ClinVar Miner

Submissions for variant NM_201596.3(CACNB2):c.994G>T (p.Val332Leu)

gnomAD frequency: 0.00002  dbSNP: rs369543094
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000646198 SCV000767957 uncertain significance Brugada syndrome 4 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 278 of the CACNB2 protein (p.Val278Leu). This variant is present in population databases (rs369543094, 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: 537365). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CACNB2 protein function with a negative predictive value of 80%. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000646198 SCV003919758 uncertain significance Brugada syndrome 4 2021-03-30 criteria provided, single submitter clinical testing CACNB2 NM_201590.2 exon 9 p.Val278Leu (c.832G>T): This variant has not been reported in the literature but is present in 0.01% (2/18382) of East Asian alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/10-18816566-G-T). This variant is present in ClinVar (Variation ID:537365). Evolutionary conservation suggests that this variant may impact the protein; however, computational predictive tools are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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