ClinVar Miner

Submissions for variant NM_000128.4(F11):c.1207G>A (p.Val403Met)

gnomAD frequency: 0.00001  dbSNP: rs281875266
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
NIHR Bioresource Rare Diseases, University of Cambridge RCV000851583 SCV000899299 likely pathogenic Coagulation factor deficiency syndrome 2019-02-01 criteria provided, single submitter research
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology RCV002222013 SCV002499624 likely pathogenic Hereditary factor XI deficiency disease criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002222013 SCV005395273 pathogenic Hereditary factor XI deficiency disease 2024-09-20 criteria provided, single submitter clinical testing Variant summary: F11 c.1207G>A (p.Val403Met) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251482 control chromosomes (gnomAD). c.1207G>A has been reported in the literature in a homozygous individual affected with Hereditary factor XI deficiency disease (Dai_2011), as well as 2 heterozygous individuals reported to have a coagulation disorder (Downes_2019). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, finding that the variant resulted in sharply decreased extracellular secretion (5.7% of wild type antigen level), as well as inhibiting secretion of heterodimers of the mutant and wild type protein (Dai_2011), suggesting a possible dominant negative effect. The following publications have been ascertained in the context of this evaluation (PMID: 21457405, 31064749). ClinVar contains an entry for this variant (Variation ID: 68173). Based on the evidence outlined above, the variant was classified as pathogenic.
UniProtKB/Swiss-Prot RCV000059005 SCV000090526 not provided not provided no assertion provided not provided

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