ClinVar Miner

Submissions for variant NM_000132.4(F8):c.296T>C (p.Val99Ala)

dbSNP: rs137852382
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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 RCV001285264 SCV001471667 pathogenic Hereditary factor VIII deficiency disease 2019-08-06 criteria provided, single submitter clinical testing The F8 c.296T>C; p.Val99Ala variant (rs137852382) is reported in the literature in multiple individuals affected with mild to moderate hemophilia A, including those with F8 activity measured between 5% and 14% of normal (Miller 2012, Factor VIII database and references therein). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The valine at codon 99 is highly conserved, and other amino acid substitutions at this codon (p.Val99Asp, p.Val99Phe) have been reported in individuals with hemophilia A and are considered disease-causing (Ravanbod 2012, Factor VIII database and references therein). Based on available information, the p.Val99Ala variant is considered to be pathogenic. References: Factor VIII database: http://f8-db.eahad.org Miller CH et al. F8 and F9 mutations in US haemophilia patients: correlation with history of inhibitor and race/ethnicity. Haemophilia. 2012 May;18(3):375-82. Ravanbod S et al. Identification of 123 previously unreported mutations in the F8 gene of Iranian patients with haemophilia A. Haemophilia. 2012 May;18(3):e340-6.

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