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    v1.0.28
    OpenPayerPolicy UpdatesGenetic & Molecular TestingProvidence Genetic Testing Coverage Update | OpenP…
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    ModifiedProvidence Health PlanPolicy 215

    Genetic and Molecular Testing

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    This policy governs medical necessity and coverage criteria for genetic and molecular testing for Providence Health Plan, Providence Health Assurance, and Providence Plan Partners, including commercial and Medicaid/OHP members. Medicare members are subject to this policy only when directed by a separate Medicare policy.

    Policy Summary
    PayerProvidence Health Plan
    PolicyGenetic and Molecular Testing
    Policy CodePolicy 215
    Change TypeModified
    Effective DateOct 1, 2026
    Last ReviewSep 1, 2026
    Next Review DateOct 1, 2026
    Key ActionFor an unlisted code submitted for a potentially covered service addressed by this policy, prior authorization is recommended to avoid post-service denial.
    SourceLink
    POLICY UPDATE CHANGES

    The October 2026 revision includes a Q3 2026 code set update.

    The policy revision history documents prior additions of criteria for inherited peripheral neuropathies and connective tissue disorders.

    6Specific clinical testing indications addressed
    4General medical necessity criteria required
    3Explicit repeat or insufficient-utility testing exclusions
    4Familial hypercholesterolemia genes specifically permitted
    6Clinical utility components evaluated
    FDA/CLIARequired test or laboratory standard

    General and Condition-Specific Coverage Criteria

    General medical necessity criteria

    Genetic and molecular testing may be considered medically necessary when all of the following criteria are met.

    General medical necessity

    • Genetic counseling: General genetic counseling requirements have been met.

    • Clinical or family-history qualification

      • Symptomatic individual: The patient is symptomatic and the clinical presentation is consistent with a known condition.
      • Asymptomatic individual: The individual has a first-degree blood relative diagnosed with the condition who has not had genetic testing and is unavailable for testing, or testing is for a known pathogenic variant confirmed in an affected first-degree blood relative.
    Policy Summary
    PayerProvidence Health Plan
    PolicyGenetic and Molecular Testing
    Policy CodePolicy 215
    Change TypeModified
    Effective DateOct 1, 2026
    Last ReviewSep 1, 2026
    Next Review DateOct 1, 2026
    Key ActionFor an unlisted code submitted for a potentially covered service addressed by this policy, prior authorization is recommended to avoid post-service denial.
    SourceLink
    On This Page
    General and Condition-Specific Coverage CriteriaCovered Clinical IndicationsEligibility and Testing RequirementsCoding and Test SpecificationsProvider Submission and Review RequirementsPolicy BackgroundDefinitionsNon-Covered Services and Testing
  1. Disease severity: The condition being tested for is associated with increased morbidity or reduced life expectancy.

  2. Clinical utility

    • Diagnostic or risk-classification value: Testing allows a definitive diagnosis or risk classification when other clinical or laboratory tests were inconclusive, or avoids more invasive diagnostic testing.
    • Management value: Testing results will guide clinical management decisions, including predictive, diagnostic, prognostic, or therapeutic decisions.

    3. Connective tissue disorders

    Connective tissue disorder testing may be considered medically necessary when all of the following are met.

    • General criteria: Criterion I is met.
    • Clinical or familial indication: Testing is used to diagnose a member with specific signs and symptoms of a connective tissue disorder, or testing is for an asymptomatic member when there is a known pathogenic variant in the family.

    Familial hypercholesterolemia

    Familial hypercholesterolemia testing may be considered medically necessary when all of the following are met.

    • General criteria: Criterion I is met.
    • Permitted genes: Testing is limited to APOB, LDLR, LDLRAP1 and/or PCSK9, as single genes or in any combination.
    • Suggestive clinical findings: Signs and symptoms are suggestive of familial hypercholesterolemia, but a molecular diagnosis has not yet been established.

    Hereditary peripheral neuropathies

    Targeted panel testing for an inherited peripheral neuropathy may be considered medically necessary when all of the following are met.

    • General criteria: Criterion I is met.
    • Neuropathy findings: The individual has signs and/or symptoms of an inherited peripheral motor or sensory neuropathy.
    • Diagnostic or reproductive-planning need: A definitive clinical diagnosis cannot be made, or a genetic diagnosis is needed to inform reproductive planning.

    Hypopituitarism

    Testing for growth hormone deficiency, hypopituitarism, or combined pituitary hormone deficiency may be medically necessary when the following criteria are met.

    • General criteria: All of Criterion I is met.
    • Multiple hormone deficiencies: The member has growth hormone deficiency and at least one other pituitary hormone deficiency.

    Macrocephaly and overgrowth

    Overgrowth and macrocephaly gene testing may be considered medically necessary when all of the following are met.

    • General criteria: Criterion I is met.
    • Macrocephaly definition: The child has an occipitofrontal circumference above the 97th percentile for age, sex and gestation; progressive enlargement on serial measurements; or, if younger than 6 months, an increase greater than 2 cm (0.8 inches) per month.

    • Syndromic or neurologic findings

      • Suggestive syndromic features: The child has history or physical-examination features suggesting a multisystem or syndromic diagnosis, such as neurocutaneous findings, cutaneous or oral fibromas, or hemangiomas.
      • Neurologic and imaging findings: The child has neurologic abnormalities or delayed development requiring intervention, and neuroimaging identifies enlarged cerebral structures.

    Non-syndromic forms of hearing loss

    Comprehensive genetic testing or next-generation sequencing for diagnosing hearing loss in children may be considered medically necessary when the following criteria are met.

    Nonsyndromic pediatric hearing loss

    • Bilateral sensorineural hearing loss: The child has bilateral sensorineural hearing loss without syndromic findings.
    • General criteria: Criterion I is met.

    Not medically necessary testing

    Testing is considered not medically necessary in the following circumstances.

    • Insufficient clinical utility: Insufficient evidence demonstrates clinical utility for the testing target or strategy.
    • Criteria not met: The applicable coverage criteria are not met.
    • Repeat germline testing: The same germline genetic content is repeated for the same genetic information.

    Clinical utility

    Clinical utility is established by evaluating the following components.

    Clinical utility evaluation

    • Utility outcomes: The test eliminates further clinical workup or invasive testing; changes clinical management to improve outcomes; discontinues unnecessary or ineffective interventions; initiates effective medication or changes medication dosing; discontinues ineffective or harmful medications; or provides prognostic information that changes prognostic classification and treatment strategy.

    Marfan syndrome without family history

    ACMG diagnostic situations for Marfan syndrome when there is no family history.

    No family history of Marfan syndrome: Any of the following is present: dilated aortic root and ectopia lentis; dilated aortic root and a clearly pathogenic FBN1 variant; dilated aortic root and multiple systemic features; or ectopia lentis and an FBN1 pathogenic variant previously associated with aortic disease.

    Marfan syndrome with family history

    ACMG diagnostic situations for Marfan syndrome when there is a positive family history.

    Positive family history of Marfan syndrome: Any of the following is present: ectopia lentis; multiple systemic features; or a dilated aortic root meeting the age-specific standard-deviation threshold.

    Thoracic aortic disease genetic testing

    ACC/AHA recommendations for genetic testing in thoracic aortic disease.

    Risk factors for heritable thoracic aortic disease: The patient has an aortic-root or ascending-aortic aneurysm or aortic dissection with syndromic features, a family history of thoracic aortic disease, or early age of disease onset.

    Bilateral sensorineural hearing loss

    UpToDate recommendation for pediatric nonsyndromic hearing loss.

    Bilateral SNHL without syndromic findings: Comprehensive genetic testing using next-generation sequencing should be performed as the initial test.

    Hearing loss

    Genetic testing for hearing loss is supported when the clinical presentation suggests a genetic etiology.

    Supported hearing-loss indications: The patient has bilateral sensorineural hearing loss, bilateral auditory neuropathy spectrum disorder, unilateral auditory neuropathy spectrum disorder when imaging for cochlear nerve dysplasia is negative and no obvious acquired cause exists, or syndromic or early-onset childhood hearing loss.

    Comprehensive testing generally has the highest diagnostic yield for bilateral disease; directed GJB2/GJB6 testing may be used when comprehensive testing is unavailable or when a known family history exists.

    Inherited peripheral neuropathies

    Genetic testing is supported for suspected inherited peripheral neuropathy.

    Inherited peripheral neuropathy: The patient displays signs or symptoms of an inherited peripheral neuropathy or a hereditary neuropathy phenotype.

    Initial testing should be guided by phenotype, inheritance pattern, and electrodiagnostic findings.

    Macrocephaly and overgrowth

    Testing is advised when macrocephaly or overgrowth has clinical features suggesting an underlying genetic syndrome.

    Macrocephaly and overgrowth indications: The patient has unexplained large head size, developmental delays, abnormal physical features, or a family history of similar conditions.

    Testing may assist diagnosis, risk management, and treatment planning.

    Connective tissue disorders

    Genetic testing is medically necessary when connective tissue or inherited cardiovascular disease is suspected.

    Connective tissue and thoracic aortic disease indications: The patient has clinical features, family history, risk factors, incomplete clinical criteria, syndromic features, or early-onset thoracic aortic disease suggesting an inherited connective tissue or cardiovascular disorder.

    Broader genomic testing may be considered when clinical criteria are met but no pathogenic variant is found.

    Familial hypercholesterolemia

    Genetic testing is recommended when familial hypercholesterolemia is suspected.

    Familial hypercholesterolemia: The clinical presentation supports suspected familial hypercholesterolemia and genetic confirmation would assist precise diagnosis, early intervention, treatment selection, or cardiovascular risk reduction.

    Hypopituitarism

    Genetic testing for congenital or familial hypopituitarism may be considered medically necessary.

    Hypopituitarism or CPHD: The patient has hypopituitarism or suspected combined pituitary hormone deficiency for which a genetic cause is clinically suspected.

    Relevant genes include HESX1, LHX3, LHX4, PROP1, POU1F1, and TPIT.

    Additional gene testing for familial hypercholesterolemia management and evaluation, including the Comprehensive Lipidemia Panel from Invitae, is considered not medically necessary. Coverage is limited to testing of APOB, LDLR, LDLRAP1, and/or PCSK9 when the applicable clinical criteria are met and a molecular diagnosis has not already been established.

    Genetic testing for an inherited peripheral neuropathy is not medically necessary when the targeted-panel criteria are not met. This includes use of non-targeted panels; testing requires compatible signs or symptoms and either an inability to establish a definitive clinical diagnosis or a need for genetic information to support reproductive planning.

    Overgrowth and macrocephaly gene testing is not medically necessary when the required criteria are not met, including the qualifying macrocephaly findings and associated syndromic, neurologic, developmental, or neuroimaging features.

    Genetic panel testing or next-generation sequencing for hearing loss is not medically necessary in patients with nonsyndromic unilateral hearing loss. Comprehensive testing is directed primarily to children with bilateral sensorineural hearing loss without syndromic findings, or to targeted evaluation when a specific syndrome is suspected.

    Broad-scope testing is not supported when it produces results with no demonstrated clinical utility, including variants of uncertain significance. Uninterpretable or clinically unactionable findings may create uncertainty and potential harm rather than improve diagnosis or management.

    Comprehensive next-generation sequencing should not routinely be performed for children with unilateral sensorineural hearing loss without syndromic findings because the diagnostic yield is low.

    Multigene genetic panel testing is considered not medically necessary for nonsyndromic unilateral hearing loss. Available evidence shows little diagnostic yield, and the hearing loss is often attributable to structural causes.

    Routine genetic testing for cryptogenic polyneuropathy is not supported when the patient does not exhibit a hereditary neuropathy phenotype. Testing may be considered when clinical findings, inheritance pattern, or electrodiagnostic features suggest an inherited neuropathy.

    Genetic and molecular testing is not medically necessary when there is insufficient evidence that the testing target or strategy has clinical utility, when applicable coverage criteria are not met, or when the same germline genetic content is repeated for the same genetic information.

    Genetic panels for nonsyndromic unilateral hearing loss are not medically necessary because available evidence demonstrates little diagnostic yield, and clinical practice guidelines advise against their routine use.

    Covered Clinical Indications

    Connective tissue disorders covered indications

    Covered when Criterion I is met and a clinical or familial indication is present.

    Connective tissue disorders

    • Criterion I is met.
    • The member has specific signs and symptoms of a connective tissue disorder, or is asymptomatic with a known pathogenic variant in the family.

    Familial hypercholesterolemia covered indications

    Covered when all of the following are met.

    Familial hypercholesterolemia

    • Criterion I is met.
    • Testing is limited to APOB, LDLR, LDLRAP1 and/or PCSK9, as single genes or in any combination.
    • Signs and symptoms are suggestive of familial hypercholesterolemia, but a molecular diagnosis has not yet been established.

    Inherited peripheral motor or sensory neuropathy

    Covered when all of the following are met.

    • Criterion I is met.
    • The individual has signs or symptoms of an inherited peripheral motor or sensory neuropathy.
    • A definitive clinical diagnosis cannot be made, or a genetic diagnosis is needed to inform reproductive planning.

    Growth hormone deficiency, hypopituitarism, or CPHD

    Covered when all of the following are met.

    • All of Criterion I is met.
    • The member has growth hormone deficiency and at least one other pituitary hormone deficiency.

    Macrocephaly and overgrowth

    Covered when all of the following are met.

    • Criterion I is met.
    • The child has an occipitofrontal circumference above the 97th percentile for age, sex and gestation; progressive enlargement on serial measurements; or, if younger than 6 months, an increase greater than 2 cm (0.8 inches) per month.

    • ANY of the following

      • The child has history or examination features suggesting a multisystem or syndromic diagnosis.
      • The child has neurologic abnormalities or delayed development requiring intervention, and neuroimaging identifies enlarged cerebral structures.

    Bilateral nonsyndromic sensorineural hearing loss in children

    Covered when all of the following are met.

    • The child has bilateral sensorineural hearing loss without syndromic findings.
    • Criterion I is met.

    Diagnosis or treatment of a genetic disorder

    Testing for diagnosis or treatment of a genetic disorder, including screening in appropriate populations, is covered when all standards are met.

    Genetic disorder testing

    • The test has proven analytical validity.
    • The test has proven clinical validity.
    • The test has demonstrated clinical utility.

    Suspected or confirmed heritable thoracic aortic disease

    Genetic testing is recommended when thoracic aortic disease is accompanied by risk factors for heritable disease.

    Heritable thoracic aortic disease

    • The patient has an aortic-root or ascending-aortic aneurysm or aortic dissection.
    • The patient has syndromic features, a family history of thoracic aortic disease, early age of disease onset, or another risk factor for heritable thoracic aortic disease.

    Suspected Marfan syndrome

    FBN1 testing may be considered when clinical suspicion exists, including when full clinical criteria are not met.

    Suspected Marfan syndrome: Clinical features, family history, physical findings, cardiovascular findings, or ophthalmologic findings support suspected Marfan syndrome.

    Physical, cardiac, and ophthalmic evaluation should precede FBN1 testing. Broader genomic testing may be considered when clinical criteria are met but no pathogenic FBN1 variant is found.

    Infants and children with bilateral sensorineural hearing loss

    Comprehensive genetic testing using next-generation sequencing is recommended for infants and children with bilateral sensorineural hearing loss without syndromic findings.

    • The patient has bilateral sensorineural hearing loss or is an infant who is deaf or hard of hearing.
    • Evaluation includes review of family history and consideration of genetic counseling and testing.

    Suspected familial hypercholesterolemia

    Molecular genetic status testing may be considered when familial hypercholesterolemia is suspected.

    Suspected familial hypercholesterolemia: The clinical presentation supports suspected familial hypercholesterolemia and molecular genetic status testing is part of the diagnostic evaluation.

    Bilateral hearing loss, ANSD, syndromic or early-onset hearing loss

    Testing is generally supported when the hearing-loss presentation suggests a genetic etiology.

    Hearing-loss indications: The patient has bilateral sensorineural hearing loss, bilateral auditory neuropathy spectrum disorder, syndromic or early-onset childhood hearing loss, or unilateral auditory neuropathy spectrum disorder with negative imaging for cochlear nerve dysplasia and no obvious acquired cause.

    Signs and symptoms of inherited peripheral neuropathy

    Testing is supported when signs or symptoms suggest an inherited peripheral neuropathy.

    Inherited peripheral neuropathy: The patient displays signs or symptoms of an inherited peripheral neuropathy or a hereditary neuropathy phenotype.

    Testing is particularly useful when a clinical diagnosis cannot be established or when a genetic diagnosis informs reproductive decisions.

    Unexplained macrocephaly or overgrowth

    Testing is advised when macrocephaly or overgrowth is unexplained and accompanied by relevant clinical features.

    Unexplained macrocephaly or overgrowth: The patient has unexplained large head size, developmental delay, abnormal physical features, or a relevant family history.

    Suspected Marfan syndrome, connective tissue or thoracic aortic disease

    Testing may be considered when inherited connective tissue, cardiovascular, or thoracic aortic disease is suspected.

    Suspected inherited cardiovascular disorder: The patient has suspected Marfan syndrome, a connective tissue disorder, inherited cardiovascular disease, or thoracic aortic disease with syndromic features or early onset.

    Testing may guide gene-based management and cascade testing of relatives.

    Suspected familial hypercholesterolemia

    Testing may be considered when familial hypercholesterolemia is suspected and results will affect care.

    • The clinical presentation supports suspected familial hypercholesterolemia.
    • Genetic confirmation would assist precise diagnosis, early intervention, treatment management, or cardiovascular risk reduction.

    Hypopituitarism or congenital CPHD

    Testing may be considered when hypopituitarism or congenital combined pituitary hormone deficiency has a suspected genetic cause.

    Hypopituitarism or congenital CPHD: The patient has hypopituitarism or suspected combined pituitary hormone deficiency for which a genetic cause is clinically suspected.

    Relevant genes include HESX1, LHX3, LHX4, PROP1, POU1F1, and TPIT.

    Eligibility and Testing Requirements

    For an asymptomatic individual, testing may be considered when a first-degree blood relative—a parent, sibling, or child—has the condition, has not had genetic testing, and is unavailable for testing. Testing may also be considered when it targets a known pathogenic variant confirmed in an affected first-degree blood relative. Relevant family history must be documented.

    For familial hypercholesterolemia, testing is limited to APOB, LDLR, LDLRAP1, and/or PCSK9, and a molecular diagnosis must not already have been established. In general, testing must provide a definitive diagnosis or risk classification when other clinical or laboratory evaluation is inconclusive, avoid more invasive diagnostic testing, and demonstrate clinical utility.

    Coding and Test Specifications

    General genetic and molecular billing examplesCPT
    81479Unlisted genetic or molecular testing code; may be used for some genetic panels.
    81599Unlisted multianalyte assay with algorithmic analysis; may be used for some genetic panels.
    81400-81408Multiple gene-specific and/or molecular pathology procedure codes.
    Genetic and molecular testing codesCPT
    0195UKLF1 targeted sequencing, including exon 13.
    0231UCACNA1A full gene analysis, including sequence changes, deletions, duplications, STR expansions, mobile element insertions, and variants in non-uniquely mappable regions.
    0232UCSTB full gene analysis, including sequence changes, deletions, duplications, STR expansions, mobile element insertions, and variants in non-uniquely mappable regions.
    0233UFXN gene analysis, including sequence changes, deletions, duplications, STR expansions, mobile element insertions, and variants in non-uniquely mappable regions.
    0234UMECP2 full gene analysis, including sequence changes, deletions, duplications, mobile element insertions, and variants in non-uniquely mappable regions.
    0235UPTEN full gene analysis, including sequence changes, deletions, duplications, mobile element insertions, and variants in non-uniquely mappable regions.
    0238UCardiac ion channelopathy genomic sequence analysis panel including ANK2, CASQ2, CAV3, KCNE1, KCNE2, KCNH2, KCNJ2, KCNQ1, RYR2, and SCN5A.
    Additional molecular pathology and genomic testing codesCPT
    0355UOncology Lynch syndrome genomic DNA sequence analysis of MLH1, MSH2, MSH6, PMS2, and EPCAM.
    0604UAllergy and immunology chronic recurrent angioedema testing for four bradykinin peptides by LC-MS/MS using whole blood.
    0605UHereditary alpha tryptasemia testing using digital PCR analysis of TPSAB1 gene copy number variation in whole blood, with genotype-specific interpretation.
    0613UUrothelial carcinoma DNA methylation and mutation analysis of six biomarkers using methylation-specific PCR and targeted next-generation sequencing of urine.
    0628UKidney disease-related genetic conditions renal disease panel using next-generation sequencing of 449 genes from saliva.
    0679UHereditary hematologic cancer whole genome sequence analysis of more than 105 genes from blood, saliva, or cultured skin fibroblasts.
    Tumor genomic testingCPT
    0696USolid-organ oncology targeted genomic sequence analysis of formalin-fixed paraffin-embedded tumor tissue, RNA analysis of 350 or more genes for RNA alterations.
    Proprietary laboratory analysis codesCPT
    0355UAPOL1 (apolipoprotein L1), risk variants (G1, G2), uniquely mappable regions, eg, chronic kidney disease
    0604UAllergy and immunology, chronic recurrent angioedema, four bradykinin peptides, liquid chromatography and tandem mass spectrometry (LC-MS/MS), whole blood, quantitative
    0605UAllergy and immunology, hereditary alpha tryptasemia, DNA analysis of TPSAB1 gene copy number variation using digital PCR, whole blood, with genotype-specific interpretation and algorithmic classification
    0613UOncology, urothelial carcinoma, DNA methylation and mutation analysis of six biomarkers (TWIST1, OTX1, ONECUT2, FGFR3, HRAS, TERT promoter region), methylation-specific PCR and targeted next-generation sequencing, urine, algorithm-reported probability index
    0628UNephrology, kidney disease-related genetic conditions, genomic analysis renal disease panel, saliva DNA, next-generation sequencing of 449 genes, with pathogenic, likely pathogenic, variant of uncertain significance, or risk allele reporting
    0679UOncology, hereditary hematologic cancer, genomic DNA whole genome sequence, including single-nucleotide variants, deletions/insertions, characterized intronic variants, copy number variants, duplications/deletions, mobile element insertions, inversions, and analysis of more than 105 genes
    0696UOncology, solid organ, targeted genomic sequence analysis, formalin-fixed paraffin-embedded tumor tissue, RNA analysis of 350 or more genes for RNA alterations, eg, gene rearrangements and splice isoforms
    Human platelet antigen, IDH, DMD, BRCA, and inherited disorder testingCPT
    81105Human Platelet Antigen 1 genotyping (HPA-1), ITGB3, common variant HPA-1a/b (L33P)
    81106Human Platelet Antigen 2 genotyping (HPA-2), GP1BA, common variant HPA-2a/b (T145M)
    81107Human Platelet Antigen 3 genotyping (HPA-3), ITGA2B, common variant HPA-3a/b (I843S)
    81108Human Platelet Antigen 4 genotyping (HPA-4), ITGB3, common variant HPA-4a/b (R143Q)
    81121IDH2 (isocitrate dehydrogenase 2), common variants, eg, R140W and R172M
    81161DMD (dystrophin), Duchenne/Becker muscular dystrophy, deletion and duplication analysis
    81163BRCA1 and BRCA2, hereditary breast and ovarian cancer, full sequence analysis
    81165BRCA1, hereditary breast and ovarian cancer, full sequence analysis
    81171AFF2, fragile X intellectual disability 2 (FRAXE), evaluation to detect abnormal or expanded alleles
    81172AFF2, characterization of alleles, including expanded size
    Inherited neurologic, metabolic, hematologic, and cancer gene testingCPT
    81173AR, spinal and bulbar muscular atrophy/Kennedy disease and X chromosome inactivation, full gene sequence
    81174AR, known familial variant
    81178ATN1, dentatorubral-pallidoluysian atrophy, evaluation to detect abnormal or expanded alleles
    81179ATXN1, spinocerebellar ataxia, evaluation to detect abnormal or expanded alleles
    81185CACNA1A, spinocerebellar ataxia, evaluation to detect abnormal or expanded alleles
    81186CACNA1A, full gene sequence
    81187CACNA1A, known familial variant
    81188CNBP, myotonic dystrophy type 2, evaluation to detect abnormal or expanded alleles
    81189CSTB, Unverricht-Lundborg disease, evaluation to detect abnormal or expanded alleles
    81190CSTB, full gene sequence
    1–10 of 37
    1/4
    Additional molecular and genetic testing codesCPT
    81302MECP2, Rett syndrome, full sequence analysis
    81303MECP2, known familial variant
    81304MECP2, duplication/deletion variants
    81305MYD88, Waldenstrom macroglobulinemia or lymphoplasmacytic leukemia, L265P variant
    81311NRAS, colorectal carcinoma, variants in exons 2 and 3
    81312PABPN1, oculopharyngeal muscular dystrophy, evaluation to detect abnormal or expanded alleles
    81315PML/RARalpha t(15;17), promyelocytic leukemia, translocation analysis with common breakpoints
    81316PML/RARalpha t(15;17), translocation analysis with a single breakpoint
    81321PTEN, Cowden syndrome or PTEN hamartoma tumor syndrome, full sequence analysis
    81322PTEN, known familial variant
    1–10 of 28
    1/3
    HBB hemoglobinopathy testingCPT
    81361HBB, sickle cell anemia, beta thalassemia, or hemoglobinopathy, common variants including HbS, HbC, and HbE
    81362HBB, known familial variant(s)
    81363HBB, duplication/deletion variant(s)
    81364HBB, full gene sequence
    Molecular pathology proceduresCPT
    81400Molecular pathology procedure, Level 1; identification of a single germline variant, such as an SNP, by techniques such as restriction enzyme digestion or melt curve analysis
    81401Molecular pathology procedure, Level 2; 2-10 SNPs, one methylated variant, one somatic variant, or detection of a dynamic mutation disorder/triplet repeat
    81402Molecular pathology procedure, Level 3; more than 10 SNPs, 2-10 methylated variants, 2-10 somatic variants, immunoglobulin and T-cell receptor gene rearrangements, or duplication/deletion variants of one exon
    81403Molecular pathology procedure, Level 4; single-exon DNA sequence analysis, more than 10 amplicons using multiplex PCR, mutation scanning, or duplication/deletion variants of 2-5 exons
    81404Molecular pathology procedure, Level 5; analysis of 2-5 exons, mutation scanning, duplication/deletion variants of 6-10 exons, or characterization of a dynamic mutation disorder/triplet repeat by Southern blot
    81406Molecular pathology procedure, Level 6; analysis of 6-10 exons, or duplication/deletion variants of 11-25 exons
    81407Molecular pathology procedure, Level 7; analysis of 11-25 exons, duplication/deletion variants of 26-50 exons, or cytogenomic array analysis for neoplasia
    81408Molecular pathology procedure, Level 8; analysis of 26-50 exons, duplication/deletion variants of more than 50 exons, or sequence analysis of multiple genes on one platform
    81410Aortic dysfunction or dilation genomic sequence analysis panel, including at least FBN1, TGFBR1, TGFBR2, COL3A1, MYH11, ACTA2, SLC2A10, SMAD3, and MYLK
    81411Aortic dysfunction or dilation duplication/deletion analysis panel, including TGFBR1, TGFBR2, MYH11, and COL3A1
    1–10 of 11
    1/2
    Molecular pathology procedure, level 4CPT
    81403Molecular pathology procedure, level 4; analysis of a single exon by DNA sequence analysis.
    81404Molecular pathology procedure, level 4; sequence analysis, analysis of more than 10 amplicons using multiplex PCR in 2 or more independent reactions, mutation scanning, or duplication/deletion variants of 2-5 exons.
    Molecular pathology procedures, levels 6-8CPT
    81406Molecular pathology procedure, level 6; analysis of 6-10 exons by DNA sequence analysis, mutation scanning, or duplication/deletion variants of 11-25 exons.
    81407Molecular pathology procedure, level 7; analysis of 11-25 exons by DNA sequence analysis, mutation scanning, or duplication/deletion variants of 26-50 exons, or cytogenomic array analysis for neoplasia.
    81408Molecular pathology procedure, level 8; analysis of 26-50 exons by DNA sequence analysis, mutation scanning, or duplication/deletion variants of more than 50 exons, or sequence analysis of multiple genes on one platform.
    Genomic sequence and duplication/deletion panelsCPT
    81410Aortic dysfunction or dilation, including Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome type IV, or arterial tortuosity syndrome; genomic sequence analysis panel, including sequencing of at least 9 genes.
    81411Aortic dysfunction or dilation; duplication/deletion analysis panel, including analyses for TGFBR1, TGFBR2, MYH11, and COL3A1.
    81412Ashkenazi Jewish associated disorders genomic sequence analysis panel, including sequencing of at least 9 genes.
    Cardiac ion-channel panels and exome sequencingCPT
    81413Cardiac ion channelopathies; genomic sequence analysis panel, including sequencing of at least 10 genes.
    81414Cardiac ion channelopathies; duplication/deletion gene analysis panel.
    81415Cardiac ion channelopathies; duplication/deletion gene analysis panel, including analysis of at least 2 genes.
    81416Exome sequence analysis for an unexplained constitutional or heritable disorder or syndrome.
    81417Each comparator exome, such as parents or siblings, reported separately in addition to the primary procedure.
    Specific inherited-disorder genomic panelsCPT
    81439Hereditary neuroendocrine tumor-related disorders; genomic sequence analysis panel of 5 or more genes, with interrogation for sequence variants and copy number variants.
    81442Noonan spectrum disorders; genomic sequence analysis panel, including sequencing of at least 12 genes.
    81443Genetic testing for severe inherited conditions; genomic sequence analysis panel, including sequencing of at least 15 genes.
    Unlisted molecular and multianalyte assaysCPT
    81479Unlisted molecular pathology.
    81595Cardiology, heart transplant; mRNA gene expression profiling by real-time quantitative PCR of 20 genes using a subfraction of peripheral blood, with an algorithm reported as a rejection risk score.
    81599Unlisted multianalyte assay with algorithmic analysis.
    Comparative genomic hybridization microarray testingHCPCS
    S3870Comparative genomic hybridization microarray testing for developmental delay, autism spectrum disorder, and/or intellectual disability.
    Occipitofrontal circumference
    Primary thresholdOFC > 97th percentile for age, sex and gestation
    MeasurementOccipitofrontal circumference (OFC)
    Clinical useQualifying macrocephaly criterion for overgrowth and macrocephaly gene testing
    Infant occipitofrontal circumference growth
    Growth thresholdOFC increases > 2 cm (0.8 inches) per month
    Age groupInfant < 6 months of age
    Clinical useAlternative qualifying macrocephaly criterion for overgrowth and macrocephaly gene testing
    Macrocephaly
    DefinitionHead circumference greater than two standard deviations above the mean for age and sex
    Policy thresholdOFC > 97th percentile for age, sex and gestation
    Additional qualifying findingsProgressive enlargement on serial measurements or, in an infant < 6 months, an increase > 2 cm (0.8 inches) per month
    Dilated aortic root without Marfan family history
    Aortic-root threshold>= 2 standard deviations above the mean for age, sex, and body surface area
    Family-history statusNo family history of Marfan syndrome
    Diagnostic pairingMay be considered with ectopia lentis, a clearly pathogenic FBN1 variant, or multiple systemic features
    Dilated aortic root under age 20 with Marfan family history
    Aortic-root threshold> 3 standard deviations
    Age groupPerson younger than 20 years
    Family-history statusPositive family history of Marfan syndrome
    Dilated aortic root over age 20 with Marfan family history
    Aortic-root threshold> 2 standard deviations
    Age groupPerson over 20 years
    Family-history statusPositive family history of Marfan syndrome
    Aortic dysfunction or dilation genomic sequence panel
    Minimum panel sizeAt least 9 genes
    Required genesFBN1, TGFBR1, TGFBR2, COL3A1, MYH11, ACTA2, SLC2A10, SMAD3, and MYLK
    Associated code81410
    Cardiac ion channelopathy genomic sequence panel
    Minimum panel sizeAt least 10 genes
    Required genesANK2, CASQ2, CAV3, KCNE1, KCNE2, KCNH2, KCNJ2, KCNQ1, RYR2, and SCN5A
    Associated code81413
    Hearing-loss genomic sequence panel
    Minimum panel sizeAt least 60 genes
    Examples of included genesCDH23, CLRN1, GJB2, GPR98, MTRNR1, MYO7A, MYO15A, PCDH15, OTOF, SLC26A4, TMC1, TMPRSS3, USH1C, USH1G, USH2A, and WFS1
    Associated testingHearing-loss genomic sequence analysis panel
    Inherited bone marrow failure syndrome panel
    Minimum panel sizeAt least 30 genes
    Condition examplesFanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, GATA2 deficiency syndrome, and congenital amegakaryocytic thrombocytopenia
    Gene examplesBRCA2, BRIP1, DKC1, FANCA, FANCB, FANCC, FANCD2, FANCE, RAD51C, RPL11, RPL35A, RPL5, RPS10, RPS19, RPS24, RPS26, RPS7, SBDS, TERT, and TINF2
    Severe inherited conditions genomic panel
    Minimum panel sizeAt least 15 genes
    Examples of conditionsCystic fibrosis, Ashkenazi Jewish-associated disorders, beta hemoglobinopathies, phenylketonuria, and galactosemia
    Associated code81443
    Noonan spectrum disorder genomic panel
    Minimum panel sizeAt least 12 genes
    Included genesBRAF, CBL, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, PTPN11, RAF1, RIT1, SHOC2, and SOS1
    Associated code81442

    Provider Submission and Review Requirements

    Prior Authorization

    Prior Authorization for Potentially Covered Unlisted Services

    For potentially covered unlisted services addressed by this policy, prior authorization is recommended before service to help avoid a post-service denial.

    • Applies to unlisted codes for services that may otherwise be covered under this policy.
    Documentation Required

    Clinical and Family-History Support

    Genetic or molecular testing may be considered medically necessary when the general criteria are met, including appropriate counseling, a consistent clinical presentation or qualifying family history, a condition associated with increased morbidity or reduced life expectancy, and established clinical utility.

    • Symptomatic patient with a presentation consistent with a known condition; or an asymptomatic individual with an affected, unavailable first-degree relative or a confirmed familial pathogenic variant.
    • Testing should provide definitive diagnosis or risk classification when other evaluation is inconclusive or avoid more invasive testing, and results must guide clinical management.
    Documentation Required

    Required Clinical and Test Documentation

    Submit complete clinical and test information with the request so clinical utility and medical necessity can be evaluated.

    • Specific gene, test name, proprietary name, or every gene and component of a custom test.
    • Testing laboratory and all relevant CPT/HCPCS codes.
    • Clinical indication, signs and symptoms, relevant prior test results, applicable family history, and how results will affect clinical decision making.
    Documentation Required

    Hereditary Neuropathy Documentation

    For suspected inherited peripheral neuropathy, document the hereditary phenotype and the clinical evaluation supporting targeted testing.

    • Include signs and symptoms of inherited peripheral motor or sensory neuropathy.
    • Document relevant clinical phenotype, inheritance pattern, and electrodiagnostic findings.
    • Where applicable, document that basic blood tests are negative and alternative causes such as diabetes, toxic medications, thyroid disease, and vasculitis have been considered or ruled out.
    Documentation Required

    Clinical Indication and Family History

    Requests should identify a specific clinical indication and include relevant family history when testing is being used to diagnose or manage an inherited condition.

    • Connective-tissue testing should be supported by clinical features, incomplete criteria, risk factors, or a known pathogenic familial variant.
    • Macrocephaly or overgrowth testing should include unexplained large head size, progressive enlargement, developmental or neurologic abnormalities, syndromic physical findings, or a relevant family history.
    • Familial hypercholesterolemia testing should be supported by suggestive signs and symptoms when a molecular diagnosis has not been established.
    Billing Rule

    Claim-Level Review of Unlisted Codes

    All unlisted codes are reviewed for medical necessity, correct coding, and pricing at the claim level.

    • Review occurs even when a service is addressed elsewhere in the policy.
    Billing Rule

    Contract and Coding Compliance

    Code inclusion or omission does not guarantee reimbursement or coverage. Claims remain subject to provider contracts, member benefits, eligibility, and potential utilization audit.

    • The policy code list is provided as a courtesy and may not be all-inclusive.
    • Confirm applicable reimbursement and coverage requirements before billing.
    Denial Risk

    General Medical Necessity Criteria Not Met

    Testing may be denied as not medically necessary when the general criteria are not met, including the required counseling, clinical or family-history basis, condition severity, and established clinical utility.

    • Document how testing will establish diagnosis or risk classification and change clinical management.
    Denial Risk

    Condition-Specific Criteria Not Met

    Condition-specific testing may be denied when the applicable criteria are not satisfied.

    • Familial hypercholesterolemia testing is limited to APOB, LDLR, LDLRAP1, and/or PCSK9 when signs and symptoms are suggestive; additional broad testing is not medically necessary.
    • Inherited peripheral neuropathy testing requires signs or symptoms plus inability to make a definitive diagnosis or a need to inform reproductive planning; non-targeted panels are not medically necessary.
    • Macrocephaly and overgrowth testing requires the specified head-size findings and qualifying syndromic, neurologic, developmental, or neuroimaging findings.
    • Hearing-loss testing is generally supported for children with bilateral sensorineural loss without syndromic findings when general criteria are met; targeted testing is preferred when a specific syndrome is suspected.
    Denial Risk

    Insufficient Utility or Repeat Germline Testing

    Testing may be denied when the target or testing strategy lacks sufficient evidence of clinical utility, when criteria are otherwise unmet, or when the same germline content is repeated for the same genetic information.

    • Do not submit repeat germline testing without documenting a distinct clinical purpose and information need.
    • Use a targeted strategy when the policy requires one; broad or non-targeted testing may lack demonstrated utility.
    Denial Risk

    Incomplete Request Documentation

    Failure to submit complete documentation may affect the outcome of medical-necessity review.

    • Include the test or gene details, laboratory, indication, signs and symptoms, prior relevant results, family history when applicable, expected clinical-management impact, and all relevant CPT/HCPCS codes.
    Note

    FDA Status Alone Does Not Establish Coverage

    FDA approval or clearance does not by itself establish medical necessity or serve as a basis for coverage.

    • Coverage remains dependent on the policy criteria, documentation, member benefits, and applicable contract requirements.
    Denial Risk

    Nonsyndromic Unilateral Hearing Loss

    Genetic panel testing or next-generation sequencing is considered not medically necessary for nonsyndromic unilateral hearing loss.

    • For children with bilateral sensorineural hearing loss, comprehensive testing may be considered when general criteria are met.
    • When clinical findings suggest a specific syndrome, use targeted testing to evaluate that syndrome.
    Denial Risk

    Unlisted Code for Non-Covered Service

    An unlisted code submitted for a non-covered service addressed by this policy will be denied as not covered.

    • Confirm whether the underlying service is covered before submitting an unlisted code.
    Billing Rule

    NCCI and MUE Edits

    Claims may be subject to CMS National Correct Coding Initiative procedure-to-procedure bundling edits and medically unlikely edits.

    • This policy does not take precedence over NCCI edits or MUEs.
    • Consult current CMS coding guidelines and applicable code combinations.
    Documentation Required

    General Genetic Counseling Requirements

    Arrange genetic counseling before testing and document that the general genetic counseling requirements have been met.

    • Counseling should address the purpose and limitations of testing, possible results and implications, privacy or discrimination considerations, and the potential impact on the patient and family.
    • Document informed consent and the counseling discussion in the request record.
    Documentation Required

    Geneticist Consultation and Directed Testing

    Use a qualified geneticist or genetics professional when indicated to evaluate the phenotype, inheritance pattern, and appropriate test strategy.

    • Direct testing toward the suspected condition and relevant genes rather than ordering broad, non-targeted testing without clinical justification.
    • Consider testing an affected relative first when feasible; document why this is not possible when the policy permits testing an unaffected individual based on family history.

    Policy Background

    This policy addresses genetic and molecular testing used to establish a diagnosis or risk classification and to guide treatment or other clinical management. Testing should demonstrate analytical validity, clinical validity, and clinical utility, supported by peer-reviewed evidence. Coverage generally depends on a consistent symptomatic presentation or a qualifying family-history scenario, disease severity, and a clear clinical benefit from the result.

    Definitions

    First-degree blood relative
    DefinitionA parent, sibling, or child
    Relationship typeBlood relative
    Policy relevanceMay support testing for an asymptomatic individual when the relative has the condition and meets the applicable family-history requirements
    Macrocephaly definition
    General definitionHead circumference greater than two standard deviations above the mean for age and sex
    Policy thresholdOFC > 97th percentile for age, sex and gestation
    Other qualifying patternsProgressive enlargement on serial measurements or an increase > 2 cm (0.8 inches) per month in an infant < 6 months of age
    Clinical utility definition
    Workup valueEliminates the need for further clinical workup or invasive testing
    Management valueChanges clinical management to improve outcomes or discontinues unnecessary, ineffective, or harmful interventions or medications
    Prognostic valueProvides prognostic information that reclassifies patients into clinically relevant categories with different treatment strategies
    Genetic test definition
    Analytes evaluatedHuman DNA, RNA, chromosomes, proteins, and certain metabolites
    PurposeDetects heritable disease-related genotypes, mutations, phenotypes, or karyotypes
    Clinical applicationUsed for clinical purposes, including diagnosis, treatment, and screening in appropriate populations
    Macrocephaly definition
    DefinitionA condition in which an individual has an abnormally large head
    Measurement criterionHead circumference greater than two standard deviations above the mean for age and sex
    Possible causesGenetic disorders, increased brain volume, or other medical conditions
    Nonsyndromic hearing loss definition
    Hearing lossPartial or total loss of hearing
    Associated findingsNot associated with other signs and symptoms
    ClassificationNonsyndromic hearing loss
    Syndromic hearing loss definition
    DefinitionHearing loss occurring with signs and symptoms affecting other parts of the body
    Examples of syndromesAlport, Branchio-Oto-Renal, Charcot Marie Tooth, Pendred, Goldenhar, and Jervell and Lange-Neilsen
    Additional examplesStickler, Usher, Turner, Waardenburg, and Treacher Collins
    Sensorineural hearing loss definition
    DefinitionHearing loss resulting from damage, disease, or other disorders affecting the inner ear or auditory nerve
    Inner-ear exampleCochlea
    Auditory nerveCranial nerve VIII
    Hypopituitarism definition
    DefinitionDecreased secretion of pituitary hormones
    Potential sourceDisease of the pituitary gland
    Other potential sourceDisease of the hypothalamus causing diminished secretion of hypothalamic-releasing hormones
    Combined pituitary hormone deficiency definition
    DefinitionImpaired production of growth hormone and at least one other anterior pituitary hormone
    Primary hormoneGrowth hormone
    Additional deficiencyAt least one other hormone produced by the anterior pituitary
    Combined pituitary hormone deficiency (CPHD) definition
    DefinitionA condition caused by deficiencies of multiple pituitary hormones
    Hormones involvedLH, FSH, growth hormone, TSH, and ACTH
    Underlying associationPathogenic variants affecting pituitary development
    Thoracic aortic disease definition
    DefinitionDisease involving the thoracic aorta, including aortic-root or ascending-aortic aneurysm or aortic dissection
    Genetic-testing risk factorsSyndromic features, family history of TAD, early disease onset, or other risk factors for heritable thoracic aortic disease
    Family evaluationThoracic aortic imaging is recommended for first-degree relatives of individuals with TAD, regardless of age of onset
    Marfan syndrome definition
    DefinitionAn inherited connective-tissue disorder
    Evaluation factorsClinical features, family history, aortic-root findings, ectopia lentis, systemic features, and pathogenic FBN1 variants
    Family evaluationAt-risk first-degree relatives may need physical, ophthalmologic, and cardiac evaluations and consideration of genetic testing
    Unilateral SNHL definition
    DefinitionSensorineural hearing loss affecting one ear
    Typical testing contextChildren with unilateral hearing loss without syndromic findings
    Testing considerationComprehensive NGS testing has a low diagnostic yield in this setting
    Hereditary neuropathy phenotype definition
    DefinitionA peripheral neuropathy phenotype suggesting an inherited neuropathy
    Clinical assessmentClinical presentation and inheritance pattern
    Diagnostic assessmentElectrodiagnostic features
    Cryptogenic polyneuropathy definition
    DefinitionPolyneuropathy for which no cause has been identified after evaluation
    Cause statusNo identified cause
    Testing relevanceGenetic testing may be considered when a hereditary neuropathy phenotype is present
    ANSD definition
    MeaningAuditory neuropathy spectrum disorder
    DefinitionA hearing disorder involving abnormal transmission of auditory signals
    Testing contextComprehensive genetic testing is recommended for bilateral ANSD and may be considered for unilateral ANSD when cochlear nerve dysplasia is excluded and no acquired cause is apparent
    Nonsyndromic unilateral hearing loss definition
    DefinitionHearing loss affecting one ear without syndromic findings
    LateralityUnilateral
    Testing statusMultigene genetic panel testing is considered not medically necessary
    TAD definition
    MeaningThoracic aortic disease
    Genetic-testing contextTesting is recommended when syndromic features or early onset suggest an inherited cardiovascular disorder
    Clinical purposeTesting may guide gene-based management and cascade testing of relatives

    Non-Covered Services and Testing

    The following services are not covered as medically necessary under this policy: additional familial hypercholesterolemia gene testing, including the Comprehensive Lipidemia Panel from Invitae; non-targeted panels for inherited peripheral neuropathy; genetic panel testing or next-generation sequencing for nonsyndromic unilateral hearing loss; testing without demonstrated clinical utility; and repeat testing of the same germline genetic content for the same genetic information.