Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001285498 | SCV001471936 | likely pathogenic | Hereditary factor VIII deficiency disease | 2020-04-07 | criteria provided, single submitter | clinical testing | The F8 c.5093T>C; p.Ile1698Thr, also known as Ile1679Thr, is reported in several individuals with mild to moderate hemophilia A (see link to F8 database and references therein). The variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The isoleucine at codon 1698 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, p.Ile1698Thr variant F8 protein has reduced thermostability (Pahl 2014). Considering available information, this variant is classified as likely pathogenic. REFERENCES Link to F8 database: http://f8-db.eahad.org/index.php Pahl S et al. Effect of F8 B domain gene variants on synthesis, secretion, activity and stability of factor VIII protein. Thromb Haemost. 2014 Jan;111(1):58-66. |