ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.543A>C (p.Leu181Phe) (rs796053170)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189191 SCV000242823 uncertain significance not provided 2013-10-10 criteria provided, single submitter clinical testing p.Leu181Phe (TTA>TTC): c.543 A>C in exon 5 of the SCN2A gene (NM_021007.2). The Leu181Phe 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 Leucine and Phenylalanine are both uncharged and non-polar amino acids, the Leu181Phe substitution is semi-conservative since Phenylalanine is a much larger amino acid. It alters a position in the loop between the S2 and S3 segments of the first transmembrane domain that is conserved in mammals but is not conserved in more distant species. In silico analysis is inconsistent with regard to the effect this variant may have on the protein structure/function. Therefore, based on the currently available information, it is unclear whether Leu181Phe is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).

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