Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000527613 | SCV000647069 | uncertain significance | Brugada syndrome 4 | 2017-03-16 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CACNB2-related disease. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CACNB2 cause disease. Therefore, this variant has been classified as a Variant of Uncertain Significance. This sequence change affects the initiator methionine of the CACNB2 mRNA and is predicted to result in an absent or truncated protein. |
| Ambry Genetics | RCV004024095 | SCV005031643 | uncertain significance | Cardiovascular phenotype | 2023-09-29 | criteria provided, single submitter | clinical testing | The p.M1? variant (also known as c.2T>C) is located in coding exon 1 of the CACNB2 gene and results from a T to C substitution at nucleotide position 2. This alters the methionine residue at the initiation codon (ATG). This amino acid position is highly conserved in available vertebrate species. Variations that modify the initiation codon (ATG) are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. However, loss of function of CACNB2 has not been established as a mechanism of disease. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |