Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001802458 | SCV002048546 | pathogenic | Hereditary factor VIII deficiency disease | 2021-01-04 | criteria provided, single submitter | clinical testing | The F8 c.437_438delAA; p.Lys146SerfsTer23 variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also 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 2 nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, several downstream frameshift variants have been reported in individuals affected with severe hemophilia A (Chen 2010, Santacroce 2008). Based on available information, this variant is considered pathogenic. References: Chen Y et al. Genetic analysis of haemophilia A in Taiwan. Haemophilia. 2010 May;16(3):538-44. Santacroce R et al. Identification of 217 unreported mutations in the F8 gene in a group of 1,410 unselected Italian patients with hemophilia A. J Hum Genet. 2008;53(3):275-84. |