Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000169428 | SCV000220838 | likely pathogenic | Wilson disease | 2014-10-24 | criteria provided, single submitter | literature only | |
| SIB Swiss Institute of Bioinformatics | RCV000169428 | SCV000883184 | likely pathogenic | Wilson disease | 2018-10-15 | criteria provided, single submitter | curation | This variant is interpreted as Likely Pathogenic, for Wilson disease, autosomal recessive. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PS3 => Well-established functional studies show a deleterious effect.The variant affects copper transport. (https://www.ncbi.nlm.nih.gov/pubmed/22240481). |
| Baylor Genetics | RCV000169428 | SCV004216499 | likely pathogenic | Wilson disease | 2022-09-03 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000169428 | SCV004296502 | pathogenic | Wilson disease | 2023-12-12 | 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 85 of the ATP7B protein (p.Gly85Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Wilson disease (PMID: 30702195, 32043565). ClinVar contains an entry for this variant (Variation ID: 189037). 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 95%. Experimental studies have shown that this missense change affects ATP7B function (PMID: 17919502, 30702195). This variant disrupts the p.Gly85 amino acid residue in ATP7B. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |