ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2953G>A (p.Val985Ile) (rs749540432)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489811 SCV000577571 uncertain significance not provided 2017-02-01 criteria provided, single submitter clinical testing The V985I variant of uncertain significance in the DSG2 gene has not been published as pathogenic or benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Nevertheless, V985I is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution also occurs at a position where amino acids with similar properties to valine are tolerated across species, and isoleucine is the wild type in at least two species. In silico analysis predicts this variant likely does not alter the protein structure/function. Moreover, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014).
Color Health, Inc RCV001184490 SCV001350469 uncertain significance Cardiomyopathy 2020-12-23 criteria provided, single submitter clinical testing This missense variant replaces valine with isoleucine at codon 985 of the DSG2 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 2/248354 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.