ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.901G>A (p.Gly301Ser) (rs1057516099)

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
Neurogenetics Laboratory - MEYER,AOU Meyer RCV000416958 SCV000494520 pathogenic Epileptic encephalopathy 2016-11-16 criteria provided, single submitter clinical testing
Baylor Genetics RCV000678149 SCV000807301 uncertain significance Early infantile epileptic encephalopathy 7 2017-09-01 criteria provided, single submitter clinical testing Likely pathogenicity based on finding it once in our laboratory de novo in a 5-year-old female with intellectual disability, hypotonia, ataxia, epilepsy (onset at 10 days, no seizures since age 1y), dysmorphisms, short stature
Invitae RCV001037300 SCV001200709 likely pathogenic Early infantile epileptic encephalopathy 2019-02-26 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 301 of the KCNQ2 protein (p.Gly301Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with KCNQ2-related epilepsy (PMID: 27864847). ClinVar contains an entry for this variant (Variation ID: 369770). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneReviews RCV000678149 SCV000484592 pathogenic Early infantile epileptic encephalopathy 7 2016-03-31 no assertion criteria provided literature only EE (epileptic encephalopathy)

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.