Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001000157 | SCV001156643 | pathogenic | not specified | 2018-10-02 | criteria provided, single submitter | clinical testing | The F9 c.1135C>T; p.Arg379Ter variant (rs137852258), also known as Arg333Ter, has been described in several individuals affected with severe hemophilia B (see link to F9 database and references therein). This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon, other truncating variants have been identified occurring further into the C terminus, and at least two of these variants result in a stable mRNA (F9 database, Li 2013, Gitschier 1985). Therefore, this nonsense variant likely results in a truncated protein and is considered pathogenic. References: Link to F9 database: http://www.factorix.org/ Li T et al. The CDC Hemophilia B mutation project mutation list: a new online resource. Mol Genet Genomic Med. 2013 Nov;1(4):238-45. Gitschier J et al. Genetic mapping and diagnosis of haemophilia A achieved through a BclI polymorphism in the factor VIII gene. Nature. 1985 Apr 25-May 1;314(6013):738-40. |
| Labcorp Genetics |
RCV001851791 | SCV002234982 | pathogenic | Hereditary factor IX deficiency disease; Thrombophilia, X-linked, due to factor 9 defect | 2023-07-16 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individuals with Hemophilia B (PMID: 1969838, 8091381, 22544209, 31026269). This sequence change creates a premature translational stop signal (p.Arg379*) in the F9 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 83 amino acid(s) of the F9 protein. This variant is not present in population databases (gnomAD no frequency). This variant is also known as Arg333Gln. ClinVar contains an entry for this variant (Variation ID: 10612). For these reasons, this variant has been classified as Pathogenic. |
| Mayo Clinic Laboratories, |
RCV004791216 | SCV005413450 | pathogenic | not provided | 2024-07-22 | criteria provided, single submitter | clinical testing | PP1_strong, PM2, PS4_moderate, PVS1_strong |
| OMIM | RCV000011358 | SCV000031590 | pathogenic | Hereditary factor IX deficiency disease | 1990-08-01 | no assertion criteria provided | literature only | |
| Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, |
RCV000011358 | SCV001424897 | pathogenic | Hereditary factor IX deficiency disease | 2019-06-01 | no assertion criteria provided | clinical testing |