Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003783794 | SCV004571548 | likely pathogenic | Hereditary factor IX deficiency disease; Thrombophilia, X-linked, due to factor 9 defect | 2023-06-28 | criteria provided, single submitter | clinical testing | 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 sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 407 of the F9 protein (p.Cys407Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hemophilia B (PMID: 7937052, 8680410, 8825645, 19699296). This variant is also known as p.C361S. This variant disrupts the p.Cys407 amino acid residue in F9. Other variant(s) that disrupt this residue have been observed in individuals with F9-related conditions (PMID: 7937052, 8594556, 10874302), which suggests that this may be a clinically significant amino acid residue. 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. |