ClinVar Miner

Submissions for variant NM_000132.3(F8):c.1569G>T (p.Leu523=) (rs782733685)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506453 SCV000603518 pathogenic not provided 2018-05-09 criteria provided, single submitter clinical testing The F8 c.1569G>T;p.Leu523Leu variant (also known as Leu504Leu) is described in the medical literature in several individuals with mild hemophilia (see link to FVIII database, Diamond 1992, Tuddenham 1991). The variant is not listed in the ClinVar database, but is listed in the dbSNP variant database (rs782733685) and in the Genome Aggregation Database in 2/178448 alleles. This is a silent variant that strengthens a novel mRNA acceptor site and computational programs (SpliceSiteFinder-like, MaxEntScan, GeneSplicer, Human Splicing Finder) predict this variant will alter RNA splicing. Additionally, this variant has been shown to alter mRNA splicing (Tavassoli 1998). Taken together, this variant is considered pathogenic for mild hemophilia A. References: Link to variant in FVIII database: Diamond C et al. Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A. Hum Mutat. 1992 1(3):248-57. Tavassoli K et al. Identification of four novel mutations in the factor VIII gene: three missense mutations (E1875G, G2088S, I2185T) and a 2-bp deletion (1780delTC). Hum Mutat. 1998 Suppl 1:S260-2. Tuddenham EG et al. Haemophilia A: database of nucleotide substitutions, deletions, insertions and rearrangements of the factor VIII gene. Nucleic Acids Res. 1991 19(18):4821-33.

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