ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.3340C>G (p.Gln1114Glu)

gnomAD frequency: 0.00001  dbSNP: rs776078563
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001909368 SCV002177829 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2023-10-25 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1114 of the DSG2 protein (p.Gln1114Glu). This variant is present in population databases (rs776078563, gnomAD 0.007%). 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: 1407862). 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 with a negative predictive value of 95%. 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.
All of Us Research Program, National Institutes of Health RCV004010844 SCV004833663 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2023-05-04 criteria provided, single submitter clinical testing This missense variant replaces glutamine with glutamic acid at codon 1114 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 1/249150 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.
Breakthrough Genomics, Breakthrough Genomics RCV004693934 SCV005193295 uncertain significance not provided criteria provided, single submitter not provided

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