ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1105A>G (p.Lys369Glu)

gnomAD frequency: 0.00001  dbSNP: rs727505208
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000156703 SCV000206424 uncertain significance not specified 2014-07-18 criteria provided, single submitter clinical testing The Lys369Glu variant in DSG2 has not been previously reported in individuals wi th cardiomyopathy or in large population studies. Computational prediction tools and conservation analysis do not provide strong support for or against an impac t to the protein. In summary, the clinical significance of the Lys369Glu variant is uncertain.
Color Diagnostics, LLC DBA Color Health RCV001525491 SCV001735624 uncertain significance Cardiomyopathy 2023-05-25 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid 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 cardiovascular disorders in the literature. This variant has been identified in 1/249420 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 RCV001850169 SCV002146224 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2023-10-10 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 369 of the DSG2 protein (p.Lys369Glu). This variant is present in population databases (rs727505208, gnomAD 0.0009%). 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: 179902). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DSG2 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.
Ambry Genetics RCV002426759 SCV002743205 uncertain significance Cardiovascular phenotype 2020-08-20 criteria provided, single submitter clinical testing The p.K369E variant (also known as c.1105A>G), located in coding exon 9 of the DSG2 gene, results from an A to G substitution at nucleotide position 1105. The lysine at codon 369 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.
All of Us Research Program, National Institutes of Health RCV003998321 SCV004819510 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2024-03-24 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid 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 cardiovascular disorders in the literature. This variant has been identified in 1/249420 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.
Blueprint Genetics RCV000157184 SCV000206908 uncertain significance Primary dilated cardiomyopathy 2014-09-29 no assertion criteria provided clinical testing

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