Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002527818 | SCV000637571 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-03-08 | 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: 463603). This missense change has been observed in individual(s) with sudden unexplained death (PMID: 29247119). This variant is present in population databases (rs764687833, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1610 of the RYR2 protein (p.Arg1610Gln). |
Ambry Genetics | RCV002341317 | SCV002639187 | uncertain significance | Cardiovascular phenotype | 2021-09-29 | criteria provided, single submitter | clinical testing | The p.R1610Q variant (also known as c.4829G>A), located in coding exon 36 of the RYR2 gene, results from a G to A substitution at nucleotide position 4829. The arginine at codon 1610 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in a sudden unexplained death cohort (Lin Y et al. Circ Cardiovasc Genet, 2017 Dec;10:). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
All of Us Research Program, |
RCV003999114 | SCV004832292 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia | 2023-12-01 | criteria provided, single submitter | clinical testing |