ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2468A>G (p.Asp823Gly)

gnomAD frequency: 0.00003  dbSNP: rs777642924
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Total submissions: 5
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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 RCV000216642 SCV000271716 uncertain significance not specified 2015-12-10 criteria provided, single submitter clinical testing The p.Asp823Gly variant in DSG2 has not been previously reported in individuals with cardiomyopathy. It has been identified in 1/66696 European chromosomes by t he Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org/; dbSNP rs 777642924). Computational prediction tools and conservation analysis suggest tha t this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Asp823Gly variant is uncertain.
Color Diagnostics, LLC DBA Color Health RCV001187397 SCV001354199 uncertain significance Cardiomyopathy 2023-06-07 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glycine at codon 823 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 been reported in an individual affected with restrictive cardiomyopathy (PMID: 35026164). This variant has been identified in 3/280738 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.
Ambry Genetics RCV002453770 SCV002738248 uncertain significance Cardiovascular phenotype 2021-06-09 criteria provided, single submitter clinical testing The p.D823G variant (also known as c.2468A>G), located in coding exon 15 of the DSG2 gene, results from an A to G substitution at nucleotide position 2468. The aspartic acid at codon 823 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003517150 SCV004335937 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2023-09-21 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DSG2 protein function. ClinVar contains an entry for this variant (Variation ID: 228632). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is present in population databases (rs777642924, gnomAD 0.003%). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 823 of the DSG2 protein (p.Asp823Gly).
All of Us Research Program, National Institutes of Health RCV003997730 SCV004821800 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2024-01-11 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glycine at codon 823 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 3/280738 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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