ClinVar Miner

Submissions for variant NM_181798.1(KCNQ1):c.635T>A (p.Phe212Tyr) (rs199472759)

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 RCV000703853 SCV000832777 uncertain significance Long QT syndrome 2018-05-15 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with tyrosine at codon 339 of the KCNQ1 protein (p.Phe339Tyr). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual referred for testing for long QT syndrome (PMID: 19716085). ClinVar contains an entry for this variant (Variation ID: 67004). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). The p.Phe339 amino acid residue in KCNQ1 has been determined to be clinically significant (PMID: 17224687, 19808498, 23291057). This suggests that variants that disrupt this residue are likely to be causative of disease. 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.
SIB Swiss Institute of Bioinformatics RCV000755757 SCV000883310 uncertain significance Long QT syndrome 1 2018-10-15 criteria provided, single submitter curation This variant is interpreted as Uncertain Significance - Insufficient Evidence, for Long QT syndrome 1, autosomal dominant. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PM5 => Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before (https://www.ncbi.nlm.nih.gov/pubmed/19808498). PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057524 SCV000089043 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.