Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001206776 | SCV001378102 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with valine at codon 690 of the DSG2 protein (p.Met690Val). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency). 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
Ambry Genetics | RCV002418689 | SCV002727667 | uncertain significance | Cardiovascular phenotype | 2020-06-08 | criteria provided, single submitter | clinical testing | The p.M690V variant (also known as c.2068A>G), located in coding exon 14 of the DSG2 gene, results from an A to G substitution at nucleotide position 2068. The methionine at codon 690 is replaced by valine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. 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. |