Submissions for variant NM_172107.4(KCNQ2):c.1058G>A (p.Arg353His)

dbSNP: rs796052645

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187896	SCV000241498	pathogenic	not provided	2020-03-06	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26007637, 25959266)
Invitae	RCV001376923	SCV001574123	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2022-07-25	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg353 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29726930). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNQ2 protein function. ClinVar contains an entry for this variant (Variation ID: 205899). This missense change has been observed in individual(s) with early infantile epileptic encephalopathy (PMID: 25959266). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 353 of the KCNQ2 protein (p.Arg353His).
GeneReviews	RCV000678162	SCV000484607	not provided	Developmental and epileptic encephalopathy, 7		no assertion provided	literature only	EE (epileptic encephalopathy)