Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001341316 | SCV001535183 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2022-07-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 842 of the DSG2 protein (p.Gly842Asp). This variant is present in population databases (rs374177723, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1038063). 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: "Possibly 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. |
| Ambry Genetics | RCV002431955 | SCV002742066 | uncertain significance | Cardiovascular phenotype | 2023-07-24 | criteria provided, single submitter | clinical testing | The p.G842D variant (also known as c.2525G>A), located in coding exon 15 of the DSG2 gene, results from a G to A substitution at nucleotide position 2525. The glycine at codon 842 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002504534 | SCV002814511 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB | 2021-09-01 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV003532956 | SCV004363221 | uncertain significance | Cardiomyopathy | 2023-10-16 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with aspartic acid at codon 842 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 been identified in 1/249042 chromosomes 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. |
| All of Us Research Program, |
RCV004005173 | SCV004822557 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2023-11-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004779085 | SCV005388117 | uncertain significance | not provided | 2024-03-24 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |