Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000497842 | SCV000590388 | pathogenic | not provided | 2017-08-15 | criteria provided, single submitter | clinical testing | A variant that is likely pathogenic has been identified in the SPG11 gene. The Q266X variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The Q266X nonsense variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, the Q266X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Labcorp Genetics |
RCV001223427 | SCV001395576 | pathogenic | Hereditary spastic paraplegia 11 | 2024-02-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln266*) 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 present in population databases (no rsID available, gnomAD 0.0009%). 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: 432638). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Genome- |
RCV001223427 | SCV002764212 | pathogenic | Hereditary spastic paraplegia 11 | criteria provided, single submitter | clinical testing |