Targeted Variant Testing (TVT)

Targeted Variant Testing (TVT) utilizes next-generation sequencing (NGS) to analyze specific genetic variants previously identified through prior testing or reported in the scientific literature. It is a targeted genetic test designed to support confirmation of findings, clarification of variant clinical significance, and evaluation of specific genetic results.

More Information

Targeted Variant Testing (TVT) is a focused genetic analysis designed to evaluate specific genetic variants of known or suspected clinical relevance. The test is typically applied when variants have been previously identified through research studies or reported by another laboratory, or when commonly described founder variants are being investigated. It may also be used to support the clarification of variant classification in cases where prior results require further evaluation.

Targeted variant testing is intended for confirmatory analysis of known variants and does not involve comprehensive genomic screening. It is particularly useful in situations where a targeted approach is sufficient to address a specific clinical question, supporting accurate interpretation of previously reported findings. Up to 10 genetic variants may be analyzed per test request, allowing flexibility when multiple variants are under investigation. This approach enables efficient and focused evaluation while maintaining high analytical accuracy.

Targeted variant testing is limited to the analysis of predefined variants and reports only the presence or absence of the specifically requested variant(s) in the individual being tested. The scope of the analysis does not extend to additional or unrelated findings. Incidental findings are not reported; however, in cases where further investigation may be clinically relevant, a recommendation for additional testing may be included.

The analysis is performed using next-generation sequencing (NGS), ensuring high accuracy and reliability of results. Variant interpretation is based on current scientific evidence and established clinical guidelines.

The test is performed in a clinical laboratory accredited to ISO 15189 and certified by CLIA and CAP, ensuring the validity, accuracy and international recognition of the results.

Genetic testing is performed by taking a blood sample or by taking genetic material from inside the cheeks (with a swab), and can be done:

• By taking the sample at Diagnostiki Athinon. Book your appointment in real-time and purchase the test online
• By taking the sample at home. We send you all the necessary collection materials to your home via courier. The courier also returns the sample to the laboratory. Purchase the test online

In certain cases, prior genetic test results are required to confirm eligibility for testing.

Test Strengths

The test is characterized by the following strengths:

• Analysis is performed in a CAP-accredited laboratory with the participation of CLIA-certified personnel.
• Advanced sequencing technologies, high-performance target enrichment methods, and precise bioinformatics pipelines ensure superior analytical performance.
• Comprehensive and clinically meaningful reports are provided.

Test Limitations

Please refer to the Test Scope & Eligibility section for more information on eligibility criteria.

This test may not reliably detect:

• Low-level mosaicism
• Variants within pseudogene regions or duplicated genomic segments

For further details, please refer to the Bioinformatics & Performance section.

Bioinformatics

The analysis is designed to target the specific genomic region harboring the targeted variant of interest. This includes the variant locus and, where applicable, adjacent bases required to ensure accurate detection.

Sequencing data is processed through a proprietary analysis and annotation pipeline that integrates state-of-the-art algorithms and industry-standard software solutions. Multiple quality control steps are embedded throughout the workflow to ensure the accuracy, validity, and consistency of the results. The pipeline is optimized to maximize sensitivity without compromising specificity.

All findings are summarized in a clear and detailed clinical report. This report includes sequencing quality metrics and coverage of the targeted region and the variant locus, and highlights any regions where coverage is limited (<20x for nuclear DNA and <1000x for mtDNA, when applicable). This ensures transparency and supports accurate clinical interpretation.

When the targeted variant is located in the mitochondrial genome, the analysis includes the relevant mitochondrial region.

Test Performance

This assay is designed to detect a predefined targeted variant based on prior clinical or molecular findings. The test is optimized for the accurate identification of the specified variant and is not intended for comprehensive analysis of the entire gene or genomic region unless otherwise stated.

The assay is based on a high-quality, clinical-grade next-generation sequencing (NGS) methodology. Depending on the nature of the targeted variant, the analysis may include detection of single nucleotide variants (SNVs), small insertions and deletions (indels), and, when applicable, copy number variants (CNVs). Details regarding the detection of different types of genetic alterations are provided in the sequencing and detection performance table (see Table).

The assay has been validated for several sample types, including EDTA blood, isolated DNA (excluding DNA from formalin-fixed paraffin-embedded tissue), saliva, and dried blood spots (filter cards). These sample types were selected to ensure reliable DNA quality and performance.

The performance metrics shown below are based on initial validation studies at an accredited clinical laboratory, with equivalent results confirmed across additional laboratory sites.

Performance of a high-quality, clinical-grade NGS sequencing assay

Coverage metrics

Performance of Mitochondrial Sequencing Assay

Mitochondrial assay coverage metrics