Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001000169 | SCV001156658 | likely pathogenic | not specified | 2019-05-06 | criteria provided, single submitter | clinical testing | The F9 c.1174A>G; p.Asn392Asp variant, also known as Asn346Asp, has been described in individuals affected with hemophilia B (see link to F9 database and references therein, Chavali 2009, Weinmann 1998). It is absent from general population databases (Exome Variant Server and Genome Aggregation Database), indicating it is not a common polymorphism. The asparagine at codon 392 is moderately conserved, but computational algorithms predict that this variant is tolerated. However, several missense changes at surrounding codons (390, 391, 393, 394, 395) have been described in individuals affected with hemophilia B, highlighting the importance of this region within the protein (see link to F9 database and references therein). Based on available information, the p.Asn392Asp variant is considered likely pathogenic. REFERENCES Link to F9 database: http://www.factorix.org/ Chavali S et al. Hemophilia B is a quasi-quantitative condition with certain mutations showing phenotypic plasticity. Genomics. 2009 Dec;94(6):433-7. Weinmann A et al. Consequences of factor IX mutations in 26 families with haemophilia B. Br J Haematol. 1998 Jan;100(1):58-61. |
| Labcorp Genetics |
RCV003769377 | SCV004571547 | likely pathogenic | Hereditary factor IX deficiency disease; Thrombophilia, X-linked, due to factor 9 defect | 2023-09-27 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 810869). This variant is also known as Asn346Asp. This missense change has been observed in individuals with hemophilia B (PMID: 9450791, 19699296; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 392 of the F9 protein (p.Asn392Asp). |