ClinVar Miner

Submissions for variant NM_001371279.1(REEP1):c.345C>A (p.Tyr115Ter)

dbSNP: rs138656911
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001047463 SCV001211425 pathogenic Hereditary spastic paraplegia 31 2024-05-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr115*) in the REEP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in REEP1 are known to be pathogenic (PMID: 18321925, 18644145, 32655478). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 18644145). ClinVar contains an entry for this variant (Variation ID: 844577). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects REEP1 function (PMID: 26201691). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV004720051 SCV005324968 likely pathogenic not provided 2023-10-27 criteria provided, single submitter clinical testing Reported in a proband with a personal and family history of hereditary spastic paraplegia (PMID: 18644145); 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 (PMID: 26201691); In vitro studies suggest decreased neurite growth in transfected murine cortical cultures (PMID: 26201691); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 22703882, 18644145, 31913854, 26201691)

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