Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001000774 | SCV001157827 | uncertain significance | Hereditary factor VIII deficiency disease | 2018-09-02 | criteria provided, single submitter | clinical testing | The F8 c.1439T>C; p.Leu480Pro variant, also known as p.Leu461Pro, is reported in the literature in a single individual affected with moderate Hemophilia A (Xue 2010). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The leucine at codon 480 is highly conserved, computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious, and structural modeling suggests that a proline at this position would sterically clash with another residue in a manner that could affect protein structure (Xue 2010). However, given the lack of clinical and functional data, the significance of the p.Leu480Pro variant is uncertain at this time. References: Xue F et al. Factor VIII gene mutations profile in 148 Chinese hemophilia A subjects. Eur J Haematol. 2010 Sep;85(3):264-72. |