ClinVar Miner

Submissions for variant NM_000218.3(KCNQ1):c.1621G>A (p.Val541Ile) (rs199472796)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000767088 SCV000234511 uncertain significance not provided 2018-02-08 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KCNQ1 gene. The V541I variant has been previously reported in at least one individual is association with LQTS (Kapplinger et al., 2009; Kapplinger et al., 2015). Thus far, no segregation data are available to further clarify the role of this variant in disease. The V541I variant is also not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, V541I is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, this variant is also classified as a variant of uncertain significance in ClinVar by another clinical laboratory (ClinVar SCV000539462.1; Landrum et al., 2016).
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000182208 SCV000539462 uncertain significance not specified 2016-07-26 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 1 LQT proband; ClinVar: Path by GeneDx
Color Health, Inc RCV000771868 SCV000904591 uncertain significance Arrhythmia 2020-11-25 criteria provided, single submitter clinical testing This missense variant replaces valine with isoleucine at codon 541 of the KCNQ1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual referred for long QT syndrome genetic testing (PMID: 19716085). This variant has been identified in 5/184336 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV001040145 SCV001203706 uncertain significance Long QT syndrome 2020-03-10 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 541 of the KCNQ1 protein (p.Val541Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs199472796, ExAC 0.008%). This variant has been observed in an individual referred for long QT syndrome genetic testing (PMID: 19716085). ClinVar contains an entry for this variant (Variation ID: 67043). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; 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.
Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues RCV001089522 SCV001244875 likely pathogenic Long QT syndrome 1 2019-07-22 criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057606 SCV000089125 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.
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000656140 SCV000678334 uncertain significance Wolff-Parkinson-White pattern 2017-07-14 no assertion criteria provided research This variant was identified in an individual with Wolff-Parkinson-White syndrome

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.