Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001949176 | SCV002211981 | uncertain significance | Brugada syndrome 4 | 2023-07-25 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1439218). This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 452 of the CACNB2 protein (p.Arg452His). |
Ambry Genetics | RCV002386772 | SCV002693128 | uncertain significance | Cardiovascular phenotype | 2023-10-26 | criteria provided, single submitter | clinical testing | The c.1355_1356delGCinsAT variant (also known as p.R452H), located in coding exon 13 of the CACNB2 gene, results from an in-frame deletion of GC and insertion of AT at nucleotide positions 1355 to 1356. This results in the substitution of the arginine residue for a histidine residue at codon 452, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and histidine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |