Print

Date Printed: October 20, 2017: 08:40 AM

Private Property of Blue Cross and Blue Shield of Florida.
This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

05-82000-28

Original Effective Date: 10/15/01

Reviewed: 12/01/16

Revised: 10/15/17

Subject: Genetic Testing

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Position Statement Billing/Coding Reimbursement Program Exceptions Definitions Related Guidelines
           
Other References Updates    
           

DESCRIPTION:

A genetic or genomic test involves an analysis of human chromosomes, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), or gene products (e.g., enzymes and other types of proteins) to detect heritable or somatic mutations, genotypes, or phenotypes related to disease and health.

There are several different types of genetic tests available today, including:

Carrier testing: Carrier testing is used to identify people who carry one copy of a gene mutation that, when present in two copies, causes a genetic disorder. This type of testing is offered to individuals who have a family history of a genetic disorder and to people in certain ethnic groups with an increased risk of specific genetic conditions. If both parents are tested, the test can provide information about a couple's risk of having a child with a genetic condition.

Diagnostic testing: Diagnostic testing is used to identify or rule out a specific genetic or chromosomal condition. In many cases, genetic testing is used to confirm a diagnosis when a particular condition is suspected based on physical signs and symptoms. Diagnostic testing can be performed before birth or at any time during a person's life, but is not available for all genes or all genetic conditions.

Newborn screening: Newborn screening is used just after birth to identify genetic disorders that can be treated early in life. Millions of babies are tested each year in the United States. All states currently test infants for phenylketonuria (a genetic disorder that causes intellectual disability if left untreated) and congenital hypothyroidism (a disorder of the thyroid gland). Most states also test for other genetic disorders.

Predictive and presymptomatic testing: Predictive and presymptomatic types of testing are used to detect gene mutations associated with disorders that appear after birth, often later in life. These tests can be helpful to people who have a family member with a genetic disorder, but who have no features of the disorder themselves at the time of testing. Predictive testing can identify mutations that increase a person's risk of developing disorders with a genetic basis, such as certain types of cancer. Presymptomatic testing can determine whether a person will develop a genetic disorder before any signs or symptoms appear.

Preimplantation testing: Preimplantation testing, also called preimplantation genetic diagnosis (PGD), is a specialized technique that can reduce the risk of having a child with a particular genetic or chromosomal disorder. It is used to detect genetic changes in embryos that were created using assisted reproductive techniques such as in-vitro fertilization. To perform preimplantation testing, a small number of cells are taken from these embryos and tested for certain genetic changes.

Prenatal testing: Prenatal testing is used to detect changes in a fetus's genes or chromosomes before birth. This type of testing is offered during pregnancy if there is an increased risk that the baby will have a genetic or chromosomal disorder. In some cases, prenatal testing can lessen a couple's uncertainty or help them make decisions about a pregnancy. However, it cannot identify all possible inherited disorders and birth defects.

Cytogenetics is a branch of genetics that is involved with heredity and the cellular components, particularly chromosomes, associated with heredity. Cytogenetic testing involves the determination of chromosome number and structure. Variations in either the chromosome number or structure can produce numerous abnormalities that may lead to cancer, syndromes, or birth defects.

POSITION STATEMENT:

NOTE: Coverage for genetic testing, screening, and counseling are applicable only under those contracts that include benefits for genetic testing, preventive health services, screening services, and medical counseling.

GENETIC TESTING TO ESTABLISH A DIAGNOSIS OF INHERITABLE DISEASE

Genetic testing meets the definition of medical necessity when used to establish a molecular diagnosis of an inheritable disease when the following criteria are met:

• The member displays clinical features, or is at direct risk of inheriting the mutation in question (presymptomatic); AND

• The result of the test will directly impact the treatment being delivered to the member; AND

• After history, physical examination, pedigree analysis, genetic counseling, and completion of conventional diagnostic studies, a definitive diagnosis remains uncertain, and one of the diagnoses listed in the table below may be suspected (the list is not all-inclusive)

OR

• For assisted reproductive technology (also known as pre-implantation genetic testing [PGT] or pre-implantation genetic diagnosis [PGD]) cases (i.e. in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), artificial insemination) where either parent is known to have a chromosomal abnormality. Results of testing must impact reproductive treatment and planning. NOTE: applicable only under those contracts that include infertility benefits.

Diagnosis Table:

Albinism (albino)

Cystic Fibrosis (CF)
(see criteria below)

Hemochromatosis
(gene sequence analysis)

Retinoblastoma

Angelman Syndrome
(see criteria below)

Duchenne Muscular Dystrophy (DMD) or Becker Muscular Dystrophy (BMD)
(see criteria below)

Huntington’s Chorea
(see criteria below)

Sickle Cell Anemia

Canavan Disease

Fabry Disease

Myotonic Dystrophy
(see criteria below)

Tuberous Sclerosis
(see criteria below)

Chromosome 22q11.2 Deletion Syndrome
(see criteria below)

Fragile X Syndrome
(see criteria below)

Niemann-Pick
(enzyme or mutation analysis)

Von Hippel-Lindau Syndrome

Charcot-Marie-Tooth Disease

Gaucher Disease
(see criteria below)

Prader-Willi Syndrome
(see criteria below)

 

The following test list includes, but is not limited to, specific indications for testing that may meet the definition of medical necessity and those for which testing is considered experimental or investigational.

Diagnosis

Criteria

Angelman Syndrome

Genetic testing for Angelman Syndrome meets the definition of medical necessity for ONE of the following:

• Cytogenic deletion is suspected on chorionic villus sampling (CVS) or amniocentesis

• Previous child diagnosed with Angelman Syndrome caused by a UBE3A mutation.

Chromosomal Microarray Analysis (CMA)

(Also referred to as genomic hybridization (CGH) or array comparative genomic hybridization (aCGH).)

1(Anora™ miscarriage test, CombiSNP™ Array for Pregnancy Loss, and CombiBAC™ Array)

Chromosome microarray (CMA) testing meets the definition of medical necessity as an alternative to karyotyping in members who are undergoing invasive diagnostic prenatal (fetal) testing,

1Chromosomal microarray analysis of fetal tissue meets the definition of medical necessity for the evaluation of pregnancy loss in cases of pregnancy loss at 20 weeks of gestation or earlier when there is a maternal history of recurrent miscarriage (defined as a history of 2 or more failed pregnancies); or in all cases of pregnancy loss after 20 weeks of gestation.

Chromosomal microarray analysis of fetal tissue in cases of miscarriage or intrauterine fetal demise is considered experimental or investigational in all other situations. There is insufficient clinical evidence to permit conclusions on net health outcomes.

The use of next generation sequencing in the setting of invasive prenatal testing is considered experimental or investigational. There is a lack of clinical data to permit conclusions on efficacy and net health outcomes.

Chromosome 22q11.2 Deletion Syndrome

Genetic testing for chromosome 22q11.2 deletion syndrome meets the definition of medical necessity in an at-risk fetus based on ultrasound findings or family history.

Cystic Fibrosis (CF)

Genetic carrier testing for cystic fibrosis meets the definition of medical necessity for ONE of the following:

• Individuals with a positive family history of CF

• Either parent has a diagnosis of CF

• Fetal echogenic bowel has been identified on ultrasound

• Couples currently planning a pregnancy or seeking prenatal testing.

Duchenne Muscular Dystrophy (DMD) or Becker Muscular Dystrophy (BMD)

Genetic testing for DMD or BMD meets the definition of medical necessity when the mother has been identified as a known carrier of DMD or BMD.

Genetic testing for DMD gene meets the definition of medical necessity for the following condition:

• For at-risk female relatives (first- and second-degree female relatives to include the proband’s mother, female siblings of the proband, female offspring of the proband, the proband’s maternal grandmother, maternal aunts, and their offspring):

• For preconception testing to determine the likelihood of an affected offspring in a woman considering a pregnancy.

Genetic testing for DMD gene mutations is considered experimental or investigational in all other prenatal situations. There is a lack of clinical data to permit conclusions on health outcomes.

Fetal RHD

(SensiGene™ Fetal RHD)

Noninvasive fetal RHD genotyping using cell-free fetal DNA is considered experimental or investigational. It is uncertain whether this testing will lead to improved health outcomes and the evidence is insufficient to determine the effects of the technology on health outcomes.

FMR1 Mutations (Including Fragile X Syndrome)

See below.

Gaucher Disease

Genetic testing for Gaucher Disease meets the definition of medical necessity for ONE of the following:

• There is an affected family member who has an identified GBA mutation or Gaucher disease

• Either parents or a previously affected sibling have an identified GBA mutation or Gaucher disease.

Huntington’s Chorea

Genetic testing for Huntington’s chorea meets the definition of medical necessity when there is a confirmed diagnosis of Huntington’s chorea in the family.

Myotonic Dystrophy

Genetic testing for myotonic dystrophy (Types 1 or 2) meets the definition of medical necessity for ONE of the following:

• At least one parent has a confirmed diagnosis of myotonic dystrophy

• At least one parent has been diagnosed as a presymptomatic carrier of myotonic dystrophy.

Prader-Willi Syndrome

Genetic testing for Prader-Willi Syndrome meets the definition of medical necessity when ONE of the following:

• Previous child diagnosed with Prader-Willi Syndrome

• Cytogenic deletion is suspected on chorionic villus sampling (CVS) or amniocentesis.

Single-Gene Disorders

Invasive diagnostic prenatal (fetal) testing for molecular analysis for single-gene disorders meets the definition of medical necessity when a pregnancy has been identified as being at high risk for:

1. Autosomal dominant conditions, at least 1 of the parents has a known pathogenic variant.

2. Autosomal recessive conditions:

• Both parents are suspected to be carriers or are known to be carriers, OR

• One parent is clinically affected and the other parent is suspected to be or is a known carrier.

3. X-linked conditions: A parent is suspected to be or is a known carrier.

AND ALL of the following are met:

• The natural history of the disease is well understood, and there is a reasonable likelihood that the disease is one with high morbidity in the homozygous or compound heterozygous state

• Any variants have a high penetrance

• The genetic test has adequate sensitivity and specificity to guide clinical decision making and residual risk is understood, AND

• An association of the marker with the disorder has been established.

Invasive diagnostic prenatal (fetal) testing for molecular analysis for single-gene disorders is considered experimental or investigational if the above criteria are not met. There is insufficient clinical evidence to permit conclusions on net health outcomes.

Tuberous Sclerosis

Genetic testing for Tuberous Sclerosis meets the definition of medical necessity for ONE of the following:

• Family history of Tuberous Sclerosis

• A specific mutation in the TSC1 and TSC2 gene has been identified in an affected family member.

Whole Exome Sequencing

Whole Genome Sequencing

See below.

For all other indications not listed above genetic testing for prenatal screening is considered experimental or investigational. This includes testing for the general population including genetic disease screening panels, as well as large comprehensive carrier screening panels (e.g. Counsyl Universal Carrier Genetic test, GoodStart Select, InheriGen, Inheritest, Natera One Disease Panel, Natera Horizon). There is a lack of clinical data to permit conclusions on net health outcomes.

Genetic testing of children to predict adult onset diseases does not meet the definition of medical necessity unless test results will guide current decisions concerning prevention and this benefit would be lost by waiting until the child has reached adulthood.

NEWBORN SCREENING

See U.S. Preventive Services Task Force (USPSTF) Recommendations at uspreventiveservicestaskforce.org.

POSTNATAL AND OTHER GENETIC TESTS

NOTE: Coverage for genetic testing, screening, and counseling are applicable only under those contracts that include benefits for genetic testing, preventive health services, screening services, and medical counseling.

To be considered genetic testing (vs. genetic screening) for indications other than to establish a diagnosis of inheritable disease, ALL of the following criteria must be met:

Diagnostic results from conventional testing and physical examination are inconclusive; AND

Results of molecular diagnostic testing are necessary to guide treatment decisions.

The following test list includes, but is not limited to, specific indications for testing that may meet the definition of medical necessity and those for which testing is considered experimental or investigational.

TEST

CRITERIA

5-Fluorouracil (5-FU)

(My5-FU™; TheraGuide®)

My5-FU™ testing or other assays for determining 5-fluorouracil area under the curve in order to adjust 5-FU dose for members with colorectal cancer or other cancers is considered experimental or investigational. The evidence is insufficient to determine the effects of the technology on health outcomes.

