Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001215693 | SCV001387451 | likely pathogenic | Hereditary spastic paraplegia 4 | 2020-01-11 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Glu442 amino acid residue in SPAST. Other variant(s) that disrupt this residue have been observed in individuals with SPAST-related conditions (PMID: 16832076, 17957230), which suggests that this may be a clinically significant amino acid residue. 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 SPAST protein function. This variant has been observed in individual(s) with hereditary spastic paraplegia (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with valine at codon 442 of the SPAST protein (p.Glu442Val). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and valine. |