ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.1231A>G (p.Lys411Glu) (rs560482778)

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 RCV000181149 SCV000233426 uncertain significance not provided 2018-11-29 criteria provided, single submitter clinical testing The K411E variant of uncertain significance in the DSC2 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 13/276812 (0.005%) alleles from individuals of multiple ethnic backgrounds in large population cohorts (Lek et al., 2016). In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Nevertheless, the K411E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Invitae RCV000812062 SCV000952364 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 11 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 411 of the DSC2 protein (p.Lys411Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs560482778, ExAC 0.02%). This variant has not been reported in the literature in individuals with DSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 199766). 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: "Benign"; Align-GVGD: "Class C0"). 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.

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.