Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001977720 | SCV002263598 | pathogenic | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2022-10-11 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on GLB1 function (PMID: 21520340). 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 GLB1 protein function. ClinVar contains an entry for this variant (Variation ID: 1475998). This missense change has been observed in individual(s) with GM1-gangliosidosis (PMID: 16941474, 21497194). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 347 of the GLB1 protein (p.Tyr347Cys). |