Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002528367 | SCV000637540 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2019-11-19 | criteria provided, single submitter | clinical testing | In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. This variant is present in population databases (rs749607906, ExAC 0.009%) but has not been reported in the literature in individuals with a RYR2-related disease. This sequence change replaces isoleucine with threonine at codon 872 of the RYR2 protein (p.Ile872Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. |
| Ambry Genetics | RCV002438348 | SCV002745591 | uncertain significance | Cardiovascular phenotype | 2022-09-12 | criteria provided, single submitter | clinical testing | The p.I872T variant (also known as c.2615T>C), located in coding exon 23 of the RYR2 gene, results from a T to C substitution at nucleotide position 2615. The isoleucine at codon 872 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |