ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.2359G>A (p.Val787Met)

dbSNP: rs1789053
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001921391 SCV002200472 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2022-02-11 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 787 of the DSC2 protein (p.Val787Met). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function.
Ambry Genetics RCV002442875 SCV002734496 uncertain significance Cardiovascular phenotype 2020-11-17 criteria provided, single submitter clinical testing The p.V787M variant (also known as c.2359G>A), located in coding exon 15 of the DSC2 gene, results from a G to A substitution at nucleotide position 2359. The valine at codon 787 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, methionine 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 RCV003533060 SCV004363065 uncertain significance Cardiomyopathy 2022-11-16 criteria provided, single submitter clinical testing This missense variant replaces valine with methionine at codon 787 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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