ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1106A>T (p.Lys369Met)

gnomAD frequency: 0.00001  dbSNP: rs375740419
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001059772 SCV001224418 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2022-06-14 criteria provided, single submitter clinical testing 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 854675). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is present in population databases (rs375740419, gnomAD 0.01%). This sequence change replaces lysine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 369 of the DSG2 protein (p.Lys369Met).
Mayo Clinic Laboratories, Mayo Clinic RCV001507399 SCV001712937 uncertain significance not provided 2019-09-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV002429681 SCV002741363 uncertain significance Cardiovascular phenotype 2021-05-05 criteria provided, single submitter clinical testing The p.K369M variant (also known as c.1106A>T), located in coding exon 9 of the DSG2 gene, results from an A to T substitution at nucleotide position 1106. The lysine at codon 369 is replaced by methionine, 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.
Fulgent Genetics, Fulgent Genetics RCV002505626 SCV002814597 uncertain significance Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB 2021-08-17 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004000111 SCV004827855 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2023-12-01 criteria provided, single submitter clinical testing This missense variant replaces lysine with methionine at codon 369 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 3/280826 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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