Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001182796 | SCV001348377 | likely benign | Cardiomyopathy | 2019-10-18 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001340500 | SCV001534314 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2020-06-21 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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. This variant is present in population databases (rs767523704, ExAC 0.006%). This sequence change replaces threonine with isoleucine at codon 238 of the DSG2 protein (p.Thr238Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. |
Ambry Genetics | RCV002365863 | SCV002665488 | uncertain significance | Cardiovascular phenotype | 2019-06-30 | criteria provided, single submitter | clinical testing | The p.T238I variant (also known as c.713C>T), located in coding exon 7 of the DSG2 gene, results from a C to T substitution at nucleotide position 713. The threonine at codon 238 is replaced by isoleucine, an amino acid with 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. |
All of Us Research Program, |
RCV004008325 | SCV004819468 | likely benign | Arrhythmogenic right ventricular cardiomyopathy | 2023-08-15 | criteria provided, single submitter | clinical testing |