Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001946397 | SCV002209599 | uncertain significance | Brugada syndrome 4 | 2021-10-14 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. This sequence change replaces glutamic acid with aspartic acid at codon 539 of the CACNB2 protein (p.Glu539Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. |
| Ambry Genetics | RCV002397964 | SCV002705818 | uncertain significance | Cardiovascular phenotype | 2022-10-07 | criteria provided, single submitter | clinical testing | The p.E539D variant (also known as c.1617G>C), located in coding exon 13 of the CACNB2 gene, results from a G to C substitution at nucleotide position 1617. The glutamic acid at codon 539 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |