Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000410994 | SCV000486474 | likely pathogenic | Wilson disease | 2016-06-14 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000410994 | SCV001205495 | pathogenic | Wilson disease | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1035 of the ATP7B protein (p.Gly1035Val). 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: 9311736, 10070620, 17587212, 21707886, 22940187). ClinVar contains an entry for this variant (Variation ID: 371021). 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%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. |
| Genome- |
RCV000410994 | SCV001977277 | pathogenic | Wilson disease | 2021-08-10 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000410994 | SCV002511726 | likely pathogenic | Wilson disease | 2022-04-21 | criteria provided, single submitter | clinical testing | Variant summary: ATP7B c.3104G>T (p.Gly1035Val) 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 248810 control chromosomes. c.3104G>T has been reported in the literature as homozygous and compound heterozygous genotypes in multiple individuals affected with Wilson Disease (example, Tatsumi_2011, Katano_2014, Kyeong Kim_2020). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV000410994 | SCV004216322 | pathogenic | Wilson disease | 2023-09-24 | criteria provided, single submitter | clinical testing |