Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001314158 | SCV001504682 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2022-09-06 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1015314). 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 sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. This variant has not been reported in the literature in individuals affected with DSC2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.008%). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 259 of the DSC2 protein (p.Gly259Asp). |
Ambry Genetics | RCV002412004 | SCV002668957 | uncertain significance | Cardiovascular phenotype | 2022-05-30 | criteria provided, single submitter | clinical testing | The p.G259D variant (also known as c.776G>A) is located in coding exon 7 of the DSC2 gene. The glycine at codon 259 is replaced by aspartic acid, an amino acid with similar properties. This change occurs in the first base pair of coding exon 7. This amino acid position is conserved. 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. |
All of Us Research Program, |
RCV004005071 | SCV004841185 | uncertain significance | Familial isolated arrhythmogenic right ventricular dysplasia | 2023-10-02 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with aspartic acid at codon 259 of the DSC2 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 2/282208 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. |