If a nucleotide triplet with an unknown nucleotide appears (ex. ANC instead of ATC), I'd want to either skip those, or mark them with a letter like 'X'.

In the first two solutions, you can use exists, e.g.:

        if ( exists $genetic_code{$codon} ) {
            $amino_acid .= $genetic_code{$codon};
        }
        else {
            $amino_acid .= $codon;
            # - OR -
            $amino_acid .= 'X';
            # or something else...
        }
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Update: Or, written more tersely, either $amino_acid .= exists $genetic_code{$codon} ? $genetic_code{$codon} : 'X'; or $amino_acid .= $genetic_code{$codon} // 'X'; (the former uses the Conditional Operator, and the latter uses Logical Defined Or instead of exists, assuming you don't have any undef values in your hash).

I do like the regex solution though, it's quite elegant.

You can combine my second and third suggestions (for nonexistent codes, this uses the defined-or solution I showed here, the exists solution would work as well):

    (my $amino_acid = $seq) =~ s{(...)}
        { $genetic_code{$1} // 'X' }esg;
    return $amino_acid;
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