Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002409983 | SCV002673344 | uncertain significance | Cardiovascular phenotype | 2021-10-11 | criteria provided, single submitter | clinical testing | The p.R261W variant (also known as c.781C>T), located in coding exon 8 of the CACNB2 gene, results from a C to T substitution at nucleotide position 781. The arginine at codon 261 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |
| Invitae | RCV003099755 | SCV003283766 | uncertain significance | Brugada syndrome 4 | 2023-11-06 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 261 of the CACNB2 protein (p.Arg261Trp). This variant is present in population databases (rs375029614, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1760764). 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. |