ZIC4 Zornitza Stark Marked gene: ZIC4 as ready
Mendeliome v0.10728 ZIC4 Zornitza Stark Added comment: Comment when marking as ready: Two individuals reported with a deletion of ZIC1 and ZIC4 and Dandy-Walker malformation.
Mendeliome v0.10726 FKBP10 Zornitza Stark Marked gene: FKBP10 as ready
Mendeliome v0.10723 FAM46A Zornitza Stark Marked gene: FAM46A as ready
Mendeliome v0.10720 DYNC1I1 Zornitza Stark Marked gene: DYNC1I1 as ready
Mendeliome v0.10719 GATA5 Zornitza Stark Marked gene: GATA5 as ready
Mendeliome v0.10719 GATA5 Zornitza Stark Phenotypes for gene: GATA5 were changed from to Congenital heart defects, multiple types, 5 - #617912
Mendeliome v0.10715 MYPN Zornitza Stark Marked gene: MYPN as ready
Mendeliome v0.10715 MYPN Zornitza Stark Phenotypes for gene: MYPN were changed from to Nemaline myopathy 11, autosomal recessive MIM#617336 AR; cardiomyopathy MIM#615248 AD
Mendeliome v0.10711 MSTO1 Zornitza Stark Marked gene: MSTO1 as ready
Mendeliome v0.10711 MSTO1 Zornitza Stark Phenotypes for gene: MSTO1 were changed from to Myopathy, mitochondrial, and ataxia, OMIM:617675; Mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome, MONDO:0044714
Mendeliome v0.10708 MSTO1 Zornitza Stark reviewed gene: MSTO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28554942, 28544275, 31604776, 31463572, 31130378, 30684668, 29339779; Phenotypes: Myopathy, mitochondrial, and ataxia, OMIM:617675, Mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome, MONDO:0044714; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10708 MDH2 Zornitza Stark Marked gene: MDH2 as ready
Mendeliome v0.10705 FOXH1 Zornitza Stark Marked gene: FOXH1 as ready
Mendeliome v0.10705 FOXH1 Zornitza Stark Phenotypes for gene: FOXH1 were changed from to Congenital heart disease; holoprosencephaly
Mendeliome v0.10701 MBOAT7 Zornitza Stark Marked gene: MBOAT7 as ready
Mendeliome v0.10698 HAND2 Krithika Murali reviewed gene: HAND2: Rating: AMBER; Mode of pathogenicity: None; Publications: 26865696, 32134193, 26676105, 30217752, 20819618; Phenotypes: Congenital heart disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10698 SIN3A Zornitza Stark Marked gene: SIN3A as ready
Mendeliome v0.10695 SYN1 Zornitza Stark Marked gene: SYN1 as ready
Mendeliome v0.10695 SYN1 Zornitza Stark Phenotypes for gene: SYN1 were changed from to Epilepsy, X-linked, with variable learning disabilities and behaviour disorders, MIM# 300491; Intellectual developmental disorder, X-linked 50, MIM# 300115
Mendeliome v0.10692 SYN1 Zornitza Stark reviewed gene: SYN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14985377, 21441247, 28973667, 21441247, 34243774; Phenotypes: Epilepsy, X-linked, with variable learning disabilities and behaviour disorders, MIM# 300491, Intellectual developmental disorder, X-linked 50, MIM# 300115; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.10692 DCC Zornitza Stark Marked gene: DCC as ready
Mendeliome v0.10689 SNX10 Zornitza Stark Marked gene: SNX10 as ready
Mendeliome v0.10686 MEOX1 Zornitza Stark Marked gene: MEOX1 as ready
Mendeliome v0.10683 OTUD6B Zornitza Stark Marked gene: OTUD6B as ready
Mendeliome v0.10680 OTUD6B Zornitza Stark changed review comment from: IDDFSDA is a severe multisystem disorder characterized by global developmental delay, microcephaly, absent speech, hypotonia, growth retardation with prenatal onset, feeding difficulties, structural brain abnormalities, congenital malformations including congenital heart disease, and musculoskeletal features. In 2017, 12 patients from 6 unrelated families with IDDFSDA identified with 4 homozygous mutations in the OTUD6B gene (WES and Sanger, and segregated with the disorder in the families). Other cases reported since. Suitable for fetal anomalies panel.; to: IDDFSDA is a severe multisystem disorder characterized by global developmental delay, microcephaly, absent speech, hypotonia, growth retardation with prenatal onset, feeding difficulties, structural brain abnormalities, congenital malformations including congenital heart disease, and musculoskeletal features. In 2017, 12 patients from 6 unrelated families with IDDFSDA identified with 4 homozygous mutations in the OTUD6B gene (WES and Sanger, and segregated with the disorder in the families). Other cases reported since.
Mendeliome v0.10680 SERPINH1 Zornitza Stark Marked gene: SERPINH1 as ready
Mendeliome v0.10677 SERPINF1 Zornitza Stark Marked gene: SERPINF1 as ready
Mendeliome v0.10674 PITX1 Zornitza Stark Marked gene: PITX1 as ready
Mendeliome v0.10671 ICAM1 Zornitza Stark Marked gene: ICAM1 as ready
Mendeliome v0.10670 IRAK3 Zornitza Stark Marked gene: IRAK3 as ready
Mendeliome v0.10669 CAPN10 Zornitza Stark Marked gene: CAPN10 as ready
Mendeliome v0.10666 SPARC Zornitza Stark Marked gene: SPARC as ready
Mendeliome v0.10666 SPARC Zornitza Stark Gene: sparc has been classified as Green List (High Evidence).
Mendeliome v0.10666 SPARC Zornitza Stark Phenotypes for gene: SPARC were changed from to Osteogenesis imperfecta, type XVII, MIM# 616507
Mendeliome v0.10665 SPARC Zornitza Stark Publications for gene: SPARC were set to
Mendeliome v0.10664 SPARC Zornitza Stark Mode of inheritance for gene: SPARC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10663 SPARC Zornitza Stark reviewed gene: SPARC: Rating: GREEN; Mode of pathogenicity: None; Publications: 26027498, 34462290; Phenotypes: Osteogenesis imperfecta, type XVII, MIM# 616507; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10663 WNT7A Seb Lunke Marked gene: WNT7A as ready
Mendeliome v0.10660 XYLT1 Seb Lunke Marked gene: XYLT1 as ready
Mendeliome v0.10658 ZIC1 Seb Lunke Marked gene: ZIC1 as ready
Mendeliome v0.10656 STRADA Zornitza Stark Marked gene: STRADA as ready
Mendeliome v0.10652 YAP1 Zornitza Stark Marked gene: YAP1 as ready
Mendeliome v0.10652 YAP1 Zornitza Stark Phenotypes for gene: YAP1 were changed from to Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mental retardation, MIM#120433
Mendeliome v0.10649 YAP1 Zornitza Stark reviewed gene: YAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24462371, 27267789, 28801591; Phenotypes: Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mental retardation, MIM#120433; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10649 WDR73 Zornitza Stark Marked gene: WDR73 as ready
Mendeliome v0.10646 USP18 Zornitza Stark Marked gene: USP18 as ready
Mendeliome v0.10643 HAND1 Krithika Murali reviewed gene: HAND1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31286141, 29016838, 29317578, 29179274, 28112363, 27942761, 26581070; Phenotypes: Congenital heart defects; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10643 ILK Paul De Fazio reviewed gene: ILK: Rating: AMBER; Mode of pathogenicity: None; Publications: 17646580, 27886618, 25163546; Phenotypes: Dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.10643 GATA5 Krithika Murali reviewed gene: GATA5: Rating: AMBER; Mode of pathogenicity: None; Publications: 28180938, 27066509, 34461831, 30229885, 28285006, 25543888, 25515806, 24796370, 23295592, 23289003, 22961344; Phenotypes: Congenital heart defects, multiple types, 5 - #617912; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10643 TBX22 Zornitza Stark Marked gene: TBX22 as ready
Mendeliome v0.10640 MYPN Ain Roesley reviewed gene: MYPN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nemaline myopathy 11, autosomal recessive MIM#617336 AR, cardiomyopathy MIM#615248 AD; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10640 MYL9 Ain Roesley edited their review of gene: MYL9: Added comment: PMID:32621347;
3rd family with non-consanguineous parents and 3 TOPs. 2 were genotyped and found to be hom for the same deletion of exon 4 as reported by PMID: 29453416

Possibly 4th proband in PMID: 33264186 but specifics including genotype were lacking and overlapping institute/hospital as PMID: 33031641; Changed publications: 32621347, 33264186
Mendeliome v0.10640 FOXH1 Krithika Murali reviewed gene: FOXH1: Rating: AMBER; Mode of pathogenicity: None; Publications: 18538293, 19933292, 32003456, 12094232, 16304598; Phenotypes: Congenital heart disease, holoprosencephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10640 LMBRD2 Zornitza Stark Phenotypes for gene: LMBRD2 were changed from Global developmental delay; Intellectual disability; Microcephaly; Seizures; Abnormality of nervous system morphology; Abnormality of the eye to Developmental delay with variable neurologic and brain abnormalities, MIM# 619694; Global developmental delay; Intellectual disability; Microcephaly; Seizures; Abnormality of nervous system morphology; Abnormality of the eye
Mendeliome v0.10639 LMBRD2 Zornitza Stark edited their review of gene: LMBRD2: Changed phenotypes: Developmental delay with variable neurologic and brain abnormalities, MIM# 619694, Global developmental delay, Intellectual disability, Microcephaly, Seizures, Abnormality of nervous system morphology, Abnormality of the eye
Mendeliome v0.10639 OGDHL Zornitza Stark Phenotypes for gene: OGDHL were changed from Neurodevelopmental disorder featuring epilepsy, hearing loss, visual impairment, and ataxia to Yoon-Bellen neurodevelopmental syndrome, MIM# 619701; Neurodevelopmental disorder featuring epilepsy, hearing loss, visual impairment, and ataxia
Mendeliome v0.10638 ANAPC7 Zornitza Stark Marked gene: ANAPC7 as ready
Mendeliome v0.10637 ANAPC7 Zornitza Stark gene: ANAPC7 was added
gene: ANAPC7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ANAPC7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANAPC7 were set to 34942119
Phenotypes for gene: ANAPC7 were set to Ferguson-Bonni neurodevelopmental syndrome, MIM# 619699
Review for gene: ANAPC7 was set to AMBER
Added comment: 11 individuals of Amish heritage reported homozygous for an intragenic deletion. Clinical features included ID, hypotonia, deafness in 5, relatively small head size (but microcephaly only in 1), and occasional congenital anomalies.

Supportive mouse model.

Amber rating in light of this being a founder variant.
Sources: Literature
Mendeliome v0.10636 DLX5 Zornitza Stark Marked gene: DLX5 as ready
Mendeliome v0.10636 DLX5 Zornitza Stark Phenotypes for gene: DLX5 were changed from to Split-hand/foot malformation 1 with sensorineural hearing loss MIM#220600; Split-hand/foot malformation 1 MIM#183600
Mendeliome v0.10633 DLX5 Zornitza Stark changed review comment from: A homozygous missense mutation (Q178P) was identified in 2 affected sisters from a consanguineous Yemeni family with split-hand/foot malformation and hearing loss, who had no detectable chromosomal aberration, Shamseldin et al. (2012).

A heterozygosity missense mutation (Q186H) was identified in a 31-year-old Chinese woman with SHFM, Wang et al. (2014).
A heterozygosity nonsense mutationIn (E39X) was identified in the probands from 2 unrelated Polish families with isolated SHFM, Sowinska-Seidler et al. (2014).

Animal model evidence - mouse; to: A homozygous missense mutation (Q178P) was identified in 2 affected sisters from a consanguineous Yemeni family with split-hand/foot malformation and hearing loss, who had no detectable chromosomal aberration, Shamseldin et al. (2012).

A heterozygosity missense mutation (Q186H) was identified in a 31-year-old Chinese woman with SHFM, Wang et al. (2014).
A heterozygosity nonsense mutationIn (E39X) was identified in the probands from 2 unrelated Polish families with isolated SHFM, Sowinska-Seidler et al. (2014).

Animal model evidence - mouse

Green for mono-allelic, Amber for bi-allelic.
Mendeliome v0.10633 DLX5 Zornitza Stark reviewed gene: DLX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22121204, 24496061, 25196357, 20534536, 12112878; Phenotypes: Split-hand/foot malformation 1 with sensorineural hearing loss MIM#220600, Split-hand/foot malformation 1 MIM#183600; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10632 GUCY2C Zornitza Stark Marked gene: GUCY2C as ready
Mendeliome v0.10632 GUCY2C Zornitza Stark Phenotypes for gene: GUCY2C were changed from to Diarrhoea 6, MIM# 614616; Meconium ileus, MIM# 614665
Mendeliome v0.10629 GUCY2C Zornitza Stark reviewed gene: GUCY2C: Rating: GREEN; Mode of pathogenicity: None; Publications: 22521417, 22436048, 25994218, 30353760, 28957388, 22521417, 33883099, 31079856; Phenotypes: Diarrhoea 6, MIM# 614616, Meconium ileus, MIM# 614665; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10629 GPC3 Zornitza Stark Marked gene: GPC3 as ready
Mendeliome v0.10627 PDCD10 Zornitza Stark Marked gene: PDCD10 as ready
Mendeliome v0.10624 LGI4 Zornitza Stark Marked gene: LGI4 as ready
Mendeliome v0.10624 LGI4 Zornitza Stark Phenotypes for gene: LGI4 were changed from to Arthrogryposis multiplex congenita, neurogenic, with myelin defect, MIM#617468
Mendeliome v0.10621 LGI4 Zornitza Stark reviewed gene: LGI4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28318499, 34288120; Phenotypes: Arthrogryposis multiplex congenita, neurogenic, with myelin defect, MIM#617468; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10621 LFNG Zornitza Stark Marked gene: LFNG as ready
Mendeliome v0.10618 SLC39A7 Zornitza Stark Phenotypes for gene: SLC39A7 were changed from Antibody deficiency; early onset infections; blistering dermatosis; failure to thrive; thrombocytopaenia to Agammaglobulinaemia 9, autosomal recessive, MIM# 619693; Antibody deficiency; early onset infections; blistering dermatosis; failure to thrive; thrombocytopaenia
Mendeliome v0.10617 SLC39A7 Zornitza Stark edited their review of gene: SLC39A7: Changed phenotypes: Agammaglobulinemia 9, autosomal recessive, MIM# 619693, Antibody deficiency, early onset infections, blistering dermatosis, failure to thrive, thrombocytopaenia
Mendeliome v0.10617 RNF220 Zornitza Stark Phenotypes for gene: RNF220 were changed from Leukodystrophy; CNS hypomyelination; Ataxia; Intellectual disability; Sensorineural hearing impairment; Elevated hepatic transaminases; Hepatic fibrosis; Dilated cardiomyopathy; Spastic paraplegia; Dysarthria; Abnormality of the corpus callosum to Leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy, MIM# 619688; Leukodystrophy; CNS hypomyelination; Ataxia; Intellectual disability; Sensorineural hearing impairment; Elevated hepatic transaminases; Hepatic fibrosis; Dilated cardiomyopathy; Spastic paraplegia; Dysarthria; Abnormality of the corpus callosum
Mendeliome v0.10616 RNF220 Zornitza Stark edited their review of gene: RNF220: Changed phenotypes: Leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy, MIM# 619688, Leukodystrophy, CNS hypomyelination, Ataxia, Intellectual disability, Sensorineural hearing impairment, Elevated hepatic transaminases, Hepatic fibrosis, Dilated cardiomyopathy, Spastic paraplegia, Dysarthria, Abnormality of the corpus callosum
Mendeliome v0.10616 SLC33A1 Zornitza Stark Marked gene: SLC33A1 as ready
Mendeliome v0.10616 SLC33A1 Zornitza Stark Phenotypes for gene: SLC33A1 were changed from to Congenital cataracts, hearing loss, and neurodegeneration, MIM# 614482; Spastic paraplegia 42, autosomal dominant, MIM# 612539
Mendeliome v0.10613 SLC33A1 Zornitza Stark reviewed gene: SLC33A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31194315, 19061983, 20461110; Phenotypes: Congenital cataracts, hearing loss, and neurodegeneration, MIM# 614482, Spastic paraplegia 42, autosomal dominant, MIM# 612539; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10613 ITPKC Zornitza Stark Marked gene: ITPKC as ready
Mendeliome v0.10611 MAMLD1 Zornitza Stark Marked gene: MAMLD1 as ready
Mendeliome v0.10608 INPP5K Zornitza Stark Marked gene: INPP5K as ready
Mendeliome v0.10608 INPP5K Zornitza Stark Phenotypes for gene: INPP5K were changed from to Muscular dystrophy, congenital, with cataracts and intellectual disability MIM#617404
Mendeliome v0.10605 IGFBP7 Zornitza Stark Marked gene: IGFBP7 as ready
Mendeliome v0.10605 IGFBP7 Zornitza Stark Phenotypes for gene: IGFBP7 were changed from to Retinal arterial macroaneurysm with supravalvular pulmonic stenosis MIM#614224
Mendeliome v0.10601 IGFBP7 Zornitza Stark reviewed gene: IGFBP7: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinal arterial macroaneurysm with supravalvular pulmonic stenosis MIM#614224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10600 KISS1R Zornitza Stark Marked gene: KISS1R as ready
Mendeliome v0.10597 IDH1 Zornitza Stark Marked gene: IDH1 as ready
Mendeliome v0.10593 HNRNPH2 Zornitza Stark Marked gene: HNRNPH2 as ready
Mendeliome v0.10590 KCNT1 Zornitza Stark Marked gene: KCNT1 as ready
Mendeliome v0.10590 KCNT1 Zornitza Stark Phenotypes for gene: KCNT1 were changed from to Epilepsy, nocturnal frontal lobe, 5, MIM# 615005; Epileptic encephalopathy, early infantile, 14, MIM# 614959
Mendeliome v0.10587 KCNT1 Zornitza Stark reviewed gene: KCNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23086397, 23086396, 31872048, 31532509; Phenotypes: Epilepsy, nocturnal frontal lobe, 5, MIM# 615005, Epileptic encephalopathy, early infantile, 14, MIM# 614959; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10587 ITPKC Ain Roesley changed review comment from: Currently no mendelian gene-disease assocation. Best known for polymorphisms associated with Kawasaki disease susceptibility.

KO mouse models looking at protein expression and effect on multiciliary beating frequency and spermatozoa, no significant defects in both; to: Currently no mendelian gene-disease association. Best known for polymorphisms associated with Kawasaki disease susceptibility.

KO mouse models looking at tissue protein expression and effect on multiciliary beating frequency and spermatozoa, no significant defects in both
Mendeliome v0.10586 PRKAR1B Zornitza Stark Phenotypes for gene: PRKAR1B were changed from Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Aggressive behavior; Abnormality of movement; Upslanted palpebral fissure to Marbach-Schaaf neurodevelopmental syndrome MIM#619680; Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Aggressive behavior; Abnormality of movement; Upslanted palpebral fissure
Mendeliome v0.10585 PRKAR1B Zornitza Stark Mode of inheritance for gene: PRKAR1B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10582 TOPORS Zornitza Stark Phenotypes for gene: TOPORS were changed from Retinitis pigmentosa 31 (MIM#609923) to Retinitis pigmentosa 31 (MIM#609923); Ciliopathy, MONDO:0005308, TOPORS-associated, AR
Mendeliome v0.10579 TLR8 Zornitza Stark Phenotypes for gene: TLR8 were changed from Immunodeficiency; bone marrow failure to Immunodeficiency; bone marrow failure; Autoinflammatory syndrome MONDO:0019751
Mendeliome v0.10577 TLR8 Zornitza Stark edited their review of gene: TLR8: Added comment: PMID 34981838: Monozygotic male twins, hemizygous for the G572V (maternally inherited), who suffer from severe autoimmune haemolytic anemia (AIHA) worsening with infections, and autoinflammation presenting as fevers, enteritis, arthritis and CNS vasculitis. Functional showed variant causes impaired stability of the TLR8 protein, cross-reactivity to TLR7 ligands and reduced ability of TLR8 to attenuate TLR7 signaling.; Changed publications: 33512449, 34981838; Changed phenotypes: Immunodeficiency, bone marrow failure, Autoinflammatory syndrome MONDO:0019751
Mendeliome v0.10577 MARS Zornitza Stark Phenotypes for gene: MARS were changed from Interstitial lung and liver disease, MIM#615486; Charcot-Marie-Tooth disease, axonal, type 2U, MIM# 616280; Trichothiodystrophy, MONDO:0018053 to Interstitial lung and liver disease, MIM#615486; Charcot-Marie-Tooth disease, axonal, type 2U, MIM# 616280; Trichothiodystrophy 9, nonphotosensitive, MIM# 619692
Mendeliome v0.10576 AARS Zornitza Stark Phenotypes for gene: AARS were changed from Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287; trichothiodystrophy, MONDO:0018053; Leukoencephalopathy, hereditary diffuse, with spheroids 2, MIM# 619661 to Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287; Spastic paraplegia 85, autosomal recessive, MIM# 619686; Ataxia, sensory, 1, autosomal dominant, MIM# 608984; Leukoencephalopathy, hereditary diffuse, with spheroids 2, MIM# 619661
Mendeliome v0.10575 RNF170 Zornitza Stark Marked gene: RNF170 as ready
Mendeliome v0.10575 RNF170 Zornitza Stark Phenotypes for gene: RNF170 were changed from to Spastic paraplegia 85, autosomal recessive, MIM# 619686; Ataxia, sensory, 1, autosomal dominant, MIM# 608984
Mendeliome v0.10573 RNF170 Zornitza Stark reviewed gene: RNF170: Rating: GREEN; Mode of pathogenicity: None; Publications: 31636353, 21115467, 32943585; Phenotypes: Spastic paraplegia 85, autosomal recessive, MIM# 619686, Ataxia, sensory, 1, autosomal dominant, MIM# 608984; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10573 INPP5K Ain Roesley changed review comment from: At least 20 probands reported thus far.
Noted that Val23Met is an Italian founder mutation and Ile50thr is a Paskitani/Bangladeshi founder; to: At least 20 probands reported thus far.
Noted that Val23Met is an Italian founder mutation and Ile50thr is a Pakistani/Bangladeshi founder
Mendeliome v0.10573 INPP5K Ain Roesley changed review comment from: At least 20 probands reported thus far.
Noted that Val23Met is an Italian founder mutation; to: At least 20 probands reported thus far.
Noted that Val23Met is an Italian founder mutation and Ile50thr is a Paskitani/Bangladeshi founder
Mendeliome v0.10573 INPP5K Ain Roesley reviewed gene: INPP5K: Rating: GREEN; Mode of pathogenicity: None; Publications: 28190456, 28190459, 28940338, 31630891, 33193651, 33792664; Phenotypes: Muscular dystrophy, congenital, with cataracts and intellectual disability MIM#617404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10573 IGFBP7 Ain Roesley reviewed gene: IGFBP7: Rating: RED; Mode of pathogenicity: None; Publications: 34519236, 31730227, 32429784; Phenotypes: Retinal arterial macroaneurysm with supravalvular pulmonic stenosis MIM#614224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10572 AARS Zornitza Stark Phenotypes for gene: AARS were changed from Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287; trichothiodystrophy, MONDO:0018053 to Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287; trichothiodystrophy, MONDO:0018053; Leukoencephalopathy, hereditary diffuse, with spheroids 2, MIM# 619661
Mendeliome v0.10571 AARS Zornitza Stark Publications for gene: AARS were set to 28493438; 25817015; 20045102; 22009580; 22206013; 30373780; 26032230; 33909043
Mendeliome v0.10570 AARS Zornitza Stark edited their review of gene: AARS: Added comment: PMID 31775912: single multigenerational family with leukoencephalopathy segregating AARS1 variant.; Changed publications: 28493438, 25817015, 20045102, 22009580, 22206013, 30373780, 26032230, 31775912; Changed phenotypes: Epileptic encephalopathy, early infantile, 29, MIM# 616339, Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287, Leukoencephalopathy, hereditary diffuse, with spheroids 2, MIM# 619661
Mendeliome v0.10570 CRACR2A Zornitza Stark Marked gene: CRACR2A as ready
Mendeliome v0.10570 CRACR2A Zornitza Stark Added comment: Comment when marking as ready: Single individual.
Mendeliome v0.10570 CRACR2A Zornitza Stark Phenotypes for gene: CRACR2A were changed from Late onset combined immunodeficiency to primary immunodeficiency disease, MONDO:0003778, CRACR2A-associated; Late onset combined immunodeficiency
Mendeliome v0.10567 PRDM13 Zornitza Stark Phenotypes for gene: PRDM13 were changed from Retinal dystrophy; Chorioretinal atrophy, progressive bifocal, MIM# 600790 to Retinal dystrophy; Chorioretinal atrophy, progressive bifocal, MIM# 600790; intellectual disability, MONDO:0001071, PRDM13-associated; ataxia with cerebellar hypoplasia, MONDO:0016054, PRDM13-associated; congenital hypogonadotropic hypogonadism, MONDO:0015770
Mendeliome v0.10564 PRDM13 Zornitza Stark Marked gene: PRDM13 as ready
Mendeliome v0.10564 PRDM13 Zornitza Stark Added comment: Comment when marking as ready: Bi-allelic variants: Recessive disease causing ID and DSD described in three reportedly unrelated families (2 consanguineous), but all are from Malta, and all share the same 13bp deletion spanning an exon-intron boundary. Mouse KO is embryonically lethal, and tissue specific KO failed to replicate many of the patients phenotypes, other than hypoplasia of the cerebellar vermis and hemispheres at P21.
Mendeliome v0.10563 ATP5A1 Naomi Baker edited their review of gene: ATP5A1: Added comment: PMID: 34954817 reports three individuals with de novo monoallelic missense variants. One of these is the recurrent p.(Arg207His) variant while the other two variants are different substitutions. The three patients presented with a variable phenotypes: (1) a 14-year-old girl who presented during the first few months of life with developmental delay, failure-to-thrive, and lactic acidosis. She recovered and had no persistent neurologic phenotype; (2) a 17-year-old boy with psychomotor delay, intellectual disability, ataxia, spastic paraparesis, and dystonia; (3) a 12-year-old girl with psychomotor retardation, spastic tetraparesis, generalized dystonia, absent speech, swallowing problems, and increased blood lactate concentrations. Enzymatic investigations of muscle tissue from patient 1 showed a decrease in ATPase activity.; Changed publications: PMID: 34954817
Mendeliome v0.10563 ATP5G3 Seb Lunke Marked gene: ATP5G3 as ready
Mendeliome v0.10561 ATP5G3 Naomi Baker edited their review of gene: ATP5G3: Added comment: Note that HGNC approved gene name is ATP5MC3.

