Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002947361 | SCV003264937 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with valine at codon 540 of the DSG2 protein (p.Met540Val). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs759101277, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
All of Us Research Program, |
RCV004007697 | SCV004828911 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2024-03-24 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with valine at codon 540 of the DSG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with DSG2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |