ClinVar Miner

Submissions for variant NM_001148.6(ANK2):c.4745G>A (p.Arg1582Gln) (rs138842207)

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Total submissions: 9
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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 RCV000171739 SCV000050745 likely benign not provided 2013-06-24 criteria provided, single submitter research
Ambry Genetics RCV000242956 SCV000319006 likely benign Cardiovascular phenotype 2018-08-27 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification;Subpopulation frequency in support of benign classification
Illumina Clinical Services Laboratory,Illumina RCV000606830 SCV000447181 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.
Invitae RCV000360584 SCV000557178 likely benign Long QT syndrome 2020-11-24 criteria provided, single submitter clinical testing
GeneDx RCV000613422 SCV000729790 likely benign not specified 2017-09-26 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.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000606830 SCV000743822 likely benign Cardiac arrhythmia, ankyrin B-related 2016-05-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000613422 SCV001361177 benign not specified 2019-08-13 criteria provided, single submitter clinical testing Variant summary: ANK2 c.4745G>A (p.Arg1582Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00076 in 281862 control chromosomes, predominantly at a frequency of 0.0015 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 150 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 found primarily in populations of Non-Finnish European origin. c.4745G>A has been reported in the literature to be found in 3 heterozygotes, and their average QTc value was reported to be in the normal range. (Ghouse_2015). This report therefore does not support a pathogenic role for the variant. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Four laboratories classified the variant as likely benign, while one classified as VUS. Based on the evidence outlined above, the variant was classified as benign.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000613422 SCV001433462 likely benign not specified 2020-01-21 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000606830 SCV000734303 likely benign Cardiac arrhythmia, ankyrin B-related no assertion criteria provided clinical testing

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