ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.62C>A (p.Thr21Asn)

gnomAD frequency: 0.00001  dbSNP: rs931909783
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001182902 SCV001348501 uncertain significance Cardiomyopathy 2019-10-08 criteria provided, single submitter clinical testing This missense variant replaces threonine with asparagine at codon 21 of the DSC2 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular 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.
Invitae RCV001876079 SCV002295724 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2023-10-28 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 21 of the DSC2 protein (p.Thr21Asn). This variant is not present in population databases (gnomAD no frequency). 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: 922713). 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 DSC2 protein function with a negative 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.

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