Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000197553 | SCV000252340 | uncertain significance | not provided | 2021-03-02 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23812641, 31325016, 32973427, 33300680) |
Ce |
RCV000197553 | SCV000780549 | likely pathogenic | not provided | 2019-08-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001233181 | SCV001405764 | likely pathogenic | Hereditary spastic paraplegia 7 | 2023-12-24 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 576 of the SPG7 protein (p.Ser576Trp). This variant is present in population databases (rs151249432, gnomAD 0.002%). This missense change has been observed in individuals with hereditary spastic paraplegia (PMID: 23812641; Invitae). ClinVar contains an entry for this variant (Variation ID: 215223). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SPG7 protein function with a positive predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Genome Diagnostics Laboratory, |
RCV001847891 | SCV002105854 | uncertain significance | Hereditary spastic paraplegia | 2022-01-04 | criteria provided, single submitter | clinical testing |