Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001000168 | SCV001156657 | pathogenic | not specified | 2019-02-14 | criteria provided, single submitter | clinical testing | The F9 c.1173T>A; p.Tyr391Ter variant, also reported as Tyr345Ter, has been described in at least one individual affected with hemophilia B (see like to F9 database and references therein, Wulff 1995). It is absent from the general population databases (Exome Variant Server and Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon; although the mRNA may not be targeted for nonsense-mediated decay, if a stable protein product is produced then it would be truncated and lack the final 71 amino acid residues which are likely crucial for normal protein function. Several downstream truncating variants have been described in individuals affected with hemophilia B and are considered pathogenic (see link to F9 database and references therein). Based on available information, p.Tyr391Ter is considered pathogenic. REFERENCES Link to F9 database: http://www.factorix.org/ Wulff K et al. Twenty-five novel mutations of the factor IX gene in haemophilia B. Hum Mutat. 1995;6(4):346-8. |