The Orthologue Alignments for each gene are downloaded from Ensembl Compara ( https://www.ensembl.org/info/genome/compara/index.html). Differences between GRCh37 and GRCh38 are due to the species used in the alignments not being the same in all cases. The data for GRCh38 are more up to date in Ensembl, but it is extremely difficult to determine which alignment is better. Alamut™ Visual Plus includes a standard set of species, but this is dependent on what is available in Ensembl Compara. These sequence alignments are used for missense predictions in AlamutTM Visual Plus.