Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001922602 | SCV002168053 | uncertain significance | Brugada syndrome 4 | 2021-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with tryptophan at codon 66 of the CACNB2 protein (p.Arg66Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs541253552, ExAC 0.02%). This variant has not been reported in the literature in individuals with CACNB2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | RCV002422998 | SCV002723411 | uncertain significance | Cardiovascular phenotype | 2022-02-07 | criteria provided, single submitter | clinical testing | The p.R66W variant (also known as c.196C>T), located in coding exon 3 of the CACNB2 gene, results from a C to T substitution at nucleotide position 196. The arginine at codon 66 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. |