Testing for genetic mutations in dipyrimidine dehydrogenase (DPYD) or thymidylate synthase (TYMS) genes to guide 5-FU dosing and/or treatment choice in members with cancer is considered experimental or investigational. The evidence is insufficient to determine the effects of the technology on health outcomes.

Acute Myeloid Leukemia (AML)

Genetic testing for FLT3 internal tandem duplication (FLT3-ITD), NPM1, and CEBPA variants meets the definition of medical necessity in cytogenetically normal AML when testing will be used to guide management decisions in members who would receive treatment other than low-dose chemotherapy or best supportive care.

Genetic testing for FLT3 internal tandem duplication (FLT3-ITD), NPM1, and CEBPA variants is considered experimental or investigational in all other situations. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Genetic testing for FLT3 tyrosine kinase domain (FLT3-TKD) variants is considered experimental or investigational. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Genetic testing for FLT3, NPM1, and CEBPA variants to detect minimal residual disease is considered experimental or investigational. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Alzheimer’s Disease

Targeted genetic testing for a known familial variant in the presenilin genes (PSEN) or amyloid-beta precursor protein (APP) gene associated with autosomal dominant early-onset Alzheimer disease meets the definition of medical necessity in an asymptomatic member to determine future risk of disease when the following criteria are met:

• The member has a close relative (ie, first- or second-degree relative) with a known familial variant associated with autosomal dominant early-onset Alzheimer disease AND

• Results of testing will inform reproductive decision making.

Genetic testing for variants in presenilin genes (PSEN) or amyloid-beta precursor protein (APP) gene associated with autosomal dominant Alzheimer disease meets the definition of medical necessity in an asymptomatic member to determine future risk of disease when the following criteria are met:

• The member has a family history of dementia consistent with autosomal dominant Alzheimer disease for whom the genetic status of the affected family members is unavailable AND

• Results of testing will inform reproductive decision making.

Genetic testing for the risk assessment of Alzheimer disease in asymptomatic members is considered experimental or investigational in all other situations. Genetic testing includes, but is not limited to, testing for the apolipoprotein E ε4 allele (APOE) or triggering receptor expressed on myeloid cells 2 (TREM2).

Cancer Susceptibility Panels

(BROCA Cancer Risk Panel, BRCAplus, BreastNext™, OvaNext™, myRisk™ NGS, ColoSeq™, ColoNext™, CancerNext™)

Genetic cancer susceptibility panels using next generation sequencing are considered experimental or investigational. There is a lack of clinical data to permit conclusions on clinical utility and net health outcomes.

CADASIL Syndrome

*Screening Tool to Select Patients for NOTCH3 Gene:

Features

No. With NOTCH3 Variant

Percent With NOTCH3 Variant

Points

Clinical:

Migraine

239/463

52%

1

Migraine with aura

65/85

76%

3

Transient ischemic attack/stroke

380/526

72%

1 (2 if <50 y)

Psychiatric disturbance

106/380

28%

1

Cognitive decline

188/434

43%

3

Radiologic:

LE

277/277

100%

3

LE extended to temporal pole

174/235

74%

1

LE extended to external capsule

228/303

75%

5

Subcortical infarcts

210/254

83%

2

Cardiovascular Disease or Aneurysm

(9p21-EarlyMICheck™ Genotype Test, deCODE MI™)

The use of genotyping for 9p21 single nucleotide polymorphisms is considered experimental or investigational, including but not limited to, identification of members who may be at increased risk of cardiovascular disease or its manifestations (e.g., MI, ischemic stroke, peripheral arterial disease, coronary artery calcification), or identification of members who may be at increased risk for aneurysmal disease (abdominal aortic aneurysms, intracranial aneurysms, polypoidal choroidal vasculopathy). There is insufficient evidence regarding the clinical utility of this testing to permit conclusions on health outcomes.

Cardiovascular Risk and/or Effectiveness of Statin Therapy

(Cardio IQ™ KIF6 Genotype, KIF6 StatinCheck™ Genotype)

KIF6 Genotyping is considered experimental or investigational for predicting cardiovascular risk and/or the effectiveness of statin therapy. There is insufficient evidence on the clinical validity of the testing to permit conclusions on health outcomes.

Celiac Disease

(HLA Typing; PROMETHEUS® Celiac PLUS)

HLA-DQ2 and HLA-DQ8 testing meets the definition of medical necessity to rule out celiac disease in individuals with discordant serologic and histologic (biopsy) findings or if persistent symptoms warrant testing despite negative serology and histology.

HLA-DQ2 and HLA-DQ8 testing for celiac disease is considered experimental or investigational in all other situations. There is insufficient clinical evidence to permit conclusions on net health outcomes.

Chromosomal Microarray Analysis (CMA)

(Also referred to as genomic hybridization (CGH) or array comparative genomic hybridization (aCGH).)

(Affymetrix CytoScan® Dx; FirstStepDx PLUS; Reveal® SNP Microarray Pediatric)

Chromosomal microarray analysis meets the definition of medical necessity as first line testing in the initial postnatal evaluation of members with any of the following:

• Apparent nonsyndromic developmental delay/intellectual disability

• Autism spectrum disorder OR

• Multiple congenital anomalies not specific to a well-delineated genetic syndrome.

Chromosomal microarray analysis is considered experimental or investigational for the evaluation of all other conditions of delayed development, including but not limited to idiopathic growth or language delay. The evidence is insufficient to determine the effects of the technology on health outcomes.

Panel testing using next-generation sequencing (NGS) is considered experimental or investigational in all cases of suspected genetic abnormality in children with developmental delay/intellectual disability, autism spectrum disorder or congenital anomalies. The evidence is insufficient to permit conclusions whether NGS panel testing improves outcomes.

Cardiac Ion Channelopathies

Includes QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), Brugada syndrome (BrS), and short QT syndrome (SQTS)

(FAMILION® Test)

Long QT Syndrome (LQTS)

Genetic testing to confirm a diagnosis of congenital LQTS meets the definition of medical necessity when signs and/or symptoms of LQTS are present but a definitive diagnosis cannot be made without genetic testing. This includes:

• Members who do not meet the clinical criteria for LQTS (i.e., those with a Schwartz score less than 4), but who have a moderate-to-high pretest probability based on the Schwartz score and/or clinical criteria.

Note: Determining the pretest probability of LQTS is not standardized. An example of a member with a moderate-to-high pretest probability of LQTS is a member with a Schwartz score of 2 – 3. Refer to Diagnostic Scoring System* for LQTS below.

Genetic testing of asymptomatic members to determine future risk of LQTS meets the definition of medical necessity when at least one of the following criteria is met:

• A close relative (ie, first-, second-, or third-degree relative) with a known LQTS mutation; OR

• A close relative diagnosed with LQTS by clinical means whose genetic status is unavailable.

Genetic testing for LQTS for all other situations not meeting criteria above, including but not limited to determining prognosis and/or directing therapy in members with known LQTS is considered experimental or investigational. There is insufficient clinical evidence to permit conclusions on net health outcomes.

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

Genetic testing to confirm a diagnosis of CPVT meets the definition of medical necessity when signs and/or symptoms of CPVT are present, but a definitive diagnosis cannot be made without genetic testing.

Genetic testing of asymptomatic members to determine future risk of CPVT meets the definition of medical necessity when at least one of the following criteria is met:

• A close relative (ie, first-, second-, or third-degree relative) with a known CPVT mutation; OR

• A close relative diagnosed with CPVT by clinical means whose genetic status is unavailable.

Genetic testing for CPVT for all other situations not meeting the criteria above is considered experimental or investigational. There is insufficient clinical evidence to permit conclusions on net health outcomes.

Brugada Syndrome (BrS)

Genetic testing to confirm a diagnosis of BrS meets the definition of medical necessity when signs and/or symptoms consistent with BrS are present but a definitive diagnosis cannot be made without genetic testing.

Genetic testing of asymptomatic members to determine future risk of BrS meets the definition of medical necessity when members have a close relative (ie, first-, second-, or third-degree relative) with a known BrS mutation.

Genetic testing for BrS for all other situations not meeting the criteria above is considered experimental or investigational. There is insufficient clinical evidence to permit conclusions on net health outcomes.

Short QT Syndrome (SQTS)

Genetic testing of asymptomatic members to determine future risk of SQTS meets the definition of medical necessity when members have a close relative (ie, first-, second-, or third-degree relative) with a known SQTS mutation.

Genetic testing for SQTS for all other situations not meeting the criteria above is considered experimental or investigational. There is insufficient clinical evidence to permit conclusions on net health outcomes.

NOTE: First-degree relatives: children, brothers, sisters and parents. Second-degree relatives: grandparents, aunts, uncles, nieces, nephews, half-siblings, and grandchildren. Third-degree relatives: great-grandparents, great-aunts, great-uncles, great-grandchildren, and first cousins.

CHARGE Syndrome

Genetic testing for CHARGE syndrome meets the definition of medical necessity to confirm a diagnosis in a member with signs/symptoms of CHARGE syndrome when a definitive diagnosis cannot be made with clinical criteria.

Genetic testing for CHARGE syndrome is considered experimental or investigational in all other situations. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Coronary Artery Disease

(Corus® CAD)

Gene expression testing to predict coronary artery disease (CAD) is considered experimental or investigational for all indications, including but not limited to prediction of the likelihood of CAD in stable, nondiabetic members. There is a lack of clinical data to permit conclusions on net health outcomes.

Cutaneous Malignant Melanoma

(Melaris®)

Genetic testing for genes associated with hereditary cutaneous malignant melanoma or associated with susceptibility to cutaneous malignant melanoma is considered experimental or investigational as how the use of the presence or absence of these genetic mutations would impact clinical care is still unknown. In addition, not finding a mutation does not exclude the presence of hereditary cutaneous malignant melanoma.

Duchenne and Becker Muscular Dystrophy

Genetic testing for DMD gene meets the definition of medical necessity for the following conditions:

• In a male with signs and symptoms of a dystrophinopathy in order to confirm the diagnosis and direct treatment.

• For at-risk female relatives (first- and second-degree female relatives to include the proband’s mother, female siblings of the proband, female offspring of the proband, the proband’s maternal grandmother, maternal aunts, and their offspring):

• To confirm or exclude the need for cardiac surveillance

• For preconception testing to determine the likelihood of an affected offspring in a woman considering a pregnancy.

• For at-risk male offspring (asymptomatic male offspring of a female carrier or an asymptomatic male sibling of a member with a DMD-associated dystrophinopathy) to confirm or exclude the need for medical and cardiac surveillance.

Genetic testing for DMD gene mutations is considered experimental or investigational in all other postnatal situations. There is a lack of clinical data to permit conclusions on health outcomes.

FMR1 Mutations (Including Fragile X Syndrome)

Genetic testing for FMR1 mutations meets the definition of medical necessity for the following member populations:

• Members seeking reproductive counseling who have a family history of fragile X syndrome or a family history of undiagnosed intellectual disability

• Prenatal testing of fetuses of known carrier mothers

• Affected members or relatives of affected members who have had a positive cytogenetic fragile X test result who are seeking further counseling related to the risk of carrier status

• Members of either sex with intellectual disability, developmental delay, or autism spectrum disorder

• Members with neurologic symptoms consistent with fragile X-associated tremor/ataxia syndrome; OR

• Women with primary ovarian failure under the age of 40 in whom fragile X-associated ovarian failure is suspected.

Genetic testing for FMR1 mutations is considered experimental or investigational for all other uses. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Hereditary Pancreatitis

Genetic testing for hereditary pancreatitis meets the definition of medical necessity for members aged 18 years and younger with unexplained acute recurrent ( greater than 1 episode) or chronic pancreatitis with documented elevated amylase or lipase levels.

Genetic testing for hereditary pancreatitis is considered experiemental or investigational in all other situations. The evidence is insufficient to determine the effects of the technology on health outcomes.

Germline Mutations of the RET Proto-Oncogene in Medullary Carcinoma of the Thyroid

Genetic testing for RET proto-oncogene point mutations meets the definition of medical necessity for the following indications:

• Asymptomatic members of families with defined RET gene mutations

• Members of families known to be affected by inherited medullary thyroid cancer, but not previously evaluated for RET mutations

• Members with sporadic medullary thyroid cancer.

Genetic testing for RET proto-oncogene point mutations is considered experimental or investigational, as there is insufficient clinical evidence to support the use of genetic testing for screening the general population. There is a lack of clinical data to permit conclusions on efficacy and net health outcomes.

Mental Health Conditions

(GeneSightRX®, GeneSight Psychotropic panel, Genecept Assay, STA2R, Proove® Opioid Risk, PROOVE Drug Metabolism Profile, PHARMAchip, SureGene, MD Tox Expanded Comprehensive Profile; MD Tox Psychiatry & Risk Factors Profile; Mental Health DNA Insight panel, Idgenetix panels.)

Genetic testing for mental health disorders or for mutations associated with mental health disorders is considered experimental or investigational as there is a lack of clinical data to permit conclusions on the clinical management of the member and net health outcomes.

Helicobacter pylori (H. pylori) Treatment

Genotyping to determine cytochrome p450 (CYP2C19) genetic polymorphisms is considered experimental or investigational for the purpose of managing the treatment of H. pylori infection. There are currently no clinical trials comparing a treatment strategy that uses genetic testing to one that does not use genetic testing and no other studies have reported an improvement in health outcomes associated with CYP2C19 testing.

Hereditary Cardiomyopathies

Genetic testing for predisposition to hypertrophic cardiomyopathy (HCM) meets the definition of medical necessity for individuals who are at risk for development of HCM, defined as having a close (first- or second- degree*) relative with established HCM, when there is a known pathogenic gene mutation present in that affected relative.

Genetic testing for predisposition to HCM is considered experimental or investigational for all other member populations, including but not limited to individuals who have a first-degree relative with clinical HCM, but in whom genetic testing is unavailable. There is a lack of clinical data to permit conclusions on the clinical management of the member and net health outcomes.

* (First-degree relatives: children, brothers, sisters and parents. Second-degree relatives: grandparents, aunts, uncles, nieces, nephews, half-siblings, and grandchildren.)

Genetic testing to determine the diagnosis or management of all other hereditary cardiomyopathies, including but not limited to, arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), dilated, restrictive, and left ventricular noncompaction cardiomyopathies, is considered experimental or investigational. There is a lack of clinical data to permit conclusions on net health outcomes.

Inherited Peripheral Neuropathy

Genetic testing meets the definition of medical necessity when the diagnosis of an inherited peripheral motor or sensory neuropathy is suspected due to signs and/or symptoms but a definitive diagnosis cannot be made without genetic testing.

Genetic testing for an inherited peripheral neuropathy is considered experimental or investigational for all other indications. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Inherited Thrombophilia

Genetic testing for inherited thrombophilia, including testing for factor V Leiden variant, prothrombin gene variants, and variants in the MTHFR gene, is considered experimental or investigational. There is a lack of clinical data to permit conclusions on clinical utility and net health outcomes.

Inflammatory Bowel Disease

  • IBD sgi Diagnostic™; Prometheus© Crohn’s Prognostic; Prometheus© IBD Serology 7)

Determination of anti-neutrophil cytoplasmic antibody (ANCA), anti-Saccharomyces cerevisiae antibody (ASCA), OmpC antibodies, and I2 antibodies is considered experimental or investigational as there is insufficient clinical evidence to support the use of determination of ANCA, ASCA, OmpC antibodies, and I2 antibodies in the work-up and monitoring of members with inflammatory bowel disease. There is insufficient evidence to support conclusions regarding effects of ANCA, ASCA, OmpC, and I2 antibodies on health outcomes.

Lactase Insufficiency

(LactoType®)

The use of targeted mutation analysis of -13910 C>T for the prediction of lactase insufficiency is considered experimental or investigational. There is insufficient evidence that the testing would affect medical management or improve clinical outcomes.

Lipoprotein(a) Variant(s) as a Decision Aid for Aspirin Treatment

(LPA-Aspirin Genetype )

The use of genetic testing for the rs3798220 allele is considered experimental or investigational in members who are being considered for treatment with aspirin to reduce risk of cardiovascular events. There is insufficient evidence to permit conclusions on how this testing would change medical management and improve health outcomes.

Neurofibromatosis (NF)

Genetic testing for neurofibromatosis meets the definition of medical necessity when the diagnosis is clinically suspected due to signs of disease, but a definitive diagnosis cannot be made without genetic testing.

Genetic testing for neurofibromatosis in at-risk relatives with no signs of disease meets the definition of medical necessity when a definitive diagnosis cannot be made without genetic testing AND at least one of the following criteria is met:

• A close relative (ie, first-, second-, or third-degree relative) has a known NF mutation; or

•A close relative has been diagnosed with neurofibromatosis but whose genetic status is unavailable.

Genetic testing for neurofibromatosis for all other situations not meeting the criteria outlined above is considered experimental or investigational. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Nonfamilial Breast Cancer

(BREVAGenplus®, City of Hope Breast Cancer Susceptibility Assay, deCODE BreastCancer™, & deCODEme Complete Scan, OncoVue®)

Testing for one or more single nucleotide polymorphisms (SNPs) to predict an individual’s risk of breast cancer is considered experimental or investigational. There is insufficient evidence on the clinical validity of the testing to permit conclusions on health outcomes.

Pain Management

(Panels: GeneSight Analgesic; MD Tox Comprehensive Profile; MD Tox Comprehensive & Risk Factors Profile; MD Tox Pain Profile; Proove® Narcotic Risk; Proove® Opioid Risk; Proove® Pain Perception; Pain Medication DNA Insight™; Millennium PGTSM.)

Genetic testing for pain management is considered experimental or investigational for all indications. The clinical utility of pharmacogenetic testing in pain management is poorly defined to permit conclusions on health outcomes.

PALB2, CHEK2 and ATM Variants

Testing for PALB2 variants for breast cancer risk assessment meets the definition of medical necessity when the following criteria (A & B) are met:

A. The member meets one of the following NCCN criteria for genetic risk:

National Comprehensive Cancer Network (NCCN) guidelines for genetic risk evaluation of women without and with breast cancer:

Member Without a History of Breast Cancer

1. A close relative with any of the following:

• A known sequence variant in a cancer susceptibility gene within the family

• ≥2 breast cancer primaries in a single individual

• ≥2 individuals with breast cancer primaries on the same side of family with at least one diagnosed ≤50 years

• Ovarian cancer

• Male breast cancer.

2. First- or second-degree relative with breast cancer ≤45 years

3. Family history of three or more of the following (especially if early onset and can include multiple primary cancers in same individual): breast, pancreatic cancer, prostate cancer (Gleason score ≥7), melanoma, sarcoma, adrenocortical carcinoma, brain tumors, leukemia, diffuse gastric cancer, colon cancer, endometrial cancer, thyroid cancer, kidney cancer, dermatologic manifestations, and/or macrocephaly, hamartomatous polyps of GI tract.

Member With a History of Breast Cancer

1.Ovarian cancer

2.Breast cancer diagnosis meeting any of the following:

• A known sequence variant in a cancer susceptibility gene within the family

• Early-age-onset breast cancer

• Triple negative (ER-, PR-, HER2-) breast cancer diagnosed ≤60 years

• Two breast cancer primaries in a single individual

• Breast cancer at any age AND

o ≥1 close blood relative with breast cancer ≤50 years, or

o ≥1 close blood relative with invasive ovarian cancer at any age, or

o ≥2 close blood relatives with breast cancer and/or pancreatic cancer at any age, or

o From a population at increased risk.

3.Male breast cancer

4.An individual of Ashkenazi Jewish descent with breast, ovarian, or pancreatic cancer at any age

5.An individual with a personal and/or family history of three or more of the following (especially if early onset and can include multiple primary cancers in same individual): breast, pancreatic cancer, prostate cancer (Gleason score ≥7), melanoma, sarcoma, adrenocortical carcinoma, brain tumors, leukemia, diffuse gastric cancer, colon cancer, endometrial cancer, thyroid cancer, kidney cancer, dermatologic manifestations, and/or macrocephaly, hamartomatous polyps of gastrointestinal (GI) tract.

B. The member has undergone testing for sequence variants in BRCA1 and BRCA2 with negative results.

Testing for PALB2 sequence variants in individuals who do not meet the criteria outlined above is considered experimental or investigational. The evidence is insufficient to determine the effects of the technology on health outcomes.

Testing for CHEK2 and/or ATM variants in the assessment of breast cancer risk is considered experimental or investigational. The evidence is insufficient to determine the effects of the technology on health outcomes.

Prostate Cancer

(4Kscore™; ConfirmMDx®; Prolaris®; PROGENSA® PCA3; Promark™; Prostarix; Prostate Core Mitomics™; Prostate Health Index (phi))

1 (Decipher®; Ki-67, Oncotype Dx® Prostate; Prolaris®, ProMark)

Genetic tests for the screening, detection, and management of prostate cancer are considered experimental or investigational. This includes, but is not limited to the following:

• Candidate gene panels

• Gene hypermethylation testing

• kallikrein markers

• Metabolomics profiles

• Mitochondrial DNA mutation testing

• PCA3 testing TMPRSS fusion genes (ERG, PTEN).

Single-nucleotide polymorphism testing (e.g. 23and me, deCODE) for cancer risk assessment of prostate cancer is considered experimental or investigational. The evidence is insufficient to determine the effects of the technology on health outcomes.

1 Gene expression analysis to guide management of prostate cancer are considered experimental or investigational for all indications. The evidence is insufficient to determine the effects of the technology on health outcomes.

PTEN Hamartoma Tumor Syndrome (PHTS)

Genetic testing for PTEN meets the definition of medical necessity to confirm the diagnosis when a member has clinical signs of a PTEN hamartoma tumor syndrome.

Targeted genetic testing for a PTEN familial variant meets the definition of medical necessity in a first-degree relative of a proband with a known PTEN pathogenic variant.

Genetic testing for PTEN is considered experiemental or investigational for all other indications. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Rett Syndrome

Genetic testing for Rett syndrome meets the definition of medical necessity to confirm a diagnosis of Rett syndrome in a child with developmental delay and signs/symptoms of Rett syndrome when a definitive diagnosis cannot be made without genetic testing or determine carrier status of a mother or a sister of a member with Rett syndrome.

All other indications for genetic testing for Rett syndrome, including carrier testing (prenatal or preconception), and testing of asymptomatic family members to determine future risk of disease, are considered experimental or investigational. Clinical utility is lacking as the yield of testing is extremely low.

ScoliScore™

The use of DNA-based prognostic tests, including the ScoliScore™ AIS Prognostic Test, to predict spinal curve progression in adolescent idiopathic scoliosis is considered experimental or investigational. There is insufficient clinical evidence in peer-reviewed literature to permit conclusions on net health outcomes.

Statin-Induced Myopathy

(Statin Induced Myopathy (SLCO1B1) Genotype, SLCO1B1 Variants)

Genetic testing for the presence of variants in the SLCO1B1 gene for the purpose of identifying members at risk of statin-induced myopathy is considered experimental or investigational. There is insufficient clinical evidence to permit conclusions on health outcomes.

Tamoxifen Treatment

Genotyping to determine cytochrome p450 (CYP2D6) genetic polymorphisms is considered experimental or investigational for the purpose of managing treatment with tamoxifen for women at high risk for or with breast cancer as the evidence is insufficient to permit conclusions regarding the use of CYP2D6 genotyping for directing endocrine therapy regimen selection.

Warfarin Dose

(eSensor® Warfarin Sensitivity; INFINITI 2C9 & VKORC1 Multiplex Assay; Verigence Warfarin Metabolism Nucleic Acid Test®)

Genotyping to determine cytochrome p450 2C9 (CYP2C9) and vitamin K epoxide reductase subunit C1 (VKORC1) genetic polymorphisms is considered experimental or investigational for the purpose of managing the administration and dosing of warfarin, including use in guiding the initial warfarin dose to decrease time to stable INR and reduce the risk of serious bleeding. There is insufficient evidence in medical literature regarding the clinical utility and impact on clinical outcomes to permit conclusions on net health outcomes.

Whole Exome Sequencing

Whole Genome Sequencing

(ExomeNext, ExomeNext-Rapid, TruGenome tests, XomeDx)

Whole exome sequencing meets the definition of medical necessity for the evaluation of unexplained congenital or neurodevelopmental disorder in children when ALL of the following criteria are met:

• The member has been evaluated by a clinician with expertise in clinical genetics and counseled about the potential risks of genetic testing

• There is potential for a change in management and clinical outcome for the member being tested

• A genetic etiology is considered the most likely explanation for the phenotype despite previous genetic testing (eg, chromosomal microarray analysis and/or targeted single-gene testing), OR when previous genetic testing has failed to yield a diagnosis and the affected member is faced with invasive procedures or testing as the next diagnostic step (eg, muscle biopsy).

Whole exome sequencing is considered experimental or investigational for the diagnosis of genetic disorders in all other situations. The evidence is insufficient to determine the effects of the technology on health outcomes.

Whole genome sequencing is considered experimental or investigational for the diagnosis of genetic disorders. The evidence is insufficient to determine the effects of the technology on health outcomes.

Whole exome sequencing and whole genome sequencing are considered experimental or investigational for screening for genetic disorders. The evidence is insufficient to determine the effects of the technology on health outcomes.

X Chromosome Abnormality Test (XCAT) for Turner Syndrome (XCAT-TS)

The use of the XCAT-TS test to detect Classic and Mosaic Turner Syndrome is considered experimental or investigational as there is insufficient clinical evidence in peer-reviewed literature to permit conclusions the test is as beneficial as the established alternatives and on net health outcomes

*Diagnostic Scoring System for LQTS

Criteria

Points

Electrocardiographic findings

* QTc >480 msec

3

* QTc 460-470 msec

2

* QTc <450 msec

1

History of torsades de pointes

2

T-wave alternans

1

Notched T-waves in three leads

1

Low heart rate for age

0.5

Clinical history

* Syncope brought on by stress

2

* Syncope without stress

1

* Congenital deafness

0.5

Family history

* Family members with definite LQTS

1

* Unexplained sudden death in immediate family members younger than 30 years of age

0.5

Genetic Counseling: Genetic counseling is covered in accordance to the member’s contract benefits for medical counseling. Pre and post genetic counseling meets the definition of medical necessity as an adjunct to the genetic test(s).

Genetic testing is considered experimental or investigational, as there is insufficient clinical evidence to support the use of genetic testing for screening the general population including genetic disease screening panels, as well as large comprehensive carrier screening panels (e.g. Counsyl Universal Carrier Genetic test, GoodStart Select, InheriGen, Inheritest, Natera One Disease Panel, Natera Horizon). There is a lack of clinical data to permit conclusions on net health outcomes.

Home testing (including self-testing home kits) is considered experimental or investigational as the accuracy and clinical validity of the tests have not been established.

The following tests are considered experimental or investigational, as there is insufficient evidence to support the use of these tests for all indications. Although there are ongoing clinical studies the current data are inadequate to permit scientific conclusions on net health outcomes:

CYTOGENETIC STUDIES (CHROMOSOMAL STUDIES)

NOTE: Coverage for cytogenetic studies and counseling are applicable only under those contracts that include benefits for cytogenetic testing, genetic testing, preventive health services, screening services, and medical counseling.

Cytogenetic studies meet the definition of medical necessity for the diagnosis and treatment of the following conditions (the list is not all-inclusive):

BILLING/CODING INFORMATION:

CPT Coding:

81161

DMD (dystrophin) (e.g., Duchenne/Becker muscular dystrophy) deletion analysis, and duplication analysis, if performed

81170

ABL1 (ABL proto-oncogene 1, nonreceptor tyrosine kinase) (eg, acquired imatinib tyrosine kinase inhibitor resistance), gene analysis, variants in the kinase domain

81200

ASPA (aspartoacylase) (e.g. Canavan disease) gene analysis, common variants (e.g. E285A, Y231X)

81205

BCKDHB (branched-chain keto acid dehydrogenase E1, beta polypeptide) (e.g. Maple syrup urine disease) gene analysis, common variants (e.g. R183P, G278S, E422X)

81206

BCR/ABL1 (t(9;22)) (e.g. chronic myelogenous leukemia) translocation analysis; major breakpoint, qualitative or quantitative

81207

BCR/ABL1 (t(9;22)) (e.g. chronic myelogenous leukemia) translocation analysis; minor breakpoint, qualitative or quantitative

81208

BCR/ABL1 (t(9;22)) (e.g. chronic myelogenous leukemia) translocation analysis; other breakpoint, qualitative or quantitative

81209

BLM (Bloom syndrome, RecQ helicase-like) (e.g. Bloom syndrome) gene analysis, 2281del6ins7 variant

81218

CEBPA (CCAAT/enhancer binding protein [C/EBP], alpha) (eg, acute myeloid leukemia), gene analysis, full gene sequence

81219

CALR (calreticulin) (eg, myeloproliferative disorders), gene analysis, common variants in exon 9

81220

CFTR (cystic fibrosis transmembrane conductance regulator) (e.g. cystic fibrosis) gene analysis; common variants (e.g. ACMG/ACOG guidelines)

81221

CFTR (cystic fibrosis transmembrane conductance regulator) (e.g. cystic fibrosis) gene analysis; known familial variants

81222

CFTR (cystic fibrosis transmembrane conductance regulator) (e.g. cystic fibrosis) gene analysis; duplication/deletion variants

81223

CFTR (cystic fibrosis transmembrane conductance regulator) (e.g. cystic fibrosis) gene analysis; full gene sequence

81224

CFTR (cystic fibrosis transmembrane conductance regulator) (e.g. cystic fibrosis) gene analysis; intron 8 poly-T analysis (e.g. male infertility)

81225

CYP2C19 (cytochrome P450, family 2, subfamily C, polypeptide 19) (e.g. drug metabolism), gene analysis, common variants (e.g. *2, *3, *4, *8, *17) (Investigational)

81226

CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (e.g. drug metabolism), gene analysis, common variants (e.g. *2, *3, *4, *5, *6, *9, *10, *17, *19, *29, *35, *41, *1XN, *2XN, *4XN) (Investigational)

81227

CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) (e.g. drug metabolism), gene analysis, common variants (e.g. *2, *3, *5, *6) (Investigational)

81228

Cytogenomic constitutional (genome-wide) microarray analysis; interrogation of genomic regions for copy number variants (e.g. Bacterial Artificial Chromosome [BAC] or oligo-based comparative genomic hybridization [CGH] microarray analysis)

81229

Cytogenomic constitutional (genome-wide) microarray analysis; interrogation of genomic regions for copy number and single nucleotide polymorphism (SNP) variants for chromosomal abnormalities

81240

F2 (prothrombin, coagulation factor II) (e.g. hereditary hypercoagulability) gene analysis, 20210G>A variant (Investigational)

81241

F5 (coagulation Factor V) (e.g. hereditary hypercoagulability) gene analysis, Leiden variant (Investigational)

81242

FANCC (Fanconi anemia, complementation group C) (e.g. Fanconi anemia, type C) gene analysis, common variant (e.g. IVS4+4A>T)

81243

FMR1 (Fragile X mental retardation 1) (e.g. fragile X mental retardation) gene analysis; evaluation to detect abnormal (e.g. expanded) alleles

81244

FMR1 (Fragile X mental retardation 1) (e.g. fragile X mental retardation) gene analysis; characterization of alleles (e.g. expanded size and methylation status)

81245

FLT3 (fms-related tyrosine kinase 3) (e.g. acute myeloid leukemia), gene analysis, internal tandem duplication (ITD) variants (ie, exons 14, 15)

81246

FLT3 (fms‐related tyrosine kinase 3) (eg, acute myeloid leukemia), gene analysis; tyrosine kinase domain (TKD) variants (eg, D835, I836) (Investigational)

81250

G6PC (glucose-6-phosphatase, catalytic subunit) (e.g. Glycogen storage disease, Type 1a, von Gierke disease) gene analysis, common variants (e.g. R83C, Q347X)

81251

GBA (glucosidase, beta, acid) (e.g. Gaucher disease) gene analysis, common variants (e.g. N370S, 84GG, L444P, IVS2+1G>A)

81252

GJB2 (gap junction protein, beta 2, 26kDa; connexin 26) (e.g., nonsyndromic hearing loss) gene analysis; full gene sequence

81253

GJB2 (gap junction protein, beta 2, 26kDa; connexin 26) (e.g., nonsyndromic hearing loss) gene analysis; known familial variants

81254

GJB6 (gap junction protein, beta 6, 30kDa, connexin 30) (e.g., nonsyndromic hearing loss) gene analysis, common variants (e.g., 309kb [del(GJB6-D13S1830)] and 232kb [del(GJB6-D13S1854)])

81255

HEXA (hexosaminidase A [alpha polypeptide]) (e.g. Tay-Sachs disease) gene analysis, common variants (e.g. 1278insTATC, 1421+1G>C, G269S)

81256

HFE (hemochromatosis) (e.g. hereditary hemochromatosis) gene analysis, common variants (e.g. C282Y, H63D)

81257

HBA1/HBA2 (alpha globin 1 and alpha globin 2) (e.g. alpha thalassemia, Hb Bart hydrops fetalis syndrome, HbH disease), gene analysis, for common deletions or variant (e.g. Southeast Asian, Thai, Filipino, Mediterranean, alpha3.7, alpha4.2, alpha20.5, and Constant Spring)

81260

IKBKAP (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein) (e.g. familial dysautonomia) gene analysis, common variants (e.g. 2507+6T>C, R696P)

81261

IGH@ (Immunoglobulin heavy chain locus) (e.g. leukemias and lymphomas, B-cell), gene rearrangement analysis to detect abnormal clonal population(s); amplified methodology (e.g. polymerase chain reaction)

81262

IGH@ (Immunoglobulin heavy chain locus) (e.g. leukemias and lymphomas, B-cell), gene rearrangement analysis to detect abnormal clonal population(s); direct probe methodology (e.g. Southern blot)

81263

IGH@ (Immunoglobulin heavy chain locus) (e.g. leukemia and lymphoma, B-cell), variable region somatic mutation analysis

81264

IGK@ (Immunoglobulin kappa light chain locus) (e.g. leukemia and lymphoma, B-cell), gene rearrangement analysis, evaluation to detect abnormal clonal population(s)

81265

Comparative analysis using Short Tandem Repeat (STR) markers; patient and comparative specimen (e.g. pre-transplant recipient and donor germline testing, post-transplant non-hematopoietic recipient germline [e.g. buccal swab or other germline tissue sample] and donor testing, twin zygosity testing, or maternal cell contamination of fetal cells)

81266

Comparative analysis using Short Tandem Repeat (STR) markers; each additional specimen (e.g. additional cord blood donor, additional fetal samples from different cultures, or additional zygosity in multiple birth pregnancies) (List separately in addition to code for primary procedure)

81267

Chimerism (engraftment) analysis, post transplantation specimen (e.g. hematopoietic stem cell), includes comparison to previously performed baseline analyses; without cell selection

81268

Chimerism (engraftment) analysis, post transplantation specimen (e.g. hematopoietic stem cell), includes comparison to previously performed baseline analyses; with cell selection (e.g. CD3, CD33), each cell type

81270

JAK2 (Janus kinase 2) (e.g. myeloproliferative disorder) gene analysis, p.Val617Phe (V617F) variant

81272

KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (eg,gastrointestinal stromal tumor [GIST], acute myeloid leukemia, melanoma),gene analysis, targeted sequence analysis (eg, exons 8, 11, 13, 17, 18)

81273

KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (eg,mastocytosis), gene analysis, D816 variant(s)

81287

MGMT (O-6-methylguanine-DNA methyltransferase) (eg, glioblastoma multiforme), methylation analysis

81290

MCOLN1 (mucolipin 1) (e.g. Mucolipidosis, type IV) gene analysis, common variants (e.g. IVS3-2A>G, del6.4kb)

81291

MTHFR (5,10-methylenetetrahydrofolate reductase) (e.g. hereditary hypercoagulability) gene analysis, common variants (e.g. 677T, 1298C) (Investigational)

81302

MECP2 (methyl CpG binding protein 2) (e.g. Rett syndrome) gene analysis; full sequence analysis

81303

MECP2 (methyl CpG binding protein 2) (e.g. Rett syndrome) gene analysis; known familial variant

81304

MECP2 (methyl CpG binding protein 2) (e.g. Rett syndrome) gene analysis; duplication/deletion variants

81310

NPM1 (nucleophosmin) (e.g. acute myeloid leukemia) gene analysis, exon 12 variants

81313

PCA3/KLK3 (prostate cancer antigen 3 [non-protein coding]/kallikrein-related peptidase 3 [prostate specific antigen]) ratio (eg, prostate cancer) (Investigational)

81314

PDGFRA (platelet-derived growth factor receptor, alpha polypeptide) (eg, gastrointestinal stromal tumor [GIST]), gene analysis, targeted sequence analysis (eg, exons 12, 18)

81315

PML/RARalpha, (t(15;17)), (promyelocytic leukemia/retinoic acid receptor alpha) (e.g. promyelocytic leukemia) translocation analysis; common breakpoints (e.g. intron 3 and intron 6), qualitative or quantitative

81316

PML/RARalpha, (t(15;17)), (promyelocytic leukemia/retinoic acid receptor alpha) (e.g. promyelocytic leukemia) translocation analysis; single breakpoint (e.g. intron 3, intron 6 or exon 6), qualitative or quantitative

81321

PTEN (phosphatase and tensin homolog) (e.g., Cowden syndrome, PTEN hamartoma tumor syndrome) gene analysis; full sequence analysis

81322

PTEN (phosphatase and tensin homolog) (e.g., Cowden syndrome, PTEN hamartoma tumor syndrome) gene analysis; known familial variant

81323

PTEN (phosphatase and tensin homolog) (e.g., Cowden syndrome, PTEN hamartoma tumor syndrome) gene analysis; duplication/deletion variant

81324

PMP22 (peripheral myelin protein 22) (e.g., Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies) gene analysis; duplication/deletion analysis

81325

PMP22 (peripheral myelin protein 22) (e.g., Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies) gene analysis; full sequence analysis

81326

PMP22 (peripheral myelin protein 22) (e.g., Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies) gene analysis; known familial variant

81330

SMPD1(sphingomyelin phosphodiesterase 1, acid lysosomal) (e.g. Niemann-Pick disease, Type A) gene analysis, common variants (e.g. R496L, L302P, fsP330)

81331

SNRPN/UBE3A (small nuclear ribonucleoprotein polypeptide N and ubiquitin protein ligase E3A) (e.g. Prader-Willi syndrome and/or Angelman syndrome), methylation analysis

81332

SERPINA1 (serpin peptidase inhibitor, clade A, alpha-1 antiproteinase, antitrypsin, member 1) (e.g. alpha-1-antitrypsin deficiency), gene analysis, common variants (e.g. *S and *Z)

81340

TRB@ (T cell antigen receptor, beta) (e.g. leukemia and lymphoma), gene rearrangement analysis to detect abnormal clonal population(s); using amplification methodology (e.g. polymerase chain reaction)

81341

TRB@ (T cell antigen receptor, beta) (e.g. leukemia and lymphoma), gene rearrangement analysis to detect abnormal clonal population(s); using direct probe methodology (e.g. Southern blot)

81342

TRG@ (T cell antigen receptor, gamma) (e.g. leukemia and lymphoma), gene rearrangement analysis, evaluation to detect abnormal clonal population(s)

81350

UGT1A1 (UDP glucuronosyltransferase 1 family, polypeptide A1) (e.g. irinotecan metabolism), gene analysis, common variants (e.g. *28, *36, *37)

81355

VKORC1 (vitamin K epoxide reductase complex, subunit 1) (e.g. warfarin metabolism), gene analysis, common variants (e.g. -1639G>A, c.173+1000C>T)

81370

HLA Class I and II typing, low resolution (e.g. antigen equivalents); HLA-A, -B, -C, -DRB1/3/4/5, and DQB1

81371

HLA Class I and II typing, low resolution (e.g. antigen equivalents); HLA-A, -B, and DRB1 (e.g. verification typing)

81372

HLA Class I typing, low resolution (e.g. antigen equivalents); complete (ie, HLA-A, -B, and C)

81373

HLA Class I typing, low resolution (e.g. antigen equivalents); 1 locus (e.g. HLA-A, -B, or C), each

81374

HLA Class I typing, low resolution (e.g. antigen equivalents); 1 antigen equivalent (e.g. B*27), each

81375

HLA Class II typing, low resolution (e.g. antigen equivalents); HLA-DRB1/3/4/5 and DQB1

81376

HLA Class II typing, low resolution (e.g. antigen equivalents); 1 locus (e.g. HLA-DRB1, DRB3/4/5, -DQB1, -DQA1, -DPB1, or DPA1), each

81377

HLA Class II typing, low resolution (e.g. antigen equivalents); 1 antigen equivalent, each

81378

HLA Class I and II typing, high resolution (ie, alleles or allele groups), HLA-A, -B, -C, and DRB1

81379

HLA Class I typing, high resolution (ie, alleles or allele groups); complete (ie, HLA-A, -B, and C)

81380

HLA Class I typing, high resolution (ie, alleles or allele groups); 1 locus (e.g. HLA-A, -B, or C), each

81381

HLA Class I typing, high resolution (ie, alleles or allele groups); 1 allele or allele group (e.g. B*57:01P), each

81382

HLA Class II typing, high resolution (ie, alleles or allele groups); 1 locus (e.g. HLA-DRB1, -DRB3, -DRB4, -DRB5, -DQB1, -DQA1, -DPB1, or DPA1), each

81383

HLA Class II typing, high resolution (ie, alleles or allele groups); 1 allele or allele group (e.g. HLA-DQB1*06:02P), each

81400

Molecular pathology procedure, Level 1 (e.g. identification of single germline variant [e.g. SNP] by techniques such as restriction enzyme digestion or melt curve analysis)

81401

Molecular pathology procedure, Level 2 (e.g. 2-10 SNPs, 1 methylated variant, or 1 somatic variant [typically using nonsequencing target variant analysis], or detection of a dynamic mutation disorder/triplet repeat)

81402

Molecular pathology procedure, Level 3 (e.g., > 10 SNPs, 2-10 methylated variants, or 2-10 somatic variants [typically using non-sequencing target variant analysis], immunoglobulin and T-cell receptor gene rearrangements, duplication/deletion variants 1 exon, loss of heterozygosity [LOH], uniparental disomy [UPD])

81403

Molecular pathology procedure, Level 4 (e.g. analysis of single exon by DNA sequence analysis, analysis of > 10 amplicons using multiplex PCR in 2 or more independent reactions, mutation scanning or duplication/deletion variants of 2-5 exons)

81404

Molecular pathology procedure, Level 5 (e.g. analysis of 2-5 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 6-10 exons, or characterization of a dynamic mutation disorder/triplet repeat by Southern blot analysis)

81405

Molecular pathology procedure, Level 6 (e.g. analysis of 6-10 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 11-25 exons, regionally targeted cytogenomic array analysis)

81406

Molecular pathology procedure, Level 7 (e.g. analysis of 11-25 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 26-50 exons, cytogenomic array analysis for neoplasia)

81407

Molecular pathology procedure, Level 8 (e.g. analysis of 26-50 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of > 50 exons, sequence analysis of multiple genes on one platform)

81408

Molecular pathology procedure, Level 9 (e.g. analysis of > 50 exons in a single gene by DNA sequence analysis)

81410

Aortic dysfunction or dilation (eg, 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 (Investigational)

81411

Aortic dysfunction or dilation (eg, 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 (Investigational)

81412

Ashkenazi Jewish associated disorders (eg, Bloom syndrome, Canavan disease, cystic fibrosis, familial dysautonomia, Fanconi anemia group C, Gaucher disease, Tay-Sachs disease), genomic sequence analysis panel, must include sequencing of at least 9 genes, including ASPA, BLM, CFTR, FANCC, GBA, HEXA, IKBKAP, MCOLN1, and SMPD1 (Investigational)

81413

Cardiac ion channelopathies (eg, 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 (eg, 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

81415

Exome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis

81416

Exome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis, each comparator exome (eg, parents, siblings) (List separately in addition to code for primary procedure)

81417

Exome (eg, unexplained constitutional or heritable disorder or syndrome); re-evaluation of previously obtained exome sequence (eg, updated knowledge or unrelated condition/syndrome)

81425

Genome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis (Investigational)

81426

Genome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis, each comparator genome (eg, parents, siblings) (List separately in addition to code for primary procedure) (Investigational)

81427

Genome (eg, unexplained constitutional or heritable disorder or syndrome); re-evaluation of previously obtained genome sequence (eg, updated knowledge or unrelated condition/syndrome) (Investigational)

81430

Hearing loss (eg, nonsyndromic hearing loss, Usher syndrome, Pendred syndrome); genomic sequence analysis panel, must include sequencing of at least 60 genes, including CDH23, CLRN1, GJB2, GPR98, MTRNR1, MYO7A, MYO15A, PCDH15, OTOF, SLC26A4, TMC1, TMPRSS3, USH1C, USH1G, USH2A, and WFS1

81431

Hearing loss (eg, nonsyndromic hearing loss, Usher syndrome, Pendred syndrome); duplication/deletion analysis panel, must include copy number analyses for STRC and DFNB1 deletions in GJB2 and GJB6 genes (Investigational)

81432

Hereditary breast cancer-related disorders (eg, hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer); genomic sequence analysis panel, must include sequencing of at least 14 genes, including ATM, BRCA1, BRCA2, BRIP1, CDH1, MLH1, MSH2, MSH6, NBN, PALB2, PTEN, RAD51C, STK11, and TP53 (investigational)

81433

Hereditary breast cancer-related disorders (eg, hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer); duplication/deletion analysis panel, must include analyses for BRCA1, BRCA2, MLH1, MSH2, and STK11 (investigational)

81434

Hereditary retinal disorders (eg, retinitis pigmentosa, Leber congenital amaurosis, cone-rod dystrophy), genomic sequence analysis panel, must include sequencing of at least 15 genes, including ABCA4, CNGA1, CRB1, EYS, PDE6A, PDE6B, PRPF31, PRPH2, RDH12, RHO, RP1, RP2, RPE65, RPGR, and USH2A (investigational)

81435

Hereditary colon cancer disorders (eg, Lynch syndrome, PTEN hamartoma syndrome, Cowden syndrome, familial adenomatosis polyposis); genomic sequence analysis panel, must include sequencing of at least 10 genes, including APC, BMPR1A, CDH1, MLH1, MSH2, MSH6, MUTYH, PTEN, SMAD4, and STK11 (Investigational)

81436

Hereditary colon cancer disorders (eg, Lynch syndrome, PTEN hamartoma syndrome, Cowden syndrome, familial adenomatosis polyposis); duplication/deletion analysis panel, must include analysis of at least 5 genes, including MLH1, MSH2, EPCAM, SMAD4 (Investigational)

81437

Hereditary neuroendocrine tumor disorders (eg, medullary thyroid carcinoma, parathyroid carcinoma, malignant pheochromocytoma or paraganglioma); genomic sequence analysis panel, must include sequencing of at least 6 genes, including MAX, SDHB, SDHC, SDHD, TMEM127, and VHL (investigational)

81438

Hereditary neuroendocrine tumor disorders (eg, medullary thyroid carcinoma, parathyroid carcinoma, malignant pheochromocytoma or paraganglioma); duplication/deletion analysis panel, must include analyses for SDHB, SDHC, SDHD, and VHL (investigational)

81439

Inherited cardiomyopathy (eg, hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy) genomic sequence analysis panel, must include sequencing of at least 5 genes, including DSG2, MYBPC3, MYH7, PKP2, and TTN

81440

Nuclear encoded mitochondrial genes (eg, neurologic or myopathic phenotypes), genomic sequence panel, must include analysis of at least 100 genes, including BCS1L, C10orf2, COQ2, COX10, DGUOK, MPV17, OPA1, PDSS2, POLG, POLG2, RRM2B, SCO1, SCO2, SLC25A4, SUCLA2, SUCLG1, TAZ, TK2, and TYMP (Investigational)

81442

Noonan spectrum disorders (eg, Noonan syndrome, cardio-faci—cutaneous syndrome, Costello syndrome, LEOPARD syndrome, Noonan-like syndrome), genomic sequence analysis panel, must include sequencing of at least 12 genes, including BRAF, CBL, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, PTPN11, RAF1, RIT1, SHOC2, and SOS1 (investigational)

81460

Whole mitochondrial genome (eg, Leigh syndrome, mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes [MELAS], myoclonic epilepsy with ragged‐red fibers [MERFF], neuropathy, ataxia, and retinitis pigmentosa [NARP], Leber hereditary optic neuropathy [LHON]), genomic sequence, must include sequence analysis of entire mitochondrial genome with heteroplasmy detection (Investigational)

81465

Whole mitochondrial genome large deletion analysis panel (eg, Kearns‐Sayre syndrome, chronic progressive external ophthalmoplegia), including heteroplasmy detection, if performed (Investigational)

81470

X‐linked intellectual disability (XLID) (eg, syndromic and non-syndromic XLID); genomic sequence analysis panel, must include sequencing of at least 60 genes, including ARX, ATRX, CDKL5, FGD1, FMR1, HUWE1, IL1RAPL, KDM5C, L1CAM,MECP2,MED12,MID1,OCRL, RPS6KA3,and SLC16A2 (Investigational)

81471

X-linked intellectual disability (XLID) (eg, syndromic and non-syndromic XLID); duplication/deletion gene analysis, must include analysis of at least 60 genes, including ARX, ATRX, CDKL5, FGD1, FMR1, HUWE1, IL1RAPL, KDM5C, L1CAM,MECP2,MED12,MID1,OCRL, RPS6KA3,and SLC16A2 (Investigational)

81493

Coronary artery disease, mRNA, gene expression profiling by real-time RT-PCR of 23 genes, utilizing whole peripheral blood, algorithm reported as a risk score (investigational)

81539

Oncology (high-grade prostate cancer), biochemical assay of four proteins (Total PSA, Free PSA, Intact PSA, and human kallikrein-2 [hK2]), utilizing plasma or serum, prognostic algorithm reported as a probability score (Investigational)

83080

Hemosiderin; b-Hexosaminidase, each assay

88230

Tissue culture for non-neoplastic disorders; lymphocyte

88233

Tissue culture for non-neoplastic disorders; skin or other solid tissue biopsy

88235

Tissue culture for non-neoplastic disorders; amniotic fluid or chorionic villus cells

88237

Tissue culture for neoplastic disorders; bone marrow, blood cells

88239

Tissue culture for neoplastic disorders; solid tumor

88240

Cryopreservation, freezing and storage of cells, each cell line

88241

Thawing and expansion of frozen cells, each aliquot

88245

Chromosome analysis for breakage syndromes; baseline Sister Chromatid Exchange (SCE), 20-25 cells

88248

Chromosome analysis for breakage syndromes; baseline breakage, score 50-100 cells, count 20 cells, 2 karyotypes (eg, for ataxia telangiectasia, Fanconi anemia, fragile X)

88249

Chromosome analysis for breakage syndromes; score 100 cells, clastogen stress (eg, diepoxybutane, mitomycin C, ionizing radiation, UV radiation)

88261

Chromosome analysis; count 5 cells, 1 karyotype, with banding

88262

Chromosome analysis; count 15-20 cells, 2 karyotypes, with banding

88263

Chromosome analysis; count 45 cells for mosaicism, 2 karyotypes, with banding

88264

Chromosome analysis; analyze 20-25 cells

88267

Chromosome analysis, amniotic fluid or chorionic villus, count 15 cells, 1 karyotype, with banding

88269

Chromosome analysis, in situ for amniotic fluid cells, count cells from 6-12 colonies, 1 karyotype, with banding

88271

Molecular cytogenetics; DNA probe, each (e.g., FISH-fluorescence in situ hybridization)

88272

Chromosomal in situ hybridization, analyze 3 – 5 cells (e.g., for derivatives and markers)

88273

Chromosomal in situ hybridization, analyze 10 – 30 cells (e.g., for microdeletions)

88274

Interphase in situ hybridization, analyze 25 – 99 cells

88275

Interphase in situ hybridization, analyze 100 – 300 cells

88280

Chromosome analysis; additional karyotypes, each study

88283

Chromosome analysis; additional specialized banding technique (eg, NOR, C-banding)

88285

Chromosome analysis; additional cells counted, each study

88289

Chromosome analysis; additional high resolution study

88291

Cytogenetics and molecular cytogenetics, interpretation and report

96040

Medical genetics and genetic counseling services, each 30 minutes face-to-face with patient/family

0004M

Scoliosis, DNA analysis of 53 single nucleotide polymorphisms (SNPs), using saliva, prognostic algorithm reported as a risk score (investigational)

0005U

Oncology (prostate) gene expression profile by real-time RT-PCR of 3 genes (ERG, PCA3, and SPDEF), urine, algorithm reported as risk score (investigational)

0007U

Drug test(s), presumptive, with definitive confirmation of positive results, any number of drug classes, urine, includes specimen verification including DNA authentication in comparison to buccal DNA, per date of service (investigational)

0008U

Helicobacter pylori detection and antibiotic resistance, DNA, 16S and 23S rRNA, gyrA, pbp1, rdxA and rpoB, next generation sequencing, formalin-fixed paraffin embedded or fresh tissue, predictive, reported as positive or negative for resistance to clarithromycin, fluoroquinolones, metronidazole, amoxicillin, tetracycline and rifabutin (investigational)

0010U

Infectious disease (bacterial), strain typing by whole genome sequencing, phylogenetic-based report of strain relatedness, per submitted isolate

0012U

Germline disorders, gene rearrangement detection by whole genome next-generation sequencing, DNA, whole blood, report of specific gene rearrangement(s)

0013U

Oncology (solid organ neoplasia), gene rearrangement detection by whole genome next-generation sequencing, DNA, fresh or frozen tissue or cells, report of specific gene rearrangement(s)

0014U

Hematology (hematolymphoid neoplasia), gene rearrangement detection by whole genome next-generation sequencing, DNA, whole blood or bone marrow, report of specific gene rearrangement(s)

0015U

Drug metabolism (adverse drug reactions), DNA, 22 drug metabolism and transporter genes, real-time PCR, blood or buccal swab, genotype and metabolizer status for therapeutic decision support (investigational)

0016U

Oncology (hematolymphoid neoplasia), RNA, BCR/ABL1 major and minor breakpoint fusion transcripts, quantitative PCR amplification, blood or bone marrow, report of fusion not detected or detected with quantitation

0017U

Oncology (hematolymphoid neoplasia), JAK2 mutation, DNA, PCR amplification of exons 12-14 and sequence analysis, blood or bone marrow, report of JAK2 mutation not detected or detected

HCPCS Coding:

G9143

Warfarin responsiveness testing by genetic technique using any method, any number of specimen(s) (investigational)

S0265

Genetic counseling, under physician supervision, each 15 minutes

S3722

Dose optimization by area under the curve (AUC) analysis, for infusional 5-fluorouracil (investigational)

S3840

DNA analysis for germline mutations of the RET Proto-Oncogene for susceptibility to multiple endocrine neoplasia Type 2

S3841

Genetic testing for retinoblastoma

S3842

Genetic testing for Von Hippel-Lindau Disease

S3844

DNA analysis of the Connexin 26 Gene (GJB2) for susceptibility to congenital, profound, deafness

S3845

Genetic testing for Alpha-Thalassemia

S3846

Genetic testing for Hemoglobin E Beta-Thalassemia

S3849

Genetic testing for Niemann-Pick Disease

S3850

Genetic testing for sickle cell anemia

S3852

DNA analysis for APOE epsilon 4 allele for susceptibility to Alzheimer’s disease (investigational)

S3853

Genetic testing for myotonic muscular dystrophy

S3861

Genetic testing, sodium channel, voltage-gated, type V, alpha subunit (SCN5A) and variants for suspected Brugada Syndrome

S3865

Comprehensive gene sequence analysis for hypertrophic cardiomyopathy

S3866

Genetic analysis for a specific gene mutation for hypertrophic cardiomyopathy (HCM) in an individual with a known HCM mutation in the family

S3870

Comparative genomic hybridization (CGH) microarray testing for developmental delay, autism spectrum disorder and/or intellectual disability

REIMBURSEMENT INFORMATION:

BCBSF has adopted the U.S. Preventive Services Task Force (USPSTF) Recommendations. In order to be covered, Services shall be provided in accordance with prevailing medical standards consistent with the USPSTF Recommendations.

Codes 83080, 88230, 88233, 88235, 88237, 88239, 88240, 88241, 88245, 88248, 88249, 88261, 88262, 88263, 88264, 88267, 88269 are limited to four (4) tests within a 12-month period.

Code 88291 is limited to twenty-five (25) of each test within a 12-month period.

Code 88271 is limited to forty-one (41) tests within a 12-month period.

Code 88280 is limited to two (2) tests within a 12-month period.

Codes 88272, 88273, 88274, 88283, 88285, 88289, S3841, S3842, S3844, S3845, S3846, S3849, S3850, S3853 and S3861 are limited to one (1) of each test within a 12-month period.

The following information is required for services subject to medical review, including services in excess of reimbursement limitations: documentation to support medical necessity: reason for test(s), previous lab results, how the results of the test will be utilized, how the results of the test will contribute to improved health outcomes, or alters patient’s treatment and or management.

LOINC Codes:

Documentation Table

LOINC Codes

LOINC
Time Frame
Modifier Code

LOINC Time Frame Modifier Codes Narrative

Physician history and physical

28626-0

18805-2

Include all data of the selected type that represents observations made six months or fewer before starting date of service for the claim

Attending physician visit note

18733-6

18805-2

Include all data of the selected type that represents observations made six months or fewer before starting date of service for the claim.

Attending physician progress note

18741-9

18805-2

Include all data of the selected type that represents observations made six months or fewer before starting date of service for the claim.

Plan of treatment

18776-5

18805-2

Include all data of the selected type that represents observations made six months or fewer before starting date of service for the claim.

Laboratory studies

26436-6

18805-2

Include all data of the selected type that represents observations made six months or fewer before starting date of service for the claim

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage products:

The following National Coverage Determinations (NCDs) were reviewed on the last guideline reviewed date and are located at cms.gov:

• Pharmacogenomic Testing for Warfarin Response (90.1)

• Cytogenetic Studies (190.3).

The following were reviewed on the last guideline reviewed date and are located at palmettogba.com:

• MolDX LCDs (M00021, V10)

• Corus CAD Test Coding and Billing Guidelines (M0009)

• KIF6 Genotype Billing and Coding Guidelines

• LPA-Aspirin Genotype Billing and Coding Guidelines

• MolDX-CDD: ConfirmMDx Epigenetic Molecular Assay (L35632)

• MolDX-CDD: Genomic Health™ Oncotype DX® Prostate Cancer Assay (L36153)

• Progensa PCA3 Assay Coding and Billing Guidelines (M00013, V11)

• SLCO1B1 Genotype Billing and Coding Guidelines.

DEFINITIONS:

None applicable.

RELATED GUIDELINES:

Assays of Genetic Expression in Tumor Tissue as a Technique to Determine Prognosis in Patients with Breast Cancer, 05-86000-26
Genetic Testing for Hereditary Breast or Ovarian Cancer, 05-82000-30

Genetic Testing for Lynch Syndrome and Other Inherited Colon Cancer Syndromes , 05-82000-31

Tumor/Genetic Markers, 05-86000-22

OTHER:

None applicable.

REFERENCES:

  1. Ackerman MJ, Priori SG, Willems S et al. HRS/EHRA Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies. This document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Heart Rhythm 2011; 8(8):1308-39.
  2. Albala D, Kemeter MJ, et al, Health Economic Impact and Prospecitve Clinical Utility of Oncotype DX® Genomic Prostate Score, Rev Urol. 2016;18(3): 123-132.
  3. American College of Medical Genetics, Position Statement on Carrier Testing for Canavan Disease, accessed at acmg.net on 09/01/09.
  4. American College of Medical Genetics, Principles of Screening: Report of the Subcommittee on Screening of the American College of Medical Genetics Clinical Practice Committee, 02/97.
  5. American College of Obstetricians and Gynecologists (ACOG) Committee Opinion No. 446: array comparative genomic hybridization in prenatal diagnosis. Obstet Gynecol 2009; 114(5):1161-3.
  6. American College of Obstetricians and Gynecologists (ACOG) Committee Opinion No. 581: the use of chromosomal microarray analysis in prenatal diagnosis. Obstet Gynecol. Dec 2013;122(6):1374-1377.
  7. American College of Obstetricians and Gynecologists (ACOG) Committee Opinion No. 690: Carrier Screening in the Age of Genomic Medicine. Obstet Gynecol. 2017 Mar;129(3):e35-e40.
  8. American Gastroenterological Association (AGA), AGA Institute medical position statement on the diagnosis and management of celiac disease. Gastroenterology 2006; 131(6):1977-80.
  9. Ashley EA, Hershberger RE, Caleshu C et al. Genetics and cardiovascular disease: a policy statement from the American Heart Association. Circulation 2012; 126(1):142-57.
  10. Bejar RL, Ebert BL, Unraveling the Molecular Pathophysiology of Myelodysplastic Syndromes, J Clin Oncol 2011; 29:504-515.
  11. Bejar RL, Stevenson K, et al, Clinical Effect of Point Mutations in Myelodysplastic Syndromes, N Engl J Med 2011;364:2496-506.
  12. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.43 Genetic Testing for Cardiac Ion Channelopathies, 01/17.
  13. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.02.13 Genetic Testing for Alzheimer’s Disease, 04/17.
  14. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.02.28 Genetic Testing for Predisposition to Inherited Hypertrophic Cardiomyopathy, 03/17.
  15. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.30 Serologic Diagnosis of Celiac Disease, archived 01/13.
  16. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.33 Genetic and Protein Biomarkers for the Diagnosis and Cancer Risk Assessment of Prostate, 10/16.
  17. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.44 Genetic Testing for Familial Cutaneous Malignant Melanoma, 03/17.
  18. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.45 Molecular Analysis for Targeted Therapy of Non-Small-Cell Lung Cancer, 10/16.
  19. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.48 Genetic Testing for Warfarin Dose, 06/17.
  20. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.57 Non-BRCA Breast Cancer Risk Assessment (e.g., OncoVue), archived 08/14.
  21. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.59 Chromosomal Microarray (CMA) Analysis for the Genetic Evaluation of Patients with Developmental Delay/Intellectual Disability or Autism Spectrum Disorder, 08/17.
  22. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.63 Use of Common Genetic Variants (Single Nucleotide Polymorphisms) to Predict Risk of Nonfamilial Breast Cancer, 04/15.
  23. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.67 KIF6 Genotyping for Predicting Cardiovascular Risk and/or Effectiveness of Statin Therapy, 07/17.
  24. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.68 Laboratory and Genetic Testing for Use of 5-Fluorouracil in Patients with Cancer, 03/17.
  25. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.70 Genetic Testing for Lipoprotein (a) Variant(s) as a Decision Aid for Aspirin Treatment, 05/15.
  26. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.71 Genotyping for 9p21 Single Nucleotide Polymorphisms to Predict Risk of Cardiovascular Disease or Aneurysm, archived 03/16.
  27. Blue Cross Blue Shield Association Medical Reference Policy Manual 2.04.72 Gene Expression Testing in the Evaluation of Patients with Stable Ischemic Heart Disease, 01/17.
  28. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.83 Genetic Testing for FMR1 Mutations (Including Fragile X Syndrome), 01/17.
  29. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.86 Genetic Testing for Duchenne and Becker Muscular Dystrophy, 03/17.
  30. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.81 Genetic Testing for Rett Syndrome, 05/17.
  31. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.82 Genetic Testing for Inherited Thrombophilia, 05/17.
  32. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.88 Genetic Testing for PTEN Hamartoma Tumor Syndrome, 02/17.
  33. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.89 Genetic Testing for the Diagnosis of Inherited Peripheral Neuropathies, 01/17.
  34. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.93 Genetic Cancer Susceptibility Panels Using Next Generation Sequencing, 05/16.
  35. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.94 Genetic Testing for Lactase Insufficiency, 04/15.
  36. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.95, Human Leukocyte Antigen (HLA) Testing for Celiac Disease, 05/15.
  37. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.96 Genetic Testing for Statin-Induced Myopathy, 11/16.
  38. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.99 Genetic Testing for Hereditary Pancreatitis, 02/17.
  39. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.102 Whole Exome and Whole Genome Sequencing for Diagnosis of Genetic Disorders, 11/16.
  40. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.106 Genetic Testing for CHARGE Syndrome, 02/17.
  41. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.107 Carrier Screening for Genetic Diseases, 04/17.
  42. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.108 Fetal RHD Genotyping Using Maternal Plasma, 05/17.
  43. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.109 Genetic Testing for Epilepsy, 02/17.
  44. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.111 Gene Expression Profiling and Protein Biomarkers for Prostate Cancer Management, 11/16.
  45. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.114 Genetic Testing for Dilated Cardiomyopathy, 02/17.
  46. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.116 Invasive Prenatal (Fetal) Diagnostic Testing, 04/17.
  47. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.121 Miscellaneous Genetic and Molecular Diagnostic Tests, 07/17.
  48. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.122 Chromosomal Microarray Analysis for the Evaluation of Pregnancy Loss, 08/17.
  49. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.124 Genetic Testing for FLT3, NPM1, and CEBPA Mutations in Cytogenetically Normal Acute Myeloid Leukemia, 01/17.
  50. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.126 Moderate Penetrance Variants Associated With Breast Cancer in Individuals at High Breast Cancer Risk, 12/16.
  51. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.131 Pharmacogenetic Testing for Pain Management, 05/17.
  52. Blue Cross Blue Shield Association Medical Policy Reference Manual 2.04.137 Genetic Testing for Neurofibromatosis, 01/17.
  53. Blue Cross Blue Shield Association Medical Policy Reference Manual 4.02.05 Preimplantation Genetic Testing, 08/17.
  54. BlueCross BlueShield Association Technology Evaluation Center (TEC). Genetic testing for predisposition to inherited hypertrophic cardiomyopathy. 2009 TEC Assessments; Volume 24, Tab 11.
  55. Blue Cross Blue Shield Association Technology Evaluation Center (TEC). TEC Special Report: Array Comparative Genomic Hybridization (aCGH) for the Genetic Evaluation of Patients with Developmental Delay/Mental Retardation and Autism Spectrum Disorder. TEC Assessments 2009; Volume 24, Tab 10.
  56. Blue Cross Blue Shield Association Technology Evaluation Center (TEC). Special Report: Chromosomal Microarray for the Genetic Evaluation of Patients With Global Developmental Delay, Intellectual Disability, and Autism Spectrum Disorder. TEC Assessments. 2015;30.
  57. Brand TC, Zhang N, Crager MR, et al. Patient-specific meta-analysis of 2 clinical validation studies to predict pathologic outcomes in prostate cancer using the 17-Gene Genomic Prostate Score. Urology. Mar 2016;89:69-75.
  58. Cameron LD, Sherman KA, Marteau TM, Brown PM, Impact of Genetic Risk Information and Type of Disease on Perceived Risk, anticipated Affect, and Expected Consequences of Genetic Tests, Health Psychology, Vol 28(3), May 2009, 307-316.
  59. Centers for Disease Control and Prevention, Genetic Testing, last updated 07/21/09.
  60. Centers for Medicare & Medicaid Services (CMS), NCD for Cytogenetic Studies (190.3); located at cms.gov.
  61. Centers for Medicare & Medicaid Services (CMS), NCD for Pharmacogenomic Testing for Warfarin Response (90.1); located at cms.gov.
  62. Chen RC, Rumble RB, et al, Active Surveillance for the Management of Localized Prostate Cancer (Cancer Care Ontario Guideline): American Society of Clinical Oncology Clinical Practice Guideline Endorsement. J Clin Oncol. 2016 Jun 20;34(18):2182-90.
  63. Christensen KD, Roberts JS, Whitehouse PJ, et al. Disclosing pleiotropic effects during genetic risk assessment for Alzheimer disease: a randomized trial. Ann Intern Med. Feb 02 2016;164(3):155-163.
  64. ClinicalTrials.gov, Face Anthropometric Pattern Recognition Technology for Computer Aided Diagnosis of Human Genetic Disorders, sponsored by Carmel Medical Center, Soroka University Medical Center and Technion, Israel Institute of Technology, accessed 08/26/09.
  65. ClinicalTrials.gov, Association Analysis Between Single Nucleotide Polymorphisms in Statin-Related Genes and The Incidence of Myopathy Among Statin-Treated Patients, sponsored by National Taiwan University Hospital, accessed 06/28/13.
  66. ClinicalTrials.gov, DNA Diagnostic System for Statin Safety and Efficacy, sponsored by Genomas, Inc., accessed 06/28/13.
  67. ClinicalTrials.gov, Genetic Characterization of Individuals with Limb Girdle Muscular Dystrophy, sponsored by Nationwide Children’s Hospital, accessed 08/26/09.
  68. ClinicalTrials.gov, Genetic Studies of X-Linked Lymphoproliferative Disease, sponsored by National Institute of Allergy and Infectious Diseases (NIAID), accessed 08/26/09.
  69. ClinicalTrials.gov, Transition From Research to Disclosure in Human Genetics, sponsored by M.D. Anderson Cancer Center, accessed 08/26/09.
  70. ECRI Institute, BreastNext Comprehensive Testing Panel (Ambry Genetics Corp.) for Informing Diagnosis and Management of Hereditary Breast and Ovarian Cancer, 11/12.
  71. England JD, Gronseth GS, Franklin G et al. Practice Parameter: evaluation of distal symmetric polyneuropathy: role of laboratory and genetic testing (an evidence-based review). Report of the American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation. Neurology 2009; 72(2):185-92.
  72. Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group Recommendation: Use of Genomic Profiling to Assess Risk for Cardiovascular Disease (CVD) and Identify Individualized Prevention Strategies, 2010; accessed at egappreviews.org 06/25/13.
  73. Garcia-Closas M, Couch FJ, Lindstrom S et al. Genome-wide association studies identify four ER negative-specific breast cancer risk loci. Nat Genet 2013; 45(4):392-8.
  74. Gastroenterological Association (AGA) Institute. Medical Position Statement on the Diagnosis and Management of Celiac Disease. Gastroenterology 2006; 131(6):1977-80.
  75. Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and the Prenatal Diagnosis Committee of the Canadian College of Medical Geneticists (CCMG), Fragile X Testing in Obstetrics and Gynaecology in Canada, Joint SOGC-CCMG Committee Opinion, No. 216, September 2008.
  76. Genzyme Genetics-Document for Request for Allowable & Maximum Units for CPT Code, 2002.
  77. Gersh BJ, Maron BJ, Bonow RO et al. 2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2011.
  78. Gittelman MC, Hertzman B, et al, PCA3 molecular urine test as a predictor of repeat prostate biopsy outcome in men with previous negative biopsies: a prospective multicenter clinical study. J Urol. 2013 Jul;190(1):64-9. Doi: 10.1016/j.juro.2013.02.018.
  79. Grody WW, Griffin JH, Taylor AK, et al. American College of Medical Genetics Consensus Statement on Factor V Leiden Mutation Testing, accessed at acmg.net on 09/01/09.
  80. Gross SJ, Pletcher BA, Monaghan KG, Carrier Screening in Individuals of Ashkenazi Jewish Descent, American College of Medical Genetics (ACMG) Practice Guideline, January 2008, Vol. 10, No. 1.
  81. Guerreiro R, Wojtas A, et al, TREM2 Variants in Alzheimer’s Disease, N Engl J Med 2013;368:117-27.
  82. Hamdy FC, Donovan JL, Lane JA, et al. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med. Oct 13 2016;375(15):1415-1424.
  83. Herman L, Froelich J, et al, Utility of a Genomic-based, Personalized Medicine Test in Patients Presenting With Symptoms Suggesting Coronary Artery Disease, J Am Board Fam Med 2014;27:258 –267.
  84. Hochheiser L, Juusola JL, et al, Economic Utility of a Blood-Based Genomic Test for the Assessment of Patients with Symptoms Suggestive of Obstructive Coronary Artery Disease, Popul Health Manag. 2014 Feb 25.
  85. Hologic Health Economics: Medical Diagnostics Dossier for the PROGENSA® PCA3 Assay, March 2016.
  86. Jonsson T, Stefansson H, et al, Variant of TREM2 Associated with the Risk of Alzheimer’s Disease, N Engl J Med 2013;368:107-16.
  87. Konety B, Zappala SM, et al, The 4Kscore® Test Reduces Prostate Biopsy Rates in Community and Academic Urology Practices, Rev Urol. 2015;17(4):231-40.
  88. Ladapo JA, Blecker S, et al, Clinical Implications of Referral Bias in the Diagnostic Performance of Exercise Testing for Coronary Artery Disease, J Am Heart Assoc. 2013 Dec 13;2(6):e000505.
  89. Ladapo JA, Lyons H, et al, Enhanced Assessment of Chest Pain and Related Symptoms in the Primary Care Setting Through the Use of a Novel Personalized Medicine Genomic Test: Results From a Prospective Registry Study, Am J Med Qual. 2014 May 5.
  90. Lansky A, Elashoff MR, Ng V et al. A gender-specific blood-based gene expression score for assessing obstructive coronary artery disease in nondiabetic patients: results of the Personalized Risk Evaluation and Diagnosis in the Coronary Tree (PREDICT) trial. Am Heart J 2012; 164(3):320-6.
  91. McPherson JA, Davis K, Yau M et al. The Clinical Utility of Gene Expression Testing on the Diagnostic Evaluation of Patients Presenting to the Cardiologist With Symptoms of Suspected Obstructive Coronary Artery Disease: Results From the IMPACT (Investigation of a Molecular Personalized Coronary Gene Expression Test on Cardiology Practice Pattern) Trial. Crit Pathw Cardiol 2013; 12(2):37-42.
  92. Manning M, Hudgins L. Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med 2010; 12(11):742-5
  93. MdxHealth Clinical Evidence Dossier, ConfirmMDx for Prostate Cancer, 2016.
  94. Michelson DJ, Shevell MI, Sherr EH et al. Evidence Report: Genetic and metabolic testing on children with global developmental delay: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2011; 77(17):1629-35.
  95. Miller DT, Adam MP, Aradhya S et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010; 86(5):749-64.
  96. Moeschler JB, Shevell M, American Academy of Pediatrics Committee on Genetics, Clinical Genetic Evaluation of the Child with Mental Retardation or Developmental Delays, Pediatrics 2006 June; 117(6): 2304-16.
  97. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology-Acute Myeloid Leukemia V2.2016.
  98. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology-Breast and/or Ovarian Cancer Genetic Assessment V2.2017.
  99. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology-Breast Cancer Screening and Diagnosis V1.2016.
  100. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology- Myelodysplastic Syndromes V1.2017.
  101. National Comprehensive Cancer Network (NCCN), Genetic/Familial High-Risk Assessment for Breast and Ovarian Cancer V2.2017.
  102. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology-Prostate Cancer V3.2016.
  103. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology-Prostate Cancer Early Detection V.2.2016.
  104. National Digestive Diseases Information Clearinghouse-Hemochromatosis, NIH Publication No. 00-4621, 03/00.
  105. National Human Genome Research Institute, coverage and Reimbursement of Genetic Tests, last updated 05/15/09.
  106. National Institutes of Health. Genetic Testing: How It Is Used for Healthcare, April 2008.
  107. National Institutes of Health. The Task Force on Genetic Testing, September 1997.
  108. National Institute of Neurological Disorders and Stroke (NINDS), Peripheral Neuropathy Fact Sheet, last updated September 19, 2012; accessed at ninds.nih.gov 06/28/13.
  109. Palmetto GBA: Corus CAD Test Coding and Billing Guidelines (M0009) located at palmettogba.com.
  110. Palmetto GBA: Local Coverage Article for MolDx: KIF6 Genotype Billing and Coding Guidelines (A51894) located at palmettogba.com.
  111. Palmetto GBA Local Coverage Article for MolDx: LPA-ASPIRIN Genotype Billing and Coding Guidelines (A51896) located at palmettogba.com.
  112. Palmetto GBA: MolDX-CDD: ConfirmMDx Epigenetic Molecular Assay (L35632), located at palmettogba.com.
  113. Palmetto GBA: MolDX-CDD: Genomic Health™ Oncotype DX® Prostate Cancer Assay (L36153), located at palmettogba.com.
  114. Palmetto GBA: Progensa PCA3 Assay Coding and Billing Guidelines (M00013, V11), located at palmettogba.com.
  115. Palmetto GBA: Local Coverage Article for MolDx: SLCO1B1 Genotype Billing and Coding Guidelines, located at palmettogba.com. .
  116. Palmetto GBA: MolDX LCDs (M00021, V8), located at palmettogba.com.
  117. Parekh DJ, Punnen S, et al, A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer. Eur Urol. 2015 Sep;68(3):464-70. Doi: 10.1016/j.eururo.2014.10.021.
  118. Pescini F, Nannucci S, Bertaccini B, et al. The Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL) Scale: a screening tool to select patients for NOTCH3 gene analysis. Stroke. Nov 2012;43(11):2871-2876.
  119. Prior TW, Carrier Screening for Spinal Muscular Atrophy, American College of Medical Genetics (ACMG) Practice Guideline, November 2008, Vol. 10, No. 11.
  120. Robson ME, Storm CD, Weitzel J et al. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol 2010; 28(5):893-901.
  121. Sherman, S, Pletcher BA, Driscoll DA, Fragile X Syndrome: Diagnostic and Carrier Testing, American College of Medical Genetics (ACMG) Practice Guideline, October 2005, Vol. 7, No. 8.
  122. Thol F, Friesen I, et al, Prognostic Significance of ASXL1 Mutations in Patients With Myelodysplastic Syndromes, J Clin Oncol 2011; 29:2499-2506.
  123. Thomas GS, Voros S, McPherson JA et al. A Blood-Based Gene Expression Test for Obstructive Coronary Artery Disease Tested in Symptomatic Nondiabetic Patients Referred for Myocardial Perfusion Imaging The COMPASS Study. Circ Cardiovasc Genet 2013; 6(2):154-62.
  124. U.S Preventive Services Task Force (USPSTF), USPSTF Recommendations, accessed at: uspreventiveservicestaskforce.org.
  125. What are the Types of Genetic Tests? Library of Medicine (US). Genetics Home Reference; accessed at ghr.nlm.nih.gov 10/31/16.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Medical Policy & Coverage Committee on 09/28/17.

GUIDELINE UPDATE INFORMATION:

11/15/03

Medical Coverage Guideline Annual review. Developed separate guideline for Genetic Testing For Miscellaneous Diagnoses. Developed separate genetic testing guidelines for the following: BRCA1 and BRCA2, colon cancer (FAP and HNPCC), and medullary carcinoma of the thyroid (RET proto-oncogene).

01/01/04

Annual HCPCS coding update: added S3853.

07/01/05

HCPCS update: added S0265.

12/15/05

Biennial review: coverage unchanged.

01/01/06

Annual HCPCS coding update: added 83900, 83907, 83908, 83909, 83914; revised 83898, 83901.

06/15/06

Revision to include new codes into limitation section.

01/01/07

Annual HCPCS coding update: added 96040; deleted 99401, 99402, 99403, and 99404.

07/15/07

Annual review, coverage statements maintained, guideline reformatted, references updated.

01/01/08

Annual HCPCS coding update: revised 83898, 83900, 83901, and 83908.

01/01/09

Annual HCPCS coding update: descriptor revised for codes 83890, 83891, 83892, 83893, 83894, 83897, 83900, 83903, 83907, 83909, and 83914.

10/15/09

Annual review: position statement, reimbursement section, guideline title and references updated.

12/15/10

Revision; description section, inheritable disease diagnosis table reimbursement and coding sections updated; prenatal test table and Other Genetic Tests section added.

07/15/10

Revision; Other Genetic Tests section updated.

10/01/11

Revision; formatting changes.

11/15/11

Revision; CPT code 88275 removed from the Reimbursement Information section.

01/01/12

Annual HCPCS update. Added codes 81200-81408.

02/15/12

Revision; Postnatal and Other Genetic Tests section, Billing/Coding Information section and references updated.

04/01/12

Quarterly HCPCS update. Deleted codes S3835, S3837, S3843, S3847, S3848, S3851, S3860, S3862.

08/15/12

Revision; Postnatal and Other Genetic Tests section updated.

10/15/12

Revision; Postnatal and Other Genetic Tests, Coding, and references updated.

01/01/13

Annual HCPCS update: added codes 81161, 81252-81254, 81321-81326; revised codes 81400-81408; deleted codes 83890-83914; updated reimbursement section. Prenatal & Postnatal Genetic Tests sections and references updated.

05/15/13

Revision; Genetic Testing to Establish a Diagnosis of Inheritable Disease and Postnatal and Other Genetic Tests sections updated; coding and references updated.

07/01/13

Quarterly HCPCS update. Added code 0004M; revised codes 81400-81408; Program Exceptions section updated.

08/15/13

Revision; Postnatal and Other Genetic Tests, Program Exceptions, and references updated.

09/15/13

Revision; experimental test list and references updated.

11/15/13

Revision; Postnatal and Other Genetic Tests section and references updated.

01/01/14

Annual HCPCS update. Added code 81287; revised codes 81371, 81376, & S3870.

02/15/14

Revision; position statement section updated.

07/01/14

Quarterly HCPCS update. Revised codes 81402 & 81404.

08/15/14

Revision; position statement section and references updated.

10/15/14

Revision; Position statement section and references updated.

01/01/15

Annual HCPCS/CPT update. Added codes 81246, 81313, 81410-81471;deleted code S3855.

03/15/15

Revision; position statement section, coding, and references updated.

07/01/15

Quarterly CPT/HCPCS update. Revised codes 81401 and 81406.

10/15/15

Revision; position statement section and references updated.

10/26/15

Revision; investigational test list updated.

11/15/15

Revision; coding section updated.

12/15/15

Revision; position statement section, coding, program exception, and references updated.

01/01/16

Annual HCPCS/CPT update; codes 81170, 81218, 81219, 81272, 81273, 81311, 81314, 81412, 81432-81434, 81437, 81438, 81442, 81493 added; codes 81355, 81401-81404, 81435, 81436, 81445-81455 revised; code S3721 deleted.

02/15/16

Revision; position statement section updated.

04/01/16

Quarterly HCPCS/CPT update; code 0010M revised.

05/15/16

Revision; Position statement section, coding, and references updated.

08/08/16

Revision; experimental test list updated.

08/31/16

Revision; Position Statement section; experimental test list updated.

11/08/16

Revision; deleted code 81311.

12/15/16

Revision; Position statement section and references updated.

01/01/17

Annual CPT/HCPCS update. Added 81413, 81414, 81439, 81539; revised 81400-81408; deleted 81280-81282, 0010M.

02/15/17

Revision; position statement section and references updated.

04/15/17

Revision; FMR1 Mutations, Acute Myeloid Leukemia, CHARGE Syndrome, Neurofibromatosis, PTEN Hamartoma Tumor Syndrome, and Cytogenetic Studies position statements added; Hereditary Pancreatitis and Inherited Peripheral Neuropathy position statements updated; description, coding, and references updated.

05/01/17

CPT Code update: code 0005U added.

06/15/17

Revision; Position statement section updated including CADASIL Syndrome position statements added and genetic testing for Alzheimer Disease position statement revised; references updated.

08/01/17

Coding Updates: Added codes 0007U, 0008U, 0010U, 0012U-0017U.

10/15/17

Revision; CMA investigational position statement added for the evaluation of all other conditions of delayed development; Diagnosis Table, coding, and references updated.

Date Printed: October 20, 2017: 08:40 AM