Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
NIHR Bioresource Rare Diseases, |
RCV000851899 | SCV000899964 | pathogenic | Abnormality of coagulation | 2019-02-01 | criteria provided, single submitter | research | |
Labcorp Genetics |
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, |
RCV003987699 | SCV004804654 | uncertain significance | Congenital factor VII deficiency | 2024-03-17 | criteria provided, single submitter | research | |
Prevention |
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. |