Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001383879 | SCV001583193 | pathogenic | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2023-09-12 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 332 of the GLB1 protein (p.Asp332Asn). This variant is present in population databases (rs781658798, gnomAD 0.004%). This missense change has been observed in individual(s) with GM1 gangliosidosis (PMID: 10839995, 19472408, 21497194, 25936995). ClinVar contains an entry for this variant (Variation ID: 1071414). 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. Experimental studies have shown that this missense change affects GLB1 function (PMID: 10839995, 10841810, 18353697). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV003327516 | SCV004034904 | pathogenic | not provided | 2023-03-07 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect; enzymatic activity assays showed <1% residual activity (Zhang et al., 2000); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25525159, 21497194, 19472408, 10839995, 18353697) |