ClinVar Miner

Submissions for variant NM_000132.3(F8):c.5399G>A (p.Arg1800His) (rs137852442)

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 RCV000010987 SCV000603524 pathogenic Hereditary factor VIII deficiency disease 2019-06-10 criteria provided, single submitter clinical testing The F8 c.5399G>A; p.Arg1800His variant (rs137852442), also known as p.Arg1781His using alternative nomenclature, has been reported in multiple patients with moderate to severe hemophilia A (Casana 2008, Higuchi 1991, Yada 2013, Factor VIII variant database). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The arginine at codon 1800 is highly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious. These predictions are consistent with activity measurements of patient samples with this variant, which exhibit 1-10% of normal clotting activity (Factor VIII variant database). Additionally, other amino acid substitutions at this codon (Cys, Gly, Leu, and Pro) have been reported in individuals with hemophilia A and are considered disease-causing (Factor VIII variant database). Based on available information, the p.Arg1800His variant is classified as pathogenic. References: Factor VIII variant database: Casana P et al. Severe and moderate hemophilia A: identification of 38 new genetic alterations. Haematologica. 2008 Jul;93(7):1091-4. Higuchi M et al. Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene. Proc Natl Acad Sci U S A. 1991; 88(16):7405-9. Yada K et al. The mild phenotype in severe hemophilia A with Arg1781His mutation is associated with enhanced binding affinity of factor VIII for factor X. Thromb Haemost. 2013; 109(6):1007-15.
OMIM RCV000010987 SCV000031214 pathogenic Hereditary factor VIII deficiency disease 1995-01-01 no assertion criteria provided literature only

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.