ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.4126A>G (p.Ile1376Val)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000824524 SCV000965424 uncertain significance Early infantile epileptic encephalopathy 2018-08-24 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 1387 of the SCN1A protein (p.Ile1387Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs764507532, ExAC 0.006%). This variant has not been reported in the literature in individuals with SCN1A-related disease. This variant identified in the SCN1A gene is located in the extracellular D3-P3 region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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