Submissions for variant NM_172107.4(KCNQ2):c.727C>T (p.Leu243Phe)

dbSNP: rs118192205

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002513155	SCV003443968	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2023-07-07	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 243 of the KCNQ2 protein (p.Leu243Phe). This missense change has been observed in individuals with KCNQ2-related conditions (PMID: 14534157, 30478917). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Leu243 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31019026). 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: 30478917). 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: 21798).
GeneReviews	RCV000678090	SCV000041653	not provided	Seizures, benign familial neonatal, 1		no assertion provided	literature only	BFNE (benign familial neonatal epilepsy)
Channelopathy-Associated Epilepsy Research Center	RCV003315303	SCV004015076	not provided	Complex neurodevelopmental disorder		no assertion provided	literature only