Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001192991 | SCV001361489 | pathogenic | GM1 gangliosidosis | 2019-03-15 | criteria provided, single submitter | clinical testing | Variant summary: GLB1 c.699delG (p.Gln234ArgfsX20) 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 3.2e-05 in 31064 control chromosomes (gnomAD) and has been reported in the literature in multiple individuals affected with infantile form of GM1 gangliosidosis (Mytsyk_2016, Utz_2017). Mytsyk et al states that c.699delG in its homozygous state resulted in very early onset of the disease. These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Institute of Medical Genetics and Applied Genomics, |
RCV001268285 | SCV001447099 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001859167 | SCV002235210 | pathogenic | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2022-02-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln234Argfs*20) 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 (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with GLB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 928700). For these reasons, this variant has been classified as Pathogenic. |
| Revvity Omics, |
RCV001268285 | SCV003828276 | likely pathogenic | not provided | 2022-09-12 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV005029738 | SCV005658107 | pathogenic | GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis | 2024-04-15 | criteria provided, single submitter | clinical testing |