Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002023027 | SCV002304715 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2022-09-19 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1512439). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 458 of the DSG2 protein (p.Arg458Ile). 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 not expected to disrupt DSG2 protein function. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. |
All of Us Research Program, |
RCV004011139 | SCV004826425 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2024-09-23 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with isoleucine at codon 458 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. |