ClinVar Miner

Submissions for variant NM_001360016.2(G6PD):c.1465C>T (p.Pro489Ser)

dbSNP: rs1603411177
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
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001000724 SCV001157769 pathogenic not specified 2018-07-24 criteria provided, single submitter clinical testing The G6PD c.1465C>T; p.Pro489Ser variant is reported in the literature in at least one individual affected with severe G6PD deficiency and anemia (Minucci 2008). In this paper, the male patient had undetectable G6PD activity, and the patient's mother was negative for the variant, suggesting a de novo mutation (Minucci 2008). This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. Additionally, another variant at this codon (c.1466C>T; p.Pro489Leu) has been reported in at least one individual with severe G6PD and is considered a class I variant (Vulliamy 1997). The proline at codon 489 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that the p.Pro489Ser variant is deleterious. Based on available information, this variant is considered to be pathogenic. References: Minucci A et al. Glucose-6-phosphate dehydrogenase Buenos Aires: a novel de novo missense mutation associated with severe enzyme deficiency. Clin Biochem. 2008 Jun;41(9):742-5. Vulliamy T et al. Hematologically important mutations: glucose-6-phosphate dehydrogenase. Blood Cells Mol Dis. 1997 Aug;23(2):302-13.
Dunham Lab, University of Washington RCV002305556 SCV002599399 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2022-08-12 criteria provided, single submitter curation Variant found in hemizygote with deficiency with CNSHA (PP4). No detectable activity in red blood cells (PS3). Not found in mother of hemizygote, so assumed de novo (PM6). Within NADP structural site (PM1). Predicted to be deleterious by SIFT and PolyPhen (PP3). Not found in gnomAD (PM2). Post_P 0.999 (odds of pathogenicity 6568, Prior_P 0.1).

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.