Whole exome sequencing

WES-based diagnostic analysis is usually clinically indicated for patients with:

• Congenital anomalies or developmental delay
• Disorders involving multiple potential disease-associated genes
• Complex, non-specific symptoms affecting multiple organ systems
• Genetically heterogeneous disorders involving many potential genes
• Severe neonatal or childhood-onset disorders
• Inconclusive results from previous genetic testing

Causative or likely causative finding: One or more pathogenic or likely pathogenic variants provide a molecular explanation that is compatible with the phenotype and expected disease mechanism. This may help guide treatment, surveillance and patient or family management.

Uncertain finding: A variant of uncertain significance (VUS) was identified in a gene associated with a disease spectrum that overlaps with the patient’s clinical presentation. However, the available evidence is insufficient to establish or exclude whether the variant itself contributes to the patient’s condition.

No causative finding identified within the analysed and reportable scope: This does not exclude a genetic aetiology. Because of the technical limitations of WES, causative variants may remain undetected. Future reanalysis may identify new clinically relevant findings as scientific knowledge advances.

Incidental or secondary findings: Genetic variants unrelated to the patient’s primary indication may be identified and may have medical relevance. Those findings are specifically defined by professional guidance, such as ACMG recommendations. Reporting depends on the type of analysis, consent process, clinical context, patient age and laboratory policy. Findings associated with adult-onset disorders for which no intervention is available should generally be excluded. The patient or legal guardian must consent to whether these findings are assessed and reported. In duo or trio analyses, each participating parent must also decide whether those findings identified in their own data may be assessed and reported. The distinction between secondary and incidental findings is that secondary findings are actively sought, whereas incidental findings are identified unexpectedly during the analysis of the primary indication

A WES-based analysis may detect variants whose genotype, zygosity, segregation and phenotypic fit are compatible with a defined disease mechanism, including autosomal-dominant, autosomal-recessive or X-linked inheritance. Trio analysis is recommended whenever possible, as it helps differentiate inherited from de novo variants, supports the interpretation of inheritance patterns and may increase diagnostic yield compared with singleton analysis.

Reliable interpretation depends on detailed clinical information about the index patient, including the phenotype, age of onset, family history and results of previous investigations.

The results may inform treatment, surveillance, specialist referral, reproductive counselling and testing of relatives. Sequence data may also be reanalysed at a later stage as new disease-associated genes are identified, variant classifications change or the clinical phenotype evolves.

Pre-test information and consent should address the clinical question, analytical and reporting scope, possible outcomes, limitations, implications for family members, data handling and the approach to secondary or incidental findings. Post-test counselling should place the result in its clinical context and address residual uncertainty, recurrence risk, family testing, reproductive implications and appropriate follow-up.

We provide expert as an integral part of the genetic testing journey. Genetic counselling is a structured, educational, impartial and non-directive communication process that supports and accompanies patients and their relatives throughout the genetic testing process. Availability of genetic counselling services may vary by country. Please to check out access in your region.

Testing is performed using based multi-gene panels.

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