PreSENTIA Hereditary Cancer

PreSENTIA is recommended for individuals who:

• Have a personal or family history suggestive of hereditary cancer
• Have a known pathogenic variant in the family
• Belong to a specific racial or ethnic group (i.e. Ashkenazi Jewish)
• Meet clinical guideline criteria for hereditary cancer testing
• Require genomic insights to guide surveillance, prevention, or specialist referral
• Have had multiple primary cancers
• Have been diagnosed with cancer at unusually young age
• Have been diagnosed with rare cancer types
• Have been diagnosed with unusual cases of a specific cancer type (i.e. breast cancer in men)

Hereditary cancer risk assessment plays a central role in identifying individuals and families who may be at increased risk of developing specific cancers. International guidelines recommend genetic evaluation for appropriate patients to support personalised risk assessment, surveillance and clinical management.

As highlighted by the :
“A hereditary cancer risk assessment is the key to identifying patients and families who may be at increased risk of developing certain types of cancer.” (1)
The further recommends that, whenever possible, genetic testing should begin with an affected family member to maximise the likelihood of identifying a clinically relevant inherited pathogenic variant (2).

PreSENTIA supports evidence-based clinical management by:

• Identifying individuals with hereditary cancer syndromes.
• Supporting personalised cancer surveillance and early detection strategies.
• Informing preventive interventions and risk-reducing measures, where appropriate.
• Guiding treatment planning when hereditary cancer status has therapeutic implications.
• Facilitating referral for genetic counselling and specialist oncology or clinical genetics services.
• Enabling cascade testing of at-risk relatives.
• Supporting care aligned with established national and international hereditary cancer management guidelines.

Every report includes:

• A clear summary of the identified genetic variant(s), where applicable.
• Classification of variants according to the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) guidelines.
• Interpretation of the clinical significance of the reported findings.
• Recommendations for appropriate clinical follow-up, including referral for genetic counselling where indicated.
• Guidance on surveillance, risk management and cascade testing for at-risk relatives, when appropriate.

PreSENTIA reports one of the following outcomes:

Clinically significant variant detected

Pathogenic and likely pathogenic variants are reported following the American College of Medical Genetics and Genomics (ACMG) classification guidelines. Clinical follow-up and review of management plans are recommended.

Variant of uncertain significance (VUS) detected

A genetic change has been detected, but it is currently unknown whether that change is associated with cancer development.

No clinically significant variant detected

No disease-causing genetic variant has been identified in the genes tested. Detailed interpretation of the results is provided. The variant summary as well as the clinical significance of the genetic alterations identified is reported, along with recommendations on the next steps after PreSENTIA.

• Results should always be interpreted in conjunction with the patient’s personal and family history and other relevant clinical findings.
• Hereditary cancer. Genetic counselling is recommended before and after testing.

Following identification of a clinically significant variant, clinicians should consider:

• Providing or recommending referral for genetic counselling, where appropriate
• Confirming the clinical significance of the findings in the context of the patient’s personal and family history
• Recommending cascade testing for at-risk relatives, where a pathogenic or likely pathogenic variant is identified
• Implementing risk-adapted cancer surveillance in accordance with established clinical guidelines
• Discussing risk-reducing strategies or prophylactic interventions, where clinically appropriate
• Referring patients to relevant specialist services, including clinical genetics or oncology, when indicated

Genetic counselling is a specialised, patient-centred, impartial, and non-directive communication process that supports patients and their families both before and after genetic testing.

Prior to genetic testing, genetic counsellors obtain a detailed medical and family history and provide education on genetic concepts, the testing process, and available options, along with the potential risks, benefits, limitations, and possible outcomes.

Upon receiving genetic test results, genetic counsellors assist in interpreting the findings and guide individuals through the implications for their own personal health and that of their family members. During post-test counselling, genetic counsellors also provide evidence-based recommendations on next steps, including strategies for prevention, surveillance, and management.

The goal of genetic counselling is to empower patients through knowledge and tailored support, enabling them to make informed and voluntary decisions.

PreSENTIA uses targeted next-generation sequencing (NGS) technology combined with validated bioinformatic analysis to identify clinically relevant genetic variants associated with hereditary cancer syndromes. The assay has been extensively validated to provide accurate, reliable and reproducible analysis across the genes included in each panel.

PreSENTIA analyses the coding regions of the selected genes*, together with clinically relevant adjacent non-coding regions, to maximise the detection of disease-causing variants. The assay is designed to detect multiple clinically relevant variant types, including:

• Single nucleotide variants (SNVs)
• Small insertions and deletions (indels) up to 50 bp
• Copy number variants (CNVs)

Sequencing data are analysed using validated, multi-engine bioinformatic pipelines that support the accurate identification, classification and interpretation of clinically relevant variants. Variants are classified according to the recommendations of the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP). Only clinically relevant variants are reported, and all positive copy number variants are confirmed using an orthogonal method.

*Coverage exceptions apply to certain genes and genomic regions that present recognised technical limitations, including repetitive sequences, regions of high homology (such as pseudogenes and segmental duplications), or regions with extreme GC content.

• American College of Obstetricians and Gynecologists. Hereditary cancer syndromes and risk assessment: ACOG Committee Opinion No. 793. Obstet Gynecol. 2019;134(6). doi:10.1097/AOG.0000000000003562. PMID:.
• National Cancer Institute. Genetic testing for hereditary cancer syndromes [Internet]. Bethesda (MD): National Cancer Institute. Available from:
  Elliott AM, Friedman JM. The importance of genetic counselling in genome-wide sequencing. Nat Rev Genet. 2018;19(12):735-6. doi:10.1038/s41576-018-0057-3.
• PMID: .
• Yang M, Kim JW. Principles of genetic counseling in the era of next-generation sequencing. Ann Lab Med. 2018;38(4):291-5. doi:10.3343/alm.2018.38.4.291. PMID:; PMCID: PMC5895857