ClinVar Miner

Submissions for variant NM_014946.4(SPAST):c.334G>T (p.Glu112Ter)

dbSNP: rs1553394603
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000627250 SCV000748241 likely pathogenic not provided 2022-10-31 criteria provided, single submitter clinical testing Reported previously in multiple unrelated individuals with pure hereditary spastic paraplegia, however, detailed segregation information was not included and some affected individuals underwent sequencing of only the SPAST gene (Hentati et al., 2000; McCorquodale et al., 2011; Nanetti et al., 2012); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 20718791, 22960362, 11087788)
Labcorp Genetics (formerly Invitae), Labcorp RCV001243896 SCV001417083 pathogenic Hereditary spastic paraplegia 4 2024-08-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu112*) in 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 (PMID: 20932283). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with hereditary spastic paraplegia (HSP) (PMID: 11087788, 12552568, 20718791, 22960362). ClinVar contains an entry for this variant (Variation ID: 523792). For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics RCV000627250 SCV001880492 pathogenic not provided 2021-01-15 criteria provided, single submitter clinical testing This variant is expected to result in the loss of a functional protein. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene.

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