ClinVar Miner

Submissions for variant NM_201590.3(CACNB2):c.218C>T (p.Ala73Val) (rs200367454)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000245027 SCV000318131 uncertain significance Cardiovascular phenotype 2018-04-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000766681 SCV000512473 uncertain significance not provided 2017-02-06 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CACNB2 gene. The A73V variant has previously been reported in one individual with idiopathic ventricular fibrillation (IVF) and was absent from 400 healthy control alleles (Burashnikov et al., 2010). The A73V variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, the A73V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000437912 SCV000538571 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: HGMD 1 proband with early repolarization syndrome. LB in Amendola 2015. ClinVar 1 star review Ambry VUS, ESP LB
Invitae RCV000693237 SCV000821097 uncertain significance Brugada syndrome 4 2018-03-16 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 73 of the CACNB2 protein (p.Ala73Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs200367454, ExAC 0.04%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with idiopathic ventricular fibrillation (PMID: 20817017). ClinVar contains an entry for this variant (Variation ID: 161209). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; 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.
Fulgent Genetics,Fulgent Genetics RCV000693237 SCV000896043 uncertain significance Brugada syndrome 4 2018-10-31 criteria provided, single submitter clinical testing
CSER_CC_NCGL; University of Washington Medical Center RCV000148447 SCV000190146 likely benign Ventricular fibrillation, idiopathic 2014-06-01 no assertion criteria provided research

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