Submissions for variant NM_000132.4(F8):c.5143C>T (p.Arg1715Ter)

dbSNP: rs137852439

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000010980	SCV002048168	pathogenic	Hereditary factor VIII deficiency disease	2020-12-18	criteria provided, single submitter	clinical testing	The F8 c.5243; p.Arg1715Ter variant (rs137852439) is reported in the literature in multiple individuals affected with severe hemophilia A, including one individual in which the variant occurred de novo (see F8 database and references therein, Lu 2018). In vitro functional analyses demonstrate that individuals with this variant have factor VIII activity of <1% (see F8 database). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and 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: F8 variant database: https://f8-db.eahad.org/ Lu Y et al. Spectrum and origin of mutations in sporadic cases of haemophilia A in China. Haemophilia. 2018 Mar;24(2):291-298.
OMIM	RCV000010980	SCV000031207	pathogenic	Hereditary factor VIII deficiency disease	1993-11-01	no assertion criteria provided	literature only
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV000010980	SCV004041804	pathogenic	Hereditary factor VIII deficiency disease	2023-10-09	no assertion criteria provided	clinical testing