ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.1124G>A (p.Arg375Gln)

gnomAD frequency: 0.00001  dbSNP: rs770412621
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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 RCV001903730 SCV002176678 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2024-07-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 375 of the DSC2 protein (p.Arg375Gln). This variant is present in population databases (rs770412621, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1405340). 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 expected to disrupt DSC2 protein function with a positive predictive value of 80%. 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 RCV003382711 SCV004097119 uncertain significance Cardiovascular phenotype 2023-09-05 criteria provided, single submitter clinical testing The p.R375Q variant (also known as c.1124G>A), located in coding exon 9 of the DSC2 gene, results from a G to A substitution at nucleotide position 1124. The arginine at codon 375 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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 RCV004010836 SCV004840143 uncertain significance Familial isolated arrhythmogenic right ventricular dysplasia 2023-12-01 criteria provided, single submitter clinical testing

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