GeneDose Genetic Response Report TruGenX

GeneDose Genetic Response Report

TruGenX

136 Ridge Road, Suite 18 • Lyndhurst, NJ 07071

Phone: 888-413-0428 • Fax: 561-898-1096

Laboratory Director: Randah Al Kana, MD

CLIA ID Number: 31D2115446

https://trugenx.com/

TruGenX Precision Medicine

This report combines (i) an analysis of the patient's DNA by TruGenX, identifying relevant genetic variants that are informative for medication efficacy, safety, and dosing, with (ii) an interpretation of the identified DNA variants by Coriell Life Sciences to bring you immediately actionable clinical guidance regarding safer, more effective medications and dosages for the patient. The Medication Report section lists the type of PGx guidance present on FDA-approved drug labels. Medications with no established FDA PGx guidance are provided solely for educational purposes. J Patient: DOE, JOHN

Date of Birth: Jan 01, 1956Gender: Male I

Physician: JOHN SMITH

Practice: EXAMPLE PRACTICE PARTNERS

Date Collected: Mar 10, 2019

Date Accessioned: Mar 13, 2019

Specimen type: Buccal Swab

Sample ID: 20P00000

Table of Contents

Genetic Summary Current Regimen Risk Chart Current Regimen Risk Detail (by severity) Thrombosis Profile ApoE Genotype Information Medications Summary Medication Report Details (by class) References Patient Information Card SNP Report

Genetic Summary Information

Pg. 1 Pg.3 Pg.4

Pg. 7 Pg.8 Pg.8

Pg. 12 Pg.34 Pg. 35

Appendix

t When multiple activities are listed, check information in Medication Report Details (Pg. 12) for specific medication of interest. Uncertain = No known diplotype/result (name) or activity

for this combination of genetic variants; Uninterpretable

Genotype.

Genetic Summary

Gene Result Activity t

ApoE E3IE4 See ApoE Genotype Info.

ATM AIA Normal response to metformin

COMT(Val158Met) GIG Multiple statuses; see per-drug detail

CYP1A2 *1Cl*1F Intermediate

CYP2B6

CYP2C19

CYP2C9

CYP2D6

CYP3A4

CYP3AS

or metabolizer *1Cl*1M

*1Al*1A

*11*17

*11*2

Extensive metabolizer

Rapid metabolizer

Multiple statuses; see per-drug detail

Uncertain n/a Allele

*1Al*1A Multiple statuses; see per-drug detail

*3Al*3A; Poor metabolizer or*3Cl*3C;or*3Al*3C

Powered by: 20P00000 - DOE, JOHN - Reported May 05, 2020

The information contained in this report is intended to be interpreted by a licensed physician or other licensed healthcare professional. This report is not

intended to take the place of professional medical advice. Decisions regarding use of prescribed medications must be made only after consulting with a

licensed physician or other licensed healthcare professional, and should consider each patient's medical history and current treatment regimen. Portions ©

2014-2019 Coriell Life Sciences, Inc.

CORI�{� LL LIFE SCIENCES

Page 1 of 35


Gene Result Activity t

CYP4F2 Not n/a Tested

DPYD *11*1 Normal function

Factor V Leiden Normal See Thrombosis Profile

MTHFR WTIWT Normal function

MTHFR (A1298C) Normal See Thrombosis Profile

MTHFR (C677T) Normal See Thrombosis Profile

Prothrombin (F2) Normal See Thrombosis Profile

SLC01B1 *11*1 Normal liver uptake activity

VKORC1 *21*2 Reduced (with respect to Warfarin)

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C O R I �{� L. L. LIFE SCIENCES

Page 2 of 35

20P00000 - DOE, JOHN - Reported May 05, 2020





GeneDose Genetic Response Report . .. f..¼TruGenX


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Current Regimen Risk Chart

This chart summarizes the various risk factors associated with each medication entered into GeneDose™ Live for JOHN DOE. The length of each colored segment represents the relative contribution of a risk category (detailed in the below legend) to the overall risk associated with the use of a medication. For further

information, consult the Current Regimen Risk Details Pg. 4 section.

Zestril, Prinivil (Lisinopril l0mg ...

Zoloft (Sertraline Hydrochloride 50mg ...

Lasix, Delone (Furosemide 20mg ...

Aldactone (Spironolactone 50mg ...

Precose (Acarbose 100mg Oral tablet)

Glucotrol (Glipizide 10mg Oral tablet)

Apresoline (Hydralazine ...

Singulair (Montelukast Sodium ...

0 5 10 15 20 25 30 35 40

0 to 5 - Few risks; 6 to 20 - Moderate risk; 20+ - Significant risk

- Genetic - Anticholinergic burden - FDA black box warning

Drug interaction - Lifestyle - Beers criteria

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Current Regimen Risk Detail

Severe Risks

American Geriatric Society guidelines

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The following products appear on the American Geriatric Society's Beers Criteria for Potentially

Inappropriate Medication Use in Older Adults:

• Furosemide 20mg Oral tablet• Sertraline Hydrochloride 50mg Oral tablet• Spironolactone 50mg Oral tablet

I Black box warning for Zestril, Prinivil (Lisinopril 10mg Oral tablet) and teratogenesis

I Black box warning for Zoloft (Sertraline Hydrochloride 50mg Oral tablet) and suicidal ideation

Major Risks

Aldactone (Spironolactone 50mg Oral tablet) has an additive effect with Zestril, Prinivil (Lisinopril 10mg Oral tablet)

• use combination with caution• monitor serum potassium• Beers Criteria recommends avoiding combination in older adults

ACE inhibitors can increase the risk of hyperkalemia developing in patients receiving spironolactone,

especially in the presence of renal impairment.

Significant regimen anticholinergic burden

The cumulative effect of taking multiple medicines with anticholinergic properties termed as

anticholinergic burden can adversely impact cognition, physical function and increase the risk of

mortality.

Moderate Risks

Genetic warning for Zoloft (Sertraline Hydrochloride 50mg Oral tablet)

The therapeutic outcome of this combination of alleles is uncertain. However, individuals with rapid

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. .

I metabolizer status may show increased enzyme activity compared to normal metabolizers but less than

ultrarapid metabolizers. No additional therapeutic recommendations.

Zoloft (Sertraline Hydrochloride 50mg Oral tablet) has an additive effect with Aldactone (Spironolactone 50mg Oral

tablet)/Lasix, Delone (Furosemide 20mg Oral tablet)

• use combination with caution• monitor serum sodium

Coadministration may increase the risk for SIADH. Hyponatremia due to SIADH has been reported

during therapy with SSRls. Hyponatremia may be potentiated by agents which can cause sodium

depletion such as diuretics.

Lasix, Delone (Furosemide 20mg Oral tablet) may cause additive hypotension with Zestril, Prinivil (Lisinopril 10mg Oral

tablet)

• use combination with caution• monitor blood pressure

Coadministration may result in severe hypotension and deterioration in renal function, including renal

failure. Use conservative initial doses of the ACE inhibitor if added to diuretic therapy.

Glucotrol (Glipizide 10mg Oral tablet) may cause increased risk of hypoglycemia with Zestril, Prinivil (Lisinopril 10mg Oral

tablet)

• use combination with caution• monitor blood glucose concentration and for changes in glycemic control

ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by

improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE

inhibitors are administered concomitantly.

Precose (Acarbose 100mg Oral tablet) may cause increased risk of hypoglycemia with Zestril, Prinivil (Lisinopril 10mg Oral

tablet)


ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by

improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE

inhibitors are administered concomitantly.

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Minor Risks

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Lasix, Delone (Furosemide 20mg Oral tablet) may aggravate underlying condition, thus reducing effectiveness of Glucotrol

(Glipizide 10mg Oral tablet)

• monitor blood glucose concentration and for changes in glycemic control

Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus. This

interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.

Lasix, Delone (Furosemide 20mg Oral tablet) alter the pharmacodynamic parameters of Precose (Acarbose 100mg Oral

tablet)


Loop diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due

to diuretic-induced hypokalemia. This interference can lead to a loss of diabetic control, so diabetic

patients should be monitored closely.

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Thrombosis Profile

Tested Genes (Alleles)

Prothrombin (F2)

Factor V Leiden

MTHFR (A1298C)

MTHFR (C677T)

General Description

Genotype

Normal

Normal

Normal

Normal

Predicted Phenotype

Normal risk expected based on the patient's genotype.

Clinical Guidance

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The absence of these variant alleles of Prothrombin (Factor II) and Factor V Leiden suggests that the patient does not have the elevated risk of thrombosis associated with these genetic markers.

Genetic analyses of three genes (four alleles) considered to increase the risk for venous thrombosis were performed using molecular genetic techniques. The presence of the Prothrombin (Factor 2) gene allele 20210A and Factor V Leiden allele 1691A are risk factors for venous thrombosis. This risk may be further increased by the use of estrogen therapy, oral contraceptives, pregnancy, and surgery.

Patients who are homozygous for MTHFR 677T or MTHFR 1298C may have a further increased risk for venous thrombosis if they also possess the Factor V Leiden 1691A allele. However the MTH FR alleles alone do not predict a significant risk for venous thrombosis.

References and Useful Information:

• Factor V Leiden Working Group; ACMG Laboratory Quality Assurance Molecular Subcommittee of the ACMG Laboratory Quality

Assurance Committee AMERICAN COLLEGE OF MEDICAL GENETICS; Standards and Guidelines for Clinical Genetics Laboratories;

2006 Edition0 Middeldorp S, Henkens CM, Koopman MM, van Pampus ECM,Hamulyak K, van der Meer J, Prins MH, BOIier HR. The incidence of

venous thromboembolism in family members of patients with factor V Leiden mutation and venous thrombosis. Ann Intern Med

1998;128:15-20. 0 Vandenbroucke JP, Koster T, Briet E, Reitsma PH, Bertina RM, Rosendaal FR. Increased risk of venous thrombosis in oral

contraceptive users who are carriers of factor V Leiden mutation. Lancet 1994;344:1453-1457. 0 Rosendaal FR, Koster T, Vandenbroucke JP, Reitsma PH. High risk of thrombosis in patients homozygous for factor V Leiden (activated

protein C resistance). Blood 1995;85(6):1504-1508. 0 Reich LM, Bower M, Key NS. Role of the geneticist in testing and counseling for inherited thrombophilia. Genet Med

2003;5:133-143. 0 Tosetto A, Rodeghiero F, Martinelli I, De Stefano V, Missiaglia E, Chiusolo P, Mannucci PM. Additional genetic risk factors for venous

thromboembolism in carriers of the factor V Leiden mutation. Br J Haematol 1998;103:871-876. 0 De Stefano V, Martinelli I, Mannucci PM, Paciaroni K, Chiusolo P, Casorelli I, Rossi E, Leone G. The risk of recurrent deep venous

thrombosis among heterozygous carriers of both factor V Leiden and the G20210A prothrombin mutation. N Engl J Med 1999;341:801-806.

• M. Adams, P.O. Smith, D. Martin, J.R. Thompson, D. Lodwick, N.J. Samani. Genetic analysis of thermolabile methylenetetrahydrofolate

reductase as a risk factor for myocardial infarction. QJM. 1996 Jun;89(6):437-44.

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ApoE Genotype lnformationt

Clinical Guidance

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Tested Genes (Alleles)

ApoE (E2, E3, E4)

Genotype Predicted Phenotype

E3IE4 E4 is often associated with a potential change in LDL

cholesterol and plasma triglyceride levels.

There is a potential increased risk of cardiovascular disease and atherosclerosis.

General Description

Genetic analysis in the ApoE gene was performed using molecular genetic techniques. The genotype is based on genotyping results for this patient at SNPs rs429358 and rs7412.

ApoE E3 is the most common allele-found in about 60% of people. The presence of E2 or E4 alleles may be a risk factor for multiple conditions including cardiovascular disease. ApoE E2 carriers may be more likely to develop familial dysbetalipoproteinemia or type Ill hyperlipoproteinemia.

t Predicted phenotype, clinical significance, relative risk, and interpretations reported for each genotype are associated with cardiovascular risk only. The interpretations should not be used to determine the relative risk of other diseases. Other factors important to understanding total risk should be considered.

Medication Summary

Cardiac

Therapeutic Class O Standard Precautions AO Caution / Info

Antiarrhythmics

0 Change recommended

Anticoagulants

Anticonvulsants

Antiplatelet Agents

Beta Blockers

Statins

Warfarin

Prasugrel

Ticagrelor

Atorvastatin

Simvastatin

Acenocoumarol

Phenytoin

Clopidogrel

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Gastroenterology

Therapeutic Class

Antidepressants

Antiemetics

Endocrine-Metabolic Agents

lmmunosuppressants

Nonsteroidal Antilnflamatory Drugs (NSAIDs)

Proton Pump Inhibitors (PPls)

Selective Serotonin Reuptake Inhibitors (SSRls)

Infectious Disease

Therapeutic Class

Antifungals

Pain

Therapeutic Class

Analgesics, Opioid

Anticonvulsants

Antidepressants

Anti psychotics

Beta Blockers


lmmunosuppressants

0 Standard Precautions

Trazodone

Cyclosporine


Ketoconazole


Methadone (CYP2B6)

Trazodone

Cyclosporine

AO Caution / Info

Celecoxib

Dexlansoprazole Esomeprazole Lansoprazole Omeprazole Pantoprazole Rabeprazole

AO Caution / Info

AO Caution / Info

Phenytoin

Moclobemide

Tacrolimus

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Citalopram Escitalopram


Voriconazole


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Pain

Therapeutic Class

Muscle Relaxants

Nonsteroidal Antilnflamatory Drugs (NSAIDs)

Opioids

Selective Serotonin Reuptake Inhibitors (SSRls)

Psychotropic

Therapeutic Class

Anti-ADHD Agents

Anticonvulsants

Antidementia Agents

Antidepressants

Anti psychotics

Anxiolytics

Beta Blockers

Central Monoamine-Depleting Agents

Central Nervous System Agents

Cho Ii nesterase Inhibitors

Hypnotics

Selective Serotonin Reuptake Inhibitors


Diclofenac

Buprenorphine Fentanyl


Methylphenidate (COMT)

Trazodone

Quetiapine

Alprazolam Buspirone Clonazepam

Eszopiclone

AO Caution / Info

Carisoprodol

Celecoxib Flurbiprofen Ibuprofen Lornoxicam Meloxicam Piroxicam

Oxycodone (CYP3AS)

Sertraline

AO Caution / Info

Phenytoin

Moclobemide

Diazepam

Sertraline

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. .

Psychotropic

Therapeutic Class 0 Standard Precautions AO Caution / Info 0 Change recommended

(SSRls)

Surgery

Therapeutic Class

Anticholinergic Agents

0 Standard Precautions AO Caution / Info 0 Change recommended

Anti emetics

Opioids Fentanyl

Other Drugs

Therapeutic Class

Anti-ADHD Agents


Amphetamine Dexmethylphenidate Dextroamphetamine Guanfacine Lisdexamfetamine

AO Caution / Info 0 Change recommended

Anticonvulsants

Antidiabetics

Anti neoplastic

Agents

Anti-Retroviral

Agents

Contraceptives

lmmunosuppressants

Glibenclamide Gliclazide Glimepiride Metformin Saxagliptin Tolbutamide

Methotrexate

Efavirenz Nevi rapine

Estrogen-containing oral contraceptives

Sirolimus

Brivaracetam

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. .

Legend Clinical Evidence Level 0 Typical response is expected 0 Change recommended A Consider alternative therapy

Additional information available Response is uncertain

Medication Report Details (by therapeutic class)

• StrongModerateEmerging

Drug Finding Recommendation Concern Evidence

Alpha-1 Blockers

Tamsulosin ♦ CYP2D6: Uncertain No recommendation for Tamsulosin is(Flomax) Allele available for this combination of variants/ FDA drug label: Actionable alleles. PGx

Analgesics, Opioid

Methadone (CYP2B6) 0 CYP2B6: Extensive Typical response is expected; no additional (Dolophine) metabolizer. Two therapeutic recommendations. FDA drug label: Not alleles showing established for PGx normal activity.

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. .


Anti-ADHD Agents

Amphetamine (Adzenys, Evekeo)

FDA drug label: Not

established for PGx

Atomoxetine (Strattera)

FDA drug label: Actionable

PGx

Dexmethylphenidate (Focalin)

FDA drug label: Not

established for PGx

Dextroamphetamine (Zenzedi, Dexedrine)

FDA drug label: Not

established for PGx

Guanfacine (Tenex, lntuniv)

FDA drug label: Not

established for PGx

Lisdexamfetamine (Vyvanse)

FDA drug label: Not

established for PGx

Methylphenidate (COMT) (Concerta, Metadate, Ritalin, Ritalin LA, Quillivant, Daytrana, Methylin)

FDA drug label: Not

established for PGx

0

0

0

0

0

COMT(Val158Met): Increased function. Two alleles with increased activity.

CYP2D6: Uncertain Allele



CYP3A4: Extensive metabolizer. Two alleles showing normal function.



Typical response is expected; no additional therapeutic recommendations.

No recommendation for Atomoxetine is available for this combination of variants/ alleles.






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. .

Drug

Antiarrhythmics

Finding Recommendation Concern Evidence

Flecainide

(Tambocor)

FDA drug label: Not

established for PGx

Propafenone

(Rythmol)


PGx

Anticholinergic Agents

Tolterodine ♦ (Detrol)


PGx

Anticoagulants

Acenocoumarol A (Sintrom, Acitrom)

FDA drug label: Not

established for PGx

Warfarin 0 (Coumadin)


PGx

Warfarin ♦ (Coumadin)


PGx




CYP2C9: Intermediate metabolizer. One allele showing normal activity and one showing reduced activity.

Multigenic: VKORC1, CYP2C9:

Intermediate metabolizer. One allele showing normal activity and one showing reduced activity.

Multigenic: CYP2C9, VKORC1, CYP4F2: Intermediate metabolizer. One allele showing normal activity and one showing reduced activity.

No recommendation for Flecainide is available for this combination of variants/ alleles.

No recommendation for Propafenone is available for this combination of variants/ alleles.

No recommendation for Tolterodine is available for this combination of variants/ alleles.

Individuals with variant CYP2C9 genotype (i.e., other than *11*1) have increased risk of adverse drug reactions after initiating or discontinuing NSAIDs. Checking INR more frequently is recommended.

Individuals with this combination of alleles may benefit from the standard dose of Warfarin. The FDA table recommends a therapeutic dose of 3-4 mg/day.

No recommendation for Warfarin is available due to absent laboratory assay results.

ADR

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. .


Anticonvulsants

Brivaracetam A CYP2C19: The therapeutic outcome of this Efficacy

FDA drug label: Actionable Uncertain combination of alleles is uncertain.

PGx metabolizer status. However, individuals with rapid One allele showing metabolizer status may show increased normal activity and enzyme activity compared to normal one showing metabolizers but less than ultrarapid increased activity. metabolizers. Such individuals have

increased metabolism; the resultant lower plasma concentrations may increase the probability of pharmacotherapy failure. However, there is insufficient evidence to allow calculation of dose adjustment. Be alert to reduced efficacy or select alternative drug.

Clobazam ♦ CYP2C19: Rapid The therapeutic outcome of this (Onfi) metabolizer status. combination of alleles is uncertain; no

FDA drug label: Actionable One allele showing additional therapeutic recommendations.

PGx normal activity andone showingincreased activity.

Phenytoin A CYP2C9: Standard loading dose. Reduce ADR

(Dilantin) Intermediate maintenance dose by 25%. Evaluate

FDA drug label: Actionable metabolizer. One response and serum concentration after

PGx allele showing 7--10 days. Be alert to adverse drug normal activity and events (e.g. ataxia, nystagmus, dysarthria, one showing sedation). reduced activity.

Antidementia Agents

Donepezil ♦ CYP2D6: Uncertain No recommendation for Donepezil is (Aricept) Allele available for this combination of variants/

FDA drug label: Actionable alleles.

PGx

-

0

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Antidepressants

Amitriptyline ♦ CYP2D6: Uncertain No recommendation for Amitriptyline is (Elavil) Allele available for this combination of variants/


PGx

Clomipramine ♦ CYP2D6: Uncertain No recommendation for Clomipramine is (Anafranil) Allele available for this combination of variants/


PGx

Desipramine ♦ CYP2D6: Uncertain No recommendation for Desipramine is (Norpramin) Allele available for this combination of variants/


PGx

Doxepin ♦ CYP2D6: Uncertain No recommendation for Doxepin is (Deptran) Allele available for this combination of variants/


PGx

Duloxetine ♦ CYP2D6: Uncertain No recommendation for Duloxetine is (Cymbalta) Allele available for this combination of variants/


PGx

lmipramine Multigenic Multiple results from uncorrelated genes. (Tofranil) CYP2C19: *11*17 No recommendation for lmipramine is

FDA drug label: Actionable CYP2D6: Uncertain available for this combination of variants/

PGx Allele alleles.

Mirtazapine ♦ CYP2D6: Uncertain No recommendation for Mirtazapine is

FDA drug label: Not Allele available for this combination of variants/

established for PGx alleles.

Moclobemide 0 CYP2C19: Rapid The therapeutic outcome of this (Manerix, Aurorix, metabolizer status. combination of alleles is uncertain. Amira, Clobemix, One allele showing However, individuals with rapid Depnil) normal activity and metabolizer status may show increased

FDA drug label: Not one showing enzyme activity compared to normal

established for PGx increased activity. metabolizers but less than ultrarapid metabolizers. No additional therapeutic recommendations.

Nortriptyline ♦ CYP2D6: Uncertain No recommendation for Nortriptyline is (Pamelor) Allele available for this combination of variants/


PGx

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Protri ptyli ne ♦ CYP2D6: Uncertain No recommendation for Protriptyline is (Vivactil) Allele available for this combination of variants/


PGx

Trazodone 0 CYP3A4: Extensive Typical response is expected; no additional (Oleptro, Desyrel) metabolizer. Two therapeutic recommendations.

FDA drug label: Not alleles showing

established for PGx normal function.

Venlafaxine ♦ CYP2D6: Uncertain No recommendation for Venlafaxine is (Effexor) Allele available for this combination of variants/

FDA drug label: Informative alleles.

PGx

Vortioxetine ♦ CYP2D6: Uncertain No recommendation for Vortioxetine is (Brintellix) Allele available for this combination of variants/


PGx

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. .

Drug

Antidiabetics


Glibenclamide

(Glyburide)

FDA drug label: Not

established for PGx

Gliclazide

FDA drug label: Not

established for PGx

Glimepiride

FDA drug label: Not

established for PGx

Metformin

(Glucophage®)

FDA drug label: Not

established for PGx

Saxagliptin

(Onglyza)

FDA drug label: Not

established for PGx

Tolbutamide

(Orinase)

FDA drug label: Not

established for PGx


CYP2C9:


CYP2C9:


ATM: Normal

response






Typical response is expected.



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. .


Anti emetics

Ondansetron ♦ CYP2D6: Uncertain No recommendation for Ondansetron is (Zofran) Allele available for this combination of variants/


PGx

Tropisetron ♦ CYP2D6: Uncertain No recommendation for Tropisetron is (Navoban, Setrovel) Allele available for this combination of variants/

FDA drug label: Not alleles.

established for PGx

Antifungals

Ketoconazole 0 CYP3A4: Extensive Typical response is expected; no additional (Nizoral) metabolizer. Two therapeutic recommendations. -FDA drug label: Not alleles showing


Voriconazole 0 CYP2C19: The therapeutic outcome of this Efficacy

-(Vfend) Uncertain combination of alleles is uncertain.

FDA drug label: Actionable metabolizer status. However, individuals with rapid

PGx One allele showing metabolizer status may show increased normal activity and enzyme activity compared to normal one showing metabolizers but less than ultrarapid increased activity. metabolizers. Such individuals have

increased metabolism of drug; the resultant lower plasma concentrations may increase the probability of pharmacotherapy failure. Select an alternative drug.

Antineoplastic Agents

Methotrexate 0 MTHFR: Normal Typical response is expected; no additional (Rheumatrex, Trexall) function. Two alleles therapeutic recommendations.

FDA drug label: Not showing normal

established for PGx activity.

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. .


Antiplatelet Agents

Clopidogrel 0 CYP2C19: The therapeutic outcome of this combination of alleles is uncertain. However, individuals with rapid metabolizer status may show increased enzyme activity compared to normal metabolizers but less than ultrarapid metabolizers. Such individuals may benefit

from the elevated plasma concentration of the active compound when taking a standard dose. They may also be at increased risk of bleeding due to elevated plasma concentrations of the active compound. No additional therapeutic recommendations.

Efficacy


PGx

Prasugrel O FDA drug label: Informative

PGx

Ticagrelor O (Brilinta)

FDA drug label: Not

established for PGx

Uncertain metabolizer status. One allele showing normal activity and one showing increased activity.

CYP2C19: Uncertain metabolizer status. One allele showing normal activity and one showing increased activity.


The therapeutic outcome of this combination of alleles is uncertain. However, individuals with rapid metabolizer status may show increased enzyme activity compared to normal metabolizers but less than ultrarapid metabolizers. Such individuals show typical response; no additional therapeutic recommendations.


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. .


Risperidone ♦ CYP2D6: Uncertain No recommendation for Risperidone is (Risperdal) Allele available for this combination of variants/


PGx

Thioridazine ♦ CYP2D6: Uncertain No recommendation for Thioridazine is

FDA drug label: Actionable Allele available for this combination of variants/

PGx alleles.

Zuclopenthixol ♦ CYP2D6: Uncertain No recommendation for Zuclopenthixol is



Anti-Retroviral Agents

Efavirenz 0 CYP2B6: Extensive Typical response is expected; no additional (Sustiva) metabolizer. Two therapeutic recommendations.

FDA drug label: Actionable alleles showing

PGx normal activity.

Nevirapine 0 CYP2B6: Extensive Typical response is expected; no additional (Viramune) metabolizer. Two therapeutic recommendations.


established for PGx normal activity.

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. .

Drug

Anxiolytics


Alprazolam (Xanax, Niravam)

FDA drug label: Not

established for PGx

Buspirone (Buspar)

FDA drug label: Not

established for PGx

Clonazepam (Klonopin)

FDA drug label: Not

established for PGx

0

0

0







Diazepam A CYP2C19: The therapeutic outcome of this Efficacy


PGx

Beta-3 Adrenergic Agonists

Mirabegron (Myrbetriq)


PGx

Uncertain metabolizer status. One allele showing normal activity and one showing increased activity.


combination of alleles is uncertain. However, individuals with rapid metabolizer status may show increased enzyme activity compared to normal metabolizers but less than ultrarapid metabolizers. Such individuals may be at an increased risk of therapeutic failure due to increased metabolic clearance. Insufficient evidence to allow calculation of dose adjustment. Be alert to symptoms of insufficient therapy.

No recommendation for Mirabegron is available for this combination of variants/ alleles.

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. .


Beta Blockers

Carvedilol

(Coreg)


PGx

Metoprolol

(Lopressor)

FDA drug label: Informative

PGx

Nebivolol

(Systolic)


PGx

Propranolol

(lnderal)


PGx

♦

♦

♦

CYP2D6: Uncertain

Allele




Central Monoamine-Depleting Agents

Tetrabenazine

(Xenazine)

FDA drug label: Testing

required


Central Nervous System Agents

Dextromethorphan

Quinidine

(Nuedexta)


recommended

Cholinergic Agonists

Cevimeline

(Evoxac)


PGx


CYP2D6: Uncertain

Allele

No recommendation for Carvedilol is available for this combination of variants/ alleles.

No recommendation for Metoprolol is available for this combination of variants/ alleles.

No recommendation for Nebivolol is available for this combination of variants/ alleles.

No recommendation for Propranolol is available for this combination of variants/ alleles.

No recommendation for Tetrabenazine is available for this combination of variants/ alleles.

No recommendation for Dextromethorphan-Quinidine is available for this combination of variants/alleles.

No recommendation for Cevimeline is available for this combination of variants/ alleles.

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. .


Cholinesterase Inhibitors

Galantamine

(Razadyne,Razadyne ER, Nivalin, Lycoremine, Reminyl)


PGx

Contraceptives

Estrogen-containing

oral contraceptives

FDA drug label: Not

established for PGx

EGFR Inhibitors

Gefitinib (lressa)


required


FS: Two wild-type alleles.



Eliglustat


required

Hypnotics

Eszopiclone

(Lunesta)

FDA drug label: Not

established for PGx



No recommendation for Galantamine is available for this combination of variants/ alleles.


No recommendation for Gefitinib is available for this combination of variants/ alleles.

No recommendation for Eliglustat is available for this combination of variants/ alleles.


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. .


lmmunosuppressants

Cyclosporine 0 CYP3A4: Extensive Typical response is expected; no additional (Gengraf, Neoral) metabolizer. Two therapeutic recommendations. -FDA drug label: Not alleles showing


Sirolimus 0 CYP3A4: Extensive Typical response is expected; no additional (Rapamune) metabolizer. Two therapeutic recommendations. -FDA drug label: Not alleles showing


Tacrolimus 0 CYP3AS: Two alleles Individuals with poor metabolizer status (Prograf, Hecoria) showing little or no have higher dose-adjusted trough

FDA drug label: Not activity. concentrations of tacrolimus; the resultant

established for PGx increased concentrations may increase the probability of pharmacotherapy success. Consider initiating therapy with the recommended starting dose. In liver transplant patients, donor genotype should be considered as well as the recipient's.

Muscle Relaxants

Carisoprodol A CYP2C19: Rapid The therapeutic outcome of this ADR&

-(Soma) metabolizer status. combination of alleles is uncertain. Efficacy

FDA drug label: Actionable One allele showing However, individuals with rapid

PGx normal activity and metabolizer status may show increased one showing enzyme activity compared to normal increased activity. metabolizers but less than ultrarapid

metabolizers. Such individuals may have reduced exposure to carisoprodol (and subsequent increased exposure to meprobamate) due to increased carisoprodol metabolism. Carisoprodol should be administered with caution.

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. .


Non-drug

ApoE A ApoE: E4 is often There is a potential increased risk of associated with a cardiovascular disease and atherosclerosis. potential change in LDL cholesterol and plasma triglyceride levels.

COMT(Val158Met) 0 COMT(Val158Met): Increased function. Two alleles with Increased function. increased activity. Two alleles with increased activity.

CYP1A2 0 CYP1A2: *1Cl*1F or No additional therapeutic *1Cl*1M recommendations.

CYP2B6 0 CYP2B6: Extensive No additional therapeutic metabolizer. Two recommendations. alleles showing normal activity.

DPYD 0 OPYD: Extensive Typical response is expected; no additional metabolizer. Two therapeutic recommendations. alleles showing normal activity.

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. .


Nonsteroidal Anti-lnflamatory Drugs (NSAIDs)

Celecoxib A CYP2C9: Intermediate metabolizers are at uncertain ADR

(Celebrex) Intermediate risk of adverse drug reaction. However,

FDA drug label: Actionable metabolizer. One note that for individuals with poor

PGx allele showing metabolizer status it is recommended to normal activity and consider a 50% reduction in dose; there one showing are no additional therapeutic reduced activity. recommendations for individuals with

extensive metabolizer status.

Diclofenac 0 CYP2C9:rs1057910: Typical response is expected; no additional (Cataflam) Two alleles showing therapeutic recommendations.

FDA drug label: Not normal activity.

established for PGx

Flurbiprofen A CYP2C9: Individuals with intermediate metabolizer ADR

(Ocufen) Intermediate status may be at an increased risk of

FDA drug label: Actionable metabolizer. One adverse drug reactions due to reduced

PGx allele showing metabolic clearance and abnormally high normal activity and plasma concentrations of the active one showing compound. Insufficient evidence to allow reduced activity. calculation of dose adjustment.

Flurbiprofen should be administered with caution.

Ibuprofen A CYP2C9: Individuals with intermediate metabolizer ADR

(Motrin, Advil) Intermediate status may be at an increased risk of

FDA drug label: Not metabolizer. One adverse drug reactions due to reduced

established for PGx allele showing metabolic clearance of drug. Insufficient normal activity and evidence to allow calculation of dose one showing adjustment. reduced activity.

Lornoxicam A CYP2C9: Individuals with intermediate metabolizer ADR (Xefo) Intermediate status may be at an increased risk of

FDA drug label: Not metabolizer. One adverse drug reactions due to reduced

established for PGx allele showing metabolic clearance of drug. Insufficient normal activity and evidence to allow calculation of dose one showing adjustment. reduced activity.

Meloxicam 0 CYP2C9: Individuals with intermediate metabolizer ADR (Mobic) Intermediate status may have increased plasma

FDA drug label: Not metabolizer. One concentrations and decreased clearance of

established for PGx allele showing meloxicam. However, there is no current normal activity and association with treatment response or one showing severity of side effects in the literature. reduced activity.

0

-

-

-

0

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. .


Piroxicam A CYP2C9: Individuals with intermediate metabolizer ADR

(Feldene) Intermediate status may be at a significantly increased -

FDA drug label: Actionable metabolizer. One risk of adverse drug reactions due to

PGx allele showing reduced metabolic clearance and high normal activity and plasma concentrations of the active one showing compound. Consider reducing dose or reduced activity. select alternative drug.

Opioids

Buprenorphine 0 CYP3A4: Extensive Typical response is expected; no additional (Butrans, Buprenex) metabolizer. Two therapeutic recommendations. -



Codeine ♦ CYP2D6: Uncertain No recommendation for Codeine is

FDA drug label: Actionable Allele available for this combination of variants/

PGx alleles.

Fentanyl 0 CYP3A4: Extensive Typical response is expected; no additional (Duragesic, Sublimaze) metabolizer. Two therapeutic recommendations.



Hydrocodone ♦ CYP2D6: Uncertain No recommendation for Hydrocodone is



Oxycodone ♦ CYP2D6: Uncertain No recommendation for Oxycodone is (Oxycontin) Allele available for this combination of variants/

FDA drug label: Not alleles.

established for PGx

Oxycodone (CYP3AS) 0 CYP3AS: Two alleles In a preliminary study, individuals with ADR&

0 (Oxycontin) showing little or no poor metabolizers status have a Efficacy

FDA drug label: Not activity. significantly higher opioid escalation index

established for PGx compared to normal (extensive) metabolizers. Though the impact of metabolizer status at CYP3AS on pain relief is currently unknown, consider reducing the initial dose. There does not appear to be an effect of this metabolizer status on the incidence of drowsiness.

Tramadol ♦ CYP2D6: Uncertain No recommendation for Tramadol is (Ultracet, Ultram) Allele available for this combination of variants/


PGx

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. .


Proton Pump Inhibitors (PPls)

Dexlansoprazole (Dexilant, Kapidex)


PGx

Esomeprazole (Nexium)


PGx

Lansoprazole (Prevacid)


PGx

A

A

A

CYP2C19: Rapid metabolizer status. One allele showing normal activity and one showing increased activity.



The therapeutic outcome of this combination of alleles is uncertain. However, individuals with rapid metabolizer status may show increased enzyme activity compared to normal metabolizers but less than ultrarapid metabolizers. Such individuals may show increased metabolism to less active compounds; the resultant decreased concentrations may increase the risk of pharmacotherapeutic failure. Consider increasing dose.



Efficacy

Efficacy

Efficacy

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. .


Omeprazole A CYP2C19: Rapid The therapeutic outcome of this (Prilosec, Zegerid) metabolizer status. combination of alleles is uncertain.

Efficacy



metabolizers. Such individuals may show increased metabolism to less active compounds; the resultant decreased concentrations may increase the risk of pharmacotherapeutic failure. Consider increasing dose.

Pantoprazole A CYP2C19: Rapid The therapeutic outcome of this (Proton ix) metabolizer status. combination of alleles is uncertain.

Efficacy




Rabeprazole A CYP2C19: Rapid The therapeutic outcome of this (Aciphex) metabolizer status. combination of alleles is uncertain.

Efficacy




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. .


Selective Serotonin Reuptake Inhibitors {SSRls)

Citalopram 0 CYP2C19: The therapeutic outcome of this Efficacy (Celexa) Uncertain combination of alleles is uncertain.



increased metabolism; the resultant lower plasma concentrations may increase the probability of pharmacotherapy failure. Consider alternative drug.

Escitalopram 0 CYP2C19: The therapeutic outcome of this Efficacy (Lexa pro) Uncertain combination of alleles is uncertain.



increased metabolism; the resultant lower plasma concentrations may increase the probability of pharmacotherapy failure. Consider alternative drug.

Fluoxetine ♦ CYP2D6: Uncertain No recommendation for Fluoxetine is (Prozac) Allele available for this combination of variants/


PGx

Fluvoxamine ♦ CYP2D6: Uncertain No recommendation for Fluvoxamine is (Luvox) Allele available for this combination of variants/


PGx

Paroxetine ♦ CYP2D6: Uncertain No recommendation for Paroxetine is (Paxil) Allele available for this combination of variants/


PGx

Sertraline 0 CYP2C19: Rapid The therapeutic outcome of this (Zoloft) metabolizer status. combination of alleles is uncertain.

FDA drug label: Not One allele showing However, individuals with rapid

established for PGx normal activity and metabolizer status may show increased one showing enzyme activity compared to normal increased activity. metabolizers but less than ultrarapid

metabolizers. No additional therapeutic recommendations.

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. .

Drug

Statins


Atorvastatin O (Lipitor, Caduet)

FDA drug label: Not

established for PGx

Simvastatin O (Zocor)


PGx

CYP3A4: Extensive metabolizer. Two alleles showing normal activity.

SLCO1B1: Normal liver uptake activity.

Vesicular monoamine transporter 2 inhibitor

Deutetrabenazine

(Austedo)


PGx



Individuals with normal SLCO1B1 liver uptake activity are expected to have a typical response to a standard dose of simvastatin.

No recommendation for Deutetrabenazine is available for this combination of variants/alleles.

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Clinical Evidence Levels

estrong

. .. f..¼TruGenX


. .

• Includes gene-drug pairs approved by the Coriell Institute for Medical Research Pharmacogenomics Advisory Group.• Includes gene-drug pairs supported by multiple studies documenting consistent effects of specific genetic variant(s) on

clinical outcomes.• Includes gene-drug pairs approved by the Dutch Pharmacogenetics Working Group (DPWG) and/or guidelines

published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium(CPIC).

w Moderate

• Includes gene-drug pairs supported by pharmacokinetic, pharmacodynamic, or molecular/cellular functional studiesshowing consistent effects of genetic variant(s).

• Includes Drug product information (e.g. This interpretation is based on guidance available in the FDA (Food and DrugAdministration) drug label for ABILIFY® (10/2013).

• Includes gene-drug pairs for which potential clinical outcomes are inferred from similar gene-drug interactions approvedby the Dutch Pharmacogenetics Working Group (DPWG), and/or guidelines published in Clinical Pharmacology andTherapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC), and/or pharmacogenomic reportsand submission from the Coriell Institute for Medical Research.

0Emerging

• Includes gene-drug pairs supported by published studies of the drug, related drug, or a probing compound of interestinvolving limited data and/or inconsistent findings.

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Page 34 of 35







Patient Information Card

This card contains an abbreviated genetic summary. It is not intended as a replacement for the complete GeneDose™ report. r--------------------------------------------------------------------------------------------------------------------------------�

: .. tlTruGenX

e•!' Precision Medicine

• !

Patient:

DOB:

1956-01-01

TruGenX

https://trugenx.com/

DOE, JOHN

Sample ID:

20P00000

Pharmacogenomic Summary

ApoE E3jE4 See full GeneDose report

Factor V Leiden Normal See full GeneDose reeort

MTHFR (A1298C) Normal See full GeneDose report

MTHFR (C677T) Normal See full GeneDose report

Prothrombin (F2) Normal See full GeneDose report

t Cut on dotted lines.

This card shows information about your genetics that relate to drug metabolism. Show to your doctors before being prescribed new medications.

ATM AJA Normal response to metformin

COMT(Val158Met) GJG Multiple statuses; see per-drug detail

CYP1A2

CYP2B6

CYP2C19

CYP2C9

CYP2D6

CYP3A4

CYP3A5

CYP4F2

OPYD

MTHFR

SLCO1B1

VKORC1

t Fold Here

*1Cj*1F or*1Cj*1M

*1AJ*1A

*1 *17

*11*2

Uncertain Allele

*1Aj*1A

*3Aj*3A; or*3Cj*3C; or*3Aj*3C

Not Tested

*11*1

WTJWT

*11*1

*21*2

Intermediate metabolizer

Extensive metabolizer

Ra id metabolizer


n/a


Poor metabolizer

n/a

Normal function

Normal function

Normal liver uptake activity

Reduced (with respect to Warfarin)

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. .. f..¼TruGenX


. .

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Page 35 of 35






Documents

GeneDose Genetic Response Report TruGenX