Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001286783 | SCV001473400 | pathogenic | Hereditary factor VIII deficiency disease | 2020-01-10 | criteria provided, single submitter | clinical testing | The F8 c.4636C>T; p.Gln1546Ter variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, 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, this 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. 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. |