Home › Pharmacogenetics guide › Understanding results

Pharmacogenetics guide

Understanding and communicating results: from genotype to recommendation

Reviewed by Dr. Daniel Wallerstorfer, molecular biologist and founder of Novogenia · Updated: 13 October 2026 · Reading time: 9 min

In short

A pharmacogenetic result reads in three layers: genotype (which genetic variants a person carries), phenotype (how fast the enzyme works) and recommendation (what a guideline says for a specific drug). For CYP2D6 and DPYD, the activity score links the first two layers. CPIC has used standardized terms since 2017, and since 2020 CPIC and DPWG have shared one translation system for CYP2D6. In conversation, a simple image helps – along with one clear rule: decisions about medication are made by the treating physician.

The word that confused everyone

For years, pharmacogenetic reports used a term that tripped up even experts: “extensive metabolizer.” All it meant was that the enzyme works normally. Many physicians had to ask what it meant. So 58 experts from clinical care, research, laboratories and informatics sat down within the Clinical Pharmacogenetics Implementation Consortium (CPIC) and agreed on standardized terms over several survey rounds – 90% endorsed the result. Since then, the term has been “normal metabolizer,” and the same terms apply to all enzymes, including TPMT and DPYD (Caudle et al., Genetics in Medicine, 2017).

Three years later came the next step. For CYP2D6, labs and guidelines translated the same genotype into different phenotypes – leading to different recommendations. CPIC and the Dutch DPWG created a shared system, which 82% of the participating experts endorsed (Caudle et al., Clinical and Translational Science, 2020).

The logical conclusion: a result is a translation in three layers – from the letter sequence of the genes to the working speed of a tool to an action. Once you know the three layers, you can read any report with confidence and explain it so that every patient understands.

Three layers: genotype, phenotype, recommendation

Picture the gene as a blueprint and the enzyme as a tool that converts a drug. Everyone has two copies of the blueprint, one from their mother and one from their father. That gives the result its three layers:

Genotype: which variants sit on the two gene copies, usually written as star alleles. “CYP2D6 *1/*4” means: one copy works normally (*1), the other does not produce a working tool (*4).
Phenotype: how fast the tool works overall. The standardized terms are poor, intermediate, normal, rapid and ultrarapid metabolizer. Which of them exist depends on the gene.
Recommendation: what a guideline such as CPIC or DPWG says about a specific drug for this phenotype.

Codeine shows how it all fits together. Codeine is a prodrug: the body first has to convert it into morphine using the CYP2D6 tool before it relieves pain.

Genotype (example)	Activity score	Phenotype	CPIC on codeine
CYP2D6 4/4	0	poor (PM)	avoid codeine because pain relief may be diminished; if an opioid is needed, consider one other than tramadol
CYP2D6 1/4	1	intermediate (IM)	dose according to the label; if there is no response, consider an opioid other than tramadol
CYP2D6 1/1	2	normal (NM)	dose according to the label
CYP2D6 1/1x2	3	ultrarapid (UM)	avoid codeine because of the risk of serious toxicity; if an opioid is needed, consider one other than tramadol

The last row is the interesting one: with “*1x2,” one gene copy is duplicated. The tool works so fast that too much morphine is produced. With prodrugs, the logic flips: a slow tool means too little effect rather than too much. With drugs that CYP2D6 breaks down, on the other hand, more of the drug stays in the body when the tool is slow. So the same result can mean the opposite depending on the drug – which is exactly why every phenotype needs the recommendation for the specific drug. Which genes affect which drugs is covered in Key genes: CYP2D6, CYP2C19 and more.

The activity score: points for every tool

CYP2D6 has many variants with very different activity, and some people carry more than two gene copies. To still arrive at a clear statement, a research group developed the activity score. They genotyped more than 25 CYP2D6 variants in 672 people and measured how fast their bodies broke down a test substance (Gaedigk et al., Clinical Pharmacology & Therapeutics, 2008).

The principle is simple – like collecting points:

Each gene copy gets points according to its function: 0 for no function, 0.25 or 0.5 for decreased function, 1 for normal function.
Duplicated copies count more than once.
The sum is the activity score.

For CYP2D6, the shared CPIC and DPWG system now applies: an activity score of 0 means poor metabolizer, 0.25 to 1 intermediate, 1.25 to 2.25 normal and above 2.25 ultrarapid. The main change was one cut-off: an activity score of 1 now counts as intermediate, no longer as normal (Caudle et al., 2020). CPIC uses an activity score for DPYD as well: 2 is normal, 1 to 1.5 intermediate, 0 to 0.5 poor.

For you, this means: if an older CYP2D6 report still says “normal” for an activity score of 1, the current guideline classifies it as intermediate. So always look at the genotype and the activity score, not just the label.

What a result does not tell you

A good report is honest about its reach. These four points belong in every interpretation:

*1 means “nothing found”: A *1 means that none of the tested variants was found. That is why the report should list which variants were read.
Gene copies count: With CYP2D6, copies can be missing (*5) or duplicated (xN). If a test does not capture them, the phenotype may come out too low or too high.
“Indeterminate” is an honest answer: If the function of a detected variant is unknown, the phenotype is “indeterminate.” CPIC then gives no recommendation – the physician decides on clinical grounds as usual.
Genes are one factor among many: The phenotype is a genetic prediction. Other drugs that slow down the same enzyme, age, and kidney and liver function all change how a drug actually works.

One more thing: genes do not change over a lifetime, but our knowledge about them does. Guidelines keep evolving, as the new CYP2D6 cut-off shows. How CPIC and DPWG build and update their recommendations is explained in Guidelines: CPIC, DPWG and drug labels.

How to explain the result

A result only delivers its value when the patient understands it and remembers it at the next prescription. This order works well:

State the purpose: Which question does the result answer, and which drugs are involved?
Use one image: The gene is the blueprint, the enzyme the tool that converts a drug.
Give the result in one sentence: for example, that this tool works more slowly than in most people.
Explain what it means today: What does it mean for current medication – and who decides?
Show what it means tomorrow: present the result with every new prescription, including at the pharmacy.
Invite questions: What is unclear, what is worrying?

These translations help in conversation:

On the report	In conversation
CYP2D6 1/4	“One gene copy works normally, the other does not.”
poor metabolizer (PM)	“The tool that converts this drug works very slowly. That is not a disease, it is information for the dose and the choice of drug.”
ultrarapid metabolizer (UM)	“The tool works especially fast. Some drugs are converted too quickly as a result.”
recommendation: consider an alternative	“There is a recommendation for this drug. What follows from it is up to the treating physician.”
indeterminate	“For this gene, no reliable statement can be made at this time.”

The golden rule: no changes without the treating physician

A result can tempt people to simply leave out a drug. That is exactly what should not happen. Decisions about medication – stopping, switching or changing the dose – are made by the treating physician. Say so clearly, even when the result seems clear-cut, and ask the patient to keep taking their medication as prescribed until that conversation.

As a pharmacist, you are the key bridge here: you spot the connection, explain it and pass it on to the practice. What that looks like in the pharmacy is described in Pharmacogenetics in the pharmacy.

Sharing the result and finding it again

A result that no one can find at the next prescription helps no one. Three things make sure it is there when it is needed:

In the record: gene, genotype, phenotype and date as a permanent entry, as visible as an allergy.
With the patient: a short summary to take along and show at the pharmacy and to other physicians.
Shared with consent: In Germany, physicians may share the result with others only with explicit consent in writing or electronic form (Section 11(3) GenDG). What else applies to consent and data protection is covered in Data protection and consent.

Because genes do not change, a well-documented result can be used again for many later prescriptions. Why exactly that speaks for testing ahead of time is covered in Pre-emptive or reactive testing?

Frequently asked questions

What does *1/*1 mean on a report?

That none of the tested variants was found on either gene copy. The lab then assumes normal function. How meaningful that is depends on which variants the test covers at all – that information belongs on every report.

Why do two reports show a different phenotype for the same gene?

Usually because the labs translated the genotype using different systems, or because one report is older. For CYP2D6, CPIC and DPWG have shared one system since 2020; since then, an activity score of 1 counts as intermediate, no longer as normal. So always compare the genotype, not just the phenotype.

Does a test need to be repeated when guidelines change?

For the variants tested, usually not: genes do not change over a lifetime. When a guideline changes, the same genotype can be reinterpreted. A new test can make sense if important variants or genes were not covered at the time.

How do I explain a "poor metabolizer" result without causing alarm?

With an image and some context: the gene is the blueprint for a tool that converts a drug. If the tool works slowly, that is not a disease but information for choosing and dosing certain drugs. Add one clear rule: do not change anything on your own; discuss it with the treating physician.

May the patient share the result with their pharmacy?

Yes. It is their result, and they can show it to anyone they like – with every new prescription, that is actually a good idea. For physicians in Germany, the rule is: they may share the result with others only with the patient’s explicit consent in writing or electronic form (Section 11(3) GenDG).

Pharmacogenetics in your practice or pharmacy?

Tell us about your setting – we will show you how the offer can work for you.

Request a project →Offer for physicians

Note: This guide is general information for businesses and professionals and does not replace medical or legal advice. The genetic traits determined in a genetic analysis are well documented (each gene included is backed by at least three independent studies); recommendations derived from them are logical conclusions, not scientifically proven. Pharmacogenetic results do not replace a medical decision: any change to medication is made only by the treating physician. Regulations can change; errors and changes excepted.