Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000794404 | SCV000933809 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2018-08-08 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with aspartic acid at codon 514 of the DSG2 protein (p.Asn514Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DSG2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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, |
RCV004001589 | SCV004829798 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2023-08-08 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with aspartic acid at codon 514 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. |