Submissions for variant NM_172107.4(KCNQ2):c.620G>A (p.Arg207Gln)

dbSNP: rs118192200

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187863	SCV000241463	pathogenic	not provided	2022-10-31	criteria provided, single submitter	clinical testing	Previously reported in an individual with myokymia due to peripheral nerve hyperexcitability, and functional studies indicate this variant alters voltage-dependent activation (Wuttke et al., 2007; Miceli et al., 2012); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 17872363, 29655203, 22455920, 32184343, 25959266, 25741868, 24375629, 22169383, 11572947, 32884139, 32506321, 33098118)
Fulgent Genetics, Fulgent Genetics	RCV000763453	SCV000894229	pathogenic	Seizures, benign familial neonatal, 1; Developmental and epileptic encephalopathy, 7	2018-10-31	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000187863	SCV001144319	pathogenic	not provided	2019-01-08	criteria provided, single submitter	clinical testing	Not found in the total gnomAD dataset, and the data is high quality (0/270462 chr). Predicted to have a damaging effect on the protein. One de novo case with parental identity confirmed.
Invitae	RCV001205287	SCV001376533	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2023-02-18	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 207 of the KCNQ2 protein (p.Arg207Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with KCNQ2-related conditions (PMID: 17872363, 25959266, 29655203, 32184343, 34711204). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 7391). 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. Experimental studies have shown that this missense change affects KCNQ2 function (PMID: 17872363, 22455920). This variant disrupts the p.Arg207 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11572947, 22169383, 22455920, 24375629). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.
OMIM	RCV000007815	SCV000028020	pathogenic	Seizures, benign familial neonatal, 1, and/or myokymia	2007-11-27	no assertion criteria provided	literature only
GeneReviews	RCV000678085	SCV000041646	not provided	Developmental and epileptic encephalopathy, 7		no assertion provided	literature only	Myokymia, EE (epileptic encephalopathy)
Channelopathy-Associated Epilepsy Research Center	RCV003315294	SCV004015066	not provided	Complex neurodevelopmental disorder		no assertion provided	literature only