Elements of clinical report Flashcards
What Genomic variants does it include?
Somatic (potentially actionable)
Somatic (biologically relevant)
Germline (Pathogenic /likely pathogenic)
Also included: Immunotherapy markers, which are?
- TMB
- MSI status
What do they mean?
if a patient is a candidate for immunotherapy or not.
Also included: Treatment implications
- FDA approved therapies, current diagnosis
- FDA approved therapies, other types
- Additional indicators (variants detected in patient sample)
What happens once the report is done?
A lab director signs off on the report so it can be returned to the appropriate physician.
Process of determining if variants detected are pathogenic. VUS or benign
variant analysis
targeted therapies added to the report based on patients unique molecular profile
Therapy application
Immunotherapy markers which are included in the report
TMB and MSI
The first step in this is to filter the raw data from sequencing
Bioinformatics pipeline
Report delivery
Report is uploaded to the portal and provider/care team is notified
How are they notified?
- 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.
What is this controlled in?
Salesforce
What does QNS mean?
Quality/Quantity not sufficient
What does ATR stand for?
Additional Tissue Request
Intro to variant classification
- Somatic vs. Germline
What is Genomic testing about?
Detection and Interpretation
What does “Wildtype” mean?
Refers to the non-mutated form of a gene. (The “normal” condition)
What’s an example of this?
If a person is “wild type” they are considered normal across the gene pool and have no mutations present.
What’s the opposite?
Mutation/ alteration/variant allele
What are the 3 main questions variant scientists need to ask?
- ) is there a mutation present?
- ) Does the mutation impact the protein?
- ) Does that impact make a difference clinically? would this need to be shown in the report.
What are the tiers to classify?
Tier I
Tier II
Tier III
Tier IV
Tier I
Variants of strong clinical significance
Tier II
Variants of potential clinical significance
Tier III
Variants of unknown clinical significance
Tier IV
Benign or likely benign variants
Wildtype meaning
“Normal” or “typical” gene form
Which are sources of evidence for variant classification?
- Medical/scientific literature
- Internal database
- Curated database
Two main types of molecular profiling in Cancer
- ) Somatic
2. ) Germline
What are Somatic variables?
- Potentially actionable
- Biologically relevant
- VUS
- Pertinent negative
What are Germline variables?
- Pathogenic
- Likely pathogenic
- Germline VUS’s (on xG report)
- benign and likely benign
Somatic characteristics
- Alteration in DNA of tumor
- Alters the associated protein
- creates an associated therapy
Somatic: biologically relevant
- Alteration in DNA of tumor
- Alters the associated protein
- No specific therapy involved
Germline (in every cell of the body)
Pathogenic or likely pathogenic
Germline characteristics
- 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
Somatic “Negative” results are also called:
Pertinent Negative
What is pertinent negative?
in these genes, the lack of a mutation has therapeutic implications.
Germline “Negative” results are also called:
Benign/likely benign
What does that mean?
no variant was detected in the genes tested or variants therefore have no clinical impact.
What does VUS stand for?
Variants of uncertain significance
What is a VUS exactly?
an alteration in DNA of every cell in the body or in the tumor.
VUS facts to know:
- 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.
If there is a reclassification on the report, what happens?
GeneDx will reclassify the variant and Tempus will issue an amended report.
Variants look different on each report, true or false?
True.
Takeaways
- 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.
Reportable somatic variants include:
- potentially actionable
- biologically relevant
- pertinent negatives
- VUS
Reportable germline variants include:
- pathogenic
- likely pathogenic
- variants of unknown significance
what does the depth of coverage mean?
how many times path reads a part of the gene. Ex. 500
TAT begins when?
The lab receives the sample
What’s the main database to be aware of?
OncoKB database (appears on our reports if we get that)
