Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000620178 | SCV000738149 | uncertain significance | Cardiovascular phenotype | 2017-09-06 | criteria provided, single submitter | clinical testing | The c.1748dupA variant, located in coding exon 13 of the CACNB2 gene, results from a duplication of A at nucleotide position 1748, causing a translational frameshift with a predicted alternate stop codon (p.D584Gfs*11). Frameshifts are typically deleterious in nature, however, this frameshift occurs at the 3' terminus of CACNB2, is not expected to trigger nonsense-mediated mRNA decay, and impacts only the last 23 amino acids of the protein. The exact functional impact of these altered amino acids is unknown at this time. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002506509 | SCV002812294 | uncertain significance | Brugada syndrome 4 | 2021-07-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002506509 | SCV003264035 | uncertain significance | Brugada syndrome 4 | 2024-01-14 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp584Glyfs*11) in the CACNB2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 23 amino acid(s) of the CACNB2 protein. This variant is present in population databases (rs750015594, gnomAD 0.006%). 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: 519502). 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. |