ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.2428C>A (p.Leu810Met) (rs754883792)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000555194 SCV000627487 uncertain significance Long QT syndrome 2018-09-13 criteria provided, single submitter clinical testing This sequence change replaces leucine with methionine at codon 1150 of the KCNH2 protein (p.Leu1150Met). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and methionine. This variant is present in population databases (rs754883792, ExAC 0.05%). This variant has not been reported in the literature in individuals with KCNH2-related disease. ClinVar contains an entry for this variant (Variation ID: 456931). This variant identified in the KCNH2 gene is located in the cytoplasmic C-terminal region of the resulting protein (PMID: 19841300, 25348405), but it is unclear how this variant impacts the function of this protein. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.