Clinical Whole Exome Sequencing

INDUSTRIAL GENOMICS/

Clinical whole exome sequencing (WES) for the diagnosis of rare genetic disorders, from first-line testing to complex diagnostic cases.

What is clinical whole exome sequencing (WES)

Clinical whole exome sequencing (WES) is a genomic diagnostic test used to analyse the coding regions of the genome in patients with suspected rare genetic disorders. By targeting all ~20,000 human protein-coding genes and mitochondrial DNA, it enables the identification of pathogenic variants associated with monogenic (Mendelian) disorders across a wide range of clinical presentations, including heterogeneous and complex conditions.

At Breda Genetics, clinical whole exome sequencing (WES) is used both as a first-line diagnostic test and in more complex cases, combining full exome coverage with expert clinical interpretation and a structured medical report. The clinical exome sequencing service is designed for hospitals, laboratories and genomic programs requiring reliable sequencing workflows and clinically actionable results.

When to use clinical exome sequencing (WES) in rare disease diagnostics

Clinical exome sequencing (WES) is typically used in patients with suspected genetic disorders when the clinical picture is not explained by a single condition or when standard diagnostic approaches are not sufficient. It is increasingly adopted as a first-line test in rare disease diagnostics, particularly in complex or heterogeneous cases.

Clinical exome sequencing may be considered in the following situations:

Patients with suspected rare genetic disorders without a clear diagnosis
Heterogeneous or complex clinical presentations involving multiple systems
Negative or inconclusive results from prior genetic testing
Conditions with high genetic heterogeneity, where multiple genes may be involved
Early diagnostic work-up when rapid and comprehensive genomic analysis is required
Cases where a targeted panel may be insufficient to capture the full genetic landscape
Cases requiring a comprehensive genomic approach rather than stepwise gene testing

What is included in the clinical whole exome sequencing service

The clinical whole exome sequencing service includes all steps required to generate clinically interpretable genomic results, from sequencing to final diagnostic reporting.

The service is structured as an integrated workflow:

Sample processing and sequencing
DNA extraction (if required), library preparation and high-coverage sequencing of all coding regions of the genome, including mitochondrial DNA.
Bioinformatic analysis
Alignment, SNV (single nucleotide variant) and CNV (copy number variation) calling, and variant annotation using validated pipelines designed for clinical applications, supported by internally developed AI-based tools enabling both targeted variant exploration and standardized large-scale data analysis.
Variant interpretation
Expert evaluation of identified variants in the context of the patient’s phenotype, including classification according to current clinical guidelines and expert review of variant evidence in complex or uncertain cases.
Clinical reporting
Delivery of a structured medical report focused on clinically relevant findings, aimed at reaching a clear diagnostic conclusion, with final interpretation guided by expert clinical judgment.
Data management and reanalysis (when applicable)
Secure data storage and the possibility of future reanalysis as new knowledge becomes available.

Depending on clinical or operational requirements, the service can be provided as a complete end-to-end solution or as a sequencing-only workflow for laboratories performing their own interpretation.

Turnaround time and operational workflow

Turnaround time and workflow reliability are critical parameters in clinical whole exome sequencing, particularly in settings where diagnostic decisions directly impact patient management.

At Breda Genetics, the clinical whole exome sequencing service is designed to ensure consistent and predictable turnaround times, supported by structured laboratory workflows and controlled processing steps.

Typical turnaround time for standard clinical whole exome sequencing ranges from approximately 3 to 4 weeks, depending on sample type and clinical complexity.

EXOME ULTRA-FAST

EXOME ULTRA-FAST is designed for situations where genomic information is needed within days rather than weeks.

→ FASTQ data in 3 working days

→ Medical Report in 5 working days

This accelerated service is designed for situations where rapid genomic information is required to support immediate clinical decision-making.

→ Explore EXOME ULTRA-FAST

From an operational perspective, the service supports:

Single-case analysis, for individual diagnostic requests
Batch processing workflows, for laboratories managing multiple samples
Sequencing-only service models, for partners performing in-house interpretation

The workflow is designed to ensure reproducibility, scalability and clear communication at each step of the process, from sample reception to final report delivery.

When clinical exome sequencing (WES) is preferred over targeted panels

Clinical whole exome sequencing is often preferred over targeted gene panels in situations where the underlying genetic cause is not clearly defined or when a broader diagnostic approach is required.

While targeted panels can be effective in well-defined clinical scenarios, they may be limited in cases with heterogeneous presentations or when multiple genes could be involved.

By analysing all coding regions of the genome, clinical whole exome sequencing allows a more comprehensive assessment, reducing the need for sequential testing and supporting a more efficient diagnostic process.

This approach is particularly relevant in complex or unresolved cases, as well as in early diagnostic workflows where a broad genomic overview is required.

While some approaches still rely on restricted “clinical exome” panels targeting a limited number of genes, these strategies may not capture the full genetic landscape in heterogeneous or complex conditions.

A comprehensive clinical whole exome sequencing approach, covering all ~20,000 human protein-coding genes and mitochondrial DNA, reduces the risk of missed diagnoses and avoids the need for sequential re-testing.

INDUSTRIAL GENOMICS/