Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Paris Brain Institute, |
RCV001391354 | SCV001451016 | pathogenic | Hereditary spastic paraplegia 4 | criteria provided, single submitter | clinical testing | ||
| Genome Diagnostics Laboratory, |
RCV001847219 | SCV002105625 | pathogenic | Hereditary spastic paraplegia | 2017-11-01 | criteria provided, single submitter | clinical testing | |
| Athena Diagnostics | RCV002473251 | SCV002771044 | pathogenic | not provided | 2021-06-15 | 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 appears to occur de novo in one individual with clinical features associated with this gene. The variant is located in a region that is considered important for protein function and/or structure. |
| Gene |
RCV002473251 | SCV003805422 | pathogenic | not provided | 2023-02-01 | criteria provided, single submitter | clinical testing | Reported in multiple individuals with hereditary spastic paraplegia in published literature (Blauwendraat et al., 2018; Ishiura et al., 2016; Kim et al., 2014; Patrono et al., 2005; Varghaei et al., 2022); Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 36 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30528841, 27108959, 24077912, 21139634, 26094131, 19289482, 15841487, 26208798, 22552817, 29246610, 25045380, 35487127, 30489674) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001391354 | SCV004029114 | pathogenic | Hereditary spastic paraplegia 4 | 2023-07-06 | criteria provided, single submitter | clinical testing | Variant summary: SPAST c.1741C>T (p.Arg581X) results in a premature termination codon in the last exon of the gene, and although it is not expected to undergo nonsense mediate decay, it is predicted to cause a truncation of the encoded protein, a commonly known mechanism for disease. The variant allele was found at a frequency of 4e-06 in 250702 control chromosomes (gnomAD). c.1741C>T has been reported in the literature in multiple individuals from several different families affected with Autosomal Dominant Spastic Paraplegia 4 (e.g. Patrono_2005, Aridon_2007, Lan_2014). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 17690846, 25421405, 15841487). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |