ClinVar Miner

Submissions for variant NM_000218.2(KCNQ1):c.341T>C (p.Leu114Pro) (rs199473448)

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 RCV001378785 SCV001576438 likely pathogenic Long QT syndrome 2017-05-15 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 114 of the KCNQ1 protein (p.Leu114Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in a family with the proband affected with congenital long QT syndrome (PMID: 12402336). ClinVar contains an entry for this variant (Variation ID: 53036). This variant identified in the KCNQ1 gene is located in the cytoplasmic N-terminal region of the resulting protein (PMID: 19841300, 25348405). Experimental studies have shown that this missense change disrupts the normal protein trafficking and stability in a dominant negative fashion (PMID: 17053194, 19114714). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 1
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057660 SCV000089179 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:12402336;PMID:17053194;PMID:19114714). 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.