Genetic Testing

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Genetic Testing

Genomic Tests and Family History by Levels of Evidence

The CDC Office of Public Health Genomics ranks the following list for levels of evidence of genomic tests and family health history in practice . This approach was based on a paper by Khoury and updated in accordance with criteria presented by a 2014 paper in Clinical Pharmacology and Therapeutics . The criteria are shown in the following figure to provide additional information to our readers.This list is updated on an ongoing basis andprovided only for informational purposes to researchers, healthcare providers, public health programs and others.

Green

FDA label requires use of test to inform choice or dose of a drug
CMS covers testing
Clinical practice guidelines based on systematic review supports testing

Yellow

FDA label mentions biomarkers*
CMS coverage with evidence development
Clinical practice guideline, not based on systematic review, supports use of test
Clinical practice guideline finds insufficient evidence but does not discourage use of test
Systematic review, without clinical practice guideline, supports use of test
Systematic review finds insufficient evidence but does not discourage use of test
Clinical practice guideline recommends dosage adjustment, but does not address testing

Red

FDA label cautions against use
CMS decision against coverage
Clinical practice guideline recommends against use of test
Clinical practice guideline finds insufficient evidence and discourages use of test
Systematic review recommends against use
Systematic review finds insufficient evidence and discourages use
Evidence available only from published studies without systematic reviews, clinical practice guidelines, FDA label or CMS labels coverage decision

*Can be reassigned to Green of Red of one or more conditions in these categories apply

Tier 1/Green category: represents genomic and family health history applications which have a base of synthesized evidence supporting implementation into practice.

Gene, Gene/Drug, Test, or Family History	Disorder/Indication	Use*	Synthesized Evidence Sources
Cancer—Breast/Ovarian
family history of breast/ovarian or other types of BRCA-related cancer	hereditary breast and ovarian cancer in women	risk prediction for referral for BRCA genetic counseling	USPSTF (2013) NCCN Guideline [PDF 836.97 KB](2013) NCCN Task Force (2011)
first-degree family history of breast cancer	chemoprevention of breast cancer	risk prediction	USPSTF (2013)
family history of known breast/ovarian cancer with deleterious BRCA mutation	hereditary breast and ovarian cancer in women	risk prediction; referral to counseling for BRCA genetic testing	USPSTF (2013)
HER2/trastuzumab	invasive breast cancer	PGx	NICE [PDF 2.00 MB] (2009) ASCO (2007) FDA-Device (2013) FDA-PGx Drug Information (2013)
HER2/pertuzumab	invasive breast cancer	PGx	FDA-Device (2013) FDA-PGx Drug Information (2013)
HER2/ado-trastuzumab emtansine	metastatic breast cancer	PGx	FDA-PGx Drug Information (2013)
HER2/everolimus	advanced HR+ HER2- breast cancer	PGx	FDA-PGx Drug Information (2013)
HER2/lapatinib (in combination with capecitabine or letrozole)	advanced or metastatic breast cancer	PGx	FDA-PGx Drug Information (2013)
HER2	invasive breast cancer	PGx	ASCO/CAP (2007) NICE [PDF 178.88 KB] (2009)
ER /fulvestrant	metastatic breast cancer	PGx	FDA-PGx Drug Information (2012)
ER/exemestane	ER+ early breast cancer	PGx	FDA-PGx Drug Information (2013) NICE [PDF 178.88 KB] (2009)
ER/anastrozole or letrozole	ER+ early invasive breast cancer	PGx	NICE [PDF 178.88 KB] (2009) FDA-PGx Drug Information [anastrozole] (2013) FDA-PGx Drug Information [letrozole] (2011)
ER and PgR	invasive breast cancer, breast cancer recurrences	PGx	ASCO/CAP (2010) NCCN Task Force (2011)
Oncotype DX® adjuvant chemotherapy	ER+/LN-/HER2- breast cancer, intermediate risk of recurrence	prognostic; guiding decision-making: adjuvant chemotherapy	NICE (2013) NCCN Task Force (2011)
Cancer—Colorectal
Testing for Lynch syndrome	newly diagnosed colorectal cancer	screening, cascade testing of relatives	EGAPP (2009)
Testing for Lynch syndrome	known Lynch syndrome in family	diagnostic, screening	EGAPP (2009) NCCN : Genetic/Familial High-Risk Assessment – Colorectal (2014)
KRAS/cetuximab, panitumumab	metastatic colorectal cancer	PGx	EGAPP [PDF 456.16 KB] (2013) NCCN (2011) ASCO (2009) FDA-Device FDA-PGx Drug Information (2013)
Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5 or CEA)	invasive colorectal cancer	prognostic	ASCO/CAP (2006) NCCN [PDF 1.27 MB] (2013) NCCN Task Force (2011)
Cancer—Gastric
HER2/trastuzumab	gastric or gastroesophageal junction adenocarcinoma	PGx	FDA-Device (2013) FDA-PGx Drug Information (2013)
c-Kit protein (CD 117)/imatinib	gastrointestinal stromal tumors	PGx	FDA-Device (2013) FDA-PGx Drug Information (2013)
Cancer—Leukemia/lymphoma
Philadelphia chromosome, T315I mutation/dasatinib	chronic myeloid leukemia, acute lymphoblastic leukemia	PGx; diagnostic	FDA-PGx Drug Information (2013)
Philadelphia chromosome/imatinib	chronic myeloid leukemia, acute lymphoblastic leukemia	PGx; diagnostic	FDA-PGx Drug Information (2013)
Philadelphia chromosome/bosutinib	chronic myelogenous leukemia	PGx; diagnostic	FDA-PGx Drug Information (2013)
Philadelphia chromosome/nilotinib	chronic myeloid leukemia	PGx; diagnostic	FDA-PGx Drug Information (2013)
PML/RARα/tretinoin	acute promyelocytic leukemia	PGx	FDA-PGx Drug Information (2004)
PML/RARα/arsenic trioxide	acute promyelocytic leukemia	PGx	FDA-PGx Drug Information (2010)
PDGFRB/imatinib	myelodysplastic/ myeloproliferative diseases	PGx	FDA-PGx Drug Information (2013)
CD25/denileukin diftitox	persistent or recurrent cutaneous T-cell lymphoma	PGx	FDA-PGx Drug Information (2011)
CD20/tositumomab	Non-Hodgkin’s lymphoma	PGx	FDA-PGx Drug Information (2012) Alberta Health Services [PDF 792.34 KB] (2013)
G6PD/rasburicase	leukemia, lymphoma, solid tumor malignancies	PGx, pretreatment screening in patients at higher risk for G6PD deficiency (e.g., African or Mediterranean ancestry)	FDA-PGx Drug Information (2009) CPIC (2014)
Chromosome 5q deletion/lenalidomide	transfusion-dependent anemia due to low-or intermediate-1-risk myelodysplastic syndromes associated with a deletion 5q	PGx	FDA-PGx Drug Information (2013)
Cancer—Lung
EGFR (exon 19 deletions and exon 21 (L858R) substitution mutations)/afatinib	metastatic non-small-cell lung cancer	PGx	FDA-Device (2013) FDA-PGx Drug Information (2013)
EGFR (exon 19 deletions and exon 21 (L858R) substitution mutations)/erlotinib	locally advanced or metastatic non-small-cell lung cancer	PGx	NICE [PDF 189.11 KB] (2012) NCCN Task Force (2011) FDA-Device (2013) FDA-PGx Drug Information (2013)
ALK gene rearrangement/crizotinib	non-small cell lung cancer	PGx	FDA-Device (2013) FDA-PGx Drug Information (2013) NCCN Task Force (2011) NCCN Guideline [PDF 1.61 MB](2013)
Cancer—Melanoma
BRAF V600E/K /trametinib	unresectable or metastatic melanoma	PGx	FDA-PGx Drug Information (2013) FDA-Device (2013)
BRAF V600E/dabrafenib	unresectable or metastatic melanoma	PGx	FDA-PGx Drug Information (2013) FDA-Device (2013)
BRAFV600E/vemurafenib	unresectable or metastatic melanoma	PGx	NICE (2012) FDA-PGx Drug Information (2013) FDA-Device (2013)
Cardiovascular disease
DNA testing and LDL-C concentration measurement	familial hypercholesterolemia	cascade testing of relatives of people diagnosed with FH	NICE (2008)
family history of cardiovascular disease before age 50 years in male relatives and age 60 years in female relatives	cholesterol screening	risk prediction	USPSTF (2008)
Infectious disease
HLA-B5701/*abacavir	HIV	PGx	DHHS Advisory Committee [PDF 1.46 MB] (2013) CPIC (2014) FDA-PGx Drug Information (2013)
CCR5-tropic HIV-1 /maraviroc	HIV	PGx	FDA-PGx Drug Information (2013) HHS Panel [PDF 1.46 MB](2013)
Other
CFTR (G551D)/ivacaftor	cystic fibrosis	PGx	FDA-PGx Drug Information (2012)
HLA-B*1502/carbamazepine	epilepsy, trigeminal neuralgia; pretreatment screening for those with ancestry in populations genetically at-risk for certain serious dermatologic reactions	PGx, pretreatment screening for those with ancestry in populations genetically at-risk for certain serious dermatologic reactions	FDA-PGx Drug Information (2013)
CYP2D6/pimozide	Tourette’s disorder	PGx-dose	FDA-PGx Drug Information (2011)
CYP2D6/tetrabenazine	chorea associated with Huntington’s disease	PGx-dose	FDA-PGx Drug Information (2011)
G6PD/pegloticase	chronic gout in adults refractory to conventional therapy	PGx, pretreatment screening in patients at higher risk for G6PD deficiency (e.g., African or Mediterranean ancestry)	FDA-PGx Drug Information (2012)
Parental history of hip fracture	osteoporosis screening in women	risk prediction	USPSTF (2011)
family history, especially siblings, with hereditary hemochromatosis	hereditary hemochromatosis	risk prediction; counseling for genetic testing among asymptomatic people	USPSTF (2006)
newborn screening panel	31 core conditions	screening	SACHDNC (2013)

*Pharmacogenomic applications have been classified in the Use column as either PGx (which may relate to drug choice, prevention of adverse events, or other uses of the information gained through testing), or PGx-dose (when specific dosing-related guidance is provided, or mention of a potential effect on dose is noted in the evidence sources cited). Additional Use categories include: screening, cascade testing, risk prediction, diagnostic, and prognostic.

Source Abbreviations: Agency for Healthcare Research and Quality (AHRQ), American College of Medical Genetics and Genomics (ACMG), American Society of Clinical Oncology (ASCO), Centers for Medicare and Medicaid Services (CMS), Clinical Pharmacogenetics Implementation Consortium (CPIC), Evaluation of Genomic Applications in Practice and Prevention (EGAPP), National Comprehensive Cancer Network (NCCN), National Institute for Health and Care Excellence (NICE), National Institutes of Health (NIH), Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children (SACHDNC), US Department of Health and Human Services (DHHS), US Food and Drug Administration (FDA), United States Preventive Services Task Force (USPSTF)

Tier 2/Yellow category: represents genomic and family health history applications have synthesized evidence that is insufficient to support routine implementation in practice; however, existing evidence may provide information for informed decision making by providers and patients.

Gene, Gene/Drug, Test, or Family History	Disorder/Indication	Use*	Synthesized Evidence Sources
Cancer—Breast
gene expression profiles	breast cancer	Recurrence: risk prediction; prognostic	EGAPP (2009)
ER-alpha and PgR status/ER-alpha (ESR1)-modulating agents	invasive breast cancer and breast cancer	PGx – recurrence risk prediction; prognostic	NCCN Task Force (2011) NCCN Task Force (2009) ASCO/CAP (2010)
CYP2D6/tamoxifen	risk for primary breast cancer or breast cancer recurrence	PGx – informing therapeutic choice	BCBSA TEC (2014)
Cancer—Colorectal
first-degree family history of colorectal cancer at a younger age or multiple affected first-degree relatives	colorectal cancer screening	risk prediction	USPSTF (2008)
BRAF c.1799T>A (p.V600E)	colon cancer	prognostic	NCCN Task Force (2011) NCCN Guideline [PDF 1.30 MB] (2013)
BRAF V600E/cetuximab, panitumumab	metastatic colorectal cancer	PGx	EGAPP [PDF 456.16 KB](2013) NCCN Task Force (2011)
UGT1A1/irinotecan	Metastatic carcinoma of the colon or rectum	PGx	FDA-PGx Drug Information (2012) EGAPP (2009)
testing for Lynch syndrome	patients meeting revised Bethesda guidelines or Amsterdam criteria	diagnostic, screening	NCCN : Genetic/Familial High-Risk Assessment – Colorectal (2014)
testing for Lynch syndrome	endometrial cancer in women under 50 years of age	diagnostic, screening	NCCN : Genetic/Familial High-Risk Assessment – Colorectal (2014)
consideration of testing for Lynch syndrome	people with 5% or higher risk of Lynch syndrome based on any prediction model	diagnostic, screening	NCCN : Genetic/Familial High-Risk Assessment – Colorectal (2014)
testing for Lynch syndrome	colorectal cancer diagnosed under 70 years of age, and those 70 and older who meet Bethesda guidelines	diagnostic, screening	NCCN : Genetic/Familial High-Risk Assessment – Colorectal (2014)
testing for Lynch syndrome	colorectal cancer in patients younger than 50 years	diagnostic, screening	NCCN : Genetic/Familial High-Risk Assessment – Colorectal (2014)
testing for Lynch syndrome	synchronous or metachronous colorectal or other Lynch syndrome-related tumors, at any age	diagnostic, screening	NCCN : Genetic/Familial High-Risk Assessment – Colorectal (2014)
testing for Lynch syndrome	MSI-H histology in colorectal cancer patients younger than 60 years	diagnostic, screening	NCCN : Genetic/Familial High-Risk Assessment – Colorectal (2014)
testing for Lynch syndrome	colorectal cancer in patient with relative (one or more first-degree) with Lynch syndrome related cancer that was diagnosed under age 50 years	diagnostic, screening	NCCN : Genetic/Familial High-Risk Assessment – Colorectal (2014)
testing for Lynch syndrome	colorectal cancer in patient with relatives (two or more first- or second-degree) with Lynch syndrome related cancer at any age	diagnostic, screening	NCCN : Genetic/Familial High-Risk Assessment – Colorectal (2014)
Cancer—Leukemia
FLT3-ITD	acute myeloid leukemia	predictive; prognostic	NCCN Task Force (2011) NCCN Guideline [PDF 852.75 KB] (2013)
CEBPA mutation	acute myeloid leukemia	predictive; prognostic	NCCN Task Force (2011) NCCN Guideline [PDF 852.78 KB] (2013)
NPM1 mutation	acute myeloid leukemia	predictive; prognostic	NCCN Task Force (2011) NCCN Guideline [PDF 852.80 KB] (2013)
KIT mutation	acute myeloid leukemia	predictive; prognostic	NCCN Task Force (2011) NCCN Guideline [PDF 852.70 KB] (2013)
Philadelphia chromosome/busulfan	chronic myelogenous leukemia	PGx	FDA-PGx Drug Information (2003)
UGT1A128*homozygotes/nilotinib	Philadelphia chromosome positive chronic myeloid leukemia	PGx	FDA-PGx Drug Information (2013)
FIP1L1-PDGFRα kinase/imatinib	hypereosinophilic syndrome and/or chronic eosinophilic leukemia	PGx-dose	FDA-PGx Drug Information (2013)
TPMT/thiopurines (mercaptopurine)	acute lymphatic leukemia	PGx-dose	CPIC (2011) FDA-PGx Drug Information (2011)
TPMT/thiopurines (thioguanine)	acute, non-lymphocytic leukemias	PGx-dose	CPIC (2011) FDA-PGx Drug Information (2004)
Cancer—Lung
KRAS mutations [except c38G>A]/anti-EGFR therapy	non–small cell lung cancer	predictive; prognostic	NCCN Task Force (2011)
Cancer—Melanoma
G6PD/dabrafenib	unresectable or metastatic melanoma	PGx	FDA-PGx Drug Information (2014)
family history of skin cancer	skin cancer screening in adults	risk prediction	USPSTF (2009)
Cancer—Other
DPD testing/5-FU (capecitabine)	Dukes’ C colon cancer, metastatic colorectal cancer, metastatic breast cancer	PGx	FDA-PGx Drug Information (2013)
family history of bladder cancer	bladder cancer screening	risk prediction	USPSTF (2011)
c-Kit D816V/imatinib	aggressive systemic mastocytosis	PGx	FDA-PGx Drug Information (2013)
TPMT/cisplatin	metastatic testicular tumors, metastatic ovarian tumors, advanced bladder cancer	PGx	FDA-PGx Drug Information (2011)
Cardiovascular
family history relevant to dyslipidemia (otherwise undefined)	lipid screening in infants, children, adolescents, or young adults (up to age 20)	risk prediction	USPSTF (2007)
first-degree family history of abdominal aortic aneurysm requiring surgical repair	abdominal aortic aneurysm screening	risk prediction	USPSTF (2005)
SLCO1B1/simvastatin	dyslipidemia	PGx-dose	CPIC (2012)
CYP2C9, VKORC1/warfarin	venous thrombosis, pulmonary embolism, thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement, myocardial infarction	PGx-dose	CMS CED (2009) ACMG (2008) FDA-PGx Drug Information CPIC (2011)
CYP2D6/metoprolol	hypertension, angina pectoris, heart failure	PGx	FDA-PGx Drug Information (2012)
CYP2D6/carvedilol	chronic heart failure, left ventricular dysfunction following myocardial infarction, hypertension	PGx	FDA-PGx Drug Information (2012)
CYP2D6/carvedilol	chronic heart failure, left ventricular dysfunction following myocardial infarction, hypertension	PGx	FDA-PGx Drug Information (2011)
CYP2D6/propafenone	atrial fibrillation	PGx	FDA-PGx Drug Information (2011)
CYP2C19/clopidogrel	non-ST-segment elevation acute coronary syndrome, ST-elevation myocardial infarction, myocardial infarction, stroke, peripheral arterial disease	PGx	FDA-PGx Drug Information (2013) CPIC (2013) AHRQ (2013)
CYP2C19/prasugrel	acute coronary syndrome managed with percutaneous coronary intervention	PGx	FDA-PGx Drug Information (2013)
CYP2C19/tricagrelor	acute coronary syndrome	PGx	FDA-PGx Drug Information (2013)
LDLR/pravastatin	hypercholesterolemia	PGx	FDA-PGx Drug Information (2012)
F5, SERPINC1/eltrombopag	thrombocytopenia	PGx	FDA-PGx Drug Information (2012)
Endocrine disorders
G6PD/chlorpropamide	glycemic control, type 2 diabetes in adults	PGx	FDA-PGx Drug Information (2011)
G6PD/glimepiride	glycemic control, type 2 diabetes in adults	PGx	FDA-PGx Drug Information (2013)
G6PD/glipizide	glycemic control, type 2 diabetes in adults	PGx	FDA-PGx Drug Information (2013)
G6PD/glyburide	glycemic control, type 2 diabetes in adults	PGx	FDA-PGx Drug Information (2013)
Gastroenterology
CYP2C19/pantoprazole	gastroesophageal reflux disease, pathological hypersecretory conditions	PGx-dose	FDA-PGx Drug Information (2013)
CYP2C19/omeprazole	duodenal ulcer, gastric ulcer, gastroesophageal reflux disease	PGx	FDA-PGx Drug Information (2013)
CYP2C19/esomeprazole	gastroesophageal reflux disease, NSAID-associated gastric ulcer, duodenal ulcer recurrence, pathological hypersecretory conditions	PGx	FDA-PGx Drug Information (2012)
CYP2C19/rabeprazole	gastroesophageal reflux disease, duodenal ulcers, pathological hypersecretory conditions	PGx	FDA-PGx Drug Information (2013)
CYP2C19, CYP1A2/dexlansoprazole	erosive esophagitis, heartburn	PGx	FDA-PGx Drug Information (2013)
Infectious Disease
G6PD/chloroquine phosphate	malaria, extraintestinal amebiasis	PGx	FDA-PGx Drug Information (2013)
G6PD/dapsone (tablet)	leprosy	PGx	FDA-PGx Drug Information DailyMed (2011)
G6PD/mafenide acetate (for 5% topical solution)	bacterial infections	PGx	FDA-PGx Drug Information (1998)
G6PD/nitrofurantoin	antibacterial, specific urinary tract infections	PGx	FDA-PGx Drug Information (2013)
G6PD/primaquine	vivax malaria, radical cure (prevention of relapse)	PGx	FDA-PGx Drug Information (2008)
G6PD/quinine sulfate	uncomplicatedPlasmodium falciparum malaria	PGx	FDA-PGx Drug Information (2013)
G6PD/sulfamethoxazole & trimethoprim	bacterial infections	PGx	FDA-PGx Drug Information (2013)
IL28B/boceprevir	chronic hepatitis C genotype 1	PGx	FDA-PGx Drug Information (2013)
IL28B/telaprevir	chronic hepatitis C genotype 1	PGx	FDA-PGx Drug Information (2013)
IL28B/peginterferon alfa-2b	chronic hepatitis C	PGx	FDA-PGx Drug Information (2013)
CYP2C19/voriconazole	invasive aspergillosis, candidemia and disseminated candidiasis, esophageal candidiasis,Scedosporium apiospermum andFusarium spp. infection	PGx-dose	FDA-PGx Drug Information (2011)
Neurology
CYP2C19/clobazam	seizures associated with Lennox-Gastaut syndrome	PGx-dose	FDA-PGx Drug Information (2013)
HLA-B1502*/phenytoin	generalized tonic-clonic status epilepticus and for seizures that occur during neurosurgery; testing pertains to risk for certain serious dermatologic reactions, which may be higher in patients of Chinese or Asian ancestry	PGx	FDA-PGx Drug Information (2013)
HLAB1502*/ carbamazepine	epilepsy, other seizure disorders, trigeminal neuralgia, bipolar disorder	PGx-dose	CPIC (2013)
CYP2D6, CYP2C19/diazepam	epilepsy	PGx	FDA-PGx Drug Information (2005)
CYP2D6/dextromethorphan and quinidine	pseudobulbar affect	PGx, PGx-dose	FDA-PGx Drug Information (2010)
Psychiatry
parental history of depression	major depressive disorder screening in adolescents	risk prediction	USPSTF (2009)
family history of depression	depression screening in adults	risk prediction	USPSTF (2009)
CYP2D6/amitriptyline	depression	PGx-dose	CPIC (2013) FDA-PGx Drug Information
CYP2D6/desipramine	depression	PGx-dose	CPIC (2013) FDA-PGx Drug Information (2012)
CYP2D6/fluoxetine	major depressive disorder, obsessive compulsive disorder, bulimia nervosa, panic disorder	PGx	FDA-PGx Drug Information (2009)
CYP2D6/imipramine	depression	PGx-dose	CPIC (2013) FDA-PGx Drug Information (2012)
CYP2D6/nortriptyline	depression	PGx-dose	CPIC (2013) FDA-PGx Drug Information (2012)
CYP2D6/trimipramine	depression	PGx-dose	CPIC (2013) FDA-PGx Drug Information (2012)
CYP2D6/venlafaxine	major depressive disorder, social anxiety disorder	PGx, PGx-dose	FDA-PGx Drug Information (2012)
CYP2C19, CYP2D6/citalopram	depression	PGx-dose	FDA-PGx Drug Information (2012)
CYP2D6/aripiprazole	schizophrenia, bipolar I disorder, major depressive disorder, autistic disorder	PGx-dose	FDA-PGx Drug Information (2013)
CYP2D6/clozapine	schizophrenia, schizoaffective disorder	PGx-dose	FDA-PGx Drug Information (2013)
CYP2D6/iloperidone	schizophrenia	PGx-dose	FDA-PGx Drug Information (2013)
CYP2D6/risperidone	schizophrenia, bipolar I disorder, autistic disorder	PGx-dose	FDA-PGx Drug Information (2012)
CYP2D6/atomoxetine	attention-deficit/hyperactivity disorder	PGx-dose	FDA-PGx Drug Information (2013)
CYP2D6/clomipramine	obsessive-compulsive disorder	PGx-dose	CPIC (2013) FDA-PGx Drug Information (2012)
CYP2D6, CYP2C19/fluvoxamine	obsessive compulsive disorder	PGx	FDA-PGx Drug Information (2012)
CYP2D6, CYP2C19/doxepin	insomnia	PGx-dose	CPIC (2013) FDA-PGx Drug Information (2010)
CYP2D6/modafinil	narcolepsy, obstructive sleep apnea, and shift work disorder	PGx-dose	FDA-PGx Drug Information (2010)
Rheumatology
CYP2C19/carisoprodol	musculoskeletal conditions	PGx	FDA-PGx Drug Information (2013)
CYP2C9/celecoxib	osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, acute pain, primary dysmenorrhea	PGx-dose	FDA-PGx Drug Information (2011)
CYP2C9/flurbiprofen	rheumatoid arthritis, osteoarthritis	PGx	FDA-PGx Drug Information (2010)
TPMT/thiopurines (azathioprine)	renal homotransplantation, rheumatoid arthritis	PGx-dose	CPIC (2011) FDA-PGx Drug Information (2011)
Other
family history of developmental dysplasia of the hip	developmental dysplasia of the hip screening in infants	risk prediction	USPSTF (2006)
family history of diabetes	gestational diabetes screening	risk prediction	USPSTF (2008)
family history of neonatal jaundice	Hyberbilirubinemia screening in infants; prevention of chronic bilirubin encephalopathy	risk prediction	USPSTF (2009)
family history of age-related macular degeneration	visual acuity screening in older adults	risk prediction	USPSTF (2009)
family history of chronic kidney disease	chronic kidney disease screening	risk prediction	USPSTF (2012)
family history for common diseases	common diseases	risk prediction	NIH State of the Science (2009)
CYP2D6/tolterodine	overactive bladder	PGx	FDA-PGx Drug Information (2012)
HPRT1/mycophenolic acid	organ rejection	PGx	FDA-PGx Drug Information (2013)
CYP2C19/drospirenone and ethinyl estradiol	pregnancy prevention, premenstrual dysphoric disorder, moderate acne	PGx	FDA-PGx Drug Information (2012)
UGT1A1/indacaterol	chronic obstructive pulmonary disease, including chronic bronchitis and/or emphysema	PGx	FDA-PGx Drug Information (2012)
CYP2D6/codeine	pain	PGx-dose	CPIC (2012) FDA-PGx Drug Information (2013)
CYP2D6/tramadol and acetaminophen	acute pain	PGx	FDA-PGx Drug Information (2013)
CYP2D6/cevimeline	dry mouth in patients with Sjögren’s Syndrome	PGx	FDA-PGx Drug Information (2013)
DPD/fluorouracil cream	multiple actinic or solar keratoses	PGx	FDA-PGx Drug Information (2003)
G6PD/dapsone (gel)	acne vulgaris	PGx	FDA-PGx Drug Information (2009)
G6PD/dapsone (tablet)	dermatitis herpetiformis	PGx	FDA-PGx Drug Information DailyMed (2011)
G6PD/(polyethylene glycol 3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate, & ascorbice acid for oral solution)	laxative, preparation for colonoscopy in adults	PGx	FDA-PGx Drug Information (2013)
G6PD/sodium nitrite	life-threatening, acute cyanide poisoning	PGx	FDA-PGx Drug Information (2012)
G6PD/succimer	lead poisoning, pediatric	PGx	FDA-PGx Drug Information (2007)
next generation sequencing/whole genome sequence	various rare familial diseases	diagnostic	BCBS TEC [PDF 210.52 KB](2013)
various molecular, cytogenetic biochemical and other tests**	single gene disorders and chromosomal abnormalities where diagnosis and management may require use of genetic tests even without formal evidence synthesis and reviews by evidence panels	diagnosis, management, carrier testing	NIH GTR (2013)

**This entry includes many genetic disorders for which there are no evidence-based recommendations, clinical guidelines or systematic reviews. However, a systematic search for evidence-based recommendations and reviews has not been conducted to date by our office. We expect further refinements in this classification in the near future.

Tier 3/Red category: represents genomic and family health history applications either have synthesized evidence culminating in recommendations against use (or discouraging use), OR no relevant synthesized evidence was identified. Such applications are not ready for routine practice, but may be considered in clinical and population research.

Gene, Gene/Drug, Test, or Family History	Disorder/Indication	Use*	Synthesized Evidence Sources
HFE	hereditary hemochromatosis	population screening	USPSTF (2006)
routine BRCA genetic counseling, routine BRCA testing	Hereditary breast/ovarian cancer, in women whose family history is not associated with an increased risk of BRCA mutations	population screening	USPSTF (2013)
panels for various genetic risk factors	common diseases	risk assessment, disease prevention	Multiple sources, for example:EGAPP (2010)
next generation sequencing/whole genome sequence	various common diseases	risk prediction	Rapidly evolving landscape; gaps in knowledge exist for analytic validity, clinical validity and clinical utility
SNP panels	type 2 diabetes	risk prediction	EGAPP [PDF 242.05 KB] (2013)
TCF7L2 genotyping	type 2 diabetes	risk prediction	EGAPP [PDF 242.05 KB] (2013)
NRAS or PIK3CA mutation analysis and/or testing for loss of PTEN or AKT protein expression/anti-EGFR therapy	metastatic colorectal cancer	PGx	EGAPP [PDF 456.16 KB] (2013) Systematic review (2011)
CYP450 testing/SSRIs	non-psychotic depression	PGx, PGx-dose	EGAPP (2007)
tumor gene expression analysis (Prolaris®, Oncotype Dx® Prostate	prostate cancer	prognostic, management	BCBS TEC (2014)
emerging genomic tests in the CDC’sGAPP Finder of theGAPP Knowledge Base	various disorders	various uses	Almost all of these applications (except when listed above) have insufficient information on analytic or clinical validity, or clinical utility

Other Abbreviations: estrogen receptor (ER), progesterone receptor (PgR), pharmacogenomics (PGx), single-nucleotide polymorphism (SNP)

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