Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000673883 | SCV000799136 | likely pathogenic | GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis | 2018-04-10 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001855604 | SCV002240476 | pathogenic | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2023-09-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Trp582*) in the GLB1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 96 amino acid(s) of the GLB1 protein. This variant is present in population databases (rs778375259, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with GM1-gangliosidosis (PMID: 21520340). ClinVar contains an entry for this variant (Variation ID: 557709). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects GLB1 function (PMID: 20175788). This variant disrupts the p.Arg590 amino acid residue in GLB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16941474, 17309651, 17664528, 23430803). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. |
Gene |
RCV003236832 | SCV003935773 | pathogenic | not provided | 2022-12-21 | criteria provided, single submitter | clinical testing | Observed in a patient reported to have infantile GM1-gangliosidosis who also possessed second GLB1 variant (Higaki et al., 2011); Nonsense variant predicted to result in protein truncation, as the last 96 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Published functional studies demonstrate a damaging effect (HIgaki et al., 2011); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23337983, 20175788, 21520340, 10744681) |