ClinVar

Description

The F9 c.1289G>A; p.Ser430Asn variant is reported in the Factor IX variant database in one individual with Hemophilia B (see link). In addition, four other alterations at this codon (p.Ser430Thr, p.Ser430Ile, p.Ser430Cys, p.Ser430Arg; also reported with the mature protein nomenclature of amino acid 384) are reported in individuals with Hemophilia B (Factor IX variant database, Giannelli 1994, Hamasaki-Katagiri 2012, Montejo 1999, Wulff 1999). The p.Ser430Asn variant is absent from the general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The serine at codon 430 is highly conserved and computational algorithms (SIFT, PolyPhen2) predict this variant to be deleterious. Based on available information, the p.Ser430Asn variant is considered likely pathogenic. REFERENCES Factor IX variant database link: http://www.factorix.org/ 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. Montejo JM et al. Identification of twenty-one new mutations in the factor IX gene by SSCP analysis. Hum Mutat. 1999;13(2):160-5. Wulff K et al. Molecular analysis of hemophilia B in Poland: 12 novel mutations of the factor IX gene. Acta Biochim Pol. 1999;46(3):721-6.