Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001205396 | SCV001376650 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2022-07-05 | criteria provided, single submitter | clinical testing | 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 missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The tyrosine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 936571). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. This variant is present in population databases (rs773961399, gnomAD 0.0009%). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 819 of the DSC2 protein (p.Cys819Tyr). |
Ambry Genetics | RCV002447061 | SCV002732220 | uncertain significance | Cardiovascular phenotype | 2019-09-20 | criteria provided, single submitter | clinical testing | The p.C819Y variant (also known as c.2456G>A), located in coding exon 15 of the DSC2 gene, results from a G to A substitution at nucleotide position 2456. The cysteine at codon 819 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species, and tyrosine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated 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, |
RCV004010643 | SCV004833882 | uncertain significance | Familial isolated arrhythmogenic right ventricular dysplasia | 2023-05-15 | criteria provided, single submitter | clinical testing | This missense variant replaces cysteine with tyrosine at codon 819 of the DSC2 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 DSC2-related disorders in the literature. This variant has been identified in 1/251188 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. |