ClinVar Miner

Submissions for variant NM_000132.4(F8):c.5813A>G (p.His1938Arg)

dbSNP: rs1603432981
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001285457 SCV001471885 likely pathogenic Hereditary factor VIII deficiency disease 2020-03-13 criteria provided, single submitter clinical testing The F8 c.5813A>G; p.His1938Arg variant is reported in the literature in multiple individuals affected with mild to moderate hemophilia A (Riccardi 2010, Factor VIII Variant Database and references therein). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The histidine at codon 1938 is highly conserved, computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious, and functional assays of patient samples with this variant suggest it has between 2% and 30% of wildtype F8 activity (Riccardi 2010, Factor VIII Variant Database). Further, another variant at the same codon (p.His1938Leu) has been reported in individuals with mild hemophilia A and is considered disease-causing (Factor VIII Variant Database). Based on available information, the p.His1938Arg variant is considered to be likely pathogenic. References: Factor VIII Variant Database: http://f8-db.eahad.org/ Riccardi F et al. Spectrum of F8 gene mutations in haemophilia A patients from a region of Italy: identification of 23 new mutations. Haemophilia. 2010 Sep 1;16(5):791-800.
Mayo Clinic Laboratories, Mayo Clinic RCV003481053 SCV004225587 likely pathogenic not provided 2022-11-16 criteria provided, single submitter clinical testing PP3, PM1_supporting, PM2, PS4_moderate

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