ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.1475G>C (p.Gly492Ala)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002644404 SCV003521383 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2023-03-10 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) performed at Invitae indicates that this missense variant is expected to disrupt DSC2 protein function. ClinVar contains an entry for this variant (Variation ID: 2201501). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 492 of the DSC2 protein (p.Gly492Ala).
Ambry Genetics RCV004072081 SCV003651957 uncertain significance Cardiovascular phenotype 2022-09-28 criteria provided, single submitter clinical testing The c.1475G>C (p.G492A) alteration is located in exon 10 (coding exon 10) of the DSC2 gene. This alteration results from a G to C substitution at nucleotide position 1475, causing the glycine (G) at amino acid position 492 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV004009527 SCV004816000 uncertain significance Familial isolated arrhythmogenic right ventricular dysplasia 2023-02-24 criteria provided, single submitter clinical testing This missense variant replaces glycine with alanine at codon 492 of the DSC2 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 DSC2-related disorders in the literature. This variant has not been identified 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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