ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.331C>T (p.Gln111Ter)

gnomAD frequency: 0.00003  dbSNP: rs200374326
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000690516 SCV000818203 pathogenic Mucopolysaccharidosis, MPS-IV-A 2023-12-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln111*) in the GALNS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GALNS are known to be pathogenic (PMID: 12442278). This variant is present in population databases (rs200374326, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type IV (PMID: 9375852). ClinVar contains an entry for this variant (Variation ID: 569803). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193733 SCV001362795 pathogenic Morquio syndrome 2020-07-27 criteria provided, single submitter clinical testing Variant summary: GALNS c.331C>T (p.Gln111X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.6e-05 in 250768 control chromosomes. c.331C>T has been reported in the literature in individuals affected with Mucopolysaccharidosis Type IVA (Morquio Syndrome A) and subsequently cited by others (example, Tomatsu_2005, Morrone_2014). These data indicate that the variant is very likely associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000690516 SCV001547663 pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter research Nonsense variant (PVS1_very strong); in vitro functional studies supportive of a damaging effect on the gene product (low in vitro enzymatic activity; PS3_supporting); the prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_strong); very low frequency in gnomAD v2.1.1 (PM2_moderate)
Genome-Nilou Lab RCV000690516 SCV002045031 pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-11-07 criteria provided, single submitter clinical testing

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.