Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001285944 | SCV001472457 | pathogenic | Hereditary factor VIII deficiency disease | 2019-12-12 | criteria provided, single submitter | clinical testing | The F8 c.6995G>A; p.Trp2332Ter variant, also known as Trp2313Stop, is reported in the literature in multiple individuals affected with moderate to severe hemophilia A (Jayandharan 2005, Johnsen 2017). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant results in a premature termination codon in the last exon of the F8 gene. While this may not lead to nonsense-mediated decay, it is expected to create a truncated protein. Additionally, another nonsense variant at this codon (c.6996G>A; p.Trp2332Ter) and several downstream truncating variants have been described in individuals with hemophilia A and are considered pathogenic (Green 2008, Johnsen 2017, Nair 2010). Based on available information, the c.6995G>A; p.Trp2332Ter variant is considered to be pathogenic. References: 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. Jayandharan G et al. Identification of factor VIII gene mutations in 101 patients with haemophilia A: mutation analysis by inversion screening and multiplex PCR and CSGE and molecular modelling of 10 novel missense substitutions. Haemophilia. 2005 Sep;11(5):481-91. Johnsen JM et al. Novel approach to genetic analysis and results in 3000 hemophilia patients enrolled in the My Life, Our Future initiative. Blood Adv. 2017 May 18;1(13):824-834. Nair PS et al. Molecular pathology of haemophilia A in Indian patients: identification of 11 novel mutations. Clin Chim Acta. 2010 Dec 14;411(23-24):2004-8. |