PMID: 34636445 reports a missense variant identified in a large single-family pedigree with dystonia and spastic paraplegia. The variant was identified via exome sequencing of the proband and a distant cousin, focussing on variants within the previously determined linkage region. The identical missense variant was also identified in a patient with childhood onset dystonic syndrome and was shown to be de novo. Functional studies of fibroblast cell lines from affected father (HSP) and proband of large family demonstrated decreased complex V function. A drosophila model containing the missense variant had reduced mobility and reduced complex V activity.

PMID: 34954817 reports de novo monoallelic missense variants in three individuals, however one of these individuals was reported in above paper. The other two patients were: (1) a-15-year-old girl with milestone delay, pyramidal signs, and generalized dystonia with prominent upper-body involvement, and (2) a 6-year-old boy with delayed psychomotor development, lower-extremity spasticity, and elevated blood lactate levels; Changed rating: GREEN; Changed publications: PMID: 34636445, 34954817
Mendeliome v0.10561 PRDM13 Seb Lunke reviewed gene: PRDM13: Rating: AMBER; Mode of pathogenicity: None; Publications: 34730112; Phenotypes: intellectual disability, MONDO:0001071, PRDM13-associated, ataxia with cerebellar hypoplasia, MONDO:MONDO:0016054. PRDM13-associated, congenital hypogonadotropic hypogonadism, MONDO:0015770 Edit; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10561 CCND2 Alison Yeung Marked gene: CCND2 as ready
Mendeliome v0.10558 PPIA Seb Lunke Marked gene: PPIA as ready
Mendeliome v0.10558 ATP5G3 Naomi Baker gene: ATP5G3 was added
gene: ATP5G3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP5G3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP5G3 were set to PMID: 34636445
Phenotypes for gene: ATP5G3 were set to Dystonia, early-onset, and/or spastic paraplegia, MIM#619681
Review for gene: ATP5G3 was set to AMBER
Added comment: Note that new gene name is ATP5MC3.

Paper reports the same missense variant identified in a large single-family pedigree with dystonia and spastic paraplegia, and also de novo in a patient with childhood onset dystonic syndrome. Drosophila model with missense variant also studied. Functional studies of fibroblast cells lines from affected father and proband demonstrated decreased complex V function.
Sources: Literature
Mendeliome v0.10558 RPL10L Alison Yeung Marked gene: RPL10L as ready
Mendeliome v0.10558 RPL10L Alison Yeung Added comment: Comment on list classification: heterozygous variants in three unrelated patients presenting with azoospermia. Given the common phenotype, need a few more cases to convert to green list.
Mendeliome v0.10557 DNHD1 Seb Lunke Marked gene: DNHD1 as ready
Mendeliome v0.10556 PRKAR1B Paul De Fazio reviewed gene: PRKAR1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 33833410; Phenotypes: Marbach-Schaaf neurodevelopmental syndrome MIM#619680; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.10556 NAA10 Ain Roesley edited their review of gene: NAA10: Added comment: For Ogden association:
lethal X-linked. 9 males from 3 families with recurrent Ser37Pro
All presenting the distinctive and recognizable phenotype, which includes mostly postnatal growth retardation, global severe developmental delay, characteristic craniofacial features, and structural cardiac anomalies and/or arrhythmias

For non-lethal syndromic ID:
reported in 10 males and (mostly de novo) in 37 females
variants causing this are missense located along the protein and 1 truncating

For syndromic microopththamia: variants are in the UTR; Changed mode of inheritance: Other
Mendeliome v0.10556 RPL10L Dean Phelan gene: RPL10L was added
gene: RPL10L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPL10L was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RPL10L were set to PMID:32111475
Phenotypes for gene: RPL10L were set to MONDO_0004983, oligo-/azoospermia
Review for gene: RPL10L was set to AMBER
Added comment: PMID:32111475 - cohort study of patients with oligo-/azoospermia identified a homozygous variant in two brothers with severe oligozoospermia. Three additional patients with oligo-/azoospermia had heterozygous variants. No RPL10L variants were found in the fertile control subjects.

A further search did not identify additional publications.
Sources: Literature
Mendeliome v0.10556 SLC35F1 Seb Lunke Marked gene: SLC35F1 as ready
Mendeliome v0.10554 MYH1 Seb Lunke Marked gene: MYH1 as ready
Mendeliome v0.10554 CRACR2A Alison Yeung Marked gene: CRACR2A as ready
Mendeliome v0.10554 PPIA Naomi Baker gene: PPIA was added
gene: PPIA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPIA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPIA were set to PMID: 34972208
Phenotypes for gene: PPIA were set to amyotrophic lateral sclerosis, MONDO:0004976
Review for gene: PPIA was set to RED
Added comment: Paper characterizes a knockout mouse model that recapitulates key features of ALS-FTD. Also identified a heterozygous missense variant in one patient with sporadic amyotrophic lateral sclerosis. Functional studies of the missense variant suggest loss-of-function.
Sources: Literature
Mendeliome v0.10553 DNHD1 Daniel Flanagan gene: DNHD1 was added
gene: DNHD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNHD1 were set to 34932939
Phenotypes for gene: DNHD1 were set to Male infertility due to sperm motility disorder (MONDO:0018395)
Review for gene: DNHD1 was set to GREEN
Added comment: Biallelic DNHD1 variants identified in 8 unrelated probands with asthenoteratozoospermia, reduced sperm motility and abnormal sperm morphology. DNHD1 knockout mice were infertile and had significantly reduced sperm concentration and motility rates, consistent with human individuals.
Sources: Literature
Mendeliome v0.10552 TOPORS Dean Phelan reviewed gene: TOPORS: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID:34132027; Phenotypes: Postaxial polydactyly:multiple lingual hamartomas:dysmorphic features; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10552 PI4KA Paul De Fazio reviewed gene: PI4KA: Rating: GREEN; Mode of pathogenicity: None; Publications: 34415310; Phenotypes: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis MIM#616531, Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis MONDO:0014679; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10552 SLC35F1 Ain Roesley gene: SLC35F1 was added
gene: SLC35F1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC35F1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SLC35F1 were set to 33821533
Phenotypes for gene: SLC35F1 were set to Rett-like syndrome
Penetrance for gene: SLC35F1 were set to unknown
Review for gene: SLC35F1 was set to RED
gene: SLC35F1 was marked as current diagnostic
Added comment: WES found a de novo heterozygous c.1037T>C; p.(I346T) (absent in gnomad v2 and v3) in a female described to have Rett-like syndrome.

Global developmental delay, generalized tonic andtonic–clonic seizure, never acquired independent walking and developed spastictetraplegia in adulthood and limited speech

no protein functional work was performed
Sources: Literature
Mendeliome v0.10552 CRACR2A Dean Phelan gene: CRACR2A was added
gene: CRACR2A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CRACR2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRACR2A were set to PMID:34908525
Phenotypes for gene: CRACR2A were set to Late onset combined immunodeficiency
Review for gene: CRACR2A was set to AMBER
Added comment: PMID:34908525 - one patient compound het (missense and PTC) with late onset combined immunodeficiency (current chest infections, panhypogammaglobulinemia and CD4+T cell lymphopenia). Functional studies showed defective JNK phosphorylation, defective SOCE and impaired cytokine production.

Further search did not identify any additional publications.
Sources: Literature
Mendeliome v0.10552 MYH1 Ain Roesley gene: MYH1 was added
gene: MYH1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYH1 were set to 33755318
Phenotypes for gene: MYH1 were set to recurrent rhabdomyolysis
Penetrance for gene: MYH1 were set to unknown
Review for gene: MYH1 was set to RED
gene: MYH1 was marked as current diagnostic
Added comment: 18 yr old male from a consaguineous family.
WES was performed and a homozygous c.1295A>C:p.K432T was found. Only 1 het in gnomad v2 and v3.
no protein functional work was done
Sources: Literature
Mendeliome v0.10552 GNAO1 Zornitza Stark Phenotypes for gene: GNAO1 were changed from Epileptic encephalopathy, early infantile, 17; Neurodevelopmental disorder with involuntary movements to Epileptic encephalopathy, early infantile, 17, MIM#615473; Neurodevelopmental disorder with involuntary movements, MIM# 617493
Mendeliome v0.10551 PAK2 Zornitza Stark Marked gene: PAK2 as ready
Mendeliome v0.10550 PAK2 Arina Puzriakova gene: PAK2 was added
gene: PAK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PAK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAK2 were set to 33693784
Phenotypes for gene: PAK2 were set to Knobloch 2 syndrome
Review for gene: PAK2 was set to RED
Added comment: Antonarakis et al., 2021 (PMID: 33693784) reported two affected siblings from a non-consanguineous New Zealand family. Both had retinal detachment and interstitial parenchymal pulmonary changes on chest X-rays, but only one child had additional significant features such as cataract, posterior encephalocele, severe DD/ID with ASD, and epilepsy. WES revealed a heterozygous PAK2 variant (c.1303 G>A, p.Glu435Lys) in both individuals that apparently occurred de novo indicating parental germ-line mosaicism; however, mosaicism could not be detected by deep sequencing of blood parental DNA. Functional studies showed that the variant, located in the kinase domain, results in a partial loss of the kinase activity.
Sources: Literature
Mendeliome v0.10550 OGDH Zornitza Stark Phenotypes for gene: OGDH were changed from Developmental delay; ataxia; seizure; raised lactate to Oxoglutarate dehydrogenase deficiency, MIM# 203740; Developmental delay; ataxia; seizure; raised lactate
Mendeliome v0.10549 OGDH Zornitza Stark edited their review of gene: OGDH: Changed phenotypes: Oxoglutarate dehydrogenase deficiency, MIM# 203740, Developmental delay, ataxia, seizure, raised lactate
Mendeliome v0.10549 TBX2 Zornitza Stark Marked gene: TBX2 as ready
Mendeliome v0.10549 TBX2 Zornitza Stark Phenotypes for gene: TBX2 were changed from to Vertebral anomalies and variable endocrine and T-cell dysfunction - MIM#618223
Mendeliome v0.10545 SLC27A4 Zornitza Stark Marked gene: SLC27A4 as ready
Mendeliome v0.10542 TBX2 Krithika Murali changed review comment from: Liu et al. (2018) reported 4 affected individuals from 2 unrelated families with congenital cardiac defects (ASD, PDA, double outlet right ventricle, pulmonary stenosis), skeletal abnormalities (camptodactyly, congenital fusion thoracic spine, hemivertebrae ).Thymus aplasia/hypoplasia, cleft palate also noted. Other associated features include - facial dysmorphisms, variable developmental delay, and endocrine system disorders (e.g. autoimmune hypothyroidism, hypoparathyroidism).

PMID23727221 and PMID30223900 - TBX2 gene and TBX2 gene promoter sequencing in congenital heart disease cohorts versus controls - not enough supportive evidence for variant pathogenicity, including no segregation data. Variants prevalent in population databases also included as likely pathogenic.

PMID 20635360 - de novo dup 17q23.2 encompassing TBX2 gene in boy with cognitive impairment, multiple congenital defects and prenatal onset growth restriction. Part of BCAS3 gene (associated with autosomal recessive Hengel-Maroofian-Schols syndrome) also included in duplication. No supportive evidence of TBX2 gene function impairment in the patient provided.; to: Liu et al. (2018) reported 4 affected individuals from 2 unrelated families with congenital cardiac defects (ASD, PDA, double outlet right ventricle, pulmonary stenosis), skeletal abnormalities (camptodactyly, congenital fusion thoracic spine, hemivertebrae ).Thymus aplasia/hypoplasia, cleft palate also noted. Other associated features include - facial dysmorphisms, variable developmental delay, and endocrine system disorders (e.g. autoimmune hypothyroidism, hypoparathyroidism).

PMID23727221 and PMID30223900 - TBX2 gene and TBX2 gene promoter sequencing in congenital heart disease cohorts versus controls - not enough supportive evidence for variant pathogenicity, including no segregation data. Variants prevalent in population databases also included as potentially disease causing.

PMID 20635360 - de novo dup 17q23.2 encompassing TBX2 gene in boy with cognitive impairment, multiple congenital defects and prenatal onset growth restriction. Part of BCAS3 gene (associated with autosomal recessive Hengel-Maroofian-Schols syndrome) also included in duplication. No supportive evidence of TBX2 gene function impairment in the patient provided.
Mendeliome v0.10542 TBX2 Krithika Murali reviewed gene: TBX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29726930, 23727221, 20635360, 30223900; Phenotypes: Vertebral anomalies and variable endocrine and T-cell dysfunction - MIM#618223; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10542 SMAD6 Zornitza Stark Marked gene: SMAD6 as ready
Mendeliome v0.10542 SMAD6 Zornitza Stark Phenotypes for gene: SMAD6 were changed from to {Radioulnar synostosis, nonsyndromic} 179300; {Craniosynostosis 7, susceptibility to} 617439; Aortic valve disease 2 MIM# 614823
Mendeliome v0.10539 SMAD6 Zornitza Stark edited their review of gene: SMAD6: Changed phenotypes: {Radioulnar synostosis, nonsyndromic} 179300, {Craniosynostosis 7, susceptibility to} 617439, Aortic valve disease 2 MIM# 614823
Mendeliome v0.10539 SMAD6 Zornitza Stark reviewed gene: SMAD6: Rating: GREEN; Mode of pathogenicity: None; Publications: 31138930, 32499606, 27606499, 22275001, 28659821, 30963242, 30848080, 30796334; Phenotypes: {Radioulnar synostosis, nonsyndromic} 179300, {Craniosynostosis 7, susceptibility to} 617439; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10539 SLC26A2 Seb Lunke Marked gene: SLC26A2 as ready
Mendeliome v0.10536 TUBB4A Zornitza Stark Marked gene: TUBB4A as ready
Mendeliome v0.10533 TWIST1 Zornitza Stark Marked gene: TWIST1 as ready
Mendeliome v0.10530 SLC25A24 Seb Lunke Marked gene: SLC25A24 as ready
Mendeliome v0.10527 ARHGEF10 Zornitza Stark Phenotypes for gene: ARHGEF10 were changed from to Slowed nerve conduction velocity, MIM# 608236
Mendeliome v0.10526 ARHGEF10 Zornitza Stark Publications for gene: ARHGEF10 were set to
Mendeliome v0.10525 ARHGEF10 Zornitza Stark Mode of pathogenicity for gene: ARHGEF10 was changed from to Other
Mendeliome v0.10524 ARHGEF10 Zornitza Stark Mode of inheritance for gene: ARHGEF10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10523 ARHGEF10 Zornitza Stark edited their review of gene: ARHGEF10: Changed rating: AMBER
Mendeliome v0.10523 MBNL1 Zornitza Stark Marked gene: MBNL1 as ready
Mendeliome v0.10522 PDK3 Zornitza Stark Marked gene: PDK3 as ready
Mendeliome v0.10522 PDK3 Zornitza Stark Phenotypes for gene: PDK3 were changed from to Charcot-Marie-Tooth disease, X-linked dominant, 6 MIM#300905; HMSN
Mendeliome v0.10519 PDK3 Arina Puzriakova reviewed gene: PDK3: Rating: ; Mode of pathogenicity: None; Publications: 34387338; Phenotypes: Charcot-Marie-Tooth disease, X-linked dominant, 6, OMIM:300905; Mode of inheritance: None
Mendeliome v0.10519 PRDM9 Zornitza Stark Marked gene: PRDM9 as ready
Mendeliome v0.10518 PRDM9 Zornitza Stark gene: PRDM9 was added
gene: PRDM9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRDM9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRDM9 were set to 34257419
Phenotypes for gene: PRDM9 were set to Inherited primary ovarian failure MONDO:0019852
Review for gene: PRDM9 was set to GREEN
Added comment: The primordial follicle pool is determined by the meiosis process, which is initiated by programmed DNA double strand breaks (DSB) and homologous recombination. PRDM9 is a meiosis-specific histone H3 methyltransferase and a major determinant of meiotic recombination hotspots in mammals. 3 pathogenic heterozygous variants in PRDM9 identified in 4 patients with POI. Functional studies showed the variants in PRDM9 impaired its methyltransferase activity. Prdm9+/- mice were subfertile, and showed increased percentage of germ cells at abnormal pachytene stage with decreased number of PRDM9-dependent DSBs and insufficient recombination.
Sources: Literature
Mendeliome v0.10517 DZIP1L Zornitza Stark Marked gene: DZIP1L as ready
Mendeliome v0.10514 PPA2 Zornitza Stark Marked gene: PPA2 as ready
Mendeliome v0.10514 PPA2 Zornitza Stark Phenotypes for gene: PPA2 were changed from to Sudden cardiac failure, alcohol-induced, 617223; Sudden cardiac failure, infantile, 617222
Mendeliome v0.10511 PPA2 Zornitza Stark reviewed gene: PPA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27523598, 34400813; Phenotypes: Sudden cardiac failure, alcohol-induced, 617223, Sudden cardiac failure, infantile, 617222; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10511 NAA20 Zornitza Stark Marked gene: NAA20 as ready
Mendeliome v0.10510 NAA20 Zornitza Stark gene: NAA20 was added
gene: NAA20 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NAA20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAA20 were set to 34230638
Phenotypes for gene: NAA20 were set to Intellectual disability; Microcephaly; Neurodevelopmental disorder MONDO:0700092
Review for gene: NAA20 was set to GREEN
Added comment: 2 consanguineous families with 5 affected individuals with developmental delay, intellectual disability, and microcephaly (-2-4SD). Exome and genome sequencing identified 2 different homozygous variants in NAA20 gene (p.Met54Val and p.Ala80Val), and segregated with affected individuals. N-terminal acetyltransferases modify proteins by adding an acetyl moiety to the first amino acid and are vital for protein and cell function. The NatB complex acetylates 20% of the human proteome and is composed of the catalytic subunit NAA20 and the auxiliary subunit NAA25. Both NAA20-M54V and NAA20-A80V were impaired in their capacity to form a NatB complex with NAA25, and in vitro acetylation assays revealed reduced catalytic activities toward different NatB substrates.
Sources: Literature
Mendeliome v0.10509 PLA2G7 Zornitza Stark Marked gene: PLA2G7 as ready
Mendeliome v0.10505 RAB23 Zornitza Stark Marked gene: RAB23 as ready
Mendeliome v0.10505 RAB23 Zornitza Stark Phenotypes for gene: RAB23 were changed from to Carpenter syndrome (MIM#201000)
Mendeliome v0.10502 DSG1 Zornitza Stark Marked gene: DSG1 as ready
Mendeliome v0.10502 DSG1 Zornitza Stark Phenotypes for gene: DSG1 were changed from to Erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper IgE, AR (MIM#615508); Keratosis palmoplantaris striata I, AD (MIM# 148700)
Mendeliome v0.10499 DPF2 Zornitza Stark Marked gene: DPF2 as ready
Mendeliome v0.10496 DNAJC19 Zornitza Stark Marked gene: DNAJC19 as ready
Mendeliome v0.10493 RAB23 Naomi Baker reviewed gene: RAB23: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:17503333, 21412941, 23599695, 25168863; Phenotypes: Carpenter syndrome (MIM#201000); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10493 DSG1 Belinda Chong reviewed gene: DSG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19558595, 29315490, 31192455, 23974871, 29229434, 33666035; Phenotypes: Erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper IgE, AR (MIM#615508), Keratosis palmoplantaris striata I, AD (MIM# 148700); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10493 KCNC1 Zornitza Stark Marked gene: KCNC1 as ready
Mendeliome v0.10491 KCNC1 Zornitza Stark changed review comment from: Additional individuals reported with different variants, causing a broad range of neurological phenotypes including ID and movement disorders.; to: Additional individuals reported with different variants, causing a broad range of neurological phenotypes including ID and movement disorders.

Likely reflects different mechanisms (LoF vs GoF).
Mendeliome v0.10489 JAK3 Zornitza Stark Marked gene: JAK3 as ready
Mendeliome v0.10486 GBE1 Zornitza Stark Marked gene: GBE1 as ready
Mendeliome v0.10483 FREM1 Zornitza Stark Marked gene: FREM1 as ready
Mendeliome v0.10480 FRAS1 Zornitza Stark Marked gene: FRAS1 as ready
Mendeliome v0.10477 SGPL1 Seb Lunke Marked gene: SGPL1 as ready
Mendeliome v0.10475 FOXP3 Zornitza Stark Marked gene: FOXP3 as ready
Mendeliome v0.10472 MMP3 Zornitza Stark Marked gene: MMP3 as ready
Mendeliome v0.10472 MMP3 Zornitza Stark Phenotypes for gene: MMP3 were changed from to {Coronary heart disease, susceptibility to, 6} 614466
Mendeliome v0.10469 MMP3 Paul De Fazio reviewed gene: MMP3: Rating: RED; Mode of pathogenicity: None; Publications: 12750310, 10351963; Phenotypes: {Coronary heart disease, susceptibility to, 6} 614466; Mode of inheritance: Unknown; Current diagnostic: yes
Mendeliome v0.10469 LRAT Zornitza Stark Marked gene: LRAT as ready
Mendeliome v0.10469 LRAT Zornitza Stark Phenotypes for gene: LRAT were changed from to Leber congenital amaurosis 14 MIM#613341; Retinal dystrophy, early-onset severe MIM#613341; Retinitis pigmentosa, juvenile MIM#613341
Mendeliome v0.10466 LRAT Zornitza Stark reviewed gene: LRAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 11381255, 18055821, 22570351, 17011878, 29973277, 24625443, 22559933, 31448181; Phenotypes: Leber congenital amaurosis 14 MIM#613341, Retinal dystrophy, early-onset severe MIM#613341, Retinitis pigmentosa, juvenile MIM#613341; Mode of inheritance: None
Mendeliome v0.10466 GRM1 Zornitza Stark Marked gene: GRM1 as ready
Mendeliome v0.10466 GRM1 Zornitza Stark Phenotypes for gene: GRM1 were changed from to Spinocerebellar ataxia 44 MIM#617691; Spinocerebellar ataxia, autosomal recessive 13 MIM#614831
Mendeliome v0.10461 GPX4 Zornitza Stark Marked gene: GPX4 as ready
Mendeliome v0.10458 SLC12A6 Zornitza Stark Phenotypes for gene: SLC12A6 were changed from Andermann syndrome; Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum; Intermediate CMT to Andermann syndrome; Agenesis of the corpus callosum with peripheral neuropathy, MIM#21800; Intermediate CMT
Mendeliome v0.10457 GPKOW Zornitza Stark Marked gene: GPKOW as ready
Mendeliome v0.10456 GNA11 Zornitza Stark Marked gene: GNA11 as ready
Mendeliome v0.10452 FOXC2 Zornitza Stark Marked gene: FOXC2 as ready
Mendeliome v0.10449 GRM1 Ain Roesley reviewed gene: GRM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22901947, 26308914, 31319223; Phenotypes: Spinocerebellar ataxia 44 MIM#617691, Spinocerebellar ataxia, autosomal recessive 13 MIM#614831; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10448 GPKOW Ain Roesley gene: GPKOW was added
gene: GPKOW was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPKOW was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GPKOW were set to 28612833
Phenotypes for gene: GPKOW were set to male-lethal microcephaly with intrauterine growth restriction
Penetrance for gene: GPKOW were set to unknown
Review for gene: GPKOW was set to RED
gene: GPKOW was marked as current diagnostic
Added comment: - multi-generational family with 5 deceased males (only 1 genotyped)
- X-exome sequencing identified NM_015698.4:c.331+5G>A, which segregated through the obligate carriers
- RNA from female carriers confirmed splicing defects, which leads to NMD

no additional reports since
Sources: Literature
Mendeliome v0.10448 HOXC13 Zornitza Stark Marked gene: HOXC13 as ready
Mendeliome v0.10445 FZD6 Zornitza Stark Marked gene: FZD6 as ready
Mendeliome v0.10440 SIX5 Zornitza Stark changed review comment from: Multiple families reported.; to: Multiple families reported. However, association between SIX5 variants and BOR is DISPUTED by ClinGen: Association has been reported in at least 6 probands in 2 publications (17357085, 24429398), however the reported variants are high in frequency in population databases, have no evidence of pathogenicity, and/or an alternate cause of disease has later been reported (21280147). This gene-disease association is supported by protein interaction and biochemical function studies (14704431, 17357085, 11950062). While EYA1 and SIX1 gene inactivation in mice leads to ear and kidney abnormalities, two independent SIX5 mouse models have cataracts and no ear or kidney abnormalities (10802667, 10802668). In summary, there is convincing evidence disputing the association between SIX5 and autosomal dominant branchio-oto-renal syndrome.
Mendeliome v0.10440 SIX5 Zornitza Stark Marked gene: SIX5 as ready
Mendeliome v0.10436 SKI Seb Lunke Marked gene: SKI as ready
Mendeliome v0.10433 SKI Seb Lunke changed review comment from: Well established gene disease association with craniosynostosis, skeletal, and cardiovascular anomalies, high-arched palate, micrognathia. Inguinal or umbilical hernia also described. Most common skeletal manifestations are arachnodactyly, pectus deformity, camptodactyly, scoliosis.

LoF not fully established on only missense described so far. Some functional work suggest potential GoF for TGF beta signalling, but not conclusive. Not enough evidence so far to go against LoF.; to: Well established gene disease association with craniosynostosis, skeletal, and cardiovascular anomalies, high-arched palate, micrognathia. Inguinal or umbilical hernia also described. Most common skeletal manifestations are arachnodactyly, pectus deformity, camptodactyly, scoliosis.

LoF not fully established as only missense described so far. Some functional work suggest potential GoF for TGF beta signalling, but not conclusive. Not enough evidence so far to go against LoF.
Mendeliome v0.10433 SKI Seb Lunke commented on gene: SKI: Well established gene disease association with craniosynostosis, skeletal, and cardiovascular anomalies, high-arched palate, micrognathia. Inguinal or umbilical hernia also described. Most common skeletal manifestations are arachnodactyly, pectus deformity, camptodactyly, scoliosis.

