ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.1051C>T (p.Arg351Ter)

gnomAD frequency: 0.00001  dbSNP: rs72555372
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000780302 SCV000746368 pathogenic Mucopolysaccharidosis, MPS-IV-B 2020-05-03 criteria provided, single submitter clinical testing
Counsyl RCV000665526 SCV000789664 pathogenic GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2017-02-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780302 SCV000917464 pathogenic Mucopolysaccharidosis, MPS-IV-B 2017-11-16 criteria provided, single submitter clinical testing Variant summary: The GLB1 c.1051C>T (p.Arg351X) variant results in a premature termination codon, predicted to cause a truncated or absent GLB1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant was found in 3/246162 control chromosomes at a frequency of 0.0000122, which does not exceed the estimated maximal expected allele frequency of a pathogenic GLB1 variant (0.0020412). The c.1051C>T has been reported in at least four affected, with residual GLB1 activity in their fibroblasts being less than 2% of normal via publications. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV001223149 SCV001395284 pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2024-01-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg351*) in the GLB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GLB1 are known to be pathogenic (PMID: 18524657). This variant is present in population databases (rs72555372, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with GM1-gangliosidosis (PMID: 10841810, 15714521). ClinVar contains an entry for this variant (Variation ID: 941). For these reasons, this variant has been classified as Pathogenic.
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Fondazione Stella Maris RCV001642195 SCV001519316 pathogenic Spastic ataxia 2021-01-04 criteria provided, single submitter research
Baylor Genetics RCV001331201 SCV001523189 pathogenic Infantile GM1 gangliosidosis 2020-10-09 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV002225254 SCV002504075 pathogenic not provided 2022-03-22 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21497194, 8922281, 25600812, 31367523, 25525159, 15714521, 22784478, 33240792, 33859490, 10841810)
OMIM RCV000000990 SCV000021140 pathogenic GM1-gangliosidosis, type I, with cardiac involvement 2019-05-14 no assertion criteria provided literature only

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