ClinVar Miner

Submissions for variant NM_000132.4(F8):c.6956C>T (p.Pro2319Leu)

dbSNP: rs137852472
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
NIHR Bioresource Rare Diseases, University of Cambridge RCV000851613 SCV000899365 pathogenic Hereditary factor IX deficiency disease 2019-02-01 criteria provided, single submitter research
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001701721 SCV004565013 pathogenic not provided 2023-03-31 criteria provided, single submitter clinical testing The F8 c.6956C>T; p.Pro2319Leu variant (rs137852472), also known as Pro2300Leu in traditional nomenclature, is reported in the literature in numerous individuals affected with mild-to-moderate hemophilia A (Higuchi 1991, see link to F8 database). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The proline at codon 2319 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.874). Additionally, other variants at this codon (c.6955C>T, p.Pro2319Ser; c.6956C>G, p.Pro2319Arg) have been reported in individuals with hemophilia A and are considered disease-causing (see link to F8 database). Based on available information, the p.Pro2319Leu variant is considered to be pathogenic. References: Link to F8 database: https://f8-db.eahad.org/ 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 Oct 1;88(19):8307-11. PMID: 1924291.
OMIM RCV000011045 SCV000031272 pathogenic Hereditary factor VIII deficiency disease 1991-10-01 no assertion criteria provided literature only
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001701721 SCV001931190 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001701721 SCV001954481 pathogenic not provided no assertion criteria provided clinical testing

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