Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV003114182 | SCV003800297 | likely pathogenic | not provided | 2022-04-14 | criteria provided, single submitter | clinical testing | The F8 c.1175C>T; p.Ser392Leu variant (rs28933668), also known as p.Ser373Leu, is reported in the literature in multiple individuals affected with mild to moderate hemophilia A (see F8 database and references therein). Functional analyses demonstrate that individuals with this variant have factor VIII activity between 8-9% (F8 database). This variant is also reported in ClinVar (Variation ID: 10205) and is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Additionally, another variant at this codon (c.1174T>C, p.Ser392Pro) has been reported in individuals with mild hemophilia A and is considered pathogenic (Schwaab 1997). The serine at codon 392 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.82). Based on available information, this variant is considered to be likely pathogenic. References: Link to F8 database: https://f8-db.eahad.org/ Schwaab R et al. Factor VIII gene mutations found by a comparative study of SSCP, DGGE and CMC and their analysis on a molecular model of factor VIII protein. Hum Genet. 1997 Dec;101(3):323-32. PMID: 9439662. |
| OMIM | RCV000010918 | SCV000031145 | pathogenic | Hereditary factor VIII deficiency disease | 1993-04-01 | no assertion criteria provided | literature only |