Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000621125 | SCV000736750 | uncertain significance | Cardiovascular phenotype | 2020-12-17 | criteria provided, single submitter | clinical testing | The p.R3248C variant (also known as c.9742C>T), located in coding exon 68 of the RYR2 gene, results from a C to T substitution at nucleotide position 9742. The arginine at codon 3248 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well 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, |
RCV001179340 | SCV001343987 | uncertain significance | Cardiomyopathy | 2023-02-16 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 3248 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 not been reported in individuals affected with RYR2-related disorders in the literature. This variant has been identified in 2/249000 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. |
| Invitae | RCV002531756 | SCV002127589 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2021-12-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 3248 of the RYR2 protein (p.Arg3248Cys). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 518975). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RYR2 protein function. 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. |
| Fulgent Genetics, |
RCV002477344 | SCV002784929 | uncertain significance | Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome | 2021-11-03 | criteria provided, single submitter | clinical testing | |
| Genomics England Pilot Project, |
RCV001542518 | SCV001760028 | likely pathogenic | Arrhythmogenic right ventricular dysplasia 2 | no assertion criteria provided | clinical testing |