ClinVar Miner

Submissions for variant NM_014946.3(SPAST):c.1116A>C (p.Arg372Ser) (rs1425976342)

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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 Inc RCV000517329 SCV000615377 uncertain significance not specified 2017-06-21 criteria provided, single submitter clinical testing
Invitae RCV000644904 SCV000766622 uncertain significance Spastic paraplegia 4, autosomal dominant 2018-12-04 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 372 of the SPAST protein (p.Arg372Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SPAST-related conditions. ClinVar contains an entry for this variant (Variation ID: 448439). 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.Arg372 amino acid residue in SPAST. Other variant(s) that disrupt this residue have been observed in individuals with SPAST-related conditions (PMID:326151), which suggests that this may be a clinically significant amino acid residue. 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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