The previous EAHAD-DB coagulation factor databases (X-linked F8 and F9) have the benefit of simplicity bestowed by each case or patient only having a single allele to consider, and in the vast majority of cases with only a single variant detected: cases/patients are therefore listed synonymously with their variant, on a single line of a spreadsheet or tabular output. However there are several features of F7 which require that a DB of F7 variants be treated unlike variants in the X-linked F8 and F9 DBs:

• The F7 DB must consider both alleles in a case instead of just a single allele
• cases often have more than one F7 variant, each in the heterozygous or homozygous state
• there are a number of common variants (“polymorphisms”) which have been shown to affect expression levels of the circulating protein
• the relationship between variants, circulating FVII protein levels and clinical bleeding severity in cases is far from simple

This has led to a different philosophy of data organisation and display for this F7 DB. For each case, every variant (i.e. every divergence from the deposited Reference Sequence) is stored separately but linked to the case, together with its genotype (heterozygous or homozygous). Every case has a unique Case No., and every Variant also has a unique Variant No.

The reference sequence used for FVII protein is NP_000122.1 and for its corresponding cDNA is NM_000131.4 . Codons and amino-acids are numbered on this site in two ways. In HGVS Numbering , codons are numbered with codon +1 coding for the first residue (Met) of the 60-residue signal peptide/propeptide (this is -60 in Legacy numbering). In Legacy numbering, codon +1 refers to that coding for the first amino-acid of the mature FVIII protein (in HGVS numbering, this is codon +61). HGVS numbering is recommended, however Legacy numbering is included on this site, as it was extensively used in FVII publications, particularly before the year 2000.

From the Advanced Search Page you can carry out a huge variety of different searches varying from simply returning the variants recorded at an amino-acid position or within a FVII domain, to complex queries that retrieve variants (for example) of a given type or phenotype, amino acid type or from a specific publication. Important: if no fields or checkboxes are filled in, the search will return ALL mutations within the F7 variant database. This can be useful as an initial stage before further sorting.

The results of each Advanced Search can be viewed mainly in three different ways. It’s the same data, but you may prefer different methods depending on your purpose.

1. After pressing Search, variants are simply listed in cDNA order with brief details and live links to case (patient) information as well as (for missense variants) structural implications and informative amino-acid alignments
2. By clicking the “Multiple/Tabular” link at the top of the Results page, a detailed screen table of all individual case/variant reports (in cDNA order) is displayed: many items in the table are sortable (including Case No), individual values can be typed in to isolate data, and there are direct links to Case Pages (see below)
3. By clicking the “Unique/Tabular” link at the top of the Results page, a summary screen table of all unique variants (in cDNA order) are displayed: many items in the table are sortable (including Variant No), individual values can be typed in to isolate data, and there are direct links to Variant Pages (see below) In addition, CSV outputs similar to the Multiple and Unique screen displays can be downloaded for DB users to sort as you will (for example in MS Excel).

Every variant found in a case (or patient) is linked to that case, and every case has a unique Case No. Whenever the Case No. value in a tabular display is clicked, it links to a summary Case Page which lists the phenotypic data in that case at the top of the page, and details of all the variants found in tabular form below.

In the DB every variant also has a unique Variant No. Whenever the Variant No. value in a tabular display is clicked, it links to a summary Variant Page which lists the genetic data in that variant at the top of the page, and details of all the individual cases in which the variant is found in tabular form below.

Many genetic variants predict replacement of an amino-acid in the secreted FVII protein (missense mutations). In order to aid interpretation of missense variants at the protein level, users can examine the location of the amino-acid in the published FVIIai structure (with or without display of complexed soluble tissue factor), inspect quantitative predictions of structural effect, and assess likely impact by use of a number of amino-acid alignments (both of FVII in different species, and human proteins closely related to FVII).

Common variants with minor allele frequencies (MAFs) above 5% are often found in F7 case genotyping. A number of these have been found to affect circulating FVII level or activity and so it is important to conserve and provide this information where it has been obtained by laboratories. Thus, all common variant test results are treated as if they were any other variant: they are all linked to their cases, and each unique common variant has a unique Variant No. There is a webpage (Variants/Common Variants) which lists these Common Variants with their characteristics where known, and Variant Pages (featuring a list of all cases with the variant) can be opened for these common variants in the same way as for other variants. However in order to simplify common variant display, where a case has been found to be homozygous for the Reference Sequence at a particular locus, the entries for that variant are suppressed in the main tabular displays, and its homozygous Reference status listed instead in the upper table of Case Pages. As a result you can see what common variants have been tested for and found normal on both alleles, but the tabular displays are not cluttered up with this information: common variants are only listed in tabular displays when they are found heterozygous or homozygous for the non-Reference variant.

Within the DB each case is linked to the publication or conference abstract that described the case and its associated genetic and phenotypic data. All case entries in the various displays have links to the relevant PubMed abstract where available.