ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.3893T>A (p.Leu1298His)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001039489 SCV001203021 pathogenic Early infantile epileptic encephalopathy 2019-11-21 criteria provided, single submitter clinical testing This sequence change replaces leucine with histidine at codon 1309 of the SCN1A protein (p.Leu1309His). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of SCN1A-related conditions (Invitae). In at least one individual this variant was observed to be de novo. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Leu1309 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20117752). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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