ClinVar Miner

Submissions for variant NM_172107.3(KCNQ2):c.1678C>T (p.Arg560Trp) (rs773171451)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187915 SCV000241517 pathogenic not provided 2018-06-12 criteria provided, single submitter clinical testing p.Arg560Trp (CGG>TGG): c.1678 C>T in exon 15 of the KCNQ2 gene (NM_172107.2) The R560W mutation in the KCNQ2 gene has been previously reported as a mutation in an individual with an onset of tonic seizures and myoclonic jerks at day 3 of life (Weckhuysen, et al., 2012). Functional studies show that the R560W mutation (reported as R532W using alternative nomenclature) alters the expression and function of the Kv7.2 and Kv7.3 potassium channels (Orhan et al., 2014). It 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. R560W alters a highly conserved position in the carboxy terminus of the KCNQ2 protein and other missense mutations have been reported in this region of the protein in association with epilepsy. Therefore, R560W is considered a disease-causing mutation, and its presence is consistent with a diagnosis of a KCNQ2-related disorder. The variant is found in EPILEPSY,INFANT-EPI panel(s).
GeneReviews RCV000678188 SCV000484637 pathogenic Early infantile epileptic encephalopathy 7 2016-03-31 no assertion criteria provided literature only EE (epileptic encephalopathy)
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000678188 SCV000930223 likely pathogenic Early infantile epileptic encephalopathy 7 2019-04-27 criteria provided, single submitter clinical testing
Invitae RCV000462637 SCV000543193 pathogenic Early infantile epileptic encephalopathy 2017-09-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 560 of the KCNQ2 protein (p.Arg560Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in 2 individuals affected with early-infantile epileptic encephalopathy (PMID: 22275249, 25880994). ClinVar contains an entry for this variant (Variation ID: 205915). An experimental study has shown that this missense change (called R532W) disrupts KCNQ2 channel function, likely due to decreased cell-surface expression of the protein (PMID: 24318194). For these reasons, this variant has been classified as Pathogenic.

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