Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001379753 | SCV001577613 | likely pathogenic | Spastic paraplegia | 2021-02-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with serine at codon 115 of the CYP2U1 protein (p.Gly115Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs766889023, ExAC 0.01%). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 CYP2U1 protein function. This variant has been observed in individual(s) with hereditary spastic paraplegia (PMID: 29034544). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. |
Genome Diagnostics Laboratory, |
RCV001847253 | SCV002104522 | likely pathogenic | Hereditary spastic paraplegia | 2021-06-10 | criteria provided, single submitter | clinical testing | |
Ce |
RCV002276241 | SCV002563818 | pathogenic | not provided | 2020-10-01 | criteria provided, single submitter | clinical testing |