ClinVar Miner

Submissions for variant NM_181798.1(KCNQ1):c.1399C>T (p.Arg467Ter) (rs794728537)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182227 SCV000234530 pathogenic not provided 2016-01-11 criteria provided, single submitter clinical testing The Arg594Stop mutation in the KCNQ1 gene has been reported in association with LQTS (Stattin et al., 2012). Also, Arg594Stop has been observed in other unrelated individuals tested for LQTS at GeneDx. Arg594Stop was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This mutation is predicted to cause loss of normal protein function either through abnormal, prematurely truncated protein, or by absence of protein product due to nonsense-mediated mRNA decay. Other nonsense mutations in KCNQ1 (Gln530Stop, Gln531Stop, Tyr536Stop, Gln601Stop, Tyr662Stop) have been reported in association with LQTS
Invitae RCV000815960 SCV000956441 pathogenic Long QT syndrome 2018-09-11 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the KCNQ1 gene (p.Arg594*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 83 amino acids of the KCNQ1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual referred for long QT syndrome testing (PMID: 23098067). ClinVar contains an entry for this variant (Variation ID: 200858). This variant disrupts the C-terminus of the KCNQ1 protein. Other variant(s) that disrupt this region (p.Arg632Glnfs*20) have been determined to be pathogenic (PMID: 10024302, 23098067, 23631430, 25187895, 19825999, 16981927). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery,Institute of Otolaryngology, Chinese PLA General Hospital RCV000770826 SCV000902325 likely pathogenic Long QT syndrome 1 2019-02-26 no assertion criteria provided case-control

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.