Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001373808 | SCV001570540 | pathogenic | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2023-09-03 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 36 of the GLB1 protein (p.Tyr36Cys). This variant is present in population databases (rs748345527, gnomAD 0.03%). This missense change has been observed in individual(s) with GM1 gangliosidosis (PMID: 26646981). ClinVar contains an entry for this variant (Variation ID: 1063917). 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. This variant disrupts the p.Tyr36 amino acid residue in GLB1. Other variant(s) that disrupt this residue have been observed in individuals with GLB1-related conditions (PMID: 23046582), which suggests that this may be a clinically significant amino acid residue. |