Genome and exome sequencing are widely used for both basic and clinical research and diagnosis. Although sequencing costs have dropped dramatically and technology and algorithms used for calling variants have greatly improved, biological interpretation remains challenging. Ingenuity Variant Analysis enables rapid identification and prioritization of variants by filtering down to a small, targeted subset using analytical tools and published biological evidence. Here we present four examples of sequence data interpretation, using small or large datasets, for hereditary to large cohort studies, as well as somatic variants analysis.