Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000642550 | SCV000764236 | pathogenic | Hereditary spastic paraplegia 11 | 2024-09-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu953*) in the SPG11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPG11 are known to be pathogenic (PMID: 19105190, 20110243, 22154821, 26556829). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SPG11-related conditions. ClinVar contains an entry for this variant (Variation ID: 534853). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282282 | SCV002571973 | likely pathogenic | Hereditary spastic paraplegia | 2022-08-11 | criteria provided, single submitter | clinical testing | Variant summary: SPG11 c.2857G>T (p.Glu953X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position are associated with Spastic paraplegia in HGMD. The variant was absent in 251164 control chromosomes (gnomAD). To our knowledge, no occurrence of c.2857G>T in individuals affected with Hereditary Spastic Paraplegia, Type 11 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Genome- |
RCV000642550 | SCV002764021 | likely pathogenic | Hereditary spastic paraplegia 11 | criteria provided, single submitter | clinical testing | ||
| Athena Diagnostics | RCV005000438 | SCV005621647 | pathogenic | not provided | 2024-09-19 | criteria provided, single submitter | clinical testing | This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity. (http://gnomad.broadinstitute.org) This variant has been identified in at least one individual tested at Athena Diagnostics with clinical features associated with this gene. |
| Fulgent Genetics, |
RCV005010624 | SCV005637908 | likely pathogenic | Amyotrophic lateral sclerosis type 5; Hereditary spastic paraplegia 11; Charcot-Marie-Tooth disease axonal type 2X | 2024-04-19 | criteria provided, single submitter | clinical testing |