Submissions for variant NM_172107.4(KCNQ2):c.506G>T (p.Cys169Phe) (rs1064793392)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000478609	SCV000565999	likely pathogenic	not provided	2015-03-15	criteria provided, single submitter	clinical testing	The C169F variant in the KCNQ2 gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The C169F variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The C169F variant is a non-conservative amino acid substitution, which occurs at a position within the helical transmembrane domain, that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (G159E and V175L) have been reported in the Human Gene Mutation Database in association with KCNQ2-related seizures (Stenson et al., 2014), supporting the functional importance of this region of the protein. The C169F variant is a good candidate for a disease-causing variants, However, the possibility it may be a rare benign variant cannot be excluded.