ClinVar Miner

Submissions for variant NM_019616.4(F7):c.781C>T (p.Arg261Trp)

gnomAD frequency: 0.00008  dbSNP: rs779589651
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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 RCV000851899 SCV000899964 pathogenic Abnormality of coagulation 2019-02-01 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001300132 SCV001489257 uncertain significance not provided 2017-10-19 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has been reported as heterozygous in an individual affected with a partial factor VII deficiency (PMID: 8844208). It is also known as Arg223Trp in the literature. This variant is present in population databases (rs779589651, ExAC 0.006%). This sequence change replaces arginine with tryptophan at codon 283 of the F7 protein (p.Arg283Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV003987699 SCV004804654 uncertain significance Congenital factor VII deficiency 2024-03-17 criteria provided, single submitter research
PreventionGenetics, part of Exact Sciences RCV003975315 SCV004795037 uncertain significance F7-related disorder 2024-01-10 no assertion criteria provided clinical testing The F7 c.847C>T variant is predicted to result in the amino acid substitution p.Arg283Trp. This variant (aka p.Arg223Trp) has been reported in individuals with Factor VII deficiency (Bernardi et al. 1996. PubMed ID: 8844208; Pshenichnikova et al. 2023. PubMed ID: 37761907). This variant has also been reported in a cohort study of patients with bleeding disorders (Downes et al. 2019. PubMed ID: 31064749. Suppl3_SNV+INDEL). This variant is reported in 0.010% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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