Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001000839 | SCV001157909 | pathogenic | Hereditary factor VIII deficiency disease | 2018-09-25 | criteria provided, single submitter | clinical testing | The F8 c.3861_3867delCTCAAAA; p.Phe1287fs variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting 7 nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, other frameshift variants in F8 have been reported in individuals with severe hemophilia A and are considered pathogenic (Bogdanova 2002, Reitter 2010, see link to F8 database and references therein). Based on available information, the p.Phe1287fs variant is considered to be pathogenic. References: Link to F8 database: http://www.factorviii-db.org/ Bogdanova N et al. Prevalence of small rearrangements in the factor VIII gene F8C among patients with severe hemophilia A. Hum Mutat. 2002 Sep;20(3):236-7. Reitter S et al. Spectrum of causative mutations in patients with haemophilia A in Austria. Thromb Haemost. 2010 Jul;104(1):78-85. |