Submissions for variant NM_172107.4(KCNQ2):c.599T>C (p.Leu200Pro)

dbSNP: rs796052622

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187857	SCV000241457	likely pathogenic	not provided	2013-07-23	criteria provided, single submitter	clinical testing	p.Leu200Pro (CTG>CCG): c.599 T>C in exon 4 of the KCNQ2 gene (NM_172107.2)The Leu200Pro missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although both Leucine and Proline are uncharged, non-polar amino acid residues, the gain of a Proline may affect the secondary structure of the KCNQ2 protein. Leu200Pro alters a highly conserved position in the S4 voltage-sensor segment of the protein and other missense mutations in this region of the protein have been reported in association with epilepsy. In addition, multiple in-silico algorithms predict Leu200Pro may be damaging to the structure/function of the protein. Therefore, based on the currently available information, Leu200Pro is a strong candidate for a disease-causing mutation, although the possibility that it is a benign variant cannot be excluded. The variant is found in INFANT-EPI panel(s).