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SAMPLE REPORT MENTAL HEALTH DNA INSIGHT® Protected Health Information PERSONAL DETAILS NAME SAMPLE PATIENT DOB Jan 1, 19XX GENDER F ETHNICITY Caucasian

ORDERING HEALTHCARE PROFESSIONAL Nilesh Dharajiya, M.D. 4755 Nexus Center Drive San Diego, CA 92121 US

Test Results Reviewed & Approved by: Laboratory Director, Nilesh Dharajiya, M.D.

Drug Class

Drug

Preferential Use

Use As Directed

TEST METHODOLOGY Genotyping by array-based evaluation of multiple molecular probes LABORATORY INFO ACCESSION NUMBER ACTIVATION CODE SPECIMEN TYPE COLLECTED DATE RECEIVED DATE REPORT DATE May Have Significant Limitations

F7715016 ABCDE-BABAB SALIVA Oct 29, 2015 Nov 2, 2015 Nov 12, 2015

May Cause Serious Adverse Events

Citalopram Escitalopram Fluoxetine

SSRIs

Fluvoxamine Paroxetine Sertraline Vilazodone Amitriptyline Clomipramine Desipramine

TCAs

Doxepin Imipramine Nortriptyline Protriptyline Trimipramine Bupropion Buspirone Duloxetine Levomilnacipran

Other Antidepressants

Mirtazapine Nefazodone Trazodone Venlafaxine Vortioxetine

See Disclaimer(s) on page 9 of this Report · Copyright © 2015 Pathway Genomics · All Rights Reserved. Patents Pending. Laboratory Director: Nilesh Dharajiya, M.D. CLIA Number: 05D1092505 · 4755 Nexus Center Drive, San Diego, CA 92121 · http://www.pathway.com/

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SAMPLE REPORT MENTAL HEALTH DNA INSIGHT® Protected Health Information

Drug Class

Drug

Preferential Use

Use As Directed

NAME GENDER ACCESSION # REPORT DATE

May Have Significant Limitations

SAMPLE PATIENT F F7715016 Nov 12, 2015

May Cause Serious Adverse Events

Aripiprazole Asenapine Clozapine Iloperidone

Atypical Antipsychotics

Lurasidone Olanzapine Paliperidone Quetiapine Risperidone Ziprasidone Haloperidol Perphenazine

Typical Antipsychotics

Pimozide Thioridazine Zuclopenthixol Carbamazepine Divalproex

Mood Stabilizers

Lamotrigine Oxcarbazepine Phenytoin Valproic acid

Norepinephrine Reuptake Inhibitor Benzodiazepines

Atomoxetine Clobazam Diazepam Dextromethorphan and Quinidine

Others

Galantamine Modafinil Tetrabenazine

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SAMPLE REPORT MENTAL HEALTH DNA INSIGHT® Protected Health Information

NAME GENDER ACCESSION # REPORT DATE

SAMPLE PATIENT F F7715016 Nov 12, 2015

May Cause Serious Adverse Events Drug Class

Drug

Comments

Mood Stabilizers

Carbamazepine

Patient has increased risk of developing Stevens-Johnson syndrome or toxic epidermal necrolysis during treatment with carbamazepine. Patient is likely to have at least one copy of the HLA-B*1502 allele that is associated with increased risk. Carbamazepine treatment should not be started in this patient unless the risk is clearly outweighed by the benefit. Patients who test positive for the HLA-B*1502 allele and have been taking carbamazepine for more than a few months without developing skin reactions have a low risk of becoming hypersensitive. HLA-B*1502-positive patients could also be advised to avoid related anticonvulsants, such as phenytoin, lamotrigine and oxcarbazepine. The genetic test for this condition is most applicable to patients of Han Chinese descent. If clinically indicated, patients of other Asian ethnicities could be advised to undergo HLA sequencing to assess their risk of carbamazepine hypersensitivity. Other HLA alleles have been shown to be associated with carbamazepine hypersensitivity in people of Caucasian and Japanese descent, in whom HLA-B*1502 is largely absent.

Lamotrigine

Patient may have increased risk of developing Stevens-Johnson syndrome or toxic epidermal necrolysis during treatment with lamotrigine. Patient is likely to have at least one copy of the HLA-B*1502 allele that may increase risk. The use of lamotrigine in this patient should be carefully considered. Patients who test positive for the HLA-B*1502 allele and have been taking lamotrigine for more than a few months without developing skin reactions have a low risk of becoming hypersensitive. HLA-B*1502-positive patients could also be advised to avoid related anticonvulsants, such as carbamazepine, phenytoin and oxcarbazepine. The genetic test for this condition is most applicable to patients of Han Chinese descent. If clinically indicated, patients of other Asian ethnicities could be advised to undergo HLA sequencing to assess their risk of lamotrigine hypersensitivity. Other HLA alleles have been shown to be associated with lamotrigine hypersensitivity in people of Caucasian and Japanese descent, in whom HLA-B*1502 is largely absent.

Oxcarbazepine

Patient has increased risk of developing Stevens-Johnson syndrome or toxic epidermal necrolysis during treatment with oxcarbazepine. Patient is likely to have at least one copy of the HLA-B*1502 allele that is associated with increased risk. The use of oxcarbazepine in this patient should be carefully considered. Patients who test positive for the HLAB*1502 allele and have been taking oxcarbazepine for more than a few months without developing skin reactions have a low risk of becoming hypersensitive. HLAB*1502-positive patients could also be advised to avoid related anticonvulsants, such as carbamazepine, phenytoin and lamotrigine. The genetic test for this condition is most applicable to patients of Han Chinese descent. If clinically indicated, patients of other Asian ethnicities could be advised to undergo HLA sequencing to assess their risk of oxcarbazepine hypersensitivity. Other risk factors may contribute to oxcarbazepine hypersensitivity in people of Caucasian and Japanese descent, in whom HLA-B*1502 is largely absent.

Phenytoin

Patient is likely to have at least one copy of HLA-B*1502 allele, therefore, has increased risk of developing serious skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis (SJS/TEN), when treated with phenytoin. The use of phenytoin in this patient should be carefully considered. HLA-B*1502-positive patients could also be advised to avoid related anticonvulsants, such as carbamazepine and oxcarbazepine. This genetic test is most applicable to patients of Han Chinese descent. If clinically indicated, patients of other Asian ethnicities may be advised to undergo HLA sequencing to assess their risk of phenytoin hypersensitivity. There are insufficient data to associate HLA-B*1502 with phenytoin hypersensitivity in other ethnicities.

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SAMPLE REPORT MENTAL HEALTH DNA INSIGHT® Protected Health Information

NAME GENDER ACCESSION # REPORT DATE

SAMPLE PATIENT F F7715016 Nov 12, 2015

May Have Significant Limitations Drug Class

Drug

Comments

SSRIs

Citalopram

Patient's SLC6A4 genotype is associated with increased risk of adverse effects, such as headache, nausea, drowsiness, agitation, sexual dysfunction or weight gain, when citalopram is used to treat major depressive disorder. Special note for Asian patients: the assay does not test for some SLC6A4 alleles that are mostly found in Asians. These untested alleles cannot be distinguished from the "S" alleles that are tested in this assay. The combined frequency of the untested alleles, whose functional impact is not well understood, is about 10% in Asians, whereas the combined frequency of the "S" alleles that can be correctly identified by this assay is about 80% in Asians. Please see the patient's genotype details at the end of the report.

Fluoxetine

Patient's SLC6A4 genotype is associated with increased risk of adverse effects, such as headache, nausea, drowsiness, agitation, sexual dysfunction or weight gain, when fluoxetine is used to treat major depressive disorder. Special note for Asian patients: the assay does not test for some SLC6A4 alleles that are mostly found in Asians. These untested alleles cannot be distinguished from "S" alleles that are tested in this assay. The combined frequency of the untested alleles, whose functional impact is not well understood, is about 10% in Asians, whereas the combined frequency of the "S" alleles that can be correctly identified by this assay is about 80% in Asians. Please see the patient's genotype details at the end of the report.

Fluvoxamine

Patient's SLC6A4 genotype is associated with increased risk of adverse effects, such as headache, nausea, drowsiness, agitation, sexual dysfunction or weight gain, when fluvoxamine is used to treat major depressive disorder. Special note for Asian patients: the assay does not test for some SLC6A4 alleles that are mostly found in Asians. These untested alleles cannot be distinguished from the "S" alleles that are tested in this assay. The combined frequency of the untested alleles, whose functional impact is not well understood, is about 10% in Asians, whereas the combined frequency of the "S" alleles that can be correctly identified by this assay is about 80% in Asians. Please see the patient's genotype details at the end of the report.

Paroxetine

Patient's SLC6A4 genotype is associated with increased risk of adverse effects, such as headache, nausea, drowsiness, agitation, sexual dysfunction or weight gain, when paroxetine is used to treat major depressive disorder. Special note for Asian patients: the assay does not test for some SLC6A4 alleles that are mostly found in Asians. These untested alleles cannot be distinguished from the "S" alleles that are tested in this assay. The combined frequency of the untested alleles, whose functional impact is not well understood, is about 10% in Asians, whereas the combined frequency of the "S" alleles that can be correctly identified by this assay is about 80% in Asians. Please see the patient's genotype details at the end of the report.

Venlafaxine

Patient's SLC6A4 genotype is associated with a decreased response to venlafaxine. Special note for Asian patients: the assay does not test for some SLC6A4 alleles that are mostly found in Asians. These untested alleles cannot be distinguished from the "S" alleles that are tested in this assay. The combined frequency of the untested alleles, whose functional impact is not well understood, is about 10% in Asians, whereas the combined frequency of the "S" alleles that can be correctly identified by this assay is about 80% in Asians. Please see the patient's genotype details at the end of the report.

Other Antidepressants

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SAMPLE REPORT MENTAL HEALTH DNA INSIGHT® Protected Health Information

NAME GENDER ACCESSION # REPORT DATE

SAMPLE PATIENT F F7715016 Nov 12, 2015

Use As Directed Drug Class

Drug

Comments

SSRIs

Escitalopram

The most recent label for this drug should be consulted for up-to-date dosing guidelines and limitations.

Sertraline Vilazodone TCAs

Amitriptyline Clomipramine

The most recent label for this drug should be consulted for up-to-date dosing guidelines and limitations.

Desipramine Doxepin Imipramine Nortriptyline Protriptyline Trimipramine Other Antidepressants

Bupropion Buspirone

The most recent label for this drug should be consulted for up-to-date dosing guidelines and limitations.

Duloxetine Levomilnacipran Mirtazapine Nefazodone Trazodone Vortioxetine Atypical Antipsychotics

Aripiprazole Asenapine

The most recent label for this drug should be consulted for up-to-date dosing guidelines and limitations.

Clozapine Iloperidone Lurasidone Olanzapine Paliperidone Quetiapine Risperidone Ziprasidone

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SAMPLE REPORT MENTAL HEALTH DNA INSIGHT® Protected Health Information

NAME GENDER ACCESSION # REPORT DATE

SAMPLE PATIENT F F7715016 Nov 12, 2015

Use As Directed (Continued) Drug Class

Drug

Comments

Typical Antipsychotics

Haloperidol

The most recent label for this drug should be consulted for up-to-date dosing guidelines and limitations.

Perphenazine Pimozide Thioridazine Zuclopenthixol Mood Stabilizers

Divalproex Valproic acid

The most recent label for this drug should be consulted for up-to-date dosing guidelines and limitations.

Norepinephrine Reuptake Inhibitor

Atomoxetine

The most recent label for this drug should be consulted for up-to-date dosing guidelines and limitations.

Benzodiazepines

Clobazam

The most recent label for this drug should be consulted for up-to-date dosing guidelines and limitations.

Diazepam Others

Dextromethorphan The most recent label for this drug should be consulted for up-to-date dosing guidelines and limitations. and Quinidine Galantamine Modafinil Tetrabenazine

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SAMPLE REPORT MENTAL HEALTH DNA INSIGHT®

NAME GENDER ACCESSION # REPORT DATE

Protected Health Information

SAMPLE PATIENT F F7715016 Nov 12, 2015

GENOTYPE/HAPLOTYPE DETAIL PHARMACOGENETICS This section lists the genetic markers that were tested. Results are organized by gene. Each gene has up to three sections, which may include a "Metabolizer Status" section, a "Genetic Result" section and an associated table with three columns. "Metabolizer Status" indicates the patient's predicted metabolizer status. "Genetic Result" indicates the haplotype, genotype or presence of a mutation. A genetic result that contains “ND” indicates that a haplotype could not be determined. “Unable To Report” indicates that no result can be provided. In the tables, results are organized by gene in three columns: 1. “Gene/Locus” refers to the gene or intergenic region where the marker is located. 2. “Marker” refers to the unique identifier of the tested marker. 3. “Genotype” refers to the combination of nucleotides at a particular marker. The letter(s) on each side of the slash refer(s) to the two copies of the patient’s DNA. "Del" indicates a deletion of the nucleotide(s) in the patient's DNA. A genotype of “- -“ indicates that a result could not be obtained.

CYP1A2 GENE/LOCUS

MARKER

CYP1A2

rs762551

GENOTYPE

C/C

CYP2B6

CYP2C9

CYP3A4

Metabolizer Status: Extensive Metabolizer

GENE/LOCUS

MARKER

CYP3A4

rs4646438

A/A

CYP3A4

rs35599367

C/C

CYP3A4

rs55901263

C/C

CYP3A4

rs55951658

A/A

CYP3A4

rs67666821

A/A

CYP3A4

rs138105638

C/C

Genetic Result: CYP2C9 *1/*1 GENE/LOCUS

MARKER

CYP2C9

rs1057910

GENOTYPE

A/A

Metabolizer Status: Extensive Metabolizer

CYP2C9

rs1799853

C/C

Genetic Result: CYP2B6 *1/*4

CYP2C9

rs9332131

A/A

GENE/LOCUS

MARKER

GENOTYPE

CYP2B6

rs2279343

A/G

CYP2B6

rs3211371

C/C

CYP2B6

rs3745274

G/G

CYP2B6

rs8192709

C/C

CYP2B6

rs28399499

A/A

CYP2D6 Metabolizer Status: Extensive Metabolizer Genetic Result: CYP2D6 *1/*1 GENE/LOCUS

MARKER

CYP2D6

rs16947

C/C

CYP2D6

rs769258

G/G

CYP2D6

rs1065852

C/C

Metabolizer Status: Extensive Metabolizer

CYP2D6

rs1080985

C/C

Genetic Result: CYP2C19 *1/*1

CYP2D6

rs3892097

G/G

CYP2C19

GENOTYPE

DRD2 GENE/LOCUS

MARKER

DRD2

rs1799732

GENOTYPE

C/C

GENOTYPE

HLA-A Genetic Result: HLA-A x/x GENE/LOCUS

MARKER

HLA Region

rs1061235

GENOTYPE

A/A

GENE/LOCUS

MARKER

CYP2D6

rs5030655

T/T

CYP2C19

rs4244285

G/G

CYP2D6

rs5030656

AAG/AAG

CYP2C19

rs4986893

G/G

CYP2D6

rs5030862

G/G

CYP2C19

rs12248560

C/C

GENE/LOCUS

MARKER

CYP2D6

rs5030863

C/C

CYP2C19

rs28399504

A/A

HLA Region

rs2844682

T/T

CYP2D6

rs5030865

C/C

CYP2C19

rs41291556

T/T

HLA Region

rs3909184

G/C

CYP2D6

rs5030867

A/A

CYP2C19

rs56337013

C/C

CYP2D6

rs28371706

C/C

CYP2C19

rs72552267

G/G

HTR2A

CYP2D6

rs28371725

G/G

GENE/LOCUS

MARKER

CYP2C19

rs72558186

T/T

CYP2D6

rs35742686

A/A

HTR2A

rs7997012

CYP2D6

rs59421388

C/C

CYP2D6

rs72549357

T/T

HLA-B Genetic Result: HLA-B *1502/x GENOTYPE

GENOTYPE

A/G

HTR2A GENE/LOCUS

MARKER

HTR2A

rs6311

GENOTYPE

A/G

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SAMPLE REPORT MENTAL HEALTH DNA INSIGHT® Protected Health Information

NAME GENDER ACCESSION # REPORT DATE

SAMPLE PATIENT F F7715016 Nov 12, 2015

HTR2C GENE/LOCUS

MARKER

HTR2C

rs1414334

GENOTYPE

G/G

HTR2C

rs3813929

G/G

POLG GENE/LOCUS

MARKER

POLG

rs113994095

GENOTYPE

G/G

POLG

rs113994097

G/G

POLG

rs113994098

G/G

SLC6A4 Genetic Result: SLC6A4 S/S GENE/LOCUS

MARKER

SLC6A4

5-HTTLPR

GENOTYPE

S/S

SLC6A4

rs25531

UGT1A4 GENE/LOCUS

MARKER

UGT1A4

rs2011425

GENOTYPE

C/C

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SAMPLE REPORT MENTAL HEALTH DNA INSIGHT® Protected Health Information

NAME GENDER ACCESSION # REPORT DATE

SAMPLE PATIENT F F7715016 Nov 12, 2015

DISCLAIMER This test was developed and its performance characteristics determined by Pathway Genomics Corporation. It has not been cleared or approved by the FDA. The laboratory is regulated under CLIA as qualified to perform high-complexity testing. This test is used for clinical purposes. It should not be regarded as investigational or for research. If you have any questions about this report or wish to speak with one of Pathway Genomics' genetic counselors, please call (877) 505.7374.

RISKS AND LIMITATIONS Risk of Laboratory Technical Problems or Laboratory Error The certified testing laboratory has standard and effective procedures in place to protect against technical and operational problems. However, such problems may still occur. The testing laboratory receives samples collected by patients and physicians. Problems in shipping to the laboratory or sample handling can occur, including but not limited to damage to the specimen or related paperwork, mislabeling, and loss or delay of receipt of the specimen. Laboratory problems can occur that might lead to inability to obtain results. Examples include, but are not limited to, sample mislabeling, DNA contamination, un-interpretable results, and human and/or testing system errors. In such cases, the testing laboratory may need to request a new sample. However, upon re-testing, results may still not be obtainable. As with all medical laboratory testing, there is a small chance that the laboratory could report inaccurate information. For example, the laboratory could report that a given genotype is present when in fact it is not. Any kind of laboratory error may lead to incorrect decisions regarding medical treatment and/or diet and fitness recommendations. If a laboratory error has occurred or is suspected, a health care professional may wish to pursue further evaluation and/or other testing. Further testing may be pursued to verify any results for any reason. Limitations The purpose of this test is to provide information about how a tested individual’s genes may affect carrier status for some inherited diseases, responses to some drugs, risk for specific common health conditions, and/or selected diet, nutrition and/or exercise responses, as well as to learn more about the tested individual’s ancient ancestry, depending upon the specific genetic testing that is ordered by the health care professional. Tested individuals should not make any changes to any medical care (including but not limited to changes to dosage or frequency of medications, diet and exercise regimens, or pregnancy planning) based on genetic testing results without consulting a health care professional. The science behind the significance or interpretation of certain testing results continues to evolve. Although great strides have been made to advance the potential usefulness of genetic testing, there is still much to be discovered. Genetic testing is based upon information, developments and testing techniques that are known today. Future research may reveal changes in the interpretation of previously obtained genetic testing results. For example, any genetic test is limited by the variants being tested. The interpretation of the significance of some variants may change as more research is done about them. Some variants that are associated with disease, drug response, or diet, nutrition and exercise response may not be tested; possibly these variants have not yet been identified in genetic studies. Many of the conditions and drug responses that are tested are dependent on genetic factors as well as nongenetic factors such as age, personal health and family health history, diet, and ethnicity. As such, an individual may not exhibit the specific drug response, disease, or diet, nutrition and exercise response consistent with the genetic test results. Another limitation for some conditions, particularly in the areas of diet and exercise, is that genetic associations have been studied and observed in Caucasian populations only, and in some cases only in one gender. In this case, the interpretations and recommendations are made in the context of Caucasian studies, but the results may or may not be relevant to tested individuals who are of non-Caucasian or mixed ethnicities or the non-studied gender. If patient ethnicity is not disclosed in the test requisition form the ethnicity field in the report will read as "Ethnicity: Not Reported". Such reports will be defaulted to phenotype list displayed for Caucasian ethnicity. Based on test results and other medical knowledge of the tested individual, health care professionals might consider additional independent testing, or consult another health care professional or genetic counselor.

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SAMPLE REPORT MENTAL HEALTH DNA INSIGHT® Protected Health Information

NAME GENDER ACCESSION # REPORT DATE

SAMPLE PATIENT F F7715016 Nov 12, 2015

RESULT STATUS DEFINITIONS Amended

Test results and/or patient information that have been revised in a way that does not impact the clinical significance of the result(s) and/or patient diagnosis, treatment or management.

Corrected

Test results and/or patient information that have been revised in a way that may impact the clinical significance of the result(s) and/or patient diagnosis, treatment or management.

Final

Pending

Test results that are available at the time of report issue or have been revised from pending status to final status.

Test results that are not available at the time of report issue. All pending results will be specified in the report.

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SAMPLE REPORT