Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001327228 | SCV001518292 | uncertain significance | Brugada syndrome 4 | 2023-09-27 | 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 expected to disrupt CACNB2 protein function. ClinVar contains an entry for this variant (Variation ID: 1026738). This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. This variant is present in population databases (rs148414498, gnomAD 0.01%). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 377 of the CACNB2 protein (p.Gln377His). |
| Ambry Genetics | RCV002322256 | SCV002608113 | uncertain significance | Cardiovascular phenotype | 2021-03-09 | criteria provided, single submitter | clinical testing | The p.Q377H variant (also known as c.1131G>C), located in coding exon 11 of the CACNB2 gene, results from a G to C substitution at nucleotide position 1131. The glutamine at codon 377 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |