Single nucleotide variants account for approximately 90% of all known pathogenic variants responsible for human diseases. Recently discovered CRISPR/Cas9 base editors can correct individual nucleotides without cutting DNA and inducing double-stranded breaks. We aimed to find all possible pathogenic variants which can be efficiently targeted by any of the currently described base editors and to present them for further selection and development of targeted therapies. ClinVar database (GRCh37_clinvar_20171203) was used to search and select mutations available for current single-base editing systems. We included only pathogenic and likely pathogenic variants for further analysis. For every potentially editable mutation we checked the presence of PAM. If a PAM was found, we analyzed the sequence to find possibility to edit only one nucleotide without changing neighboring nucleotides. The code of the script to search Clinvar database and to analyze the sequences was written in R and is available in the appendix. We analyzed 21 editing system currently reported in 9 publications. Every system has different working characteristics such as the editing window and PAM sequence. C > T base editors can precisely target 3196 mutations (46% of all pathogenic T > C variants), and A > G editors – 6900 mutations (34% of all pathogenic G > A variants). Protein engineering helps to develop new enzymes with a narrower window of base editors as well as using new Cas9 enzymes with different PAM sequences. But, even now the list of mutations which can be targeted with currently available systems is huge enough to choose and develop new targeted therapies.

中文翻译：

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可针对单碱基编辑的致病变异的基因组规模分析。

单核苷酸变异约占导致人类疾病的所有已知致病变异的 90%。最近发现的 CRISPR/Cas9 碱基编辑器可以在不切割 DNA 和诱导双链断裂的情况下纠正单个核苷酸。我们的目标是找到所有可能的致病变异，这些变异可以被当前描述的任何碱基编辑器有效靶向，并将它们呈现给进一步选择和开发靶向疗法。ClinVar 数据库 (GRCh37_clinvar_20171203) 用于搜索和选择当前单碱基编辑系统可用的突变。我们仅包括致病性和可能的​​致病性变异进行进一步分析。对于每个潜在的可编辑突变，我们检查了 PAM 的存在。如果找到 PAM，我们分析了该序列以寻找仅编辑一个核苷酸而不改变相邻核苷酸的可能性。用于搜索 Clinvar 数据库和分析序列的脚本代码是用 R 编写的，可在附录中找到。我们分析了目前在 9 篇出版物中报道的 21 种编辑系统。每个系统都有不同的工作特性，例如编辑窗口和 PAM 序列。C > T 碱基编辑器可以精确定位 3196 个突变（占所有致病性 T > C 变异的 46%），而 A > G 编辑器 – 6900 个突变（占所有致病性 G > A 变异的 34%）。蛋白质工程有助于开发具有更窄碱基编辑器窗口的新酶，以及使用具有不同 PAM 序列的新 Cas9 酶。但，