ClinVar Miner

Submissions for variant NM_000132.3(F8):c.6967C>T (p.Arg2323Cys) (rs137852473)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000011046 SCV001158495 pathogenic Hereditary factor VIII deficiency disease 2019-05-20 criteria provided, single submitter clinical testing The F8 c.6967C>T; p.Arg2323Cys variant (rs137852473) is reported in the literature in multiple individuals affected with moderate to severe hemophilia A (see link to FVIII database and references therein, Johnsen 2017, Lu 2018). This variant is reported in ClinVar (Variation ID: 10333), and is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The arginine at codon 2323 is highly conserved, and/ computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, other amino acid substitutions at this codon (Gly, His, Leu) have been reported in individuals with mild hemophilia and are considered pathogenic (FVIII database and references therein). Based on available information, this variant is considered to be pathogenic. References: Link to FVIII database: http://www.factorviii-db.org 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. Lu Y et al. Spectrum and origin of mutations in sporadic cases of haemophilia A in China. Haemophilia. 2018 Mar;24(2):291-298.
OMIM RCV000011046 SCV000031273 pathogenic Hereditary factor VIII deficiency disease 1992-04-01 no assertion criteria provided literature only

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