Interpreting Your Genome Flashcards
Mutations that are in the databases are often assumed to have. . .
Mutations that are in the databases are often assumed to have 100% penetrance
This is almost certainly an overestimate
For interpretation of denovo variants. . .
- Beware mutations in genes where LoF is not a known disease mechanism
- Use caution interpreting LoF at the 3’ end of a gene
- Use caution with splice variants that are predicted to skip an exon but leave the protein intact
- Use caution in the presence of multiple transcripts (redundancy)
Differential diagnosis is a form of. . .
. . . Bayesian thinking
Whenever a whole exome seq is ordered, the clinician must discuss with the patient the possibility of. . .
. . . incidental findings
It is the responsibility of _____ to provide comprehensive pre- and posttest counseling to the patient.
It is the responsibility of the ordering clinician/team to provide comprehensive pre- and posttest counseling to the patient.
Mutation
a permanent change in the nucleotide sequence
polymorphism
as a variant with a frequency above 1%
Variants may be described as. . .
- pathogenic
- likely pathogenic
- uncertain significance
- likely benign
- benign
All assertions of pathogenicity should include. . .
. . . reference to a certain condition and an inheritance pattern
e.g., c.1521_1523delCTT (p.Phe508del), pathogenic, cystic fibrosis, autosomal recessive
What does the “likely” in “likely benign” and “likely pathogenic” mean?
Greater than 90% certainty of a variant either being disease-causing or benign
a common, albeit arbitrary, definition
You see a patient who is found to have a BRCA1 mutation that is known to be pathogenic on whole exome sequencing which was done for another cause. Should the mutation be included in the report and given the patient?
Yes, if the patient agreed to receive incidental findings
