Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001371380 | SCV001567939 | uncertain significance | Hereditary factor IX deficiency disease; Thrombophilia, X-linked, due to factor 9 defect | 2020-10-19 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the Leu383 (also known as Leu337) amino acid residue in F9 have been observed in affected individuals (PMID: 23913812, 22639855, 19699296, 23617593). This suggests that it is a clinically significant residue, and that variants that disrupt this residue are likely to be causative of disease. 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 not expected to disrupt F9 protein function. This variant has not been reported in the literature in individuals with F9-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 383 of the F9 protein (p.Leu383Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. |