Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271793 | SCV002555752 | uncertain significance | not specified | 2022-06-08 | criteria provided, single submitter | clinical testing | Variant summary: GALNS c.374C>A (p.Pro125Gln) results in a non-conservative amino acid change located in the Sulfatase, N-terminal domain (IPR000917) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250910 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.374C>A in individuals affected with Mucopolysaccharidosis Type IVA (Morquio Syndrome A) and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Neuberg Centre For Genomic Medicine, |
RCV003445156 | SCV004171854 | uncertain significance | Mucopolysaccharidosis, MPS-IV-A | criteria provided, single submitter | clinical testing | ||
| Labcorp Genetics |
RCV003445156 | SCV004460830 | likely pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2023-05-07 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Pro125 amino acid residue in GALNS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9375852, 10814710, 15241807, 24035930, 30458289). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 1698516). This variant has not been reported in the literature in individuals affected with GALNS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 125 of the GALNS protein (p.Pro125Gln). |