ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.2512G>A (p.Val838Met)

gnomAD frequency: 0.00001  dbSNP: rs1986695514
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001247273 SCV001420683 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2023-02-03 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 971484). 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 valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 838 of the DSC2 protein (p.Val838Met).
Ambry Genetics RCV002436970 SCV002745158 uncertain significance Cardiovascular phenotype 2022-03-21 criteria provided, single submitter clinical testing The p.V838M variant (also known as c.2512G>A), located in coding exon 16 of the DSC2 gene, results from a G to A substitution at nucleotide position 2512. The valine at codon 838 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003156329 SCV003845705 uncertain significance not provided 2022-09-21 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function
Color Diagnostics, LLC DBA Color Health RCV003532921 SCV004363061 uncertain significance Cardiomyopathy 2023-04-18 criteria provided, single submitter clinical testing This missense variant replaces valine with methionine at codon 838 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.
All of Us Research Program, National Institutes of Health RCV004004909 SCV004833653 uncertain significance Familial isolated arrhythmogenic right ventricular dysplasia 2023-05-04 criteria provided, single submitter clinical testing This missense variant replaces valine with methionine at codon 838 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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