Gastroenterology

Genetic testing is clinically relevant for the following indications, including but not limited to:

• Suspected requiring diagnostic clarification or exclusion
• Seronegative villous atrophy or suspected coeliac disease in individuals already on a gluten-free diet
• Chronic or recurrent of unexplained cause, including paediatric and early-onset presentations
• Persistent symptoms following lactose ingestion when first-line investigations are inconclusive

Genetic testing may be considered when a gastrointestinal disorder is unexplained, presents at an early age, occurs repeatedly within a family, or cannot be clarified by serological and clinical findings alone. Identifying or excluding an underlying genetic cause can support clinical decision-making, inform the aetiological work-up, and clarify potential implications for family members.

• A pathogenic or likely pathogenic variant establishes the specific molecular diagnosis, identifying the causative gene and condition.
• A variant of uncertain significance (VUS) is an unclear finding: current evidence is insufficient to classify it as likely benign or likely pathogenic, and reanalysis can be offered after a few years as evidence accumulates.
• In other cases, no pathogenic variant is detected in the analysed genes. The presence of a pathogenic variant cannot, however, be entirely excluded: the causative change may lie in a gene not yet linked to the condition, or in a regulatory region that current methods cannot reliably capture.
• Each variant is classified according to criteria.

Testing is performed using based multi-gene panels and targeted genotyping, depending on the clinical indication.

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