Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001802699 | SCV002049741 | likely pathogenic | Hereditary factor VIII deficiency disease | 2021-03-11 | criteria provided, single submitter | clinical testing | The F8 c.1430G>T; p.Gly477Val variant, also known as G458V, is reported in the literature in multiple individuals affected with mild to moderate hemophilia A (Castaman 2009, Frusconi 2002, Markoff 2009, see link to F8 database). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The glycine at codon 477 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.919). Based on available information, this variant is considered to be likely pathogenic. References: Link to F8 database: https://f8-db.eahad.org/ Castaman G et al. Molecular and phenotypic determinants of the response to desmopressin in adult patients with mild hemophilia A. J Thromb Haemost. 2009 Nov;7(11):1824-31. Frusconi S et al. Identification of seven novel mutations of F8C by DHPLC. Hum Mutat. 2002 Sep;20(3):231-2. Markoff A et al. Combined homology modelling and evolutionary significance evaluation of missense mutations in blood clotting factor VIII to highlight aspects of structure and function. Haemophilia. 2009 Jul;15(4):932-41. |