Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002533536 | SCV000827359 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-03-09 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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. ClinVar contains an entry for this variant (Variation ID: 576232). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1052 of the RYR2 protein (p.Glu1052Lys). |
| ARUP Laboratories, |
RCV000757728 | SCV000886066 | uncertain significance | not provided | 2018-04-11 | criteria provided, single submitter | clinical testing | The RYR2 c.3154G>A; p.Glu1052Lys variant, to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is absent from the general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The glutamic acid at position 1052 is highly conserved, considering 10 species, and computational analyses of the effects of the p.Glu1052Lys variant on protein structure and function predict a deleterious effect (SIFT: damaging, PolyPhen-2: possibly damaging). Based on the available information, the clinical significance of the p.Glu1052Lys variant cannot be determined with certainty. |