Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000466731 | SCV000545824 | pathogenic | Spastic paraplegia | 2023-08-16 | criteria provided, single submitter | clinical testing | 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 FA2H protein function. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 148 of the FA2H protein (p.Pro148Leu). This variant is present in population databases (rs372350326, gnomAD 0.003%). This missense change has been observed in individual(s) with autosomal recessive hereditary spastic paraplegia (PMID: 29980238; Invitae). 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. ClinVar contains an entry for this variant (Variation ID: 406877). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV000622305 | SCV000741671 | likely pathogenic | Inborn genetic diseases | 2016-07-12 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV002248676 | SCV002520062 | likely pathogenic | not provided | 2021-11-19 | criteria provided, single submitter | clinical testing | PP3, PM2, PM3, PS4_moderate |