ClinVar Miner

Submissions for variant NM_000132.3(F8):c.1648C>G (p.Arg550Gly) (rs137852417)

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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 RCV000757245 SCV000885395 likely pathogenic not provided 2017-10-13 criteria provided, single submitter clinical testing The F8 c.1648C>G, p.Arg550Gly variant (rs137852417), also known as Arg531Gly, has been reported in two individuals with mild hemophilia A (Higuchi 1991, Tavassoli 1998). Other missense variants at this position (p.Arg550Cys, p.Arg550His, p.Arg550Leu) have also been reported in multiple individuals diagnosed with hemophilia A (Eckhardt 2013). The variant is listed as pathogenic in ClinVar (Variation ID: 10224), and is not observed in the general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database). The arginine at position 550 is highly conserved, and computational algorithms (Align GVGD, Mutation Taster, PolyPhen-2, SIFT) predict that the variant has an impact on F8 protein structure or function. Based on the above information, the p.Arg550Gly variant is classified as likely pathogenic. References: Eckhardt C et al. Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A. Blood. 2013; 122(11):1954-62. Higuchi M et al. Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis. Proc Natl Acad Sci U S A. 1991; 88(19):8307-11. Tavassoli K et al. Molecular diagnostics of 15 hemophilia A patients: characterization of eight novel mutations in the factor VIII gene, two of which result in exon skipping. Hum Mutat. 1998; 12(5):301-3.
OMIM RCV000010937 SCV000031164 pathogenic Hereditary factor VIII deficiency disease 1991-10-01 no assertion criteria provided literature only

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