ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2339C>T (p.Ala780Val)

gnomAD frequency: 0.00002  dbSNP: rs547406532
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001170378 SCV001332953 likely benign Cardiomyopathy 2023-05-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001444786 SCV001647797 likely benign Arrhythmogenic right ventricular dysplasia 10 2022-02-19 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001170378 SCV001735609 uncertain significance Cardiomyopathy 2022-11-15 criteria provided, single submitter clinical testing This missense variant replaces alanine with valine at codon 780 of the DSG2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 33/280200 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.
GeneDx RCV000870771 SCV001766042 uncertain significance not provided 2021-12-02 criteria provided, single submitter clinical testing Reported in a patient diagnosed with Fazio-Londe disease and ARVC who also harbored a homozygous nonsense variant in the SLC52A3 gene and a second missense variant in the DSG2 gene (Alfares et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID# 701986; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 24238504, 26582918, 28454995)
Ambry Genetics RCV002442855 SCV002732369 likely benign Cardiovascular phenotype 2022-12-08 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
All of Us Research Program, National Institutes of Health RCV004003065 SCV004821781 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2023-11-30 criteria provided, single submitter clinical testing This missense variant replaces alanine with valine at codon 780 of the DSG2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 33/280200 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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