Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003091546 | SCV003476830 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2022-03-21 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 694 of the DSG2 protein (p.Ala694Gly). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. 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 glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. |
Ambry Genetics | RCV003377875 | SCV004096439 | uncertain significance | Cardiovascular phenotype | 2023-09-03 | criteria provided, single submitter | clinical testing | The p.A694G variant (also known as c.2081C>G), located in coding exon 14 of the DSG2 gene, results from a C to G substitution at nucleotide position 2081. The alanine at codon 694 is replaced by glycine, 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. |
Gene |
RCV004765667 | SCV005379625 | uncertain significance | not provided | 2023-11-22 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Prevention |
RCV003898784 | SCV004716192 | uncertain significance | DSG2-related disorder | 2023-12-21 | no assertion criteria provided | clinical testing | The DSG2 c.2081C>G variant is predicted to result in the amino acid substitution p.Ala694Gly. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |