Hereditary Cancer Syndrome Multigene Panels · Hereditary cancer syndrome multi-gene panels include...

Lab Management Guidelines V1.0.2020

Hereditary Cancer Syndrome Multigene Panels

MOL.TS.182.Av1.0.2020

Introduction

Hereditary cancer syndrome multigene panel testing is addressed by this guideline.

Procedures addressed

The inclusion of any procedure code in this table does not imply that the code is under management or requires prior authorization. Refer to the specific Health Plan's procedure code list for management requirements.

Procedures addressed by this guideline

Procedure codes

APC Sequencing 81201

APC Deletion/Duplication Analysis 81203

ATM Sequencing 81408

BRCA1/2 Sequencing 81163

BRCA1/2 Deletion/Duplication Analysis 81164

BRCA1 Sequencing 81165

BRCA1 Deletion/Duplication Analysis 81166

BRCA2 Sequencing 81216

BRCA2 Deletion/Duplication Analysis 81167

Chromosomal Microarray [BAC], Constitutional

81228

Chromosomal Microarray [SNP], Constitutional

81229

MLH1 Sequencing 81292

MLH1 Deletion/Duplication Analysis 81294

MSH2 Sequencing 81295

MSH2 Deletion/Duplication Analysis 81297

MSH6 Sequencing 81298

MSH6 Deletion/Duplication Analysis 81300

PMS2 Sequencing 81317

PMS2 Deletion/Duplication Analysis 81319

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Procedure codes

PTEN Sequencing 81321

PTEN Deletion/Duplication Analysis 81323

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 10 genes, always including BRCA1, BRCA2,CDH1, MLH1, MSH2, MSH6, PALB2, PTEN, STK11, and TP53

81432

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

81433

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

81435

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, and STK11

81436

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

81437


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Procedure codes

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

81438

BRCAplus , Ambry Genetics 0129U

BreastNext, Ambry Genetics, Ambry Genetics

0102U

ColoNext, Ambry Genetics, Ambry Genetics

0101U

OvaNext, Ambry Genetics, Ambry Genetics

0103U

Miscellaneous hereditary cancer syndrome gene tests

81400


81401


81402


81403


81404


81405


81406


81407


81408


81479


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What are hereditary cancer syndromes

Definition

A hereditary cancer syndrome is when a mutation in a single gene causes a significantly increased risk for certain cancers. Hereditary cancer syndromes are usually characterized by a pattern of specific cancer types occurring together in the same family, younger ages of cancer diagnosis than usual, or other co-existing non-cancer conditions.

Prevalence

Most cancer is sporadic and believed to be caused by a mix of behavioral or lifestyle, environmental, and inherited risk factors. However, about 5-10% of cancers are believed to have a major inherited component.1

Hereditary cancer syndromes

There are at least 50 hereditary cancer syndromes.1 This table lists some of the most common along with associated cancers.2

Syndrome Associated cancers

Hereditary breast and ovarian cancer syndrome (HBOC)

• breast

• ovarian, fallopian tube, or primary peritoneal cancer

• pancreatic

• prostate

Lynch syndrome • colorectal

• endometrial

• small bowel

• stomach

• ovarian

• pancreatic

• ureteral and renal pelvis

• biliary tract

• brain

• sebaceous adenoma

• keratoacanthoma tumors


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Familial adenomatous polyposis • colorectal and other gastrointestinal cancers

• gastrointestinal tract polyps such as adenomas and fundic gland

• osteomas

• desmoids

• thyroid cancer

• hepatoblastoma

MUTYH-associated polyposis • colorectal and other gastrointestinal cancers

• adenomas

• hyperplastic polyps

Cowden syndrome • benign and malignant tumors of the breast, endometrium, and thyroid

• cancer and polyps (hamartomas) in the colon and rectum

Li Fraumeni syndrome • soft tissue sarcoma

• osteosarcoma

• leukemia

• melanoma

• breast

• pancreas

• colon

• adrenal cortex

• stomach

• esophagus

• brain


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Peutz-Jeghers syndrome • polyps (hamartomas) in the stomach

• small intestine and colon

• pancreas

• lung

• breast

• uterine

• ovarian

Overlapping clinical findings

Many hereditary cancer syndromes can include the same types of cancer and therefore have overlapping clinical findings. For example, breast cancer is a feature of HBOC caused by BRCA mutations, Li Fraumeni syndrome, Cowden syndrome, and others. Sometimes, the pattern of cancers in the family or pathognomonic features makes the underlying syndrome clear. However, in many cases it can be difficult to reliably diagnose hereditary cancer syndromes based on clinical and family history alone.

Test information

Introduction

Testing for hereditary cancer syndromes may include multigene panel testing.

Sanger Sequencing

Until recently, most sequencing tests used the Sanger sequencing methodology that was originally developed in the 1970s. Sanger sequencing is labor intensive and did not lend itself to high-throughput applications.

Next-generation sequencing (NGS)

NGS, which is also sometimes called massively parallel sequencing, has been developing since about 2005 to allow larger scale and more efficient gene sequencing. NGS relies on sequencing many copies of small pieces of DNA simultaneously and using bioinformatics to assemble the sequence.

The efficiency of NGS has led to an increasing number of large, multi-gene testing panels. NGS panels that test several genes at once are particularly well-suited to conditions caused by more than one gene or where there is considerable clinical overlap between conditions making it difficult to reliably narrow down likely causes. As


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a result, several laboratories have begun to combine genes involved in causing various hereditary cancer syndromes, which often have both of those characteristics.

Detection rate of NGS

NGS may not perform as well as Sanger sequencing in some applications. Results may also be obtained that cannot be adequately interpreted based on the current knowledgebase.

o When a sequence variation is identified that has not been previously characterized or shown to cause the disorder in question, it is called a variant of uncertain significance (VUS). VUSs are relatively common findings when sequencing large amounts of DNA with NGS.

o Under certain circumstances, technologies used in multi-gene testing may fail to identify mutations that might be identifiable through single-gene testing. If high clinical suspicion remains for a particular syndrome after negative multi-gene test results, consultation with the testing lab, additional targeted genetic testing, or both may be warranted.

Hereditary cancer syndrome multi-gene panels

Hereditary cancer syndrome multi-gene panels include a wide variety of genes and may be focused on the genetic causes of a particular cancer type or broad detection of common hereditary cancer syndromes.

Multi-gene tests vary in technical specifications. For example, different labs may have different depth of coverage, extent of Intron/Exon Boundary analysis, or methodology of large Deletion/Duplication Analysis.

Because genes can be easily added or removed from multi-gene tests over time by a given lab, medical records must document

the genes included in the specific multi-gene test used from each patient, and

the labs that performed the panels.

Moderate risk genes

Panels may also include genes believed to be associated with cancer, but with a more modest impact on risk than recognized hereditary cancer syndromes. Results for such genes are of less clear value because there often are not clear management recommendation for mutation-positive individuals.


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Guidelines and evidence

Introduction

This section includes relevant guidelines and evidence pertaining to hereditary cancer syndrome panel testing.

National Comprehensive Cancer Network (NCCN)

The National Comprehensive Cancer Network (NCCN) makes the following general recommendations for using multi-gene panels in evaluating risk for breast and ovarian cancer and now includes this option in some management algorithms:3 ,4

“Because of their complexity, multi-gene testing is ideally offered in the context of professional genetic expertise for pre- and post-test counseling.”

“Testing of an individual without a cancer diagnosis should only be considered when an appropriate affected family member is unavailable for testing.”

“When more than one gene can explain an inherited cancer syndrome, then multi-gene testing may be more efficient and/or cost effective. As commercially available tests differ in the specific genes analyzed (as well as classification of variants and many other factors), choosing the specific laboratory and test panel is important. Multi-gene testing can include ‘intermediate’ penetrant (moderate-risk) genes. For many of these genes, there is limited data on the degree of cancer risk and there are no clear guidelines on risk management for carriers of mutations. Not all genes included on available multi-gene tests are necessarily clinically actionable.” If a moderate risk gene mutation is identified, “gene carriers should be encouraged to participate in clinical trials or genetic registries.”

“As is the case with high-risk genes, it is possible that the risks associated with moderate-risk genes may not be entirely due to that gene alone, but may be influenced by gene/gene or gene/environment interactions. In addition, certain pathogenic/likely pathogenic variant in genes may post higher or lower risk than other pathogenic/likely pathogenic variants in that same gene. Therefore, it may be difficult to use a known pathogenic/likely pathogenic variant alone to assign risk for relatives."

“Mutations in many breast cancer susceptibility genes involved in DNA repair may be associated with the rare autosomal recessive condition, Fanconi anemia.” Therefore, multi-gene testing may unexpectedly reveal that an individual and their family are at an increased risk for this condition.

“There is an increased likelihood of finding variants of unknown significance when testing for mutations in multiple genes.”

American Society of Breast Surgeons

The American Society of Breast Surgeons (2019) published a consensus guideline on genetic testing for hereditary breast cancer. They state the following:


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“Breast surgeons, genetic counselors, and other medical professionals knowledgeable in genetic testing can provide patient education and counseling and make recommendations to their patients regarding genetic testing and arrange testing. When the patient’s history and/or test results are complex, referral to a certified genetic counselor or genetics professional may be useful. Genetic testing is increasingly provided through multi-gene panels. There are a wide variety of panels available, with different genes on different panels. There is a lack of consensus among experts regarding which genes should be tested in different clinical scenarios. There is also variation in the degree of consensus regarding the understanding of risk and appropriate clinical management of mutations in some genes.”

“Genetic testing should be made available to all patients with a personal history of breast cancer. Recent data support that genetic testing should be offered to each patient with breast cancer (newly diagnosed or with a personal history). If genetic testing is performed, such testing should include BRCA1/BRCA2 and PALB2, with other genes as appropriate for the clinical scenario and family history. For patients with newly diagnosed breast cancer, identification of a mutation may impact local treatment recommendations (surgery and potentially radiation) and systemic therapy. Additionally, family members may subsequently be offered testing and tailored risk reduction strategies.”

“Genetic testing should be made available to all patients with a personal history of breast cancer. Every patient being seen by a breast surgeon, who had genetic testing in the past and no pathogenic variant was identified, should be re-evaluated and updated testing considered. In particular, a patient who had negative germline BRCA1 and 2 testing, who is from a family with no pathogenic variants, should be considered for additional testing.1 Genetic testing performed prior to 2014 most likely would not have had PALB2 or other potentially relevant genes included and may not have included testing for large genomic rearrangements in BRCA1 or BRCA2.”

“Genetic testing should be made available to patients without a history of breast cancer who meet NCCN guidelines. Unaffected patients should be informed that testing an affected relative first, whenever possible, is more informative than undergoing testing themselves. When it is not feasible to test the affected relative first, then the unaffected family member should be considered for testing if they are interested, with careful pre-test counseling to explain the limited value of “uninformative negative” results. It is also reasonable to order a multi-gene panel if the family history is incomplete (i.e., a case of adoption, patient is uncertain of exact type of cancer affecting family members, among others) or other cancers are found in the family history, as described above.”

American College of Medical Genetics

The American College of Medical Genetics has a policy statement that offers general guidance on the clinical application of large-scale sequencing focusing primarily on whole exome and whole genome testing. However, some of the recommendations


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regarding counseling around unexpected results, variants of unknown significance, and minimum requirements for reporting apply to many NGS applications.5

Criteria

Introduction

Requests for hereditary cancer syndrome panel testing are reviewed using these criteria.

Criteria

This guideline applies to all hereditary cancer syndrome panels, which are defined as assays that simultaneously test for more than one hereditary cancer syndrome. This guideline does not apply when testing more than one gene related to the same hereditary cancer syndrome (e.g., Lynch syndrome).

Medical necessity coverage generally relies on criteria established for testing individual hereditary cancer syndromes. See the Coverage Guidance table for examples of genes known to be included in currently available hereditary cancer syndrome multi-gene panels with coverage guidance. This is not intended to be a complete list of available genes as these panels are evolving rapidly.

However, this guideline takes into account the efficiency gains from simultaneously testing multiple candidate genes. Therefore, coverage requirements rely to some degree on how the panel will be billed. Panels may be billed in a variety of ways:

Gene sequencing portion:

o A separate CPT code for sequencing each gene studied or a subset (e.g., 81201, 81294, 81297, etc.)

o A single CPT code developed specifically for a particular type of panel (e.g., 81432, 81435, 81437)

o A single unlisted CPT code (e.g., 81479)

Deletion/duplication analysis portion:

o A separate CPT code for deletion/duplication analysis of each gene studied or a subset (e.g., 81203, 81292, 81294, 81404, 81479, etc.)

o A single CPT code developed specifically for a particular type of panel (e.g., 81433, 81436, 81438)

o Microarray analysis (e.g., 81228 or 81229)

o Part of a single unlisted CPT code for the sequencing and deletion/duplication portions of the panel (e.g., 81479)


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Hereditary cancer syndrome multi-gene panels will be reimbursed when the following criteria are met:

Panel will be billed with separate procedure codes for each gene analyzed (however, please note that the billed amount should not exceed the list price of the test).

o The medical necessity of each billed procedure will be assessed independently. See the Coverage Guidance table for gene-specific policy guidance.

When a patient meets medical necessity criteria for any hereditary cancer syndrome gene(s) included in a multi-gene panel, genetic testing for the clinically indicated gene(s) will be reimbursed. This includes the sequencing and deletion/duplication† components.

Any genes that are included in a multi-gene panel but do NOT meet medical necessity criteria will NOT be reimbursed. It will be at the laboratory, provider, and patient’s discretion to determine if a multi-gene panel remains the preferred testing option.

o Sequencing and/or deletion/duplication analysis† of any hereditary cancer syndrome gene(s) should only be performed once per lifetime and will therefore only be reimbursed once per lifetime. If gene testing was previously performed, and is now being included in a panel, such testing will not be separately reimbursable regardless of whether clinical coverage criteria are met, OR

Panel will be billed with a single procedure code to represent all genes being sequenced, with or without another single procedure code representing the deletion/duplication analysis† portion. Code(s) may be specific to that panel or an unlisted code, such as 81479.

o No previous hereditary cancer syndrome testing has been performed

Medical necessity must be established for at least two conditions included in the panel (e.g., hereditary breast and ovarian cancer and Li Fraumeni syndrome). Note that this is two conditions and not two genes (i.e., meeting criteria for only Lynch syndrome, which is caused by mutations in at least 5 genes, would not fulfill criteria alone).

Although not a complete list, the following are considered separate conditions: Hereditary breast cancer - this includes both BRCA1/2 and PALB2.

Lynch syndrome

Li-Fraumeni

Familial adenomatous polyposis

Cowden syndrome


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o Testing for one condition was performed and billed separately. A multi-gene panel is now being considered as a reflex and will be billed at a rate comparable to single syndrome pricing (e.g., myRisk update).

Medical necessity must be established for at least one condition included in the panel in addition to the already tested condition (e.g., hereditary breast and ovarian cancer was already performed, but Lynch syndrome criteria are also met).

Note that if BRCA1/2 testing was already performed and PALB2 criteria are now met, PALB2 testing alone would be reimbursable and not a reflex panel test (e.g. myRisk Update).

† When deletion/duplication testing is not part of a single panel CPT code being billed, deletion/duplication testing should be billed in only one of the following ways:

A separate CPT code for deletion/duplication analysis of each individual gene (may include non-specific molecular pathology tier 2 codes or unlisted code 81479), or

A single CPT code specific to the performed deletion/duplication analysis panel, or

A single microarray procedure

Procedure codes representing multiple methods for deletion/duplication testing will not be reimbursable for the same panel (e.g., test-specific deletion/duplication procedure codes and microarray will not both be reimbursable for the same panel).

Coverage guidance

The following table describes coverage guidance for genes associated with hereditary cancer syndromes.

Coverage Guidance for Genes Included in Hereditary Cancer Syndrome Multi-Gene Panels

Condition Test Name CPT Claim Code Reimbursement

Birt-Hogg-Dube syndrome

FLCN Sequencing

81479 FLCNSEQ MOL.CU.109

FLCN Deletion/Duplication Analysis

81479 FLCNDD MOL.CU.109

Cowden syndrome, PTEN hamartoma tumor syndrome

PTEN Deletion/Duplication Analysis

81323 NONE MOL.TS.223

PTEN Sequencing



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Cutaneous malignant melanoma

CDK4 Deletion/Duplication Analysis

81479 CDK4DD MOL.TS.170

CDK4 Exon 2 Sequencing

81479 CDK4EX2 MOL.TS.170

CDKN2A Deletion/Duplication Analysis

81479 CDKN2A MOL.TS.170

CDKN2A Sequencing

81404 CDKN2A MOL.TS.170

Familial adenomatous polyposis

APC Deletion/Duplication Analysis


APC Sequencing


Familial breast and/or ovarian cancer

AKT1 Deletion/Duplication Analysis

81479 AKT1DD Not reimbursed

AKT1 Sequencing

81479 AKT1SEQ Not reimbursed

ATM Deletion/Duplication Analysis

81479 ATM Not reimbursed

ATM Sequencing

81408 ATM Not reimbursed

BARD1 Deletion/Duplication Analysis

81479 BARD1DD Not reimbursed

BARD1 Sequencing

81479 BARD1SEQ Not reimbursed

BRIP1 Deletion/Duplication Analysis

81479 BRIP1DD Not reimbursed

BRIP1 Sequencing

81479 BRIP1 Not reimbursed

CHEK2 Deletion/Duplication Analysis

81479 CHEK2DD Not reimbursed


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CHEK2 Sequencing

81479 CHEK2SEQ Not reimbursed

FAM175A Deletion/Duplication Analysis

81479 FAM175ADD Not reimbursed

FAM175A Sequencing

81479 FAM175ASEQ Not reimbursed

GEN1 Deletion/Duplication Analysis

81479 GEN1DD Not reimbursed

GEN1 Sequencing

81479 GEN1SEQ Not reimbursed

MRE11A Deletion/Duplication Analysis

81479 MRE11ADD Not reimbursed

MRE11A Sequencing

81479 MRE11ASEQ Not reimbursed

NBN Deletion/Duplication Analysis

81479 NBNDD Not reimbursed

NBN Sequencing

81479 NBNSEQ Not reimbursed

RAD50 Deletion/Duplication Analysis

81479 RAD50DD Not reimbursed

RAD50 Sequencing

81479 RAD50SEQ Not reimbursed

RAD51 Deletion/Duplication Analysis

81479 RAD51DD Not reimbursed

RAD51 Sequencing

81479 RAD51SEQ Not reimbursed

RAD51C Deletion/Duplication Analysis

81479 RAD51CDD Not reimbursed

RAD51C Sequencing

81479 RAD51CSEQ Not reimbursed


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RAD51D Deletion/Duplication Analysis

81479 RAD51DDD Not reimbursed

RAD51D Sequencing

81479 RAD51DSEQ Not reimbursed

SMARCA4 Deletion/Duplication Analysis

81479 SMARCA4DD Not reimbursed

SMARCA4 Sequencing

81479 SMARCA4SEQ Not reimbursed

XRCC2 Deletion/Duplication Analysis

81479 XRCC2DD Not reimbursed

XRCC2 Sequencing

81479 XRCC2SEQ Not reimbursed

XRCC3 Deletion/Duplication Analysis

81479 XRCC3DD Not reimbursed

XRCC3 Sequencing

81479 XRCC3SEQ Not reimbursed

Familial colorectal cancer

AXIN2 Deletion/Duplication Analysis

81479 AXIN2DD Not reimbursed

AXIN2 Sequencing

81479 AXIN2SEQ Not reimbursed

GALNT12 Deletion/Duplication Analysis

81479 GALNT12DD Not reimbursed

GALNT12 Sequencing

81479 GALNT12SEQ Not reimbursed

MLH3 Deletion/Duplication Analysis

81479 MLH3DD Not reimbursed

MLH3 Sequencing

81479 MLH3SEQ Not reimbursed

POLE Sequencing

81479 POLESEQ Not reimbursed


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POLD1 Sequencing

81479 POLD1SEQ Not reimbursed

Familial cutaneous telangiectasia and cancer syndrome

ATR Deletion/Duplication Analysis

81479 ATRDD Not reimbursed

ATR Sequencing

81479 ATRSEQ Not reimbursed

Familial pancreatic cancer

PRSS1 Deletion/Duplication Analysis

81479 PRSS1 Not reimbursed

PRSS1 Sequencing

81404 PRSS1 Not reimbursed

Familial prostate cancer

HOXB13 Deletion/Duplication Analysis

81479 HOXB13DD Not reimbursed

HOXB13 Sequencing

81479 HOXB13SEQ Not reimbursed

Familial renal cell carcinoma

MITF Sequencing

81479 MITFSEQ Not reimbursed

MITF Deletion/Duplication Analysis

81479 MITFDD Not reimbursed

Familial Wilms tumor

WT1 Sequencing

81405 WT1 MOL.CU.109

Hereditary breast and ovarian cancer

BRCA1/2 Sequencing


BRCA1/2 Deletion/Duplication Analysis


BRCA1 Sequencing


BRCA1 Deletion/Duplication Analysis


BRCA2 Sequencing



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BRCA2 Deletion/Duplication Analysis


Hereditary breast and pancreatic cancer

PALB2 Sequencing

81406 PALB2 MOL.TS.251

Hereditary diffuse gastric cancer

CDH1 Sequencing

81406 CDH1 MOL.CU.109

CTNNA1 Deletion/Duplication Analysis

81479 CTNNA1DD MOL.CU.109

CTNNA1 Sequencing

81479 CTNNA1SEQ MOL.CU.109

Hereditary leiomyomatosis with renal cell cancer

FH Sequencing 81405 FH MOL.CU.109

Hereditary mixed polyposis syndrome

GREM1 Deletion/Duplication Analysis

81479 GREM1DD Not reimbursed

GREM1 Sequencing

81479 GREM1SEQ Not reimbursed

Hereditary mixed polyposis syndrome, Juvenile polyposis syndrome

BMPR1A Deletion/Duplication Analysis

81479 BMPR1ADD MOL.CU.109

BMPR1A Sequencing

81479 BMPR1ASEQ MOL.CU.109

Hereditary papillary renal cell carcinoma

MET Sequencing

81479 METSEQ MOL.CU.109

MET Deletion/Duplication Analysis

81479 METDD MOL.CU.109

Hereditary paraganglioma-pheochromocytoma syndromes

SDHA Sequencing

81406 SDHA MOL.CU.109

SDHB Deletion/Duplication Analysis

81479 SDHB MOL.CU.109


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SDHB Sequencing

81405 SDHB MOL.CU.109

SDHC Deletion/Duplication Analysis

81404 SDHC MOL.CU.109

SDHC Sequencing

81405 SDHC MOL.CU.109

SDHD Deletion/Duplication Analysis

81479 SDHD MOL.CU.109

SDHD Sequencing

81404 SDHD MOL.CU.109

MAX Sequencing

81479 MAXSEQ MOL.CU.109

MAX Deletion/Duplication Analysis

81479 MAXDD MOL.CU.109

SDHAF2 Sequencing

81479 SDHAF2SEQ MOL.CU.109

SDHAF2 Deletion/Duplication Analysis

81479 SDHAF2DD MOL.CU.109

TMEM127 Sequencing

81479 TMEM127SEQ MOL.CU.109

TMEM127 Deletion/Duplication Analysis

81479 TMEM127DD MOL.CU.109

Juvenile polyposis syndrome

SMAD4 Deletion/Duplication Analysis

81405 SMAD4 MOL.CU.109

SMAD4 Sequencing

81406 SMAD4 MOL.CU.109

Li-Fraumeni syndrome

TP53 Deletion/Duplication Analysis

81479 TP53 MOL.TS.193

TP53 Sequencing

81405 TP53 MOL.TS.193


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TP53 Targeted Sequencing

81404 TP53 MOL.TS.193

Lynch syndrome

EPCAM Deletion/Duplication Analysis

81403 EPCAM MOL.TS.197

MLH1 Deletion/Duplication Analysis


MLH1 Sequencing


MSH2 Deletion/Duplication Analysis


MSH2 Sequencing


MSH6 Deletion/Duplication Analysis


MSH6 Sequencing


PMS2 Deletion/Duplication Analysis


PMS2 Sequencing


Multiple endocrine neoplasia type 1

MEN1 Deletion/Duplication Analysis

81404 MEN1 MOL.CU.109

MEN1 Sequencing

81405 MEN1 MOL.CU.109

Multiple endocrine neoplasia, type 2A

RET Sequencing

81406 RET MOL.CU.109

RET Targeted Sequencing

81405 RET MOL.CU.109

MUTYH-associated polyposis

MUTYH Deletion/Duplication Analysis

81479 MUTYH MOL.TS.206


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MUTYH Sequencing

81406 MUTYH MOL.TS.206

Neurofibromatosis type 1

NF1 Deletion/Duplication Analysis

81479 NF1 MOL.CU.109

NF1 Sequencing

81408 NF1 MOL.CU.109

Peutz-Jeghers syndrome

STK11 Deletion/Duplication Analysis

81404 STK11 MOL.TS.216

STK11 Sequencing

81405 STK11 MOL.TS.216

Tumor predisposition syndrome

BAP1 Deletion/Duplication Analysis

81479 BAP1DD Not reimbursed

BAP1 Sequencing

81479 BAP1SEQ Not reimbursed

Unknown phenotype

CHEK1 Deletion/Duplication Analysis

81479 CHEK1DD Not reimbursed

CHEK1 Sequencing

81479 CHEK1SEQ Not reimbursed

RAD51B Deletion/Duplication Analysis

81479 RAD51BDD Not reimbursed

RAD51B Sequencing

81479 RAD51BSEQ Not reimbursed

von Hippel-Lindau syndrome

VHL Deletion/Duplication Analysis

81403 VHL MOL.TS.233

VHL Sequencing

81404 VHL MOL.TS.233

Not reimbursed

Gene testing is not reimbursed strictly for hereditary cancer indications. In general, this category applies to genes that have only a low to moderate impact on cancer risk (compared to high penetrance cancer syndrome-causing genes) and no clear management guidelines associated with identifying a mutation.


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References

Introduction

These references are cited in this guideline.

1. National Cancer Institute. Fact Sheets: Genetic Testing for Hereditary Cancer Syndromes (Reviewed March 15, 2019). Available at: http://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-testing-fact-sheet

2. Hampel H et al. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2015; 17(1):70-87. Available at: https://www.acmg.net/docs/gim2014147a.pdf

3. National Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Breast and Ovarian. Version 3.2019. Available at: http://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf

4. National Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Colorectal. Version 1.2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf

5. The American Society of Breast Surgeons. Official Statement: Consensus guideline on genetic testing for hereditary breast cancer. 2019. Available at: https://www.breastsurgeons.org/docs/statements/Consensus-Guideline-on-Genetic-Testing-for-Hereditary-Breast-Cancer.pdf

6. ACMG Board of Directors. Points to consider in the clinical application of genomic sequencing. Genet Med. 2012 Aug;14(8):759-61.


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http://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-testing-fact-sheet

http://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-testing-fact-sheet


https://www.breastsurgeons.org/docs/statements/Consensus-Guideline-on-Genetic-Testing-for-Hereditary-Breast-Cancer.pdf

https://www.breastsurgeons.org/docs/statements/Consensus-Guideline-on-Genetic-Testing-for-Hereditary-Breast-Cancer.pdf

https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf

http://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf

https://www.acmg.net/docs/gim2014147a.pdf

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