Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001001039 | SCV001158153 | pathogenic | Hereditary factor VIII deficiency disease | 2019-01-24 | criteria provided, single submitter | clinical testing | The F8 c.6638C>T; p.Ser2213Phe variant, also reported as Ser2194Phe, has been described in at least one individual affected with severe hemophilia A (Guillet 2006). It is absent from general population databases (Exome Variant Server and Genome Aggregation Database), indicating it is not a common polymorphism. The serine at codon 2213 is highly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious. Additionally, other variants at this codon (c.6638C>G; p.Ser2213Cys, c.6637T>C; p.Ser2213Pro, and c.6638C>A; p.Ser2213Tyr) have been reported in individuals with severe hemophilia A and are considered pathogenic (see link to F8 database and references therein, Santacroce 2008). Based on available information, the p.Ser2213Phe variant is considered pathogenic. REFERENCES Link to F8 database: http://www.factorviii-db.org/ Guillet B et al. Detection of 95 novel mutations in coagulation factor VIII gene F8 responsible for hemophilia A: results from a single institution. Hum Mutat. 2006 Jul;27(7):676-85. Santacroce R et al. Identification of 217 unreported mutations in the F8 gene in a group of 1,410 unselected Italian patients with hemophilia A. J Hum Genet. 2008;53(3):275-84. |