Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002642006 | SCV002286186 | likely pathogenic | Catecholaminergic polymorphic ventricular tachycardia 1 | 2024-02-23 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 3774 of the RYR2 protein (p.Gln3774Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with RYR2-related conditions (PMID: 29032884). ClinVar contains an entry for this variant (Variation ID: 1496297). 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 with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |