ClinVar Miner

Submissions for variant NM_181798.1(KCNQ1):c.263T>G (p.Val88Gly) (rs368011737)

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 RCV000559784 SCV000627396 uncertain significance Long QT syndrome 2017-03-13 criteria provided, single submitter clinical testing This sequence change replaces valine with glycine at codon 215 of the KCNQ1 protein (p.Val215Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. This variant is present in population databases (rs368011737, ExAC 0.002%) but has not been reported in the literature in individuals with a KCNQ1-related disease. This variant identified in the KCNQ1 gene is located in the transmembrane S3 region of the resulting protein (PMID: 19841300, 25348405). For more information about the location of this variant, please visit www.invitae.com/KCNQ1-topology. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. A different missense substitution at this codon (p.Val215Met) has been determined to be pathogenic (PMID: 16414944, 19841300, 20421371, 23098067, 23392653). This suggests that the valine residue is critical for KCNQ1 protein function and that other missense substitutions at this position may also be pathogenic. In summary, this variant is a rare missense change that affects a residue that is important for protein function. However, in the absence of confirmed segregation or functional studies, at this time this change has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000764972 SCV000896149 uncertain significance Atrial fibrillation, familial, 3; Beckwith-Wiedemann syndrome; Long QT syndrome 1; Jervell and Lange-Nielsen syndrome 1; Short QT syndrome 2 2018-10-31 criteria provided, single submitter clinical testing

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.