Submissions for variant NM_000404.4(GLB1):c.171C>G (p.Tyr57Ter)

dbSNP: rs398123350

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000675686	SCV000227122	pathogenic	not provided	2013-08-30	criteria provided, single submitter	clinical testing
Counsyl	RCV000671504	SCV000796486	likely pathogenic	GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis	2017-12-18	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000675686	SCV002024830	pathogenic	not provided	2021-08-03	criteria provided, single submitter	clinical testing
Invitae	RCV002513824	SCV003525322	pathogenic	Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis	2022-05-15	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 92900). This premature translational stop signal has been observed in individual(s) with GM1-gangliosidosis (PMID: 15365997). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr57*) 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). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003987350	SCV004803984	pathogenic	GM1 gangliosidosis	2024-01-30	criteria provided, single submitter	clinical testing	Variant summary: GLB1 c.171C>G (p.Tyr57X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant was absent in 249514 control chromosomes. c.171C>G has been reported in the literature at a homozygous state in at-lease one individual affected with infantile form of GM1 Gangliosidosis (Georgiou_2004). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in absence of the total and mRNA of GLB1 in the cultured fibroblasts in the patient carrying homozygous c.171C>G via Northen blot analysis (Georgiou_2004). The following publication has been ascertained in the context of this evaluation (PMID: 15365997). ClinVar contains an entry for this variant (Variation ID: 92900). Based on the evidence outlined above, the variant was classified as pathogenic.
Mayo Clinic Laboratories, Mayo Clinic	RCV000675686	SCV000801395	pathogenic	not provided	2017-11-13	no assertion criteria provided	clinical testing