Submissions for variant NM_172107.4(KCNQ2):c.1658G>T (p.Arg553Leu)

dbSNP: rs118192234

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000423974	SCV000516635	pathogenic	not provided	2017-11-08	criteria provided, single submitter	clinical testing	The R553L missense variant in the KCNQ2 gene has been reported previously as de novo in apatient with Ohtahara syndrome (Kato et al., 2013). It was not observed in approximately 6,500 individuals ofEuropean and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not acommon benign variant in these populations. The R553L variant is a non-conservative amino acidsubstitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge,size and/or other properties. This substitution occurs at a position that is conserved across species. Differentmissense variants in the same residue (R553W, R553Q) as well as multiple missense variants in nearbyresidues have been reported in the Human Gene Mutation Database in association with KCNQ2-relateddisorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore,R553L is considered a pathogenic variant.
GeneReviews	RCV000678186	SCV000484635	not provided	Developmental and epileptic encephalopathy, 7		no assertion provided	literature only	EE (epileptic encephalopathy)