With the decreasing cost of DNA sequencing and the improvement of the bioinformatics tools, high-throughput sequencing combined with targeted-exon sequence capture technology has been widely applied in clinical diagnosis, especially for the Mendelian inheritable diseases. However, the utilization of gene mutation results in clinic genetic diagnosis is a comprehensive judgment. The article described four key factors affecting the clinical interpretation of the gene testing results, including the clinical utility, guideline of data analysis, the correlation between gene mutations and clinical manifestations, and the ethical issues of genetic testing.The article was expected to help the researchers and/or the institutions to make a better understanding of the application and interpretation of genetic testing results, and to make a step forward to standardize the genetic testing reports and the development of clinical genetic diagnosis.