Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001902391 | SCV002137802 | uncertain significance | Brugada syndrome 4 | 2022-10-24 | 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: 1375258). This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 339 of the CACNB2 protein (p.Ile339Arg). |
| Ambry Genetics | RCV002334786 | SCV002643727 | uncertain significance | Cardiovascular phenotype | 2021-06-23 | criteria provided, single submitter | clinical testing | The p.I339R variant (also known as c.1016T>G), located in coding exon 10 of the CACNB2 gene, results from a T to G substitution at nucleotide position 1016. The isoleucine at codon 339 is replaced by arginine, an amino acid with similar 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. |