ModifiedUnitedHealthcarePolicy CS048NJ.R

Genetic Testing for Cardiac Disease (for New Jersey Only)

Policy governs coverage of multi-gene and related genetic testing for inherited cardiac arrhythmias, cardiomyopathies, and thoracic aortic disease for members in New Jersey. It addresses when testing is considered medically necessary, tests considered unproven, and applicable billing codes.

Policy Summary

PayerUnitedHealthcare

PolicyGenetic Testing for Cardiac Disease (for New Jersey Only)

Policy CodePolicy CS048NJ.R

Change TypeContent and operational updatesmaterial clarification

Effective DateJan 1, 2026

Next Review Date

Key ActionProvide documentation of clinical diagnosis, family history, and relevant diagnostic testing (ECG/Holter/exercise) to support prior authorization and coverage.

SourceLink

POLICY UPDATE CHANGES

Replaced language about genetic testing for cardiomyopathies, arrhythmias, or aortic vascular disease being unproven for all other indications with clarified wording that all other genetic testing for these conditions not listed as medically necessary is unproven and not medically necessary; noted exception for chromosome microarray analysis for isolated severe congenital heart disease.

Added language about medical records documentation requirements used for reviews, specifying documentation may be required to assess clinical criteria and listing required elements.

Added referenced links to related Medical Policies including Chromosome Microarray Testing (Non-Oncology Conditions), FDA Cleared or Approved Companion Diagnostic Testing, and Molecular Oncology Testing for Hematologic Cancer Diagnosis, Prognosis, and Treatment Decisions.

Updated Description of Services, Clinical Evidence, FDA, and References sections to reflect current information and archived previous policy version CS048NJ.Q.

NJGeographic scope

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

multi-geneCovered modality

NMNCAD genomic tests

CS048NJ.QArchived version

Coverage Criteria and Medical Necessity

inv-09: BrS - Index testing

BrS - Index testing — Brugada Syndrome (BrS) - Covered when ALL of the following are met:

ALL of the following

Index patient has a clinical diagnosis of Brugada syndrome (BrS) demonstrated by a Type I ECG pattern in standard or high precordial leads that is either spontaneous or drug-induced by sodium-channel blockade in the presence of supporting clinical features or a relevant family history.
Genetic testing includes sequencing of SCN5A (the primary gene associated with BrS) as part of a diagnostic evaluation for the index case.
Genes with disputed, refuted, or limited evidence for BrS clinical validity are excluded from routine diagnostic reporting; rare variants in such genes should not be reported routinely in a diagnostic setting.
Variant-specific or predictive testing is performed for family members only after identification of a disease-causative SCN5A pathogenic or likely pathogenic variant in the proband.
Predictive genetic testing of related children for pathogenic SCN5A variants may be offered from birth onward when a P/LP variant has been identified in the family.

Covered Indications and Eligibility

inv-95: Comprehensive list of diagnoses considered for coverage (hereditary arrhythmia syndromes, cardiomyopathies, HTAD).

Comprehensive list of diagnoses considered for coverage (hereditary arrhythmia syndromes, cardiomyopathies, HTAD).

Covered_diagnoses_list: Brugada syndrome; CPVT; LQTS; SQTS; Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C); Hypertrophic cardiomyopathy (HCM); Dilated cardiomyopathy (DCM); Left ventricular noncompaction (LVNC); Thoracic aortic disease/HTAD

These diagnoses are referenced as covered indications when criteria in the policy are met

inv-96: Index patients with high-probability clinical diagnosis (e.g., LQTS with Schwartz Score >=3.5; young unexplained cardiac arrest) — indications for testing

Index patients with high-probability clinical diagnosis (e.g., LQTS with Schwartz Score ≥3.5; young patients with unexplained cardiac arrest) — indications for testing

High_probability_index_patients: Index patients meeting high-probability diagnostic criteria for inherited arrhythmia syndromes (eg LQTS with Schwartz Score ≥3.5) or young patients with unexplained cardiac arrest or recurrent exertional syncope -> molecular testing of definitive genes recommended

Applicable Codes and Coding Guidance

Applicable CPT and Proprietary Codesmixed

0237U	Cardiac ion channelopathies (e.g., Brugada syndrome, long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia), genomic sequence analysis panel including ANK2, CASQ2, CAV3, KCNE1, KCNE2, KCNH2, KCNJ2, KCNQ1, RYR2 , and SCN5A, including small sequence changes in exonic and intronic regions, deletions, duplications, mobile element insertions, and variants in non-uniquely mappable regions.
0401U	Cardiology (coronary heart disease [CHD]), 9 genes (12 variants), targeted variant genotyping, blood, saliva, or buccal swab, algorithm reported as a genetic risk score for a coronary event.
0439U	Cardiology (coronary heart disease [CHD]), DNA, analysis of 5 single-nucleotide polymorphisms (SNPs) and 3 DNA methylation markers, qPCR and digital PCR, whole blood, algorithm reported as a 4-tiered risk score for a 3-year risk of symptomatic CHD.
0440U	Cardiology (coronary heart disease [CHD]), DNA, analysis of 10 single-nucleotide polymorphisms (SNPs) and 6 DNA methylation markers, qPCR and digital PCR, whole blood, algorithm reported as detected or not detected for CHD.
0466U	Cardiology (coronary artery disease [CAD]), DNA, genome-wide association studies (564,856 single-nucleotide polymorphisms [SNPs], targeted variant genotyping), patient lifestyle and clinical data, buccal swab, algorithm reported as polygenic risk to acquired heart disease.
81410	Aortic dysfunction or dilation (e.g., Marfan syndrome, Loeys Dietz syndrome, Ehler Danlos syndrome type IV, arterial tortuosity syndrome); genomic sequence analysis panel, must include sequencing of at least 9 genes, including FBN1, TGFBR1, TGFBR2, COL3A1, MYH11, ACTA2, SLC2A10, SMAD3, and MYLK.
81411	Aortic dysfunction or dilation (e.g., Marfan syndrome, Loeys Dietz syndrome, Ehler Danlos syndrome type IV, arterial tortuosity syndrome); duplication/deletion analysis panel, must include analyses for TGFBR1, TGFBR2, MYH11, and COL3A1.
81413	Cardiac ion channelopathies (e.g., Brugada syndrome, long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia); genomic sequence analysis panel, must include sequencing of at least 10 genes, including ANK2, CASQ2, CAV3, KCNE1, KCNE2, KCNH2, KCNJ2, KCNQ1, RYR2, and SCN5A.
81414	Cardiac ion channelopathies (e.g., Brugada syndrome, long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia); duplication/deletion gene analysis panel, must include analysis of at least 2 genes, including KCNH2 and KCNQ1.
81439	Hereditary cardiomyopathy (e.g., hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy), genomic sequence analysis panel, must include sequencing of at least 5 cardiomyopathy-related genes (e.g., DSG2, MYBPC3, MYH7, PKP2, TTN).

1–10 of 12

1/2

Regulatory/lab accreditation referencesmixed

No codes listed

No codes listed in referencesmixed

No codes listed

inv-42: Panel size

Panel sizePanels or microarray profiles with five or more genes

ScopeApplies to multi-gene NGS panels and microarray profiles used for cardiac-related syndromes

ExclusionsSingle-gene tests and panels with fewer than five genes are outside this specific panel-size threshold guidance

inv-43: Top risk quantile

Top risk quantileTop decile (highest 10%)

ContextUsed in studies of genome-wide polygenic scores for coronary artery disease (GPSCAD) to identify individuals at increased sudden-death risk

Provider Actions, Documentation, and Prior Authorization

Note

Genetic Counseling Recommended

Pre-test genetic counseling is strongly recommended to inform the person being tested about the advantages, limitations, and potential outcomes of genetic testing.

Prior Authorization

Prior Authorization and Laboratory Accreditation

Prior authorization may be required for multi-gene panel testing. Providers should verify benefit terms and obtain any required prior authorization before ordering testing. If prior authorization is required, testing must be performed by a CLIA-regulated laboratory and the request should include documentation of the clinical indication.

Check member benefit plan, state and federal mandates for coverage prior to testing.
If prior authorization is requested, include clinical documentation and confirm laboratory CLIA status.

Not Medically Necessary / Exclusions

Genetic tests and proprietary gene-expression or polygenic risk assays for coronary artery disease (CAD), gene expression profiling, and other cardiac genetic risk profiles are considered unproven and not covered. This includes the named proprietary assays and CPT/proprietary codes listed in the policy (for example, tests described by codes such as 0237U, 0401U, 0439U, 0440U, 0466U), and gene-expression/mRNA profiling for CAD.

Testing that includes genes with limited, disputed, or refuted evidence for disease causation—or excessively broad multi-gene panels performed without specific clinical justification—are not covered because they raise VUS rates and lack established clinical validity. The policy addresses panels and microarray profiles with five or more genes and recommends using curated, evidence-based gene lists for panel composition to avoid unnecessary uncertainty.

Routine testing for common single‑variant AF risk markers or panels intended for population-level AF risk prediction is not clinically useful and is not covered. The policy notes that searching for common AF-associated variants has not demonstrated clinical utility for individual management and should not be used for population risk prediction in clinical practice.

Direct-to-consumer cardiovascular genetic tests are cautioned against in routine clinical care because of variable quality, inconsistent methodology, limited oversight, and insufficient evidence of clinical utility. The AHA and this policy note that these tests lack standardized reporting and counseling and therefore are not considered appropriate for routine clinical management.

Genetic testing is not covered for isolated or incidental left ventricular noncompaction (LVNC) when left ventricular function is normal, there are no syndromic features, and there is no family history suggestive of inherited disease. Genetic testing may be appropriate for LVNC when a cardiologist has established the diagnosis and there are associated clinical or familial features, but isolated incidental LVNC without additional findings should not be tested.

Definitions and Diagnostic Thresholds

inv-79: First-Degree Relative

DefinitionParents, siblings, and offspring.

UseReferenced for determining at-risk relatives eligible for cascade or family-history–based testing

SourceNCCN definition cited in policy

inv-80: Second-Degree Relative

DefinitionHalf-siblings, aunts/uncles, grandparents, grandchildren, and nieces/nephews affected on the same side of the family.

UseUsed to establish eligibility for family-history–based testing when a second-degree relative is affected

Source

Background and Clinical Context

Inherited arrhythmias and cardiomyopathies are genetic disorders that affect cardiac ion channels or myocardial structure and can result in syncope, ventricular arrhythmia, heart failure, and sudden cardiac death. Genetic evaluation (including multi-gene NGS panels and, where appropriate, chromosome microarray analysis) can aid diagnosis, inform prognosis, and guide management and family screening when applied in patients with a compatible phenotype and adequate pre‑test probability.

Quick Provider Guidance

Documentation Required

Document pre‑test genetic counseling (strong recommendation)

Pre‑test genetic counseling is strongly recommended to discuss test advantages, limitations, and implications; document counseling in the medical record prior to or at the time of testing.

Counseling should be provided by qualified experts and documented; include counseling notes with authorization if available.

Note

Use identified causal gene to inform family screening and involve specialties/counseling

When a causal gene is identified, use results to guide family screening and clinical action; ensure appropriate genetic counseling and specialty involvement for management decisions related to HTAD and cardiomyopathies.

Document how identified variants will change management and the plan for cascade testing in the record.

Revision History and References

The reference sections in the policy excerpts list supporting literature, but no explicit additional coverage exclusions are stated in those reference entries beyond the policy’s exclusions and not‑medically‑necessary lists.

The referenced citation lists do not themselves include not‑medically‑necessary (NMN) statements; NMN language is provided in the policy body and exclusion lists rather than within the bibliographic reference entries.

2026-01-01Operational / related policies added

2026-01-01Material change — coverage rationale clarified

Policy Summary

PayerUnitedHealthcare

PolicyGenetic Testing for Cardiac Disease (for New Jersey Only)

Policy CodePolicy CS048NJ.R

Change TypeContent and operational updatesmaterial clarification

Effective DateJan 1, 2026

Next Review Date

Key ActionProvide documentation of clinical diagnosis, family history, and relevant diagnostic testing (ECG/Holter/exercise) to support prior authorization and coverage.

SourceLink

On This Page

Schwartz Score >= 3.5 or equivalent syndrome diagnostic scores

Also appropriate when syndromic features indicate single-gene testing

inv-97: Cascade/variant-specific testing for relatives after identification of a disease-causing variant in a proband

Cascade/variant-specific testing for relatives after identification of a disease-causing variant in a proband

Cascade_testing_after_proband_variant: When a pathogenic/likely pathogenic variant has been identified in a proband, variant-specific genetic testing is recommended for at-risk relatives; in LQTS and many arrhythmia syndromes, predictive testing in children is recommended from birth onwardany age (LQTS often from birth)

Variant-specific testing preferred over broad panels for relatives

inv-98: Index patients meeting diagnostic criteria for specific inherited arrhythmia syndromes or cardiomyopathies — phenotype-driven testing

Index patients meeting diagnostic criteria for specific inherited arrhythmia syndromes or cardiomyopathies — phenotype-driven testing

Phenotype_driven_index_testing: Index patients who meet diagnostic criteria for LQTS, CPVT, BrS, SQTS, familial AF, HCM, ACM/ARVC, or familial DCM -> gene sequencing/testing recommended with gene lists varying by condition as specified in guidelinesdiagnostic criteria per syndrome

Pre-test phenotyping (ECG, Holter, echo, exercise testing) and genetic counseling recommended

inv-99: Probands with confirmed or suspected inherited cardiomyopathy and at-risk family members after identification of a P/LP variant.

Probands with confirmed or suspected inherited cardiomyopathy and at-risk family members after identification of a P/LP variant.

Cardiomyopathy_probands_and_relatives: Probands with confirmed or suspected HCM, DCM, ACM, or LVNC -> genetic testing recommended per condition-specific first-tier gene lists; predictive testing of relatives via variant-specific assays when a P/LP variant is identified

Document three-generation family history and provide genetic counseling

inv-100: Comprehensive genetic testing for patients with phenotypic features of ACM (including post-mortem cases).

Comprehensive genetic testing for patients with phenotypic features of ACM (including post-mortem cases).

ACM_comprehensive_testing: Recommend comprehensive genetic testing for patients with phenotypic ACM, including post-mortem cases; include first-tier definitive genes and consider testing the most severely affected family member first in multiaffected families

Variant-specific testing for relatives and predictive testing in children (>10–12 years) recommended

inv-101: Genetic testing for probands with DCM and family history of DCM...

Genetic testing for probands with DCM and family history of DCM, for DCM with family history of premature unexpected sudden death, or with clinical features suggestive of a specific genetic disease.

DCM_proband_testing: Recommend genetic testing for probands with DCM and family history of DCM or premature unexpected sudden death, or when clinical features suggest a genetic etiology (eg conduction disease, severe systolic dysfunction, malignant arrhythmia)

Initial tier should include genes with definitive/strong evidence (BAG3, DES, FLNC, LMNA, MYH7, PLN, RBM20, SCN5A, TNNC1, TNNT2, TTN, DSP)

inv-102: Genetic testing for patients with a cardiologist-established clinical diagnosis of LVNC or LVNC with syndromic features.

Genetic testing for patients with a cardiologist-established clinical diagnosis of LVNC or LVNC with syndromic features.

LVNC_testing_recommendation: Genetic testing may be useful for patients with cardiologist-established LVNC phenotype or LVNC with syndromic features; do not perform testing for isolated incidental LVNC with normal LV function, no syndromic features, and no family history

Variant-specific testing for relatives after identification of P/LP variant recommended

inv-103: Genetic testing for individuals with thoracic aortic aneurysm or dissection who have risk factors for HTAD...

Genetic testing for individuals with thoracic aortic aneurysm or dissection who have risk factors for HTAD or clinical features suggestive of syndromic aortopathy.

