ClinVar Miner

Submissions for variant NM_014946.3(SPAST):c.1238C>T (p.Ser413Leu)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000799219 SCV000938873 pathogenic Spastic paraplegia 4, autosomal dominant 2018-08-10 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 413 of the SPAST protein (p.Ser413Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in individuals affected with hereditary spastic paraplegias (HSP) (PMID: 20550563, 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. For these reasons, this variant has been classified as Pathogenic.

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