ClinVar Miner

Submissions for variant NM_201596.3(CACNB2):c.1534del (p.Ser512fs)

dbSNP: rs767341738
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000456064 SCV000538573 uncertain significance not specified 2017-03-01 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: The p.Ser512fs in CACNB2 has not been previously reported in individuals with cardiomyopathy or in large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 512 and leads to a premature termination codon 57 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. LoF not a known disease mechanism. In summary, the clinical significance of the p.Ser512fs variant is uncertain.
Ambry Genetics RCV002379406 SCV002697220 uncertain significance Cardiovascular phenotype 2022-07-19 criteria provided, single submitter clinical testing The c.1372delT variant, located in coding exon 13 of the CACNB2 gene, results from a deletion of one nucleotide at nucleotide position 1372, causing a translational frameshift with a predicted alternate stop codon (p.S458Lfs*57). This alteration is expected to result in premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of CACNB2 has not been clearly established as a mechanism of disease. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.
Fulgent Genetics, Fulgent Genetics RCV002506085 SCV002816615 uncertain significance Brugada syndrome 4 2021-11-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002506085 SCV005718003 uncertain significance Brugada syndrome 4 2024-09-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser458Leufs*57) in the CACNB2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 149 amino acid(s) of the CACNB2 protein. This variant is present in population databases (rs767341738, gnomAD 0.0009%). 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: 402478). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.

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