ClinVar Miner

Submissions for variant NM_201596.3(CACNB2):c.1267A>T (p.Met423Leu)

gnomAD frequency: 0.00001  dbSNP: rs779536902
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002004787 SCV002232646 uncertain significance Brugada syndrome 4 2021-09-17 criteria provided, single submitter clinical testing This sequence change replaces methionine with leucine at codon 369 of the CACNB2 protein (p.Met369Leu). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and leucine. This variant is present in population databases (rs779536902, ExAC 0.003%). This variant has not been reported in the literature in individuals with CACNB2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV002425318 SCV002744016 uncertain significance Cardiovascular phenotype 2024-08-11 criteria provided, single submitter clinical testing The p.M369L variant (also known as c.1105A>T), located in coding exon 11 of the CACNB2 gene, results from an A to T substitution at nucleotide position 1105. The methionine at codon 369 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002004787 SCV002787016 uncertain significance Brugada syndrome 4 2021-08-09 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV002004787 SCV003828868 uncertain significance Brugada syndrome 4 2022-06-28 criteria provided, single submitter clinical testing

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