ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.402T>G (p.Tyr134Ter)

dbSNP: rs1183869568
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
GeneDx RCV000760339 SCV000890198 pathogenic not provided 2018-07-05 criteria provided, single submitter clinical testing The Y134X variant has been reported previously in association with Fabry disease (Ashton-Prolla et al. 2000). The Y134X variant is not observed in large population cohorts (Lek et al., 2016). This nonsense variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. We interpret this variant as pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003479214 SCV004223745 pathogenic Fabry disease 2023-11-01 criteria provided, single submitter clinical testing Variant summary: GLA c.402T>G (p.Tyr134X) 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. The variant was absent in 183470 control chromosomes (gnomAD). c.402T>G has been reported in the literature in at least one individual affected with the classic form of Fabry Disease (e.g., Ashton-Prolla_2000). These data suggest the variant is very likely to be associated with disease. The following publication was ascertained in the context of this evaluation (PMID: 10916280). One submitter has reported clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003479214 SCV004299644 pathogenic Fabry disease 2023-12-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr134*) in the GLA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GLA are known to be pathogenic (PMID: 10666480, 12175777). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Fabry disease (PMID: 10916280). ClinVar contains an entry for this variant (Variation ID: 620102). For these reasons, this variant has been 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.