Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000000736 | SCV001547971 | uncertain significance | Mucopolysaccharidosis, MPS-IV-A | 2021-02-01 | criteria provided, single submitter | curation | Absent from gnomAD v2.1.1 (PM2_moderate) |
| Invitae | RCV000000736 | SCV004297054 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2023-10-25 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 487 of the GALNS protein (p.Asn487Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with mucopolysaccharidosis IVA (PMID: 7581409). 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: 701). 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 GALNS protein function with a positive predictive value of 95%. This variant disrupts the p.Asn487 amino acid residue in GALNS. Other variant(s) that disrupt this residue have been observed in individuals with GALNS-related conditions (PMID: 7581409, 25545067, 34387910), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000000736 | SCV000020886 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 1995-01-01 | no assertion criteria provided | literature only |