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

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

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    Saliva
  • null
    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

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.  

Take the first step with WES

Specimen Requirements
SAMPLE TYPE REQUIREMENTS SHIPPING CONDITIONS

Blood

Draw blood in an EDTA (purple-top) tube(s) and send 3-5 cc for adults/children or 3 cc for infants < 2 years.

Ship at room temperature in an insulated container by overnight courier. Do not heat or freeze. The sample must arrive within 7 days.

Buccal Swab

Collect with ORAcollect•Dx (OCD-100) self-collection kit (provided by Baylor Genetics with instructions). We highly recommend the sample be collected by a healthcare professional.

Ship at room temperature in an insulated container by overnight courier. Do not heat or freeze.

Cultured Skin Fibroblast

Send 2 T25 flasks at 80-100% confluence.

Ship at room temperature in an insulated container by overnight courier. Do not heat or freeze. The sample must arrive within 7 days.

Purified DNA

Send at least 20ug of purified DNA (minimal concentration of 50ng/uL; A260/A280 of ~1.7).

Ship at room temperature in an insulated container by overnight courier. Do not heat or freeze. The sample must arrive within 7 days.

How It Works:

Order appropriate testing for your patient.

The patient’s sample is collected.

The patient’s sample is sent to Baylor Genetics.

StartingAt5Days

Results are sent to the physician.

Discuss the results with the patient.

More questions? Please contact us by calling 1.800.411.4363.

Fan Xia
Senior Vice President, Clinical Genomics
Linyan Meng
AVP, Clinical Reporting
Molecular findings among patients referred for clinical whole exome-sequencing

Yang, Y., Muzny, D. M., Xia, F., Niu, Z., Person, R., Ding, Y., Ward, P., Braxton, A., Wang, M., Buhay, C., Veeraraghavan, N., Hawes, A., Chiang, T., Leduc, M., Beuten, J., Zhang, J., He, W., Scull, J., Willis, A., Landsverk, M., … Eng, C. M. (2014). Molecular findings among patients referred for clinical whole-exome sequencing. JAMA312(18), 1870–1879. https://doi.org/10.1001/jama.2014.14601. PMID: 25326635.

Use of exome sequencing for infants in intensive care units: Ascertainment of severe single-gene disorders and effect on medical management

Meng, L., Pammi, M., Saronwala, A., Magoulas, P., Ghazi, A. R., Vetrini, F., Zhang, J., He, W., Dharmadhikari, A. V., Qu, C., Ward, P., Braxton, A., Narayanan, S., Ge, X., Tokita, M. J., Santiago-Sim, T., Dai, H., Chiang, T., Smith, H., Azamian, M. S., … Lalani, S. R. (2017). Use of Exome Sequencing for Infants in Intensive Care Units: Ascertainment of Severe Single-Gene Disorders and Effect on Medical Management. JAMA Pediatrics171(12), e173438. https://doi.org/10.1001/jamapediatrics.2017.3438. PMID: 28973083.

Clinical exome sequencing for fetuses with ultrasound abnormalities and a suspected mendelian disorder

Normand, E. A., Braxton, A., Nassef, S., Ward, P. A., Vetrini, F., He, W., Patel, V., Qu, C., Westerfield, L. E., Stover, S., Dharmadhikari, A. V., Muzny, D. M., Gibbs, R. A., Dai, H., Meng, L., Wang, X., Xiao, R., Liu, P., Bi, W., Xia, F., … Yang, Y. (2018). Clinical exome sequencing for fetuses with ultrasound abnormalities and a suspected Mendelian disorder. Genome Medicine10(1), 74. https://doi.org/10.1186/s13073-018-0582-x. PMID: 30266093. 

CNVs cause autosomal recessive genetic diseases with or without involvement of SNV/indels

CNVs cause autosomal recessive genetic diseases with or without involvement of SNV/indels. Yuan B, Wang L, Liu P, Shaw C, Dai H, Cooper L, Zhu W, Anderson SA, Meng L, Wang X, Wang Y, Xia F, Xiao R, Braxton A, Peacock S, Schmitt E, Ward PA, Vetrini F, He W, Chiang T, Muzny D, Gibbs RA, Beaudet AL, Breman AM, Smith J, Cheung SW, Bacino CA, Eng CM, Yang Y, Lupski JR, Bi W. Genet Med. 2020 Jun 24. PMID: 32576985

Contribution of uniparental disomy in a clinical trio exome cohort of 2,675 patients

Contribution of uniparental disomy in a clinical trio exome cohort of 2675 patients. Wang L, Liu P, Bi W, Sim T, Wang X, Walkiewicz M, Leduc MS, Meng L, Xia F, Eng CM, Yang Y, Yuan B, Dai H. Mol Genet Genomic Med. 2021 Sep 29; e1792. PMID: 34587367.

Retrospective analysis of a clinical exome sequencing cohort reveals the mutational spectrum and identifies candidate disease-associated loci for BAFopathies

Retrospective analysis of a clinical exome sequencing cohort reveals the mutational spectrum and identifies candidate disease-associated loci for BAFopathies. Chen CA, Lattier J, Zhu W, Rosenfeld J, Wang L, Scott TM, Du H, Patel V, Dang A, Magoulas P, Streff H, Sebastian J, Svihovec S, Curry K, Delgado MR, Hanchard NA, Lalani S, Marom R, Madan-Khetarpal S, Saenz M, Dai H, Meng L, Xia F, Bi W, Liu P, Posey JE, Scott DA, Lupski JR, Eng CM, Xiao R, Yuan B.  Genet Med. 2021 Nov 16; S1098-3600(21)05245-X. PMID: 34906496

Sequencing individual genomes with recurrent deletions reveals allelic architecture and disease loci for autosomal recessive traits

Yuan, B., Schulze, K. V., Assia Batzir, N., Sinson, J., Dai, H., Zhu, W., Bocanegra, F., Fong, C. T., Holder, J., Nguyen, J., Schaaf, C. P., Yang, Y., Bi, W., Eng, C., Shaw, C., Lupski, J. R., & Liu, P. (2022). Sequencing individual genomes with recurrent genomic disorder deletions: an approach to characterize genes for autosomal recessive rare disease traitsGenome Medicine14(1), 113. PMID: 36180924.

Reanalysis of Clinical Exome Sequencing Data

Reanalysis of Clinical Exome Sequencing Data. Liu P, Meng L, Normand EA, Xia F, Song X, Ghazi A, Rosenfeld J, Magoulas PL, Braxton A, Ward P, Dai H, Yuan B, Bi W, Xiao R, Wang X, Chiang T, Vetrini F, He W, Cheng H, Dong J, Gijavanekar C, Benke PJ, Bernstein JA, Eble T, Eroglu Y, Erwin D, Escobar L, Gibson JB, Gripp K, Kleppe S, Koenig MK, Lewis AM, Natowicz M, Mancias P, Minor L, Scaglia F, Schaaf CP, Streff H, Vernon H, Uhles CL, Zackai EH, Wu N, Sutton VR, Beaudet AL, Muzny D, Gibbs RA, Posey JE, Lalani S, Shaw C, Eng CM, Lupski JR, Yang Y. N Engl J Med. 2019 Jun 20; 380(25):2478-2480. PMID: 31216405

Prenatal Diagnostic Exome Sequencing: A Review

Westerfield L., Braxton A., Walkiewicz, M. Prenatal Diagnostic Exome Sequencing: A Review. Current Genetic Medicine Reports (2017) 5: 75. https://doi.org/10.1007/s40142-017-0120-y.

Phenotypic and molecular characterisation of CDK13-related congenital heart defects, dysmorphic facial features and intellectual developmental disorders

Bostwick, B. L., McLean, S., Posey, J. E., Streff, H. E., Gripp, K. W., Blesson, A., Powell-Hamilton, N., Tusi, J., Stevenson, D. A., Farrelly, E., Hudgins, L., Yang, Y., Xia, F., Wang, X., Liu, P., Walkiewicz, M., McGuire, M., Grange, D. K., Andrews, M. V., Hummel, M., … Lalani, S. R. (2017) Phenotypic and molecular characterisation of CDK13-related congenital heart defects, dysmorphic facial features and intellectual developmental disorders. Genome Medicine 9:73. PMID: 28807008.

An Organismal CNV Mutator Phenotype Restricted to Early Human Development

An Organismal CNV Mutator Phenotype Restricted to Early Human Development. Liu P, Yuan B, Carvalho CM, Wuster A, Walter K, Zhang L, Gambin T, Chong Z, Campbell IM, Coban Akdemir Z, Gelowani V, Writzl K, Bacino CA, Lindsay SJ, Withers M, Gonzaga-Jauregui C, Wiszniewska J, Scull J, Stankiewicz P, Jhangiani SN, Muzny DM, Zhang F, Chen K, Gibbs RA, Rautenstrauss B, Cheung SW, Smith J, Breman A, Shaw CA, Patel A, Hurles ME, Lupski JR. Cell. 2017. Feb 23;168(5):830-842.e7. PMID: 28235197

Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation

Posey, J. E., Harel, T., Liu, P., Rosenfeld, J. A., James, R. A., Coban Akdemir, Z. H., Walkiewicz, M., Bi, W., Xiao, R., Ding, Y., Xia, F., Beaudet, A. L., Muzny, D. M., Gibbs, R. A., Boerwinkle, E., Eng, C. M., Sutton, V. R., Shaw, C. A., Plon, S. E., Yang, Y., … Lupski, J. R. (2017) Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation. New England Journal of Medicine, (1):21. PMID: 27959697

Whole-exome sequencing in the molecular diagnosis of individuals with congenital anomalies of the kidney and urinary tract and identification of a new causative gene.

Bekheirnia MR, Bekheirnia N, Bainbridge MN, Gu S, Coban Akdemir ZH, Gambin T, Janzen NK, Jhangiani SN, Muzny DM, Michael M, Brewer ED, Elenberg E, Kale AS, Riley AA, Swartz SJ, Scott DA, Yang Y, Srivaths PR, Wenderfer SE, Bodurtha J, Applegate CD, Velinov M, Myers A, Borovik L, Craigen WJ, Hanchard NA, Rosenfeld JA, Lewis RA, Gonzales ET, Gibbs RA, Belmont JW, Roth DR, Eng C, Braun MC, Lupski JR, Lamb DJ. Whole-exome sequencing in the molecular diagnosis of individuals with congenital anomalies of the kidney and urinary tract and identification of a new causative gene. 2016, Genet Med. epub. doi:10.1038/gim.2016.131

Molecular diagnostic experience of whole-exome sequencing in adult patients

Posey JE, Rosenfeld JA, James RA, Bainbridge M, Niu Z, Wang X, Dhar S, Wiszniewski W, Akdemir ZH, Gambin T, Xia F, Person RE, Walkiewicz M, Shaw CA, Sutton VR, Beaudet AL, Muzny D, Eng CM, Yang Y, Gibbs RA, Lupski JR, Boerwinkle E, Plon SE. Molecular diagnostic experience of whole-exome sequencing in adult patients. Genet Med. 2016 Jul;18(7):678. PMID: 26633545

Clinical whole exome sequencing for the diagnosis of Mendelian disorders

Yang Y, Muzny DM, Reid JG,  Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z,  Hardison M,  Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon, SE,  Lupski JR, Beaudet AL,  Gibbs RA, Eng CM. Clinical whole exome sequencing for the diagnosis of Mendelian disorders. N Engl J Med. 2013 Oct ;369(16): 1502. PMID: 24088041

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