Submissions for variant NM_000133.4(F9):c.1004G>T (p.Cys335Phe)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003486523	SCV004241031	likely pathogenic	Hereditary factor IX deficiency disease	2023-12-13	criteria provided, single submitter	clinical testing	Variant summary: F9 c.1004G>T (p.Cys335Phe) results in a non-conservative amino acid change located in the Serine proteases, trypsin domain profile (IPR001254) 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 183414 control chromosomes. c.1004G>T has been reported in the literature in individuals affected with Factor IX Deficiency (Hemophilia B) (Dou_2023, Driscoll_1996, Herbert_2004, Rowley_1995). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 36163649, 8602635, 15613048, 8825645). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.