Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001037153 | SCV001200552 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2022-03-18 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 816 of the DSG2 protein (p.Phe816Tyr). ClinVar contains an entry for this variant (Variation ID: 836109). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is not present in population databases (gnomAD no frequency). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). |
Ambry Genetics | RCV002454270 | SCV002737989 | uncertain significance | Cardiovascular phenotype | 2022-09-05 | criteria provided, single submitter | clinical testing | The p.F816Y variant (also known as c.2447T>A), located in coding exon 15 of the DSG2 gene, results from a T to A substitution at nucleotide position 2447. The phenylalanine at codon 816 is replaced by tyrosine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |