ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.553-2A>T

dbSNP: rs2125533195
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV002249057 SCV002516354 likely pathogenic Infantile GM1 gangliosidosis 2022-05-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003094010 SCV003231890 pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2022-09-15 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This sequence change affects an acceptor splice site in intron 5 of the GLB1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GLB1 are known to be pathogenic (PMID: 18524657). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with GM1-gangliosidosis (PMID: 27679996). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1685330). For these reasons, this variant has been classified as Pathogenic.
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV004698866 SCV005200767 pathogenic GLB1-related disorder 2024-04-01 criteria provided, single submitter clinical testing PVS1, PM2, PM3

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.