Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001228446 | SCV001400846 | pathogenic | Hereditary spastic paraplegia 4 | 2023-01-31 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 955753). This variant is also known as 1593C>T. This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 15667412). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln490*) in the SPAST gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPAST are known to be pathogenic (PMID: 20932283). |
Athena Diagnostics Inc | RCV002473231 | SCV002771048 | pathogenic | not provided | 2022-01-13 | criteria provided, single submitter | clinical testing | This variant is expected to result in the loss of a functional protein. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In published literature, this variant is referred to as c.1593C>T. This variant segregates with disease in at least one family. |
Molecular Genetics, |
RCV001228446 | SCV004812692 | pathogenic | Hereditary spastic paraplegia 4 | 2023-03-30 | criteria provided, single submitter | clinical testing | This sequence change in SPAST is a nonsense variant predicted to cause a premature stop codon, p.(Gln490*), in biologically-relevant-exon 12/17 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (ClinGen). This variant is absent from gnomAD v2.1 and v3.1. This variant has been reported in at least two probands with hereditary spastic paraplegia and has been reported to segregate with disease in four affected family members from a single family (PMID: 15667412; LOVD). Based on the classification scheme RMH Modified ACMG Guidelines v1.5.1, this variant is classified as PATHOGENIC. Following criteria are met: PVS1, PS4_Supporting, PM2_Supporting, PP1. |