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Understanding
Whole Genome Sequencing

The Most Comprehensive First-Tier Test for Diagnosing Rare Disease and Unexplained Symptoms

Rare Disease is Often Unanswered. We Want to Help Change That.

Many rare genetic diseases – especially with pediatric patients – present nonspecific or overlapping clinical features (e.g. global developmental delay, intellectual disability), making the differential diagnosis challenging without genetic testing. Unfortunately, many patients undergo traditional genetic testing methods that look at only a few genes, missing the underlying genetic cause. This can lead to frequent misdiagnosis and delaying care.

The Consequences of Delayed Diagnosis

Up to 1 in 10

Americans have a rare disease1,2

Up to 85%

of rare diseases are genetic or have a genetic component2-5

5-7

years is the average time to reach a diagnosis1,6-8

30%

of pediatric patients with a rare disease will die before their 5th birthday9

33%

of critically ill infants in the NICU with a suspected genetic disease will die before getting their diagnosis10,11

With Whole Genome Sequencing That Could All Change

Guideline recommended Whole Genome Sequencing (WGS) is the most comprehensive first-tier test that uses next-generation sequencing to analyze up to 98% of the human genome and detect most types of disease-causing genetic variants. WGS offers higher diagnostic potential and resolution to uncover the genetic cause of complex, atypical or unexplained conditions. Increasingly recognized as a standard of care, we have the opportunity to help bring closure to their diagnostic odyssey.

A Breakthrough in Rare Disease Diagnosis

Compared to traditional* testing methods which has limited coverage of the genome, WGS can evaluate the entire genome in a single test enabling:
  • Higher Diagnostic Yield12-19**
  • Faster Diagnosis15***
  • Improved Clinical Management16
  • Reduced Medical Costs15

*Chromosomal microarray (CMA) and targeted panels. **Varies across cohorts of disease. ***Avoids repeated genetic testing with traditional methods.

Genome Coverage
Genome Coverage Chart
With pediatric and adult patients, WGS is used to help determine the etiology of a patient’s symptoms when a genetic condition is suspected in nonacute clinical presentation.
Higher
Diagnostic Yield

WGS has demonstrated a diagnostic yield ranging from 27% to 41% in outpatient pediatric cohorts across different clinical indications. Compared to traditional testing methods (12% to 24%), WGS offers a significantly higher likelihood of finding a diagnosis.12,13-15

Faster
Diagnosis

With its superior diagnostic yield, WGS promises fasters answers, with an average time to results in weeks, versus 4 to 5 years with traditional testing methods.21

Improved Clinical
Management

WGS has been shown to impact clinical management in 49% to 75% of pediatric outpatients a with a positive diagnosis, when implemented early in the diagnostic pathway.22,23

Reduced
Medical Cost

WGS is increasingly being covered24 as a medically necessary25 test across major payers and Medicaid for non-acute clinical presentation that are nonspecific and do not align with a well-defined syndrome. As more patients getting access to WGS, they have the potential to undergo fewer tests and lower the cost of diagnosis and care management.

In acute clinical cases when time is critical, Rapid Whole Genome Sequencing (rWGS) can be utilized to help quickly identify genetic causes of a patient’s symptoms. Unlike standard WGS, rWGS delivers results in days—not weeks—enabling faster diagnosis and care decisions.
Higher
Diagnostic Yield

rWGS has demonstrated a diagnostic yield range of 31% to 43% in NICU patient cohorts across different clinical indications. Compared to traditional testing methods (3% to 20%) rWGS provides a higher likelihood of finding a diagnosis.16-19

Faster Diagnosis

Approximately one-third of critically ill infants die before receiving a diagnosis and offering rWGS can lead to a shorter time (days versus weeks) to diagnosis and inform care faster.

Improved Clinical
Management

rWGS has shown to have a higher diagnostic efficacy, changing clinical management for NICU patients by two-fold compared to traditional testing.16

Reduced
Medical Cost

Undiagnosed NICU patients have higher resource utilization and longer hospital stays, the cost of which is absorbed by the hospital or the patient’s family. However, studies have found that early diagnosis with rWGS can lead to faster discharges and save an average of $12K to $15K per infant.20

Indications for WGS and rWGS include:

Society Recommended Indications

  • Congenital Anomalies (such as cardiac, skeletal, and genitourinary anomalies)
  • Developmental Delays
  • Epilepsy
  • Intellectual Disability
  • Neurodevelopmental Disorders

Additional Indications

  • Autism Spectrum Disorder
  • Cardiac Arrest
  • Cerebral Palsy
  • Extensive Differential Diagnosis
  • Failure to Thrive
  • Hypotonia
  • Immunodeficiencies
  • Metabolic Disturbances
  • Neuromuscular Disorders
  • Previous Genetic Testing Uninformative
  • Prolonged and/or Recurrent Hospital Stays
  • Respiratory Insufficiency at Term
  • Vision and Hearing Loss
Recommended by Medical Societies

The promise of WGS to improve diagnosis and management of rare disease is being validated in clinical practice and recognized by medical societies across the world as a first or second-tier diagnostic test for rare disease.

