Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000010974 | SCV000885393 | pathogenic | Hereditary factor VIII deficiency disease | 2021-10-02 | criteria provided, single submitter | clinical testing | The F8 c.4379delA; p.Asn1460IlefsTer5 variant (rs387906455) also reported as c.4550delA; p.Asn1441IlefsTer5, is reported in multiple patients with severe hemophilia A (Naylor 1993, Tuddenham 1991, Wang 2010, Factor VIII variant database). This variant is also reported in ClinVar (Variation ID: 10261). It is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by deleting a single nucleotide, so it 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/ Naylor J et al. Characteristic mRNA abnormality found in half the patients with severe haemophilia A is due to large DNA inversions. Hum Mol Genet. 1993; 2(11):1773-8. Tuddenham EG et al. Haemophilia A: database of nucleotide substitutions, deletions, insertions and rearrangements of the factor VIII gene. Nucleic Acids Res. 1991; 19(18):4821-33. Wang X et al. The prevalence of factor VIII inhibitors and genetic aspects of inhibitor development in Chinese patients with haemophilia A. Haemophilia. 2010; 16(4):632-9. |
| Mendelics | RCV000010974 | SCV001142125 | pathogenic | Hereditary factor VIII deficiency disease | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| 3billion | RCV000010974 | SCV003841678 | pathogenic | Hereditary factor VIII deficiency disease | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000010261 / PMID: 1923751). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |
| Center for Genomic Medicine, |
RCV000010974 | SCV004809647 | likely pathogenic | Hereditary factor VIII deficiency disease | 2024-04-04 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000010974 | SCV000031201 | pathogenic | Hereditary factor VIII deficiency disease | 1993-11-01 | no assertion criteria provided | literature only | |
| Pele Pequeno Principe Research Institute, |
RCV000010974 | SCV002573789 | pathogenic | Hereditary factor VIII deficiency disease | no assertion criteria provided | clinical testing |