LoF not fully established on only missense described so far. Some functional work suggest potential GoF for TGF beta signalling, but not conclusive. Not enough evidence so far to go against LoF.
Mendeliome v0.10433 KEL Zornitza Stark Marked gene: KEL as ready
Mendeliome v0.10431 COX15 Zornitza Stark Marked gene: COX15 as ready
Mendeliome v0.10431 COX15 Zornitza Stark Phenotypes for gene: COX15 were changed from to Mitochondrial complex IV deficiency, nuclear type 6, MIM# 615119
Mendeliome v0.10428 COX15 Zornitza Stark reviewed gene: COX15: Rating: GREEN; Mode of pathogenicity: None; Publications: 33746038, 32232962, 26959537, 21412973, 12474143, 15235026; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 6, MIM# 615119; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10428 TECRL Zornitza Stark Marked gene: TECRL as ready
Mendeliome v0.10427 TECRL Zornitza Stark gene: TECRL was added
gene: TECRL was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: TECRL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TECRL were set to 17666061; 27861123; 30790670; 33367594
Phenotypes for gene: TECRL were set to Ventricular tachycardia, catecholaminergic polymorphic, 3, MIM# 614021
Review for gene: TECRL was set to GREEN
Added comment: DEFINITIVE by ClinGen
Homozygous or cpd heterozygous pathogenic variants in TECRL have been identified in patients with CPVT in at least 3 families in the literature with functional evidence.
- 17666061 one consanguineous family with 4 affected relatives (siblings or 1stcousins)
- 27861123 consanguineous family with 8 affected relatives (siblings or 1stcousins)
- 30790670 reported in a single family with one child with features of CPVT
-A multi-centre review published in 2020 provided an update on these cases and described two additional CPVT cases (homozygous p.Tyr197Ter nonsense variant and homozygous exon 2 deletion) and a family with three children with sudden cardiac death, where one was homozygous for the c.331+1G>A splice donor variant, PMID 33367594
Sources: Expert Review
Mendeliome v0.10426 CCDC115 Zornitza Stark Marked gene: CCDC115 as ready
Mendeliome v0.10423 C2orf71 Zornitza Stark Marked gene: C2orf71 as ready
Mendeliome v0.10420 SH3PXD2B Zornitza Stark Marked gene: SH3PXD2B as ready
Mendeliome v0.10420 SH3PXD2B Zornitza Stark Phenotypes for gene: SH3PXD2B were changed from to Frank-ter Haar syndrome, MIM# 249420
Mendeliome v0.10417 SH3PXD2B Zornitza Stark reviewed gene: SH3PXD2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 24105366, 20137777, 34538861, 33234702, 31978614; Phenotypes: Frank-ter Haar syndrome, MIM# 249420; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10417 SETBP1 Zornitza Stark Marked gene: SETBP1 as ready
Mendeliome v0.10415 SETBP1 Zornitza Stark changed review comment from: GoF variants cause Schinzel-Giedion syndrome, whereas LoF variants cause SETBP1-haploinsufficiency syndrome, over 40 individuals reviewed in PMID 34807554.; to: GoF variants cause Schinzel-Giedion syndrome, a severe multi-system disorder characterized by recognizable facial characteristics, severe-profound intellectual disability, intractable epilepsy, cortical visual impairment, deafness, and congenital anomalies such as cardiac defects, urogenital defects, and bone abnormalities. Causative pathogenic variants are clustered within a 12-base pair hot spot region in exon 4.

LoF variants cause SETBP1-haploinsufficiency syndrome, characterized by hypotonia and mild motor developmental delay; intellectual abilities ranging from normal to severe disability; speech and language disorder; behavioral problems (most commonly attention/concentration deficits and hyperactivity, impulsivity), and refractive errors and strabismus. Over 40 individuals reviewed in PMID 34807554.
Mendeliome v0.10414 SETBP1 Zornitza Stark reviewed gene: SETBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20436468, 25217958, 34807554; Phenotypes: Schinzel-Giedion midface retraction syndrome, MIM# 269150, Mental retardation, autosomal dominant 29, MIM# 616078; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10414 SCN4A Zornitza Stark Marked gene: SCN4A as ready
Mendeliome v0.10414 SCN4A Zornitza Stark Phenotypes for gene: SCN4A were changed from to Hyperkalemic periodic paralysis, type 2, MIM# 170500; Hypokalemic periodic paralysis, type 2, MIM# 613345; Myasthenic syndrome, congenital, 16, MIM# 614198; Myotonia congenita, atypical, acetazolamide-responsive , MIM#608390; Paramyotonia congenita , MIM#168300
Mendeliome v0.10411 SCN4A Zornitza Stark reviewed gene: SCN4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 34671263; Phenotypes: Hyperkalemic periodic paralysis, type 2, MIM# 170500, Hypokalemic periodic paralysis, type 2, MIM# 613345, Myasthenic syndrome, congenital, 16, MIM# 614198, Myotonia congenita, atypical, acetazolamide-responsive , MIM#608390, Paramyotonia congenita , MIM#168300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10411 ING1 Zornitza Stark Phenotypes for gene: ING1 were changed from to Squamous cell carcinoma, head and neck, somatic, MIM# 275355
Mendeliome v0.10410 ING1 Zornitza Stark edited their review of gene: ING1: Changed phenotypes: Squamous cell carcinoma, head and neck, somatic, MIM# 275355
Mendeliome v0.10410 TRAP1 Zornitza Stark Marked gene: TRAP1 as ready
Mendeliome v0.10407 BRWD3 Zornitza Stark Marked gene: BRWD3 as ready
Mendeliome v0.10404 BRWD3 Zornitza Stark changed review comment from: More than 10 unrelated families reported, overgrowth, and in particular macrocephaly.; to: More than 10 unrelated families reported with ID, overgrowth, and in particular macrocephaly.
Mendeliome v0.10404 BRWD3 Zornitza Stark changed review comment from: More than 10 unrelated families reported, overgrowth, and in particular macrocephaly reported.; to: More than 10 unrelated families reported, overgrowth, and in particular macrocephaly.
Mendeliome v0.10404 ING1 Seb Lunke Marked gene: ING1 as ready
Mendeliome v0.10404 ING1 Seb Lunke Added comment: Comment when marking as ready: Cancer association only. Red for mendeliome.
Mendeliome v0.10403 BCKDHB Zornitza Stark Marked gene: BCKDHB as ready
Mendeliome v0.10400 BCKDHA Zornitza Stark Marked gene: BCKDHA as ready
Mendeliome v0.10397 FSCN2 Seb Lunke Marked gene: FSCN2 as ready
Mendeliome v0.10397 FSCN2 Seb Lunke Phenotypes for gene: FSCN2 were changed from to Retinitis pigmentosa 30 MIM#607921; Macular degeneration
Mendeliome v0.10393 FSCN2 Seb Lunke reviewed gene: FSCN2: Rating: RED; Mode of pathogenicity: None; Publications: 11527955, 16043865, 16280978, 17251446, 18450588; Phenotypes: Retinitis pigmentosa 30 MIM#607921, Macular degeneration; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10393 AUTS2 Zornitza Stark Phenotypes for gene: AUTS2 were changed from Mental retardation, autosomal dominant 26, MIM#615834 to Intellectual developmental disorder, autosomal dominant 26, MIM# 615834
Mendeliome v0.10392 AUH Zornitza Stark Marked gene: AUH as ready
Mendeliome v0.10389 ATP8B1 Zornitza Stark Marked gene: ATP8B1 as ready
Mendeliome v0.10389 ATP8B1 Zornitza Stark changed review comment from: Well established gene-disease association, early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver failure.

Spectrum of severity, with missense variants causing milder/benign disease. Mono-allelic variants linked to cholestasis of pregnancy.; to: Spectrum of severity, with missense variants causing milder/benign disease. Mono-allelic variants linked to cholestasis of pregnancy.
Mendeliome v0.10389 ATP8B1 Zornitza Stark changed review comment from: Well established gene-disease association, early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver failure.

Spectrum of severity. Mono-allelic variants linked to cholestasis of pregnancy.; to: Well established gene-disease association, early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver failure.

Spectrum of severity, with missense variants causing milder/benign disease. Mono-allelic variants linked to cholestasis of pregnancy.
Mendeliome v0.10389 ATP8B1 Zornitza Stark changed review comment from: Well established gene-disease association, early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver failure.; to: Well established gene-disease association, early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver failure.

Spectrum of severity. Mono-allelic variants linked to cholestasis of pregnancy.
Mendeliome v0.10384 RNF213 Zornitza Stark Marked gene: RNF213 as ready
Mendeliome v0.10382 DRD5 Zornitza Stark Marked gene: DRD5 as ready
Mendeliome v0.10381 AXIN1 Zornitza Stark Marked gene: AXIN1 as ready
Mendeliome v0.10378 ASL Zornitza Stark Marked gene: ASL as ready
Mendeliome v0.10377 ASL Zornitza Stark Phenotypes for gene: ASL were changed from to Argininosuccinic aciduria MIM#207900; Urea cycle disorders and inherited hyperammonaemias; disorder of amino acid metabolism
Mendeliome v0.10375 ARG1 Zornitza Stark Marked gene: ARG1 as ready
Mendeliome v0.10375 ARG1 Zornitza Stark Gene: arg1 has been classified as Green List (High Evidence).
Mendeliome v0.10375 ARG1 Zornitza Stark Phenotypes for gene: ARG1 were changed from to Argininaemia MIM#207800; Urea cycle disorders and inherited hyperammonaemias; disorder of arginine metabolism
Mendeliome v0.10374 ARG1 Zornitza Stark Publications for gene: ARG1 were set to
Mendeliome v0.10373 ARG1 Zornitza Stark Mode of inheritance for gene: ARG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10372 TWIST2 Zornitza Stark Marked gene: TWIST2 as ready
Mendeliome v0.10372 TWIST2 Zornitza Stark Phenotypes for gene: TWIST2 were changed from to Ablepharon-macrostomia syndrome, MIM# 200110; Barber-Say syndrome, MIM# 209885; Focal facial dermal dysplasia 3, Setleis type, MIM# 227260
Mendeliome v0.10369 TWIST2 Zornitza Stark reviewed gene: TWIST2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26119818, 20691403, 21931173, 26119818; Phenotypes: Ablepharon-macrostomia syndrome, MIM# 200110, Barber-Say syndrome, MIM# 209885, Focal facial dermal dysplasia 3, Setleis type, MIM# 227260; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10369 APTX Zornitza Stark Marked gene: APTX as ready
Mendeliome v0.10369 APTX Zornitza Stark Phenotypes for gene: APTX were changed from to Ataxia, early-onset, with oculomotor apraxia and hypoalbuminaemia MIM#208920
Mendeliome v0.10366 APTX Zornitza Stark reviewed gene: APTX: Rating: GREEN; Mode of pathogenicity: None; Publications: 30986824, 26256098, 11586299; Phenotypes: Ataxia, early-onset, with oculomotor apraxia and hypoalbuminaemia MIM#208920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10366 ALDH4A1 Zornitza Stark Marked gene: ALDH4A1 as ready
Mendeliome v0.10363 VLDLR Zornitza Stark Marked gene: VLDLR as ready
Mendeliome v0.10363 VLDLR Zornitza Stark Phenotypes for gene: VLDLR were changed from to Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1, MIM# 224050
Mendeliome v0.10360 VLDLR Zornitza Stark reviewed gene: VLDLR: Rating: GREEN; Mode of pathogenicity: None; Publications: 16080122, 18326629, 10380922; Phenotypes: Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1, MIM# 224050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10360 CSTF2 Zornitza Stark Marked gene: CSTF2 as ready
Mendeliome v0.10359 CSTF2 Zornitza Stark gene: CSTF2 was added
gene: CSTF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CSTF2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CSTF2 were set to 32816001
Phenotypes for gene: CSTF2 were set to Intellectual disability
Review for gene: CSTF2 was set to AMBER
Added comment: Four individuals from a single family, spanning two generations, segregating a missense variant. Functional data, including a mouse model and a gene reporter assay.
Sources: Literature
Mendeliome v0.10358 ALAD Zornitza Stark Marked gene: ALAD as ready
Mendeliome v0.10354 HMGCR Zornitza Stark Marked gene: HMGCR as ready
Mendeliome v0.10352 FLVCR2 Zornitza Stark Marked gene: FLVCR2 as ready
Mendeliome v0.10349 FLT4 Zornitza Stark Marked gene: FLT4 as ready
Mendeliome v0.10349 FLT4 Zornitza Stark Phenotypes for gene: FLT4 were changed from to Congenital heart defects, multiple types, 7, MIM# 618780; Lymphatic malformation 1, MIM# 153100
Mendeliome v0.10346 FLT4 Zornitza Stark reviewed gene: FLT4: Rating: GREEN; Mode of pathogenicity: None; Publications: 9817924, 10835628, 12960217, 30232381; Phenotypes: Congenital heart defects, multiple types, 7, MIM# 618780, Lymphatic malformation 1, MIM# 153100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10343 STAG3 Zornitza Stark Phenotypes for gene: STAG3 were changed from Premature ovarian failure 8 MIM#615723 to Premature ovarian failure 8 MIM#615723; Spermatogenic failure 61, MIM# 619672
Mendeliome v0.10341 FBLN5 Zornitza Stark Marked gene: FBLN5 as ready
Mendeliome v0.10341 FBLN5 Zornitza Stark Phenotypes for gene: FBLN5 were changed from to Cutis laxa, autosomal recessive, type IA, MIM#219100; Neuropathy, hereditary, with or without age-related macular degeneration (MIM#608895)
Mendeliome v0.10338 FBLN5 Zornitza Stark changed review comment from: Cutis laxa: >3 families reported with bi-allelic variants and functional data including mouse model. Single individual reported in 2003 with mono-allelic disease (large intragenic duplication).

Neuropathy +/- macular degeneration:
PMID: 32757322
- 38 individuals from 19 families
- all missense, R373C, D329V and R331H
- some carriers were subjectively healthy although pes cavus, diminished or absent deep tendon reflexesor NCV studies indicate peripheral neuropathy

PMID: 31945625
- 1 family with 2 affecteds, R373C
- 1 obligate carrier presented no symptoms

PMID: 28332470
- 3 affecteds in 1 family with R373C; to: Cutis laxa: >3 families reported with bi-allelic variants and functional data including mouse model. Single individual reported in 2003 with mono-allelic disease (large intragenic duplication).
Mendeliome v0.10338 FBLN5 Zornitza Stark reviewed gene: FBLN5: Rating: GREEN; Mode of pathogenicity: None; Publications: 12618961, 3232707, 22829427, 11805835, 32757322, 31945625, 23328402, 28332470; Phenotypes: Cutis laxa, autosomal recessive, type IA, MIM#219100, Neuropathy, hereditary, with or without age-related macular degeneration (MIM#608895); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10333 CITED2 Zornitza Stark Marked gene: CITED2 as ready
Mendeliome v0.10333 CITED2 Zornitza Stark Phenotypes for gene: CITED2 were changed from to Atrial septal defect 8 - MIM#614433; Ventricular septal defect 2 - MIM#614431
Mendeliome v0.10330 VPS53 Zornitza Stark reviewed gene: VPS53: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pontocerebellar hypoplasia, type 2E, OMIM #615851; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10330 VPS53 Zornitza Stark Phenotypes for gene: VPS53 were changed from to Pontocerebellar hypoplasia, type 2E, OMIM #615851
Mendeliome v0.10327 NKX2-6 Zornitza Stark Marked gene: NKX2-6 as ready
Mendeliome v0.10327 NKX2-6 Zornitza Stark Phenotypes for gene: NKX2-6 were changed from to Conotruncal heart malformations - MIM#217095; Persistent truncus arteriosus - MIM#217095
Mendeliome v0.10321 CITED2 Krithika Murali reviewed gene: CITED2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33706167, 33439552, 31515672, 29536580; Phenotypes: Atrial septal defect 8 - MIM#614433, Ventricular septal defect 2 - MIM#614431; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10321 YY1 Zornitza Stark Marked gene: YY1 as ready
Mendeliome v0.10318 NKX2-6 Krithika Murali reviewed gene: NKX2-6: Rating: GREEN; Mode of pathogenicity: None; Publications: 24421281, 15649947, 32198970, 25380965, 25319568; Phenotypes: Conotruncal heart malformations - MIM#217095, Persistent truncus arteriosus - MIM#217095; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10318 GM2A Zornitza Stark Marked gene: GM2A as ready
Mendeliome v0.10318 GM2A Zornitza Stark Phenotypes for gene: GM2A were changed from to GM2-gangliosidosis, AB variant MIM#272750
Mendeliome v0.10313 VPS53 Alison Yeung Marked gene: VPS53 as ready
Mendeliome v0.10313 VPS53 Alison Yeung reviewed gene: VPS53: Rating: GREEN; Mode of pathogenicity: None; Publications: 24577744, 12920088; Phenotypes: Pontocerebellar hypoplasia, type 2E, OMIM #615851; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10313 GLI1 Zornitza Stark Marked gene: GLI1 as ready
Mendeliome v0.10312 WNT10B Alison Yeung Marked gene: WNT10B as ready
Mendeliome v0.10312 GM2A Ain Roesley reviewed gene: GM2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 28417072, 28192816, 27402091, 33819415; Phenotypes: GM2-gangliosidosis, AB variant MIM#272750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10312 GLI1 Ain Roesley gene: GLI1 was added
gene: GLI1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GLI1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GLI1 were set to 34721536; 31621941; 31549748; 30620395
Phenotypes for gene: GLI1 were set to Polydactyly, postaxial, type A8 MIM#618123; Polydactyly, preaxial I MIM#174400
Penetrance for gene: GLI1 were set to unknown
Review for gene: GLI1 was set to GREEN
gene: GLI1 was marked as current diagnostic
Added comment: >10 unrelated probands reported, both AD and AR reported
Sources: Literature
Mendeliome v0.10312 ADAMTS2 Zornitza Stark Marked gene: ADAMTS2 as ready
Mendeliome v0.10312 ADAMTS2 Zornitza Stark Phenotypes for gene: ADAMTS2 were changed from to Ehlers-Danlos syndrome, dermatosparaxis type (MIM# 225410)
Mendeliome v0.10309 ADAMTS2 Zornitza Stark reviewed gene: ADAMTS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 26765342, 28306229; Phenotypes: Ehlers-Danlos syndrome, dermatosparaxis type (MIM# 225410); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10308 AGA Zornitza Stark changed review comment from: Aspartylglucosaminuria (AGU) is a severe autosomal recessive lysosomal storage disorder that involves the central nervous system and causes skeletal abnormalities as well as connective tissue lesions. The most characteristic feature is progressive mental retardation. Multiple families and mouse model.; to: Aspartylglucosaminuria (AGU) is a severe autosomal recessive lysosomal storage disorder that involves the central nervous system and causes skeletal abnormalities as well as connective tissue lesions. The most characteristic feature is progressive ID. Multiple families and mouse model.
Mendeliome v0.10308 ACAT1 Zornitza Stark Marked gene: ACAT1 as ready
Mendeliome v0.10306 ACADS Zornitza Stark Marked gene: ACADS as ready
Mendeliome v0.10303 ACADM Zornitza Stark Marked gene: ACADM as ready
Mendeliome v0.10301 CYP26B1 Zornitza Stark Marked gene: CYP26B1 as ready
Mendeliome v0.10298 CTU2 Zornitza Stark Marked gene: CTU2 as ready
Mendeliome v0.10295 CTDP1 Zornitza Stark Marked gene: CTDP1 as ready
Mendeliome v0.10295 CTDP1 Zornitza Stark Phenotypes for gene: CTDP1 were changed from to Congenital cataracts, facial dysmorphism, and neuropathy, MIM# 604168
Mendeliome v0.10292 CTDP1 Zornitza Stark reviewed gene: CTDP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14517542, 24690360, 25529582; Phenotypes: Congenital cataracts, facial dysmorphism, and neuropathy, MIM# 604168; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10291 CRELD1 Zornitza Stark commented on gene: CRELD1: Three families reported with heterozygous missense variants and heterotaxy phenotype. However, supporting evidence of pathogenicity for some of the variants is relatively weak.
Mendeliome v0.10290 SPIDR Zornitza Stark Marked gene: SPIDR as ready
Mendeliome v0.10290 SPIDR Zornitza Stark Phenotypes for gene: SPIDR were changed from Primary ovarian insufficiency to Ovarian dysgenesis 9, MIM# 619665
Mendeliome v0.10289 SPIDR Zornitza Stark reviewed gene: SPIDR: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Ovarian dysgenesis 9, MIM# 619665; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10288 MED12 Zornitza Stark Phenotypes for gene: MED12 were changed from Ohdo syndrome, X-linked MIM#300895; Lujan-Fryns syndrome MIM#309520; Opitz-Kaveggia syndrome MIM#305450; Hardikar syndrome, OMIM #612726 to Ohdo syndrome, X-linked MIM#300895; Lujan-Fryns syndrome MIM#309520; Opitz-Kaveggia syndrome MIM#305450; Hardikar syndrome, MIM# 301068
Mendeliome v0.10287 MED12 Zornitza Stark edited their review of gene: MED12: Changed phenotypes: Hardikar syndrome, MIM# 301068
Mendeliome v0.10287 TNR Zornitza Stark Phenotypes for gene: TNR were changed from Spastic para- or tetraparesis; Axial muscular hypotonia; Intellectual disability; Transient opisthotonus to Neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus, MIM# 619653; Spastic para- or tetraparesis; Axial muscular hypotonia; Intellectual disability; Transient opisthotonus
Mendeliome v0.10286 TNR Zornitza Stark edited their review of gene: TNR: Changed phenotypes: Neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus, MIM# 619653, Spastic para- or tetraparesis, Axial muscular hypotonia, Intellectual disability, Transient opisthotonus
Mendeliome v0.10286 CTSB Zornitza Stark Marked gene: CTSB as ready
Mendeliome v0.10280 MSR1 Zornitza Stark Marked gene: MSR1 as ready
Mendeliome v0.10280 MSR1 Zornitza Stark Phenotypes for gene: MSR1 were changed from to Barrett esophagus/esophageal adenocarcinoma, MIM# 614266
Mendeliome v0.10276 MSR1 Zornitza Stark reviewed gene: MSR1: Rating: RED; Mode of pathogenicity: None; Publications: 12958598, 21791690; Phenotypes: Barrett esophagus/esophageal adenocarcinoma, MIM# 614266; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10276 CPAMD8 Zornitza Stark Marked gene: CPAMD8 as ready
Mendeliome v0.10272 USP53 Zornitza Stark changed review comment from: Another 7 unrelated families with cholestasis reported. Jaundice began at age <7 months. Cholestasis was transient, with documented resolution of hyperbilirubinaemia in all (oldest patient aged 5 years). One individual had deafness.; to: Another 11 unrelated families with cholestasis reported. Jaundice began at age <7 months. Cholestasis was transient, with documented resolution of hyperbilirubinaemia in all (oldest patient aged 15 years). Childhood-onset deafness reported in two families.
Mendeliome v0.10272 USP53 Zornitza Stark Phenotypes for gene: USP53 were changed from Cholestasis; deafness to Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss, MIM# 619658
Mendeliome v0.10271 USP53 Zornitza Stark edited their review of gene: USP53: Changed phenotypes: Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss 619658
Mendeliome v0.10271 HOXB1 Zornitza Stark Marked gene: HOXB1 as ready
Mendeliome v0.10270 HOXB1 Zornitza Stark Phenotypes for gene: HOXB1 were changed from to Facial paresis, hereditary congenital, 3, MIM# 614744; MONDO:0013880
Mendeliome v0.10268 HOXB1 Zornitza Stark reviewed gene: HOXB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22770981, 26007620, 27144914; Phenotypes: Facial paresis, hereditary congenital, 3, MIM# 614744; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10268 COLEC10 Zornitza Stark Marked gene: COLEC10 as ready
Mendeliome v0.10265 COL4A3BP Zornitza Stark Marked gene: COL4A3BP as ready
Mendeliome v0.10265 COL4A3BP Zornitza Stark Phenotypes for gene: COL4A3BP were changed from to Mental retardation, autosomal dominant 34, MIM# 616351
Mendeliome v0.10262 COL4A3BP Zornitza Stark reviewed gene: COL4A3BP: Rating: GREEN; Mode of pathogenicity: None; Publications: 25533962; Phenotypes: Mental retardation, autosomal dominant 34, MIM# 616351; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10260 MIB1 Zornitza Stark changed review comment from: Comment when marking as ready: Amber for LVNC/cardiomyopathy. Green for congenital heart disease.; to: Comment when marking as ready: RED for LVNC/cardiomyopathy. Amber for congenital heart disease.
Mendeliome v0.10260 ZBTB20 Zornitza Stark Marked gene: ZBTB20 as ready
Mendeliome v0.10257 MIB1 Chern Lim changed review comment from: Luxan 2013 (PMID: 23314057):
- V943F, seg with LVNC in 1 fam, (gnomADv2: 43 hets).
- R530X, seg with LVNC in 1 fam, (gv2: 13 hets).

Li 2018 (PMID: 30322850):
- in 4 CHD patients: p.Q237H (gv2v3 absent), p.W271G (gv2v3 absent), p.S520R (v2 5 hets) and p.T312Kfs*55 (NMD-pred, absent but many comparables in gnomAD).
- HEK293T cells transfection studies showed: T312Kfs*55 and W271G strongly impaired MIB1 function on substrate ubiquitination, while Q237H and S520R had slight or no obvious changes. Interaction between MIB1 and JAG1 is severely interrupted by p.T312Kfs*55 and p.W271G, but not really in the other 2 missense.
- Overexpression of wt or mutant in zebrafish all resulted in dysmorphic pheno, therefore not informative.

DCM-association = none by Clingen (9/4/2020), ref Luxan 2013 and other pprs, and mentioned gnomAD had too many LoF variants.

De Ligt 2012 (PMID: 23033978): de novo R174H (gnomADv2: 7 hets), indvl with severe ID who also has a de novo R47* in WAC (an AD ID gene with LoF established, variant is P in ClinVar), no other pt-specific pheno provided.

Kaplanis 2021 (PMID: 33057194): Developmental disorders paper.
- 2 missense variants, de novo: 18-19383967-G-A (p.Glu491Lys, gv2 1 het, gv3 absent, GeneDx), 18-19378124-C-T (Thr391Ile, gv2v3 absent, DDD, de novo, no mention of heart pheno).
- Of 6 PTVs, 4 had at least 10 hets each in gnomADv2.; to: Luxan 2013 (PMID: 23314057):
- V943F, seg with LVNC in 1 fam, (gnomADv2: 43 hets).
- R530X, seg with LVNC in 1 fam, (gv2: 13 hets).

Li 2018 (PMID: 30322850):
- in 4 CHD patients: p.Q237H (gv2v3 absent), p.W271G (gv2v3 absent), p.S520R (v2 5 hets) and p.T312Kfs*55 (NMD-pred, absent but many comparables in gnomAD).
- HEK293T cells transfection studies showed: T312Kfs*55 and W271G strongly impaired MIB1 function on substrate ubiquitination, while Q237H and S520R had slight or no obvious changes. Interaction between MIB1 and JAG1 is severely interrupted by p.T312Kfs*55 and p.W271G, but not really in the other 2 missense.
- Overexpression of wt or mutant in zebrafish all resulted in dysmorphic pheno, therefore not informative.

