Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV000010914 | SCV002050002 | likely pathogenic | Hereditary factor VIII deficiency disease | 2020-11-25 | criteria provided, single submitter | clinical testing | The F8 c.986G>A; p.Cys329Tyr variant (rs137852409), also known as p.Cys310Tyr, is reported in the literature in individuals affected with severe hemophilia A (see link to FVIII database, Antonarakis 1995, Salviato 2007). This variant is also reported in ClinVar (Variation ID: 10201), and is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. Additionally, other amino acid substitutions at this codon (Ser, Phe, Arg) have been reported in individuals with moderate to severe hemophilia A (see link to FVIII database, Antonarakis 1995). The cysteine at codon 329 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.937). Based on available information, this variant is considered to be likely pathogenic. References: Link to FVIII database: https://f8-db.eahad.org Antonarakis SE et al. Molecular etiology of factor VIII deficiency in hemophilia A. Hum Mutat. 1995;5(1):1-22. Salviato R et al. F8 gene mutation profile and ITT response in a cohort of Italian haemophilia A patients with inhibitors. Haemophilia. 2007 Jul;13(4):361-72. |
OMIM | RCV000010914 | SCV000031141 | pathogenic | Hereditary factor VIII deficiency disease | 1995-01-01 | no assertion criteria provided | literature only |