Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV005234642 | SCV005878825 | likely pathogenic | not provided | 2024-10-30 | criteria provided, single submitter | clinical testing | The F8 c.1717T>C; p.Cys573Arg variant (rs2073368036) is reported in the literature in individuals affected with hemophilia A (Chen 2021, Janczar 2019, Johnsen 2022). This variant is absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. Additionally, other variants at this codon (c.1718G>T; p.Cys573Phe; c.1718G>A; p.Cys573Tyr) have been reported in individuals with hemophilia A and are considered disease causing (See F8 database and references therein). Computational analyses predict that this variant is deleterious (REVEL: 0.948). Based on available information, this variant is considered to be likely pathogenic. References: Link to F8 database: https://dbs.eahad.org/ Chen J et al. The spectrum of FVIII gene variants detected by next generation sequencing in 236 Chinese non-inversion hemophilia A pedigrees. Thromb Res. 2021 Jun;202:8-13. PMID: 33706050. Janczar S et al. Recurrent and novel disease-causing F8 variants in boys with severe haemophilia A in Poland. Haemophilia. 2019 Jul;25(4):e311-e314. PMID: 31134694. Johnsen JM et al. Results of genetic analysis of 11?341 participants enrolled in the My Life, Our Future hemophilia genotyping initiative in the United States. J Thromb Haemost. 2022 Sep;20(9):2022-2034. PMID: 35770352. |