ClinVar Miner

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

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Total submissions: 4
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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 2020-01-03 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.
Integrated Genetics/Laboratory Corporation of America 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.
OMIM RCV000000972 SCV000021122 pathogenic Infantile GM1 gangliosidosis 1991-09-01 no assertion criteria provided literature only

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