ClinVar

Description

The F9 c.1256T>G; p.Val419Gly variant (rs137852280) is reported in the literature individuals affected with moderate hemophilia B (Li 2012, Miller 2012). This variant is reported in ClinVar (Variation ID: 618116), and is absent from general population databases (Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The valine at codon 419 is moderately conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious. Additionally, another variant at this codon (c.1256T>A; p.Val419Glu) has been described in individuals with severe hemophilia B and is considered pathogenic (Giannelli 1994, Hamasaki-Katagiri 2012). Based on available information, this variant is considered likely pathogenic. References: Giannelli F et al. Haemophilia B: database of point mutations and short additions and deletions, fifth edition, 1994. Nucleic Acids Res. 1994 Sep;22(17):3534-46. Hamasaki-Katagiri N et al. Analysis of F9 point mutations and their correlation to severity of haemophilia B disease. Haemophilia. 2012 Nov;18(6):933-40. Li T et al. Mutation analysis of a cohort of US patients with hemophilia B. Am J Hematol. 2014 Apr;89(4):375-9. Miller CH et al. F8 and F9 mutations in US haemophilia patients: correlation with history of inhibitor and race/ethnicity. Haemophilia. 2012 May;18(3):375-82.