Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001380937 | SCV001579163 | pathogenic | Hereditary factor IX deficiency disease; Thrombophilia, X-linked, due to factor 9 defect | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 55 of the F9 protein (p.Phe55Ile). This variant is present in population databases (rs759987427, gnomAD 0.001%). This missense change has been observed in individuals with Hemophilia B (PMID: 8091381, 10595634, 15921378, 19699296). This variant is also known as p.Phe9Ile. ClinVar contains an entry for this variant (Variation ID: 1069182). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on F9 protein function. This variant disrupts the p.Phe55 amino acid residue in F9. Other variant(s) that disrupt this residue have been observed in individuals with F9-related conditions (PMID: 10647899, 22639855), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |