Description
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 382 of the GUSB protein (p.Arg382Cys). This variant is present in population databases (rs121918173, gnomAD 0.01%). This missense change has been observed in individual(s) with mucopolysaccharidosis type VII (PMID: 1779626, 8644704, 29620724). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 894). 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 GUSB protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects GUSB function (PMID: 1779626, 8644704). This variant disrupts the p.Arg382 amino acid residue in GUSB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8644704, 31497474). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
