ClinVar Miner

Submissions for variant NM_014946.3(SPAST):c.734C>G (p.Ser245Ter) (rs1553314896)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000516292 SCV000615396 pathogenic not provided 2015-10-27 criteria provided, single submitter clinical testing
GeneDx RCV000516292 SCV000680742 pathogenic not provided 2017-11-28 criteria provided, single submitter clinical testing The S245X nonsense variant in the SPAST gene has been reported previously in multiple individualswith pure hereditary spastic paraplegia (Lindsey et al., 2000; Kim et al., 2014). This pathogenicvariant is predicted to cause loss of normal protein function either through protein truncation ornonsense-mediated mRNA decay. Additionally, the S245X variant is not observed in large populationcohorts (Lek et al., 2016). The presence of S245X is consistent with a diagnosis of spastic paraplegia type 4.
Invitae RCV000535751 SCV000645361 pathogenic Spastic paraplegia 4, autosomal dominant 2017-03-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 245 (p.Ser245*) of the SPAST gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPAST are known to be pathogenic. This particular variant has been reported in several families and individuals affected with hereditary spastic paraplegia (PMID: 11015453, 16832076, 24451228, 25045380). For these reasons, this variant has been classified as Pathogenic.

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