ClinVar Miner

Submissions for variant NM_000132.4(F8):c.6719C>T (p.Pro2240Leu)

dbSNP: rs1174359623
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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 RCV001286914 SCV001473541 likely pathogenic Hereditary factor VIII deficiency disease 2019-10-01 criteria provided, single submitter clinical testing The F8 c.6719C>T; p.Pro2240Leu variant, also known as Pro2221Leu for legacy numbering, has been reported in multiple individuals with hemophilia A (Johnsen 2017, see F8 database). Other variants at this codon (p.Pro2240Arg, p.Pro2240Thr, p.Pro2240Ser) have also been associated with hemophilia A (Faridi 2012, Johnsen 2017). The p.Pro2240Leu variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The proline at codon 2240 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Based on available information, this variant is considered to be likely pathogenic. References: Faridi N et al. Small mutations in hemophilia A: identification of 3 novel mutations in Indian cases. Haemophilia. (2012) 18S3: 137. Johnsen JM et al. Novel approach to genetic analysis and results in 3000 hemophilia patients enrolled in the My Life, Our Future initiative. Blood Adv. 2017 May 18;1(13):824-834. Link to F8 Variant Database: http://f8-db.eahad.org/index.php

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