Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003755087 | SCV004375273 | pathogenic | Mucopolysaccharidosis type 1 | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 367 of the IDUA protein (p.Ala367Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with IDUA-related conditions (PMID: 22112002, 27392569; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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. For these reasons, this variant has been classified as Pathogenic. |