Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV003656621 | SCV001473108 | pathogenic | not provided | 2023-11-29 | criteria provided, single submitter | clinical testing | The F8 c.6682C>T; p.Arg2228Ter variant (rs137852355), also known as Arg2209Ter, is reported in the literature in several individuals with severe hemophilia A (Gitschier 1985, Lyu 2016, see F8 variant database link). This variant is also reported ClinVar (Variation ID: 10086), and is absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. This variant induces an early termination codon and results in a truncated protein (Zimmermann 2014). Based on available information, this variant is considered to be pathogenic. References: Link to F8 variant database for p.Arg2228Ter: http://www.factorviii-db.org/advance_search_results.php?dosearch=1&nucleotide=6682 Gitschier J et al. Detection and sequence of mutations in the factor VIII gene of haemophiliacs. Nature. 1985 May 30-Jun 5;315(6018):427-30. PMID: 2987704. Lyu C et al. Identification of mutations in the F8 and F9 gene in families with haemophilia using targeted high-throughput sequencing. Haemophilia. 2016 Sep;22(5):e427-34. PMID: 27292088. Zimmermann MA et al. Expression studies of mutant factor VIII alleles with premature termination codons with regard to inhibitor formation. Haemophilia. 2014 May;20(3):e215-21. PMID: 24602271. |
| OMIM | RCV000010798 | SCV000031025 | pathogenic | Hereditary factor VIII deficiency disease | 1988-09-01 | no assertion criteria provided | literature only |