Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002376281 | SCV002683816 | uncertain significance | Cardiovascular phenotype | 2021-10-12 | criteria provided, single submitter | clinical testing | The p.R424G variant (also known as c.1270C>G), located in coding exon 12 of the CACNB2 gene, results from a C to G substitution at nucleotide position 1270. The arginine at codon 424 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV003774147 | SCV004660606 | uncertain significance | Brugada syndrome 4 | 2023-05-19 | 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 CACNB2 protein function. ClinVar contains an entry for this variant (Variation ID: 1765347). This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. This variant is present in population databases (rs551742573, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 424 of the CACNB2 protein (p.Arg424Gly). |