Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001803547 | SCV002048365 | likely pathogenic | Hereditary factor VIII deficiency disease | 2020-11-10 | criteria provided, single submitter | clinical testing | The F8 c.5219G>T; p.Arg1740Met variant (rs1444273117), also known as Arg1721Met in traditional nomenclature, has been reported in at least 4 individuals with hemophilia A (David 2006, Guillet 2006, Johnsen 2017, Vinciguerra 2006). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The arginine at codon 1740 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL 0.802). Additionally, this variant occurs in the last nucleotide of exon 14, a highly conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant may alter splicing. Based on available information, this variant is considered to be likely pathogenic. References: David D et al. The spectrum of mutations and molecular pathogenesis of hemophilia A in 181 Portuguese patients. Haematologica. 2006 Jun;91(6):840-3. Guillet B et al. Detection of 95 novel mutations in coagulation factor VIII gene F8 responsible for hemophilia A: results from a single institution. Hum Mutat. 2006 Jul;27(7):676-85. Johnsen JM et al. Novel approach to genetic analysis and results in 3000 hemophilia patients enrolled in the My Life, Our Future initiative. Blood Adv. 2017 May 18;1(13):824-834. Vinciguerra C et al. Characterisation of 96 mutations in 128 unrelated severe haemophilia A patients from France. Description of 62 novel mutations. Thromb Haemost. 2006 Apr;95(4):593-9. |