Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002531466 | SCV000821158 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2020-10-06 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RYR2-related disease. This variant is present in population databases (rs759774382, ExAC 0.01%). This sequence change replaces histidine with arginine at codon 1805 of the RYR2 protein (p.His1805Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. |
Ambry Genetics | RCV003279006 | SCV004009356 | uncertain significance | Cardiovascular phenotype | 2023-06-10 | criteria provided, single submitter | clinical testing | The p.H1805R variant (also known as c.5414A>G), located in coding exon 37 of the RYR2 gene, results from an A to G substitution at nucleotide position 5414. The histidine at codon 1805 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |