Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centogene AG - |
RCV001250224 | SCV001424429 | pathogenic | GM1 gangliosidosis | criteria provided, single submitter | clinical testing | ||
Invitae | RCV001349145 | SCV001543473 | pathogenic | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2023-11-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 419 of the GLB1 protein (p.Arg419Trp). This variant is present in population databases (rs747709527, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of GM1 gangliosidosis and/or GLB1-related conditions (PMID: 31761138, 33083013). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.1399C>T p.(Arg467Trp). ClinVar contains an entry for this variant (Variation ID: 973576). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV003238855 | SCV003936697 | likely pathogenic | not provided | 2022-12-29 | criteria provided, single submitter | clinical testing | 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: 31761138, 33083013) |