Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756608 | SCV000884475 | uncertain significance | not provided | 2017-08-07 | criteria provided, single submitter | clinical testing | The c.815G>A; p.Arg272His variant has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. It is absent from general population databases such as 1000 Genomes, NHLBI GO Exome Sequencing Project (ESP), and the Genome Aggregation Database (gnomAD). The arginine at position 272 is highly conserved considering 10 species (Alamut v2.9.0) and computational analyses of the effects of the p.Arg272His variant on protein structure and function indicates deleterious effects (SIFT: damaging, MutationTaster: disease causing, PolyPhen-2: probably damaging). Altogether, there is not enough evidence to classify the p.Arg272His variant with certainty. |
| Color Diagnostics, |
RCV001179696 | SCV001344406 | uncertain significance | Cardiomyopathy | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with histidine at codon 272 of the RYR2 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). 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 | RCV002533793 | SCV001567266 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-02-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 272 of the RYR2 protein (p.Arg272His). 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: 618352). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. This variant is not present in population databases (gnomAD no frequency). |