Why is genetic testing important?

Why Genetic Testing Matters

Genetic testing provides critical clinical utility by enabling precise diagnosis, guiding treatment decisions, preventing disease in at-risk family members, and informing reproductive planning—benefits that extend far beyond the individual tested to families and society. 1

Core Clinical Benefits for Patients

Diagnostic Precision and Medical Management

• Establishing an etiologic diagnosis prevents unnecessary testing, provides anticipatory guidance, and enables specific treatment strategies even when immediate therapy is unavailable. 1
• Genetic diagnosis allows for gene-specific management recommendations that can be life-saving—for example, distinguishing sarcomeric hypertrophic cardiomyopathy from LAMP2, PRKAG2, or PTPN11-related cardiac hypertrophy, which require entirely different clinical approaches. 1
• In cardiomyopathy specifically, genetic testing enables prognostication and guides critical interventions like ICD placement for primary prevention in LMNA pathogenic variant carriers with DCM or asymptomatic male ARVC carriers. 1

Disease Prevention and Early Intervention

• Genetic testing identifies medically actionable findings that enable life-saving interventions for both patients and their at-risk relatives. 1
• Early treatment of presymptomatic carriers improves outcomes and decreases hospitalization and death from conditions like heart failure. 1
• Testing ends the costly "diagnostic odyssey" that burdens patients psychologically and financially while wasting healthcare resources. 1

Critical Family and Reproductive Implications

Cascade Screening Benefits

• At-risk family members can obtain testing to determine if they carry causative mutations, enabling early intervention before disease develops. 1
• Genetic testing and cascade screening for conditions like HCM have proven cost-effective in both Australia and the United States. 1
• The American College of Medical Genetics and Genomics emphasizes that enabling disease avoidance in families should be considered overt medical utility, not merely "personal" utility. 1

Reproductive Decision-Making

• Genetic diagnosis enables specific and informed reproductive decision-making and family planning. 1
• Testing provides accurate recurrence risk information for families and affected individuals. 1

Broader Healthcare System Value

Research and Clinical Trial Access

• A specific diagnosis is commonly required for patients to participate in clinical trials, and without etiologic diagnosis, patients remain disenfranchised from research opportunities. 1
• Understanding disease etiology propels research and increases clinical trial accrual, benefiting society as a whole. 1

Psychosocial and Support Benefits

• Genetic diagnosis enables involvement in disease support groups and provides social support for families. 1
• Testing brings resolution to the diagnostic uncertainty that creates substantial psychological burden. 1

Pharmacogenetic Applications

Personalized Drug Therapy

• Genetic testing guides drug selection and dosing to improve efficacy and avoid adverse effects. 1
• The Clinical Pharmacogenetics Implementation Consortium has published 36 pharmacogenetic drug guidelines covering variants in 15 genes with strong clinical evidence. 1
• Testing identifies individuals at risk of severe idiosyncratic adverse events, enabling alternative treatment strategies. 1

Important Caveats

Interpretation Challenges

• Variant interpretation remains challenging in non-Caucasian, non-northern European populations due to limited representation in reference databases. 1
• Results may include variants of uncertain significance (VUS) that require careful counseling and may need reinterpretation over time. 1

Testing Strategy

• Testing should ideally begin with the family member who has the most definitive diagnosis and severe manifestations to maximize diagnostic yield. 1
• Trio testing (parents and patient) reduces variants requiring interpretation and minimizes false-positive results. 1

Beyond Individual Benefit

The ACMG explicitly rejects the narrow view that clinical utility only applies to the individual tested, asserting that genetic information's value extends to families and society through disease prevention, reproductive planning, and research advancement. 1 This represents a fundamental shift from traditional medical models that focus solely on treating existing disease in individual patients.