Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001810851 | SCV001474481 | pathogenic | not provided | 2019-08-08 | criteria provided, single submitter | clinical testing | The F9 c.1070G>A; p.Gly357Glu variant (rs137852275), also known as 31053G>A, p.Gly311Glu or factor IX Amagasaki, is reported in the literature in multiple individuals affected with moderate to severe hemophilia A (Chavali 2009, Giannelli 1994, Hamasaki-Katagiri 2012, see link to FIX database and references therein). This variant is reported in ClinVar (Variation ID: 10647), and is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The glycine at codon 357 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Functional assays show a complete loss of coagulant and esterase activities (Miyata 1991). Additionally, other amino acid substitutions at this codon (c.1069G>A; p.Gly357Arg, c.1070G>T; p.Gly357Val) have been reported in individuals with hemophilia B and are considered pathogenic (Chavali 2009, Giannelli 1994, Hamasaki-Katagiri 2012, FIX database and references therein). Based on available information, this variant is considered to be pathogenic. References: Link to FIX database: http://www.factorix.org Chavali S et al. Hemophilia B is a quasi-quantitative condition with certain mutations showing phenotypic plasticity. Genomics. 2009 Dec;94(6):433-7. 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. Miyata T et al. Factor IX Amagasaki: a new mutation in the catalytic domain resulting in the loss of both coagulant and esterase activities. Biochemistry. 1991 Nov 26;30(47):11286-91. |
| OMIM | RCV000011393 | SCV000031625 | pathogenic | Hereditary factor IX deficiency disease | 1991-11-26 | no assertion criteria provided | literature only |