Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002523277 | SCV000541703 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2016-09-09 | criteria provided, single submitter | clinical testing | 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. 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: "Probably Damaging"; Align-GVGD: "Class C15"). 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. This sequence change replaces leucine with phenylalanine at codon 2123 of the RYR2 protein (p.Leu2123Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. |