Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002533221 | SCV000760614 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-10-24 | 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 not expected to disrupt RYR2 protein function. ClinVar contains an entry for this variant (Variation ID: 532339). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. This variant is present in population databases (rs755148895, gnomAD 0.006%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 4031 of the RYR2 protein (p.Thr4031Ala). |
| Color Diagnostics, |
RCV000771485 | SCV000903967 | uncertain significance | Cardiomyopathy | 2023-05-24 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with alanine at codon 4031 of the RYR2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 been identified in 7/279702 chromosomes 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. |
| Mayo Clinic Laboratories, |
RCV001509129 | SCV001715672 | uncertain significance | not provided | 2020-04-21 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002343257 | SCV002651628 | uncertain significance | Cardiovascular phenotype | 2019-09-26 | criteria provided, single submitter | clinical testing | The p.T4031A variant (also known as c.12091A>G), located in coding exon 90 of the RYR2 gene, results from an A to G substitution at nucleotide position 12091. The threonine at codon 4031 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and alanine is the reference amino acid in other 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. |
| Fulgent Genetics, |
RCV002507087 | SCV002815857 | uncertain significance | Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome | 2021-09-21 | criteria provided, single submitter | clinical testing |