ClinVar Miner

Submissions for variant NM_014946.4(SPAST):c.1785C>G (p.Ser595Arg)

dbSNP: rs145206063
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001063727 SCV001228586 likely pathogenic Hereditary spastic paraplegia 4 2019-12-26 criteria provided, single submitter clinical testing This sequence change replaces serine with arginine at codon 595 of the SPAST protein (p.Ser595Arg). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and arginine. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 missense change has been observed in individual(s) with clinical features of hereditary spastic paraplegia (PMID: 24824479, Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency).

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