Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000181178 | SCV000233455 | uncertain significance | not provided | 2011-10-04 | criteria provided, single submitter | clinical testing | This missense change is denoted Glu426Lys (aka E426K) at the protein level and c.1276 G>A at the cDNA level. The Glu426Lys variant in the DSC2 gene has not been reported previously as a disease-causing mutation or as a benign polymorphism, to our knowledge. Glu426Lys results in a non-conservative amino acid substitution of a negatively charged Glutamic acid residue with a positively charged Lysine residue at a position that is conserved across species throughout evolution. Although no disease-causing mutations have been reported in nearby codons, several in silico algorithms conform and predict Glu426Lys to be a deleterious, disease-causing variant that is probably damaging to the structure/function of the protein (Adzhubei IA et al 2010; Kumar P et al 2009 ). The variant is found in ARVC panel(s). |
Color Diagnostics, |
RCV003532013 | SCV004363097 | uncertain significance | Cardiomyopathy | 2021-09-15 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with lysine at codon 426 of the DSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with arrhythmogenic right ventricular dysplasia/cardiomyopathy (PMID: 24585727, 25820315, 28588093). 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. |