Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001993984 | SCV002257631 | likely pathogenic | Mucopolysaccharidosis type 1 | 2021-11-05 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Pro533 amino acid residue in IDUA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1301941, 10911525, 16435195, 21521498, 23786846, 24036510, 24368159). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 533 of the IDUA protein (p.Pro533Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with IDUA-related conditions. 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 IDUA protein function. 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. |