Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV002279938 | SCV000235197 | pathogenic | not provided | 2022-08-19 | criteria provided, single submitter | clinical testing | Has been reported in individuals with CPVT seen at GeneDx and in published literature (Hayashi et al., 2009; Jabbari et al., 2013; Guidicessi et al., 2019; Gerber et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); Located in one of the three hot-spot regions of the RYR2 gene, where the majority of pathogenic missense variants occur (PMID: 19632629); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24025405, 19398665, 26256814, 26132555, 31112425, 19632629, 32553227) |
Invitae | RCV002515335 | SCV003524140 | pathogenic | Catecholaminergic polymorphic ventricular tachycardia 1 | 2023-11-15 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 4091 of the RYR2 protein (p.Ala4091Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of autosomal dominant catecholaminergic polymorphic ventricular tachycardia (PMID: 19398665, 26256814, 31112425). ClinVar contains an entry for this variant (Variation ID: 201325). 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%. For these reasons, this variant has been classified as Pathogenic. |
Medical Research Institute, |
RCV000190127 | SCV000221977 | uncertain significance | Long QT syndrome | no assertion criteria provided | research |