ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.203G>A (p.Arg68Gln) (rs572237881)

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
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000175606 SCV000227123 pathogenic not provided 2015-02-19 criteria provided, single submitter clinical testing
Counsyl RCV000673880 SCV000799133 uncertain significance GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2018-04-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001201192 SCV001372261 likely pathogenic GM1 gangliosidosis 2020-06-22 criteria provided, single submitter clinical testing Variant summary: GLB1 c.203G>A (p.Arg68Gln) results in a conservative amino acid change located in the Glycoside hydrolase 35, catalytic domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 249456 control chromosomes. c.203G>A has been reported in the literature in at least one individual affected with GM1 Gangliosidosis (Hofer_2009). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Hofer_2009). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic, and one laboratory classified the variant as uncertain significance. In addition, p.R68W has been reported to associate with Gangliosidosis GM1 (HGMD database), indicating R68 is critical for GLB1 function. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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.