ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.638G>A (p.Arg213Gln)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000032979 SCV000151520 likely pathogenic Early infantile epileptic encephalopathy 7 2013-04-15 criteria provided, single submitter clinical testing
GeneDx RCV000187867 SCV000241467 pathogenic not provided 2018-02-01 criteria provided, single submitter clinical testing p.Arg213Gln (CGG>CAG): c.638 G>A in exon 4 of the KCNQ2 gene (NM_172107.2)The Arg213Gln mutation in the KCNQ2 gene has been reported previously in association with neonatal epileptic encephalopathy (Weckhuysen et al., 2012). This variant is a non-conservative amino acid substitution of a positively charged Arginine residue with an uncharged Glutamine residue It alters a highly conserved position in the S4 (voltage sensor) segment of the protein, and a different amino acid substitution at the same position (Arg213Trp) has been reported in association with benign familial neonatal seizures (Sadewa et al., 2007). The variant is found in EPILEPSY panel(s).
Invitae RCV000698323 SCV000826983 likely pathogenic Early infantile epileptic encephalopathy 2018-05-02 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 213 of the KCNQ2 protein (p.Arg213Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with neonatal epileptic encephalopathy in a family (PMID: 22275249, 25982755) and has been reported in an individual affected with neonatal seizures (PMID: 26993267). ClinVar contains an entry for this variant (Variation ID: 39760). Experimental studies have shown that this missense change affects channel opening in response to depolarization, although they are present in the membrane, and increase cell firing frequency (PMID: 23440208, 22455920, 24318194). 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.
Fulgent Genetics,Fulgent Genetics RCV000763452 SCV000894228 pathogenic Benign familial neonatal seizures 1; Early infantile epileptic encephalopathy 7 2018-10-31 criteria provided, single submitter clinical testing
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV000032979 SCV001164157 pathogenic Early infantile epileptic encephalopathy 7 2017-08-10 criteria provided, single submitter clinical testing
OMIM RCV000032979 SCV000056754 pathogenic Early infantile epileptic encephalopathy 7 2012-01-01 no assertion criteria provided literature only
GeneReviews RCV000032979 SCV000484570 pathogenic Early infantile epileptic encephalopathy 7 2016-03-31 no assertion criteria provided literature only EE (epileptic encephalopathy)

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