Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003509969 | SCV004318551 | uncertain significance | Brugada syndrome 4 | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 260 of the CACNB2 protein (p.Gly260Arg). This variant is present in population databases (rs750929086, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. 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 CACNB2 protein function with a positive predictive value of 80%. 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. |