ClinVar Miner

Submissions for variant NM_014946.4(SPAST):c.1374T>G (p.Ser458Arg)

dbSNP: rs1036039694
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000693187 SCV000821046 pathogenic Hereditary spastic paraplegia 4 2024-05-22 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 458 of the SPAST protein (p.Ser458Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SPAST-related conditions (PMID: 25045380; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 571926). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SPAST protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.

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