ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1256A>T (p.Asp419Val)

dbSNP: rs760135423
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000469010 SCV000551009 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2022-10-27 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 419 of the DSG2 protein (p.Asp419Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 410367). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Color Diagnostics, LLC DBA Color Health RCV001189976 SCV001357377 uncertain significance Cardiomyopathy 2023-09-28 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with valine at codon 419 of the DSG2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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 1/249268 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.
AiLife Diagnostics, AiLife Diagnostics RCV002223213 SCV002501258 uncertain significance not provided 2022-01-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV002418410 SCV002678452 uncertain significance Cardiovascular phenotype 2022-06-16 criteria provided, single submitter clinical testing The p.D419V variant (also known as c.1256A>T), located in coding exon 9 of the DSG2 gene, results from an A to T substitution at nucleotide position 1256. The aspartic acid at codon 419 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002489067 SCV002783194 uncertain significance Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB 2021-08-24 criteria provided, single submitter clinical testing

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