Submissions for variant NM_172107.4(KCNQ2):c.802C>T (p.Leu268Phe)

dbSNP: rs1057516094

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neurogenetics Laboratory - MEYER, AOU Meyer	RCV000416991	SCV000494521	likely pathogenic	Epileptic encephalopathy	2016-11-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001815323	SCV002064061	likely pathogenic	not provided	2021-12-01	criteria provided, single submitter	clinical testing
Invitae	RCV001865254	SCV002181022	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2021-07-28	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Leu268 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27535030; Invitae). 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 protein function (PMID: 32179837). 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: 369763). This missense change has been observed in individual(s) with developmental and epileptic encephalopathy (PMID: 25880994). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with phenylalanine at codon 268 of the KCNQ2 protein (p.Leu268Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine.
GeneReviews	RCV000678140	SCV000484580	not provided	Developmental and epileptic encephalopathy, 7		no assertion provided	literature only	EE (epileptic encephalopathy)