ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.872C>T (p.Ser291Leu)

gnomAD frequency: 0.00001  dbSNP: rs755952123
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000621507 SCV000737975 uncertain significance Cardiovascular phenotype 2017-04-13 criteria provided, single submitter clinical testing The p.S291L variant (also known as c.872C>T), located in coding exon 7 of the DSC2 gene, results from a C to T substitution at nucleotide position 872. The serine at codon 291 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species, and leucine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV001190258 SCV001357709 uncertain significance Cardiomyopathy 2023-08-02 criteria provided, single submitter clinical testing This missense variant replaces serine with leucine at codon 291 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 3/251422 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 RCV001860391 SCV002182886 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 291 of the DSC2 protein (p.Ser291Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs755952123, ExAC 0.001%). 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: 519431). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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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