ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.5234G>A (p.Cys1745Tyr) (rs1559103294)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000701720 SCV000830533 uncertain significance Early infantile epileptic encephalopathy 2018-05-18 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 1756 of the SCN1A protein (p.Cys1756Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with severe epileptic encephalopathy and Lennox-Gastaut syndrome (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. The observation of one or more missense substitutions at this codon (p.Cys1756Gly, p.Cys1756Tyr) in affected individuals suggests that this may be a clinically significant residue (PMID: 19563458, Invitae). 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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