ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.901C>T (p.Arg301Ter) (rs398123224)

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 RCV000157879 SCV000110141 pathogenic not provided 2015-03-05 criteria provided, single submitter clinical testing
GeneDx RCV000157879 SCV000207810 pathogenic not provided 2018-05-14 criteria provided, single submitter clinical testing The R301X mutation in the GLA gene has been reported in association with the classic Fabry phenotype (Eng et al., 1994). R301X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Approximately 60-70% of females with a single GLA mutation have some disease manifestations, and 10% of these individuals present with a disease severity that is similar to that of affected males (Bennett et al., 2002). The variant is found in GLA panel(s).
Integrated Genetics/Laboratory Corporation of America RCV000781418 SCV000919436 pathogenic Fabry disease 2018-02-21 criteria provided, single submitter clinical testing Variant summary: GLA c.901C>T (p.Arg301X) 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 (eg. c.996_999delACAG, p.Gln333fsX14; c.1021G>T, p.Glu341X; c.1033_1034delTC, p.Ser345fsX29). The variant allele was found at a frequency of 4.6e-05 in 21574 control chromosomes (gnomAD). c.901C>T has been reported in the literature in multiple individuals affected with Fabry Disease (Bouwman_2013, Lukas_2013, Schafer_2005, Blaydon_2001, Nakano_2013). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Shin_2008, Ries_2005). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. 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.