ClinVar Miner

Submissions for variant NM_181798.1(KCNQ1):c.974G>A (p.Arg325Gln) (rs145229963)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000057583 SCV000234492 uncertain significance not provided 2017-11-20 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KCNQ1 gene. The R452Q variant has not been published in association with arrhythmia, to our knowledge, however, it has been observed in at least one Caucasian individual from a ostensibly healthy control population (Kapa et al., 2009; Giudicessi et al., 2012; Kapplinger et al., 2015). It has been observed both independently, and in conjunction with additional cardiogenetic variants, in other individuals referred for LQTS genetic testing at GeneDx, although no informative segregation data are available to further clarify the role of this variant in disease. The R452Q variant is also observed in 23/126020 (0.02%) alleles from individuals of European (non-Finnish) ancestry in large population cohorts (Lek et al., 2016). In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Additionally, although a missense variant at the same residue (R452W) has been reported in association with LQTS (Tester et al., 2005), the clinical significance of this variant remains to be definitively determined.
Ambry Genetics RCV000246256 SCV000320292 uncertain significance Cardiovascular phenotype 2017-06-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Illumina Clinical Services Laboratory,Illumina RCV000284895 SCV000370296 uncertain significance Romano-Ward syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000337547 SCV000370297 uncertain significance Familial atrial fibrillation 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000398200 SCV000370298 uncertain significance short QT syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000297971 SCV000370299 uncertain significance Long QT syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000355198 SCV000370300 uncertain significance Jervell and Lange-Nielsen syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000297971 SCV000543296 uncertain significance Long QT syndrome 2018-11-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 452 of the KCNQ1 protein (p.Arg452Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs145229963, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with KCNQ1-related disease. ClinVar contains an entry for this variant (Variation ID: 67030). 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 tolerated, but 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 RCV000764975 SCV000896152 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
Color RCV000777767 SCV000913736 uncertain significance Arrhythmia 2018-04-07 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant is a missense variant located in the C terminus outside of highly conserved region of the KCNH2 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact 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 nor has the variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 29/275918 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057583 SCV000089102 not provided not provided no assertion provided literature only This variant has been reported in the following publications (PMID:19841300).

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.