ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.1342C>T (p.Arg448Ter) (rs118192226)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000720328 SCV000851205 pathogenic Seizures 2016-09-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense),Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000187902 SCV000701213 pathogenic not provided 2016-05-24 criteria provided, single submitter clinical testing
GeneDx RCV000187902 SCV000241504 pathogenic not provided 2018-04-17 criteria provided, single submitter clinical testing The R448X variant in the KCNQ2 gene has been reported previously in association with benign familial neonatal seizures and benign familial neonatal-infantile seizures (Zara et al., 2013; Yum et al., 2010; Moulard et al., 2001). The R448X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, the presence of R448X is consistent with the diagnosis of a KCNQ2-related disorder in this individual.
GeneReviews RCV000020970 SCV000041613 pathogenic Benign familial neonatal seizures 1 2016-03-31 no assertion criteria provided literature only BFNIS (benign familial neonatal-infantile seizures)
Invitae RCV000463586 SCV000543196 pathogenic Early infantile epileptic encephalopathy 2016-06-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 448 (p.Arg448*) of the KCNQ2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNQ2 are known to be pathogenic. This particular variant has been reported in individuals and families with benign familial neonatal epilepsy (PMID: 23360469, 25982755, 20119593, 11690625). For these reasons, this variant has been classified as Pathogenic.

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.