ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.1658G>A (p.Arg553Gln)

dbSNP: rs118192234
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187913 SCV000241515 pathogenic not provided 2022-02-19 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect with in vitro functional analysis showing that R553Q alters KCNQ2 channel function (Soldovieri et al., 2014; Ambrosino et al., 2015); Not observed in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); This substitution is predicted to be within the C-terminal cytoplasmic domain; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 11690625, 26073431, 16686649, 18698150, 19380078, 12754513, 28976808, 31780880, 27535030, 20437616, 32718099, 27602407, 24375629)
CeGaT Center for Human Genetics Tuebingen RCV000187913 SCV001247374 pathogenic not provided 2017-10-01 criteria provided, single submitter clinical testing
Invitae RCV001248564 SCV001422062 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2023-10-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 553 of the KCNQ2 protein (p.Arg553Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with KCNQ2-related disease (PMID: 24375629, 29933521). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 21767). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects KCNQ2 function (PMID: 24375629, 26073431). This variant disrupts the p.Arg553 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23621294, 27535030). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000678060 SCV000041618 not provided Seizures, benign familial neonatal, 1 no assertion provided literature only BFNE (benign familial neonatal epilepsy)

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