Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001366260 | SCV001562559 | pathogenic | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2023-03-10 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with clinical features of GM1 gangliosidosis (PMID: 33240792; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 463 of the GLB1 protein (p.Leu463Pro). ClinVar contains an entry for this variant (Variation ID: 1057305). For these reasons, this variant has been classified as Pathogenic. 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 GLB1 protein function. |