Flowchart for annotation with VariO. All existing information for the variation should be available when starting annotation. Reference sequence is needed to indicate the position of the variation. With this information can be generated the variation type annotation. The effects on function, structure and property are annotated based on the obtained information. The methods used for obtaining the results are indicated by Evidence Codes terms. Literature and database references are used to indicate the origin of the annotated data. It is essential that the database using VariO annotations provides information about all relevant reference states such as reference sequence and wild type protein properties.