ClinVar Miner

Submissions for variant NM_000238.3(KCNH2):c.2255G>A (p.Arg752Gln) (rs121912512)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER_CC_NCGL; University of Washington Medical Center RCV000148536 SCV000190249 uncertain significance Long QT syndrome 2014-06-01 no assertion criteria provided research
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058100 SCV000089620 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:12621127). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Invitae RCV000148536 SCV000253679 likely pathogenic Long QT syndrome 2015-04-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 752 of the KCNH2 protein (p.Arg752Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant has been reported in the literature and is present in population databases (rs121912512, <0.01%). It was reported in the homozygous state in a case of infantile long QT syndrome that presented in utero. ClinVar contains entries for this variant (RCV000058100, RCV000015516, RCV000148536). Experimental studies have shown that this missense change does not transmit current vitro and is also trafficking deficient (PMID: 12621127, 25417810). A different missense substitution at this codon, p.Arg752Trp, is considered Pathogenic for long QT syndrome (PMID: 11854117, 16432067, 18441445, 23098067, 25417810). This indicates that the arginine residue at this position is important for KCNH2 protein function. In summary, this is a rare variant that has been observed in the homozygous state in a case of early onset long QT syndrome and it affects an amino acid that is known to be necessary for normal protein activity. As a result, this variant has been classified as Likely Pathogenic.
OMIM RCV000015516 SCV000035781 pathogenic Long QT syndrome 2 2003-05-01 no assertion criteria provided literature only

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.