ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.1051C>T (p.Arg351Ter) (rs72555372)

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Total submissions: 5
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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
Integrated Genetics/Laboratory Corporation of America 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 2019-09-05 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. This variant is present in population databases (rs72555372, ExAC 0.003%). This variant has been observed to be homozygous or in combination with another GLB1 variant in individuals affected with GM1-gangliosidosis (PMID: 10841810, 15714521). ClinVar contains an entry for this variant (Variation ID: 941). Loss-of-function variants in GLB1 are known to be pathogenic (PMID: 18524657). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000000990 SCV000021140 pathogenic GM1-gangliosidosis, type I, with cardiac involvement 2019-05-14 no assertion criteria provided literature only

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