ClinVar Miner

Submissions for variant NM_000132.4(F8):c.650T>C (p.Leu217Pro)

dbSNP: rs2124134359
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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 RCV001802744 SCV002049873 likely pathogenic Hereditary factor VIII deficiency disease 2021-09-17 criteria provided, single submitter clinical testing The F8 c.650T>C; p.Leu217Pro variant, also known as Leu198Pro, is reported in the literature in multiple individuals affected with severe hemophilia A (F8 database and references therein, Lu 2018). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Additionally, other amino acid substitutions at this codon (Arg, Phe, His) have been reported in individuals with mild to severe hemophilia A (F8 database, Markoff 2018). The leucine at codon 217 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.956). Based on available information, this variant is considered to be likely pathogenic. References: Link to F8 database: https://f8-db.eahad.org/index.php Lu Y et al. Spectrum and origin of mutations in sporadic cases of haemophilia A in China. Haemophilia. 2018 Mar;24(2):291-298. PMID: 29381227. 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. PMID: 19473423.

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