ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.647C>T (p.Thr216Ile)

dbSNP: rs780448272
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001804689 SCV002052001 uncertain significance Cardiomyopathy 2023-11-01 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 216 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 cardiovascular disorders in the literature. This variant has been identified in 1/251196 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.
Invitae RCV001869530 SCV002287351 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2021-04-17 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 216 of the DSC2 protein (p.Thr216Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs780448272, ExAC 0.002%). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with DSC2-related conditions.
All of Us Research Program, National Institutes of Health RCV004009108 SCV004819331 uncertain significance Familial isolated arrhythmogenic right ventricular dysplasia 2023-11-20 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 216 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 cardiovascular disorders in the literature. This variant has been identified in 1/251196 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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