Practice-Based Insights into Adult Genetic Medicine: High Diagnostic Yield, Indication-Specific Results, and Patterns of Test Utilization across 10,000 Patient Encounters

Abstract

Genetic medicine has become a routine component of clinical care, yet the evidence guiding its implementation remains heavily weighted toward pediatric populations, with limited practice-level data to inform adult referral pathways, test selection, or service delivery. We analyzed eight years of electronic health record (EHR)-linked data from a high-volume adult genetics clinic (9,867 visits) within a major academic health system to define referral patterns, test utilization, and genetic testing outcomes across indications and demographic groups. While most visits were in-person and led by a genetics-trained physician, genetic counselor-only visits accounted for 12% of all encounters and telemedicine remained a substantial component of follow-up care, comprising 39% of follow-up visits from 2023 onward. Genetic testing was ordered for 52% of all new patients, with significant indication-specific variation in ordering propensity. Overall, 24% of all tests returned a diagnostic result. Diagnostic yield differed markedly by testing modality: exome sequencing yielded diagnoses in 40% of patients, whereas next-generation sequencing panels, the most frequently ordered testing type, yielded diagnoses in only 16%. Although diagnostic yield declined with increasing patient age, it remained above 17% in every age stratum, with the yield of exome/genome sequencing remaining above 30% across all age groups. Outcomes varied significantly by referral indication, with some indications yielding significantly high rates of pathogenic findings, and others more often yielding negative or uncertain results. Operational factors significantly shaped practice: test type and laboratory utilization shifted significantly over time in step with payer and testing lab policy changes. Together, these practice-based data establish adult genetics as a high-yield and important clinical domain. Our findings provide actionable evidence to inform age- and indication-aware triage, guide workforce planning, promote adult-focused practice guidelines, better inform payor reimbursement policies, and advance the integration of genomic medicine into routine adult patient care.