ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.2087G>A (p.Gly696Asp) (rs199473022)

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
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000454975 SCV000539430 uncertain significance not specified 2016-03-31 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 2 probands (Tester 2005 and Itoh 2015); ExAC: 1/3460 European; ClinVar: 1 Path; Immunoblot analysis (nZ2) of transiently transfected HEK293 cells revealed the the mutation trafficked similar to WT (Fig. 6b; Andersen 2014).
Color RCV000771782 SCV000904466 uncertain significance Arrhythmia 2018-07-22 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the cytoplasmic domain of the KCNH2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in an individual affected with long QT syndrome (PMID: 18675227). This variant has also been identified in 16/170694 chromosomes (13/67262 non-Finnish European chromosomes) in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Invitae RCV000795860 SCV000935338 uncertain significance Long QT syndrome 2018-08-10 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 1036 of the KCNH2 protein (p.Gly1036Asp). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. While this variant is present in population databases (rs199473022), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individuals affected with Long QT syndrome (PMID: 15840476, 18675227). ClinVar contains an entry for this variant (Variation ID: 67469). Experimental studies have shown that this missense change disrupts protein function in vitro (PMID: 18675227). 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.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058197 SCV000089717 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:15840476;PMID:18675227;PMID:19841300). 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.