ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1933A>G (p.Met645Val) (rs199472974)

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 RCV000181830 SCV000234133 pathogenic not provided 2013-11-22 criteria provided, single submitter clinical testing p.Met645Val (ATG>GTG): c.1933 A>G in exon 7 of the KCNH2 gene (NM_000238.2). The Met645Val mutation in the KCNH2 gene has been reported as a de novo mutation identified in a neonate with bradycardia, heart failure, ventricular tachycardia, and syncope (Lupoglazoff J et al., 2004). Met645Val was not observed in 200 control alleles (Lupoglazoff J et al., 2004) and it was not observed inapproximately 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. Mutations at this residue (Met645Ile, Met645Arg, Met645Leu) and in nearby residues (Val644Leu, Val644Phe, Gly648Ser) have been reported in association with LQTS, further supporting the functional importance of this residue and this region of the protein. In summary, Met645Val in the KCNH2 gene is interpreted as a disease-causing mutation. The variant is found in LQT panel(s).
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058060 SCV000089580 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:14998624). 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.