Supplemental Table 1: Exome Sequencing Consent and Secondary Findings Reporting Strategy
1
2
3
4
5
6
7
a
Guideline
Provide clinicians ordering exome
sequencing with detailed consent form to
explain complexity of whole exome
sequencing, including the possibility for the
identification of secondary findings.
Categorization of secondary findings: A)
Recessive disease carrier status; B) Cancer
predisposition; C) Adult-onset disease
predisposition (non-cancer); D) Earlyonset diseaseb
Provide patients with the option to consent
to the receipt of a secondary findings report.
Reiterate technical limitations of exome
sequencing with specific regard to the
incomplete gene coverage to ensure that
patients understand that negative secondary
findings do not rule out the possibility of a
mutation in a gene associated with one of
the disease categories.
Childrenc not offered secondary findings
reports for adult-onset predisposition or
recessive disease carrier status (categories
A-C)
Given that the impact and significance of
secondary findings differs widely from that
of primary results, report secondary
findings separately from the primary exome
report.
Provide only known, disease-causing
mutations in characterized genes. Do not
report variants of uncertain significance.
Rationale/ Support
Supported by American College of Medical Genetics (ACMG)
Policy Statementa: "2. Pre-test counseling should be done by a
medical geneticist or an affiliated genetic counselor and should
include a formal consent process…. 8. Laboratories and clinics
utilizing WGS/WES should have clear policies in place related to
disclosure of secondary findings. Patients should be informed of
those policies and the types of secondary findings that will be
reported back to them and under what circumstances."
Supported by ACMG Policy Statement: "3. Prior to initiating
WGS/WES, participants should be counseled regarding... the
likelihood and type of incidental results that could be generated..."
Supported by ACMG Policy Statement: "8. ...Patients should be
given the option of not receiving certain or secondary findings."
Supported by ACMG Policy Statement: "3. Prior to initiating
WGS/WES, participants should be counseled regarding the
expected outcomes of testing... and what results will or will not be
disclosed."
Standard guidelines for genetic testing in minors (eg. American
Society of Human Geneticsd, American College of Medical
Geneticse, AMA Code of Ethics, European Society of Human
Geneticsf) .
Supported by ACMG Policy Statement: "3. Prior to initiating
WGS/WES, participants should be counseled regarding the
expected outcomes of testing, the likelihood and type of incidental
results that could be generated, and what results will or will not be
disclosed."
Supported by ACMG Policy Statement: "13. [Patients] should be
informed of... the virtual certainty of finding variants of uncertain
significance. The threshold for determining which results should be
returned to individuals seeking screening should be set significantly
higher than that set for diagnostic testing due to the much lower a
priori chance of disease in such individuals."
American College of Medical Genetics and Genomics (ACMG) Policy Statement "Points to Consider in the Clinical Application of
Genomic Sequencing." e-publication: http://www.acmg.net/StaticContent/PPG/Clinical_Application_of_Genomic_Sequencing.pdf
b
Early-onset disease: A condition in which manifestation of clinical symptoms may occur during childhood
c
Children = <18 years old
d
American Society of Human Genetics Board of Directors, American College of Medical Genetics Board of Directors (1995). Points
to consider: ethical, legal, and psychosocial implications of genetic testing in children and adolescents. AJHG 57, 1233-1241.
e
AMA Code of Medical Ethics’ Opinions on Genetic Testing. (2009) American Medical Association Journal of Ethics
f
European Society of Human Genetics (2009) EJHG 17, 720–721.