Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000845499 | SCV000987601 | uncertain significance | Primary familial dilated cardiomyopathy | criteria provided, single submitter | clinical testing | ||
Labcorp Genetics |
RCV001367915 | SCV001564286 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2020-10-08 | criteria provided, single submitter | clinical testing | 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 684849). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with threonine at codon 862 of the DSG2 protein (p.Ser862Thr). The serine residue is moderately conserved and there is a small physicochemical difference between serine and threonine. |
All of Us Research Program, |
RCV004002899 | SCV004816654 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2023-04-03 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with threonine at codon 862 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. |