Two In Cis Variants-Two Worlds Apart

Precision oncology emphasizes genotyping as one of the mainstays of oncological decision-making. The core information element exchanged between the laboratory and the oncologist is the precise mutation. Specifically, it is the written representation typically in the form of a variant description at the DNA or protein level. These annotations can be confusing, and many commercial laboratories have abandoned DNA-level annotations. Here we present a complex double-point mutation to illustrate a situation where a formally "correct" reporting nomenclature can obscure clinically relevant and potentially clinically actionable information. KEY POINTS: The Human Genome Variation Society (HGVS) currently recommends that "two variants separated by one or more nucleotides should be described individually and not as a combined 'delins' (deletion-inserion)." There remains confusion about the appropriate nomenclature to report variants and the significance of these variants among clinicians. It is the clinically integrated molecular-genetic interpretation that will help clinicians make informed decisions to improve patient care.