ClinVar Miner

Submissions for variant NM_014946.3(SPAST):c.1684C>T (p.Arg562Ter) (rs121908518)

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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 RCV000517099 SCV000615391 pathogenic not provided 2015-12-07 criteria provided, single submitter clinical testing
Invitae RCV000644889 SCV000766607 pathogenic Spastic paraplegia 4, autosomal dominant 2017-11-22 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SPAST gene (p.Arg562*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 55 amino acids of the SPAST protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with hereditary spastic paraplegia in several families (PMID: 17597328, 27084228) and has been reported in individuals affected with hereditary spastic paraplegia (PMID: 10699187, 20718791, 24381312, 27084228, 18701882). Experimental studies have shown that this nonsense change results in reduced levels of SPAST protein, decreased neurite length, decreased neurite arborization, and severely disrupted microtubule structures (PMID: 24381312). For these reasons, this variant has been classified as Pathogenic.

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