Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001980135 | SCV002229606 | pathogenic | Wilson disease | 2023-09-12 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1000 of the ATP7B protein (p.Gly1000Arg). This variant is present in population databases (rs751078884, gnomAD 0.003%). This missense change has been observed in individual(s) with Wilson disease (PMID: 30120852, 30230192, 30702195, 31059521). ClinVar contains an entry for this variant (Variation ID: 1448460). 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. Experimental studies have shown that this missense change affects ATP7B function (PMID: 20333758). For these reasons, this variant has been classified as Pathogenic. |
| All of Us Research Program, |
RCV001980135 | SCV004845435 | pathogenic | Wilson disease | 2023-07-19 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with arginine at codon 1000 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). A functional study in yeast has shown the mutant protein to exhibit significantly reduced levels of expression and inability to complement ccc2 function under low iron conditions (PMID: 20333758). This variant has been observed in over ten individuals affected with Wilson disease, including six individuals who were reported to be homozygous or compound heterozygous with a known pathogenic variant in the same gene (PMID: 16088907, 18728530, 23486543, 30120852, 30230192, 30702195, 31059521, 33010844, 31708252). This variant has been identified in 1/244084 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. |
| Baylor Genetics | RCV001980135 | SCV005053102 | pathogenic | Wilson disease | 2023-11-23 | criteria provided, single submitter | clinical testing |