Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000169142 | SCV000220362 | likely pathogenic | Wilson disease | 2014-05-30 | criteria provided, single submitter | literature only | |
ARUP Laboratories, |
RCV000169142 | SCV001158354 | likely pathogenic | Wilson disease | 2019-04-06 | criteria provided, single submitter | clinical testing | The ATP7B c.3301G>A; p.Gly1101Arg variant (rs786204483) is reported in two individuals with Wilson disease who are homozygous for the variant (reported as G1102R in Thomas 1995). Functional assays show the variant protein is unable to complement ccc2 function under low iron conditions, supportive of it being deleterious. (Luoma 2010). This variant is reported in ClinVar (Variation ID: 188808). It is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The glycine at codon 1101 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Based on available information, this variant is considered to be likely pathogenic. REFERENCES Luoma LM et al. Functional analysis of mutations in the ATP loop of the Wilson disease copper transporter, ATP7B. Hum Mutat. 2010 May;31(5):569-77. Thomas GR et al. The Wilson disease gene: spectrum of mutations and their consequences. Nat Genet. 1995 Feb;9(2):210-7. |
Invitae | RCV000169142 | SCV001400226 | pathogenic | Wilson disease | 2023-05-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects ATP7B function (PMID: 20333758). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ATP7B protein function. ClinVar contains an entry for this variant (Variation ID: 188808). This missense change has been observed in individual(s) with Wilson disease (PMID: 7626145, 23551039, 31059521). This variant is present in population databases (rs786204483, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1101 of the ATP7B protein (p.Gly1101Arg). |
Centogene AG - |
RCV000169142 | SCV001424371 | pathogenic | Wilson disease | criteria provided, single submitter | clinical testing | ||
Genome- |
RCV000169142 | SCV001977258 | likely pathogenic | Wilson disease | 2021-08-10 | criteria provided, single submitter | clinical testing | |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV000169142 | SCV002073143 | pathogenic | Wilson disease | criteria provided, single submitter | clinical testing | The missense variant p.G1101R in ATP7B (NM_000053.4) has been previously reported in homozygous state in affected patients (Singh N et al; Aggarwal A et al). Functional studies show a detrimental effect (Luoma LM et al). The p.G1101R variant is observed in 1/30,602 (0.0033%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. There is a moderate physicochemical difference between glycine and arginine. The p.G1101R missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glycine residue at codon 1101 of ATP7B is conserved in all mammalian species. The nucleotide c.3301 in ATP7B is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic. | |
Arcensus | RCV000169142 | SCV002564598 | pathogenic | Wilson disease | 2013-02-01 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000169142 | SCV004216279 | pathogenic | Wilson disease | 2023-10-22 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000169142 | SCV004238469 | pathogenic | Wilson disease | 2023-09-23 | criteria provided, single submitter | clinical testing |