ClinVar Miner

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

dbSNP: rs796053134
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Total submissions: 4
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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

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