Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002522774 | SCV000541670 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2023-04-12 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 613 of the RYR2 protein (p.Val613Ala). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RYR2 protein function. ClinVar contains an entry for this variant (Variation ID: 404197). |
| Ambry Genetics | RCV002411426 | SCV002715056 | uncertain significance | Cardiovascular phenotype | 2020-01-10 | criteria provided, single submitter | clinical testing | The p.V613A variant (also known as c.1838T>C), located in coding exon 19 of the RYR2 gene, results from a T to C substitution at nucleotide position 1838. The valine at codon 613 is replaced by alanine, an amino acid with similar properties. 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. |
| Fulgent Genetics, |
RCV002506089 | SCV002815860 | uncertain significance | Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome | 2021-11-17 | criteria provided, single submitter | clinical testing |