ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.1369C>T (p.Arg457Ter) (rs72555359)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667074 SCV000791469 pathogenic GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2017-05-19 criteria provided, single submitter clinical testing
Invitae RCV001058421 SCV001222988 pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2020-08-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg457*) in the GLB1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs72555359, ExAC 0.001%). This variant has been observed in individual(s) with GM1 gangliosidosis (PMID:1909089, 25936995, 28976722, 30548430). ClinVar contains an entry for this variant (Variation ID: 924). Loss-of-function variants in GLB1 are known to be pathogenic (PMID: 18524657). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001174734 SCV001338023 pathogenic GM1 gangliosidosis 2020-01-06 criteria provided, single submitter clinical testing Variant summary: GLB1 c.1369C>T (p.Arg457X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.6e-05 in 249532 control chromosomes (gnomAD). c.1369C>T has been reported in the literature in individuals affected with GM1 gangliosidosis (e.g. Nishimoto_1991, Santamaria_2007, Matalonga_2015). These data indicate that the variant is likely to be associated with disease. Cells expressing the variant were shown to have indetectable levels of acid beta-galactosidase enzymatic activity (Nishimoto_1991). One Clin Var submitter (evaluation after 2014 ) cited the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Nilou-Genome Lab RCV000000972 SCV001810449 pathogenic Infantile GM1 gangliosidosis 2021-07-22 criteria provided, single submitter clinical testing
OMIM RCV000000972 SCV000021122 pathogenic Infantile GM1 gangliosidosis 1991-09-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.