ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.2009_2010del (p.Lys670fs)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002720675 SCV003005138 likely pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2023-04-05 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts a region of the GLB1 protein in which other variant(s) (p.Val677Gly) have been observed in individuals with GLB1-related conditions (PMID: 33558080). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1961404). This frameshift has been observed in individual(s) with clinical features of GM1-gangliosidosis (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the GLB1 gene (p.Lys670Argfs*51). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 8 amino acid(s) of the GLB1 protein and extend the protein by 42 additional amino acid residues.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003324044 SCV004028686 uncertain significance not specified 2023-07-10 criteria provided, single submitter clinical testing Variant summary: GLB1 c.2009_2010delAA (p.Lys670ArgfsX51) causes a frameshift which results in an extension of the protein. The variant was absent in 249478 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2009_2010delAA in individuals affected with Mucopolysaccharidosis Type IVB (Morquio Syndrome B) and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance.

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.