Table 1 Pharmacogenomics gene variant evidence code assignments based on strength of evidence for a drug interaction phenotype

1

Clinical outcomes studies

Consistent effect of genetic variant on drug of interest^a

Clinically relevant

2

PK or PD study

Consistent effect of genetic variant on drug of interest^a

Potential clinical relevance

3

Molecular/cellular functional studies

Consistent effect of genetic variant on drug of interest^a

Potential clinical relevance

4n^, 4scd^, 4se^, 4ae^, 4ad, or 4dp

Molecular/cellular functional studies

^aConsistent effect of genetic variant on probe drug (industry standard substrate used for evaluating enzyme function) and includes analysis of mutation type (based on the six categories defined in table footnote^b)

Potential clinical relevance

5n^, 5scd^, 5se^, 5ae^, 5ad, or 5dp

Clinical outcomes studies

^aConsistent effect of genetic variant on another drug(s) and includes analysis of the mutation type (based on the six categories defined in table footnote^b)

Potential clinical relevance

6n^, 6scd^, 6se^, 6ae^, 6ad, or 6dp

PK or PD study

^aConsistent effect of genetic variant on another drug(s) and includes analysis of the mutation type (based on the six categories defined in table footnote^b)

Potential clinical relevance

7n^, 7scd^, 7se^, 7ae^, 7ad, or 7dp

Molecular/cellular functional studies

^aConsistent effect of genetic variant on another drug(s) and includes analysis of the mutation type (based on the six categories defined in table footnote^b)

Potential clinical relevance

8

Molecular/cellular functional studies

Effect of genetic variant on a probe drug only

Clinical relevance unknown

9

Clinical outcomes studies

Effect of genetic variant on another drug only, or drug-specific altered activity for other drugs, or inconsistent effect on drug of interest

Clinical relevance unknown

10

PK or PD study

Effect of genetic variant on another drug only, or drug-specific altered activity for other drugs, or inconsistent effect on drug of interest

Clinical relevance unknown

11

Molecular/cellular functional studies

Effect of genetic variant on another drug only, or drug-specific altered activity for other drugs, or inconsistent effect on drug of interest

Clinical relevance unknown

12

Clinical outcomes studies, PK or PD study, or molecular/cellular functional studies

Genotype frequency data suggestive of very rare or ‘private’ mutation, defined as a genetic variant found in a single individual or single family without being reported in reference populations

Clinical relevance unknown

13

Genetic variation screening studies, without additional functional or clinical studies

Insufficient data

Clinical relevance unknown

14

Clinical outcomes studies, PK or PD study, or molecular/cellular functional studies

Demonstrates no effect of the genetic variant on drug response. Includes variants that have evidence for association with drug response but attributed to linkage disequilibrium with another variant with defined function

Clinical relevance unsupported