ClinVar Miner

Submissions for variant NM_201596.3(CACNB2):c.827A>C (p.Asp276Ala)

dbSNP: rs889646922
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001322673 SCV001513554 uncertain significance Brugada syndrome 4 2023-12-23 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 222 of the CACNB2 protein (p.Asp222Ala). This variant is present in population databases (no rsID available, 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: 1022730). 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 expected to disrupt CACNB2 protein function with a positive 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001322673 SCV002048441 uncertain significance Brugada syndrome 4 2021-04-13 criteria provided, single submitter clinical testing The CACNB2 c.665A>C; p.Asp222Ala variant (rs889646922), to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is found on a single chromosome in the Genome Aggregation Database (1/251076 alleles), indicating it is not a common polymorphism. The aspartate at codon 222 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.715). However, due to limited information, the clinical significance of the p.Asp222Ala variant is uncertain at this time.
AiLife Diagnostics, AiLife Diagnostics RCV002224062 SCV002502346 uncertain significance not provided 2021-09-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV002366187 SCV002661667 uncertain significance Cardiovascular phenotype 2023-05-21 criteria provided, single submitter clinical testing The p.D222A variant (also known as c.665A>C), located in coding exon 7 of the CACNB2 gene, results from an A to C substitution at nucleotide position 665. The aspartic acid at codon 222 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.
Fulgent Genetics, Fulgent Genetics RCV001322673 SCV002785861 uncertain significance Brugada syndrome 4 2021-09-03 criteria provided, single submitter clinical testing

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