ClinVar Miner

Submissions for variant NM_000132.4(F8):c.2163G>T (p.Met721Ile)

dbSNP: rs1218576358
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
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002273142 SCV002557798 pathogenic Hereditary factor VIII deficiency disease 2022-06-24 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as pathogenic. The following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with haemophilia A (MIM#306700). (I) 0109 - This gene is associated with X-linked recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from methionine to isoleucine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools and very highly conserved with a minor amino acid change. (SP) 0602 - Variant is located in a hotspot region or cluster of pathogenic variants (DECIPHER). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. Two alternative variants, c.2163G>A and c.2163G>C, resulting in the same substitution, Met721Ile (also referred to as Met702Ile due to alternative nomenclature, have previously been reported in at least three patients with severe haemophilia A (PMID: 11858487, 18387975, 29296726, 32166871 (EAHAD F8 database)) (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 0702 - Other missense variants comparable to the one identified in this case have strong previous evidence for pathogenicity. Four alternative changes (Met721Leu, Met721Val, Met721Thr and Met721Lys) have been reported in individuals with haemophilia A (ClinVar, PMID: 21910785, 29296726, 26897466). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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.