Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001802450 | SCV002048519 | likely pathogenic | Hereditary factor VIII deficiency disease | 2021-06-03 | criteria provided, single submitter | clinical testing | The F8 c.6118T>G; p.Cys2040Gly variant, also known as p.Cys2021Gly, is reported in the literature in multiple individuals affected with mild to moderate hemophilia A (see F8 database and references therein, Eckhardt 2013). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Additionally, another variant at this codon (c.6119G>A, p.Cys2040Tyr) has been reported in individuals with mild to moderate hemophilia A and is considered disease causing (F8 database, Green 2008). The cystine at codon 2040 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.772). Based on available information, this variant is considered to be likely pathogenic. References: Factor VIII variant database: https://f8-db.eahad.org/index.php 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. PMID: 23926300. Green PM et al. Haemophilia A mutations in the UK: results of screening one-third of the population. Br J Haematol. 2008 Oct;143(1):115-28. PMID: 18691168. |