Submissions for variant NM_000133.4(F9):c.1190C>T (p.Ala397Val)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003050661	SCV003445848	pathogenic	Hereditary factor IX deficiency disease; Thrombophilia, X-linked, due to factor 9 defect	2022-04-14	criteria provided, single submitter	clinical testing	This variant disrupts the p.Ala397 amino acid residue in F9. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9590153, 10874302, 22639855). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 397 of the F9 protein (p.Ala397Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hemophilia B (PMID: 18624698, 27865967). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt F9 protein function. For these reasons, this variant has been classified as Pathogenic.