ClinVar Miner

Submissions for variant NM_000132.3(F8):c.382T>C (p.Ser128Pro) (rs1603436638)

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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 RCV001002229 SCV001160104 likely pathogenic Hereditary factor VIII deficiency disease 2018-11-20 criteria provided, single submitter clinical testing The F8 c.382T>C; p.Ser128Pro variant, also known as p.Ser109Pro, is reported in the literature in one individual affected with severe hemophilia A (Gorziza 2013). This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The serine at codon 128 is highly conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, other variants in adjacent codons (c.385G>A; p.Glu129Lys and c.386A>T; p.Glu129Val) have been reported in individuals with severe hemophilia A (Maugard 1998, Reitter 2010). Based on available information, the p.Ser128Pro variant is considered to be likely pathogenic. REFERENCES Gorziza et al. Genetic changes in severe haemophilia A: new contribution to the aetiology of a complex disease. Blood Coagul Fibrinolysis. 2013 Mar;24(2):164-9. Maugard et al. Protein truncation test: detection of severe haemophilia a mutation and analysis of factor VIII transcripts. Hum Mutat. 1998;11(1):18-22. Reitter et al. Spectrum of causative mutations in patients with haemophilia A in Austria. Thromb Haemost. 2010 Jul;104(1):78-85.

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