Fig. 1.

Three types of compound variants that lead to incorrect consequence prediction when handled in a localized manner, i.e. each variant separately rather than jointly. (A) Multiple SNVs in the same codon result in a TAG stop codon rather than an amino acid change. (B) A deletion locally predicted as frame-shifting is followed by a frame-restoring variant. Two amino acids are deleted and one changed, the functional consequence on protein function is likely much less severe. (C) Two SNVs separated by an intron occur within the same codon in the spliced transcript. Unchanged areas are shaded for readability. All three examples were encountered in real data (Color version of this figure is available at Bioinformatics online.)