Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000010872 | SCV001471660 | pathogenic | Hereditary factor VIII deficiency disease | 2021-01-14 | criteria provided, single submitter | clinical testing | The F8 c.209_212delTTGT; p.Phe70Ter variant (rs387906434), also known as c.208_211delTTTG, is published in the medical literature in numerous individuals with severe hemophilia A (Becker 1996, Habart 2003, Liu 1998, F8 database and references therein). Samples from affected individuals with this variant typically exhibit less than 1% of wildtype clotting activity (Habart 2003, Liu 1998, F8 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 deletes 4 nucleotides, leads to an immediate stop codon and is predicted to result in a truncated protein or mRNA subject to non-sense mediated decay. Considering available information, this variant is considered to be pathogenic. References: Link to F8 database: http://www.factorviii-db.org Becker J et al. Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: family studies indicate a mutation type-dependent sex ratio of mutation frequencies. Am J Hum Genet. 1996 Apr;58(4):657-70. |
| Genetics and Molecular Pathology, |
RCV000010872 | SCV002556570 | pathogenic | Hereditary factor VIII deficiency disease | 2021-05-05 | criteria provided, single submitter | clinical testing | |
| Neuberg Centre For Genomic Medicine, |
RCV000010872 | SCV004047428 | pathogenic | Hereditary factor VIII deficiency disease | criteria provided, single submitter | clinical testing | The F8 c.209_212del (p.Phe70Ter) variant has been reported in hemizygous state in individuals affected with Hemophilia A (Habart 2003). This variant has been reported to the ClinVar database as Pathogenic. The p.Phe70Ter variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. | |
| Mayo Clinic Laboratories, |
RCV004791212 | SCV005413486 | pathogenic | not provided | 2024-04-16 | criteria provided, single submitter | clinical testing | PM2_moderate, PM6, PS4_moderate, PVS1 |
| OMIM | RCV000010872 | SCV000031099 | pathogenic | Hereditary factor VIII deficiency disease | 1995-01-01 | no assertion criteria provided | literature only |