Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001001417 | SCV001158652 | pathogenic | not specified | 2019-03-19 | criteria provided, single submitter | clinical testing | The F9 c.892C>T; p.Arg298Ter variant (rs137852250), also known as Arg252Ter in the mature protein, is published in the medical literature in individuals with severe hemophilia B (Belvini 2005, Chen 1989, Jayandharan 2009). The variant is reported in the ClinVar database (Variation ID: 10603) but 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 and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Considering available information, this variant is classified as pathogenic. References: Belvini D et al. Molecular genotyping of the Italian cohort of patients with hemophilia B. Haematologica. 2005 May;90(5):635-42. Chen SH et al. Factor IXPortland: a nonsense mutation (CGA to TGA) resulting in hemophilia B. Am J Hum Genet. 1989 Apr;44(4):567-9. Jayandharan GR et al. Polymorphism in factor VII gene modifies phenotype of severe haemophilia. Haemophilia. 2009 Nov;15(6):1228-36. |
Labcorp Genetics |
RCV002512971 | SCV003445790 | pathogenic | Hereditary factor IX deficiency disease; Thrombophilia, X-linked, due to factor 9 defect | 2023-10-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg298*) in the F9 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 164 amino acid(s) of the F9 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with clinical features of F9-related conditions (PMID: 2929599, 22544209, 32155688, 32875744). This variant is also known as c.30875 (p.Arg252Ter). ClinVar contains an entry for this variant (Variation ID: 10603). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000011349 | SCV000031581 | pathogenic | Hereditary factor IX deficiency disease | 1989-04-01 | no assertion criteria provided | literature only |