Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001803531 | SCV002048307 | likely pathogenic | Hereditary factor VIII deficiency disease | 2020-12-09 | criteria provided, single submitter | clinical testing | The F8 c.5308G>A; p.Glu1770Lys variant, also known as p.Glu1751Lys, is reported in the literature in a single individual affected with severe hemophilia A (Jayandharan 2005). In vitro functional analyses demonstrate that this individual had factor VIII activity of <1% (Jayandharan 2005). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The glutamic acid at codon 1770 is moderately conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.891). Based on available information, this variant is considered to be likely pathogenic. References: 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. |