ClinVar Miner

Submissions for variant NM_001148.6(ANK2):c.4744C>T (p.Arg1582Trp) (rs35249198)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171787 SCV000050798 benign not specified 2013-06-24 criteria provided, single submitter research
Invitae RCV000157108 SCV000260827 benign Long QT syndrome 2020-11-25 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001094874 SCV000447180 likely benign Cardiac arrhythmia, ankyrin B-related 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx RCV000171787 SCV000516867 benign not specified 2016-12-13 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000621628 SCV000735007 benign Cardiovascular phenotype 2016-10-23 criteria provided, single submitter clinical testing Subpopulation frequency in support of benign classification
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000171787 SCV000918427 benign not specified 2018-03-06 criteria provided, single submitter clinical testing Variant summary: ANK2 c.4744C>T (p.Arg1582Trp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0024 in 278208 control chromosomes in the gnomAD database, predominantly within the Finnish subpopulation at a frequency of 0.01, including 2 homozygotes. The observed variant frequency within Finnish control individuals in the gnomAD database is approximately 1000 fold of the estimated maximal expected allele frequency for a pathogenic variant in ANK2 causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is a benign polymorphism. c.4744C>T has been reported in the literature in heterozygosity in healthy individuals without arrhythmia or elongation of the QT interval (Ghouse 2015). This report provides further support about the benign nature of the variant. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, without evidence for independent evaluation, classifying the variant as benign(2)/VUS(1). Based on the evidence outlined above, the variant was classified as benign.
Blueprint Genetics RCV000157108 SCV000206831 likely benign Long QT syndrome 2014-05-16 no assertion criteria provided clinical testing

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