Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001905309 | SCV002132959 | pathogenic | Hereditary factor IX deficiency disease; Thrombophilia, X-linked, due to factor 9 defect | 2021-04-18 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with hemophilia B (PMID: 8990015, Invitae). This variant is also known as Phe349Ile in the literature. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Phe395 amino acid residue in F9. Other variant(s) that disrupt this residue have been observed in individuals with F9-related conditions (PMID: 11013449, 19699296), which suggests that this may be a clinically significant amino acid residue. 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with isoleucine at codon 395 of the F9 protein (p.Phe395Ile). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and isoleucine. |