Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002447610 | SCV002680808 | uncertain significance | Cardiovascular phenotype | 2021-06-28 | criteria provided, single submitter | clinical testing | The p.A2825D variant (also known as c.8474C>A), located in coding exon 57 of the RYR2 gene, results from a C to A substitution at nucleotide position 8474. The alanine at codon 2825 is replaced by aspartic acid, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
All of Us Research Program, |
RCV004005772 | SCV004832940 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia | 2023-04-10 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with aspartic acid at codon 2825 of the RYR2 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 RYR2-related disorders in the literature. 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. |