ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.3866T>C (p.Phe1289Ser) (rs794727224)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000175413 SCV000226890 uncertain significance not provided 2014-08-29 criteria provided, single submitter clinical testing
Invitae RCV000544348 SCV000633852 uncertain significance Early infantile epileptic encephalopathy 2019-07-12 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with serine at codon 1289 of the SCN1A protein (p.Phe1289Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SCN1A-related disease. ClinVar contains an entry for this variant (Variation ID: 194932). This variant identified in the SCN1A gene is located in the transmembrane DIII-S3 region of the resulting protein (PMID: 25348405), 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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