ClinVar Miner

Submissions for variant NM_000133.4(F9):c.354G>A (p.Trp118Ter)

gnomAD frequency: 0.00001  dbSNP: rs1234002716
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001000173 SCV001156662 pathogenic not specified 2019-06-04 criteria provided, single submitter clinical testing The F9 c.354G>A; p.Trp118Ter variant (rs1234002716), also reported as Trp72Ter, has been described in at least one individual affected with hemophilia B (Giannelli 1994). It is absent from general population databases (Exome Variant Server and Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, another variant at codon 118 that results in an early termination codon (c.353G>A; p.Trp118Ter) has been described in several individuals affected with hemophilia B (see link to F9 database and references therein). Based on available information, the c.354G>A variant is considered pathogenic. REFERENCES Link to F9 database: http://www.factorix.org/ Giannelli F et al. Haemophilia B: database of point mutations and short additions and deletions, fifth edition, 1994. Nucleic Acids Res. 1994 Sep;22(17):3534-46.
Labcorp Genetics (formerly Invitae), Labcorp RCV001858906 SCV002234980 pathogenic Hereditary factor IX deficiency disease; Thrombophilia, X-linked, due to factor 9 defect 2021-08-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp118*) in the F9 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in F9 are known to be pathogenic (PMID: 20301668). This variant is not present in population databases (ExAC no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of hemophilia B (PMID: 7937052, 11013449). ClinVar contains an entry for this variant (Variation ID: 810873). For these reasons, this variant has been classified as Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.