ClinVar Miner

Submissions for variant NM_014946.4(SPAST):c.1112T>C (p.Leu371Pro)

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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 RCV002926582 SCV003254392 pathogenic Hereditary spastic paraplegia 4 2025-01-06 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 371 of the SPAST protein (p.Leu371Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of hereditary spastic paraplegia (PMID: 35487127; internal data). ClinVar contains an entry for this variant (Variation ID: 2046361). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SPAST protein function with a positive predictive value of 80%. This variant disrupts the p.Leu371 amino acid residue in SPAST. Other variant(s) that disrupt this residue have been observed in individuals with SPAST-related conditions (PMID: 27957547, 30476002), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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