Hereditary Cancer Germline Testing Across 21 European Countries: Why the Same Patient Can Receive a Different Diagnosis

Key Takeaways

• A survey mapping hereditary cancer germline testing across 21 European countries (20 EU member states + Norway), published in the European Journal of Human Genetics (2026). Every country has adopted multigene panel testing — but the range of genes tested differs sharply between countries.
• HBOC panels span from fewer than 20 genes to pan-cancer panels of up to 226. High-risk genes (BRCA1/2) appear everywhere, but whether moderate-risk genes are included varies, creating diagnostic disparities at the variant-reporting stage.
• WES is offered in routine care in 12 of 21 countries (57%), as the next step for complex cases where panel testing was uninformative or for phenotypes suggesting rare genes outside standard panels. At least 6 countries do not provide it through public healthcare — whether a patient can move to broader testing depends on where they live.
• Clinical implication: what scope to investigate is the clinician’s call, but because panel gene content varies even for the same indication, the intended scope and the scope actually tested can diverge. A negative result carries meaning only across the range the panel actually covered.
• Pairing genome-wide sequencing (WES/WGS) with ACMG secondary findings (SF) reporting opens the chance to review actionable cancer-predisposition variants regardless of the referral phenotype or panel composition.

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A patient with the same suspected hereditary cancer can have an actionable variant identified — or missed — depending on which country and which laboratory handles the case. Often what separates those outcomes is not the patient’s genome, but the composition of the panel applied to them.

A study in the European Journal of Human Genetics put numbers to this gap, mapping hereditary cancer germline testing across 21 European countries (20 EU member states plus Norway) (Kiljańczyk et al., 2026). Conducted as a structured survey of national representatives in the ERN GENTURIS network, it covers the full care pathway — panel composition, WES/WGS availability, and who may order testing.

The study never names a “correct” panel. What the data reveal instead is that the diagnostic scope is frequently narrowed before the patient is ever tested. So the question it poses to clinicians is less “which panel should I choose?” and more “does the panel actually test the scope I ordered?”

The scope narrows before referral, through panel composition

All 21 countries offer HBOC panels, yet the standard panel ranges from fewer than 20 genes (centered on BRCA1/2, PALB2, TP53, CHEK2) to larger panels adding moderate-risk genes such as ATM, BARD1, RAD51C/D, and BRIP1. Some pan-cancer panels reach up to 226 genes.

The clinically important point: high-risk genes like BRCA1/2 are universal, but inclusion of moderate-risk genes is not. As the authors note, this variability translates into diagnostic disparities “already at the variant-reporting level.” The decision that narrows the diagnostic scope is made when the panel is chosen — before any result is seen — and an actionable variant can be missed as a result.

The route to widen the scope exists, but unevenly

The field’s response to this gap is genome-wide sequencing (WES/WGS). WES is offered in routine care in 12 of 21 countries (57%), and its role is well-defined — complex cases where panel testing was uninformative, or phenotypes pointing to rare genes absent from standard panels. WGS is used in 6 countries, limited to scenarios such as exploring non-coding regions after a negative WES.

The constraint is that this next step is blocked in some settings. At least 6 countries do not provide or reimburse WES through public healthcare. When there is no route to widen testing after a negative first-tier result, that first test effectively becomes the final scope. This is why the authors call not for one technology over another, but for equitable access and harmonized care pathways.

Keeping phenotype and panel from narrowing the scope

This is where genome-wide testing and ACMG secondary findings (SF) reporting become relevant. The ACMG SF list (v3.3, 2025) is built around medically actionable genes and includes many of the predisposition genes this study examines — BRCA1/2, the Lynch syndrome MMR genes (MLH1, MSH2, MSH6, PMS2), TP53, PALB2, APC, and MUTYH. Sequencing on a WES/WGS backbone and reporting SF therefore opens the opportunity to review these actionable variants regardless of the original indication or the panel a patient passed through.

In this context, 3billion provides ACMG SF analysis for every patient, with the patient’s voluntary consent and independent of phenotype. A patient referred for a rare genetic disease is reviewed within the same analysis for actionable variants, including hereditary cancer predisposition. It is one practical answer to the concern this study raises — not letting the referral phenotype quietly define the limits of the diagnosis.

What this leaves for the clinic

The study does not recommend a specific technology or panel. What it points to instead is structure — that the route to broaden testing, when clinically warranted, should not be blocked by where a patient lives.

What scope to investigate is entirely the clinician’s call. What is harder to control comes next — whether the panel actually tests the scope that was ordered. A negative result carries meaning only across the range the panel actually covered, and because panel gene content varies even for the same indication, the intended diagnostic scope and the scope actually tested can diverge.

If it would help to discuss germline testing strategy or secondary-findings reporting scope for hereditary cancer, please feel free to get in touch.

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Frequently Asked Questions

Q1. What did this study examine?
It mapped how hereditary cancer germline testing is actually delivered across 21 European countries (20 EU member states + Norway). National representatives in the ERN GENTURIS network reported on panel composition, WES/WGS availability, founder-variant first-tier testing, use of deceased-patient tissue, laboratory accreditation, and test-ordering rights. It focused on technical availability and did not capture real-world access metrics such as waiting times or reimbursement.

Q2. How much does hereditary cancer panel testing differ between countries?
All 21 countries offer HBOC panels, but the standard panel ranges from fewer than 20 genes to as many as 226. High-risk genes such as BRCA1/2 are universal, while moderate-risk genes (ATM, BARD1, RAD51C/D, and others) vary by country. Colorectal (Lynch) panels are offered in 20 countries and prostate cancer panels in 19.

Q3. What role does WES play in hereditary cancer diagnosis?
At the time of the survey, 12 of 21 countries (57%) offered WES in routine care. It is used mainly as the next step for complex cases where panel testing was uninformative, or for phenotypes suggesting rare genes outside standard panels. WGS is used in 6 countries for limited scenarios, such as non-coding analysis after a negative WES.

Q4. Which is better, panel testing or WES?
The study does not compare the two or recommend either. This is not a binary choice but a question of scope and access. A negative result carries meaning only across the range the panel actually covered, so when broader testing (an extended panel, WES/WGS) is clinically warranted, the route to it should not be blocked by where a patient lives.

Q5. How do ACMG secondary findings (SF) relate to hereditary cancer?
The ACMG SF list (v3.3, 84 genes) centers on medically actionable genes and includes major hereditary cancer predisposition genes — BRCA1/2, the Lynch MMR genes, TP53, PALB2, APC, and MUTYH. Reporting SF alongside WES/WGS allows these actionable variants to be reviewed regardless of the original referral indication.

Q6. What is the clinical takeaway?
What scope to investigate is the clinician’s call, but because panel gene content varies even for the same indication, the intended scope and the scope actually tested can diverge. A negative result carries meaning only across the range the panel actually covered, and access to a route for broadening testing depends on where a patient lives.