ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2702A>G (p.Lys901Arg) (rs886039190)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000247972 SCV000320573 uncertain significance Cardiovascular phenotype 2015-11-25 criteria provided, single submitter clinical testing The p.K901R variant (also known as c.2702A>G), located in coding exon 15 of the DSG2 gene, results from an A to G substitution at nucleotide position 2702. The lysine at codon 901 is replaced by arginine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 5998 samples (11996 alleles) with coverage at this position. This amino acid position is not 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 variant remains unclear.
Invitae RCV001056576 SCV001221026 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2019-12-19 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 901 of the DSG2 protein (p.Lys901Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 264559). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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