Submissions for variant NM_172107.4(KCNQ2):c.2234C>T (p.Pro745Leu)

gnomAD frequency: 0.00001  dbSNP: rs1057518569

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000414686	SCV000492338	uncertain significance	not specified	2016-11-29	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the KCNQ2 gene. The P745L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P745L variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P745L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution alters a conserved position predicted to be within the C-terminal cytoplasmic domain. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in Human Gene Mutation Database in association with KCNQ2- related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Diagnostic Laboratory, Strasbourg University Hospital	RCV001089800	SCV001244214	uncertain significance	Intellectual disability	2020-04-15	no assertion criteria provided	clinical testing