ClinVar Miner

Submissions for variant NM_000218.2(KCNQ1):c.160_168dup (p.Ile54_Pro56dup) (rs397515877)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000035343 SCV000058991 benign not specified 2017-05-18 criteria provided, single submitter clinical testing p.Ile54_Pro56dup in Exon 1 of KCNQ1: This variant is not expected to have clinic al significance because it has been identified in 2.9% (250/8370) of African ch romosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitu; dbSNP rs561562768). It has been reported in two individuals with cardia c arrhythmias (1/182 LQTS, Berge 2008; 1/231 AF, Abraham 2010) and segregated in three affected individuals in one family, though phenotypes were unknown in 2 o ther mutation carriers (Abraham 2010). In addition, one study demonstrated some alteration of channel properties (Abraham 2010) although this study was only in vitro such that correlation to a clinical phenotype was not possible. This varia nt was also identified in several healthy control cohorts (0.3% 4/1488 chromosom es, Ackerman 2003; 1/364 chromosomes, Arnestad 2007; 2.1% (2/94) African-America n control chromosomes, Abraham 2010) and is now listed in the KCNQ1 database as a benign variant ( In summary, given t he high frequency of the variant in spite of the reports in the literature, this variant is benign for a reasonably penetrant disease variant and insufficient b iological evidence for a clinically relevant impact to protein function, we have classified this variant as likely benign.
GeneDx RCV000035343 SCV000234378 likely benign not specified 2017-10-30 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.
Invitae RCV001080143 SCV000259853 benign Long QT syndrome 2020-11-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV000250643 SCV000318444 uncertain significance Cardiovascular phenotype 2013-02-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV000250643 SCV000318524 uncertain significance Cardiovascular phenotype 2013-03-02 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000035343 SCV000343643 benign not specified 2016-08-17 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852643 SCV000995348 likely benign Ventricular fibrillation 2019-05-20 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000035343 SCV001372409 likely benign not specified 2020-06-02 criteria provided, single submitter clinical testing Variant summary: KCNQ1 c.160_168dupATCGCGCCC (p.Ile54_Pro56dup) results in an in-frame duplication that is predicted to duplicate 3 amino acids into the encoded protein. The variant allele was found at a frequency of 0.0073 in 35616 control chromosomes, predominantly at a frequency of 0.03 within the African or African-American subpopulation in the gnomAD database, including 3 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 300 fold of the estimated maximal expected allele frequency for a pathogenic variant in KCNQ1 causing Arrhythmia phenotype (0.0001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.160_168dupATCGCGCCC has been reported in the literature in individuals affected with Arrhythmia as well as in control population (e.g. Abraham_2010, Berge_2008, Ackerman_2003, Tester_2005_01, Kapa_2009, Hassnan_2017, Millat_2014). In a family with familial atrial fibrillation, this variant was found in four affected members and also in an unaffected carrier suggesting an inconclusive co-segregation of this variant with disease (Abraham_2010). This family however, was not comprehensively screened for mutations in all susceptibility genes. Co-occurrences with other pathogenic variants have been reported (KCNQ1 c.674C>T, p.Ser225Leu; KCNH2 c.1841C>T, p.Ala614Val) in our internal database. In vitro functional study detected partial defect of the channel properties (Abraham_2010), suggesting that it could be a functional polymorphism. Five ClinVar submitters (evaluation after 2014) cite the variant as likely benign (n=2) or benign (n=3). Based on the evidence outlined above, the variant was classified as likely benign.
OMIM RCV000114749 SCV000148632 pathogenic Atrial fibrillation, familial, 3 2010-01-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.