Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001389302 | SCV001590616 | pathogenic | Wilson disease | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 1047 of the ATP7B protein (p.Asp1047Val). 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: 23843956, 27022412, 27398169, 30384382). ClinVar contains an entry for this variant (Variation ID: 1075644). 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 not expected to disrupt ATP7B protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
Mayo Clinic Laboratories, |
RCV001508711 | SCV001715046 | likely pathogenic | not provided | 2019-07-23 | criteria provided, single submitter | clinical testing | PS4_moderate, PM2, PM3, PP4 |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001389302 | SCV001748743 | pathogenic | Wilson disease | 2023-05-26 | criteria provided, single submitter | clinical testing | Variant summary: ATP7B c.3140A>T (p.Asp1047Val) results in a non-conservative amino acid change located in the ATP loop domain (Dong_2016) and P-type ATPase, haloacid dehalogenase domain (IPR044492) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 249210 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3140A>T has been widely reported in the literature among both homozygous and compound heterozygous, phenotypically well-characterized Chinese individuals affected with classic features of Wilson Disease (e.g., Mak_2008, Gu_2013, Dong_2016, Hua_2016, Xiao_2019, Zhang_2022). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 27022412, 23843956, 27398169, 18760268, 30384382, 35220961). Three ClinVar submitters (evaluation after 2014) have cited the variant, and all submitters classified the variant as pathogenic (n = 1) or likely pathogenic (n = 2). Based on the evidence outlined above, the variant was classified as pathogenic. |
Genome- |
RCV001389302 | SCV001977273 | likely pathogenic | Wilson disease | 2021-08-10 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001508711 | SCV004033260 | pathogenic | not provided | 2023-08-01 | criteria provided, single submitter | clinical testing | ATP7B: PM3:Very Strong, PM2 |
Baylor Genetics | RCV001389302 | SCV004216376 | pathogenic | Wilson disease | 2023-07-20 | criteria provided, single submitter | clinical testing |