Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV000010838 | SCV002049136 | pathogenic | Hereditary factor VIII deficiency disease | 2021-10-26 | criteria provided, single submitter | clinical testing | The F8 c.1171C>T; p.Arg391Cys variant (rs137852364), also known as Arg372Cys, is reported in the literature in multiple individuals affected with mild to severe hemophilia A (see F8 database and references therein, Feng 2021). This variant is reported in ClinVar (Variation ID: 10125) and is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Additionally, other amino acid substitutions at this codon (His, Leu, Gly, Pro) have been reported in individuals with hemophilia A and are considered pathogenic (F8 database). The arginine at codon 391 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.924). Based on available information, this variant is considered to be pathogenic. References: Link to F8 database: https://f8-db.eahad.org/index.php Feng Y et al. Mutation analysis in the F8 gene in 485 families with haemophilia A and prenatal diagnosis in China. Haemophilia. 2021 Jan;27(1):e88-e92.PMID: 33245802. |
OMIM | RCV000010838 | SCV000031065 | pathogenic | Hereditary factor VIII deficiency disease | 1990-04-15 | no assertion criteria provided | literature only |