DCM-association = none by Clingen (9/4/2020), ref Luxan 2013 and other pprs, and mentioned gnomAD had too many LoF variants.

De Ligt 2012 (PMID: 23033978): de novo R174H (gnomADv2: 7 hets), indvl with severe ID who also has a de novo R47* in WAC (an AD ID gene with LoF established, variant is P in ClinVar), no other pt-specific pheno provided.

Kaplanis 2021 (PMID: 33057194): Developmental disorders paper.
- 2 missense variants, de novo: 18-19383967-G-A (p.Glu491Lys, gv2 1 het, gv3 absent), 18-19378124-C-T (Thr391Ile, gv2v3 absent, DDD, de novo, no mention of heart pheno).
- Of 6 PTVs, 4 had at least 10 hets each in gnomADv2.
Mendeliome v0.10257 ABO Zornitza Stark Marked gene: ABO as ready
Mendeliome v0.10255 TLR1 Zornitza Stark Marked gene: TLR1 as ready
Mendeliome v0.10250 REL Zornitza Stark changed review comment from: Second unrelated individual reported, homozygous splice site variant.

Immunodeficiency-92 (IMD92) is an autosomal recessive primary immunodeficiency characterized by the onset of recurrent infections in infancy or early childhood. Infectious agents are broad, including bacterial, viral, fungal, and parasitic, including Cryptosporidium and Mycobacteria. Patient lymphocytes show defects in both T- and B-cell proliferation, cytokine secretion, and overall function, and there is also evidence of dysfunction of NK, certain antigen-presenting cells, and myeloid subsets.; to: Second unrelated individual reported, with a different homozygous splice site variant.

Immunodeficiency-92 (IMD92) is an autosomal recessive primary immunodeficiency characterized by the onset of recurrent infections in infancy or early childhood. Infectious agents are broad, including bacterial, viral, fungal, and parasitic, including Cryptosporidium and Mycobacteria. Patient lymphocytes show defects in both T- and B-cell proliferation, cytokine secretion, and overall function, and there is also evidence of dysfunction of NK, certain antigen-presenting cells, and myeloid subsets.
Mendeliome v0.10250 REL Zornitza Stark edited their review of gene: REL: Added comment: Second unrelated individual reported, homozygous splice site variant.

Immunodeficiency-92 (IMD92) is an autosomal recessive primary immunodeficiency characterized by the onset of recurrent infections in infancy or early childhood. Infectious agents are broad, including bacterial, viral, fungal, and parasitic, including Cryptosporidium and Mycobacteria. Patient lymphocytes show defects in both T- and B-cell proliferation, cytokine secretion, and overall function, and there is also evidence of dysfunction of NK, certain antigen-presenting cells, and myeloid subsets.; Changed rating: AMBER; Changed publications: 31103457, 34623332; Changed phenotypes: Immunodeficiency 92, MIM# 619652, Combined immunodeficiency, T cells: normal, decreased memory CD4, poor proliferation, B cells: low, mostly naive, few switched memory B cells, impaired proliferation, Recurrent infections with bacteria, mycobacteria, salmonella and opportunistic organisms, Defective innate immunity
Mendeliome v0.10248 SLC26A5 Zornitza Stark commented on gene: SLC26A5: Another publication identified, plus another individual with bi-allelic variants reported by a diagnostic laboratory. This gene-disease association is supported by mouse models, biochemical function studies and expression studies (12239568, 10821263, 11423665, 12719379, 18466744, 27091614, 17998209). Classified as LIMITED by ClinGen in 2017.
Mendeliome v0.10248 SEMA7A Zornitza Stark Marked gene: SEMA7A as ready
Mendeliome v0.10248 SEMA7A Zornitza Stark Added comment: Comment when marking as ready: AMBER for PFIC. RED for other associations.
Mendeliome v0.10244 SEMA7A Paul De Fazio changed review comment from: Koh et al 2006 (PMID:16372136) identified an association between common polymorphisms and decreased bone mineral density in 560 postmenopausal Korean women.

Zhao et al 2020 (PMID:31650878) identified a heterozygous splice variant at -3 (absent from gnomad) in a young woman with Kallman syndrome. It was inherited from her father, who had retarded pubertal development but a normal sense of smell.

Pan et al 2021 (PMID:34585848) identified a homozygous missense variant (gnomad: 107 hets 0 homs) in a child with progressive familial intrahepatic cholestasis. Mouse knock-ins recapitulated the patient phenotype.

Low evidence for association with disease.; to: Koh et al 2006 (PMID:16372136) identified an association between common polymorphisms and decreased bone mineral density in 560 postmenopausal Korean women.

Zhao et al 2020 (PMID:31650878) identified a heterozygous splice variant at -3 (absent from gnomad) in a young woman with Kallman syndrome. It was inherited from her father, who had retarded pubertal development but a normal sense of smell.

Pan et al 2021 (PMID:34585848) identified a homozygous missense variant (gnomad: 107 hets 0 homs) in a child with progressive familial intrahepatic cholestasis. Homozygous mice recapitulated the patient phenotype.

Rated amber due to 1 patient and mouse model in PMID:34585848.
Mendeliome v0.10244 SEMA7A Paul De Fazio changed review comment from: There is no conclusive evidence of association with monogenic disease for this gene.

Koh et al 2006 (PMID:16372136) identified an association between common polymorphisms and decreased bone mineral density in 560 postmenopausal Korean women.

Zhao et al 2020 (PMID:31650878) identified a heterozygous splice variant at -3 (absent from gnomad) in a young woman with Kallman syndrome. It was inherited from her father, who had retarded pubertal development but a normal sense of smell.

Pan et al 2021 (PMID:34585848) identified a homozygous missense variant (gnomad: 107 hets 0 homs) in a child with progressive familial intrahepatic cholestasis. Mouse knock-ins recapitulated the patient phenotype.; to: Koh et al 2006 (PMID:16372136) identified an association between common polymorphisms and decreased bone mineral density in 560 postmenopausal Korean women.

Zhao et al 2020 (PMID:31650878) identified a heterozygous splice variant at -3 (absent from gnomad) in a young woman with Kallman syndrome. It was inherited from her father, who had retarded pubertal development but a normal sense of smell.

Pan et al 2021 (PMID:34585848) identified a homozygous missense variant (gnomad: 107 hets 0 homs) in a child with progressive familial intrahepatic cholestasis. Mouse knock-ins recapitulated the patient phenotype.

Low evidence for association with disease.
Mendeliome v0.10244 CLMP Zornitza Stark Marked gene: CLMP as ready
Mendeliome v0.10241 ERF Zornitza Stark Marked gene: ERF as ready
Mendeliome v0.10238 EOGT Zornitza Stark Marked gene: EOGT as ready
Mendeliome v0.10235 ADSL Zornitza Stark Marked gene: ADSL as ready
Mendeliome v0.10232 KCND2 Zornitza Stark Marked gene: KCND2 as ready
Mendeliome v0.10230 EYA1 Zornitza Stark Marked gene: EYA1 as ready
Mendeliome v0.10230 EYA1 Zornitza Stark Phenotypes for gene: EYA1 were changed from to Anterior segment anomalies with or without cataract MIM#602588; Branchiootic syndrome 1 MIM#602588; Branchiootorenal syndrome 1, with or without cataracts MIM#113650
Mendeliome v0.10227 EYA1 Zornitza Stark reviewed gene: EYA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9359046, 13269867; Phenotypes: Anterior segment anomalies with or without cataract MIM#602588, Branchiootic syndrome 1 MIM#602588, Branchiootorenal syndrome 1, with or without cataracts MIM#113650; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10227 FBXL4 Zornitza Stark Marked gene: FBXL4 as ready
Mendeliome v0.10224 GALE Zornitza Stark Marked gene: GALE as ready
Mendeliome v0.10224 GALK1 Zornitza Stark Marked gene: GALK1 as ready
Mendeliome v0.10223 FOXRED1 Zornitza Stark Marked gene: FOXRED1 as ready
Mendeliome v0.10222 FOXRED1 Zornitza Stark Phenotypes for gene: FOXRED1 were changed from to Mitochondrial complex I deficiency, nuclear type 19 MIM#618241
Mendeliome v0.10219 FREM2 Zornitza Stark Marked gene: FREM2 as ready
Mendeliome v0.10215 GALK1 Zornitza Stark Phenotypes for gene: GALK1 were changed from to Galactokinase deficiency with cataracts MIM#230200; Disorders of galactose metabolism
Mendeliome v0.10212 GATA4 Zornitza Stark Marked gene: GATA4 as ready
Mendeliome v0.10212 GATA4 Zornitza Stark Phenotypes for gene: GATA4 were changed from to Atrial septal defect 2 MIM#607941; Atrioventricular septal defect 4 MIM#614430; Ventricular septal defect 1 MIM#614429
Mendeliome v0.10208 COMT Zornitza Stark Marked gene: COMT as ready
Mendeliome v0.10206 FOXRED1 Ain Roesley reviewed gene: FOXRED1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33613441; Phenotypes: Mitochondrial complex I deficiency, nuclear type 19 MIM#618241; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.10205 SMAD2 Zornitza Stark Phenotypes for gene: SMAD2 were changed from Aortic and arterial aneurysmal disease; connective tissue disease; congenital heart disease to Loeys-Dietz syndrome 6, MIM# 619656; Congenital heart defects, multiple types, 8, with or without heterotaxy, MIM# 619657
Mendeliome v0.10204 SMAD2 Zornitza Stark reviewed gene: SMAD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Loeys-Dietz syndrome 6, MIM# 619656, Congenital heart defects, multiple types, 8, with or without heterotaxy, MIM# 619657; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10204 GATA4 Ain Roesley reviewed gene: GATA4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12845333, 18055909, 15689439, 33413087, 30455927; Phenotypes: Atrial septal defect 2 MIM#607941, Atrioventricular septal defect 4 MIM#614430, Ventricular septal defect 1 MIM#614429; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.10204 NPC1 Daniel Flanagan gene: NPC1 was added
gene: NPC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPC1 were set to 12408188; 9211849
Phenotypes for gene: NPC1 were set to Niemann-Pick disease, type C1/ type D (MIM#257220)
Review for gene: NPC1 was set to GREEN
Added comment: Biallelic NPC1 variants cause Niemann-Pick disease, type C1/ type D. Prenatal manifestation: hydrops fetalis.
Sources: Literature
Mendeliome v0.10204 KCND2 Eleanor Williams gene: KCND2 was added
gene: KCND2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCND2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCND2 were set to 24501278; 16934482; 29581270; 34245260
Phenotypes for gene: KCND2 were set to global developmental delay, HP:0001263; seizure, HP:0001250
Mode of pathogenicity for gene: KCND2 was set to Other
Review for gene: KCND2 was set to GREEN
Added comment: 6 new unrelated cases with developmental delay reported in PMID: 34245260 (Zhang et al 2021), 3 of whom had seizures. All had heterozygous missense variants of KCND2 in sites known to be critical for channel gating (E323K, P403A, two individuals, V404L, two individuals and V404M). Functional studies suggest that these missense changes cause both a partial loss-of-function (LOF) and gain-of-function (GOF). The V404 change appears to increase epileptic seizure susceptibility with the 3 patients with a V404 change showing this phenotype.

PMID:24501278 - Lee et al, 2014 - reports pair of monozygotic twin boys with infantile onset severe refractory epilepsy and autism. A de novo heterozygous missense variant was identified by WES - V404M.

PMID: 29581270 - Lin et al, 2018 - performed functional work that shows V404M enhances inactivation of channels that have not yet opened and dramatically impairs the inactivation of channels that have opened.

PMID:16934482 - Singh et al, 2006 - reports a patient with cognative impairment who also went on to have seizures starting from age 13 with a 5 bp deletion in KCND2 leading to premature stop codon. The proband's asymptomatic father also shared this variant.
Sources: Literature
Mendeliome v0.10204 EIF2B2 Zornitza Stark Marked gene: EIF2B2 as ready
Mendeliome v0.10204 EIF2B2 Zornitza Stark Phenotypes for gene: EIF2B2 were changed from to Leukoencephalopathy with vanishing white matter, MIM#603896; Ovarioleukodystrophy, MIM# 603896
Mendeliome v0.10201 EIF2B2 Zornitza Stark changed review comment from: Multiple families reported, marked phenotypic variability.; to: Multiple families reported, marked phenotypic variability, age of onset from infancy to adulthood.
Mendeliome v0.10201 EIF2B2 Zornitza Stark reviewed gene: EIF2B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21484434, 14566705, 28041799, 30266093, 28597716; Phenotypes: Leukoencephalopathy with vanishing white matter, MIM#603896, Ovarioleukodystrophy, MIM# 603896; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10201 CHRNB2 Zornitza Stark Marked gene: CHRNB2 as ready
Mendeliome v0.10198 CHRNB1 Zornitza Stark Marked gene: CHRNB1 as ready
Mendeliome v0.10195 CHRNA3 Zornitza Stark Phenotypes for gene: CHRNA3 were changed from CAKUT; dysautonomia to Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT, MIM# 191800
Mendeliome v0.10194 CHRNA3 Zornitza Stark changed review comment from: Five individuals from three unrelated families.; to: Five individuals from three unrelated families.

Onset is in utero or early childhood.

Affected individuals have impaired neuronal bladder and ureteral innervation causing coordination defects that result in secondary structural defects of the renal system, including hydronephrosis, vesicoureteral reflux (VUR), and small kidneys, that may result in chronic kidney disease as well as recurrent urinary tract infections (UTIs). Surgical treatment of VUR is not effective. Most individuals also have additional autonomic features, most commonly impaired pupillary reflex and sometimes orthostatic hypotension.
Mendeliome v0.10194 CHD8 Zornitza Stark Marked gene: CHD8 as ready
Mendeliome v0.10191 CCDC22 Zornitza Stark Marked gene: CCDC22 as ready
Mendeliome v0.10187 RNF212 Zornitza Stark Marked gene: RNF212 as ready
Mendeliome v0.10181 ADCY5 Zornitza Stark edited their review of gene: ADCY5: Added comment: Neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD) is an autosomal recessive complex neurologic disorder characterized by severe global developmental delay with axial hypotonia, impaired intellectual development, poor overall growth, and abnormal involuntary hyperkinetic movements, including dystonia, myoclonus, spasticity, and orofacial dyskinesia. It is the most severe manifestation of ADCY5-related dyskinetic disorders. Five individuals from 2 families reported.

Autosomal recessive hyperkinetic movement disorder with dyskinesia, myoclonus, chorea, and dystonia-2 (HYDMCD2) is characterized by the onset of abnormal involuntary movements, mainly affecting the limbs and causing walking difficulties, in the first decade. The severity is variable; some patients have orofacial dyskinesia, resulting in speech difficulties, or develop neuropsychiatric features, including anxiety and social withdrawal. Cardiomyopathy has rarely been described and may be a manifestation of the disorder. Eight individuals from 2 families reported.; Changed publications: 22782511, 24700542, 33051786, 32647899, 33704598, 34631954, 28971144, 30975617; Changed phenotypes: Dyskinesia, familial, with facial myokymia, MIM# 606703, MONDO:0011707, Hyperkinetic movement disorder with dyskinesia, myoclonus, chorea, and dystonia-2 (HYDMCD2), MIM#619647, Neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD), MIM#619651; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10181 CANT1 Zornitza Stark Marked gene: CANT1 as ready
Mendeliome v0.10177 CAMK2A Zornitza Stark Marked gene: CAMK2A as ready
Mendeliome v0.10177 CAMK2A Zornitza Stark Phenotypes for gene: CAMK2A were changed from to Mental retardation, autosomal recessive 63 MIM#618095; Mental retardation, autosomal dominant 53 MIM#617798
Mendeliome v0.10174 CAMK2A Zornitza Stark reviewed gene: CAMK2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32600977, 29784083, 29560374; Phenotypes: Mental retardation, autosomal recessive 63 MIM#618095, Mental retardation, autosomal dominant 53 MIM#617798; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.10174 AGRP Zornitza Stark Marked gene: AGRP as ready
Mendeliome v0.10172 C1QBP Zornitza Stark Marked gene: C1QBP as ready
Mendeliome v0.10169 BOLA3 Zornitza Stark Marked gene: BOLA3 as ready
Mendeliome v0.10166 B9D2 Zornitza Stark Marked gene: B9D2 as ready
Mendeliome v0.10162 EBP Zornitza Stark Marked gene: EBP as ready
Mendeliome v0.10159 DYM Zornitza Stark Marked gene: DYM as ready
Mendeliome v0.10156 DOCK6 Zornitza Stark Marked gene: DOCK6 as ready
Mendeliome v0.10153 DNMT3A Zornitza Stark Phenotypes for gene: DNMT3A were changed from Tatton-Brown-Rahman syndrome, OMIM# 615879; primordial dwarfism with intellectual disability and microcephaly to Tatton-Brown-Rahman syndrome, MIM# 615879; Heyn-Sproul-Jackson syndrome, MIM# 618724
Mendeliome v0.10152 DNAH9 Zornitza Stark Marked gene: DNAH9 as ready
Mendeliome v0.10152 DNAH9 Zornitza Stark Phenotypes for gene: DNAH9 were changed from to Ciliary dyskinesia, primary, 40, MIM# 618300
Mendeliome v0.10149 DNAH9 Zornitza Stark reviewed gene: DNAH9: Rating: GREEN; Mode of pathogenicity: None; Publications: 30471717, 30471718; Phenotypes: Ciliary dyskinesia, primary, 40, MIM# 618300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10149 NEK10 Zornitza Stark Phenotypes for gene: NEK10 were changed from Primary ciliary dyskinesia; bronchiectasis to Ciliary dyskinesia, primary, 44, MIM# 618781
Mendeliome v0.10148 NEK10 Zornitza Stark edited their review of gene: NEK10: Changed phenotypes: Ciliary dyskinesia, primary, 44, MIM# 618781
Mendeliome v0.10148 NFIX Zornitza Stark Marked gene: NFIX as ready
Mendeliome v0.10148 NFIX Zornitza Stark Phenotypes for gene: NFIX were changed from to Sotos syndrome 2 (MIM#614753); Marshall-Smith syndrome, MIM# 602535
Mendeliome v0.10145 NFIX Zornitza Stark reviewed gene: NFIX: Rating: GREEN; Mode of pathogenicity: None; Publications: 33034087, 29897170, 30548146, 25118028; Phenotypes: Sotos syndrome 2 (MIM#614753), Marshall-Smith syndrome, MIM# 602535; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10145 GFM1 Zornitza Stark Marked gene: GFM1 as ready
Mendeliome v0.10142 GJA3 Zornitza Stark Marked gene: GJA3 as ready
Mendeliome v0.10142 GJA3 Zornitza Stark Phenotypes for gene: GJA3 were changed from to Cataract 14, multiple types MIM#601885
Mendeliome v0.10139 NECTIN4 Zornitza Stark Marked gene: NECTIN4 as ready
Mendeliome v0.10136 GJC2 Zornitza Stark Marked gene: GJC2 as ready
Mendeliome v0.10136 GJC2 Zornitza Stark Phenotypes for gene: GJC2 were changed from to Spastic paraplegia 44, autosomal recessive MIM#613206; Leukodystrophy, hypomyelinating, 2 MIM#608804; Lymphatic malformation 3 MIM#613480
Mendeliome v0.10133 EPHB4 Zornitza Stark Marked gene: EPHB4 as ready
Mendeliome v0.10133 EPHB4 Zornitza Stark Phenotypes for gene: EPHB4 were changed from to Capillary malformation-arteriovenous malformation 2 (MIM#618196), AD; Lymphatic malformation 7 (MIM#617300), AD
Mendeliome v0.10130 EPHB4 Zornitza Stark reviewed gene: EPHB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 27400125, 28687708, 29444212, 29905864, 30578106, 30819650; Phenotypes: Capillary malformation-arteriovenous malformation 2 (MIM#618196), AD, Lymphatic malformation 7 (MIM#617300), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10130 WNT4 Zornitza Stark Marked gene: WNT4 as ready
Mendeliome v0.10126 WWOX Zornitza Stark Marked gene: WWOX as ready
Mendeliome v0.10126 WWOX Zornitza Stark Phenotypes for gene: WWOX were changed from to Spinocerebellar ataxia, autosomal recessive 12, MIM# 614322; Developmental and epileptic encephalopathy 28, MIM# 616211
Mendeliome v0.10123 WWOX Zornitza Stark reviewed gene: WWOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 24456803, 25411445, 32051108, 32037574, 24369382, 34831305, 33916893; Phenotypes: Spinocerebellar ataxia, autosomal recessive 12, MIM# 614322, Developmental and epileptic encephalopathy 28, MIM# 616211; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10123 ZNF750 Zornitza Stark Marked gene: ZNF750 as ready
Mendeliome v0.10119 GLB1 Zornitza Stark Marked gene: GLB1 as ready
Mendeliome v0.10119 GLB1 Zornitza Stark Phenotypes for gene: GLB1 were changed from to GM1-gangliosidosis, type I MIM#230500; GM1-gangliosidosis, type II MIM# 230600; GM1-gangliosidosis, type III MIM#230650; Mucopolysaccharidosis type IVB (Morquio) MIM#253010
Mendeliome v0.10116 LACC1 Bryony Thompson changed review comment from: At least 43 cases with biallelic variants (7 different variants) from 17 consanguineous families reported.
Sources: Literature; to: At least 43 cases with biallelic variants (7 different variants) from 17 mainly consanguineous families reported.
Sources: Literature
Mendeliome v0.10116 LACC1 Bryony Thompson Marked gene: LACC1 as ready
Mendeliome v0.10115 LACC1 Bryony Thompson gene: LACC1 was added
gene: LACC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LACC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LACC1 were set to 25220867; 27881174; 30872671; 33718577
Phenotypes for gene: LACC1 were set to Juvenile arthritis MIM#618795
Review for gene: LACC1 was set to GREEN
Added comment: At least 43 cases with biallelic variants (7 different variants) from 17 consanguineous families reported.
Sources: Literature
Mendeliome v0.10114 TRIM27 Zornitza Stark Marked gene: TRIM27 as ready
Mendeliome v0.10114 TRIM27 Zornitza Stark Phenotypes for gene: TRIM27 were changed from to parkinson's disease
Mendeliome v0.10112 CR1 Zornitza Stark Marked gene: CR1 as ready
Mendeliome v0.10111 ASTL Zornitza Stark Marked gene: ASTL as ready
Mendeliome v0.10111 ASTL Zornitza Stark gene: ASTL was added
gene: ASTL was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ASTL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASTL were set to 34704130
Phenotypes for gene: ASTL were set to Oocyte maturation defect 11, MIM# 619643
Review for gene: ASTL was set to RED
Added comment: Oocyte maturation defect-11 (OOMD11) is characterized by reduced or absent fertility and poor embryonic outcomes with assisted reproductive technology. Single family with two affected siblings reported.
Sources: Expert list
Mendeliome v0.10110 TERB2 Zornitza Stark Marked gene: TERB2 as ready
Mendeliome v0.10107 SPIDR Bryony Thompson gene: SPIDR was added
gene: SPIDR was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPIDR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPIDR were set to 34794894; 34697795; 27967308
Phenotypes for gene: SPIDR were set to Primary ovarian insufficiency
Review for gene: SPIDR was set to AMBER
Added comment: 3 POI cases from 2 unrelated families with homozygous nonsense variants, and in vitro functional assays demonstrating both variants alter SPIDR activity in homologous recombination.
Sources: Literature
Mendeliome v0.10106 BCAS3 Zornitza Stark Phenotypes for gene: BCAS3 were changed from Syndromic neurodevelopmental disorder to Hengel-Maroofian-Schols syndrome, MIM# 619641
Mendeliome v0.10105 BCAS3 Zornitza Stark reviewed gene: BCAS3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hengel-Maroofian-Schols syndrome, MIM# 619641; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10105 REC8 Bryony Thompson Marked gene: REC8 as ready
Mendeliome v0.10104 ATP6V1B2 Zornitza Stark Marked gene: ATP6V1B2 as ready
Mendeliome v0.10103 REC8 Bryony Thompson gene: REC8 was added
gene: REC8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: REC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: REC8 were set to 34794894; 15515002; 34707299
Phenotypes for gene: REC8 were set to Primary ovarian insufficiency
Review for gene: REC8 was set to AMBER
Added comment: PMID: 34707299 - a French POI case with compound het predicted loss of function variants
PMID: 15515002 - Rec8-/- female mice demonstrated ovarian dysgenesis and lack of ovarian follicles at reproductive maturity.
PMID: 27603904 - 2 sisters with POI segregating a missense in REC8 inherited from the unaffected mother (p.Gln154Arg) and a missense in GDF9 inherited from the father. Possible digenic inheritance.
Sources: Literature
Mendeliome v0.10100 MSH5 Bryony Thompson changed review comment from: A homozygous missense mutation (p.D487Y) in two sisters with POI. Also, homologous mutation in mice results in atrophic ovaries without oocytes, and in vitro functional study revealed that mutant MSH5 impaired DNA homologous recombination repair. Null mouse model is viable, but sterile. A case with congenital adrenal hyperplasia, ovarian failure and Ehlers-Danlos syndrome had a de novo t(6;14)(p21;q32) translocation, including CYP21A2,TNXB and MSH5.
Sources: Literature; to: 4 unrelated male azoospermia cases with 3 different homozygous frameshift/missense variants. A homozygous missense mutation (p.D487Y) in two sisters with POI. Also, homologous mutation in mice results in atrophic ovaries without oocytes, and in vitro functional study revealed that mutant MSH5 impaired DNA homologous recombination repair. Null mouse model is viable, but sterile. A case with congenital adrenal hyperplasia, ovarian failure and Ehlers-Danlos syndrome had a de novo t(6;14)(p21;q32) translocation, including CYP21A2,TNXB and MSH5.
Sources: Literature
Mendeliome v0.10100 MSH5 Bryony Thompson changed review comment from: A homozygous missense mutation (p.D487Y) in two sisters with POI. Also, homologous mutation in mice results in atrophic ovaries without oocytes, and in vitro functional study revealed that mutant MSH5 impaired DNA homologous recombination repair. Null mouse model is viable, but sterile. A case with congenital adrenal hyperplasia, ovarian failure and Ehlers-Danlos syndrome had a de novo t(6;14)(p21;q32) translocation, including CYP21A2,TNXB and MSH5.
Sources: Literature; to: 4 unrelated male azoospermia cases with 3 different homozygous frameshift/missense variants. A homozygous missense mutation (p.D487Y) in two sisters with POI. Also, homologous mutation in mice results in atrophic ovaries without oocytes, and in vitro functional study revealed that mutant MSH5 impaired DNA homologous recombination repair. Null mouse model is viable, but sterile. A case with congenital adrenal hyperplasia, ovarian failure and Ehlers-Danlos syndrome had a de novo t(6;14)(p21;q32) translocation, including CYP21A2,TNXB and MSH5.
Sources: Literature
Mendeliome v0.10100 MSH4 Bryony Thompson Marked gene: MSH4 as ready
Mendeliome v0.10100 MSH5 Bryony Thompson edited their review of gene: MSH5: Changed rating: GREEN; Changed publications: 28175301, 9916805, 24970489, 34755185; Changed phenotypes: Azoospermia, Premature ovarian failure 13 MIM#617442
Mendeliome v0.10099 ASXL2 Zornitza Stark Marked gene: ASXL2 as ready
Mendeliome v0.10096 MSH4 Bryony Thompson gene: MSH4 was added
gene: MSH4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MSH4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MSH4 were set to 34794894; 10809667; 12478991; 28541421; 32741963; 33437391; 34755185; 33448284
Phenotypes for gene: MSH4 were set to Primary ovarian insufficiency; azoospermia
Review for gene: MSH4 was set to GREEN
Added comment: PMID: 34755185 - 2 siblings, 1 with non-obstructive azoospermia and 1 with POI, both homozygous for a stopgain variant. 1 male with non-obstructive azoospermia and biallelic variants.
PMID: 33448284 - 2 sisters with POI and 3 brothers with azoospermia in a consanguineous family with a homozygous missense variant (p.Ser754Leu)
PMID: 33437391 - 1 case with non-obstructive azoospermia with a homozygous stopgain variant
PMID: 32741963 - 2 unrelated cases with spermatogenic arrest with homozygous missense variants (p.Pro638Leu; p. Ser754Leu)
PMID: 28541421 - 2 sisters with POI and homozygous for a splice site variant
PMID: 10809667 - Msh4-/- male mice are infertile and Msh4-/- female mice lacked most oocytes in the ovaries.
Sources: Literature
Mendeliome v0.10095 ASPH Zornitza Stark Marked gene: ASPH as ready
Mendeliome v0.10092 ARHGAP29 Zornitza Stark Marked gene: ARHGAP29 as ready
Mendeliome v0.10092 ARHGAP29 Zornitza Stark Gene: arhgap29 has been classified as Green List (High Evidence).
Mendeliome v0.10092 ARHGAP29 Zornitza Stark Phenotypes for gene: ARHGAP29 were changed from to Cleft palate; cleft lip with or without cleft palate
Mendeliome v0.10091 ARHGAP29 Zornitza Stark Publications for gene: ARHGAP29 were set to
Mendeliome v0.10090 ARHGAP29 Zornitza Stark Mode of inheritance for gene: ARHGAP29 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10089 ARHGAP29 Zornitza Stark reviewed gene: ARHGAP29: Rating: GREEN; Mode of pathogenicity: None; Publications: 27350171, 23008150; Phenotypes: Cleft palate, cleft lip with or without cleft palate; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10089 GJA3 Ain Roesley reviewed gene: GJA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10205266, 15286166, 15448617, 21681855, 22312188, 22550389, 22876138; Phenotypes: Cataract 14, multiple types MIM#601885; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.10089 GJC2 Ain Roesley reviewed gene: GJC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19056803, 31431325, 25059390, 20537300, 21266381; Phenotypes: Spastic paraplegia 44, autosomal recessive MIM#613206, Leukodystrophy, hypomyelinating, 2 MIM#608804, Lymphatic malformation 3 MIM#613480; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10088 MEIOB Bryony Thompson gene: MEIOB was added
gene: MEIOB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MEIOB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MEIOB were set to 34794894; 24068956; 31000419; 28206990
Phenotypes for gene: MEIOB were set to Spermatogenic failure 22 MIM#617706; primary ovarian insufficiency
Review for gene: MEIOB was set to GREEN
Added comment: At least 6 cases in 3 families, plus a mouse model for spermatogenic failure. A single family and a mouse model for POI.
PMID: 28206990 - 4 infertile brothers with a homozygous missense variant.
PMID: 32741963 - 2 unrelated males with complete spermatocytic arrest and homozygous truncating variants.
PMID: 24068956 - infertile male and female null mouse model.
PMID: 31000419 - Single family with a homozygous splicing variant in 2 sisters with POI.
Sources: Literature
Mendeliome v0.10087 GLB1 Ain Roesley reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24156116; Phenotypes: GM1-gangliosidosis, type I MIM#230500, GM1-gangliosidosis, type II MIM# 230600, GM1-gangliosidosis, type III MIM#230650, Mucopolysaccharidosis type IVB (Morquio) MIM#253010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10087 HELQ Bryony Thompson Marked gene: HELQ as ready
Mendeliome v0.10087 HELQ Bryony Thompson commented on gene: HELQ: A single POI heterozygous for a frameshift variant (c.3095delA;p.Tyr1032Serfs*4), and a null mouse model (both homozygous and heterozygous) with subfertility and germ cell attrition.
Mendeliome v0.10086 HELQ Bryony Thompson gene: HELQ was added
gene: HELQ was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HELQ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HELQ were set to 34794894; 24005329; 33095795
Phenotypes for gene: HELQ were set to Primary ovarian insufficiency
Review for gene: HELQ was set to AMBER
Added comment: Sources: Literature
Mendeliome v0.10085 TRIM27 Ain Roesley reviewed gene: TRIM27: Rating: RED; Mode of pathogenicity: None; Publications: 34419804; Phenotypes: parkinson's disease; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.10085 AP3B2 Zornitza Stark Marked gene: AP3B2 as ready
Mendeliome v0.10082 ANTXR2 Zornitza Stark Marked gene: ANTXR2 as ready
Mendeliome v0.10079 SLC29A3 Zornitza Stark Marked gene: SLC29A3 as ready
Mendeliome v0.10076 TBC1D32 Zornitza Stark Phenotypes for gene: TBC1D32 were changed from Orofaciodigital syndrome type IX to Orofaciodigital syndrome type IX; syndromic hypopituitarism
Mendeliome v0.10073 BLOC1S1 Zornitza Stark Marked gene: BLOC1S1 as ready
Mendeliome v0.10071 CLCN7 Zornitza Stark Marked gene: CLCN7 as ready
Mendeliome v0.10068 TMEM260 Zornitza Stark changed review comment from: Seven unrelated families reported.; to: Seven unrelated families reported. Clinical features: ventricular septal defects (12/12), mostly secondary to truncus arteriosus (10/12), elevated creatinine levels (6/12), horse-shoe kidneys (1/12) and renal cysts (1/12) in patients.
Mendeliome v0.10066 SNIP1 Zornitza Stark edited their review of gene: SNIP1: Added comment: A single (founder) variant NM_024700.4:c.1097A>G, p.(Glu366Gly) has been reported in over 30 cases of Psychomotor retardation, epilepsy, and craniofacial dysmorphism OMIM:614501 in the Amish community (PMIDs: 22279524; 34570759). Cases are homozygous for this variant and unaffected members of the families are heterozygous or wt. Overexpression of the equivalent mouse variant in mouse inner medullary collecting duct cells, resulted in a more aggregated appearance in the nucleus compared to wildtype. The variant protein maybe unstable as Western blots showed reduced levels of the variant protein (PMID: 22279524). Whole transcriptomic analysis of patient blood was performed in PMID: 34570759. This revealed 11 upregulated and 32 downregulated genes, of which 24 had previously been associated with neurological disease.; Changed rating: AMBER; Changed publications: 22279524, 34570759
Mendeliome v0.10066 TAF4 Zornitza Stark Marked gene: TAF4 as ready
Mendeliome v0.10065 TAF4 Zornitza Stark gene: TAF4 was added
gene: TAF4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TAF4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TAF4 were set to 33875846; 28191890
Phenotypes for gene: TAF4 were set to Neurodevelopmental disorder
Review for gene: TAF4 was set to AMBER
Added comment: Three individuals reported with de novo LoF variants as part of large cohorts, limited phenotypic information available.
Sources: Literature
Mendeliome v0.10062 PLK1 Zornitza Stark Marked gene: PLK1 as ready
Mendeliome v0.10058 PRRX1 Zornitza Stark Marked gene: PRRX1 as ready
Mendeliome v0.10055 MMP15 Zornitza Stark Marked gene: MMP15 as ready
Mendeliome v0.10054 MMP15 Zornitza Stark gene: MMP15 was added
gene: MMP15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MMP15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMP15 were set to 33875846
Phenotypes for gene: MMP15 were set to Cholestasis; Congenital heart disease
Review for gene: MMP15 was set to AMBER
Added comment: Three individuals from two families with bi-allelic variants and very similar phenotype including rare combination of symtoms (Alagille-like) cholestasis with hepatomegaly and congenital heart disease.
Sources: Literature
Mendeliome v0.10053 RPA1 Zornitza Stark Marked gene: RPA1 as ready
Mendeliome v0.10052 RPA1 Zornitza Stark gene: RPA1 was added
gene: RPA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPA1 were set to 34767620
Phenotypes for gene: RPA1 were set to Bone marrow failure; T- and B-cell lymphopaenia; pulmonary fibrosis; skin manifestations; short telomeres
Mode of pathogenicity for gene: RPA1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: RPA1 was set to GREEN
Added comment: 4 individuals with gain of function variants with bone marrow failure, myelodysplastic syndrome, T- and B-cell lymphopaenia, pulmonary fibrosis, or skin manifestations reported.
Sources: Literature
Mendeliome v0.10051 AXIN2 Zornitza Stark Marked gene: AXIN2 as ready
Mendeliome v0.10048 ATP9A Zornitza Stark Marked gene: ATP9A as ready
Mendeliome v0.10046 ECM1 Zornitza Stark Marked gene: ECM1 as ready
Mendeliome v0.10044 ECM1 Zornitza Stark changed review comment from: PMID: 11929856 - Hamada et al 2002 - looked at 6 different unrelated consanguineous families (from Saudi Arabia, Kuwait, Pakistan, The Netherlands, UK, and a group of South African families with a probable common ancestor) with a clinical diagnosis of Lipoid proteinosis (LP)/Urbach–Wiethe disease. They performed a genome-wide linkage analysis and identified a region and then looked at the expression of candidate genes in fibroblasts from patients compared to controls. ECM1 was found to have lower expression levels. 6 homozygous deletion variants were identified in the patients. In one family they established that the parents were heterozygous for the variant.

