ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1935G>A (p.Met645Ile) (rs199472973)

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
GeneDx RCV000431767 SCV000515912 uncertain significance not provided 2018-10-11 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KCNH2 gene. The M645I variant hasbeen previously reported in association with LQTS (Kapplinger et al., 2009; Issa et al., 2015). TheM645I variant was not observed in approximately 6,500 individuals of European and AfricanAmerican ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benignvariant in these populations. This substitution occurs at a position that is conserved across species, andin silico analysis predicts this variant is probably damaging to the protein structure/function. Missensevariants in the same residue (M645V, M645L, M645R) and in nearby residues (F640V, F640L, S641F,V644L, G648S, S649P) have been reported in the Human Gene Mutation Database in association withLQTS (Stenson et al., 2014). Nevertheless, the M645I variant is a conservative amino acidsubstitution, which is not likely to impact secondary protein structure as these residues share similarproperties. Thus, this variant lacks observation in a significant number of affected individuals,segregation data, and functional evidence, which would further clarify its pathogenicity.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058062 SCV000089582 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.

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.