MEDICAL POLICY Genetic Testing

Transcription

1 POLICY PG0041 EFFECTIVE /01/12 LAST REVIEW... 04/22/16 MEDICAL POLICY Genetic Testing GUIDELINES This policy does not certify benefits or authorization of benefits, which is designated by each individual policyholder contract. Paramount applies coding edits to all medical claims through coding logic software to evaluate the accuracy and adherence to accepted national standards. This guideline is solely for explaining correct procedure reporting and does not imply coverage and reimbursement. DESCRIPTION A genetic test is the analysis of human DNA, RNA, chromosomes, proteins, or certain metabolites in order to detect alterations related to a heritable or acquired disorder. This can be accomplished by directly examining the DNA or RNA that makes up a gene (direct testing), looking at markers co-inherited with a disease-causing gene (linkage testing), assaying certain metabolites (biochemical testing), or examining the chromosomes (cytogenetic testing). Clinical genetic tests are those in which specimens are examined and results reported to the provider or patient for the purpose of diagnosis, prevention or treatment in the care of individual patients. Genetic testing is performed for a variety of intended uses: Diagnostic testing (to diagnose disease) Predictive testing (generally performed to gather genetic data that can assist in clinical management, including therapeutic decision for an individual. Pre-symptomatic genetic testing (to predict future disease) Carrier testing (to identify carriers of genetic mutations) Prenatal testing (offered during pregnancy to identify fetuses that have certain diseases) Pre-implantation genetic testing (done in conjunction with invitro fertilization to determine whether embryos for implantation carry genes that could cause disease) Newborn screening (to test newborns shortly after birth to determine whether they have certain diseases known to cause problems with health and development) Pharmacogenetic testing (to determine the likelihood of an individual being responsive to a particular drug and/or to predict serious toxicity from a drug in order to optimize drug selection or drug dosage) Research genetic testing (used to help with research and development of gene-based therapy) Several hundred genetic tests are currently in use, and more are being developed. Although genetic testing can provide helpful information for diagnosing, treating, and preventing illness, there are limitations. For example, in a healthy patient, a positive result from a non-malignant genetic test does not always mean the patient will develop a disease. On the other hand, in some situation, a negative result does not guarantee the patient will not have a certain disorder. POLICY Some genetic testing requires prior authorization or may be non-covered. A provider must refer to the Paramount prior authorization list and specific medical policy in reference to specific tests for coverage determinations (this list may not be all-inclusive): PG0065 Colorectal Cancer Screening (81401, 81528) PG0067 Genetic Testing for Breast and Ovarian Cancers (81162, 81211, 81212, 81213, 81214, 81215, 81216, 81217, 81432, 81433, 81445, 81455) PG0125 DNA-Based Testing for Adolescent Idiopathic Scoliosis (AIS) (0004M) PG0280 Long QT Syndrome (LQTS) (81280, 81281, 81282, 81406) PG0287 Cell-Free DNA Tests For Fetal Aneuploidy (81420, 81507, 0009M) PG0296 Comparative Genomic Hybridization (CGH) (81228 & 81229) PG0298 Afirma Thyroid FNA Analysis (81545) PG0301 Genetic Expression Assays for Breast Cancer Prognosis (81519, 81479, 0008M) PG0302 Genetic Testing for Colorectal Cancer ( , , , 81403) PG0334 ThyroSeq (81545) PG0336 PTEN Gene Testing ( , 81432, 81435, 81436, 81445, 81455)

2 - 2 - PG0340 AlloMap Molecular-Expression Blood Test (81595) PG0355 Genetic Testing for Hereditary Thrombophilia (81240, 81241, 81291) PG0357 Gene Expression Profiling for Colorectal Cancer (81525) PG0360 Genetic Testing for FMR1 Mutations Including Fragile X Syndrome (81243, 81244) PG0362 Vectra DA (81490) PG0363 CORUS CAD (81493) PG0364 Cancer Type ID (81540) PG0368 GeneSight Assay for Refractory Depression (81479) Genetic testing codes that require prior authorization for : 81162, 81201, 81202, 81203, , 81225, 81226, 81227, 81228, 81229, 81235, 81242, 81243, 81244, 81251, , 81287, 81288, , , , 81332, , 81420, 81432, 81435, 81436, 81445, 81450, 81455, 81479, 81504, 81509, 81519, Genetic testing codes that do not require prior authorization for : 81170, , 81210, , 81245, 81246, 81250, , , 81270, 81272, 81273, 81275, 81276, 81310, 81311, , , 81350, 81355, , 81437, 81528, 81545, Genetic testing codes that are non-covered for : 81161, 81200, 81205, 81209, 81224, 81240, 81241, 81252, 81253, 81254, 81257, 81260, 81290, 81291, , 81330, 81331, 81410, 81411, 81412, , , 81430, 81431, 81433, 81434, 81438, 81440, 81442, 81460, 81465, 81470, 81471, 81490, 81493, 81500, 81503, , 81525, , 81540, 0008M Genetic testing codes that require prior authorization for : 81162, 81201, 81202, 81203, , 81225, 81226, 81227, 81228, 81229, 81235, , 81287, 81288, , , , 81332, , 81420, 81432, 81435, 81436, 81445, 81450, 81455, 81479, 81493, 81504, 81509, 81519, 81599, 0008M Genetic testing codes that do not require prior authorization for : 81170, , 81210, , 81245, 81246, 81250, , , 81270, 81272, 81273, 81275, 81276, 81310, 81311, , , 81350, 81355, , 81437, 81490, 81525, 81528, 81540, 81545, Genetic testing codes that are non-covered for : 81161, 81200, 81205, 81209, 81224, 81240, 81241, 81242, 81243, 81244, 81251, 81252, 81253, 81254, 81257, 81260, 81290, 81291, , , 81330, 81331, 81410, 81411, 81412, , , 81430, 81431, 81433, 81434, 81438, 81440, 81442, 81460, 81465, 81470, 81471, 81500, 81503, , Genetic testing codes that require prior authorization for : 81162, 81200, 81201, 81202, 81203, 81205, 81209, , 81224, 81225, 81226, 81227, 81228, 81229, 81235, 81240, 81241, 81242, 81243, 81244, 81251, 81252, 81253, 81254, 81257, 81260, , 81287, 81288, 81290, 81291, , , , , , 81410, 81411, 81412, , 81420, , , 81438, 81440, 81442, 81445, 81450, 81455, 81460, 81465, 81470, 81471, 81479, 81509, 81519, Genetic testing codes that do not require prior authorization for : 81170, , 81210, , 81245, 81246, 81250, , , 81270, 81272, 81273, 81275, 81276, 81310, 81311, , , 81350, 81355, , 81437, 81528, 81545, Genetic testing codes that are non-covered for : 81161, 81490, 81493, , 81525, , 81540, 0008M All Product Lines

3 - 3 - Cytogenetic studies ( ) do not require prior authorization for all product lines. Code has a limit of 25 units per 365 days. Proprietary MAA codes 0001M-0004M, 0006M, 0007M, 0009M, 0010M are non-covered for all product lines.,, Coverage and authorization for genetic testing is determined by review. The testing must have direct effect on the management and clinical care of the individual being tested, and must contain all of the following criteria: The genetic disorder is associated with a significant disability or has a lethal natural history The risk of the significant disability or lethality from the genetic disorder cannot be determined through other diagnostic testing A specific mutation, or set of mutations, has been proven valid in the scientific literature to be reliable, associated with the disease The results of the genetic test could impact the medical management of the individual being tested The genetic test will likely result in an anticipated improvement in net health outcomes for the individual being tested (i.e. the disease is treatable or preventable) When requesting prior authorization review, the patient s medical history/record and details of the lab facility providing the requested service must be provided. An approved request will only be given to a specific lab for a specific provider for a specific service. Genetic testing may be denied as experimental or not medically necessary based on the information submitted. The physician, lab or facility ordering the service will be financially responsible if prior authorization is not obtained. Members who choose to proceed with unauthorized genetic testing bear the responsibility for the cost. The provider should always secure a Waiver of Responsibility prior to providing the testing to assure member understanding of their financial responsibility. While most genetic testing requires prior authorization, the following services have been reviewed by The Plan s medical staff with the determination that they are not medically supported and therefore are non-covered (this list may not be all-inclusive): PG-0111 VeriStrat (81538) PG-0119 DecisionDX-UM PG0122 In Vitro Chemoresistance and Chemosensitivity Assays (81535, 81536) PG0181 Topographic Genotyping Paramount covers cytogenetic studies ( ) when they are reasonable and necessary for the diagnosis or treatment of the following conditions: Genetic disorders (e.g., mongolism) in a fetus Failure of sexual development Chronic myelogenous leukemia Acute leukemias lymphoid (FAB L1-L3), myeloid (FAB M0-M7), and unclassified Mylodysplasia NOTE: Molecular cytogenetics; DNA probe each (88271) will have a limit of 25 units per 365 days. Modifier 91 will not allow for additional units. CODING/BILLING INFORMATION The appearance of a code in this section does not necessarily indicate coverage. Codes that are covered may have selection criteria that must be met. Payment for supplies may be included in payment for other services rendered. Tier 1 Molecular Pathology Procedures DMD (dystrophin) (e.g., Duchenne/Becker muscular dystrophy) deletion analysis, and duplication analysis, Non-covered Non-covered Non-covered

4 - 4 - if performed BRCA1, BRCA2 (breast cancer 1 and 2) (eg, hereditary breast and ovarian cancer) gene analysis; full sequence analysis and full duplication/deletion analysis ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase) (eg, acquired imatinib tyrosine kinase inhibitor resistance), gene analysis, variants in the kinase domain ASPA (aspartoacylase) (e.g., Canavan disease) gene analysis, common variants (e.g., E285A, Y231X) APC (adenomatous polyposis coli) (e.g., familial adenomatosis polyposis [FAP], attenuated FAP) gene analysis; full gene sequence APC (adenomatous polyposis coli) (e.g., familial adenomatosis polyposis [FAP], attenuated FAP) gene analysis; known familial variants APC (adenomatous polyposis coli) (e.g., familial adenomatosis polyposis [FAP], attenuated FAP) gene analysis; duplication/deletion variants BCKDHB (branched-chain keto acid dehydrogenase E1, beta polypeptide) (e.g., Maple syrup urine disease) gene analysis, common variants (e.g., R183P, G278S, E422X) BCR/ABL1 (t(9;22)) (e.g., chronic myelogenous leukemia) translocation analysis; major breakpoint, qualitative or quantitative BCR/ABL1 (t(9;22)) (e.g., chronic myelogenous leukemia) translocation analysis; minor breakpoint, qualitative or quantitative BCR/ABL1 (t(9;22)) (e.g., chronic myelogenous leukemia) translocation analysis; other breakpoint, qualitative or quantitative BLM (Bloom syndrome, RecQ helicase-like) (e.g., Bloom syndrome) gene analysis, 2281del6ins7 variant BRAF (B-Raf proto-oncogene, serine/threonine kinase) (e.g., colon cancer, melanoma), gene analysis, V600 variant(s) BRCA1, BRCA2 (breast cancer 1 and 2) (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis and common duplication/deletion variants in BRCA1 (i.e., exon 13 del 3.835kb, exon 13 dup 6kb, exon del 26kb, exon 22 del 510bp, exon 8-9 del 7.1kb) BRCA1, BRCA2 (breast cancer 1 and 2) (e.g., hereditary breast and ovarian cancer) gene analysis; 185delAG, 5385insC, 6174delT variants BRCA1, BRCA2 (breast cancer 1 and 2) (e.g., hereditary breast and ovarian cancer) gene analysis; uncommon duplication/deletion variants BRCA1 (breast cancer 1) (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis and common duplication/deletion variants (i.e., exon 13 del 3.835kb, exon 13 dup 6kb, exon del 26kb, exon 22 del 510bp, exon 8-9 del 7.1kb) BRCA1 (breast cancer 1) (e.g., hereditary breast and ovarian cancer) gene analysis; known familial variant BRCA2 (breast cancer 2) (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis BRCA2 (breast cancer 2) (e.g., hereditary breast and ovarian cancer) gene analysis; known familial variant PG0067 Genetic Testing for Breast and Ovarian Cancers Non-covered Non-covered PG0302 Genetic Testing for Colorectal Cancer PG0302 Genetic Testing for Colorectal Cancer PG0302 Genetic Testing for Colorectal Cancer Non-covered Non-covered Non-covered Non-covered PG0067 Genetic Testing for Breast and Ovarian Cancers PG0067 Genetic Testing for Breast and Ovarian Cancers PG0067 Genetic Testing for Breast and Ovarian Cancers PG0067 Genetic Testing for Breast and Ovarian Cancers PG0067 Genetic Testing for Breast and Ovarian Cancers PG0067 Genetic Testing for Breast and Ovarian Cancers PG0067 Genetic Testing for Breast and Ovarian Cancers

5 CEBPA (CCAAT/enhancer binding protein [C/EBP], alpha) (eg, acute myeloid leukemia), gene analysis, full gene sequence CALR (calreticulin) (eg, myeloproliferative disorders), gene analysis, common variants in exon CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; common variants (e.g., ACMG/ACOG guidelines) CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; known familial variants CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; duplication/deletion variants CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; full gene sequence CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; intron 8 poly-t analysis (e.g., male infertility) CYP2C19 (cytochrome P450, family 2, subfamily C, polypeptide 19) (e.g., drug metabolism), gene analysis, common variants (e.g., *2, *3, *4, *8, *17) 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) CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) (e.g., drug metabolism), gene analysis, common variants (e.g., *2, *3, *5, *6) 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) Cytogenomic constitutional (genome-wide) microarray analysis; interrogation of genomic regions for copy number and single nucleotide polymorphism (SNP) variants for chromosomal abnormalities EGFR (epidermal growth factor receptor) (e.g., nonsmall cell lung cancer) gene analysis, common variants (e.g., exon 19 LREA deletion, L858R, T790M, G719A, G719S, L861Q) (LCD L32288) F2 (prothrombin, coagulation factor II) (e.g., hereditary hypercoagulability) gene analysis, 20210G>A variant F5 (coagulation Factor V) (e.g., hereditary hypercoagulability) gene analysis, Leiden variant FANCC (Fanconi anemia, complementation group C) (e.g., Fanconi anemia, type C) gene analysis, common variant (e.g., IVS4+4A>T) FMR1 (Fragile X mental retardation 1) (e.g., fragile X mental retardation) gene analysis; evaluation to detect abnormal (e.g., expanded) alleles FMR1 (Fragile X mental retardation 1) (e.g., fragile X mental retardation) gene analysis; characterization of alleles (e.g., expanded size and methylation status) FLT3 (fms-related tyrosine kinase 3) (eg, acute myeloid leukemia), gene analysis; internal tandem duplication (ITD) variants (i.e., exons 14, 15) FLT3 (fms-related tyrosine kinase 3) (eg, acute myeloid leukemia), gene analysis; tyrosine kinase Non-covered Non-covered PG0296 Comparative Genomic Hybridization (CGH) PG0296 Comparative Genomic Hybridization (CGH) PG0355 Genetic Testing for Hereditary Thrombophilia PG0355 Genetic Testing for Hereditary Thrombophilia Non-covered PG0360 Genetic Testing for FMR1 Mutations Including Fragile X Syndrome PG0360 Genetic Testing for FMR1 Mutations Including Fragile X Syndrome

6 - 6 - domain (TKD) variants (eg, D835, I836) G6PC (glucose-6-phosphatase, catalytic subunit) (e.g., Glycogen storage disease, Type 1a, von Gierke disease) gene analysis, common variants (e.g., R83C, Q347X) GBA (glucosidase, beta, acid) (e.g., Gaucher disease) gene analysis, common variants (e.g., N370S, 84GG, L444P, IVS2+1G>A) GJB2 (gap junction protein, beta 2, 26kDa, connexin 26) (e.g., nonsyndromic hearing loss) gene analysis; full gene sequence (LCD L32288) GJB2 (gap junction protein, beta 2, 26kDa; connexin 26) (e.g., nonsyndromic hearing loss) gene analysis; known familial variants (LCD L32288) 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)]) (LCD L32288) HEXA (hexosaminidase A [alpha polypeptide]) (e.g., Tay-Sachs disease) gene analysis, common variants (e.g., 1278insTATC, G>C, G269S) HFE (hemochromatosis) (e.g., hereditary hemochromatosis) gene analysis, common variants (e.g., C282Y, H63D) 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) 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., T>C, R696P) 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) 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) IGH@ (Immunoglobulin heavy chain locus) (e.g., leukemia and lymphoma, B-cell), variable region somatic mutation analysis IGK@ (Immunoglobulin kappa light chain locus) (e.g., leukemia and lymphoma, B-cell), gene rearrangement analysis, evaluation to detect abnormal clonal population(s) 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) 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 Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered

7 - 7 - to code for primary procedure) Chimerism (engraftment) analysis, post transplantation specimen (e.g., hematopoietic stem cell), includes comparison to previously performed baseline analyses; without cell selection 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 JAK2 (Janus kinase 2) (e.g., myeloproliferative disorder) gene analysis, p.val617phe (V617F) variant 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) KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (eg, mastocytosis), gene analysis, D816 variant(s) KRAS (Kirsten rat sarcoma viral oncogene homolog) (e.g., carcinoma) gene analysis, variants in exon 2 (eg, codons 12 and 13) (KRAS (Kirsten rat sarcoma viral oncogene homolog) (eg, carcinoma) gene analysis; additional variant(s) (eg, codon 61, codon 146) Long QT syndrome gene analyses (e.g., KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP, SNTA1, and ANK2); full sequence analysis Long QT syndrome gene analyses (e.g., KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP, SNTA1, and ANK2); known familial sequence variant Long QT syndrome gene analyses (e.g., KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP, SNTA1, and ANK2); duplication/deletion variants MGMT (O-6-methylguanine-DNA methyltransferase) (e.g., glioblastoma multiforme), methylation analysis LH1 (mutl homolog 1, colon cancer, nonpolyposis type 2) (eg, hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; promoter methylation analysis MCOLN1 (mucolipin 1) (e.g., Mucolipidosis, type IV) gene analysis, common variants (e.g., IVS3-2A>G, del6.4kb) MTHFR (5,10-methylenetetrahydrofolate reductase) (e.g., hereditary hypercoagulability) gene analysis, common variants (e.g., 677T, 1298C) MLH1 (mutl homolog 1, colon cancer, nonpolyposis type 2) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis MLH1 (mutl homolog 1, colon cancer, nonpolyposis type 2) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; known familial variants MLH1 (mutl homolog 1, colon cancer, nonpolyposis type 2) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; PG0280 Long QT Syndrome (LQTS) PG0280 Long QT Syndrome (LQTS) PG0280 Long QT Syndrome (LQTS) Non-covered Non-covered PG0355 Genetic Testing for Hereditary Thrombophilia PG0302 Genetic Testing for Colorectal Cancer PG0302 Genetic Testing for Colorectal Cancer PG0302 Genetic Testing for Colorectal Cancer

8 - 8 - duplication/deletion variants MSH2 (muts homolog 2, colon cancer, nonpolyposis type 1) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis MSH2 (muts homolog 2, colon cancer, nonpolyposis type 1) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; known familial variants MSH2 (muts homolog 2, colon cancer, nonpolyposis type 1) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; duplication/deletion variants MSH6 (muts homolog 6 [E. coli]) (e.g. hereditary nonpolyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis MSH6 (muts homolog 6 [E. coli]) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; known familial variants MSH6 (muts homolog 6 [E. coli]) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; duplication/deletion variants Microsatellite instability analysis (e.g., hereditary nonpolyposis colorectal cancer, Lynch syndrome) of markers for mismatch repair deficiency (e.g., BAT25, BAT26), includes comparison of neoplastic and normal tissue, if performed MECP2 (methyl CpG binding protein 2) (e.g., Rett syndrome) gene analysis; full sequence analysis MECP2 (methyl CpG binding protein 2) (e.g., Rett syndrome) gene analysis; known familial variant MECP2 (methyl CpG binding protein 2) (e.g., Rett syndrome) gene analysis; duplication/ deletion variants NPM1 (nucleophosmin) (e.g., acute myeloid leukemia) gene analysis, exon 12 variants NRAS (neuroblastoma RAS viral [v-ras] oncogene homolog) (eg, colorectal carcinoma), gene analysis, variants in exon 2 (eg, codons 12 and 13) and exon 3 (eg, codon 61) PCA3/KLK3 (prostate cancer antigen 3 [non-protein coding]/kallikrein-related peptidase 3 [prostate specific antigen]) ratio (eg, prostate cancer) PDGFRA (platelet-derived growth factor receptor, alpha polypeptide) (eg, gastrointestinal stromal tumor [GIST]), gene analysis, targeted sequence analysis (eg, exons 12, 18) 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 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 PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full PG0302 Genetic Testing for Colorectal Cancer PG0302 Genetic Testing for Colorectal Cancer PG0302 Genetic Testing for Colorectal Cancer PG0302 Genetic Testing for Colorectal Cancer PG0302 Genetic Testing for Colorectal Cancer PG0302 Genetic Testing for Colorectal Cancer PG0302 Genetic Testing for Colorectal Cancer Non-covered Non-covered Non-covered PG0302 Genetic Testing for Colorectal Cancer

9 - 9 - sequence analysis PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; known familial variants PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; duplication/deletion variants PTEN (phosphatase and tensin homolog) (e.g., Cowden syndrome, PTEN hamartoma tumor syndrome) gene analysis; full sequence analysis (LCD L32288) PTEN (phosphatase and tensin homolog) (e.g., Cowden syndrome, PTEN hamartoma tumor syndrome) gene analysis; known familial variant (LCD L32288) PTEN (phosphatase and tensin homolog) (e.g., Cowden syndrome, PTEN hamartoma tumor syndrome) gene analysis; duplication/deletion variant (LCD L32288) PMP22 (peripheral myelin protein 22) (e.g., Charcot- Marie-Tooth, hereditary neuropathy with liability to pressure palsies) gene analysis; duplication/deletion analysis (LCD L32288) PMP22 (peripheral myelin protein 22) (e.g., Charcot- Marie-Tooth, hereditary neuropathy with liability to pressure palsies) gene analysis; full sequence analysis (LCD L32288) PMP22 (peripheral myelin protein 22) (e.g., Charcot- Marie-Tooth, hereditary neuropathy with liability to pressure palsies) gene analysis; known familial variant (LCD L32288) SMPD1(sphingomyelin phosphodiesterase 1, acid lysosomal) (e.g., Niemann-Pick disease, Type A) gene analysis, common variants (e.g., R496L, L302P, fsp330) SNRPN/UBE3A (small nuclear ribonucleoprotein polypeptide N and ubiquitin protein ligase E3A) (e.g., Prader-Willi syndrome and/or Angelman syndrome), methylation analysis 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) 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) 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) TRG@ (T cell antigen receptor, gamma) (e.g., leukemia and lymphoma), gene rearrangement analysis, evaluation to detect abnormal clonal population(s) UGT1A1 (UDP glucuronosyltransferase 1 family, polypeptide A1) (e.g., irinotecan metabolism), gene analysis, common variants (e.g., *28, *36, *37) VKORC1 (vitamin K epoxide reductase complex, subunit 1) (e.g., warfarin metabolism), gene analysis, PG0302 Genetic Testing for Colorectal Cancer PG0302 Genetic Testing for Colorectal Cancer PG0336 PTEN Gene Testing PG0336 PTEN Gene Testing PG0336 PTEN Gene Testing Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered

10 common variant(s) (e.g., -1639G>A, c c>t) HLA Class I and II typing, low resolution (e.g., antigen equivalents); HLA-A, -B, -C, -DRB1/3/4/5, and -DQB HLA Class I and II typing, low resolution (e.g., antigen equivalents); HLA-A, -B, and -DRB1/3/4/5 (e.g., verification typing) HLA Class I typing, low resolution (e.g., antigen equivalents); complete (i.e., HLA-A, -B, and -C) HLA Class I typing, low resolution (e.g., antigen equivalents); one locus (e.g., HLA-A, -B, or -C), each HLA Class I typing, low resolution (e.g., antigen equivalents); one antigen equivalent (e.g., B*27), each HLA Class II typing, low resolution (e.g., antigen equivalents); HLA-DRB1/3/4/5 and -DQB HLA Class II typing, low resolution (e.g., antigen equivalents); one locus (e.g., HLA-DRB1/3/4/5, - DQB1, -DQA1, -DPB1, or -DPA1), each HLA Class II typing, low resolution (e.g., antigen equivalents); one antigen equivalent, each HLA Class I typing, high resolution (i.e., alleles or allele groups); complete (i.e., HLA-A, -B, and -C) HLA Class I typing, high resolution (i.e., alleles or allele groups); complete (i.e., HLA-A, -B, and -C) HLA Class I typing, high resolution (i.e., alleles or allele groups); one locus (e.g., HLA-A, -B, or -C), each HLA Class I typing, high resolution (i.e., alleles or allele groups); one allele or allele group (e.g., B*57:01P), each HLA Class II typing, high resolution (i.e., alleles or allele groups); one locus (e.g., HLA-DRB1, -DRB3, - DRB4, -DRB5, -DQB1, -DQA1, -DPB1, or -DPA1), each HLA Class II typing, high resolution (i.e., alleles or allele groups); one allele or allele group (e.g., HLA- DQB1*06:02P), each Tier 2 Molecular Pathology Procedures Molecular pathology procedure, Level 1 analysis)(e.g., identification of single germline variant [e.g., SNP] by techniques such as restriction enzyme digestion or melt curve analysis) ALL REQUIRE PRIOR AUTHORIZATION for all product lines Non-covered genes for all product lines (this list may not be all-inclusive): ABCC8, F1388del ACADM, K304E AGTR1, 1166A>C BCKDHA, Y438n CCR5, del CLRN1, N48K DPYD, IVS14+1G>A FGFR1, P252R FGFR3, P250R FKTN, retro ins v GNE, M712T

11 Molecular pathology procedure, Level 1 analysis)(e.g., identification of single germline variant [e.g., SNP] by techniques such as restriction enzyme digestion or melt curve analysis) 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) HPA-6 HPA-9 IVD, A282V LCT, C>T NEB, exon 55 PCDH15, R245X SHOC2, S2G SLCO1B1, V174A SMN1, exon 7 del SRY, fgs TOR1A, var for all product lines PG0065 Colorectal Cancer Screening Non-covered genes for all product lines (this list may not be all-inclusive): ABCC8, cv ACADM, cv ADRB2, cv AFF2, detect abn APOB, cv APOE, cv AR, alleles ATN1 ATXN1 ATXN10 ATXN2 ATXN3 ATXN7 ATXN8OS CACNA1A CBS, cv CFH_ARMS2, cv CNBP CSTB CYP3A4, cv CYP3A5, cv DEK/NUP214, ta DMPK, detect eval EML4_ALK, ta or ia ETV6/NTRK3 EWSR1_ATF1 FGFR3, cv FLG, cv FUS/DDIT3 FXN, alleles GALC, cv GALT, cv H19, ma HBB, cv HTT, alleles KCNQ1OT1, ma

12 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) Molecular pathology procedure, Level 3 (eg, >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 of 1 exon, loss of heterozygosity [LOH], uniparental disomy [UPD]) Molecular pathology procedure, Level 4 (eg, 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) LRRK2, cv MED12, cv MEG3_DLK1, ma MLL_AFF1, ta qual quan MLL_MLLT3, ta, qual quan MT-ATP6, cv MT-ND4, MT-ND6, cv MT-ND5, cv MT-RNR1, cv MT-TK, cv MT-TL1, cv MT-TS1_MT-RNR1, cv NOD2 NPM1_ALK, ta PABPN1 PPP2R2B PRSS1, cv PYGM, cv SEPT9, ma SMN1_SMN2, dosage SMN1_SMN2, dup_del SS18_SSX1, ta SS18_SSX2, ta TBP, aa for all product lines Non-covered genes for all product lines (this list may not be all-inclusive): C18q C1p-/19q, del COL1A1/PDGFB, mbp qual quan CYP21A2, cv ESR1_PGR, ratio MEFV, cv MPL, cv TRD, delta UPD, str for all product lines PG0302 Genetic Testing for Colorectal Cancer Non-covered genes for all product lines (this list may not be all-inclusive): ACADS, kfv ACADVL, kfv ACTA2, kfv ANG, fgs ARX, d_d BTD, kfv CASR, kfv CDH1, kfv CEL, exon 11 COL1A2, kfv CTNNB1, tsa

13 Molecular pathology procedure, Level 4 (eg, 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) CTNNB1, tsa CYP21A2, kfv DAZ_SRY, cdel DHCR7, kfv DLAT, kfv DLD, kfv DNMT3A, tsa ENG, kfv F12, ts ex 9 F9, kfv FBN1, kfv FGFR2, kfv FGFR3, exon 7 FGFR3, kfv FH, kfv GAA, kfv GALT, kfv GJB1, fgs GLA, kfv GNAQ, cv GRN, kfv HBB, dup_del HEXA, kfv HRAS, exon 2 JAG1, kfv KCNC3, tsa KCNJ11, fgs KCNJ2, fgs Killer cell imm-like receptor KRAS, exon 3 KRAS, kfv LDLR, kfv MAPT, kfv MC4R, fgs MECP2, kfv MEFV, kfv MEN1, kfv MICA, cv MMACHC, kfv MPL, exon 10 MT-RNR1, fgs MT-RNR1_MT-TS1, kfv MT-TS1, fgs NDP, d_d NHLRC1, fgs NR0B1, kfv PC, kfv PDHA1, kfv PDHB, kfv PDHX, kfv PHOX2B, dup_del PLN, fgs

14 Molecular pathology procedure, Level 4 (eg, 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) Molecular pathology procedure, Level 5 (eg, 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) PRSS1, kfv PTPN11, kfv RHD, del a RHD, maternal SDH, kfv SH2D1A, dup_del SMN1, kfv TGFBR1, kfv TGFBR2, kfv TTR, kfv TWIST, kfv TWIST1, dup_del UBA1, tsa VKORC1, kfv for all product lines Non-covered genes for all product lines (this list may not be all-inclusive): ACADS, tsa AFF2, characterize AQP2, fgs ARX, fgs AVPR2, fgs BBS10, fgs BTD, fgs C10orf2, fgs CAV3, fgs CD40LG, fgs CLRN1, fgs COX6B1, fgs CPT2, fgs CRX, fgs CSTB, fgs CYP1B1, fgs DMPK, characterize alleles EGR2, fgs EMD, Dup_del EPM2A, fgs FGF23, fgs FGFR2, tsa FGFR3, tsa FHL1, fgs FKRP, fgs FOXG1, fgs FSHMD1A, ab a FSHMD1A, hap FXN, fgs GH1, fgs GP1BB, fgs HBA1_HBA2, dup_del HBB, fgs HNF1B, dup_del HRAS, fgs

15 Molecular pathology procedure, Level 5 (eg, 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) HSD11B2, fgs HSD3B2, fgs HSPB1, fgs INS, fgs KCNJ1, fgs KCNJ10, fgs LITAF, fgs MEFV, fgs MEN1, dup_del MMACHC, fgs MPV17, dup_del NDP, fgs NDUFA1, fgs NDUFAF2, fgs NDUFS4, fgs NIPA1, fgs NLGN4X, dup_del NPC2, fgs NR0B1, fgs PDX1, fgs PHOX2B, fgs PIK3CA, tsa PLP1, Dup_del PQBP1, Dup_del PRNP, fgs PROP1, fgs PRPH2, fgs RAF1, tsa RHO, fgs RP1, fgs SCN1B, fgs SCO2, fgs SDHC, dup_del SDHD, fgs SGCG, dup_del SH2D1A, fgs SLC16A2, dup_del SLC25A20, dup_del SLC25A4, fgs SOD1, fgs SPINK1, fgs STK11, dup_del TACO1, fgs THAP1, fgs TOR1A, fgs TP53, 2-5 exons TTPA, fgs TTR, fgs TWIST1, fgs TYR, fgs USH1G, fgs VWF, tsa

16 Molecular pathology procedure, Level 5 (eg, 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) Molecular pathology procedure, Level 6 (eg, analysis of 6-10 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of exons, regionally targeted cytogenomic array analysis) ZEB2, dup_del ZNF41, fgs for all product lines Non-covered genes for all product lines (this list may not be all-inclusive): ABCD1, fgs ACADS, fgs ACTA2, fgs ACTC1, fgs ANKRD1, fgs APTX, fgs AR, fgs ARSA, fgs BCKDHA, fgs BCS1L, fgs BMPR2, dup_del CASQ2, fgs CASR, fgs CDKL5, dup_del CHRNA4, fgs CHRNB2, fgs COX10, fgs COX15, fgs CYP11B1, fgs CYP17A1, fgs CYP21A2, fgs DBT, dup_del DCX, fgs DES, fgs DFNB59, fgs DGUOK, fgs DHCR7, fgs EIF2B2, fgs EMD, fgs ENG, dup_del EYA1, dup_del F9, fgs FGFR1, fgs FH, fgs FKTN, fgs FTSJ1, dup_del GABRG2, fgs GCH1, fgs GDAP1, fgs GFAP, fgs GHR, fgs GHRHR, fgs GLA, fgs HBA1_HBA2, fgs HNF1A, fgs

17 Molecular pathology procedure, Level 6 (eg, analysis of 6-10 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of exons, regionally targeted cytogenomic array analysis) HNF1B, fgs HTRA1, fgs IDS, fgs IL2RG, fgs ISPD, fgs KRAS, fgs LAMP2, fgs LDLR, dup_del MMAA, fgs MMAB, fgs MPI, fgs MPV17, fgs MPZ, fgs MTM1, dup_del MYL2, fgs MYL3, fgs MYOT, fgs NDUFS7, fgs NDUFS8, fgs NDUFV1, fgs NEFL, fgs NF2, dup_del NLGN3, fgs NLGN4X, fgs NPHP1, dup_del NPHS2, fgs NSD1, dup_del OTC, fgs PAFAH1B1, dup_del PARK2, dup_del PCCA, dup_del PCDH19, fgs PDHA1, dup_del PDHB, fgs PINK1, fgs PLP1, fgs POU1F1, fgs PQBP1, fgs PRX, fgs PSEN1, fgs RAB7A, fgs RAI1, fgs REEP1, fgs RPS19, fgs RRM2B, fgs SCO1, fgs SDHB, fgs SDHC, fgs SGCA, fgs SGCB, fgs SGCD, fgs SGCE, dup_del

18 Molecular pathology procedure, Level 6 (eg, analysis of 6-10 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of exons, regionally targeted cytogenomic array analysis) Molecular pathology procedure, Level 7 (e.g., analysis of exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of exons, cytogenomic array analysis for neoplasia) SGCG, fgs SHOC2, fgs SHOX, fgs SIL1, fgs SLC16A2, fgs SLC22A5, fgs SLC25A20, fgs SLC2A1, fgs SMAD4, dup_del SMN1, fgs SPAST, dup_del SPG7, dup_del SPRED1, fgs STAT3, tsa STK11, fgs SURF1, fgs TARDBP, fgs TBX5, fgs TCF4, dup_del TGFBR1, fgs TGFBR2, fgs THRB, fgs_tsa >5 exons TK2, fgs TNNC1, fgs TNNI3, fgs TP53, fgs or tsa >5 exons TPM1, fgs TSC1, dup_del TYMP, fgs WT1, fgs ZEB2, fgs for all product lines PG0280 Long QT Syndrome (LQTS) Non-covered genes for all product lines (this list may not be all-inclusive): ACADVL, fgs ACTN4, fgs AFG3L2, fgs AIRE, fgs ALDH7A1, fgs ANO5, fgs APP, fgs ASS1, fgs ATL1, fgs ATP1A2, fgs ATP7B, fgs BBS1, fgs BBS2, fgs BCKDHB, fgs BEST1, fgs BMPR2, fgs

19 Molecular pathology procedure, Level 7 (e.g., analysis of exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of exons, cytogenomic array analysis for neoplasia) BRAF, fgs BSCL2, fgs BTK, fgs CACNB2, fgs CAPN3, fgs CBS, fgs CDH1, fgs CDKL5, fgs CLCN1, fgs CLCNKB, fgs CNTNAP2, fgs COL6A2, dup_del CPT1A, fgs CRB1, fgs CREBBP, dup_del DBT, fgs DLAT, fgs DLD, fgs DSC2, fgs DSG2, fgs DSP, fgs EFHC1, fgs EIF2B3, fgs EIF2B4, fgs EIF2B5, fgs ENG, fgs EYA1, fgs F8, dup_del FAH, fgs FASTKD2, fgs FIG4, fgs FTSJ1, fgs FUS, fgs GAA, fgs GALC, fgs GALT, fgs GARS, fgs GCDH, fgs GCK, fgs GLUD1, fgs GNE, fgs GRN, fgs HADHA, fgs HADHB,fgs HEXA, fgs HLCS, fgs HNF4A, fgs IDUA, fgs INF2, fgs IVD, fgs JAG1, dup_del JUP, fgs

20 Molecular pathology procedure, Level 7 (e.g., analysis of exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of exons, cytogenomic array analysis for neoplasia) KAL1, fgs KCNH2, fgs KCNQ1, fgs KCNQ2, fgs LDB3, fgs LDLR, fgs LEPR, fgs LHCGR, fgs LMNA, fgs LRP5, fgs MAP2K1, fgs MAP2K2, fgs MAPT, fgs MCCC1, fgs MCCC2, fgs MFN2, fgs Microarray, Neoplasia MTM1, fgs MUT, fgs MUTYH, fgs NDUFS1, fgs NF2, fgs NOTCH3, tsa NPC1, fgs NPHP1, fgs NSD1, fgs OPA1, dup_del OPTN, fgs PAFAH1B1, fgs PAH, fgs PALB2, fgs PARK2, fgs PAX2, fgs PC, fgs PCCA, fgs PCCB, fgs PCDH15, dup_del PCSK, fgs PDHA1, fgs PDHX, fgs PHEX, fgs PKD2, fgs PKP2, fgs PNKD, fgs POLG, fgs POMGNT1, fgs POMT1, fgs POMT2, fgs PRKAG2, fgs PRKCG, fgs PSEN2, fgs PTPN11, fgs

21 Molecular pathology procedure, Level 7 (e.g., analysis of exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of exons, cytogenomic array analysis for neoplasia) Molecular pathology procedure, Level 8 (e.g., analysis of exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of >50 exons, sequence analysis of multiple genes on one platform) SCN1A (sodium channel, voltagegated, type 1, alpha subunit) (e.g., generalized epilepsy with febrile seizures), full gene sequence PYGM, fgs RAF1, fgs RPE65, fgs RYR1, tsa SCN4A, fgs SCNN1A, fgs SCNN1B, fgs SCNN1G, fgs SDHA, fgs SETX, fgs SGCE, fgs SH3TC2, fgs SLC26A4, fgs SLC37A4, fgs SLC9A6, fgs SMAD4, fgs SOS1, fgs SPAST, fgs SPG7, fgs STXBP1, fgs TAZ, fgs TCF4, fgs TH, fgs TMEM43, fgs TNNT2, fgs TRPC6, fgs TSC1, fgs TSC2, dup_del UBE3A, fgs UMOD, fgs VWF, etsa WAS, fgs for all product lines Non-covered genes for all product lines (this list may not be all-inclusive): ABCC8, fgs AGL, fgs AHI1, fgs ASPM, fgs CACNA1A, fgs CHD7, fgs COL4A4, fgs COL4A5, dup_del COL6A1, fgs COL6A2, fgs COL6A3, fgs CREBBP, fgs F8, fgs JAG1, fgs KDM5C, fgs KIAA0196, fgs L1CAM, fgs

22 81407 Molecular pathology procedure, Level 8 (e.g., analysis of exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of >50 exons, sequence analysis of multiple genes on one platform) SCN1A (sodium channel, voltagegated, type 1, alpha subunit) (e.g., generalized epilepsy with febrile seizures), full gene sequence Molecular pathology procedure, Level 9 (e.g., analysis of >50 exons in a single gene by DNA sequence analysis) FBN1 (fibrillin 1) (e.g., Marfan syndrome), full gene sequence NF1 (neurofibromin 1) (e.g., neurofibromatosis, type 1), full gene sequence RYR1 (ryanodine receptor 1, skeletal) (e.g., malignant hyperthermia), full gene sequence VWF (von Willebrand factor) (e.g., von Willebrand disease types 1 and 3), full gene sequence LAMB2, fgs MYBPC3, fgs MYH6, fgs MYH7, fgs MYO7A, fgs NOTCH1, fgs NPHS1, fgs OPA1, fgs PCDH15, fgs PKD1, fgs PLCE1, fgs SCN1A, fgs SCN5A, fgs SLC12A1, fgs SLC12A3, fgs SPG11, fgs SPTBN2, fgs TMEM67, fgs TSC2, fgs USH1C, fgs VPS13B, dup_del WDR62, fgs for all product lines Non-covered genes for all product lines (this list may not be all-inclusive): ABCA4, fgs ATM, fgs CDH23, fgs CEP290, fgs COL1A1, fgs COL1A2, fgs COL4A1, fgs COL4A3, fgs COL4A5, fgs DMD, fgs DYSF, fgs FBN1, fgs ITPR1, fgs LAMA2, fgs LRRK2, fgs MYH11, fgs NEB, fgs NF1, fgs PKHD1, fgs RYR1, fgs RYR2, fgs or tsa > 50 USH2A, fgs VPS13B, fgs VWF, fgs Unlisted molecular pathology procedure for all product lines PG0301 Genetic Expression Assays for Breast Cancer Prognosis

23 Unlisted molecular pathology procedure PG0368 GeneSight Assay for Refractory Depression Non-covered genes for all product lines (this list may not be all-inclusive): Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) BLUEPRINT HTTLPR myrisk 4q25-AF 9p21 ABCB1, cv ACADM, fgs ACADM, panel ACADVL, d_d ACADVL, panel ACSL4, fgs ACVRL1, d_d ACVRL1, ENG ACVRL1, ENG, kfv ACVRL1, ENG, SMAD4 ADAMTS13 ADRA2A AFP AGA AGXT ALDOB ALG6, fgs ALPL, fgs ALPL, kfv ANK3 ANKK1 APC, panel APP, panel ARSB, fgs AR-V7 ARX, panel ASHKENAZI JEWISH PNL, < 9 ASXL, dup_del ASXL1, fgs ASXL1, tsa ATP7A, fgs ATRX AZF BAALC BAG3 BARD1 BCOR, tsa BDNF BLM, fgs BMPR1A BMPR2, panel BRAF, panel BSND, fgs

24 Unlisted molecular pathology procedure C9ORF72 CACNA1C CALR CAPN3, dup_del CARD11 CASK, fgs CBL, tsa CC2D2A, fgs CCM, panel CCM2 CCM2, panel CCM3 CD79B CDH1, dup_del CDH1, panel CDH1, tsa CDKL5, panel CDKN1C CFTR, panel CFTR, PRSS1, SPINK1 CHEK2, kfv CHEK2, panel CLLU1 CLN3 COL3A1, dup_del COL3A1, fgs COL4A5, panel COMT CPOX, fgs CPOX, kfv CRTAP, kfv CRYAB CSF3R, ma CSF3R, tsa CTRC CTSA, fgs CYP1A1 CYP1A2 CYP1B1, tsa CYP21A2, panel CYP2B6 CYP2C8 CYP3A4, CYP3A5 CYP4F2 CYP7B1, fgs DDR2 DMD, panel DMPK, panel DNM2, fgs DRD, panel DRD1 DRD2

25 Unlisted molecular pathology procedure DRD4 EDA, tsa EGFR, KRAS, ALK EGFR, KRAS, BRAF EGFR, tsa EGFRvIII EIF2B1, fgs EIF2B2, panel ELANE EPOR ETV6 EZH2 F2, F5 F2, F5, MTHFR FBN1, dup_del FBN1, panel FBN1, tsa FECH, fgs FECH, kfv FGD1 FGD4, fgs FGF8, fgs FGFR panel FKBP10, fgs FKBP10, kfv FKBP5 FKTN, 1167 FLCN, fgs FMR1, panel FOXG1, dup_del FOXG1, panel FUCA1, fgs FXN, panel G6PD GAA, cv GABRA6 GALC, panel GALNS, fgs GATA1 GBA, fgs GCH1, del GCK, panel GJB, panel GJC2, fgs GLB1, fgs GLI3, fgs GNA11 GNAS GNRH1, fgs GNRHR, fgs GNS, fgs GRIK1

26 Unlisted molecular pathology procedure GRIK4 GYS2, fgs HADHA, tsa HAX1 HBA1, fgs HGSNAT, fgs HIF2A HLA, hybrid HNF1A, panel HNF1B, panel HNF4A, panel HOXB13 HP, panel HP1 HSPB8, fgs HTR2, panel HTR2A, cv HTR2C, cv IFITM5, fgs IFNL3 IGHMBP2 INSR ITGA2 JAG1, panel JAK2, panel JAK3 KDM6A, fgs KEL KIF5A, fgs KIF6 KISS1R, fgs KIT, fgs KMT2A/MLL-PTD KMT2D, sa KRAS, panel KRAS, tsa KRIT1, dup_del KRIT1, fgs KRIT1, panel L1CAM, panel LCHAD LMNA, dup_del LPA LPA, ASA MAN2B MANBA MCCC1, MCCC2, panel MCM6 MCPH1, fgs MCT8 MECP2, panel MEF2C, del

27 Unlisted molecular pathology procedure MEF2C, fgs MEF2C, panel MEFV, panel MEN1, panel MET Microarray, panel MID1, fgs MLL MLYCD, fgs MLYCD, kfv MTMR2, fgs MUTYH, dup_del MUTYH, panel MYH3, exon 17 MYLK, fgs NAA10 NAGLU, fgs NAT2 NBN1 NCF1 NDRG1, fgs NET NEU1, fgs NF1, dup_del NF1, panel NF2, panel NPC1_NPC2, fgs NPC1_NPC2, kfv NSD1, panel NTRK1, fgs OPHN1, fgs OPRD1 OPRK1 OPRM1 OTC, dup_del OTC, panel OXCT1, fgs P3H1, kfv PABP2 PALB2, panel PARK7, dup_del PARK7, fgs PAX6, panel PDCD10, dup_del PDCD10, fgs PDCD10, panel PHD2 PHF6, fgs PINK1, dup_del PLOD1 PLOD2, fgs PLP1, panel

28 Unlisted molecular pathology procedure PMM2, fgs PMP22, panel POLG, tsa PRKG1, fgs PROK2, fgs PROKR2, fgs PRRT2, fgs PTCH PTEN, tsa PTPN11, tsa PTPN22 RAD21, tsa RAS, panel RASA1 RB1 REEP1, dup_del RhCE RPL19 RPL26 RPS6KA3, fgs RRM1 RUNX1, tsa SBDS SBF2, fgs SCA1 SCA10 SCA12 SCA13, tsa SCA14 SCA17 SCA2 SCA5 SCA6 SCA7 SCA8 SCN1A, dup_del SCN1A, panel SDH, kfv SDH, panel SDHAF2, fgs SDHB, panel SDHC, panel SDHD, panel SEPT9, fgs SEPT9, panel SERPINA1, fgs SERPINA1, panel SERPINA10, rs SERPING1, kfv SETBP1, tsa SF3B1, tsa SFTPB

29 Unlisted molecular pathology procedure SFTPC SGCA, dup_del SGSH, fgs SHANK2, fgs SHANK3 shox, panel SLC22A5, dup_del SLC22A5, panel SLC25A13, fgs SLC47A1 SLC6A4 SLC6A8, fgs SLCO1B1, tsa SLCO2A1, kfv SMAD3, fgs SMAD3, kfv SMAD4, kfv SMAD4, panel SMC1A, fgs SMC3, tsa SMN1_SMN2, fgs SMN1_SMN2, panel SMPD1, fgs SNCA, dup_del SNCA, fgs SPAST, panel SPG21, kfv SPRED1, dup_del SPTLC1, fgs SPTLC2, fgs SRSF2, tsa STAG2, tsa STAR STK11, panel STR, panel SULT4A1 SYNGAP1, fgs SYT, panel SYT-SSX, ta TACI, fgs TACR3, fgs TBX5, panel TERT/TERC TET2, fgs TET2, tsa TGFB2, kfv TGFBR1/TGFBR2 TMEM216, cv TMEM216, fgs TP53, panel TRB, panel TRPV4, fgs

30 Unlisted molecular pathology procedure TSC1, TSC2 U2AF1, tsa UBQL1 UBQLN2 UGT2B15, tsa UGT2B7, tsa VCP VEGF, fgs VEGF, tsa VEGFR2 VWF, D1472H VWF, panel WNK1, fgs WRAP53 WT1, tsa YARS, fgs ZAP70, ma ZFYVE26, fgs ZRSR2, tsa Molecular Multianalyte Assays (MAA) 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 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 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 Exome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis 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) Exome (eg, unexplained constitutional or heritable disorder or syndrome); re-evaluation of previously obtained exome sequence (eg, updated knowledge or unrelated condition/syndrome) Fetal chromosomal aneuploidy (eg, trisomy 21, monosomy X) genomic sequence analysis panel, circulating cell-free fetal DNA in maternal blood, must include analysis of chromosomes 13, 18, and 21 Genome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis Genome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis, each comparator genome (eg, parents, siblings) (List Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered Non-covered PG0287 Cell-Free DNA Tests For Fetal Aneuploidy Non-covered Non-covered Non-covered Non-covered