ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.1117G>A (p.Gly373Ser) (rs727504348)

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
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727357 SCV000707842 likely pathogenic not provided 2018-06-18 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000154469 SCV000917447 likely pathogenic Fabry disease 2018-07-10 criteria provided, single submitter clinical testing Variant summary: GLA c.1117G>A (p.Gly373Ser) results in a non-conservative amino acid change located in the Alpha galactosidase A, C-terminal beta-sandwich domain (IPR035373) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 87732 control chromosomes (ExAC). The variant, c.1117G>A, has been reported in the literature in individuals affected with Fabry Disease (Okumiya_1995, Ishii_2007, Thurberg_2017, Coutinho_2017) but also with HCM and DCM (Alfares_2015, Walsh_2017). These data indicate that the variant is likely to be associated with disease. Two publications report experimental evidence evaluating an impact on protein function, however, they do not present convincing conclusions about the variant effect (Okumiya_1995, Ishii_2007). 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 likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Mendelics RCV000154469 SCV001141976 pathogenic Fabry disease 2019-05-28 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000844704 SCV000204138 likely pathogenic Fabry disease; Hypertrophic cardiomyopathy 2013-02-11 no assertion criteria provided clinical testing proposed classification - variant undergoing re-assessment, contact laboratory

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.