Submissions for variant NM_000132.4(F8):c.3091_3094del (p.Lys1031fs)

dbSNP: rs1375894900

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000509008	SCV002048416	pathogenic	Hereditary factor VIII deficiency disease	2021-01-15	criteria provided, single submitter	clinical testing	The F8 c.3091_3094delAAGA; p.Lys1031LeufsTer9 variant (rs1375894900), also reported as c.3093delAAGA, c.3261delAAGA, and c.3092-3095delAAGA, is reported in the literature in multiple individuals affected with severe hemophilia A (see F8 database and references therein, Ljung 1999). In vitro functional analyses demonstrate that individuals with this variant have factor VIII of <1% (F8 database). This variant is also reported in ClinVar (Variation ID: 369689). This variant is 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 four nucleotides, so it 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: Link to F8 database: https://f8-db.eahad.org/ Ljung RC et al. Origin of mutation in sporadic cases of haemophilia A. Br J Haematol. 1999 Sep;106(4):870-4.
Molecular Genetics and Enzymology, National Research Centre	RCV000509008	SCV000328624	pathogenic	Hereditary factor VIII deficiency disease	2016-03-15	no assertion criteria provided	research	This mutation is associated with a severe hemophilia A patient
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	RCV000509008	SCV001424872	pathogenic	Hereditary factor VIII deficiency disease	2019-06-01	no assertion criteria provided	clinical testing