Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001973941 | SCV002264896 | likely pathogenic | Hereditary factor IX deficiency disease; Thrombophilia, X-linked, due to factor 9 defect | 2021-10-11 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ala279 amino acid residue in F9. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 2066105, 23093250, 27529981, 27865967, 29656491). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 has not been reported in the literature in individuals affected with F9-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with proline at codon 279 of the F9 protein (p.Ala279Pro). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and proline. |