AAP

American Academy of Pediatrics recommends genome or exome sequencing as a first or second-tier test. (See Clinical Report)

  • Indications: Global Developmental Delay | Intellectual Disability | Congenital Anomalies

AES

American Epilepsy Society (AES) recommends genome or exome sequencing as a first-tier test. (See Guideline)

  • Indications: Unexplained Epilepsy

ACMG

American College of Medical Genetics and Genomics (ACMG) recommends genome or exome sequencing as a first or second-tier test. (See Guideline)

  • Indications: Developmental Delay | Intellectual Disability | Congenital Anomalies

NSGC

National Society of Genetic Counselors (NSGC) recommends genome or exome sequencing as a first-tier test. (See Guideline)

  • Indications: Unexplained Epilepsy

IPCHiP

International Precision Child Health Partnership (IPCHiP) recommends rapid genome or rapid exome sequencing as a first-line option. (See Consensus)

  • Indication: NICU patients with Unexplained Hypotonia

Global Medical Society

  • European Society of Human Genetics (See Recommendation)
  • Royal Australasian College of Physicians Paediatrics and Child Health Division (See Guidance)
  • CMDA Chinese Medical Doctor Association, Medical Genetics Branch​ (See Consensus)

Whole Genome Sequencing (WGS) can sequence most of the genome, analyzing both coding and non-coding regions, whereas Whole Exome Sequencing (WES) only analyzes the coding region. Comparatively, WGS has an incremental higher diagnostic yield compared to WES because it can analyze areas of the genome variant types that WES cannot – this gives patients a slightly better advantage to finding a genetic cause to their symptoms. Both tests, however, are great options to help understand the genetic etiology of a patient with rare disease or unexplained symptoms.
WGS
WES – Learn More
Diagnostic Yield
(Across NICU and Outpatient Cohorts)
27% to 43%
24% to 37%
Analyzes Coding Region
(85% of disease-causing variants exist in the coding region)
Yes
Yes
Analyzes Non-Coding Regions
Yes
No
Single Nucleotide Variant (SNV)
Yes
Yes
Copy Number Variant (CNV)
Yes
Limited
Mitochondrial DNA (mtDNA)
Yes
No – Separate Test Needed
Short Tandem Repeats (STR)
Yes
No
Regions of Homozygosity (ROH)
Yes
No
Uniparental Disomy (UPD)
Yes
No
Rapid Test Available
Yes
Yes
  1. Global Genes. Allies in Rare Disease. https://globalgenes.org/rare-disease-facts/. Accessed June 28, 2025.
  2. Bick D, Jones M, Taylor SL, Taft RJ, Belmont J. Case for genome sequencing in infants and children with rare, undiagnosed or genetic diseases. J Med Genet. 2019;56(12):783-791. doi:10.1136/jmedgenet-2019-106111
  3. Nguengang Wakap S, Lambert DM, Olry A, et al. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur J Hum Genet. 2020;28(2):165-173. doi:10.1038/s41431-019-0508-0
  4. Ferreira CR. The burden of rare diseases. Am J Med Genet A. 2019;179(6):885-892. doi:10.1002/ajmg.a.61124
  5. Tisdale A, Watson M, McCormack C, et al. The IDeaS initiative: pilot study to assess the impact of rare diseases on patients and healthcare systems. Orphanet J Rare Dis. 2021;16(1):429. doi:10.1186/s13023-021-02061-3
  6. Global Commission on Rare Disease. Global Commission to End the Diagnostic Odyssey for Children with a Rare Disease. https://www.globalrarediseasecommission.com/. Accessed June 28, 2025.
  7. Global Genes. Rare Disease Impact Report: Insights from Patients and the Medical Community. https://globalgenes.org/wp-content/uploads/2013/04/ShireReport-1.pdf. Published 2013. Accessed June 28, 2025.
  8. Posada de la Paz M, Taruscio D, Groft SC. Rare diseases epidemiology: update and overview. In: Posada de la Paz M, Taruscio D, Groft SC, eds. Rare Diseases Epidemiology: Update and Overview. 2nd ed. Cham, Switzerland: Springer; 2017:11-18. https://link.springer.com/book/10.1007/978-3-319-67144-4
  9. Dumbuya JS, Zeng C, Deng L, et al. The impact of rare diseases on the quality of life in paediatric patients: current status. Front Public Health. 2025;13:1531583. doi:10.3389/fpubh.2025.1531583
