Individualized insights for personalized care    

Advance understanding of genetic disease

For millions of individuals affected by rare disease — 80% of which are genetic in origin1 — knowing the underlying genetic cause is a critical first step in ending their diagnostic odyssey. Whole exome sequencing (WES) is recommended by the American College of Medical Genetics and Genomics (ACMG) as a first-line testing option to find underlying causes of rare genetic disorders in those who present with one or more congenital abnormalities or developmental delay and intellectual disability with onset prior to age 18.2

Mayo Clinic Laboratories’ whole exome sequencing test utilizes next-generation sequencing to investigate approximately 20,000 genes in patients with suspected hereditary disorders. Not only is WES recommended to identify genetic variants in individuals with congenital abnormalities, it is also recommended for patients with clinical features or family histories suggestive of underlying genetic disease but not distinguishable through other genetic tests.

By the numbers

50%

50% of patients who underwent WES testing were clinically impacted3

36%

36% of patients who underwent WES testing received genetic diagnosis4,5 

18%

18% of patients who underwent WES testing received alternative treatment recommendations6




Accurate answers, tailored management

Designed to detect single nucleotide variants, small insertions or deletions, deletion-insertions (delins), and copy number variants, our WES test’s precision provides answers that profoundly impact a patient’s medical journey.

  • Covers 99% of bases at a read depth of over 30X.
  • Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletion-insertions less than 40 base pairs (bp), and above 95% for deletions up to 75 bp and insertions up to 47 bp.
  • Detects multi-exon deletions/duplications. In some instances, single exon resolution can be achieved; however, the reliability of detection is variable due to isolated reduction in sequence coverage or inherent genomic complexity.

Variant identification not only enables insight into which gene(s) might be causing the disorder but can offer important information for family members about their risk for inheriting the same condition. Results also enable medical management and treatment targeted toward a specific diagnosis. Moreover, answers can put to rest a patient’s search for a cause, ending the diagnostic odyssey.

Key testing

WESDX  | Whole Exome Sequencing for Hereditary Disorders , Varies

Advantages

  • Aligns with ACMG’s evidence-based, 2021 clinical guidelines.
  • Provides a comprehensive, cost-effective testing alternative to establish molecular diagnosis in individuals who might otherwise require multiple tests.
  • Allows identification of genetic origin of conditions with more than one underlying cause.
  • Useful for identifying rare disorders and newly described conditions.
  • Optional reporting of medically actionable variants unrelated to the testing indication, including ACMG-approved secondary findings associated with hereditary cancer syndromes, cardiac syndromes, malignant hyperthermia, familial hypercholesterolemia, and others.
  • Allows for novel gene associations to be made.
  • Data generated from WES can be reanalyzed to detect gene disease associations unknown at the time of original evaluation.

CMPRE | Family Member Comparator Specimen for Exome Sequencing, Varies

Advantages

  • Improves diagnostic yield by sending one or more family members.
  • Enables the analysis of duos, trios, non-traditional trios, or quads.

Test in Focus

Cherisse Marcou, Ph.D., co-director of the Clinical Genomics Laboratory, and Marissa Ellingson, M.S., CGC, laboratory genetic counselor, discuss whole exome sequencing at Mayo Clinic Laboratories. The comprehensive evaluation uses next-generation sequencing to detect for single nucleotide variants, small insertions or deletions, deletion-insertions, and copy number variants in approximately 20,000 genes, enabling precision answers to accurately diagnose, manage, and treat patients with identified inherited disorders.

Improving the value of testing

Mayo Clinic Laboratories’ approach to whole exome sequencing includes gathering samples from biological parents of affected individuals, when possible, to help compare and contextualize test results. These comparator specimens assist with result interpretation and increase the diagnostic yield of the testing. Each WES order is carefully reviewed by a team of genetic counselors who ensure the indication for test ordering is clinically appropriate. A diagnosis is identified in trio-based whole exome sequencing in approximately 25% to 37% of cases.4-6

Beyond the test result

Mayo Clinic Laboratories’ WES test is backed by a team of laboratory scientists, genetic counselors, and clinicians who are integrated into the clinical practice at Mayo Clinic. This collaboration allows for direct consultation with practicing clinicians in instances of complex or unclear cases. WES results are interpreted by a collaborative team who consider previous evaluations and test results from genetic studies, biochemical testing, and imaging studies as part of the genetic data review. Genetic disease experts are available to answer questions about test findings or the need for additional testing.

Learn more about how to order these tests at your institution.


References

  1. Rare Genetic Diseases (genome.gov)
  2. Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG)
  3. Vissers LELM, van Nimwegen KJM, Schieving JH, et al. A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology. Genet Med. 2017;19(9):1055-1063.
  4. Clark MM, Stark Z, Farnaes L, et al. Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected genetic diseases. NPJ Genom Med. 2018;3:16. Published 2018 Jul 9.
  5. Srivastava S, Love-Nichols JA, Dies KA, et al. Correction: Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders. Genet Med. 2020;22(10):1731-1732.
  6. Kuperberg M, Lev D, Blumkin L, et al. Utility of whole exome sequencing for genetic diagnosis of previously undiagnosed pediatric neurology patients. J Child Neurol. 2016;31(14):1534-1539.
  7. Yang Y, Muzny DM, Xia F, et al: Molecular findings among patients referred for clinical whole-exome sequencing. JAMA. 2014 Nov;312(18):1870-1879. doi:10.1001/jama.2014.14601
  8. Lee H, Deignan JL, Dorrani N, et al: Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA. 2014 Nov;312(18):1880-1887. doi:10.1001/jama.2014.14604
  9. Farwell KD, Shahmirzadi L, El-Khechen D, et al: Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from 500 unselected families with undiagnosed genetic conditions. Genet Med. 2015 Jul;17(7):578-586. doi:10.1038/gim.2014.154