ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.5279T>G (p.Ile1760Ser)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001057675 SCV001222179 pathogenic Early infantile epileptic encephalopathy 2019-06-17 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with serine at codon 1771 of the SCN1A protein (p.Ile1771Ser). The isoleucine residue is highly conserved and there is a large physicochemical difference between isoleucine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with early-onset epilepsy (Invitae). 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.Ile1771 amino acid residue in SCN1A. Other variants that disrupt this residue have been observed in individuals with SCN1A-related conditions (PMID: 18330841, 18930999), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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