ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1281A>T (p.Arg427Ser)

gnomAD frequency: 0.00001  dbSNP: rs370547219
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000487007 SCV000567828 uncertain significance not provided 2020-09-02 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge
Color Diagnostics, LLC DBA Color Health RCV001176568 SCV001340588 uncertain significance Cardiomyopathy 2023-02-08 criteria provided, single submitter clinical testing This missense variant replaces arginine with serine at codon 427 of the DSG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with DSG2-related disorders in the literature. This variant has been identified in 2/236004 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001204581 SCV001375794 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2022-05-03 criteria provided, single submitter clinical testing 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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"). ClinVar contains an entry for this variant (Variation ID: 419778). This variant is present in population databases (rs370547219, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 427 of the DSG2 protein (p.Arg427Ser).
Ambry Genetics RCV002383920 SCV002695281 uncertain significance Cardiovascular phenotype 2022-10-02 criteria provided, single submitter clinical testing The p.R427S variant (also known as c.1281A>T) is located in coding exon 10 of the DSG2 gene. The arginine at codon 427 is replaced by serine, an amino acid with dissimilar properties. This change occurs in the first base pair of coding exon 10. 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.
All of Us Research Program, National Institutes of Health RCV004002315 SCV004819525 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2024-07-02 criteria provided, single submitter clinical testing This missense variant replaces arginine with serine at codon 427 of the DSG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/236004 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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