PMID: 28720532 - Afifi et al 2017 - studied 12 patients from 10 unrelated consanguineous Egyptian families with a clinical diagnosis of lipoid proteinosis. The patients reported progressive hoarseness of voice and easily damaged skin by minor trauma or friction. Homozygous ECM1 variants were detected in affected members in all families: 1 family had a missense variant, 5 families had splice site variants and 4 families had indels predicted to cause frameshifts. Parents were found to be heterozygous for the variants.

PMID: 33159951 - Zhu et al 2021 - a novel homozygous three-nucleotide duplication (c.506_508dupCTG) in ECM in two siblings affected with LP from a consanguineous Chinese family.; to: Lipoid proteinosis of Urbach and Wiethe is a rare autosomal recessive disorder typified by generalized thickening of skin, mucosae, and certain viscera. Classic features include beaded eyelid papules and laryngeal infiltration leading to hoarseness. The disorder is clinically heterogeneous, with affected individuals displaying differing degrees of skin scarring and infiltration, variable signs of hoarseness and respiratory distress, and in some cases neurologic abnormalities such as temporal lobe epilepsy. Histologically, there is widespread deposition of hyaline (glycoprotein) material and disruption/reduplication of basement membrane

PMID: 11929856 - Hamada et al 2002 - looked at 6 different unrelated consanguineous families (from Saudi Arabia, Kuwait, Pakistan, The Netherlands, UK, and a group of South African families with a probable common ancestor) with a clinical diagnosis of Lipoid proteinosis (LP)/Urbach–Wiethe disease. They performed a genome-wide linkage analysis and identified a region and then looked at the expression of candidate genes in fibroblasts from patients compared to controls. ECM1 was found to have lower expression levels. 6 homozygous deletion variants were identified in the patients. In one family they established that the parents were heterozygous for the variant.

PMID: 28720532 - Afifi et al 2017 - studied 12 patients from 10 unrelated consanguineous Egyptian families with a clinical diagnosis of lipoid proteinosis. The patients reported progressive hoarseness of voice and easily damaged skin by minor trauma or friction. Homozygous ECM1 variants were detected in affected members in all families: 1 family had a missense variant, 5 families had splice site variants and 4 families had indels predicted to cause frameshifts. Parents were found to be heterozygous for the variants.

PMID: 33159951 - Zhu et al 2021 - a novel homozygous three-nucleotide duplication (c.506_508dupCTG) in ECM in two siblings affected with LP from a consanguineous Chinese family.
Mendeliome v0.10041 SMPX Zornitza Stark edited their review of gene: SMPX: Added comment: PMID 33974137: Four different missense variants were identified in ten patients from nine families in five different countries. Haplotype analysis of patients with similar ancestry revealed two different founder mutations in Southern Europe and France, indicating that the prevalence in these populations may be higher. Clinical features: adult-onset, usually distal more than proximal limb muscle weakness, slowly progressing over decades with preserved walking. Lower limb muscle imaging showed a characteristic pattern of muscle involvement and fatty degeneration. Histopathological and electron microscopic analysis of patient muscle biopsies revealed myopathic findings with rimmed vacuoles and the presence of sarcoplasmic inclusions, some with amyloid-like characteristics. In silico predictions and subsequent cell culture studies showed that the missense mutations increase aggregation propensity of the SMPX protein. In cell culture studies, overexpressed SMPX localized to stress granules and slowed down their clearance.; Changed publications: 21549342, 21549336, 21893181, 22911656, 28542515, 33974137; Changed phenotypes: Deafness, X-linked 4, MIM# 300066, Distal myopathy, adult-onset
Mendeliome v0.10041 PIEZO1 Zornitza Stark Phenotypes for gene: PIEZO1 were changed from Lymphatic malformation 6, 616843; Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, 194380 to Lymphatic malformation 6, 616843; Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, 194380; Erythrocytosis
Mendeliome v0.10039 PIEZO1 Zornitza Stark reviewed gene: PIEZO1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 33181827; Phenotypes: Erythrocytosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10039 CNKSR2 Zornitza Stark Marked gene: CNKSR2 as ready
Mendeliome v0.10036 FGF5 Zornitza Stark Marked gene: FGF5 as ready
Mendeliome v0.10035 FGF5 Zornitza Stark gene: FGF5 was added
gene: FGF5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FGF5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FGF5 were set to 24989505
Phenotypes for gene: FGF5 were set to Hypertrichosis
Review for gene: FGF5 was set to GREEN
Added comment: Two families reported, aware of additional unpublished case.
Sources: Literature
Mendeliome v0.10034 ANK3 Zornitza Stark Phenotypes for gene: ANK3 were changed from Mental retardation, autosomal recessive, 37, MIM# 615493 to Mental retardation, autosomal recessive, 37 615493; Intellectual disability, autosomal dominant
Mendeliome v0.10031 ANK3 Zornitza Stark edited their review of gene: ANK3: Added comment: PMID 34218362: four unrelated novel, and two previously published patients with heterozygos ANK3 LoF variants are reported/summarized.; Changed rating: GREEN; Changed publications: 23390136, 28687526, 34218362; Changed phenotypes: Mental retardation, autosomal recessive, 37 615493, Intellectual disability, autosomal dominant
Mendeliome v0.10031 HIBADH Zornitza Stark Marked gene: HIBADH as ready
Mendeliome v0.10027 LAMB1 Zornitza Stark edited their review of gene: LAMB1: Added comment: Association between mono-allelic variants and adult-onset leukoencephalopathy:

LAMB1 variants found in 5 families with cerebral small vessel disease. 4 are truncating frameshifts (and 2 of the families have the same frameshift), 1 is a canonical splice. All families had adult onset of symptoms ranging from 20-63yo. All have white matter hypersignals. ‘These variants are associated with a novel phenotype characterized by the association of a hippocampal type episodic memory defect and a diffuse vascular leukoencephalopathy.’; Changed publications: 23472759, 25925986, 29888467, 25925986, 32548278, 34606115; Changed phenotypes: Lissencephaly 5, MIM# 615191, Cystic leukoencephalopathy, Adult-onset leukoencephalopathy; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10027 OGDHL Melanie Marty edited their review of gene: OGDHL: Changed phenotypes: Neurodevelopmental disorder featuring epilepsy, hearing loss, visual impairment and ataxia
Mendeliome v0.10027 OGDHL Melanie Marty edited their review of gene: OGDHL: Changed phenotypes: Neurodevelopmental disorder featuring epilepsy, hearing loss and visual impairment
Mendeliome v0.10027 OGDHL Alison Yeung Marked gene: OGDHL as ready
Mendeliome v0.10026 SLIRP Zornitza Stark Marked gene: SLIRP as ready
Mendeliome v0.10025 FOXR1 Zornitza Stark Marked gene: FOXR1 as ready
Mendeliome v0.10024 OGDHL Melanie Marty gene: OGDHL was added
gene: OGDHL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: OGDHL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OGDHL were set to PMID: 34800363
Phenotypes for gene: OGDHL were set to Neurodevelopmental disorder featuring epilepsy, hearing loss, visual impairment, and ataxia
Review for gene: OGDHL was set to GREEN
Added comment: Nine individuals from eight unrelated families carrying bi-allelic variants in OGDHL with a range of neurological and neurodevelopmental phenotypes including epilepsy, hearing
loss, visual impairment, gait ataxia, microcephaly, and hypoplastic corpus callosum.

Homozygous and compound heterozygous variants reported. Variant types reported include missense, PTCs and a synonymous variant that was shown to affect splicing.

Functional studies with a CRISPR-Cas9-mediated tissue knockout with cDNA rescue system showed that the missense variants result in loss-of-function.
Sources: Literature
Mendeliome v0.10024 TAB2 Zornitza Stark Marked gene: TAB2 as ready
Mendeliome v0.10024 TAB2 Zornitza Stark Phenotypes for gene: TAB2 were changed from to Mitral valve disease, cardiomyopathy, short stature and hypermobility, Noonan syndrome-like; Congenital heart defects, nonsyndromic, 2 (MIM#614980)
Mendeliome v0.10021 FAAH2 Zornitza Stark Marked gene: FAAH2 as ready
Mendeliome v0.10019 FOXR1 Paul De Fazio changed review comment from: 1 patient described with a de novo missense variant. Phenotypes include: postnatal microcephaly, progressive brain atrophy, skeletal abnormalities, brain abnormalities, ophthalmic abnormalities, neuromuscular abnornmalities, and dysmorphic features.

In vitro functional evidence is supportive of pathogenicity (variant causes protein instability and abnormal nuclear aggregation).

A mouse knockout has comparable phenotypes, and a severe survival deficit.

Rated amber (1 patient, functional evidence, mouse model).
Sources: Literature; to: 1 patient described with a de novo missense variant. Phenotypes include: postnatal microcephaly, progressive brain atrophy, skeletal abnormalities, brain abnormalities, ophthalmic abnormalities, neuromuscular abnormalities, and dysmorphic features. A variant in ATP1A3 was considered to have contributed to the final phenotype.

In vitro functional evidence is supportive of pathogenicity (variant causes protein instability and abnormal nuclear aggregation).

A mouse knockout has comparable phenotypes, and a severe survival deficit.

Rated amber (1 patient, functional evidence, mouse model).
Sources: Literature
Mendeliome v0.10019 SLIRP Belinda Chong gene: SLIRP was added
gene: SLIRP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLIRP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLIRP were set to 34426662
Phenotypes for gene: SLIRP were set to Mitochondrial encephalomyopathy with complex I and IV deficiency
Review for gene: SLIRP was set to RED
Added comment: Single Dutch non-consanguineous patient having mitochondrial encephalomyopathy with complex I and complex IV deficiency, whole exome sequencing revealed two compound heterozygous variants (NM_031210.5:c.248_252del; NP_112487.1:p.(Ile83Argfs*10) and NC_000014.8:g.78177003 A > G; NM_031210.5:c.98-178 A > G) in SLIRP. Report SLIRP variants as a novel cause of mitochondrial encephalomyopathy with OXPHOS deficiency
Sources: Literature
Mendeliome v0.10019 OGDH Zornitza Stark Marked gene: OGDH as ready
Mendeliome v0.10018 OGDH Zornitza Stark gene: OGDH was added
gene: OGDH was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: OGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OGDH were set to 32383294
Phenotypes for gene: OGDH were set to Developmental delay; ataxia; seizure; raised lactate
Review for gene: OGDH was set to AMBER
Added comment: Two siblings reported with homozygous missense variant in this gene and global developmental delay, elevated lactate, ataxia and seizure. Fibroblast analysis and modeling of the mutation in Drosophila were used to evaluate pathogenicity of the variant. Note previous report of an individual with developmental delay, hypotonia, and movement disorders and metabolic decompensation and biochemical evidence of OGDH deficiency but genetic testing not done.
Sources: Literature
Mendeliome v0.10017 FOXR1 Paul De Fazio gene: FOXR1 was added
gene: FOXR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOXR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXR1 were set to 34723967
Phenotypes for gene: FOXR1 were set to Postnatal microcephaly, progressive brain atrophy and global developmental delay
Review for gene: FOXR1 was set to AMBER
gene: FOXR1 was marked as current diagnostic
Added comment: 1 patient described with a de novo missense variant. Phenotypes include: postnatal microcephaly, progressive brain atrophy, skeletal abnormalities, brain abnormalities, ophthalmic abnormalities, neuromuscular abnornmalities, and dysmorphic features.

In vitro functional evidence is supportive of pathogenicity (variant causes protein instability and abnormal nuclear aggregation).

A mouse knockout has comparable phenotypes, and a severe survival deficit.

Rated amber (1 patient, functional evidence, mouse model).
Sources: Literature
Mendeliome v0.10017 TAB2 Chern Lim reviewed gene: TAB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34456334; Phenotypes: Mitral valve disease, cardiomyopathy, short stature and hypermobility, Congenital heart defects, nonsyndromic, 2 (MIM#614980); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.10017 FAAH2 Ain Roesley changed review comment from: PMID: 34645488;
- 1x nonsense variant inherited from normal mother
- proband presented with a classical Zellweger syndrome phenotype including global developmental delay, seizure disorder, severe hypotonia, failure to thrive, adrenal insufficiency and elevated very long-chain fatty acids and liver enzymes
- this variant has 2 hemizygotes in gnomAD

PMID: 25885783;
- 1x missense inherited from normal mother and absent in normal brother
- presented with autistic features, anxiety, pseudoseizures, ataxia, supranuclear gaze palsy, and isolated learning disabilities
- biochemical studies on patient fibroblasts confirmed a defect in FAAH2 activity resulting in altered levels of endocannabinoid metabolites.
- BUT this variant has 30 hemizygotes in gnomoad
Sources: Literature; to: PMID: 34645488;
- 1x nonsense variant inherited from normal mother
- proband presented with a classical Zellweger syndrome phenotype including global developmental delay, seizure disorder, severe hypotonia, failure to thrive, adrenal insufficiency and elevated very long-chain fatty acids and liver enzymes
- this variant has 2 hemizygotes in gnomAD

PMID: 25885783;
- 1x missense inherited from normal mother and absent in normal brother
- presented with autistic features, anxiety, pseudoseizures, ataxia, supranuclear gaze palsy, and isolated learning disabilities
- biochemical studies on patient fibroblasts confirmed a defect in FAAH2 activity resulting in altered levels of endocannabinoid metabolites.
- BUT this variant has 30 hemizygotes in gnomAD
Sources: Literature
Mendeliome v0.10017 FAAH2 Ain Roesley gene: FAAH2 was added
gene: FAAH2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FAAH2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FAAH2 were set to PMID: 34645488
Penetrance for gene: FAAH2 were set to unknown
Review for gene: FAAH2 was set to RED
gene: FAAH2 was marked as current diagnostic
Added comment: PMID: 34645488;
- 1x nonsense variant inherited from normal mother
- proband presented with a classical Zellweger syndrome phenotype including global developmental delay, seizure disorder, severe hypotonia, failure to thrive, adrenal insufficiency and elevated very long-chain fatty acids and liver enzymes
- this variant has 2 hemizygotes in gnomAD

PMID: 25885783;
- 1x missense inherited from normal mother and absent in normal brother
- presented with autistic features, anxiety, pseudoseizures, ataxia, supranuclear gaze palsy, and isolated learning disabilities
- biochemical studies on patient fibroblasts confirmed a defect in FAAH2 activity resulting in altered levels of endocannabinoid metabolites.
- BUT this variant has 30 hemizygotes in gnomoad
Sources: Literature
Mendeliome v0.10017 NT5E Zornitza Stark Marked gene: NT5E as ready
Mendeliome v0.10017 NT5E Zornitza Stark Phenotypes for gene: NT5E were changed from to Calcification of joints and arteries, MIM# 211800
Mendeliome v0.10014 NT5E Zornitza Stark reviewed gene: NT5E: Rating: GREEN; Mode of pathogenicity: None; Publications: 21288095; Phenotypes: Calcification of joints and arteries, MIM# 211800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10014 ARPC4 Bryony Thompson Marked gene: ARPC4 as ready
Mendeliome v0.10014 ARPC4 Bryony Thompson Gene: arpc4 has been classified as Green List (High Evidence).
Mendeliome v0.10014 ARPC4 Bryony Thompson Classified gene: ARPC4 as Green List (high evidence)
Mendeliome v0.10014 ARPC4 Bryony Thompson Gene: arpc4 has been classified as Green List (High Evidence).
Mendeliome v0.10013 ARPC4 Bryony Thompson gene: ARPC4 was added
gene: ARPC4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARPC4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARPC4 were set to DOI:https://doi.org/10.1016/j.xhgg.2021.100072
Phenotypes for gene: ARPC4 were set to Microcephaly; mild motor delays; significant speech impairment
Review for gene: ARPC4 was set to GREEN
Added comment: 7 affected individuals from 6 families (gonadal mosaicism was confirmed in the mother of the 2 affected siblings) with a recurrent missense variant (NM_005718.4:c.472C>T; p.R158C). The variant was associated with a decreased amount of F-actin in cells from two affected individuals.
Sources: Literature
Mendeliome v0.10012 TNFRSF11A Zornitza Stark Marked gene: TNFRSF11A as ready
Mendeliome v0.10009 RNF125 Zornitza Stark Marked gene: RNF125 as ready
Mendeliome v0.10006 ERMAP Zornitza Stark Marked gene: ERMAP as ready
Mendeliome v0.10004 UNC93B1 Zornitza Stark Marked gene: UNC93B1 as ready
Mendeliome v0.9999 PLS3 Zornitza Stark Marked gene: PLS3 as ready
Mendeliome v0.9996 MMP9 Zornitza Stark Marked gene: MMP9 as ready
Mendeliome v0.9993 EDN3 Zornitza Stark Marked gene: EDN3 as ready
Mendeliome v0.9993 EDN3 Zornitza Stark Phenotypes for gene: EDN3 were changed from to Central hypoventilation syndrome, congenital, MIM# 209880; Waardenburg syndrome, type 4B, MIM# 613265; {Hirschsprung disease, susceptibility to, 4}, MIM# 613712
Mendeliome v0.9990 EDN3 Zornitza Stark reviewed gene: EDN3: Rating: GREEN; Mode of pathogenicity: None; Publications: 8630502, 11303518, 9359047, 10231870, 30171849, 27370713; Phenotypes: Central hypoventilation syndrome, congenital, MIM# 209880, Waardenburg syndrome, type 4B, MIM# 613265, {Hirschsprung disease, susceptibility to, 4}, MIM# 613712; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9990 DLL3 Zornitza Stark Marked gene: DLL3 as ready
Mendeliome v0.9986 SMAD2 Zornitza Stark Phenotypes for gene: SMAD2 were changed from Aortic and arterial aneurysmal disease; connective tissue disease to Aortic and arterial aneurysmal disease; connective tissue disease; congenital heart disease
Mendeliome v0.9984 CARD10 Zornitza Stark Marked gene: CARD10 as ready
Mendeliome v0.9984 CARD10 Zornitza Stark Gene: card10 has been classified as Red List (Low Evidence).
Mendeliome v0.9984 CARD10 Zornitza Stark gene: CARD10 was added
gene: CARD10 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CARD10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CARD10 were set to 32238915
Phenotypes for gene: CARD10 were set to Immunodeficiency 89 and autoimmunity, MIM# 619632
Review for gene: CARD10 was set to RED
Added comment: A pair of siblings reported with adult onset of recurrent infections, allergies, microcytic anaemia, and Crohn disease. Homozygous missense variant.
Sources: Expert list
Mendeliome v0.9983 TBX21 Zornitza Stark Marked gene: TBX21 as ready
Mendeliome v0.9979 SMAD2 Melanie Marty changed review comment from: 9 individuals from 5 families with wide spectrum of autosomal dominant aortic and arterial aneurysmal disease combined with connective tissue disease similar to Marfan syndrome and Loeys-Dietz syndrome.; to: 10 individuals from 5 families with wide spectrum of autosomal dominant aortic and arterial aneurysmal disease combined with connective tissue disease similar to Marfan syndrome and Loeys-Dietz syndrome.
Mendeliome v0.9979 SMAD2 Melanie Marty commented on gene: SMAD2: PMID: 30157302 - Two distinct phenotypes associated with pathogenic variants in SMAD2: complex congenital heart disease with or without laterality defects and other congenital anomalies, and a late-onset vascular phenotype characterized by arterial aneurysms with connective tissue abnormalities. No genotype/phenotype correlation has been established so far.

