ClinVar Miner

Submissions for variant NM_014946.4(SPAST):c.1411G>T (p.Gly471Cys)

dbSNP: rs1679558360
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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 RCV001062437 SCV001227237 uncertain significance Hereditary spastic paraplegia 4 2020-03-14 criteria provided, single submitter clinical testing 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. This sequence change replaces glycine with cysteine at codon 471 of the SPAST protein (p.Gly471Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with hereditary spastic paraplegia (Invitae). 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 variant disrupts the p.Gly471 amino acid residue in SPAST. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17560499, 26671083). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.

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