Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002544724 | SCV000813289 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2023-08-04 | criteria provided, single submitter | clinical testing | 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) performed at Invitae indicates that this missense variant is not expected to disrupt RYR2 protein function. ClinVar contains an entry for this variant (Variation ID: 566068). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 3231 of the RYR2 protein (p.Met3231Thr). |
| Color Diagnostics, |
RCV001805800 | SCV002052588 | uncertain significance | Cardiomyopathy | 2023-04-21 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with threonine at codon 3231 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 2/249094 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. |
| Fulgent Genetics, |
RCV002493141 | SCV002797014 | uncertain significance | Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome | 2021-10-31 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003163100 | SCV003868929 | uncertain significance | Cardiovascular phenotype | 2023-02-03 | criteria provided, single submitter | clinical testing | The p.M3231T variant (also known as c.9692T>C), located in coding exon 68 of the RYR2 gene, results from a T to C substitution at nucleotide position 9692. The methionine at codon 3231 is replaced by threonine, an amino acid with similar properties. This alteration has been reported in a whole exome sequencing cohort (Landstrom AP et al. Circ Arrhythm Electrophysiol, 2017 Apr;10:). This amino acid position is 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. |