HTAD_testing_indications: Individuals with thoracic aortic root/ascending aneurysm or dissection and risk factors for HTAD or syndromic features -> genetic testing to identify P/LP variants is recommended; obtain multigenerational family history and provide genetic counseling

Panel testing typically includes established HTAD genes (eg FBN1, TGFBR1/2, SMAD3, TGFB2, ACTA2, MYH11, MYLK, LOX, PRKG1)

inv-104: Evaluation for heritable thoracic aortic aneurysm/dissection where syndrome features or family history suggest HTAD

Evaluation for heritable thoracic aortic aneurysm/dissection where syndrome features or family history suggest HTAD

HTAD_evaluation: When syndrome features or family history suggest HTAD, perform targeted gene testing or multi-gene panel including ClinGen/AHA-listed genes with strong evidence; identification of causal gene should guide management and family screening

Recognize that many non-syndromic families remain gene-negative (~70%)

inv-105: Inherited cardiomyopathies and arrhythmia syndromes (e.g., HCM, DCM, ARVC/ACM, LQTS, Brugada, CPVT) referenced as contexts where genetic testing is evaluated.

Inherited cardiomyopathies and arrhythmia syndromes referenced as contexts where genetic testing is evaluated.

Referenced_conditions: HCM, DCM, ARVC/ACM, LQTS, Brugada, CPVT and related inherited cardiovascular conditions are contexts in which genetic testing is evaluated and may be covered when policy criteria are met

These contexts are supported by guideline and GeneReviews citations

Eligibility for genetic testing is determined by the specific clinical criteria in this policy. Generally, testing is reserved for index patients with a diagnostic or high-probability phenotype, and for at‑risk family members when a pathogenic/likely pathogenic (P/LP) variant has been identified. Detailed, condition-specific criteria (e.g., LQTS Schwartz Score thresholds, cardiomyopathy phenotypes, and family-history requirements) are provided in the condition sections of the policy and must be met to support coverage.

For Long QT Syndrome (LQTS), acquired causes of QT prolongation (for example, electrolyte abnormalities, interacting medications, or structural heart disease) must be excluded before offering molecular genetic testing. When a familial pathogenic/likely pathogenic variant is known in the family, relatives should be offered variant-specific (single-site) testing rather than repeat broad panel testing; predictive testing of related children may be recommended from birth onward in many arrhythmia syndromes.

ImplicationTop-decile status was associated with higher absolute and relative risk in cohort analyses, but clinical utility requires further research

Check Benefit Terms / Potential Prior Authorization

Benefit coverage is determined by the federal, state, or contractual requirements and applicable laws. Medical records documentation may be required to assess whether the member meets clinical criteria for coverage but does not guarantee coverage.

Verify applicable benefit terms before use of this policy.
UnitedHealthcare may use third-party criteria tools to assist in benefit administration.

Denial Risk

Phenotype Required for Arrhythmia Genetic Testing

Genetic testing should be driven by phenotype and pre-test probability. For inherited arrhythmia syndromes, a diagnostic ECG or other disease-specific diagnostic criteria should be present before testing; testing without a diagnostic phenotype is discouraged.

Genetic testing for arrhythmia syndromes is generally not recommended without diagnostic ECG evidence or high pre-test probability.
Pre-test probability tools and documented phenotyping should guide gene selection.

Note

Larger Panels Increase VUS Rates

Larger gene panels may increase the detection rate of pathogenic/likely pathogenic variants but also increase the frequency of variants of uncertain significance (VUS), which can limit clinical utility and lead to uncertain results.

Consider targeted or tiered testing when the phenotype strongly suggests a limited set of genes.
Discuss VUS likelihood with the patient during pre-test counseling.

Documentation Required

Required Clinical Documentation and Phenotyping

Clinical documentation must support the medical necessity of testing. Documentation should include the proband's clinical history, disease-appropriate phenotyping, a three-generation family history, and results of relevant diagnostic testing (e.g., ECG, Holter, exercise testing, echocardiography, MRI). When applicable, include diagnostic scores (e.g., Schwartz Score for LQTS) and focused cardiovascular examination findings.

Three-generation pedigree and family history.
Documented clinical phenotype, relevant diagnostic test results (ECG, Holter, echo, MRI).
Diagnostic scoring when relevant (e.g., Schwartz Score ≥ 3.5 for LQTS).
Document genetic counseling when performed.

Denial Risk

Excluded Scenario for LVNC and Denial Triggers

Specific scenarios are excluded or discouraged: genetic testing should not be performed for isolated (incidental) LVNC with normal LV function, no syndromic features, and no family history. Failure to document a confirmed or suspected diagnosis of an inherited cardiomyopathy or relevant family history may result in non-coverage.

Isolated incidental LVNC with normal LV function, no syndromic features, and no family history — do not perform genetic testing.
Lack of documented clinical indication or family history may trigger non-coverage.

Note

Familial Variant and Cascade Testing Expectation

When a familial pathogenic or likely pathogenic variant is known, variant-specific (single-site) testing of at-risk relatives (cascade testing) is recommended rather than broad panel testing. Cascade (targeted) testing should be offered to first-degree relatives after identification of a P/LP variant in the proband.

Perform testing of the most severely or earliest affected family member first when multiple affected relatives exist.
Offer targeted variant testing to at-risk relatives (cascade testing) after a proband variant is identified.

Denial Risk

Denial Triggers and Unproven Tests

Denial or non-coverage may occur when services do not meet the policy's clinical criteria or lack sufficient medical record documentation. Tests not listed as medically necessary in this policy are considered unproven.

Services lacking required clinical documentation may be denied.
Genetic tests for coronary artery disease and other unproven gene expression/genetic profile tests for cardiac disease are not medically necessary.

Note

Step Therapy / Utilization Management

No specific step therapy rules are described in this policy excerpt. Providers should follow standard utilization management processes as applicable and check benefit terms for any additional requirements.

UnitedHealthcare reserves the right to modify policies and may use third-party tools to administer benefits.

Routine use of genomic risk scores, polygenic risk scoring, or gene expression profiling to predict coronary artery disease is not supported by current evidence and is not covered. Major society statements note that while PRS and gene-expression approaches show associations with CAD, their clinical actionability, standardization, and incremental benefit over traditional risk factors remain unproven.

Any genetic testing for cardiomyopathies, arrhythmias, or aortic vascular disease that is not explicitly identified as medically necessary in the policy is considered unproven and therefore not covered. Providers should confirm that the requested test and the genes included align with the policy’s listed covered indications before proceeding; documentation supporting clinical indication and family history is expected.

NCCN definition cited in policy

inv-81: Schwartz Score

DefinitionDiagnostic criteria for long QT syndrome using ECG findings, clinical history, and family history; total score classifies low, intermediate, or high probability.

Scoring thresholds≤1.0 = low probability; 1.5–3.0 = intermediate probability; ≥3.5 = high probability (supports molecular testing)

ComponentsIncludes ECG features (QTc intervals, torsades de pointes, T-wave abnormalities), clinical history (syncope), and family history

inv-82: Prolonged QTc

DefinitionProlonged QTc on ECG diagnostic for LQTS: QTc >470 msec (males) or >480 msec (females).

Clinical roleUsed as an objective ECG criterion to support a diagnosis of congenital LQTS prior to genetic testing

NotesSome individuals with LQTS may not demonstrate ECG changes (10–40% may be ECG-negative)

inv-85: CPVT diagnostic score

DefinitionCPVT diagnostic score — a scoring metric for catecholaminergic polymorphic ventricular tachycardia used to stratify diagnostic certainty.

ThresholdScores >3.5 indicate diagnostic-level phenotype warranting molecular genetic testing

Clinical useGuides decision to perform molecular testing of established CPVT-susceptibility genes (eg, RYR2, CASQ2, CALM1-3, TRDN, TECRL)

inv-86: Proband

DefinitionProband — the index case in a family who is the first to be identified and tested for a genetic condition.

RoleTesting the proband is the preferred first step before cascade or variant-specific testing of relatives

DocumentationProband clinical history, phenotype, and test results should be documented to support subsequent family testing

inv-87: Cascade testing

DefinitionCascade testing — targeted, variant-specific genetic testing of relatives after a disease-causative variant is identified in the proband.

Preferred approachVariant-specific testing is recommended for at-risk relatives rather than repeat broad multi-gene panels when a familial P/LP variant is known

Accompanying stepsClinical screening (ECG, echocardiography) is recommended as first-line for relatives alongside or prior to genetic testing

inv-88: Genetic proband

DefinitionGenetic proband — in families with multiple affected members, the most severely and/or earliest-affected individual prioritized for genetic testing.

RationaleTesting the genetic proband maximizes the likelihood of identifying a disease-causing variant for cascade testing

Guideline supportRecommended in ACM guidance and HFSA/ACMG statements for cardiomyopathies

inv-89: P/LP variant

DefinitionP/LP variant — a pathogenic or likely pathogenic genetic variant for which cascade testing of at-risk relatives is recommended.

ImplicationIdentification of a P/LP variant in a proband warrants variant-specific testing and clinical screening of relatives

DocumentationClassification should follow accepted variant interpretation standards (eg, ACMG guidelines) as referenced by policy sources

inv-90: HTAD

DefinitionHTAD — Heritable thoracic aortic aneurysms and dissections.

Clinical relevanceIdentification of causal genes can guide clinical management and family risk assessment despite ~70% of non‑syndromic families testing negative

Common genesAHA lists multiple strong/definitive HTAD genes used in panels (eg, FBN1, TGFBR1/2, ACTA2, MYH11)

inv-91: Polygenic risk score (PRS)

DefinitionPolygenic risk score (PRS) — a genome-wide polygenic score for coronary artery disease (GPSCAD/PRS) used to quantify inherited polygenic risk.

Study contextPRS top-decile has been associated with higher sudden-death risk in cohort analyses, but clinical utility is not established and requires further research

Policy stanceEvidence is insufficient to support routine clinical use of PRSs for CAD risk prediction according to the policy excerpts

inv-92: Multigene Test

DefinitionMultigene Test — term referenced to the National Cancer Institute Dictionary of Genetics Terms (contextual definition).

ApplicationRefers to tests that evaluate multiple genes simultaneously (eg, disease-specific NGS panels), as discussed in policy

SourceNCI Dictionary cited in policy references

inv-93: Genotype-phenotype correlation

DefinitionGenotype–phenotype correlation — the relationship between specific genetic variants and clinical manifestations in cardiac disease.

UtilityUsed to inform prognosis and management decisions (eg, certain gene/variant combinations predict adverse events or milder courses in LVNC/HCM)

EvidenceDiscussed in systematic reviews and guideline documents referenced in the policy (eg, van Waning et al.)

inv-94: Gene validity

DefinitionGene validity — evaluation of the evidence supporting a gene's role in a specific cardiac condition (definitive/strong vs. disputed/refuted).

Policy implicationGenes with disputed or limited evidence should be excluded from first-tier panels to reduce VUS and improve clinical utility

Source evidencePolicy cites gene-validity evaluations and guideline-based gene lists to define first-tier testing

Revised coverage rationale to state that all other genetic testing for cardiomyopathies, arrhythmias, or aortic vascular disease not listed as medically necessary is unproven and not medically necessary, and explicitly noted an exception for chromosome microarray analysis for isolated severe congenital heart disease.

2026-01-01Material addition — documentation requirements

Added language specifying medical records documentation expectations used for reviews, including that documentation may be required to assess clinical criteria and listing required elements; noted that documentation does not guarantee coverage.

2026-01-01Operational — content updates and archivalLatest

Updated Description of Services, Clinical Evidence, FDA, and References sections to reflect current information and archived prior policy version CS048NJ.Q.

Consistent with the policy’s general coverage rationale, testing not listed as medically necessary is considered unproven and not medically necessary. In addition, the policy clarifies documentation expectations for medical-record review: clinical history, family history, focused diagnostic testing (e.g., ECG, Holter, exercise testing), and evidence of genetic counseling may be required to substantiate medical necessity, although documentation does not guarantee coverage.

Genomic risk scores and gene expression testing for coronary artery disease currently lack established clinical actionability. Society statements and systematic reviews identify methodological limitations, transferability issues across ancestries, and insufficient evidence that these tests change management or outcomes; therefore they are not considered established, actionable testing for routine clinical use.