Hematologie Biologique, CHU Montpellier, University of Montpellier, Montpellier, France.
Department of Structural and Molecular Biology, University College London, London, UK.
Hum Mutat. 2020 Jul;41(7):1209-1219. doi: 10.1002/humu.24025. Epub 2020 Apr 29.
Hereditary blood coagulation factor VII (FVII) deficiency is a rare autosomal recessive bleeding disorder resulting from variants in the gene encoding FVII (F7). Integration of genetic variation with functional consequences on protein function is essential for the interpretation of the pathogenicity of novel variants. Here, we describe the integration of previous locus-specific databases for F7 into a single curated database with enhanced features. The database provides access to in silico analyses that may be useful in the prediction of variant pathogenicity as well as cross-species sequence alignments, structural information, and functional and clinical severity described for each variant, where appropriate. The variant data is shared with the F7 Leiden Open Variation Database. The updated database now includes 221 unique variants, representing gene variants identified in 728 individuals. Single nucleotide variants are the most common type (88%) with missense representing 74% of these variants. A number of variants are found with relatively high minor allele frequencies that are not pathogenic but contribute significantly to the likely pathogenicity of coinherited variants due to their effect on FVII plasma levels. This comprehensive collection of curated information significantly aids the assessment of pathogenicity.
遗传性凝血因子 VII（FVII）缺乏症是一种罕见的常染色体隐性出血性疾病，由编码 FVII（F7）的基因突变引起。将遗传变异与对蛋白质功能的功能后果进行整合，对于解释新型变异的致病性至关重要。在这里，我们描述了将 F7 的先前局部数据库整合到具有增强功能的单个经过整理的数据库中的过程。该数据库可访问可能有助于预测变异致病性的计算机分析，以及跨物种序列比对、结构信息以及每个变异的功能和临床严重程度（在适当情况下）的信息。变异数据与 F7 莱顿开放变异数据库共享。更新后的数据库现在包括 221 个独特的变体，代表在 728 个人中鉴定出的基因变体。单核苷酸变体是最常见的类型（88%），其中错义占这些变体的 74%。由于它们对 FVII 血浆水平的影响，一些变体的次要等位基因频率相对较高，但并非致病性，而是由于它们对共遗传变体的致病性有重要影响。这种经过整理的综合信息的收集极大地有助于评估致病性。
