Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
All of Us Research Program, |
RCV004012204 | SCV004832659 | likely pathogenic | Wilson disease | 2023-06-26 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with arginine at codon 943 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). To our knowledge, functional studies have not been reported for this variant. This variant has been observed in the homozygous state in one individual affected with autosomal recessive Wilson disease (PMID: 16088907), indicating that this variant contributes to disease. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Different variants affecting the same codon, p.Gly943Ser and p.Gly943Asp, are considered to be disease-causing (ClinVar Variation ID: 3856, 189058), suggesting that glycine at this position is important for the protein function. Based on the available evidence, this variant is classified as Likely Pathogenic. |