ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1864C>T (p.Leu622Phe) (rs199473525)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000552720 SCV000627444 uncertain significance Long QT syndrome 2017-03-15 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 622 of the KCNH2 protein (p.Leu622Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (rs199473525, ExAC no frequency). This variant has been reported in an individual affected with long QT syndrome (PMID: 26669661) and in an individual with a clinical suspicion of long QT syndrome (PMID: 15840476). ClinVar contains an entry for this variant (Variation ID: 67301). This variant identified in the KCNH2 gene is located in the pore region of the resulting protein (PMID: 19841300, 25348405). For more information about the location of this variant, please visit www.invitae.com/KCNH2-topology. Experimental studies have shown that this missense change alters the expression or potassium selectivity of in vitro expressed KCNH2, though the clinical significance of this observation is uncertain (PMID: 23471968). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058019 SCV000089539 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:15840476). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

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.