Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002584751 | SCV003490040 | likely pathogenic | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2024-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 281 of the GLB1 protein (p.His281Arg). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with GLB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2173809). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt GLB1 protein function with a positive predictive value of 95%. This variant disrupts the p.His281 amino acid residue in GLB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11511921, 18546276, 21214877, 21497194). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005406592 | SCV006073011 | uncertain significance | not specified | 2025-04-18 | criteria provided, single submitter | clinical testing | Variant summary: GLB1 c.842A>G (p.His281Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 249516 control chromosomes. 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.842A>G in individuals affected with Mucopolysaccharidosis Type IVB (Morquio Syndrome B) and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2173809). Based on the evidence outlined above, the variant was classified as uncertain significance. |