To compare six reading frames of a nucleotide query with six reading frames of a nucleotide database, both sequences must be translated.
BLASTN: Nucleotide vs nucleotide → no translation.
BLASTX: Nucleotide query (translated) vs protein database.
TBLASTN: Protein query vs translated nucleotide database.
TBLASTX: Translates the nucleotide query into 6 frames AND translates the nucleotide database into 6 frames → 36-frame comparison.
Thus, TBLASTX is the only tool performing 6×6 frame comparison.