ClinVar

Description

This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Trp453 amino acid residue in F9. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7937052, 18540896, 19699296, 22639855). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with X-linked recessive factor IX deficiency (hemophilia B) (PMID: 7937052, 22103590, Invitae). This variant is also known as Trp407Stop (W407Stop) in the literature. This sequence change results in a premature translational stop signal in the F9 gene (p.Trp453*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 9 amino acids of the F9 protein.