Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genomic Research Center, |
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 |