Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001287809 | SCV001474539 | likely pathogenic | Hereditary factor VIII deficiency disease | 2019-09-04 | criteria provided, single submitter | clinical testing | The F8 c.1504G>T; p.Val502Phe variant is reported in the literature in several individuals affected with mild hemophilia A (Eckhardt 2013, Factor VIII database and references therein). Affected individuals with this variant exhibit F8 activity measured between 14% and 18% of normal (Eckhardt 2013, Factor VIII database). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The valine at codon 502 is highly conserved, and other amino acid substitutions at this codon (p.Val502Asp, p.Val502Gly) have been reported in individuals with hemophilia A and are considered disease-causing (Eckhardt 2013, Fernandez-Lopez 2005, Factor VIII database and references therein). Based on available information, the p.Val502Phe variant is considered to be likely pathogenic. References: Factor VIII database: http://f8-db.eahad.org Eckhardt CL et al. Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A. Blood. 2013 Sep 12;122(11):1954-62. Fernandez-Lopez O et al. The spectrum of mutations in Southern Spanish patients with hemophilia A and identification of 28 novel mutations. Haematologica. 2005 May;90(5):707-10. |