Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001955726 | SCV002218725 | uncertain significance | Mucopolysaccharidosis, MPS-IV-A | 2022-02-12 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 492 of the GALNS protein (p.Ala492Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with GALNS-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 GALNS protein function. This variant disrupts the p.Ala492 amino acid residue in GALNS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24726177, 32860008). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Fulgent Genetics, |
RCV001955726 | SCV002781872 | uncertain significance | Mucopolysaccharidosis, MPS-IV-A | 2021-07-12 | criteria provided, single submitter | clinical testing |