ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.998A>G (p.Tyr333Cys)

dbSNP: rs370107958
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
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital RCV001733793 SCV001984726 likely pathogenic not specified 2020-09-13 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV002290745 SCV002581088 likely pathogenic Mucopolysaccharidosis, MPS-IV-B 2022-08-11 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002290745 SCV005076090 pathogenic Mucopolysaccharidosis, MPS-IV-B 2024-04-16 criteria provided, single submitter clinical testing Variant summary: GLB1 c.998A>G (p.Tyr333Cys) results in a non-conservative amino acid change located in the catalytic domain (IPR031330), affecting a residue which is part of the substrate binding pocket (PMID: 22128166) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 249536 control chromosomes (gnomAD). c.998A>G has been reported in the literature in 2 homozygous siblings, affected with Mucopolysaccharidosis Type IVB (Morquio Syndrome B) (Mayer_2009, Giugliani_1987). One of these publications also reported experimental evidence evaluating an impact on protein function and demonstrated deficient beta-galactosidase activities in fibroblasts derived from these patients (Giugliani_1987). These data indicate that the variant is likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 19091613, 3121219 , 32071837 ). ClinVar contains an entry for this variant (Variation ID: 1301844). Based on the evidence outlined above, the variant was classified as 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.