ClinVar Miner

Submissions for variant NM_014946.4(SPAST):c.1223C>T (p.Ala408Val)

dbSNP: rs1553317043
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000713460 SCV000844068 uncertain significance not provided 2021-12-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001209308 SCV001380736 uncertain significance Hereditary spastic paraplegia 4 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 408 of the SPAST protein (p.Ala408Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hereditary spastic paraplegia (PMID: 23400676). ClinVar contains an entry for this variant (Variation ID: 586656). 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%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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