ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1013A>T (p.Lys338Met)

gnomAD frequency: 0.00001  dbSNP: rs1454000095
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001765281 SCV001997911 uncertain significance not provided 2019-10-08 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect
Fulgent Genetics, Fulgent Genetics RCV002489769 SCV002784048 uncertain significance Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB 2021-07-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002540363 SCV003035222 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2022-07-11 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 338 of the DSG2 protein (p.Lys338Met). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1309112). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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 RCV003163856 SCV003859074 uncertain significance Cardiovascular phenotype 2023-02-16 criteria provided, single submitter clinical testing The p.K338M variant (also known as c.1013A>T), located in coding exon 8 of the DSG2 gene, results from an A to T substitution at nucleotide position 1013. The lysine at codon 338 is replaced by methionine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV004009007 SCV004836125 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2023-11-28 criteria provided, single submitter clinical testing

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