Genetic testing analyzes a person’s deoxyribonucleic acid (DNA) to identify changes in the genetic code that may influence health or disease risk. Germline genetic testing focuses on the inherited genetic information passed down from parents to children through reproductive cells. Understanding this inherent blueprint provides insights into an individual’s predisposition to certain health conditions that may run in a family.
Germline vs. Somatic Testing
Germline and somatic testing analyze genetic material differently, based on the origin and heritability of the DNA changes they detect. Germline variants are present in every cell of the body because they originated in the egg or sperm cell from which the person developed. These changes are inherited from a parent and can be passed down to one’s children, making them the focus of hereditary risk assessment. Germline testing typically uses a sample of non-affected tissue, such as blood, saliva, or a cheek swab, because the inherited DNA sequence is uniform across all cells.
In contrast, somatic variants are acquired changes that occur in a single cell after conception and are not inherited. These changes are commonly found in tumor cells, driving cancer development, which is why somatic testing is often called tumor testing. The somatic change is only present in the tumor tissue and cannot be passed on to offspring. Somatic testing requires a sample of the affected tissue, such as a biopsy, to identify these specific mutations that guide treatment decisions for a current disease.
The distinction is significant: a germline change is an inherited blueprint flaw, while a somatic change is an acquired modification. Although some tumor testing can incidentally detect a germline variant, confirming its nature requires a separate test on a blood or saliva sample. Identifying an inherited germline variant is important for the individual’s health management and for assessing the risk to their close biological relatives.
Primary Reasons for Testing
Germline testing is used in several clinical scenarios to understand an individual’s genetic risk for hereditary conditions.
Diagnostic Testing
This testing aims to confirm or rule out a suspected hereditary condition in a person already experiencing symptoms. It is used when a patient’s clinical presentation aligns with a known genetic syndrome, such as Lynch syndrome or Marfan syndrome. Pinpointing the genetic cause refines the diagnosis and informs specific treatment or management strategies.
Predictive or Pre-symptomatic Testing
This is performed on healthy individuals who have a strong family history of a hereditary condition. The purpose is to assess the future risk of developing a disease that may manifest later in life, such as inherited breast or ovarian cancer associated with BRCA1 and BRCA2 gene variants. Finding a pathogenic variant allows the person to implement enhanced surveillance or risk-reducing interventions.
Carrier Screening
Carrier screening determines if a person carries a gene variant that could be passed on to their children, even if the person is healthy. This is relevant for family planning, as it identifies couples at increased risk of having a child with a recessive genetic disorder like cystic fibrosis. Identifying carrier status allows prospective parents to receive genetic counseling and consider options for managing reproductive risk.
The Testing Procedure
The process for germline genetic testing begins with a pre-test consultation with a genetic counselor or trained healthcare provider. The counselor reviews the patient’s personal and family health history to determine the appropriate test. They also discuss the potential outcomes, risks, and benefits to ensure informed consent, helping the patient understand the implications before testing.
Sample collection is a simple, non-invasive process, often involving a blood draw or saliva sample. These samples contain the cells harboring the individual’s complete germline DNA sequence. The collected sample is sent to a specialized laboratory, where technicians isolate the DNA and use sequencing technology to read the specific genes or regions being analyzed.
The entire process, from collection to final report, typically takes several weeks. Once the laboratory analysis is complete, the results are sent back to the ordering provider or genetic counselor. A post-test consultation is then scheduled to interpret the findings and discuss the implications for the patient’s medical management and family members.
What the Results Reveal
Germline genetic testing yields one of three results, each carrying distinct clinical meaning.
Positive Result
A positive result indicates that a pathogenic or likely pathogenic variant was found in one of the genes tested. This change is known to increase disease risk. While it signifies a predisposition, it generally cannot predict the exact age a condition might manifest or if it will develop at all. It triggers the need for a personalized medical management plan and has implications for the patient’s first-degree relatives, who have a fifty percent chance of carrying the same variant.
Negative Result
A negative result means that no known pathogenic variant was identified in the genes analyzed. This is often reassuring, but it does not equate to a zero lifetime risk of disease, as it does not account for all genetic causes or non-genetic factors. If a pathogenic variant is already known in the family, a negative result confirms the individual did not inherit that specific familial variant, significantly reducing their risk.
Variant of Unknown Significance (VUS)
A VUS represents a change in the DNA sequence that has not been classified as either disease-causing or harmless. VUS results are common, especially with large multi-gene panel testing, and present a challenge due to insufficient evidence to determine their clinical impact. In most cases, a VUS is eventually reclassified as benign. Until that determination is made, it is generally considered non-actionable, and medical management relies on personal and family history alone. Post-test genetic counseling helps the patient understand the nuances of all results.