Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001001991 | SCV001159804 | pathogenic | Hereditary factor VIII deficiency disease | 2018-07-03 | criteria provided, single submitter | clinical testing | The F8 c.1271+1G>A variant has been described in individuals with severe hemophilia A (see link to F8 database and references therein). It is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant abolishes the canonical splice donor site of intron 8, which is likely to disrupt gene function. Additionally, another variant at this nucleotide position (c.1271+1G>T) has been reported in an individual with hemophilia A, and RNA analysis of this individual's blood demonstrated that this alteration results in a cryptic splice site activation of exon 8, leading to an out-of-frame protein product (Lannoy 2012). Based on available information, the c.1271+1G>A variant is considered pathogenic. References: Link to FVIII database: http://www.factorviii-db.org/ Lannoy N et al. Computational and molecular approaches for predicting unreported causal missense mutations in Belgian patients with haemophilia A. Haemophilia. 2012 May;18(3):e331-9. |