Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002523283 | SCV000541723 | likely pathogenic | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-07-05 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 4635 of the RYR2 protein (p.Ile4635Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of polymorphic ventricular tachycardia (PMID: 31112425; Invitae). ClinVar contains an entry for this variant (Variation ID: 404236). 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. 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. |
| Fulgent Genetics, |
RCV005010335 | SCV005643829 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome | 2024-02-07 | criteria provided, single submitter | clinical testing | |
| Stanford Center for Inherited Cardiovascular Disease, |
RCV000786205 | SCV000924924 | uncertain significance | not provided | 2017-01-03 | no assertion criteria provided | provider interpretation | Given the lack of case data we consider this variant a variant of uncertain significance and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). Per our searches, the variant is novel. It is not listed in ClinVar (as of 3 Jan 2017). The variant is not listed in the Genome Aggregation Consortium Dataset (gnomAD; http://gnomad.broadinstitute.org/), which currently includes variant calls on >140,000 unrelated individuals of African, Asian, European, Latino, and Ashkenazi descent. The average coverage at that site is not yet listed in gnomAD, however nearly all appear to have coverage greater than 20x. Note that gnomAD is still in beta, with the following warning “This resource is still in early beta mode and we are actively working to improve the filtering of variant calls. All data on this website should be treated with caution.†The variant is also not listed in the ExAC, which currently includes variant calls on >60,000 unrelated individuals of African, Asian, European, Latino, and Ashkenazi descent. The average coverage at that site in ExAC is 32x. Another variant is present at the same codon, p.Ile4635Met seen in 1 of 59771 individuals in ExAC and 1 of 125682 individuals in gnomAD. |