Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001176600 | SCV001340628 | uncertain significance | Cardiomyopathy | 2023-09-14 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with lysine at codon 2710 of the RYR2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RYR2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Invitae | RCV002516215 | SCV001540560 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2023-08-18 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 2710 of the RYR2 protein (p.Asn2710Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 235054). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Ambry Genetics | RCV002417980 | SCV002681727 | uncertain significance | Cardiovascular phenotype | 2019-08-06 | criteria provided, single submitter | clinical testing | The p.N2710K variant (also known as c.8130T>G), located in coding exon 54 of the RYR2 gene, results from a T to G substitution at nucleotide position 8130. The asparagine at codon 2710 is replaced by lysine, an amino acid with similar properties. This change occurs in the first base pair of coding exon 54. 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. |
| Stanford Center for Inherited Cardiovascular Disease, |
RCV000223925 | SCV000280452 | uncertain significance | not specified | 2013-04-26 | no assertion criteria provided | clinical testing | Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Asn2710Lys (c.8130T>G) in the RYR2 gene. This variant is novel. This is a semi conservative amino acid change with a polar, neutrally charged Asparagine replaced with a polar, positively charged Lysine. Asparagine is conserved at position 2710 only through mammals. In silico analysis (PolyPhen2) predicts the amino acid change to be possibly damaging to protein structure and/or function. No variants have been reported at this codon or nearby codons. |