PMID: 30157302, PMID: 23665959 - 5 individuals reported with the CHD phenotype
Mendeliome v0.9979 SMAD2 Melanie Marty edited their review of gene: SMAD2: Added comment: PMID: 30157302 - Two distinct phenotypes associated with pathogenic variants in SMAD2: complex congenital heart disease with or without laterality defects and other congenital anomalies, and a late-onset vascular phenotype characterized by arterial aneurysms with connective tissue abnormalities. No genotype/phenotype correlation has been established so far.

PMID: 30157302, PMID: 23665959 - 5 individuals reported with the CHD phenotype; Changed publications: 29967133, 30157302, 23665959; Changed phenotypes: Aortic and arterial aneurysmal disease, connective tissue disease, congenital heart disease
Mendeliome v0.9979 DHCR24 Zornitza Stark Marked gene: DHCR24 as ready
Mendeliome v0.9976 EMD Zornitza Stark Marked gene: EMD as ready
Mendeliome v0.9976 EMD Zornitza Stark Phenotypes for gene: EMD were changed from to Emery-Dreifuss muscular dystrophy 1, X-linked MIM#310300
Mendeliome v0.9973 MTPAP Zornitza Stark Marked gene: MTPAP as ready
Mendeliome v0.9970 EMD Belinda Chong reviewed gene: EMD: Rating: GREEN; Mode of pathogenicity: None; Publications: 21697856 31802929; Phenotypes: Emery-Dreifuss muscular dystrophy 1, X-linked MIM#310300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.9970 GTPBP3 Zornitza Stark Marked gene: GTPBP3 as ready
Mendeliome v0.9967 GRIP1 Zornitza Stark Marked gene: GRIP1 as ready
Mendeliome v0.9965 GRIP1 Zornitza Stark changed review comment from: Typical features include cryptophthalmos, syndactyly, and abnormalities of the respiratory and urogenital tract. At least 5 families reported.; to: Typical features include cryptophthalmos, syndactyly, and abnormalities of the respiratory and urogenital tract. At least 5 families reported.

'Mild' bi-allelic variants also postulated to cause isolated CAKUT, PMID 24700879.
Mendeliome v0.9964 GRHL3 Zornitza Stark Marked gene: GRHL3 as ready
Mendeliome v0.9961 GNPTAB Zornitza Stark Marked gene: GNPTAB as ready
Mendeliome v0.9958 AMMECR1 Zornitza Stark Marked gene: AMMECR1 as ready
Mendeliome v0.9958 AMMECR1 Zornitza Stark Phenotypes for gene: AMMECR1 were changed from to Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis, MIM# 300990
Mendeliome v0.9955 AMMECR1 Zornitza Stark reviewed gene: AMMECR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27811305, 28089922, 29193635; Phenotypes: Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis, MIM# 300990; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.9955 AMACR Zornitza Stark Marked gene: AMACR as ready
Mendeliome v0.9952 NADSYN1 Zornitza Stark Phenotypes for gene: NADSYN1 were changed from Multiple congenital abnormalities; absent kidneys; cardiac; limb; vertebral to Vertebral, cardiac, renal, and limb defects syndrome 3, MONDO:0030077; Vertebral, cardiac, renal, and limb defects syndrome 3, OMIM:618845
Mendeliome v0.9951 NADSYN1 Zornitza Stark edited their review of gene: NADSYN1: Changed phenotypes: Vertebral, cardiac, renal, and limb defects syndrome 3, MONDO:0030077, Vertebral, cardiac, renal, and limb defects syndrome 3, OMIM:618845
Mendeliome v0.9951 DMC1 Bryony Thompson Marked gene: DMC1 as ready
Mendeliome v0.9950 DMC1 Bryony Thompson gene: DMC1 was added
gene: DMC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DMC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DMC1 were set to 34794894; 29331980; 9660954; 9660953; 18166824
Phenotypes for gene: DMC1 were set to Primary ovarian insufficiency; non-obstructive azoospermia
Review for gene: DMC1 was set to GREEN
Added comment: PMID: 34515795 - a homozygous frameshift (p. Glu10Asnfs*31) cosegregated with non-obstructive azoospermia in 1 brother and diminished ovarian reserve (not primary ovarian insufficiency) in 2 sisters in a non-consanguineous family. Further homozygous knockout mice study demonstrated total failure of follicle development and spermatogenesis in male mice.
PMID: 29331980 - a homozygous missense (p.Asp36Asn) cosegregated with non-obstructive azoospermia and POI phenotypes in a single family.
PMID: 18166824 - a POI case identified with a homozygous missense (p.Met200Val, 185 homozygotes in gnomAD v2.1), which is too common for a recessive Mendelian disease
PMID: 9660954, 9660953 - both male and female knockout mice are sterile
Sources: Literature
Mendeliome v0.9949 CPEB1 Bryony Thompson Marked gene: CPEB1 as ready
Mendeliome v0.9948 CPEB1 Bryony Thompson gene: CPEB1 was added
gene: CPEB1 was added to Mendeliome. Sources: Literature
SV/CNV tags were added to gene: CPEB1.
Mode of inheritance for gene: CPEB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CPEB1 were set to 34794894; 33095795; 32354341; 30689869; 11702780
Phenotypes for gene: CPEB1 were set to Primary ovarian insufficiency
Review for gene: CPEB1 was set to AMBER
Added comment: Large CNVs including CPEB1 mainly reported, but also include BNC1.
PMID: 33095795 - 1 POI case with missense variant p.R87C, which has 101 hets in gnomAD v2.1 (too common for a Mendelian dominantly inherited disease). Also another POI case with an 83.8Kb deletion including CPEB1.
PMID: 32354341 - 1 primary amenorrhea case heterozygous deletion of exons 8-12 of CPEB1
PMID: 30689869 - 6 POI cases (including previously reported) with a 15q25.2 deletion including CPEB1, but also including POI gene BNC1. Also, a homozygous microdeletion involving CPEB1 intron 1 in one case.
PMID: 11702780 - knockout mouse model had vestigial ovaries devoid of oocytes
Sources: Literature
Mendeliome v0.9947 CD44 Zornitza Stark Marked gene: CD44 as ready
Mendeliome v0.9944 BCAM Zornitza Stark Marked gene: BCAM as ready
Mendeliome v0.9943 DDR2 Zornitza Stark Marked gene: DDR2 as ready
Mendeliome v0.9943 DDR2 Zornitza Stark Phenotypes for gene: DDR2 were changed from to Spondylometaepiphyseal dysplasia, short limb-hand type, MIM#271665; Warburg-Cinotti syndrome, MIM# 618175
Mendeliome v0.9940 DDR2 Zornitza Stark reviewed gene: DDR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19110212, 20223752, 30449416; Phenotypes: Spondylometaepiphyseal dysplasia, short limb-hand type, MIM#271665, Warburg-Cinotti syndrome, MIM# 618175; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9939 MSX2 Zornitza Stark Marked gene: MSX2 as ready
Mendeliome v0.9939 MSX2 Zornitza Stark Phenotypes for gene: MSX2 were changed from to Craniosynostosis 2 (MIM#604757); Parietal foramina 1 (MIM#168500); Parietal foramina with cleidocranial dysplasia (MIM#168550)
Mendeliome v0.9936 AKT2 Zornitza Stark Marked gene: AKT2 as ready
Mendeliome v0.9936 BNC1 Bryony Thompson Marked gene: BNC1 as ready
Mendeliome v0.9932 BNC1 Bryony Thompson gene: BNC1 was added
gene: BNC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BNC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BNC1 were set to 34794894; 30010909; 16624857; 32962729; 32894148; 30689869; 27301361
Phenotypes for gene: BNC1 were set to Premature ovarian failure 16 MIM#618723
Review for gene: BNC1 was set to GREEN
Added comment: PMID: 30010909 - a heterozygous frameshift variant segregates with POF in 6 affected females in a Chinese family. A female mouse model of the human Bnc1 frameshift mutation exhibited infertility.
PMID: 32962729 - 1 POF case with p.Asp575Val (which has 89 hets in gnomAD v2.1) and 1 POF case with biallelic missense variants (p.Asp568Val & p.Leu525Pro).
SCV001364363.1 - 1 POF case submitted by Medical Cytogenetics and Molecular Genetics Laboratory,IRCCS Istituto Auxologico Italiano to ClinVar with NM_001717.4(BNC1):c.2273C>T (p.Thr758Ile)
PMID: 32894148, 30689869, 27301361 - large CNVs involving BNC1 reported in POF cases
PMID: 16624857 - knockdown of the gene in mouse oocytes lead to subfertility
Sources: Literature
Mendeliome v0.9931 ACVR1 Zornitza Stark Phenotypes for gene: ACVR1 were changed from Fibrodysplasia ossificans progressiva, MIM# 135100 to Fibrodysplasia ossificans progressiva, MIM# 135100; Congenital heart disease
Mendeliome v0.9929 ACVR1 Zornitza Stark changed review comment from: Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. FOP has a prevalence of approximately 1 in 2 million worldwide, and shows no geographic, ethnic, racial, or gender preference. Individuals with FOP appear normal at birth except for great toe abnormalities: the great toes are short, deviated, and monophalangic. Ossification occurs progressively over the course of a lifetime in an inevitable and unpredictable episodic manner.

Multiple unrelated families reported. The R206H variant is recurrent.; to: Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. FOP has a prevalence of approximately 1 in 2 million worldwide, and shows no geographic, ethnic, racial, or gender preference. Individuals with FOP appear normal at birth except for great toe abnormalities: the great toes are short, deviated, and monophalangic. Ossification occurs progressively over the course of a lifetime in an inevitable and unpredictable episodic manner.

Multiple unrelated families reported. The R206H variant is recurrent.

Note variants in this gene are also associated with congenital heart disease, PMID 29089047.
Mendeliome v0.9929 ACVR1 Zornitza Stark edited their review of gene: ACVR1: Changed publications: 16642017, 29089047; Changed phenotypes: Fibrodysplasia ossificans progressiva, MIM# 135100, Congenital heart disease
Mendeliome v0.9929 MSX2 Daniel Flanagan reviewed gene: MSX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23949913, 27884935, 23918290, 2359311, 22948472, 19533795, 10742103, 14571277; Phenotypes: Craniosynostosis 2 (MIM#604757), Parietal foramina 1 (MIM#168500), Parietal foramina with cleidocranial dysplasia (MIM#168550); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9929 ACVR1 Zornitza Stark Marked gene: ACVR1 as ready
Mendeliome v0.9926 MOCS2 Zornitza Stark Marked gene: MOCS2 as ready
Mendeliome v0.9923 ANKRD31 Bryony Thompson Marked gene: ANKRD31 as ready
Mendeliome v0.9922 ANKRD31 Bryony Thompson gene: ANKRD31 was added
gene: ANKRD31 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ANKRD31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANKRD31 were set to 34794894; 34257419; 31003867
Phenotypes for gene: ANKRD31 were set to Premature ovarian failure
Review for gene: ANKRD31 was set to GREEN
Added comment: Three unrelated cases with premature ovarian failure and loss of function variants (2 with c.985C>T, p.Gln329* and 1 with c.1565-2A>G). Ankrd31-deficient female mouse model has reduced oocyte reserves.
Sources: Literature
Mendeliome v0.9921 ACO2 Zornitza Stark Marked gene: ACO2 as ready
Mendeliome v0.9921 ACO2 Zornitza Stark Phenotypes for gene: ACO2 were changed from to Infantile cerebellar-retinal degeneration, MIM#614559; Optic atrophy 9, MIM# 616289
Mendeliome v0.9918 ACO2 Zornitza Stark edited their review of gene: ACO2: Changed phenotypes: Infantile cerebellar-retinal degeneration, MIM#614559, Optic atrophy 9, MIM# 616289
Mendeliome v0.9918 ACO2 Zornitza Stark edited their review of gene: ACO2: Added comment: At least 10 unrelated families reported. I am not convinced this gene causes two separate disorders, more likely a spectrum. OA has been reported as an isolated finding in one family, and a feature of a more complex and severe neurological presentation in the rest.; Changed publications: 22405087, 25351951, 30689204, 32519519, 25351951
Mendeliome v0.9918 DAZL Bryony Thompson Marked gene: DAZL as ready
Mendeliome v0.9917 DAZL Bryony Thompson gene: DAZL was added
gene: DAZL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DAZL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DAZL were set to 34794894; 33095795; 16884537; 9288969
Phenotypes for gene: DAZL were set to Primary ovarian insufficiency
Review for gene: DAZL was set to AMBER
Added comment: PMID: 33095795 - Single POI case with heterozygous stopgain (c.640C>T:p.Q214*).
PMID: 16884537 - 4 heterozygous unrelated early menopause/POI cases with heterozygous missense (all rare in gnomAD v2.1, except p.Asn10His which has 14 hets)
PMID: 9288969 - supporting knockout mouse model
Sources: Literature
Mendeliome v0.9915 DAG1 Zornitza Stark reviewed gene: DAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21388311, 25934851, 24052401, 25503980; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, 613818, Walker-Warburg syndrome and tectocerebellar dysgraphia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9915 CYP17A1 Zornitza Stark Marked gene: CYP17A1 as ready
Mendeliome v0.9912 CYP11B1 Zornitza Stark Marked gene: CYP11B1 as ready
Mendeliome v0.9909 CYP11A1 Zornitza Stark Marked gene: CYP11A1 as ready
Mendeliome v0.9909 CYP11A1 Zornitza Stark Phenotypes for gene: CYP11A1 were changed from to Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete, MIM# 613743
Mendeliome v0.9906 CYP11A1 Zornitza Stark reviewed gene: CYP11A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12161514, 16705068, 18182448, 28425981; Phenotypes: Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete, MIM# 613743; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9906 CWC27 Zornitza Stark Marked gene: CWC27 as ready
Mendeliome v0.9903 PPIB Zornitza Stark Marked gene: PPIB as ready
Mendeliome v0.9900 POLR3H Bryony Thompson Marked gene: POLR3H as ready
Mendeliome v0.9899 POLR3H Bryony Thompson gene: POLR3H was added
gene: POLR3H was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POLR3H was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3H were set to 34794894; 30830215
Phenotypes for gene: POLR3H were set to Primary ovarian insufficiency
Review for gene: POLR3H was set to AMBER
Added comment: A homozygous missense variant (p.Asp50Gly) was identified homozygous in 2 unrelated families. A mull mouse model was embryonic lethal, but a mouse model homozygous for the missense were viable and showed delayed pubertal development, characterised by late first oestrus or preputial separation.
Sources: Literature
Mendeliome v0.9898 POLR2C Bryony Thompson Marked gene: POLR2C as ready
Mendeliome v0.9897 POLR2C Bryony Thompson gene: POLR2C was added
gene: POLR2C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POLR2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR2C were set to 34794894; 29367954
Phenotypes for gene: POLR2C were set to Primary ovarian insufficiency
Review for gene: POLR2C was set to AMBER
Added comment: One family with POI segregating a nonsense variant (p.Lys152Ter) and a case with sporadic POI with a splice region variant (c.206-3C>T). Knockdown of the gene in an embryonic carcinoma cell line resulted in decreased protein production and impaired cell proliferation.
Two missense in premature ovarian failure cases submitted to ClinVar by Shandong Provincial Hospital Affiliated to Shandong University (SCV001877131.1, SCV001877153.1).
Sources: Literature
Mendeliome v0.9896 ELAC2 Zornitza Stark Marked gene: ELAC2 as ready
Mendeliome v0.9893 KHDRBS1 Bryony Thompson Marked gene: KHDRBS1 as ready
Mendeliome v0.9892 KHDRBS1 Bryony Thompson gene: KHDRBS1 was added
gene: KHDRBS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KHDRBS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KHDRBS1 were set to 34794894; 29808484; 28938739; 20881015
Phenotypes for gene: KHDRBS1 were set to Premature ovarian failure
Review for gene: KHDRBS1 was set to GREEN
Added comment: 4 cases in 3 unrelated families and a supporting mouse model
PMID: 28938739 - missense (c.460A > G, p.M154V) identified in a Chinese mother and daughter with POI, and another missense (c.263C > T, p.P88L) identified in an idiopathic POI case.
SCV001364312.1 - case with POI and missense (p.Pro421Leu) submitted by an Italian institute (ClinVar ID: 929733)
PMID: 29808484 - missense (p.Pro296Leu) identified in a POI case, which also has a heterozygous missense in FGFR2. There are 12 hets with Pro296Leu in gnomAD v2.1. This case is not included in the final case count.
PMID: 20881015 - supporting null mouse model. Female mice were subfertile.
Sources: Literature
Mendeliome v0.9891 CUL4B Zornitza Stark Marked gene: CUL4B as ready
Mendeliome v0.9891 CUL4B Zornitza Stark Phenotypes for gene: CUL4B were changed from to Mental retardation, X-linked, syndromic 15 (Cabezas type), MIM# 300354
Mendeliome v0.9888 CUL4B Zornitza Stark reviewed gene: CUL4B: Rating: GREEN; Mode of pathogenicity: None; Publications: 17236139, 19377476; Phenotypes: Mental retardation, X-linked, syndromic 15 (Cabezas type), MIM# 300354; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.9888 CTSK Zornitza Stark Marked gene: CTSK as ready
Mendeliome v0.9886 CTCF Zornitza Stark Marked gene: CTCF as ready
Mendeliome v0.9886 CTCF Zornitza Stark Phenotypes for gene: CTCF were changed from to Mental retardation, autosomal dominant 21 (MIM#615502)
Mendeliome v0.9883 CTCF Zornitza Stark reviewed gene: CTCF: Rating: GREEN; Mode of pathogenicity: None; Publications: 23746550, 31239556; Phenotypes: Mental retardation, autosomal dominant 21 (MIM#615502); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9883 CSNK2A1 Zornitza Stark Marked gene: CSNK2A1 as ready
Mendeliome v0.9880 CRYGD Zornitza Stark Marked gene: CRYGD as ready
Mendeliome v0.9880 CRYGD Zornitza Stark Phenotypes for gene: CRYGD were changed from to Cataract 4, multiple types, MIM# 115700
Mendeliome v0.9877 CRYGD Zornitza Stark reviewed gene: CRYGD: Rating: GREEN; Mode of pathogenicity: None; Publications: 9927684, 10915766, 12676897, 17724170; Phenotypes: Cataract 4, multiple types, MIM# 115700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9877 CRYGC Zornitza Stark Marked gene: CRYGC as ready
Mendeliome v0.9877 CRYGC Zornitza Stark Phenotypes for gene: CRYGC were changed from to Cataract 2, multiple types, MIM# 604307
Mendeliome v0.9874 CRYGC Zornitza Stark reviewed gene: CRYGC: Rating: GREEN; Mode of pathogenicity: None; Publications: 10521291, 10914683, 12011157, 19204787, 22052681; Phenotypes: Cataract 2, multiple types, MIM# 604307; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9874 CRYBB3 Zornitza Stark Marked gene: CRYBB3 as ready
Mendeliome v0.9874 CRYBB3 Zornitza Stark Phenotypes for gene: CRYBB3 were changed from to Cataract 22, MIM# 609741
Mendeliome v0.9871 CRYBB3 Zornitza Stark reviewed gene: CRYBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 15914629, 23508780, 34356085, 33594837, 33510601; Phenotypes: Cataract 22, MIM# 609741; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9871 CRYBB2 Zornitza Stark Marked gene: CRYBB2 as ready
Mendeliome v0.9871 CRYBB2 Zornitza Stark Phenotypes for gene: CRYBB2 were changed from to Cataract 3, multiple types, MIM# 601547
Mendeliome v0.9868 CRYBB2 Zornitza Stark reviewed gene: CRYBB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 9158139, 10634616, 11424921, 17234267; Phenotypes: Cataract 3, multiple types, MIM# 601547; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9868 CRYBB1 Zornitza Stark Marked gene: CRYBB1 as ready
Mendeliome v0.9868 CRYBB1 Zornitza Stark Phenotypes for gene: CRYBB1 were changed from to Cataract 17, multiple types, MIM# 611544
Mendeliome v0.9865 CRYBB1 Zornitza Stark reviewed gene: CRYBB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12360425, 16110300, 17460281, 21972112; Phenotypes: Cataract 17, multiple types, MIM# 611544; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9865 TNFAIP3 Zornitza Stark Marked gene: TNFAIP3 as ready
Mendeliome v0.9862 SFTPA1 Zornitza Stark Phenotypes for gene: SFTPA1 were changed from Idiopathic pulmonary fibrosis to Idiopathic pulmonary fibrosis; Interstitial lung disease 1, MIM# 619611
Mendeliome v0.9861 SFTPA1 Zornitza Stark edited their review of gene: SFTPA1: Changed phenotypes: Idiopathic pulmonary fibrosis, Interstitial lung disease 1, MIM# 619611
Mendeliome v0.9861 PI4KA Zornitza Stark Phenotypes for gene: PI4KA were changed from Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531; Neurodevelopmental syndrome with hypomyelinating leukodystrophy to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531; Neurodevelopmental syndrome with hypomyelinating leukodystrophy; Spastic paraplegia 84, autosomal recessive, MIM# 619621
Mendeliome v0.9860 PI4KA Zornitza Stark edited their review of gene: PI4KA: Changed phenotypes: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531, Neurodevelopmental syndrome with hypomyelinating leukodystrophy, Spastic paraplegia 84, autosomal recessive, MIM# 619621
Mendeliome v0.9860 UCP2 Zornitza Stark Marked gene: UCP2 as ready
Mendeliome v0.9856 CRYBA4 Zornitza Stark Marked gene: CRYBA4 as ready
Mendeliome v0.9856 CRYBA4 Zornitza Stark Phenotypes for gene: CRYBA4 were changed from to Cataract 23, MIM# 610425
Mendeliome v0.9853 CRYBA4 Zornitza Stark reviewed gene: CRYBA4: Rating: GREEN; Mode of pathogenicity: None; Publications: 16960806, 16960806, 20577656; Phenotypes: Cataract 23, MIM# 610425; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9853 CRYBA1 Zornitza Stark Marked gene: CRYBA1 as ready
Mendeliome v0.9853 CRYBA1 Zornitza Stark Phenotypes for gene: CRYBA1 were changed from to Cataract 10, multiple types, MIM# 600881
Mendeliome v0.9850 CRYBA1 Zornitza Stark reviewed gene: CRYBA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9788845, 14598164, 34419537, 33827296, 31488069; Phenotypes: Cataract 10, multiple types, MIM# 600881; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9850 CRYAA Zornitza Stark Marked gene: CRYAA as ready
Mendeliome v0.9850 CRYAA Zornitza Stark Phenotypes for gene: CRYAA were changed from to Cataract 9, multiple types, MIM# 604219
Mendeliome v0.9847 CRYAA Zornitza Stark reviewed gene: CRYAA: Rating: GREEN; Mode of pathogenicity: None; Publications: 9467006, 11006246, 16735993, 17724170, 23255486; Phenotypes: Cataract 9, multiple types, MIM# 604219; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9847 CALU Zornitza Stark Marked gene: CALU as ready
Mendeliome v0.9846 EDNRA Zornitza Stark Marked gene: EDNRA as ready
Mendeliome v0.9843 DVL3 Zornitza Stark Marked gene: DVL3 as ready
Mendeliome v0.9840 IRF6 Zornitza Stark Marked gene: IRF6 as ready
Mendeliome v0.9838 IRF6 Zornitza Stark Marked gene: IRF6 as ready
Mendeliome v0.9835 MATN3 Zornitza Stark Marked gene: MATN3 as ready
Mendeliome v0.9832 INPPL1 Zornitza Stark Marked gene: INPPL1 as ready
Mendeliome v0.9829 MAF Zornitza Stark Marked gene: MAF as ready
Mendeliome v0.9826 LRP4 Zornitza Stark Marked gene: LRP4 as ready
Mendeliome v0.9823 MLC1 Zornitza Stark Marked gene: MLC1 as ready
Mendeliome v0.9820 MMP13 Zornitza Stark Marked gene: MMP13 as ready
Mendeliome v0.9818 MBTPS2 Zornitza Stark Marked gene: MBTPS2 as ready
Mendeliome v0.9818 MBTPS2 Zornitza Stark Phenotypes for gene: MBTPS2 were changed from to Osteogenesis imperfecta, type XIX, (MIM301014); IFAP syndrome with or without BRESHECK syndrome (MIM#308205); Keratosis follicularis spinulosa decalvans, X-linked (MIM#308800); Olmsted syndrome, X-linked (MIM#300918)
Mendeliome v0.9815 IHH Zornitza Stark Marked gene: IHH as ready
Mendeliome v0.9810 KCTD1 Zornitza Stark Marked gene: KCTD1 as ready
Mendeliome v0.9810 KCTD1 Zornitza Stark Phenotypes for gene: KCTD1 were changed from to Scalp-ear-nipple syndrome MIM#181270
Mendeliome v0.9807 KCNJ2 Zornitza Stark Marked gene: KCNJ2 as ready
Mendeliome v0.9804 MID1 Zornitza Stark Marked gene: MID1 as ready
Mendeliome v0.9801 KAT6A Zornitza Stark Marked gene: KAT6A as ready
Mendeliome v0.9801 KAT6A Zornitza Stark Phenotypes for gene: KAT6A were changed from to Arboleda-Tham syndrome MIM#616268
Mendeliome v0.9800 MESP2 Zornitza Stark Marked gene: MESP2 as ready
Mendeliome v0.9795 ZNF365 Zornitza Stark Marked gene: ZNF365 as ready
Mendeliome v0.9794 CRLF1 Zornitza Stark Marked gene: CRLF1 as ready
Mendeliome v0.9791 CPT2 Zornitza Stark Marked gene: CPT2 as ready
Mendeliome v0.9788 COX7B Zornitza Stark Marked gene: COX7B as ready
Mendeliome v0.9788 COX7B Zornitza Stark Phenotypes for gene: COX7B were changed from to Linear skin defects with multiple congenital anomalies 2, MIM#300887
Mendeliome v0.9785 COX7B Zornitza Stark reviewed gene: COX7B: Rating: GREEN; Mode of pathogenicity: None; Publications: 23122588; Phenotypes: Linear skin defects with multiple congenital anomalies 2, MIM#300887; 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 v0.9785 COQ4 Zornitza Stark Marked gene: COQ4 as ready
Mendeliome v0.9785 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from to Coenzyme Q10 deficiency, primary, 7, MIM# 616276
Mendeliome v0.9782 COQ4 Zornitza Stark reviewed gene: COQ4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25658047, 26185144, 33704555; Phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9782 COLEC11 Zornitza Stark Marked gene: COLEC11 as ready
Mendeliome v0.9779 MBTPS2 Daniel Flanagan reviewed gene: MBTPS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27380894, 19361614, 21426410; Phenotypes: Osteogenesis imperfecta, type XIX, (MIM301014), IFAP syndrome with or without BRESHECK syndrome (MIM#308205), Keratosis follicularis spinulosa decalvans, X-linked (MIM#308800), ?Olmsted syndrome, X-linked (MIM#300918); 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 v0.9779 KCTD1 Ain Roesley reviewed gene: KCTD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23541344, 31324836; Phenotypes: Scalp-ear-nipple syndrome MIM#181270; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.9779 KAT6A Ain Roesley reviewed gene: KAT6A: Rating: GREEN; Mode of pathogenicity: None; Publications: 30245513; Phenotypes: Arboleda-Tham syndrome MIM#616268; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.9779 COG1 Zornitza Stark Marked gene: COG1 as ready
Mendeliome v0.9776 NEBL Bryony Thompson Added comment: Comment on list classification: Limited gene-disease vailidity, Classification - 09/25/2020 by ClinGen Dilated Cardiomyopathy GCEP. Evidence Summary: NEBL was evaluated for autosomal dominant dilated cardiomyopathy (DCM). Human genetic evidence supporting this gene-disease relationship includes case-level data. Arimura and colleagues (2000, PMID: 11140941) analyzed 83 DCM patients and 311 healthy controls, identifying 4 missense variants of unknown significance (VUSs) in 4 DCM cases. High minor allele frequencies (MAFs) and lack of segregation excluded these variants as evidence. Purevjav and colleagues (2010, PMID: 20951326) investigated a total of 260 DCM patients and 300 unrelated ethnic matched controls by direct DNA sequencing. Authors identified 4 missense VUSs. One of these variants (Q128R) was downgraded in level of evidence due to the lack of segregation. The other 3 variants were not scored because of their MAF. Perrot and colleagues (2016, PMID: 27186169) investigated a total of 389 patients with DCM, HCM, or LVNC, 320 Caucasian sex-matched controls and 192 Caucasian sex-matched blood donors and identified 3 missense VUSs in 4 families. One of these variants was also carried by healthy relatives and therefore was excluded, however this may be explained by reduced penetrance. The 2 other variants lacked segregation as well and therefore were also excluded. In addition, this gene-disease association is supported by animal models. Mastronotaro and colleagues (2015, PMID: 25987543) created a NEBL knockout mice that exhibited normal cardiac function up to 9 months of age but after 2 weeks of transaortic constriction (TAC), these mice showed Z-line widening since the age of 5 months and upregulation of cardiac stress genes (basal and after TAC) However, absence of clinical DCM features in KO-NEBL mice as well as Western Blot analysis which contradicted previous findings by showing a similar protein expression between knockout and wild-type mice, excluding it as evidence. Purevjav and colleagues (2010, PMID: 20951326) generated a transgenic mouse overexpressing WT or mutant NEBL under the control of the α-MyHC promoter (4 variants were tested). Mice overexpressing p.K60N or p.Q128R variants died within 1 year because of severe heart enlargement and heart failure. Mice overexpressing p.G202R or p.A592E were born and developed normally but after 6 months displayed reduced stress tolerance, cardiac enlargement due to left ventricle dilation, myocyte disarray, and interstitial cell infiltration. In summary, there is limited evidence to support this gene-disease relationship. More evidence is needed to support the relationship of NEBL and autosomal dominant DCM. This classification was approved by the ClinGen Dilated Cardiomyopathy Working Group on October 11, 2019 (SOP Version 7). Gene Clinical Validity Standard Operating Procedures (SOP) - SOP7
Mendeliome v0.9775 SPATA5L1 Zornitza Stark Phenotypes for gene: SPATA5L1 were changed from Intellectual disability; spastic-dystonic cerebral palsy; epilepsy; hearing loss to Neurodevelopmental disorder with hearing loss and spasticity, MIM# 619616; Deafness, autosomal recessive 119, MIM# 619615
Mendeliome v0.9774 SPATA5L1 Zornitza Stark changed review comment from: Note some of the affected individuals had isolated deafness, hence two OMIM phenotypes have been associated with this gene. All were of Ashkenazi Jewish origin, and had the p.Ile466Met founder variant, either hmz or compound het with another variant.; to: Note some of the affected individuals had isolated deafness, hence two OMIM phenotypes have been associated with this gene. All were of Ashkenazi Jewish origin, and had the p.Ile466Met founder variant, compound het with another variant.
Mendeliome v0.9774 SPATA5L1 Zornitza Stark edited their review of gene: SPATA5L1: Added comment: Note some of the affected individuals had isolated deafness, hence two OMIM phenotypes have been associated with this gene. All were of Ashkenazi Jewish origin, and had the p.Ile466Met founder variant, either hmz or compound het with another variant.; Changed publications: 34626583; Changed phenotypes: Neurodevelopmental disorder with hearing loss and spasticity, MIM# 619616, Deafness, autosomal recessive 119, MIM# 619615
Mendeliome v0.9774 SPATA5L1 Zornitza Stark reviewed gene: SPATA5L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hearing loss and spasticity, MIM# 619616; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9774 MEIS2 Zornitza Stark Marked gene: MEIS2 as ready
Mendeliome v0.9774 MEIS2 Zornitza Stark Phenotypes for gene: MEIS2 were changed from to Cleft palate, cardiac defects, and mental retardation (MIM#600987)
Mendeliome v0.9771 LAMA4 Zornitza Stark Marked gene: LAMA4 as ready
Mendeliome v0.9771 LAMA4 Zornitza Stark Phenotypes for gene: LAMA4 were changed from to Cardiomyopathy, dilated, 1JJ (MIM#615235)
Mendeliome v0.9767 LAMA4 Zornitza Stark reviewed gene: LAMA4: Rating: RED; Mode of pathogenicity: None; Publications: 17646580, 26406308, 27532257; Phenotypes: Cardiomyopathy, dilated, 1JJ (MIM#615235); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9764 ATP1A2 Zornitza Stark Phenotypes for gene: ATP1A2 were changed from Alternating hemiplegia of childhood 1, MIM#104290; Hydrops fetalis, microcephaly, arthrogryposis, extensive cortical malformations; Developmental and epileptic encephalopathy, polymicrogyria to Alternating hemiplegia of childhood 1, MIM#104290; Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies, MIM# 619602; Developmental and epileptic encephalopathy, polymicrogyria
Mendeliome v0.9762 MED17 Zornitza Stark changed review comment from: 5 individuals from 3 families now reported with intellectual disability and variable other neurological features including ataxia and seizures.; to: Over 10 families now reported with intellectual disability and variable other neurological features including ataxia, microcephaly and seizures.

Note the c.1112T>C (p.L371P) variant is a founder variant in the Caucasus-Jewish families.
Mendeliome v0.9762 CNTNAP2 Zornitza Stark Marked gene: CNTNAP2 as ready
Mendeliome v0.9759 CKAP2L Zornitza Stark Marked gene: CKAP2L as ready
Mendeliome v0.9756 P3H1 Zornitza Stark Marked gene: P3H1 as ready
Mendeliome v0.9753 CHST3 Zornitza Stark Marked gene: CHST3 as ready
Mendeliome v0.9750 IL1RAPL1 Zornitza Stark Marked gene: IL1RAPL1 as ready
Mendeliome v0.9747 IFITM5 Zornitza Stark Marked gene: IFITM5 as ready
Mendeliome v0.9743 CHRND Zornitza Stark Marked gene: CHRND as ready
Mendeliome v0.9740 CHRNA1 Zornitza Stark Marked gene: CHRNA1 as ready
Mendeliome v0.9737 MAFB Zornitza Stark Marked gene: MAFB as ready
Mendeliome v0.9737 MAFB Zornitza Stark Phenotypes for gene: MAFB were changed from to Multicentric carpotarsal osteolysis syndrome (MIM#166300); Duane retraction syndrome 3, MIM# 617041
Mendeliome v0.9734 ASIP Zornitza Stark Marked gene: ASIP as ready
Mendeliome v0.9733 MAFB Daniel Flanagan reviewed gene: MAFB: Rating: GREEN; Mode of pathogenicity: None; Publications: 23956186, 30208859; Phenotypes: Multicentric carpotarsal osteolysis syndrome (MIM#166300); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9733 CHKB Zornitza Stark Marked gene: CHKB as ready
Mendeliome v0.9733 CHKB Zornitza Stark Phenotypes for gene: CHKB were changed from to Muscular dystrophy, congenital, megaconial type, MIM# 602541
Mendeliome v0.9730 CHKB Zornitza Stark reviewed gene: CHKB: Rating: GREEN; Mode of pathogenicity: None; Publications: 21665002, 23692895, 24997086; Phenotypes: Muscular dystrophy, congenital, megaconial type, MIM# 602541; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9730 CHAMP1 Zornitza Stark Marked gene: CHAMP1 as ready
Mendeliome v0.9730 CHAMP1 Zornitza Stark Phenotypes for gene: CHAMP1 were changed from to Mental retardation, autosomal dominant 40 (MIM#616579)
Mendeliome v0.9727 CHAMP1 Zornitza Stark reviewed gene: CHAMP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27148580, 26340335; Phenotypes: Mental retardation, autosomal dominant 40 (MIM#616579); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9727 CFTR Zornitza Stark Marked gene: CFTR as ready
Mendeliome v0.9725 ETV6 Zornitza Stark Marked gene: ETV6 as ready
Mendeliome v0.9722 BSG Zornitza Stark Marked gene: BSG as ready
Mendeliome v0.9720 TPCN2 Zornitza Stark Marked gene: TPCN2 as ready
Mendeliome v0.9717 MYO9B Zornitza Stark Marked gene: MYO9B as ready
Mendeliome v0.9714 HKDC1 Zornitza Stark Marked gene: HKDC1 as ready
Mendeliome v0.9714 HKDC1 Zornitza Stark gene: HKDC1 was added
gene: HKDC1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: HKDC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HKDC1 were set to 30085091
Phenotypes for gene: HKDC1 were set to Retinitis pigmentosa 92, MIM# 619614
Review for gene: HKDC1 was set to RED
Added comment: Two unrelated Chinese men reported with relatively late-onset RP, and same homozygous missense variant.
Sources: Expert Review
Mendeliome v0.9713 CENPJ Zornitza Stark Marked gene: CENPJ as ready
Mendeliome v0.9713 CENPJ Zornitza Stark Phenotypes for gene: CENPJ were changed from to Microcephaly 6, primary, autosomal recessive, MIM# 608393, MONDO:0012029; Seckel syndrome 4, MIM# 613676, MONDO:0013358
Mendeliome v0.9710 CENPJ Zornitza Stark reviewed gene: CENPJ: Rating: GREEN; Mode of pathogenicity: None; Publications: 20522431, 23166506, 15793586, 20978018, 22775483, 32677750, 32549991; Phenotypes: Microcephaly 6, primary, autosomal recessive, MIM# 608393, MONDO:0012029, Seckel syndrome 4, MIM# 613676, MONDO:0013358; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9710 CDON Zornitza Stark Marked gene: CDON as ready
Mendeliome v0.9707 CDON Zornitza Stark changed review comment from: >5 unrelated families reported, however note some of the variants are present at a very low frequentcy in gnomad (1-4) and some are inherited. Mouse model.; to: >5 unrelated families reported, however note some of the variants are present at a very low frequentcy in gnomad (1-4) and some are inherited. Mouse model.

Note single report of bi-allelic variants in association with coloboma: PMID 32729136
Mendeliome v0.9707 CDH3 Zornitza Stark Marked gene: CDH3 as ready
Mendeliome v0.9707 CDH3 Zornitza Stark Phenotypes for gene: CDH3 were changed from to Ectodermal dysplasia, ectrodactyly, and macular dystrophy, MIM# 225280; Hypotrichosis, congenital, with juvenile macular dystrophy, MIM# 601553
Mendeliome v0.9704 CDH3 Zornitza Stark reviewed gene: CDH3: Rating: GREEN; Mode of pathogenicity: None; Publications: 11544476, 15805154, 28061825, 22140374; Phenotypes: Ectodermal dysplasia, ectrodactyly, and macular dystrophy, MIM# 225280, Hypotrichosis, congenital, with juvenile macular dystrophy, MIM# 601553; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9704 MICAL1 Zornitza Stark Marked gene: MICAL1 as ready
Mendeliome v0.9704 EFHC1 Bryony Thompson Added comment: Comment on list classification: ClinGen Epilepsy GCEP gene-disease association curation: Disputed - We have disregarded the very limited functional evidence in light of the complete lack of genetic evidence connecting EFHC1 and epilepsy. In summary, there is convincing evidence disputing the association between EFHC1 and epilepsy. All variants in EFHC1 associated with epilepsy have contradictory evidence for disease association (too common in ExAC/gnomAD, with minor allele frequencies (MAF) of 2.857e-5 to 0.05973). More evidence is needed to either support or refute the role EFHC1 plays in this disease. Classification - 07/27/2018, reviewed Sept 2021
Mendeliome v0.9702 MICAL1 Bryony Thompson gene: MICAL1 was added
gene: MICAL1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MICAL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MICAL1 were set to 29394500; 21638339
Phenotypes for gene: MICAL1 were set to Autosomal dominant epilepsy with auditory features (ADEAF)
Review for gene: MICAL1 was set to AMBER
Added comment: Two families with supporting in vitro functional assays. Assessment of expression pattern of Mical-1 in the temporal neocortex of patients with intractable temporal epilepsy and pilocarpine-induced rat model, suggests Mical-1 may associate with inner pathophysiological modulation in epilepsy.
Sources: Expert list
Mendeliome v0.9701 CPA6 Bryony Thompson Added comment: Comment on list classification: ClinGen Epilepsy GCEP has reviewed both inheritances for gene-disease associations with epilepsy: AR disease is Disputed - There is contradictory case level and experimental data regarding any association between CPA6 and autosomal recessive epilepsy. Classification - 07/29/2021 AD disease is Refuted- There is very limited evidence supporting a gene-disease association. Many of the reported pathogenic variants have been subsequently identified as having a high minor allele frequency in population databases. Classification - 07/29/2021
Mendeliome v0.9697 ADSSL1 Zornitza Stark Marked gene: ADSSL1 as ready
Mendeliome v0.9694 BRAT1 Zornitza Stark Marked gene: BRAT1 as ready
Mendeliome v0.9694 BRAT1 Zornitza Stark Phenotypes for gene: BRAT1 were changed from to Neurodevelopmental disorder with cerebellar atrophy and with or without seizures, MIM#618056; Rigidity and multifocal seizure syndrome, lethal neonatal, MIM# 614498
Mendeliome v0.9691 BRAT1 Zornitza Stark changed review comment from: At least 4 individuals reported from unrelated families and bi-allelic variants in this gene.
Sources: Expert list; to: Biallelic mutations in the BRAT1 gene, encoding BRCA1-associated ATM activator 1, result in variable phenotypes, from rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL) to neurodevelopmental disorder and cerebellar atrophy with or without seizures (NEDCAS), without obvious genotype-phenotype associations.

Multiple families reported with each.
Mendeliome v0.9691 BRAT1 Zornitza Stark edited their review of gene: BRAT1: Changed publications: 26483087, 26494257, 27282546, 22279524, 23035047, 25319849, 25500575, 34747546; Changed phenotypes: Neurodevelopmental disorder with cerebellar atrophy and with or without seizures, MIM#618056, Rigidity and multifocal seizure syndrome, lethal neonatal, MIM# 614498
Mendeliome v0.9691 SRCAP Zornitza Stark Phenotypes for gene: SRCAP were changed from Floating-Harbor syndrome MIM#136140; Neurodevelopmental disorder, non-Floating Harbor to Floating-Harbor syndrome MIM#136140; Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, MIM# 619595
Mendeliome v0.9690 SRCAP Zornitza Stark edited their review of gene: SRCAP: Changed phenotypes: Floating-Harbor syndrome MIM#136140, Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, MIM# 619595
Mendeliome v0.9688 BMPR1B Zornitza Stark Marked gene: BMPR1B as ready
Mendeliome v0.9685 BMPER Zornitza Stark Marked gene: BMPER as ready
Mendeliome v0.9682 BMPER Zornitza Stark commented on gene: BMPER: Perinatal lethal skeletal dysplasia.

The primary skeletal characteristics include small chest, abnormal vertebral segmentation, and posterior rib gaps containing incompletely differentiated mesenchymal tissue. Consistent craniofacial features include ocular hypertelorism, epicanthal folds, depressed nasal bridge with short nose, and low-set ears. The most commonly described extraskeletal finding is nephroblastomatosis with cystic kidneys, but other visceral findings have been described in some cases.

At least 5 unrelated families reported.
Mendeliome v0.9682 BMP4 Zornitza Stark Marked gene: BMP4 as ready
Mendeliome v0.9679 BMP2 Zornitza Stark Marked gene: BMP2 as ready
Mendeliome v0.9679 BMP2 Zornitza Stark Phenotypes for gene: BMP2 were changed from to Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1, MIM# 617877
Mendeliome v0.9676 BMP2 Zornitza Stark reviewed gene: BMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29198724; Phenotypes: Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1, MIM# 617877; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9676 BMP1 Zornitza Stark Marked gene: BMP1 as ready
Mendeliome v0.9673 BIN1 Zornitza Stark Marked gene: BIN1 as ready
Mendeliome v0.9673 BIN1 Zornitza Stark Phenotypes for gene: BIN1 were changed from to Centronuclear myopathy 2, MIM# 255200
Mendeliome v0.9670 BIN1 Zornitza Stark reviewed gene: BIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17676042; Phenotypes: Centronuclear myopathy 2, MIM# 255200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9670 BHLHA9 Zornitza Stark Marked gene: BHLHA9 as ready
Mendeliome v0.9667 DLL4 Zornitza Stark Marked gene: DLL4 as ready
Mendeliome v0.9664 BFSP2 Zornitza Stark Marked gene: BFSP2 as ready
Mendeliome v0.9664 BFSP2 Zornitza Stark Phenotypes for gene: BFSP2 were changed from to Cataract 12, multiple types, MIM# 611597
Mendeliome v0.9661 BFSP2 Zornitza Stark reviewed gene: BFSP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10729115, 10739768, 15570218, 24654948, 21836522; Phenotypes: Cataract 12, multiple types, MIM# 611597; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9661 B3GAT3 Zornitza Stark changed review comment from: More than 5 unrelated families reported.; to: 26 patients from 13 families with variable phenotypes resembling Larsen, Antley-Bixler, Shprintzen-Goldberg, and Geroderma osteodysplastica syndromes. Multiple skeletal and cardiac abnormalities reported.
Mendeliome v0.9661 HR Zornitza Stark Marked gene: HR as ready
Mendeliome v0.9661 HR Zornitza Stark Phenotypes for gene: HR were changed from to Alopecia universalis MIM#203655; Atrichia with papular lesions MIM#209500
Mendeliome v0.9659 HPSE2 Zornitza Stark Marked gene: HPSE2 as ready
Mendeliome v0.9655 HNRNPK Zornitza Stark Marked gene: HNRNPK as ready
Mendeliome v0.9652 HES7 Zornitza Stark Marked gene: HES7 as ready
Mendeliome v0.9649 DIS3L2 Zornitza Stark Marked gene: DIS3L2 as ready
Mendeliome v0.9646 DDX3X Zornitza Stark Marked gene: DDX3X as ready
Mendeliome v0.9643 SIK3 Zornitza Stark Marked gene: SIK3 as ready
Mendeliome v0.9641 HSD17B3 Zornitza Stark Marked gene: HSD17B3 as ready
Mendeliome v0.9638 HR Ain Roesley reviewed gene: HR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alopecia universalis MIM#203655, Atrichia with papular lesions MIM#209500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.9638 MYH10 Zornitza Stark Marked gene: MYH10 as ready
Mendeliome v0.9637 C9orf3 Zornitza Stark Marked gene: C9orf3 as ready
Mendeliome v0.9636 C9orf3 Zornitza Stark gene: C9orf3 was added
gene: C9orf3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C9orf3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C9orf3 were set to 34596301
Phenotypes for gene: C9orf3 were set to Dystonia 31, MIM# 619565
Review for gene: C9orf3 was set to GREEN
Added comment: Dystonia-31 (DYT31) is an autosomal recessive progressive neurologic disorder characterized by involuntary muscle twisting movements and postural abnormalities affecting the upper and lower limbs, neck, face, and trunk. Some patients may have orofacial dyskinesia resulting in articulation and swallowing difficulties. The age at onset ranges from childhood to young adulthood. There are usually no additional neurologic symptoms, although late-onset parkinsonism was reported in 1 family.

5 individuals from 4 unrelated families reported.

HGNC approved name is AOPEP.
Sources: Literature
Mendeliome v0.9634 ASXL1 Zornitza Stark Marked gene: ASXL1 as ready
Mendeliome v0.9631 ASXL1 Zornitza Stark changed review comment from: Bohring-Opitz syndrome is a malformation syndrome characterized by severe intrauterine growth retardation, poor feeding, profound ID, trigonocephaly, prominent metopic suture, exophthalmos, nevus flammeus of the face, upslanting palpebral fissures, hirsutism, and flexion of the elbows and wrists with deviation of the wrists and metacarpophalangeal joints -- many of these features would be identifiable antenatally.; to: Bohring-Opitz syndrome is a malformation syndrome characterized by severe intrauterine growth retardation, poor feeding, profound ID, trigonocephaly, prominent metopic suture, exophthalmos, nevus flammeus of the face, upslanting palpebral fissures, hirsutism, and flexion of the elbows and wrists with deviation of the wrists and metacarpophalangeal joints.

Multiple individuals reported.
Mendeliome v0.9631 ASNS Zornitza Stark Marked gene: ASNS as ready
Mendeliome v0.9631 ASNS Zornitza Stark Phenotypes for gene: ASNS were changed from to Asparagine synthetase deficiency, MIM#615574
Mendeliome v0.9628 SIK3 Krithika Murali gene: SIK3 was added
gene: SIK3 was added to Mendeliome. Sources: Expert list,Literature
Mode of inheritance for gene: SIK3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SIK3 were set to 30232230; 22318228
Phenotypes for gene: SIK3 were set to ?Spondyloepimetaphyseal dysplasia, Krakow type - #618162
Review for gene: SIK3 was set to AMBER
Added comment: Biallelic SIK3 variants reported in 2 siblings from a consanguineous family with an uncharacterised skeletal dysplasia. Radiographic features included widened/flared metaphyses with irregular ossifications, motheaten long bones, fragmentation of the proximal metacarpals, rounded vertebral bodies, and a distinctive transverse gap seen in the tibias.

In addition to the skeletal phenotype, the siblings manifested significant developmental delay with brain MRI abnormalities, a severe unclassified immunodeficiency, and normal parathyroid hormone concentration with mild hypercalcemia.

One sibling had a more severe phenotype, particularly immunodeficiency, and died of Epstein-Barr virus induced small muscle cancer at 10 years of age.

Mouse models support impaired chondrocyte development with skeletal dysplasia phenotye.
Sources: Expert list, Literature
Mendeliome v0.9628 ANTXR1 Zornitza Stark Marked gene: ANTXR1 as ready
Mendeliome v0.9625 ANOS1 Zornitza Stark Marked gene: ANOS1 as ready
Mendeliome v0.9622 LTBP4 Zornitza Stark Marked gene: LTBP4 as ready
Mendeliome v0.9619 EFEMP2 Zornitza Stark Marked gene: EFEMP2 as ready
Mendeliome v0.9619 EFEMP2 Zornitza Stark Phenotypes for gene: EFEMP2 were changed from to Autosomal recessive cutis laxa type 1B (ARCL1B), MIM# 614437
Mendeliome v0.9616 EFEMP2 Zornitza Stark reviewed gene: EFEMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30140196, 23532871, 31548410, 19664000; Phenotypes: Autosomal recessive cutis laxa type 1B (ARCL1B), MIM# 614437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9616 MYH10 Krithika Murali gene: MYH10 was added
gene: MYH10 was added to Mendeliome. Sources: Expert list,Literature
Mode of inheritance for gene: MYH10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYH10 were set to 24825879; 24901346; 25356899; 22495309; 25003005
Phenotypes for gene: MYH10 were set to Microcephaly; Intellectual Disability
Review for gene: MYH10 was set to GREEN
Added comment: De novo variants were identified in 5 unrelated individuals with moderate-severe ID and developmental delay.

