ClinVar Miner

Submissions for variant NM_201596.3(CACNB2):c.1522G>A (p.Ala508Thr)

gnomAD frequency: 0.00003  dbSNP: rs759958799
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000170870 SCV000223425 uncertain significance not provided 2014-02-21 criteria provided, single submitter clinical testing p.Ala453Thr (GCT>ACT): c.1357 G>A in exon 13 of the CACNB2 gene (NM_000724.3). A variant of unknown significance has been identified in the CACNB2 gene. To our knowledge, the A453T variant has not been published as a disease-causing mutation or as a benign polymorphism. The A453T variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A453T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis predicts this variant likely does not alter the protein structure/function. No disease-causing mutations have been reported in nearby residues in the in association with Brugada syndrome suggesting this region of the protein may be tolerant to change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in BRUGADA panel(s).
Ambry Genetics RCV000620970 SCV000737786 benign Cardiovascular phenotype 2022-05-06 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV001088490 SCV001008318 likely benign Brugada syndrome 4 2023-11-01 criteria provided, single submitter clinical testing

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