Elements of clinical report

Question 1

What Genomic variants does it include?

Answer 1

Somatic (potentially actionable)
Somatic (biologically relevant)
Germline (Pathogenic /likely pathogenic)

Question 2

Also included: Immunotherapy markers, which are?

Answer 2

• TMB

- MSI status

Question 3

What do they mean?

Answer 3

if a patient is a candidate for immunotherapy or not.

Question 4

Also included: Treatment implications

Answer 4

• FDA approved therapies, current diagnosis
• FDA approved therapies, other types
• Additional indicators (variants detected in patient sample)

Question 5

What happens once the report is done?

Answer 5

A lab director signs off on the report so it can be returned to the appropriate physician.

Question 6

Process of determining if variants detected are pathogenic. VUS or benign

Answer 6

variant analysis

Question 7

targeted therapies added to the report based on patients unique molecular profile

Answer 7

Therapy application

Question 8

Immunotherapy markers which are included in the report

Answer 8

TMB and MSI

Question 9

The first step in this is to filter the raw data from sequencing

Answer 9

Bioinformatics pipeline

Question 10

Report delivery

Answer 10

Report is uploaded to the portal and provider/care team is notified

Question 11

How are they notified?

Answer 11

• Fax report
• email-based delivery (no PHI) contains a link to a secure portal
• custodian path labs may opt-in to receive a report via fax.

Question 12

What is this controlled in?

Answer 12

Salesforce

Question 13

What does QNS mean?

Answer 13

Quality/Quantity not sufficient

Question 14

What does ATR stand for?

Answer 14

Additional Tissue Request

Question 15

Intro to variant classification

Answer 15

• Somatic vs. Germline

Question 16

What is Genomic testing about?

Answer 16

Detection and Interpretation

Question 17

What does “Wildtype” mean?

Answer 17

Refers to the non-mutated form of a gene. (The “normal” condition)

Question 18

What’s an example of this?

Answer 18

If a person is “wild type” they are considered normal across the gene pool and have no mutations present.

Question 19

What’s the opposite?

Answer 19

Mutation/ alteration/variant allele

Question 20

What are the 3 main questions variant scientists need to ask?

Answer 20

1. ) is there a mutation present?
2. ) Does the mutation impact the protein?
3. ) Does that impact make a difference clinically? would this need to be shown in the report.

Question 21

What are the tiers to classify?

Answer 21

Tier I
Tier II
Tier III
Tier IV

Question 22

Tier I

Answer 22

Variants of strong clinical significance

Question 23

Tier II

Answer 23

Variants of potential clinical significance

Question 24

Tier III

Answer 24

Variants of unknown clinical significance

Question 25

Tier IV

Answer 25

Benign or likely benign variants

Question 26

Wildtype meaning

Answer 26

“Normal” or “typical” gene form

Question 27

Which are sources of evidence for variant classification?

Answer 27

• Medical/scientific literature
• Internal database
• Curated database

Question 28

Two main types of molecular profiling in Cancer

Answer 28

1. ) Somatic

2. ) Germline

Question 29

What are Somatic variables?

Answer 29

• Potentially actionable
• Biologically relevant
• VUS
• Pertinent negative

Question 30

What are Germline variables?

Answer 30

• Pathogenic
• Likely pathogenic
• Germline VUS’s (on xG report)
• benign and likely benign

Question 31

Somatic characteristics

Answer 31

• Alteration in DNA of tumor
• Alters the associated protein
• creates an associated therapy

Question 32

Somatic: biologically relevant

Answer 32

• Alteration in DNA of tumor
• Alters the associated protein
• No specific therapy involved

Question 33

Germline (in every cell of the body)

Answer 33

Pathogenic or likely pathogenic

Question 34

Germline characteristics

Answer 34

• alteration in DNA of every cell in the body
• known to alter the associated protein
• leads to an increased risk of certain cancers
• partial explanation for development of current cancer

Question 35

Somatic “Negative” results are also called:

Answer 35

Pertinent Negative

Question 36

What is pertinent negative?

Answer 36

in these genes, the lack of a mutation has therapeutic implications.

Question 37

Germline “Negative” results are also called:

Answer 37

Benign/likely benign

Question 38

What does that mean?

Answer 38

no variant was detected in the genes tested or variants therefore have no clinical impact.

Question 39

What does VUS stand for?

Answer 39

Variants of uncertain significance

Question 40

What is a VUS exactly?

Answer 40

an alteration in DNA of every cell in the body or in the tumor.

Question 41

VUS facts to know:

Answer 41

• NOT clinically actionable
• NOT a false positive
• Classified as a VUS because there is no evidence, not enough evidence to say what it is.
• may be reclassified in the future
• Germline VUS reported for xG but not xT
• Somatic VUS’s exist, and are reported by Tempus on xT.

Question 42

If there is a reclassification on the report, what happens?

Answer 42

GeneDx will reclassify the variant and Tempus will issue an amended report.

Question 43

Variants look different on each report, true or false?

Answer 43

True.

Question 44

Takeaways

Answer 44

• detecting and classification are important.
• scientists use multiple lines of evidence to classify
• somatic variants include those that are potentially actionable, biologically relevant and pertinent negatives.
• germline variants include pathogenic/likely pathogenic variants as well as variants of unknown significance.

Question 45

Reportable somatic variants include:

Answer 45

• potentially actionable
• biologically relevant
• pertinent negatives
• VUS

Question 46

Reportable germline variants include:

Answer 46

• pathogenic
• likely pathogenic
• variants of unknown significance

Question 47

what does the depth of coverage mean?

Answer 47

how many times path reads a part of the gene. Ex. 500

Question 48

TAT begins when?

Answer 48

The lab receives the sample

Question 49

What’s the main database to be aware of?

Answer 49

OncoKB database (appears on our reports if we get that)