ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.1085G>A (p.Trp362Ter) (rs140385286)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000578726 SCV000680748 pathogenic not provided 2018-10-31 criteria provided, single submitter clinical testing The W362X variant in the SPG11 gene has been reported previously, along with a frameshift variant, in association with hereditary spastic paraplegia in multiple affected family members (de Bot et al., 2013). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret W362X as a pathogenic variant.
Invitae RCV000642546 SCV000764232 pathogenic Spastic paraplegia 11, autosomal recessive 2019-10-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp362*) in the SPG11 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs140385286, ExAC 0.002%). This variant has been reported in combination with a second pathogenic variant in a family affected with hereditary spastic paraplegia type 11 (PMID: 23443022). ClinVar contains an entry for this variant (Variation ID: 488833). Loss-of-function variants in SPG11 are known to be pathogenic (PMID: 19105190, 20110243, 22154821, 26556829). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000763352 SCV000894042 pathogenic Amyotrophic lateral sclerosis type 5; Spastic paraplegia 11, autosomal recessive; Charcot-Marie-Tooth disease, axonal type 2X 2018-10-31 criteria provided, single submitter clinical testing

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