Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001219286 | SCV001391218 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 184 of the DSG2 protein (p.Thr184Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs372605499, ExAC 0.002%). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; 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 | RCV004032356 | SCV005018094 | uncertain significance | Cardiovascular phenotype | 2023-11-23 | criteria provided, single submitter | clinical testing | The p.T184I variant (also known as c.551C>T), located in coding exon 6 of the DSG2 gene, results from a C to T substitution at nucleotide position 551. The threonine at codon 184 is replaced by isoleucine, 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. |