INVITAE DIAGNOSTIC TESTING

RESULTS

Patient name: GILSON FERNEY BOHORQUEZ LOPEZ Sample type: Blood Report date: 03/18/2021
DOB: 09/20/1989 Sample collection date: 02/24/2021 Invitae #: RQ2061101
Sex: Male Sample accession date: 03/04/2021 Clinical team: Andrea Davila Rodriguez
MRN: 1030562683 GENETICA HUMANA

Reason for testing Test performed

Diagnostic test for a personal history of disease Sequence analysis and deletion/duplication testing of the 18 genes listed
in the Genes Analyzed section.
Invitae RASopathies Comprehensive Panel

RESULT:
NEGATIVE

About this test

This diagnostic test evaluates 18 gene(s) for variants (genetic changes) that are associated with genetic disorders. Diagnostic
genetic testing, when combined with family history and other medical results, may provide information to clarify individual
risk, support a clinical diagnosis, and assist with the development of a personalized treatment and management strategy.

Next steps

This test did not identify any pathogenic variants known to cause disease. This result should be discussed with a healthcare
provider, such as a genetic counselor, to learn about the appropriate next steps for further evaluation. Clinical follow up may still
be warranted. This result should be interpreted within the context of additional laboratory results, family history and clinical
findings.

Register your test at www.invitae.com/patients to download a digital copy of your results. You can also access
educational resources about how your results can help inform your health.

Laboratory Director: Kristin Gibson, PhD, FACMG, NYCQ, CGMB, ErCLG

Invitae 1400 16th Street, San Francisco, CA 94103 · clientservices@invitae.com · 800.436.3037
© 2021 Invitae Corporation Page 1 of 5
 INVITAE DIAGNOSTIC TESTING
RESULTS
Patient name: GILSON FERNEY BOHORQUEZ DOB: 09/20/1989
LOPEZ

Clinical summary

No reportable genetic variants were identified by this analysis, however, this individual may still be at risk for certain
medical conditions based on other factors such as family history, genetic causes not evaluated with this test, or other
environmental influences. Follow up of this individual and surveillance of their family members may still be indicated.

Laboratory Director: Kristin Gibson, PhD, FACMG, NYCQ, CGMB, ErCLG

Invitae 1400 16th Street, San Francisco, CA 94103 · clientservices@invitae.com · 800.436.3037
© 2021 Invitae Corporation Page 2 of 5
 INVITAE DIAGNOSTIC TESTING
RESULTS
Patient name: GILSON FERNEY BOHORQUEZ DOB: 09/20/1989
LOPEZ

Genes analyzed

This table represents a complete list of genes analyzed for this individual, including the relevant gene transcript(s). If more than one transcript is listed for a single
gene, variants were reported using the first transcript listed unless otherwise indicated in the report. Results are negative unless otherwise indicated in the report.
Benign and Likely Benign variants are not included in this report but are available upon request. An asterisk (*) indicates that this gene has a limitation. Please see
the Limitations section for details.

GENE TRANSCRIPT
A2ML1 NM_144670.4
BRAF NM_004333.4
CBL NM_005188.3
HRAS NM_005343.2
KRAS NM_004985.4
MAP2K1 NM_002755.3
MAP2K2 NM_030662.3
NF1* NM_000267.3
NRAS NM_002524.4
PTPN11 NM_002834.3
RAF1 NM_002880.3
RASA1 NM_002890.2
RIT1 NM_006912.5
RRAS NM_006270.4
SHOC2 NM_007373.3
SOS1 NM_005633.3
SOS2 NM_006939.2
SPRED1 NM_152594.2

Laboratory Director: Kristin Gibson, PhD, FACMG, NYCQ, CGMB, ErCLG

Invitae 1400 16th Street, San Francisco, CA 94103 · clientservices@invitae.com · 800.436.3037
© 2021 Invitae Corporation Page 3 of 5
 INVITAE DIAGNOSTIC TESTING
RESULTS
Patient name: GILSON FERNEY BOHORQUEZ DOB: 09/20/1989
LOPEZ

Methods

Genomic DNA obtained from the submitted sample is enriched for targeted regions using a hybridization-based protocol, and sequenced using
Illumina technology. Unless otherwise indicated, all targeted regions are sequenced with ≥50x depth or are supplemented with additional analysis.
Reads are aligned to a reference sequence (GRCh37), and sequence changes are identified and interpreted in the context of a single clinically
relevant transcript, indicated below. Enrichment and analysis focus on the coding sequence of the indicated transcripts, 20bp of flanking intronic
sequence, and other specific genomic regions demonstrated to be causative of disease at the time of assay design. Promoters, untranslated
regions, and other non-coding regions are not otherwise interrogated. For some genes only targeted loci are analyzed (indicated in the table
above). Exonic deletions and duplications are called using an in-house algorithm that determines copy number at each target by comparing the
read depth for each target in the proband sequence with both mean read-depth and read-depth distribution, obtained from a set of clinical
samples. Markers across the X and Y chromosomes are analyzed for quality control purposes and may detect deviations from the expected sex
chromosome complement. Such deviations may be included in the report in accordance with internal guidelines. All clinically significant
observations are confirmed by orthogonal technologies, except individually validated variants and variants previously confirmed in a first-degree
relative. Confirmation technologies include any of the following: Sanger sequencing, Pacific Biosciences SMRT sequencing, MLPA, MLPA-seq,
Array CGH. Array CGH confirmation of NGS CNV calling performed by Invitae Corporation (1400 16th Street, San Francisco, CA 94103,
#05D2040778). The following analyses are performed if relevant to the requisition. For PMS2 exons 12-15, the reference genome has been
modified to force all sequence reads derived from PMS2 and the PMS2CL pseudogene to align to PMS2, and variant calling algorithms are
modified to support an expectation of 4 alleles. If a rare SNP or indel variant is identified by this method, both PMS2 and the PMS2CL
pseudogene are amplified by long-range PCR and the location of the variant is determined by Pacific Biosciences (PacBio) SMRT sequencing of
the relevant exon in both long-range amplicons. If a CNV is identified, MLPA or MLPA-seq is run to confirm the variant. If confirmed, both PMS2
and PMS2CL are amplified by long-range PCR, and the identity of the fixed differences between PMS2 and PMS2CL are sequenced by PacBio from
the long-range amplicon to disambiguate the location of the CNV. Technical component of confirmatory sequencing is performed by Invitae
Corporation (1400 16th Street, San Francisco, CA 94103, #05D2040778). Technical component of Fibroblast cell-culturing and gDNA extraction
from skin punch biopsy is performed by Invitae Corporation (5 Technology Drive, Irvine CA 92618, #05D1052995).
A PMID is a unique identifier referring to a published, scientific paper. Search by PMID at http://www.ncbi.nlm.nih.gov/pubmed.
An rsID is a unique identifier referring to a single genomic position, and is used to associate population frequency information with sequence
changes at that position. Reported population frequencies are derived from a number of public sites that aggregate data from large-scale
population sequencing projects, including ExAC (http://exac.broadinstitute.org), gnomAD (http://gnomad.broadinstitute.org), and dbSNP
(http://ncbi.nlm.nih.gov/SNP).
A MedGen ID is a unique identifier referring to an article in MedGen, NCBI's centralized database of information about genetic disorders and
phenotypes. Search by MedGen ID at http://www.ncbi.nlm.nih.gov/medgen. An OMIM number is a unique identifier referring to a
comprehensive entry in Online Mendelian Inheritance of Man (OMIM). Search by OMIM number at http://omim.org/.
Invitae uses information from individuals undergoing testing to inform variant interpretation. If "Invitae" is cited as a reference in the variant
details this may refer to the individual in this requisition and/or historical internal observations.

Limitations

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions
<15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full
exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at
virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or
isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations,
etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected.
Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly
guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test
definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an
extracted genomic DNA sample. In very rare cases (such as circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion, or
maternal cell contamination), the analyzed DNA may not represent the patient's constitutional genome.
NF1: Sequencing analysis for exons 41, 48 includes only cds +/- 10 bp.

Laboratory Director: Kristin Gibson, PhD, FACMG, NYCQ, CGMB, ErCLG

Invitae 1400 16th Street, San Francisco, CA 94103 · clientservices@invitae.com · 800.436.3037
© 2021 Invitae Corporation Page 4 of 5
 INVITAE DIAGNOSTIC TESTING
RESULTS
Patient name: GILSON FERNEY BOHORQUEZ DOB: 09/20/1989
LOPEZ

Disclaimer

DNA studies do not constitute a definitive test for the selected condition(s) in all individuals. It should be realized that there are possible sources of error.
Errors can result from trace contamination, rare technical errors, rare genetic variants that interfere with analysis, recent scientific developments, and
alternative classification systems. This test should be one of many aspects used by the healthcare provider to help with a diagnosis and treatment plan,
but it is not a diagnosis itself. This test was developed and its performance characteristics determined by Invitae. It has not been cleared or approved by
the FDA. The laboratory is regulated under the Clinical Laboratory Improvement Act (CLIA) as qualified to perform high-complexity clinical tests (CLIA ID:
05D2040778). This test is used for clinical purposes. It should not be regarded as investigational or for research.

This report has been reviewed and approved by:

Dianalee McKnight, Ph.D., FACMG Clinical Molecular Geneticist

Laboratory Director: Kristin Gibson, PhD, FACMG, NYCQ, CGMB, ErCLG

Invitae 1400 16th Street, San Francisco, CA 94103 · clientservices@invitae.com · 800.436.3037
© 2021 Invitae Corporation Page 5 of 5
 NEGATIVE RESULTS GUIDE

Yourresults
What negative geneticmean
test for
results
you were negative. This means that no significant genetic changes (“pathogenic variants”
or “mutations”) were found. Your risk for disease could still be influenced by a combination of unidentified
genetic, personal, lifestyle and/or environmental risk factors.

Create a planWhether orhealthcare

with your not you develop
providera disease is not determined by your genetics alone. It is still important to share
your genetic test results with your healthcare provider so they can help you make informed medical decisions.

Your
What negative genetic
results meantest
forwas negative,
your family however, your family members have their own unique genetic makeup.
Genetic testing can help them understand their overall chance of developing a genetic disease.

Although
We (and others) your
are here totest
helpdidn’t find any genetic changes, you may still have questions about your results or your
personal or family medical history. A genetic counselor can help.

Log in to your patient portal (invitae.com) to view your results, search for a local or Invitae genetic counselor,
or join Invitae’s Patient Insight Network (PIN), a community where you can connect with other patients and share your
experience.

This information in this results guide is meant to be used along with your genetic test results and other health information. It is not meant to replace a discussion with your
healthcare provider and should not be considered or interpreted as medical advice.

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