Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000618525 | SCV000735389 | uncertain significance | Cardiovascular phenotype | 2016-05-25 | criteria provided, single submitter | clinical testing | The p.M3739I variant (also known as c.11217G>A), located in coding exon 81 of the RYR2 gene, results from a G to A substitution at nucleotide position 11217. The methionine at codon 3739 is replaced by isoleucine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6135 samples (12270 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
| Invitae | RCV002531736 | SCV002190787 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-03-19 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 518524). 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 expected to disrupt RYR2 protein function. This variant has not been reported in the literature in individuals affected with RYR2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 3739 of the RYR2 protein (p.Met3739Ile). |
| Agnes Ginges Centre for Molecular Cardiology, |
RCV001254758 | SCV001430851 | likely pathogenic | Catecholaminergic polymorphic ventricular tachycardia | 2019-07-03 | no assertion criteria provided | research | This variant has been identified as part of our research program. Refer to the 'condition' field for the phenotype of the proband identified with this variant. For further information please feel free to contact us. |