Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001000187 | SCV001156682 | pathogenic | not specified | 2018-12-23 | criteria provided, single submitter | clinical testing | The F9 c.416G>A; p.Gly139Asp variant, also known as p.Gly93Asp in traditional nomenclature, is reported in the literature in individuals affected with moderate to severe hemophilia B (Nielsen 1992, Wulff 1995, Yu 2012, Factor IX database). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The glycine at codon 139 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, another variant at this codon (p.Gly139Ser) has been reported in individuals with moderate to severe hemophilia B and is considered pathogenic (Balraj 2012, Factor IX database). Based on available information, the p.Gly139Asp variant is considered to be pathogenic. References: Factor IX database: http://www.factorix.org Balraj P et al. Factor IX mutations in haemophilia B patients in Malaysia: a preliminary study. Malays J Pathol. 2012 Jun;34(1):67-9. Nielsen LR et al. Screening for mutations in the gene encoding factor IX. J Inherit Metab Dis. 1992;15(3):339-41. Wulff K et al. Twenty-five novel mutations of the factor IX gene in haemophilia B. Hum Mutat. 1995;6(4):346-8. Yu T et al. Spectrum of F9 mutations in Chinese haemophilia B patients: identification of 20 novel mutations. Pathology. 2012 Jun;44(4):342-7. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689950 | SCV005185332 | pathogenic | Hereditary factor IX deficiency disease | 2024-05-08 | criteria provided, single submitter | clinical testing | Variant summary: F9 c.416G>A (p.Gly139Asp) results in a non-conservative amino acid change located in the EGF like domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 183210 control chromosomes. c.416G>A has been reported in the literature in multiple individuals affected with Factor IX Deficiency (Hemophilia B) (examples:Wulff_1995, Yu_2012, HamasakiKatagiri_2012). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 28193338, 8680410, 22639855). ClinVar contains an entry for this variant (Variation ID: 810876). Based on the evidence outlined above, the variant was classified as pathogenic. |