Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000657638 | SCV000779383 | pathogenic | not provided | 2018-05-17 | criteria provided, single submitter | clinical testing | The R398X nonsense variant in the SPG7 gene has been reported previously in association with spastic paraplegia type 7 when present in the homozygous state or in trans with another disease-causing variant (Pfeffer et al., 2015; Yahikozawa et al., 2015; Schlipf et al., 2011). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R398X variant is observed in 1/7200 (0.006%) alleles from individuals of East Asian background in large population cohorts (Lek et al., 2016). We interpret R398X as a pathogenic variant. |
Invitae | RCV001855358 | SCV002233924 | pathogenic | Hereditary spastic paraplegia 7 | 2023-06-28 | 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: 545964). This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 21623769, 25681447). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Arg398*) in the SPG7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPG7 are known to be pathogenic (PMID: 21623769, 22964162). |
Ce |
RCV000657638 | SCV002563366 | pathogenic | not provided | 2020-09-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001855358 | SCV004034075 | not provided | Hereditary spastic paraplegia 7 | no assertion provided | literature only |