Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001244248 | SCV001417454 | uncertain significance | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2024-10-26 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 677 of the GLB1 protein (p.Val677Gly). This variant is present in population databases (rs767685019, gnomAD 0.003%). This missense change has been observed in individual(s) with GLB1-related conditions (PMID: 33558080; internal data). 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: 968996). 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 not expected to disrupt GLB1 protein function with a negative predictive value of 95%. 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. |
OMIM | RCV001391311 | SCV001593277 | pathogenic | Mucopolysaccharidosis, MPS-IV-B | 2021-05-12 | no assertion criteria provided | literature only |