Other reported phenotypic features include microcephaly (4/5), IUGR/failure to thrive (4/5), cerebral atrophy (3/5), hydrocephalus (2/5), congenital bilateral hip dysplasia (2/5), cerebellar atrophy (1/5), congenital diaphragmatic hernia (1/5), cranial nerve palsy (1/5), nystagmus (1/5), dysplastic kidney (1/5).

Defects in heart development, body wall closure and other birth defects noted in mouse models.
Sources: Expert list, Literature
Mendeliome v0.9616 CSF2RB Zornitza Stark Marked gene: CSF2RB as ready
Mendeliome v0.9616 CSF2RB Zornitza Stark Phenotypes for gene: CSF2RB were changed from to Surfactant metabolism dysfunction, pulmonary, 5, MIM#614370
Mendeliome v0.9613 CSF2RB Zornitza Stark reviewed gene: CSF2RB: Rating: GREEN; Mode of pathogenicity: None; Publications: 21205713, 27514590, 7568173, 30846703; Phenotypes: Surfactant metabolism dysfunction, pulmonary, 5, MIM#614370; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9613 CSF2RA Zornitza Stark Marked gene: CSF2RA as ready
Mendeliome v0.9613 CSF2RA Zornitza Stark Phenotypes for gene: CSF2RA were changed from to Surfactant metabolism dysfunction, pulmonary, 4, MIM# 300770
Mendeliome v0.9610 CSF2RA Zornitza Stark reviewed gene: CSF2RA: Rating: GREEN; Mode of pathogenicity: None; Publications: 20622029, 25425184, 18955570; Phenotypes: Surfactant metabolism dysfunction, pulmonary, 4, MIM# 300770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9607 COG6 Zornitza Stark changed review comment from: More than 5 unrelated families reported. Key features include growth retardation, developmental delay, microcephaly, liver and gastrointestinal disease, joint contractures and episodic fever. Ectodermal signs such as hypohidrosis/hyperthermia, hyperkeratosis and tooth anomalies are prominent. Note Shaheen syndrome, MIM#615328 is an allelic disorder, with overlapping clinical features, but normal transferring isoforms recorded creating confusion about whether it represents a distinct entity.; to: More than 5 unrelated families reported. Key features include growth retardation, developmental delay, microcephaly, liver and gastrointestinal disease, joint contractures and episodic fever. Ectodermal signs such as hypohidrosis/hyperthermia, hyperkeratosis and tooth anomalies are prominent. Note Shaheen syndrome, MIM#615328 is an allelic disorder, with overlapping clinical features, but normal transferrin isoforms recorded creating confusion about whether it represents a distinct entity.
Mendeliome v0.9604 OTUD7A Zornitza Stark edited their review of gene: OTUD7A: Added comment: Additional patient reported in PMID 33381903, with hypotonia, ID and seizures. Bi-allelic LoF variants. Some supportive functional data.; Changed rating: AMBER; Changed publications: 31997314, 29395075, 29395074, 33381903
Mendeliome v0.9604 GNAQ Zornitza Stark Marked gene: GNAQ as ready
Mendeliome v0.9604 GNAQ Zornitza Stark Phenotypes for gene: GNAQ were changed from to Sturge-Weber syndrome, somatic, mosaic 185300; Capillary malformations, congenital, 1, somatic, mosaic 163000; Phacomatosis pigmentovascularis
Mendeliome v0.9600 GNAQ Zornitza Stark reviewed gene: GNAQ: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30920161; Phenotypes: Sturge-Weber syndrome, somatic, mosaic 185300, Capillary malformations, congenital, 1, somatic, mosaic 163000, Phacomatosis pigmentovascularis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9600 AKR1C2 Zornitza Stark Marked gene: AKR1C2 as ready
Mendeliome v0.9596 AMER1 Zornitza Stark Marked gene: AMER1 as ready
Mendeliome v0.9593 ALG1 Zornitza Stark Marked gene: ALG1 as ready
Mendeliome v0.9590 NUP85 Eleanor Williams reviewed gene: NUP85: Rating: ; Mode of pathogenicity: None; Publications: 34170319; Phenotypes: intellectual disability, Primary autosomal recessive microcephaly and Seckel syndrome spectrum disorders (MCPH–SCKS); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9590 TUB Zornitza Stark Marked gene: TUB as ready
Mendeliome v0.9586 KSR2 Zornitza Stark Marked gene: KSR2 as ready
Mendeliome v0.9586 KSR2 Zornitza Stark gene: KSR2 was added
gene: KSR2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KSR2 was set to Other
Publications for gene: KSR2 were set to 29273807; 24209692
Phenotypes for gene: KSR2 were set to Obesity
Review for gene: KSR2 was set to RED
Added comment: PMID: 24209692 Targeted deletion of Ksr2 leads to obesity in mice, suggesting a role in energy homeostasis. PMID: 29273807 GWAS identified KSR2 (13 genes studied) implicated in extreme obesity.
Sources: Expert Review
Mendeliome v0.9581 POMC Zornitza Stark Marked gene: POMC as ready
Mendeliome v0.9579 MLIP Zornitza Stark Marked gene: MLIP as ready
Mendeliome v0.9576 SPRED2 Zornitza Stark Phenotypes for gene: SPRED2 were changed from developmental delay; intellectual disability; cardiac defects; short stature; skeletal anomalies; a typical facial gestalt to Rasopathy; developmental delay; intellectual disability; cardiac defects; short stature; skeletal anomalies; a typical facial gestalt
Mendeliome v0.9575 CACNA1A Zornitza Stark Marked gene: CACNA1A as ready
Mendeliome v0.9572 KIAA0391 Zornitza Stark Marked gene: KIAA0391 as ready
Mendeliome v0.9572 KIAA0391 Zornitza Stark Added comment: Comment when marking as ready: Note gene is referred to as PRORP in the manuscript, but HGNC approved name is KIAA0391.
Mendeliome v0.9570 STT3A Zornitza Stark Marked gene: STT3A as ready
Mendeliome v0.9569 KIAA0391 Lucy Spencer changed review comment from: Four unrelated families with multisystem disease associated with bi-allelic variants in PRORP. Affected individuals presented with variable phenotypes comprising sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and brain white matter changes.

-1 consanguineous family with homozygous missense in 3 affected sisters, het parents unaffected. Siblings had profound bilateral SNHL in infancy. In teens developed primary amenorrhea/Perrault syndrome, and hypergonadotropic hypogonadism.
-1 unrelated male with compound het missense, each inherited from an unaffected parent. Hearing loss noted at 3, diagnosed at 5.
-1 unrelated male compound het for a missense and a frameshift. appendicular hypertonia in infancy, mild dysmorphism. Severe global dev delay at 20 months. Normal hearing at 18 months, but at 3 years had bilateral SNHL.
-an affected mother and her 2 affected children (son and daughter), homozygous for a missense. Father is heterozygous and unaffected. Son has psychotic disorder, autistic traits. Sister had intrauterine growth retardation, global developmental delay, and seizures in the first years of life. Mother presented with retrobulbar optic neuritis and tonic pupil at 39 years of age, then with asthenia, myalgias, memory loss, and frequent headaches.

All variants are in p.400s.
Sources: Literature; to: Four unrelated families with multisystem disease associated with bi-allelic variants in PRORP. Affected individuals presented with variable phenotypes comprising sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and brain white matter changes.

-1 consanguineous family with homozygous missense in 3 affected sisters, het parents unaffected. Siblings had profound bilateral SNHL in infancy. In teens developed primary amenorrhea/Perrault syndrome, and hypergonadotropic hypogonadism.
-1 unrelated male with compound het missense, each inherited from an unaffected parent. Hearing loss noted at 3, diagnosed at 5.
-1 unrelated male compound het for a missense and a frameshift. appendicular hypertonia in infancy, mild dysmorphism. Severe global dev delay at 20 months. Normal hearing at 18 months, but at 3 years had bilateral SNHL.
-an affected mother and her 2 affected children (son and daughter), homozygous for a missense. Father is heterozygous and unaffected. Son has psychotic disorder, autistic traits. Sister had intrauterine growth retardation, global developmental delay, and seizures in the first years of life. Mother presented with retrobulbar optic neuritis and tonic pupil at 39 years of age, then with asthenia, myalgias, memory loss, and frequent headaches.

All variants are in p.400s.
Sources: Literature
Mendeliome v0.9567 KIAA0391 Lucy Spencer gene: KIAA0391 was added
gene: KIAA0391 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIAA0391 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0391 were set to PMID: 34715011
Added comment: Four unrelated families with multisystem disease associated with bi-allelic variants in PRORP. Affected individuals presented with variable phenotypes comprising sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and brain white matter changes.

-1 consanguineous family with homozygous missense in 3 affected sisters, het parents unaffected. Siblings had profound bilateral SNHL in infancy. In teens developed primary amenorrhea/Perrault syndrome, and hypergonadotropic hypogonadism.
-1 unrelated male with compound het missense, each inherited from an unaffected parent. Hearing loss noted at 3, diagnosed at 5.
-1 unrelated male compound het for a missense and a frameshift. appendicular hypertonia in infancy, mild dysmorphism. Severe global dev delay at 20 months. Normal hearing at 18 months, but at 3 years had bilateral SNHL.
-an affected mother and her 2 affected children (son and daughter), homozygous for a missense. Father is heterozygous and unaffected. Son has psychotic disorder, autistic traits. Sister had intrauterine growth retardation, global developmental delay, and seizures in the first years of life. Mother presented with retrobulbar optic neuritis and tonic pupil at 39 years of age, then with asthenia, myalgias, memory loss, and frequent headaches.

All variants are in p.400s.
Sources: Literature
Mendeliome v0.9567 SPATA5L1 Zornitza Stark Marked gene: SPATA5L1 as ready
Mendeliome v0.9566 MLIP Michelle Torres gene: MLIP was added
gene: MLIP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MLIP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MLIP were set to 34581780
Review for gene: MLIP was set to GREEN
Added comment: PMID: 34581780: 7 individuals with 6 families with truncating (one splice that also resulted in a frameshift variant) biallelic variants (used NM_1281746).

In 3 patients patients’ skeletal muscle, these variants were shown to cause reduction overall RNA expression levels of the predominant MLIP isoform.

Patients presented with a consistent phenotype characterized by mild muscle weakness, exercise-induced muscle pain, variable susceptibility to episodes of rhabdomyolysis, and persistent basal elevated serum creatine kinase levels.
Sources: Literature
Mendeliome v0.9566 SPRED2 Zornitza Stark Marked gene: SPRED2 as ready
Mendeliome v0.9565 KPNA3 Zornitza Stark Marked gene: KPNA3 as ready
Mendeliome v0.9565 KPNA3 Zornitza Stark Phenotypes for gene: KPNA3 were changed from infantile onsetHereditary Spastic Paraplegia to Hereditary Spastic Paraplegia, infantile onset
Mendeliome v0.9564 SPATA5L1 Paul De Fazio gene: SPATA5L1 was added
gene: SPATA5L1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPATA5L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5L1 were set to 34626583
Phenotypes for gene: SPATA5L1 were set to Intellectual disability; spastic-dystonic cerebral palsy; epilepsy; hearing loss
Review for gene: SPATA5L1 was set to GREEN
gene: SPATA5L1 was marked as current diagnostic
Added comment: 47 individuals from 26 unrelated families from various ethnicities with biallelic variants reported. Phenotypes include ID, hearing impairment, movement disorder, abnormal MRI, hypotonia, visual impairment, epilepsy, and microcephaly.
Sources: Literature
Mendeliome v0.9563 SPRED2 Dean Phelan gene: SPRED2 was added
gene: SPRED2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPRED2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPRED2 were set to PMID: 34626534
Phenotypes for gene: SPRED2 were set to developmental delay; intellectual disability; cardiac defects; short stature; skeletal anomalies; a typical facial gestalt
Review for gene: SPRED2 was set to GREEN
Added comment: PMID: 34626534
Homozygosity for three different variants c.187C>T (p.Arg63∗), c.299T>C (p.Leu100Pro), and c.1142_1143delTT (p.Leu381Hisfs∗95) were identified in four subjects from three families. All variants severely affected protein stability, causing accelerated degradation, and variably perturbed SPRED2 functional behaviour. The clinical phenotype of the four affected individuals included developmental delay, intellectual disability, cardiac defects, short stature, skeletal anomalies, and a typical facial gestalt as major features, without the occurrence of the distinctive skin signs characterizing Legius syndrome.
Sources: Literature
Mendeliome v0.9563 KPNA3 Ain Roesley gene: KPNA3 was added
gene: KPNA3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KPNA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KPNA3 were set to 34564892
Phenotypes for gene: KPNA3 were set to infantile onsetHereditary Spastic Paraplegia
Penetrance for gene: KPNA3 were set to Complete
Review for gene: KPNA3 was set to GREEN
gene: KPNA3 was marked as current diagnostic
Added comment: 8 affecteds from 5 families with infantile-onset pure HSP
all missense variants, in vitro functional demonstrated reduced cargo binding
Noted that 1 individual had 2 de novo missense in the gene and though 1 is less deleterious than the other in the functional assays, authors were not able to rule out either one as a VUS
Sources: Literature
Mendeliome v0.9562 PHF6 Zornitza Stark Marked gene: PHF6 as ready
Mendeliome v0.9559 PCSK1 Zornitza Stark Marked gene: PCSK1 as ready
Mendeliome v0.9556 SLC4A3 Zornitza Stark Marked gene: SLC4A3 as ready
Mendeliome v0.9555 EHBP1L1 Zornitza Stark Marked gene: EHBP1L1 as ready
Mendeliome v0.9543 EHBP1L1 Krithika Murali gene: EHBP1L1 was added
gene: EHBP1L1 was added to Mendeliome. Sources: Expert list,Literature
Mode of inheritance for gene: EHBP1L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EHBP1L1 were set to 34645488; 26833786
Phenotypes for gene: EHBP1L1 were set to Non-immune hydrops fetalis
Review for gene: EHBP1L1 was set to AMBER
Added comment: No OMIM gene disease association.

Biallelic EHBP1L1 variants identified in 2 consanguineous families from Saudi Arabia with non-immune hydrops fetalis resulting in recurrent fetal loss. Supportive mouse models for this phenotype also reported.
Sources: Expert list, Literature
Mendeliome v0.9539 COL3A1 Krithika Murali gene: COL3A1 was added
gene: COL3A1 was added to Mendeliome. Sources: Expert list,Literature
Mode of inheritance for gene: COL3A1 was set to Other
Phenotypes for gene: COL3A1 were set to Ehlers-Danlos syndrome, vascular type - MIM#130050; Polymicrogyria with or without vascular-type EDS - #618343
Review for gene: COL3A1 was set to GREEN
Added comment: ClinGen validated gene-disease relationship with autosomal dominant vascular EDS

Also well-established phenotype with polymicrogyria with biallelic variants in COL3A1


AD - Ehlers Danlos vascular type
AR - Polymicrogyria with or without vascular type EDS
Sources: Expert list, Literature
Mendeliome v0.9538 CDH1 Krithika Murali gene: CDH1 was added
gene: CDH1 was added to Mendeliome. Sources: Expert list,Literature
Mode of inheritance for gene: CDH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CDH1 were set to Blepharocheilodontic syndrome 1- MIM#119580; Cleft lip and palate
Review for gene: CDH1 was set to GREEN
Added comment: Well-established gene-disease association with blepharocheilodontic syndrome (BDC) and orofacial clefting.

Gene also associated with cancer predisposition - diffuse gastric cancer (juvenile onset reported) and lobular breast cancer.
Sources: Expert list, Literature
Mendeliome v0.9538 GRIK2 Zornitza Stark Phenotypes for gene: GRIK2 were changed from Mental retardation, autosomal recessive, 6 MIM# 611092; Nonsyndromic neurodevelopmental disorder, autosomal dominant to Mental retardation, autosomal recessive, 6 MIM# 611092; Neurodevelopmental disorder with impaired language and ataxia and with or without seizures, MIM# 619580
Mendeliome v0.9537 CACNA1C Krithika Murali gene: CACNA1C was added
gene: CACNA1C was added to Mendeliome. Sources: Expert list,Literature
Mode of inheritance for gene: CACNA1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CACNA1C were set to Timothy syndrome - MIM# 601005; Neurodevelopmental abnormalities and epilepsy, no OMIM#; Long QT syndrome 8- MIM#618447
Review for gene: CACNA1C was set to GREEN
Added comment: Well-established gene-disease association with Timothy Syndrome

Rodan et al. (2021) reported 25 individuals from 22 families with heterozygous truncating and missense variants in CACNA1C. The individuals presented with developmental delays, intellectual disability, autism, hypotonia, ataxia, and epilepsy BUT absence of classic features of Timothy syndrome or long QT syndrome.
Sources: Expert list, Literature
Mendeliome v0.9537 ATP13A2 Krithika Murali gene: ATP13A2 was added
gene: ATP13A2 was added to Mendeliome. Sources: Expert list,Literature
Mode of inheritance for gene: ATP13A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP13A2 were set to 1694263
Phenotypes for gene: ATP13A2 were set to Kufor-Rakeb syndrome - MIM#606693
Review for gene: ATP13A2 was set to GREEN
Added comment: Well-established gene-disease association with Kufor-Rakeb syndrome, a form of autosomal recessive hereditary parkinsonism and dementia showing juvenile onset, as well as neuronal ceroid lipofucinosis (NCL) features in some families. Also associated with adult-onset hereditary spastic paraparesis.
Sources: Expert list, Literature
Mendeliome v0.9537 ACTC1 Krithika Murali gene: ACTC1 was added
gene: ACTC1 was added to Mendeliome. Sources: Expert list,Literature
Mode of inheritance for gene: ACTC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACTC1 were set to 26061005; 17947298; 31430208; 18403758; 30384889
Phenotypes for gene: ACTC1 were set to Atrial septal defect 5, MIM# 612794; Cardiomyopathy, dilated, 1R - MIM# 613424; Cardiomyopathy, hypertrophic, 11 - #612098
Review for gene: ACTC1 was set to GREEN
Added comment: Four families reported with congenital heart disease and variants in this gene. Note gene is also associated with cardiomyopathies, including paediatric-onset dilated and hypertrophic cardiomyopathy.
Sources: Expert list, Literature
Mendeliome v0.9537 CEP19 Zornitza Stark Marked gene: CEP19 as ready
Mendeliome v0.9537 CEP19 Zornitza Stark Phenotypes for gene: CEP19 were changed from Morbid obesity and spermatogenic failure MIM#615703 to Morbid obesity and spermatogenic failure MIM#615703; Bardet-Biedl syndorme
Mendeliome v0.9536 MUC5B Zornitza Stark Marked gene: MUC5B as ready
Mendeliome v0.9536 MUC5B Zornitza Stark Phenotypes for gene: MUC5B were changed from to {Pulmonary fibrosis, idiopathic, susceptibility to}, MIM# 178500
Mendeliome v0.9532 MUC5B Zornitza Stark reviewed gene: MUC5B: Rating: RED; Mode of pathogenicity: None; Publications: 21506741, 21506748; Phenotypes: {Pulmonary fibrosis, idiopathic, susceptibility to}, MIM# 178500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9532 AHDC1 Zornitza Stark Marked gene: AHDC1 as ready
Mendeliome v0.9529 AGTR1 Zornitza Stark Marked gene: AGTR1 as ready
Mendeliome v0.9529 AGTR1 Zornitza Stark Phenotypes for gene: AGTR1 were changed from to Renal tubular dysgenesis, MIM# 267430
Mendeliome v0.9526 AGTR1 Zornitza Stark reviewed gene: AGTR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116425; Phenotypes: Renal tubular dysgenesis, MIM# 267430; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9526 AGT Zornitza Stark Marked gene: AGT as ready
Mendeliome v0.9526 AGT Zornitza Stark Phenotypes for gene: AGT were changed from to Renal tubular dysgenesis, MIM# 267430
Mendeliome v0.9523 AGT Zornitza Stark reviewed gene: AGT: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116425, 34234805, 33163725; Phenotypes: Renal tubular dysgenesis, MIM# 267430; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9523 PANK4 Zornitza Stark Phenotypes for gene: PANK4 were changed from Congenital posterior cataract to Cataract 49, MIM# 619593; Congenital posterior cataract
Mendeliome v0.9522 PANK4 Zornitza Stark edited their review of gene: PANK4: Changed phenotypes: Cataract 49, MIM# 619593, Congenital posterior cataract
Mendeliome v0.9522 ADAMTS17 Zornitza Stark Marked gene: ADAMTS17 as ready
Mendeliome v0.9522 ADAMTS17 Zornitza Stark Phenotypes for gene: ADAMTS17 were changed from to Weill-Marchesani 4 syndrome, recessive, MIM# 613195
Mendeliome v0.9519 ADAMTS17 Zornitza Stark reviewed gene: ADAMTS17: Rating: GREEN; Mode of pathogenicity: None; Publications: 19836009, 22486325, 24940034, 30712880; Phenotypes: Weill-Marchesani 4 syndrome, recessive, MIM# 613195; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9519 ACY1 Zornitza Stark Marked gene: ACY1 as ready
Mendeliome v0.9516 ACE Zornitza Stark Marked gene: ACE as ready
Mendeliome v0.9516 ACE Zornitza Stark Phenotypes for gene: ACE were changed from to Renal tubular dysgenesis, MIM# 267430
Mendeliome v0.9513 ACE Zornitza Stark reviewed gene: ACE: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116425, 22095942; Phenotypes: Renal tubular dysgenesis, MIM# 267430; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9513 ACADVL Zornitza Stark Marked gene: ACADVL as ready
Mendeliome v0.9511 TFE3 Zornitza Stark Phenotypes for gene: TFE3 were changed from TFE3-associated neurodevelopmental disorder; Intellectual disability; Epilepsy; Coarse facial features to Intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies, MIM# 301066; Intellectual disability; Epilepsy; Coarse facial features
Mendeliome v0.9510 TFE3 Zornitza Stark edited their review of gene: TFE3: Changed phenotypes: Intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies, MIM# 301066, Intellectual disability, Epilepsy, Coarse facial features
Mendeliome v0.9510 FAN1 Zornitza Stark Marked gene: FAN1 as ready
Mendeliome v0.9510 FAN1 Zornitza Stark Phenotypes for gene: FAN1 were changed from to Interstitial nephritis, karyomegalic, MIM# 614817
Mendeliome v0.9507 FAN1 Zornitza Stark reviewed gene: FAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22772369, 16678356, 7847351, 8546134; Phenotypes: Interstitial nephritis, karyomegalic, MIM# 614817; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9504 MANBA Zornitza Stark changed review comment from: Variable severity. Well established gene-disease association.; to: Bi-allelic variants and lysosomal storage disorder: Variable severity. Well established gene-disease association.
Mendeliome v0.9504 MANBA Zornitza Stark changed review comment from: Two mono-allelic variants reported in association with isolated nystagmus. Note bi-allelic variants cause a lysosomal storage disorder.; to: Two mono-allelic variants reported in association with isolated nystagmus.
Mendeliome v0.9504 MANBA Zornitza Stark edited their review of gene: MANBA: Added comment: Two mono-allelic variants reported in association with isolated nystagmus. Note bi-allelic variants cause a lysosomal storage disorder.; Changed publications: 30552791, 25741867; Changed phenotypes: Mannosidosis, beta, MIM# 248510, MONDO:0009562, Nystagmus, autosomal dominant; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9502 ETHE1 Zornitza Stark commented on gene: ETHE1: Severe metabolic disorder characterized by neurodevelopmental delay and regression, prominent pyramidal and extrapyramidal signs, recurrent petechiae, orthostatic acrocyanosis, and chronic diarrhoea. Brain MRI shows necrotic lesions in deep gray matter structures.
Mendeliome v0.9502 ETHE1 Zornitza Stark Marked gene: ETHE1 as ready
Mendeliome v0.9499 RHO Zornitza Stark Marked gene: RHO as ready
Mendeliome v0.9499 RHO Zornitza Stark Phenotypes for gene: RHO were changed from to Night blindness, congenital stationary, autosomal dominant 1, MIM# 610445; Retinitis pigmentosa 4, autosomal dominant or recessive, MIM# 613731
Mendeliome v0.9496 RHO Zornitza Stark reviewed gene: RHO: Rating: GREEN; Mode of pathogenicity: None; Publications: 18487375, 27812022, 31213501, 1303237; Phenotypes: Night blindness, congenital stationary, autosomal dominant 1, MIM# 610445, Retinitis pigmentosa 4, autosomal dominant or recessive, MIM# 613731; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9496 RDH12 Zornitza Stark Marked gene: RDH12 as ready
Mendeliome v0.9493 RD3 Zornitza Stark Marked gene: RD3 as ready
Mendeliome v0.9490 IFT74 Zornitza Stark Phenotypes for gene: IFT74 were changed from Bardet-Biedl syndrome 20, MIM# 617119; Joubert syndrome; Spermatogenic failure 58, MIM# 619585 to Bardet-Biedl syndrome 20, MIM# 617119; Joubert syndrome 40, MIM# 619582; Spermatogenic failure 58, MIM# 619585
Mendeliome v0.9489 IFT74 Zornitza Stark edited their review of gene: IFT74: Changed phenotypes: Bardet-Biedl syndrome 20, MIM# 617119, Joubert syndrome 40, MIM# 619582, Spermatogenic failure 58, MIM# 619585
Mendeliome v0.9489 EXOSC5 Zornitza Stark Phenotypes for gene: EXOSC5 were changed from Short stature; Motor developmental delays; Cerebellar hypoplasia; Ataxia to Cerebellar ataxia, brain abnormalities, and cardiac conduction defects, MIM# 619576; Short stature; Motor developmental delays; Cerebellar hypoplasia; Ataxia
Mendeliome v0.9488 EXOSC5 Zornitza Stark reviewed gene: EXOSC5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebellar ataxia, brain abnormalities, and cardiac conduction defects, MIM# 619576; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9488 PRPH2 Zornitza Stark edited their review of gene: PRPH2: Changed phenotypes: Leber congenital amaurosis 18, MIM#608133, Macular dystrophy, vitelliform, 3, MIM#608161, Retinitis pigmentosa 7 and digenic form, MIM#608133, Choroidal dystrophy, central areolar 2, MIM#613105, Macular dystrophy, patterned, 1, MIM#169150 Retinitis punctata albescens, MIM#136880