  10. Wojcik MH, Schwartz TS, Yamin I, et al. Genetic disorders and mortality in infancy and early childhood: delayed diagnoses and missed opportunities. Genet Med. 2018;20(11):1396-1404. doi:10.1038/gim.2018.17
  11. Posada de la Paz M, Taruscio D, Groft SC. Rare diseases epidemiology: update and overview. Adv Exp Med Biol. 2017;1031:589-604.
  12. Lindstrand A, Eisfeldt J, Pettersson M, et al. From cytogenetics to cytogenomics: whole-genome sequencing as a first-line test comprehensively captures the diverse spectrum of disease-causing genetic variation underlying intellectual disability. Genome Med. 2019;11(1):68. doi:10.1186/s13073-019-0675-1
  13. Costain G, Jobling R, Walker S, et al. Periodic reanalysis of whole-genome sequencing data enhances the diagnostic advantage over standard clinical genetic testing. Eur J Hum Genet. 2018;26(5):740-744. doi:10.1038/s41431-018-0114-6
  14. Stavropoulos DJ, Merico D, Jobling R, et al. Whole genome sequencing expands diagnostic utility and improves clinical management in pediatric medicine. NPJ Genom Med. 2016;1:15012. doi:10.1038/npjgenmed.2015.12
  15. Lionel AC, Costain G, Monfared N, et al. Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test. Genet Med. 2018;20(4):435-443. doi:10.1038/gim.2017.119
  16. NICUSeq Study Group; Krantz ID, Medne L, et al. Effect of whole-genome sequencing on the clinical management of acutely ill infants with suspected genetic disease: a randomized clinical trial. JAMA Pediatr. 2021;175(12):1218-1226. doi:10.1001/jamapediatrics.2021.3496
  17. Petrikin JE, Cakici JA, Clark MM, et al. The NSIGHT1-randomized controlled trial: rapid whole-genome sequencing for accelerated etiologic diagnosis in critically ill infants. NPJ Genom Med. 2018;3:6. doi:10.1038/s41525-018-0045-8
  18. Wu B, Kang W, Wang Y, et al. Application of full-spectrum rapid clinical genome sequencing improves diagnostic rate and clinical outcomes in critically ill infants in the China Neonatal Genomes Project. Crit Care Med. 2021;49(10):1674-1683. doi:10.1097/CCM.0000000000005052
  19. Farnaes L, Hildreth A, Sweeney NM, et al. Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization. NPJ Genom Med. 2018;3:10. doi:10.1038/s41525-018-0049-4
  20. Dimmock DP, Clark MM, Gaughran M, et al. Project Baby Bear: rapid precision care incorporating rWGS in 5 California children’s hospitals demonstrates improved clinical outcomes and reduced costs of care. Am J Hum Genet. 2021;108(7):1231-1238. doi:10.1016/j.ajhg.2021.05.005
  21. Soden SE, Saunders CJ, Willig LK, et al. Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders. Sci Transl Med. 2014;6(265):265ra168. doi:10.1126/scitranslmed.3010076
  22. Scocchia A, Wigby KM, Masser-Frye D, et al. Clinical whole genome sequencing as a first-tier test at a resource-limited dysmorphology clinic in Mexico. NPJ Genom Med. 2019;4:5. doi:10.1038/s41525-018-0076-1
  23. Bick D, Fraser PC, Gutzeit MF, et al. Successful application of whole genome sequencing in a medical genetics clinic. J Pediatr Genet. 2016;6(2):61-76.
  24. Data on file.
  25. Whole Exome and Whole Genome Sequencing (Non-Oncology Conditions): Medical Policy. https://www.uhcprovider.com/. Accessed August 25, 2025.

The society recommendations, performance characteristics and advantages of whole genome sequencing (WGS) or rapid whole genome sequencing presented on this page reflect WGS and rWGS as a general clinical methodology. They do not specifically recommend Baylor Genetics or represent specific analytical or clinical validation data for the Baylor Genetics WGS or rWGS tests.

The information provided on this website is intended solely for use by qualified healthcare professionals. It is designed to support, not replace, the clinical judgment of medical practitioners. The content, recommendations, is for informational and educational purposes only and should not be considered as medical advice for patients. Individuals seeking medical guidance should consult a licensed healthcare provider.

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