ClinVar Miner

Submissions for variant NM_000133.4(F9):c.190T>C (p.Cys64Arg)

dbSNP: rs137852224
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 RCV001001440 SCV001158678 likely pathogenic not specified 2019-03-18 criteria provided, single submitter clinical testing The F9 c.190T>C; p.Cys64Arg variant (rs137852224), traditionally known as Cys16Arg, is published in the medical literature and gene-specific databases in individuals with hemophilia B (see link to F9 database and references therein). The variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The amino acid at this position is highly conserved and computational algorithms (PolyPhen-2, SIFT) predict this variant is deleterious. Considering available information, this variant is classified as likely pathogenic. References: Link to F9 database: http://www.factorix.org
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004587010 SCV005076761 likely pathogenic Hereditary factor IX deficiency disease 2024-04-10 criteria provided, single submitter clinical testing Variant summary: F9 c.190T>C (p.Cys64Arg) results in a non-conservative amino acid change located in the Gamma-carboxyglutamic acid-rich (GLA) domain (IPR000294) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 183087 control chromosomes (gnomAD). c.190T>C has been reported in the literature in individuals affected with Factor IX Deficiency (Hemophilia B) (examples: Ludwig_1992, Manno_2003, Hu_2017). These data indicate that the variant is likely to be associated with disease. At least one publication reported this variant reduced clotting activity (Chavali_2009). The following publications have been ascertained in the context of this evaluation (PMID: 19699296, 29037559, 1346077, 12515715). ClinVar contains an entry for this variant (Variation ID: 811523). Based on the evidence outlined above, the variant was classified as likely 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.