ClinVar Miner

Submissions for variant NM_000132.3(F8):c.601G>A (p.Gly201Arg) (rs1229954426)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001000703 SCV001157744 likely pathogenic Hereditary factor VIII deficiency disease 2018-07-12 criteria provided, single submitter clinical testing The F8 c.601G>A; p.Gly201Arg variant, also known as p.Gly182Arg, is reported in the literature in at least one individual affected with mild hemophilia A (Chen 2010). In addition, another nucleotide substitution that introduces the same missense change (c.601G>C, p.Gly201Arg) was reported in at least one individual with moderate hemophilia A (Green 2008). Other variants at this codon (c.601G>T, p.Gly201Trp; c.602G>A, p.Gly201Glu) have been reported in individuals with severe hemophilia A (Djambas Khayat 2008, Hallden 2012). The c.601G>A; p.Gly201Arg variant is not reported in ClinVar, and is also absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The glycine at codon 201 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. This variant occurs in the last nucleotide of exon 4, and splicing algorithms (Alamut v.2.11) predict that this variant may impact splicing by weakening the nearby canonical donor splice site. Based on available information, this variant is considered to be likely pathogenic. References: Chen YC et al. Genetic analysis of haemophilia A in Taiwan. Haemophilia. 2010 May;16(3):538-44. Djambas Khayat C et al. Molecular analysis of F8 in Lebanese haemophilia A patients: novel mutations and phenotype-genotype correlation. Haemophilia. 2008 Jul;14(4):709-16 Green PM et al. Haemophilia A mutations in the UK: results of screening one-third of the population. Br J Haematol. 2008 Oct;143(1):115-28. Hallden C et al. Origin of Swedish hemophilia A mutations. J Thromb Haemost. 2012 Dec;10(12):2503-11.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.