Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000010800 | SCV002049823 | pathogenic | Hereditary factor VIII deficiency disease | 2021-11-11 | criteria provided, single submitter | clinical testing | The F8 c.6403C>T; p.Arg2135Ter variant (rs137852356), also known as Arg2116Ter, has been reported in multiple patients diagnosed with severe hemophilia A (see link to Factor VIII database, Higuchi 1989, Jayandharan 2009, Millar 1991, Tavasolli 1997, Wang 2010, Yousouffian 1986). This variant is also reported in ClinVar (Variation ID: 10088), but is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Factor VIII variant database: http://www.factorviii-db.org/advance_search_results.php?dosearch=1&codon=2135 Higuchi M et al. Molecular defects in hemophilia A: identification and characterization of mutations in the factor VIII gene and family analysis. Blood. 1989 Aug 15;74(3):1045-51. PMID: 2473810. Jayandharan G et al.Polymorphism in factor VII gene modifies phenotype of severe haemophilia. Haemophilia. 2009 Nov;15(6):1228-36. PMID: 19686262. Millar D et al. The molecular genetics of haemophilia A: screening for point mutations in the factor VIII gene using the restriction enzyme TaqI. Hum Genet. 1991 Sep;87(5):607-12. PMID: 1840568. Tavassoli K et al. Mutational analysis of ectopic factor VIII transcripts from hemophilia A patients: identification of cryptic splice site, exon skipping and novel point mutations. Hum Genet. 1997 Oct;100(5-6):508-11. PMID: 9341862. Wang X et al. The prevalence of factor VIII inhibitors and genetic aspects of inhibitor development in Chinese patients with haemophilia A. Haemophilia. 2010 Jul 1;16(4):632-9. PMID: 20331753. Youssoufian H et al. Recurrent mutations in haemophilia A give evidence for CpG mutation hotspots. Nature. 1986 Nov 27-Dec 3;324(6095):380-2. PMID: 3097553. |
| Mayo Clinic Laboratories, |
RCV002284167 | SCV002573777 | pathogenic | not provided | 2021-09-21 | criteria provided, single submitter | clinical testing | PM2, PS4_Moderate, PVS1 |
| Gene |
RCV002284167 | SCV005201771 | pathogenic | not provided | 2023-06-23 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 24602271, 20331753, 3097553, 33706050, 29381227, 32897612, 35014236, 29296726) |
| OMIM | RCV000010800 | SCV000031027 | pathogenic | Hereditary factor VIII deficiency disease | 1986-11-27 | no assertion criteria provided | literature only |