ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.2657T>C (p.Leu886Ser) (rs796053118)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189120 SCV000242752 likely pathogenic not provided 2014-01-06 criteria provided, single submitter clinical testing The Leu886Ser missense change in the SCN2A gene 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. This variant is a non-conservative amino acid substitution of a non-polar Leucine residue with a polar Serine residue. It alters a highly conserved position in the S5 subunit of the second transmembrane domain. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. However, based on the currently available information, it is unclear whether Leu886Ser is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).
Invitae RCV000640628 SCV000762222 uncertain significance Benign familial neonatal-infantile seizures; Early infantile epileptic encephalopathy 11 2017-10-28 criteria provided, single submitter clinical testing This sequence change replaces leucine with serine at codon 886 of the SCN2A protein (p.Leu886Ser). The leucine residue is highly conserved and there is a large physicochemical difference between leucine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN2A-related disease. ClinVar contains an entry for this variant (Variation ID: 206972). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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