ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.446G>C (p.Gly149Ala) (rs199472865)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000706355 SCV000835399 uncertain significance Long QT syndrome 2018-06-21 criteria provided, single submitter clinical testing This sequence change replaces glycine with alanine at codon 149 of the KCNH2 protein (p.Gly149Ala). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and alanine. This variant is present in population databases (rs199472865, ExAC 0.01%). This variant has been observed in an individual who was referred for long QT syndrome genetic testing (PMID: 19716085). ClinVar contains an entry for this variant (Variation ID: 67506). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Fulgent Genetics,Fulgent Genetics RCV000765948 SCV000897369 uncertain significance Short QT syndrome 1; Long QT syndrome 2 2018-10-31 criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058235 SCV000089755 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:19716085). 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.