ClinVar Miner

Submissions for variant NM_201590.3(CACNB2):c.1774C>T (p.Arg592Trp) (rs546669133)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000387951 SCV000361819 uncertain significance Brugada syndrome 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000486501 SCV000568074 uncertain significance not specified 2015-10-22 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CACBN2 gene. The R591W variant has not beenpublished as a pathogenic variant or reported as a benign variant to our knowledge. However, it has been seen in oneother individual who had DNA-based testing for Comprehensive Arrhythmia at GeneDx. The R591W variant is anon-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differin polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved acrossspecies. In silico analysis predicts this variant is probably damaging to the protein structure/function. Although theR591W variant was not observed in approximately 6,500 individuals of European and African American ancestry inthe NHLBI Exome Sequencing Project, the 1000 Genomes Project reports R591W was observed in 1/694 (approx.0.1%) alleles from individuals of Ad Mixed American background; specifically 1/208 (approx. 0.5%) alleles fromPuerto Ricans from Puerto Rico. Furthermore, no missense variants in nearby residues have been reported in theHuman Gene Mutation Database and by GeneDx in association with arrhythmia (Stenson et al., 2014), suggestingthat this region of the protein may not harbor disease-causing variants.
Fulgent Genetics,Fulgent Genetics RCV000764884 SCV000896044 uncertain significance Brugada syndrome 4 2018-10-31 criteria provided, single submitter clinical testing

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