ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.2131A>G (p.Ile711Val) (rs199473532)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181838 SCV000234141 pathogenic not provided 2013-11-26 criteria provided, single submitter clinical testing p.Ile711Val (ATC>GTC): c.2131 A>G in exon 8 of the KCNH2 gene (NM_000238.2)The Ile711Val mutation in the KCNH2 gene has been reported in one individual with LQTS and it was absent from 2,600 control alleles (Kapplinger J et al., 2009). Ile711Val results in a conservative amino acid substitution of one non-polar amino acid with another at a position that is conserved across species. Mutations in nearby residues (Ser706Cys, Ser706Phe, Ala715Val) have been reported in association with LQTS, further supporting the functional importance of this region of the protein. Furthermore, the Ile711Val mutation was not observed with any significant frequency inapproximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project.In summary, Ile711Val in the KCNH2 gene is interpreted as a disease-causing mutation. The variant is found in LQT panel(s).
Color RCV000777696 SCV000913629 uncertain significance Arrhythmia 2019-11-08 criteria provided, single submitter clinical testing
Invitae RCV000148537 SCV001408834 uncertain significance Long QT syndrome 2019-08-01 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 711 of the KCNH2 protein (p.Ile711Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs199473532, ExAC 0.006%). This variant has been observed in individuals with clinical features of long QT syndrome (PMID: 19716085, 26746457). ClinVar contains an entry for this variant (Variation ID: 67367). This variant has been reported to affect KCNH2 protein function (PMID: 25417810). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058087 SCV000089607 not provided Congenital long QT syndrome no assertion provided literature only This variant has been reported as associated with Long QT syndrome in the following publications (PMID:19716085). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
CSER _CC_NCGL, University of Washington RCV000148537 SCV000190250 uncertain significance Long QT syndrome 2014-06-01 no assertion criteria provided research

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.