Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000010972 | SCV000885401 | pathogenic | Hereditary factor VIII deficiency disease | 2021-02-10 | criteria provided, single submitter | clinical testing | The F8 c.4328_4331delAAGA; p.Lys1443IlefsTer21 variant (rs387906454), also published as codon 1422 4bp del and codon 1423 4 bp del, is described in the literature in several individuals affected with severe hemophilia (Habart 2003, Naylor 1993, Waseem 1999, FVIII variant database and references therein). Individuals carrying this variant exhibit <1% of normal F8 clotting activity (FVIII variant database and references therein). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting four nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Considering available information, this variant is considered pathogenic for severe hemophilia. References: FVIII variant database: https://f8-db.eahad.org/ Habart D et al. Thirty-four novel mutations detected in factor VIII gene by multiplex CSGE: modeling of 13 novel amino acid substitutions. J Thromb Haemost. 2003 Apr;1(4):773-81. Naylor JA et al. Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients. Hum Mol Genet. 1993 Jan;2(1):11-7. Waseem NH et al. Start of UK confidential haemophilia A database: analysis of 142 patients by solid phase fluorescent chemical cleavage of mismatch. Haemophilia Centres. Thromb Haemost. 1999 Jun;81(6):900-5. |
| OMIM | RCV000010972 | SCV000031199 | pathogenic | Hereditary factor VIII deficiency disease | 1993-11-01 | no assertion criteria provided | literature only |