Abstract
Massively parallel sequencing (MPS) has become an important tool for identifying medically significant variants in both research and the clinic. Accurate variation and genotype-phenotype databases are critical in our ability to make sense of the vast amount of information that MPS generates. The purpose of this review is to summarize the state of the art of variation and genotype-phenotype databases, how they can be used, and opportunities to improve these resources. Our working assumption is that the objective of the clinical genomicist is to identify highly penetrant variants that could explain existing disease or predict disease risk for individual patients or research participants. We have detailed how current databases contribute to this goal providing frequency data, literature reviews and predictions of causation for individual variants. For variant annotation, databases vary greatly in their ease of use, the use of standard mutation nomenclature, the comprehensiveness of the variant cataloging and the degree of expert opinion. Ultimately, we need a dynamic and comprehensive reference database of medically important variants that is easily cross referenced to exome and genome sequence data and allows for an accumulation of expert opinion.