ClinVar Miner

Submissions for variant NM_000132.3(F8):c.5954G>A (p.Arg1985Gln) (rs1490417405)

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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 RCV000756107 SCV000883825 pathogenic not provided 2017-07-17 criteria provided, single submitter clinical testing The F8 c.5954G>A; p.Arg1985Gln variant, also known as Arg1966Gln for legacy nomenclature, has been identified in multiple individuals with mild hemophilia A (David 2006, Fernandez-Lopez 2005, Green 2008, Jayandharan 2005, Liu 1998, Liu 2002, Theophilus 2001). This variant is found in the general population with a low overall frequency of 0.0006% (1/178245 alleles) in the Genome Aggregation Database, indicating it is not a common polymorphism. The arginine at codon 1985 is highly conserved, and computational algorithms (SIFT, PolyPhen2) predict this missense variant to be damaging to the protein. Taken together, we consider this variant to be pathogenic for mild hemophilia A. References: Factor VIII database: http://www.factorviii-db.org David D et al. The spectrum of mutations and molecular pathogenesis of hemophilia A in 181 Portuguese patients. Haematologica. 2006; 91(6):840-3. Fernandez-Lopez O et al. The spectrum of mutations in Southern Spanish patients with hemophilia A and identification of 28 novel mutations. Haematologica. 2005; 90(5):707-10. Green P et al. Haemophilia A mutations in the UK: results of screening one-third of the population. Br J Haematol. 2008; 143(1):115-28. Jayandharan G et al. Identification of factor VIII gene mutations in 101 patients with haemophilia A: mutation analysis by inversion screening and multiplex PCR and CSGE and molecular modelling of 10 novel missense substitutions. Haemophilia. 2005; 11(5):481-91. Liu M et al. A domain mutations in 65 haemophilia A families and molecular modelling of dysfunctional factor VIII proteins. Br J Haematol. 1998; 103(4):1051-60. Liu M et al. Non-inversion factor VIII mutations in 80 hemophilia A families including 24 with alloimmune responses. Thromb Haemost. 2002; 87(2):273-6. Theophilus B et al. Site and type of mutations in the factor VIII gene in patients and carriers of haemophilia A. Haemophilia. 2001; 7(4):381-91.
NIHR Bioresource Rare Diseases, University of Cambridge RCV000852168 SCV000899824 pathogenic Hereditary factor IX deficiency disease 2019-02-01 criteria provided, single submitter research

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