ClinVar Miner

Submissions for variant NM_014946.4(SPAST):c.493A>G (p.Thr165Ala)

dbSNP: rs770141489
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Paris Brain Institute, Inserm - ICM RCV001391485 SCV001451332 uncertain significance Spastic paraplegia criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003633580 SCV004460252 uncertain significance Hereditary spastic paraplegia 4 2023-12-13 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 165 of the SPAST protein (p.Thr165Ala). This variant is present in population databases (rs770141489, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SPAST-related conditions. ClinVar contains an entry for this variant (Variation ID: 989090). 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 not expected to disrupt SPAST protein function with a negative predictive value of 95%. 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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