Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002526079 | SCV000637602 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2017-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with proline at codon 2393 of the RYR2 protein (p.Ser2393Pro). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and proline. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a RYR2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant occurs within one of the three regions of the RYR2 gene (N-terminal domain, central domain, or channel region) where other pathogenic variants have been reported to cluster (PMID: 19926015). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |