Diagnosis made possible with Whole Exome Sequencing

When a patient’s medical history and physical exam suggests an underlying genetic cause, we recommend Whole Exome Sequencing through Baylor Genetics.

Whole exome sequencing (WES) is comprehensive genetic testing which assesses the exome, the set of all exons (protein-coding sections within genes) within the human genome. Most genetic conditions are caused by variants found within these exons.

Older testing technologies only look at one or a few genes at a time, which is time-consuming and leads to several rounds of testing to reach a diagnosis. Using next-generation sequencing, WES accelerates the testing process by simultaneously analyzing thousands of genes at the same time.

Finding the reason for your patient’s medical condition can be life changing. Results provide treatment options, inform medical management, and open additional research opportunities so you can focus on the best care for your patient.

When a patient’s medical history and physical exam strongly suggests an underlying genetic cause, we recommend Whole Exome Sequencing.

Whole exome sequencing (WES) is available to patients who are searching for a unifying diagnosis for multiple medical issues. Unlike older technology where only one gene could be tested at a time, Baylor Genetics uses state-of-the-art technology to study a person’s exome. The exome refers to all our exons, which are the important protein-coding sections of DNA that are contained in our genes. The majority of DNA changes that may cause a genetic disorder are found in exons.

Scientists know what the sentences should say. Sequencing is a technology that looks at each letter in every sentence of DNA in the exome allowing scientists to compare the DNA of a person who has medical issues to the DNA from a person without medical issues. WES simultaneously looks at thousands of portions of genetic material at the same time. However, this technology cannot see all genetic changes that may lead to genetic conditions, which is why additional testing may be recommended. Finding an answer to your patient’s medical condition through whole exome sequencing can be life changing. Results can open options to treatment and additional research opportunities through Baylor College of Medicine.

Baylor Genetics Exome Diagnosis Rates

The exome diagnosis rate at Baylor Genetics is ~33% for trio (regular), ~35% for prenatal trio, and ~51% for rapid trio. Ordering the exome test with a shorter turnaround time can impact health outcomes in a significant way, especially for younger patients.

Indications for Testing:

MULTIPLE CONGENITAL ANOMALIES

AUTISM SPECTRUM DISORDERS

NEURODEVELOPMENTAL DISORDERS

DEVELOPMENTAL DELAY

INTELLECTUAL DISABILITY

PREVIOUS GENETIC TESTING WAS UNINFORMATIVE

FAILURE TO THRIVE

DYSMORPHIC FEATURES

EPILEPSY SYNDROMES

PATIENTS WITH AN EXTENSIVE DIFFERENTIAL DIAGNOSIS

Baylor Genetics Exome Diagnosis Rates

The exome diagnosis rate at Baylor Genetics is approximately 30% for proband or trio exome, and approximately 40% for prenatal trio and critical trio exome. Ordering the exome test with a shorter turn-around time can impact health outcomes in a significant way, especially for younger patients.

Indications for Testing

EXHAUSTED GENETIC TESTING OPTIONS

PATIENTS WITH A LONG LIST OF DIFFERENTIAL DIAGNOSES

ATYPICAL PRESENTATION OF DISEASE

	PROBAND WES	RAPID PROBAND WES	DUO WES	RAPID DUO WES	TRIO WES	RAPID TRIO WES
Test Code	1500	1729	1603	1723	1600	1722
Consent	REQUIRED	REQUIRED	REQUIRED	REQUIRED	REQUIRED	REQUIRED
Parents Needed	RECOMMENDED	RECOMMENDED	REQUIRED	REQUIRED	REQUIRED	REQUIRED
Parental Report Included
TAT (weeks)	3	5 days	3	5 days	3	5 Days
Can Elect to Receive Incidental Finding
Raw Data Available
Consent Available in Other Language

Saliva
Blood

Prenatal WES Trio is used when prenatal imaging detects an anomaly that strongly suggests there is an underlying genetic etiology. Prenatal WES Trio is often considered after fetal chromosomal microarray analysis or other prenatal testing has been non-diagnostic.

FETAL REPORT INCLUDES:
• Pathogenic or likely pathogenic variants in disease genes related to the prenatal indications.
• Variants in disease genes unrelated to the prenatal indications, but likely to cause severe childhood-onset disorders.

Test Code	1622
Consent	REQUIRED
Parents Needed	REQUIRED
Method of Parent Testing	EXOME
TAT (weeks)	2 (not including tissue culture)

Can Elect to Receive Incidental Finding

FETAL

PARENTAL

Raw Data Available
Consent Available in Other Language

RNA Sequencing

RNA Sequencing (RNAseq) is a reflex option to our
WGS offerings to help reclassify qualifying variants.

Sample Requirements (if additional sample is required)	Blood in EDTA
TAT (days)	28
Report	Provided as an updated (addendum) report

Rapid WES Testing
When a baby is critically ill, rapid results are necessary. Both biological parents must be available for this test.

Proband Only Testing
Proband WES is an option when biological parents are not available.

Duo Testing
Duo WES is an option when one biological parent is available.

Trio Testing
Trio WES has the highest diagnostic rate of all WES testing options and is available when both biological parents are available.

BluePrint Custom Panel (1300)
The BluePrint panel is a genetic test that enables ordering a customized panel of up to 1,000 genes based on a patient’s clinical symptoms.

Total BluePrint Panel (1390)
The Total BluePrint Panel will analyze all exonic regions of the 4,800 known Mendelian disease-causing genes simultaneously to identify the rare changes in an individual’s DNA that are contributing to your patient’s medical condition.

Adult Screening Exome Sequencing (1605)
The Adult Screening Exome Sequencing test is used when an individual’s medical history and physical exam findings are normal, but the person desires information about the potential future risk of developing a genetic disorder.

Positive Results
Positive or “abnormal” results mean there is a change in the genetic material related to the patient’s medical issues.

Negative Results
Negative results mean no relevant genetic change could be detected using WES. Genetic testing, while highly accurate, might not detect a change present in the genes tested. This can be due to limitations of the information available about the genes being tested, or limitations of the testing technology.

Results of Unclear Significance
WES can detect change(s) in DNA that do not have a clear meaning known as a variant of uncertain significance (VUS). Every person has changes in their DNA; not all of these changes cause medical issues. Studies of family members may help resolve the uncertainty. As our understanding of genetics increases, it may also be possible to determine the significance of these variants.

ACMG Secondary Findings
The American College of Medical Genetics (ACMG) has published guidelines for the reporting of medically actionable or secondary findings (PMID:34012068). These guidelines include a list of genes, which are updated occasionally, that are considered medically actionable and indicate laboratories should report pathogenic (disease-causing) findings in these genes. These findings are available on an opt-in basis.

Potentially Clinical Significant Findings in Genes With No Known Disease Association (Trio Only)
Rare variants in candidate genes for which there is limited available evidence of disease association. Relevant rare homozygous, hemizygous, compound heterozygous, and/or de novo variants are reported. The variants reported within this category will be classified as of uncertain significance. Any relevant literature will be referenced when available. Further information would be required to understand if any human disease association exists. These findings are available on an opt-in basis.

Incidental Findings
Medically actionable variants are changes found in genes known to be associated with disease but not associated with your current symptoms or clinical presentation. These variants are reported as they may cause severe, early-onset disease or may have implications for treatment and prognosis. These findings are available on an opt-in basis.

	PROBAND WES	RAPID PROBAND WES	DUO WES	RAPID DUO WES	TRIO WES	RAPID TRIO WES	BLUEPRINT CUSTOM PANEL	TOTAL BLUEPRINT PANEL	ADULT SCREENING EXOME
Test Code	1500	1729	1603	1723	1600	1722	1300	1390	1605
Consent	REQUIRED	REQUIRED	REQUIRED	REQUIRED	REQUIRED	REQUIRED	REQUIRED	MD ONLY	REQUIRED
Parents Needed	RECOMMENDED	RECOMMENDED	REQUIRED	REQUIRED	REQUIRED	REQUIRED	RECOMMENDED	RECOMMENDED	RECOMMENDED
Parental Report Included
TAT (weeks)	3	5 days	3	5 days	3	5 Days	3	3	3
Can Elect to Receive Incidental Finding									Standard Reporting
Raw Data Available
Consent Available in Other Language

Saliva
Blood

Prenatal WES Trio is used when prenatal imaging detects an anomaly that strongly suggests there is an underlying genetic etiology. Prenatal WES Trio is often considered after fetal chromosomal microarray analysis or other prenatal testing has been non-diagnostic.

FETAL REPORT INCLUDES:
• Pathogenic or likely pathogenic variants in disease genes related to the prenatal indications.
• Variants in disease genes unrelated to the prenatal indications, but likely to cause severe childhood-onset disorders.

Test Code	1622
Consent	REQUIRED
Parents Needed	REQUIRED
Method of Parent Testing	EXOME
TAT (weeks)	2 (not including tissue culture)

Can Elect to Receive Incidental Finding

FETAL

PARENTAL

Raw Data Available
Consent Available in Other Language

RNA Sequencing (RNAseq) is a reflex option to our WGS offerings to help reclassify qualifying variants of uncertain significance (VUS).

Sample Requirements (if additional sample is required)	Blood in EDTA
TAT (days)	28
Report	Provided as an updated (addendum) report