Understanding Your Negative Result

A guide to understanding your risk and taking action

RECEIVING HEALTHCARE PROVIDER

Physician Name, MDMyriad Healthcare Partners320 Wakara WaySalt Lake City, UT 84108

SPECIMEN

Specimen Type: BuccalDraw Date: Aug 15, 2017Accession Date: Aug 30, 2017Report Date: Sept 4, 2017

PATIENT

Name: Case Study 1Date of Birth: Feb 20, 1977Patient ID: 0000Gender: FemaleAccession #: 00000000-000Requisition #: 000000ORDERING PHYSICIAN: Physician Name, MD

Myriad myRisk® Hereditary Cancer Test

myRisk Genetic Result

CONFIDENTIAL

© 2017 Myriad Genetics, Inc. | 320 Wakara Way, Salt Lake City, Utah 84108 | PH: 1-800-469-7423 FX: 801-584-3615The format and contents of this report are proprietary and may not be copied or used without permission, except for purposes of diagnosing, counseling and treating the patient identifi ed in the report and members of his or her family. Myriad, Myriad myRisk, riskScore, BRACAnalysis, COLARIS, myVision and their respective logos are either trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and other jurisdictions. myRisk Genetic Result: Page 1 of 3

Details About Non-Clinically Signifi cant Variants: All individuals carry DNA changes (i.e., variants), and most variants do not increase an individual’s risk of cancer or other diseases. When identifi ed, variants of uncertain signifi cance (VUS) are reported. Likely benign variants (Favor Polymorphisms) and benign variants (Polymorphisms) are not reported and available data indicate that these variants most likely do not cause increased cancer risk. Present evidence does not suggest that non-clinically signifi cant variant fi ndings be used to modify patient medical management beyond what is indicated by the personal and family history and any other clinically signifi cant fi ndings.

Variant Classifi cation: Myriad’s myVision® Variant Classifi cation Program performs ongoing evaluations of variant classifi cations. In certain cases, healthcare providers may be contacted for more clinical information or to arrange family testing to aid in variant classifi cation. When new evidence about a variant is identifi ed and determined to result in clinical signifi cance and management change, that information will automatically be made available to the healthcare provider through an amended report.

ADDITIONAL FINDINGS: NO VARIANT(S) OF UNCERTAIN SIGNIFICANCE (VUS) IDENTIFIED

MYRISK GENETIC RESULT: NEGATIVENo clinically signifi cant mutation identifi ed.

CLINICAL HISTORY ANALYSIS: NO MODIFIED MEDICAL MANAGEMENT GUIDELINES WERE IDENTIFIED BASED ON THE INFORMATION PROVIDED.Other clinical factors may infl uence individualized management. This analysis may be incomplete if details about cancer diagnoses, ages, family relationships or other factors were omitted or ambiguous.

BREAST CANCER RISKSCORE™: REMAINING LIFETIME RISK 15.2%See riskScore™ Interpretation Section for more information.

CONFIDENTIAL

© 2017 Myriad Genetics, Inc. | 320 Wakara Way, Salt Lake City, Utah 84108 | PH: 1-800-469-7423 FX: 801-584-3615The format and contents of this report are proprietary and may not be copied or used without permission, except for purposes of diagnosing, counseling and treating the patient identifi ed in the report and members of his or her family. Myriad, Myriad myRisk, riskScore, BRACAnalysis, COLARIS, myVision and their respective logos are either trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and other jurisdictions.

Indication for Testing: It is our understanding that this individual was identifi ed for testing due to a personal or family history suggestive of a hereditary predisposition for cancer.

Associated Cancer Risks and Clinical Management: Please see the “myRisk Management Tool” associated with this report for a summary of cancer risk and professional society medical management guidelines that may be useful in developing a plan for this patient based on test results and reported personal/family history, if applicable. Testing of other family members may assist in the interpretation of this patient’s test result.

Analysis Description: The Technical Specifi cations summary (MyriadPro.com/myRisk) describes the analysis, method, performance, nomenclature, and interpretive criteria of this test. The classifi cation and interpretation of all variants identifi ed in this assay refl ects the current state of scientifi c understanding at the time this report was issued, and may change as new scientifi c information becomes available. The interpretation of this test may be impacted if the patient has a hematologic malignancy or an allogeneic bone marrow transplant.

ADDITIONAL INFORMATION

GENES ANALYZED

Unless otherwise noted sequencing and large rearrangement analyses were performed on the following genes:

APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM (large rearrangement only), MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53. Sequencing was performed for select regions of POLE and POLD1. and large rearrangement analysis was performed for select regions of GREM1 (see technical specifi cations).

**Other genes not analyzed with this test may also be associated with cancer.

Name: Case Study 1 DOB: Feb 20, 1977 Accession #: 00000000-000 Report Date: Sept 4, 2017

myRisk Genetic Result

myRisk Genetic Result: Page 2 of 3

THE CLASSIFICATION AND INTERPRETATION OF ALL VARIANTS IDENTIFIED IN THIS ASSAY REFLECTS THE CURRENT STATE OF MYRIAD’S SCIENTIFIC UNDERSTANDING AT THE TIME THIS REPORT WAS ISSUED. VARIANT CLASSIFICATION AND INTERPRETATION MAY CHANGE FOR A VARIETY OF REASONS, INCLUDING BUT NOT LIMITED TO, IMPROVEMENTS TO CLASSIFICATION TECHNIQUES, AVAILABILITY OF ADDITIONAL SCIENTIFIC INFORMATION, AND OBSERVATION OF A VARIANT IN MORE PATIENTS.

CLASSIFICATION DISCLAIMER

CONFIDENTIAL

© 2017 Myriad Genetics, Inc. | 320 Wakara Way, Salt Lake City, Utah 84108 | PH: 1-800-469-7423 FX: 801-584-3615The format and contents of this report are proprietary and may not be copied or used without permission, except for purposes of diagnosing, counseling and treating the patient identifi ed in the report and members of his or her family. Myriad, Myriad myRisk, riskScore, BRACAnalysis, COLARIS, myVision and their respective logos are either trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and other jurisdictions.

CONFIDENTIAL

Breast Cancer riskScore™ - Remaining Lifetime Risk

General Population

This Patient

3530 40 45 >502520151050

20% Risk Threshold

13%

BREAST CANCER RISKSCORE™ INTERPRETATION

The breast cancer riskScore™ provides an estimate of the remaining lifetime risk for breast cancer. A risk estimate greater than 20% is associated with specifi c modifi ed medical recommendations, including consideration of more aggressive breast cancer screening and additional risk reduction measures. If applicable, details of these recommendations are provided in the accompanying myRisk Medical Management Tool or other supplemental material. Women with a risk estimate below 20% may still be appropriate for consideration of modifi ed medical management based on other clinical factors or estimates from other breast cancer risk models, such as Tyrer-Cuzick, Claus, and Gail.

BREAST CANCER RISKSCORE™ ANALYSIS DESCRIPTION

The breast cancer riskScore™ provides 5-year and remaining lifetime breast cancer risks, based on an analysis of genetic markers combined with patient clinical and family history data. The Technical Specifi cations summary (https://www.myriadpro.com/documents-and-forms/technical-specifi cations/) describes the analysis, method, performance and interpretive criteria of this test. In some cases, due to biological or technical limitations, analyses of all ___ biomarkers may not be performed. It is unlikely that data from the un-analyzed markers would have a large impact on breast cancer risk estimates provided. ___/86 markers were analyzed for this patient. Clinical and family history data used for this analysis is shown in the Clinical and Cancer Family History Information section of this report. The accuracy of this information can signifi cantly affect the provided breast cancer risk estimates.

15.2%RESULT: 15.2% Remaining Lifetime Risk for Breast Cancer

0.7% 5-Year Risk for Breast Cancer

Breast Cancer riskScore™

15.2%

These test results should only be used in conjunction with the patient’s clinical history and any previous analysis of appropriate family members. The patient’s clinical history and test results should not be disclosed to a third party, unless related to treatment or payment for treatment, without the patient’s express written authorization. It is strongly recommended that these results be communicated to the patient in a setting that includes appropriate counseling. This test was developed and its performance characteristics determined by Myriad Genetic Laboratories. It has not been cleared or approved by the U.S. Food and Drug Administration (FDA). The FDA has determined that clearance or approval for laboratory-developed tests is not required.

This Authorized Signature pertains to this laboratory report:

Benjamin B. Roa, PhDDiplomate ABMGLaboratory Director

Richard J. Wenstrup, MDDiplomate ABMGChief Medical Offi cer

Please contact Myriad Medical Services at 1-800-469-7423 X 3850 to discuss any questions regarding this result.

myRisk Genetic Result: Page 3 of 3

Name: Case Study 1 DOB: Feb 20, 1977 Accession #: 00000000-000 Report Date: Sept 4, 2017

myRisk Genetic Result

Average Risk Above Average Risk

Breast Cancer riskScore™

CONFIDENTIAL

© 2017 Myriad Genetics, Inc. | 320 Wakara Way, Salt Lake City, Utah 84108 | PH: 1-800-469-7423 FX: 801-584-3615The format and contents of this report are proprietary and may not be copied or used without permission, except for purposes of diagnosing, counseling and treating the patient identifi ed in the report and members of his or her family. Myriad, Myriad myRisk, riskScore, BRACAnalysis, COLARIS, myVision and their respective logos are either trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and other jurisdictions.

Name: Case Study 1 DOB: Feb 20, 1977 Accession #: 00000000-000 Report Date: Sept 4, 2017

Clinical & Cancer Family History Information

PERSONAL / FAMILY CANCER HISTORY SUMMARY*

FAMILY MEMBER CANCER / CLINICAL DIAGNOSIS AGE AT DIAGNOSIS

Patient None - -

Mother Ovarian 60

NUMBER OF PATIENT’S FEMALE RELATIVES

Daughters: 0 Sisters: 1 Maternal Aunts: 1 Paternal Aunts: 1

The clinical information displayed here was provided by a qualifi ed healthcare provider on the Test Request Form and other documents, and was not verifi ed by Myriad. Family members listed as “other” are not included in a Tyrer-Cuzick breast cancer risk estimate or other personal/family history assessments. For more information see the Specifi cations for Personal/Family History Analysis at https://new.myriadpro.com/documents-and-forms/technical-specifi cations/.

PATIENT CLINICAL HISTORY SUMMARY

Woman’s age 40 Hormone Replacement Therapy (HRT) No

Ancestry White/Non-hispanic - HRT: Treatment type N/A

Height 5’ 8” - HRT: Current user No

Weight 145 lbs. - Number of years ago started N/A

Age of menarche 13 - Additional years of intended use N/A

Patient’s menopausal status Pre-menopausal - HRT: Past user No

- Age of onset N/A - Number of years ago ended N/A

Age of fi rst live birth 28 Breast biopsy No

Clinical & Family History Information: Page 1 of 1

Your test result may include three parts: your Genetic Test Result, your breast cancer riskScore™

(if applicable), and your Clinical History Analysis.

Genetic Test ResultA. Your Myriad myRisk® Hereditary Cancer result

summary is shown on the first page of your report.

1. Your myRisk Genetic Result is NEGATIVE. This

means that you tested negative for any clinically

significant changes (called mutations) in the

genes analyzed on myRisk. Based on this, your

risk for a hereditary cancer syndrome is lower

but not completely ruled out.

2. Your result may also contain a breast cancer

riskScore™. If this analysis was performed, your

score was below 20% and additional details

will be provided on the following page of your

Genetic Test Result (see D.)

3. Your Clinical History Analysis did not identify

any modified medical management based on

the personal clinical risk factors and cancer

family history you reported to your provider.

B. Your testing may have found one or more

“Variants of Uncertain Significance (VUS).” A VUS

is not currently known to be associated with an

increased cancer risk. Myriad has made a lifetime

commitment to understanding the nature of

these variants. If new evidence about a variant is

identified, that information will be made available

to your healthcare provider who will then contact

you with updated information. It is important to

understand that medical interventions should not

be based on the VUS result.

C. You can find a list of all genes tested in the

Genes Analyzed section.

D. If the riskScore™ was performed, this page of

your Genetic Test Result will contain details of the

analysis. This page displays an estimate of your

remaining lifetime risk for breast cancer as well as

your risk over the next five years. You can compare

your risk to the general population using the graph

provided. A riskScore is only calculated for women

under age 85, of soley European ancestry, and

without a personal history of breast cancer, LCIS or

atypical hyperplasia.

E. The Clinical and Cancer Family History Information Page displays the information

regarding your clinical history and personal and

cancer family history you reported.

PART ONE:

1 Understanding Your Result

A

B

C

D

E

Negative result with SINGLE-SITE testing: If a member of your family has tested positive for a mutation, your provider may have ordered testing for only that mutation to see if you carry it. This is known as single-site testing. If you get a negative single site test result, you DO NOT carry the same mutation that is in your family. Because single-site testing does not look for other mutations or assess risk from family history, there are limitations to the information.

CONFIDENTIAL

© 2017 Myriad Genetics, Inc. | 320 Wakara Way, Salt Lake City, Utah 84108 | PH: 1-800-469-7423 FX: 801-584-3615The format and contents of this report are proprietary and may not be copied or used without permission, except for purposes of diagnosing, counseling and treating the patient identifi ed in the report and members of his or her family. Myriad, Myriad myRisk, riskScore, BRACAnalysis, COLARIS, myVision and their respective logos are either trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and other jurisdictions.

CONFIDENTIAL

Myriad myRisk® Hereditary Cancer Test

myRisk Management Tool

ADDITIONAL FINDINGS: NO VARIANT(S) OF UNCERTAIN SIGNIFICANCE (VUS) IDENTIFIED

TYRER-CUZICK BREAST CANCER RISK CALCULATION:

LIFETIME BREAST CANCER RISK: 13.6% 5-YEAR BREAST CANCER RISK: 0.7%

The Tyrer-Cuzick breast cancer risk estimate is not calculated if one or more of the following conditions apply: the woman is known to carry a mutation in a gene associated with breast cancer risk, age is 85 or older, or if the sample was submitted with a version of the Test Request Form that does not include all of the fi elds required to collect the clinical information used in the calculation. Version 7.02 of the Tyrer-Cuzick model was used for this risk estimate. Tyrer-Cuzick model Versions 7.02 and 8.0 are available for download at the EMS-Trials website, http://www.ems-trials.org/riskevaluator.

RECEIVING HEALTHCARE PROVIDER

Physician Name, MDMyriad Healthcare Partners320 Wakara WaySalt Lake City, UT 84108

SPECIMEN

Specimen Type: BuccalDraw Date: Aug 15, 2017Accession Date: Aug 30, 2017Report Date: Sept 4, 2017

PATIENT

Name: Case Study 1Date of Birth: Feb 20, 1977Patient ID: 0000Gender: FemaleAccession #: 00000000-000Requisition #: 000000ORDERING PHYSICIAN: Physician Name, MD

myRisk Management Tool: Page 1 of 2

MYRISK GENETIC RESULT: NEGATIVENo clinically signifi cant mutation identifi ed.

CLINICAL HISTORY ANALYSIS: NO MODIFIED MEDICAL MANAGEMENT GUIDELINES WERE IDENTIFIED BASED ON THE INFORMATION PROVIDED.Other clinical factors may infl uence individualized management. This analysis may be incomplete if details about cancer diagnoses, ages, family relationships or other factors were omitted or ambiguous.

BREAST CANCER RISKSCORE™: REMAINING LIFETIME RISK 15.2%See riskScore™ Interpretation Section for more information.

Your future risk of cancer is influenced by your Genetic Test Result, your personal clinical history

and your family history of cancer. The myRisk Management Tool provides a summary of your

future risks based on your genetic result and the information provided to Myriad, but additional

risk factors may be present and should be discussed with your provider.

myRisk Management Tool*

Information for Family Members

F. Your analysis did not identify you as a candidate for modified medical management based on your genetic result and the information you reported. However, other clinical factors may influence

individualized management. Your healthcare provider will work with

you to determine the best medical management plan for you.

G. Your Tyrer-Cuzick breast cancer risk calculation was either less than

20% or was not calculated. Tyrer-Cuzick is a model used to predict

a woman’s risk of developing breast cancer which was developed by

leading researchers. A Tyrer-Cuzick risk estimate will only be calculated

if you are a woman, have never had breast cancer and have no relatives

with a known genetic mutation. Tyrer-Cuzick takes into consideration

your family history of cancer and other personal clinical risk factors.

While your risk estimate did not identify you as a candidate for

modified medical management at this time, talk to your doctor about

your specific cancer risks.

Be sure to contact your healthcare provider on a regular basis for

updated information or to share any changes in your medical status or

family’s cancer history.

Since no mutations were found in the genes we tested, your

relatives may not need genetic testing.**

In some cases, genetic testing should be offered to another relative,

especially if they have been diagnosed with a cancer associated with the

suspected hereditary cancer genes for which you were tested. This can

provide more information about hereditary risk for you and others in your

family. Talk to your healthcare provider to help determine whether any

further genetic testing should be offered to you or to a family member.

* Patients with negative results on single-site testing will not receive a myRisk Management Tool.

** Relatives of patients tested for a single site may want to consider genetic testing.

PART TWO:

PART THREE:

2

3

Understanding Your Risk

If you have additional questions about your result please contact your healthcare provider. Myriad’s Medical Services team is also available to help:

(800) 469-7423 x3850 / helpmed@myriad.com

F

G

Hereditary Cancer Testing Provided by: Myriad Genetic Laboratories, Inc. 320 Wakara Way, Salt Lake City, UT 84108

Myriad, the Myriad logo, Myriad myRisk, the Myriad myRisk logo, riskScore the riskScore logo, mySupport360, and the mySupport360 logo are either trademarks

or registered trademarks of Myriad Genetics, Inc. in the United States and other jurisdictions. ©2017, Myriad Genetic Laboratories, Inc. MRHCNEGPET / 7-17

Your healthcare provider is always your number one resource. You are also

invited to visit www.mySupport360.com, the Myriad program offering

information and support for patients. You will find valuable information that will

help you better understand your test result, and you can join a community of

people who are on the same hereditary cancer testing journey as you.

You may also contact Myriad’s Medical Services team at 1-800-469-7423 x3850

to speak to a genetic counselor.

Resources

Next Steps

PATIENT SUPPORT

Schedule any follow-up appointments

Speak with your family members about your result and encourage them to see their healthcare provider about cancer prevention and testing

Consider speaking with a genetic counselor about your test result and family history

Working with your healthcare provider, the two of you will determine the appropriate next steps for you. Here are some possible actions to consider: