Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001002512 | SCV001160471 | likely pathogenic | not specified | 2019-04-10 | criteria provided, single submitter | clinical testing | The F9 c.88+5_88+8delGTTT variant, also published as c.88+1_4delGTTT and 118-121delGTTT, is reported in the literature in multiple individuals affected with hemophilia B (Belvini 2005, Radic 2013, Factor IX database and references therein). Samples from affected individuals with this variant exhibit F9 activity at 1% or less of wildtype (Radic 2013, Factor IX database), indicative of moderate to severe disease. This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This is an intronic variant that deletes four nucleotides adjacent to the intron 1 splice donor, and computational analyses (Alamut v.2.11) predict that this variant impacts splicing by weakening this canonical donor splice site, though RNA analyses would be required to confirm these predictions. Based on available information, this variant is considered to be likely pathogenic. References: Factor IX database: http://www.factorix.org Belvini D et al. Molecular genotyping of the Italian cohort of patients with hemophilia B. Haematologica. 2005 May;90(5):635-42. Radic CP et al. Assessment of the F9 genotype-specific FIX inhibitor risks and characterisation of 10 novel severe F9 defects in the first molecular series of Argentinian patients with haemophilia B. Thromb Haemost. 2013 Jan;109(1):24-33. |
| Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, |
RCV001265099 | SCV001424893 | pathogenic | Hereditary factor IX deficiency disease | 2019-06-01 | no assertion criteria provided | clinical testing |