ClinVar Miner

Submissions for variant NM_000218.2(KCNQ1):c.1702G>A (p.Gly568Arg) (rs199472807)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000250706 SCV000320027 likely pathogenic Cardiovascular phenotype 2017-12-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057622 SCV000089141 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:15840476;PMID:19716085;PMID:19841300). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000678815 SCV000805001 pathogenic not specified 2016-02-29 no assertion criteria provided clinical testing
GeneDx RCV000505735 SCV000234521 pathogenic not provided 2018-06-06 criteria provided, single submitter clinical testing The G568R pathogenic variant in the KCNQ1 gene has been previously reported in multiple individuals in association with LQTS (Tester et al., 2005; Kapa et al., 2009; Kapplinger et al., 2009; Goldenberg et al., 2011; Giudicessi et al., 2012; Medlock et al., 2012; Barshshet et al., 2012; Giudicessi et al., 2013; Poterucha et al., 2015; Robinson et al., 2015). This variant has also been identified independently in multiple unrelated individuals with LQTS referred for genetic testing at GeneDx. Additionally, G568R has been shown to segregate with LQTS in multiple affected relatives from unrelated families, as reported by Giudicessi et al. (2013) and observed at GeneDx. This variant is not observed in large population cohorts (Lek et al., 2016). The G568R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Furthermore, in silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Finally, pathogenic/likely pathogenic missense variants at the same residue (G568A), and in nearby residues (S566Y, S566F, I567T), have been reported at GeneDx and/or in HGMD in association with LQTS (Stenson et al., 2014), supporting the functional importance of this residue and region of the protein.In summary, G568R in the KCNQ1 gene is interpreted as a pathogenic variant.

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.