Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001232496 | SCV001405058 | pathogenic | Wilson disease | 2023-12-03 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1178 of the ATP7B protein (p.Thr1178Ala). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with Wilson disease (PMID: 18034201, 21034864, 23235335, 24094725, 31059521). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 959197). 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 with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV001232496 | SCV001977248 | likely pathogenic | Wilson disease | 2021-08-10 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001232496 | SCV002103723 | pathogenic | Wilson disease | 2022-02-03 | criteria provided, single submitter | clinical testing | Variant summary: ATP7B c.3532A>G (p.Thr1178Ala) results in a non-conservative amino acid change located in the P-type ATPase, haloacid dehalogenase domain (IPR044492) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 249588 control chromosomes (gnomAD). c.3532A>G has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Wilson Disease (e.g. Mak_2008, Wan_2010, Singh_2019, Xiao_2021). These data indicate that the variant is very likely to be associated with disease. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Gene |
RCV003317461 | SCV004021600 | likely pathogenic | not provided | 2023-07-18 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16696937, 22692182, 30275481, 31059521, 24094725, 23235335, 18034201, 21034864, 35470480, 34400371, 35193651, 34324271) |
Baylor Genetics | RCV001232496 | SCV004216272 | pathogenic | Wilson disease | 2023-10-25 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001232496 | SCV002086806 | pathogenic | Wilson disease | 2020-07-23 | no assertion criteria provided | clinical testing |