For millions of individuals affected by rare diseases — 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 abnormality or developmental delay and intellectual disability with onset prior to age 18.2
Mayo Clinic Laboratories’ WES 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.
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36%
36% of patients who underwent WES testing received genetic diagnosis4,5
18%
18% of patients with diagnostic results from WES testing received alternate treatment recommendations6
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 with diagnostic results from WES testing received alternate treatment recommendations6
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 with diagnostic results from WES testing received alternate treatment recommendations6
Designed to detect single nucleotide variants, small insertions or deletions, deletion-insertions (delins), and copy number variants, our WES test provides personalized answers that profoundly impact a patient’s medical journey.
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 of 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.
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.
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.
In this month's "Hot Topic," Nicole Boczek, Ph.D., assistant professor and laboratory director in the Department of Laboratory Medicine and Pathology, and Sarah Barnett, M.S., CGC, discuss diagnostic exploratory testing, explain why it’s important to the field of many specialty practice areas, and help determine which testing may be the most valuable for a given patient.
In this month's "Hot Topic," Megan Hoenig, M.S., M.P.H., CGC, a licensed and certified genetic counselor with the Division of Laboratory Genetics and Genomics at Mayo Clinic Laboratories, describes the principles and benefits of Familial Variant Targeted Testing (FMTT).
Cherisse Marcou, Ph.D., and Marissa Ellingson, M.S., CGC, discuss whole exome sequencing (WES) at Mayo Clinic Laboratories. The comprehensive evaluation uses next-generation sequencing to detect for single nucleotide variants, small insertions or deletions, and copy number variants on approximately 20,000 genes, enabling precision answers to accurately diagnose, manage, and treat patients with identified inherited illness.
Before testing at Mayo Clinic Laboratories, Barbara Domaille, Deborah Neville, Pamela Neville, and Rylie Ronnenberg thought there could be a genetic connection to the hip problems they shared. After the testing, they knew for sure.
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Comparator 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
In this month's "Hot Topic," Megan Hoenig, M.S., M.P.H., CGC, a licensed and certified genetic counselor with the Division of Laboratory Genetics and Genomics at Mayo Clinic Laboratories, describes the principles and benefits of Familial Variant Targeted Testing (FMTT).
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
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
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
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
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
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
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
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