Submissions for variant NM_001040142.2(SCN2A):c.4025T>C (p.Leu1342Pro)

dbSNP: rs796053134

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000189147	SCV000242779	likely pathogenic	not provided	2012-09-11	criteria provided, single submitter	clinical testing	p.Leu1342Pro (CTG>CCG):c.4025 T>C in exon 22 of the SCN2A gene (NM_021007.2). The Leu1342Pro missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Leu1342Pro in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. Although Leucine and Proline are both uncharged, non-polar amino acids, the gain of a bulky Proline residue could alter the secondary structure of the protein. Leu1342Pro alters a highly conserved position in the S5 segment of the third transmembrane domain, and multiple in silico algorithms predict it is damaging to protein structure/function. Therefore, based on the currently available information, Leu1342Pro 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).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001252986	SCV001428474	pathogenic	Developmental and epileptic encephalopathy, 11	2019-01-21	criteria provided, single submitter	clinical testing	This variant was identified as de novo (maternity and paternity confirmed).
Neurology Department, Shenzhen Children's Hospital	RCV001847841	SCV002099481	pathogenic	West syndrome	2022-02-16	no assertion criteria provided	clinical testing
Channelopathy-Associated Epilepsy Research Center	RCV002319455	SCV002605510	not provided	Complex neurodevelopmental disorder		no assertion provided	literature only