Submissions for variant NM_172107.4(KCNQ2):c.641G>A (p.Arg214Gln)

dbSNP: rs1057518555

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000700920	SCV000829697	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2023-07-19	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg214 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11175290, 11784811). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects KCNQ2 function (PMID: 28283543). 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: 578032). This missense change has been observed in individual(s) with KCNQ2-related conditions (PMID: 31152295). 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 glutamine, which is neutral and polar, at codon 214 of the KCNQ2 protein (p.Arg214Gln).
Department of Clinical Genetics, Medical University of Lodz	RCV003987673	SCV004803186	pathogenic	Seizures, benign familial neonatal, 1	2023-07-27	criteria provided, single submitter	literature only
GeneDx	RCV004721564	SCV005328001	pathogenic	not provided	2023-12-13	criteria provided, single submitter	clinical testing	Published function studies demonstrate the p.(R214Q) variant moderately affects KCNQ2 channel function (PMID: 18515377, 17227916, 34650221); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; This variant is associated with the following publications: (PMID: 28283543, 11784811, 11175290, 17227916, 34650221, 18515377, 35856407, 31152295, 37405542)