ClinVar Miner

Submissions for variant NM_000132.3(F8):c.2167G>A (p.Ala723Thr) (rs137852436)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506851 SCV000603510 pathogenic not provided 2017-08-03 criteria provided, single submitter clinical testing The F8 c.2167G>A, p.Ala723Thr variant (also known as Ala704Thr) has been reported in multiple patients diagnosed with mild to moderate hemophilia A (Higuchi 1991, Markoff 2009, Factor VIII variant database). It is listed in the dbSNP variant database (rs137852436), and observed in the general population with a frequency of 0.0006 percent (1/177107 alleles) in the Genome Aggregation Database. The alanine at residue 723 is highly conserved, and computational algorithms (Align GVGD, Mutation Taster, PolyPhen-2) predict that the variant has an impact on the protein. Based on the above information, the variant is classified as pathogenic. REFERENCES Link to Factor VIII variant database: http://www.factorviii-db.org/newstructure.php?aa_first=Ala&mut_id=809&aa_last=Thr Higuchi M et al. Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7405-9. Markoff A et al. Combined homology modelling and evolutionary significance evaluation of missense mutations in blood clotting factor VIII to highlight aspects of structure and function. Haemophilia. 2009 Jul;15(4):932-41.
NIHR Bioresource Rare Diseases, University of Cambridge RCV000852072 SCV000899597 pathogenic Hereditary factor IX deficiency disease 2019-02-01 criteria provided, single submitter research
OMIM RCV000010959 SCV000031186 pathogenic Hereditary factor VIII deficiency disease 1995-01-01 no assertion criteria provided literature only

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