ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.966C>A (p.Asp322Glu) (rs398123226)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000367678 SCV000331016 pathogenic not provided 2018-05-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780289 SCV000917440 pathogenic Fabry disease 2018-02-21 criteria provided, single submitter clinical testing Variant summary: GLA c.966C>A (p.Asp322Glu) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 87728 control chromosomes. c.966C>A has been reported in the literature in multiple individuals affected with Fabry Disease,including largre family with co-segregation (Adalsteinsdottir_2017). 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 leukocyte -GalA activity was less than 10% in all affected male family members reported in Adalsteinsdottir, 2017. In addition, another alteration of the same nucleotide, c.966C>G, leading to the same protein change, p.D322E, was reported in pt presented with classical FD (Lee, 2010). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory 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.