ClinVar Miner

Submissions for variant NM_201596.3(CACNB2):c.1433G>A (p.Arg478His)

gnomAD frequency: 0.00004  dbSNP: rs781646326
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001247665 SCV001421101 uncertain significance Brugada syndrome 4 2023-11-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 424 of the CACNB2 protein (p.Arg424His). This variant is present in population databases (rs781646326, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 560634). 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 with a negative 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.
Ambry Genetics RCV002369809 SCV002683553 uncertain significance Cardiovascular phenotype 2023-03-06 criteria provided, single submitter clinical testing The p.R424H variant (also known as c.1271G>A), located in coding exon 12 of the CACNB2 gene, results from a G to A substitution at nucleotide position 1271. The arginine at codon 424 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital RCV000678782 SCV000804962 uncertain significance Brugada syndrome 2017-06-28 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.