Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Advanced Laboratory Medicine, |
RCV000852429 | SCV000995113 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2017-08-30 | criteria provided, single submitter | clinical testing | |
Ai |
RCV002223960 | SCV002503456 | uncertain significance | not provided | 2020-07-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002453932 | SCV002617911 | uncertain significance | Cardiovascular phenotype | 2020-09-22 | criteria provided, single submitter | clinical testing | The p.C114Y variant (also known as c.341G>A), located in coding exon 4 of the CACNB2 gene, results from a G to A substitution at nucleotide position 341. The cysteine at codon 114 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV003106082 | SCV003782975 | uncertain significance | Brugada syndrome 4 | 2022-04-06 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 114 of the CACNB2 protein (p.Cys114Tyr). This variant is present in population databases (rs773215003, 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: 691656). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0". The tyrosine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |