Genomic Testing Nomenclature

Genomic test results using DNA extracted from tumor tissue frequently demonstrate a complex molecular signature that is different from that of normal tissue for any given patient. Test results provide a synopsis of the genomic variants that have been identified and categorized by potential actionability with regard to treatment options.

This resource provides some explanation of commonly used terminology included in test reports.

Types of genomic alterations/changes reported

Somatic or acquired variants arise in cancers and alter the normal sequence pattern of DNA. They occur when cells are damaged during replication, by viruses or by exposure to carcinogens, such as tobacco smoke or radiation.

Table 1. Types of Genomic Variants/Alterations

Alteration	Type of variant	Description	Example
Point Mutation	Single nucleotide variant (SNV) or nucleotide change	Substitution, deletion, duplication, insertions, or a combination	BRAF V600E (substitution)
Amplification	Copy number variant (CNV)	change in the number of copies of a cancer-related gene	ERBB2 Amplification
Fusion	Structural rearrangement	May include chromosome translocations, deletions, duplication, or inversions	EML4-ALK recurrent inversion mutation in non-small cell lung cancer

Reporting the impact of genomic variants

Variants may or may not have an impact on the function of the gene. Genomic variations that do impact function may be activating, resulting in a gain of function of the protein, or inactivating, resulting in a loss of function.¹ The significance of the change depends on the location of the variant, the type of genetic aberration, and the normal function of the protein.

Genomic variants are classified into three general categories:

Benign or likely benign: variants do not have any functional consequences and are often seen commonly in the general population. You may also see these referred to as “polymorphisms.”
Pathogenic or likely pathogenic: variants impact the function of the gene in some way. Most accurately, these are referred to as “variants that impact function”. More commonly, these may be referred to as “mutations.”
Variants of unknown significance or VUS are changes in the gene for which the impact is unknown. This may be because they are rare and there is not enough data available to be conclusive about their functional impact. Over time, VUS are likely to be re-classified as benign or pathogenic as more data are amassed.

Genomic Marker Notations and Abbreviations

The combination of numbers and letters provides a variant’s location, type of aberration and protein change.

“c.” prefix denotes standard variant nomenclature based on coding DNA reference sequences

“p.” prefix denotes standard variant nomenclature based on protein-level amino acid sequences

For more information

Sequence Variant Nomenclature: recommendations for the description of sequence variants. Nomenclature authorized by Human Genome Variation Society (HGVS), Human Variome Project (HVP), and the HUman Genome Organization (HUGO).

Types of Molecular Tumor Testing: description of different types of genomic variants/alterations and testing methodology.

References

1. Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, et al. Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn. 2017;19(1):4-23.

Updated 2/5/2020