ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.1667G>A (p.Gly556Glu)

gnomAD frequency: 0.00002  dbSNP: rs977269905
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001984765 SCV002211942 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2023-10-04 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 556 of the DSC2 protein (p.Gly556Glu). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1434979). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamic acid 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.
GeneDx RCV002307798 SCV002601402 uncertain significance not provided 2022-05-10 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
Fulgent Genetics, Fulgent Genetics RCV001984765 SCV002786232 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2021-09-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV003303451 SCV004001794 uncertain significance Cardiovascular phenotype 2023-06-09 criteria provided, single submitter clinical testing The p.G556E variant (also known as c.1667G>A), located in coding exon 12 of the DSC2 gene, results from a G to A substitution at nucleotide position 1667. The glycine at codon 556 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is well 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.

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