Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002529899 | SCV000760606 | likely benign | Catecholaminergic polymorphic ventricular tachycardia 1 | 2023-06-17 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000765088 | SCV000896297 | uncertain significance | Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001766367 | SCV002008096 | uncertain significance | not provided | 2019-09-24 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar (ClinVar Variant ID# 532332; Landrum et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Not located in one of the three hot-spot regions of the RYR2 gene, where the majority of pathogenic missense variants occur (Medeiros-Domingo et al., 2009) |
| Ambry Genetics | RCV002458037 | SCV002617662 | uncertain significance | Cardiovascular phenotype | 2022-09-09 | criteria provided, single submitter | clinical testing | The p.D1220E variant (also known as c.3660T>A), located in coding exon 30 of the RYR2 gene, results from a T to A substitution at nucleotide position 3660. The aspartic acid at codon 1220 is replaced by glutamic acid, an amino acid with highly similar properties. This alteration has been reported in a case report with a family history of sudden unexplained death in which other cardiac-related alterations were identified (Jaouadi H et al. Herz, 2021 Apr;46:94-102). This amino acid position is highly conserved in available 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. |
| Color Diagnostics, |
RCV003532214 | SCV004360570 | uncertain significance | Cardiomyopathy | 2022-11-09 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glutamic acid at codon 1220 of the RYR2 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 been reported in an individual affected with sudden cardiac death and in the mother, who had a history of syncopes and received implantable cardioverter defibrillator after the sudden death of another two children (PMID: 31970460). 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. |