Genetic Testing & Coverage Glossary
Plain-English definitions of the terms that decide whether a genetic test is ordered correctly and paid for. Written for ordering clinicians, genetic counselors, molecular labs, and revenue-integrity teams — not consumers. Each entry stands on its own, so you can link to any single term.
ACMG (American College of Medical Genetics and Genomics)
The professional body whose variant-classification framework (Pathogenic, Likely Pathogenic, Uncertain Significance, Likely Benign, Benign) is the standard for interpreting genetic variants. ACMG also publishes clinical testing guidance.
Cascade testing
Testing the biological relatives of a person found to carry a pathogenic variant. One positive result can identify at-risk family members who were never patients — a major reason genetic results extend beyond the individual.
Carrier screening
Testing to determine whether a person carries a variant for a recessive or X-linked condition (e.g., cystic fibrosis). Relevant to reproductive planning; coded and covered differently from diagnostic testing.
CLIA (Clinical Laboratory Improvement Amendments)
The U.S. federal standards a laboratory must meet to run clinical tests. Medicare coverage of genetic testing requires the test to be performed in a CLIA-certified laboratory.
Clinical utility
Evidence that a test's result actually changes patient management or outcomes. Payers (and MolDX) require demonstrated clinical utility — not just accuracy — to consider a test "reasonable and necessary."
Clinical validity
How well a test result predicts the presence, absence, or risk of a condition. Distinct from analytical validity (whether the assay measures what it claims) and clinical utility (whether it changes care).
Companion diagnostic
A test that identifies patients likely to benefit from (or be harmed by) a specific drug. Often the basis for Medicare coverage of somatic tumor sequencing under NCD 90.2.
CPIC (Clinical Pharmacogenetics Implementation Consortium)
An international consortium that publishes peer-reviewed, evidence-based guidelines for gene–drug pairs — how a patient's genotype should inform prescribing. The evidence base behind credible pharmacogenomic decision support.
DEX Z-Code
A unique identifier assigned through the DEX Diagnostics Exchange registry that specifies exactly which molecular test was performed. In MolDX regions, molecular-test claims generally must carry the correct Z-Code to be paid. See Medicare coverage for genetic testing.
GenCC (Gene Curation Coalition)
A coalition that harmonizes gene–disease validity assertions across major curation groups, so labs and clinicians can see a consolidated view of how strongly a gene is linked to a condition.
Gene–disease validity
The strength of scientific evidence that variation in a particular gene causes a particular disease (classified from Definitive down to Disputed/Refuted). A well-built panel only includes genes with established validity. See ClinGen and GenCC.
Germline vs. somatic
Germline variants are inherited and present in every cell (relevant to hereditary risk and cascade testing). Somatic variants are acquired, typically within a tumor (relevant to treatment selection). Coverage rules and codes differ for each.
ICD-10-CM
The U.S. diagnosis code set. On a genetic-testing claim, the ICD-10-CM code establishes medical necessity — the documented reason the test was needed. See ICD-10 codes for genetic testing.
LCD (Local Coverage Determination)
A coverage rule issued by a Medicare Administrative Contractor (MAC) for its region when no national rule applies. Its Billing & Coding article lists the CPT and ICD-10-CM codes the MAC accepts. Most genetic tests are governed by LCDs.
Letter of Medical Necessity (LMN)
A physician's written justification explaining why a specific test is medically necessary for a specific patient — frequently required for prior authorization or appeals of genetic-testing denials.
MAC (Medicare Administrative Contractor)
A regional private company that processes Medicare claims and issues LCDs. The patient's geography determines the MAC — and therefore which local coverage rules apply.
Medical necessity
The payer standard that a service is appropriate and needed for the diagnosis or treatment of a condition. For genetic testing, medical necessity is proven by linking the test to a documented, matching diagnosis code and a covered indication.
MolDX
A program (developed by Palmetto GBA, used by several MACs) that identifies molecular diagnostic tests, sets coverage, and determines reimbursement — including the DEX Z-Code and Technical Assessment process. See Medicare coverage.
NCCN (National Comprehensive Cancer Network)
An alliance of cancer centers whose guidelines include widely referenced testing criteria for hereditary cancer syndromes. Payers often align hereditary-cancer coverage to NCCN criteria.
NCD (National Coverage Determination)
A Medicare coverage rule that applies nationwide; MACs must follow it. NCD 90.2 is the key one for next-generation sequencing in cancer.
NGS (Next-Generation Sequencing)
High-throughput sequencing that reads many genes (or a whole exome/genome) at once. Its Medicare coverage in cancer is set by NCD 90.2.
PanelApp
A crowdsourced, expert-reviewed knowledge base (originated by Genomics England) that rates genes for a condition as green/amber/red — used to keep gene panels evidence-based.
Pharmacogenomics (PGx)
The study of how a person's genes affect their response to drugs. Actionable PGx pairs a gene with a specific medication (e.g., CYP2C19 and clopidogrel). See pharmacogenomic decision support.
Prior authorization (PA)
A payer's requirement to approve a test before it is performed. Missing or mismatched documentation at the PA stage is a leading cause of genetic-testing denials.
Utilization management (UM)
The processes that ensure tests are ordered appropriately, coded correctly, and supported by medical necessity before a sample is run — reducing avoidable denials and inappropriate testing.
Variant of uncertain significance (VUS)
A genetic variant whose effect on disease risk is not yet established. A VUS is generally not, by itself, a basis for changing clinical management.
This glossary is educational and simplified; definitions of coverage terms reflect general 2026 usage and vary by payer and over time. Verify specifics against current CMS/MAC policy and professional guidelines.