3 May 2023

Test Background

The Claritas Clinical Exome is the ideal first test for patients with genetic and phenotypic heterogeneity or the next step for a patient with complex syndromic features and a history of negative molecular test results.

The Claritas Clinical Exome uses an innovative dual-capture, dual sequencing platform method unique to the industry. This “Orthogonal Approach” simultaneously confirms ~95% of all exome variants, providing the highest confidence clinical results.

Test Characteristics

  • 99.0% analytical sensitivity and 99.998% positive predictive value
  • Orthogonal approach using Illumina NextSeq™ with simultaneous confirmation of 95% of variants on the Thermo Fisher (formerly Life Technologies) Ion Proton™; reported variants that are not orthogonally confirmed are confirmed with Sanger sequencing
  • Mean coverage of >100x for both the Illumina NextSeq and Thermo Fisher Ion Proton
  • Protein coding sequences and 8 bp of adjacent intronic sequences are analyzed 
  • SNVs, insertions, and deletions less than 8 bp are detected
  • Companion high resolution deletion/duplication analysis (test code C0164) increases detection rate for copy number variants and larger indels.
  • Mitochondrial DNA analysis is available by request at no additional cost. Average sequencing depth for the mitochondrial genome is >200x with >90% covered at >100x. Heteroplasmy as low as 5% may be detected, with an analytical sensitivity of 93% in blood samples; analytical sensitivity is >99% for detection of heteroplasmy at 10%.

Special Notes

  1. This study can be ordered for the proband alone by submitting a sample from the affected individual, or as a trio with parental samples included in the analysis.
  2. Use Claritas’ Informed Consent document as a support resource for discussing the Claritas Clinical Exome.
  3. By default, Claritas Genomics investigates a list of genes, referred to as Secondary Findings that are recommended by the American College of Genetics and Genomics. Variants in these genes can lead to health issues and have evidence-based management and/or treatment plans. Only those findings that are identified in the patient will be evaluated in the parental samples. The proband and the parent(s) may choose to opt-out of having these genes evaluated. See the Informed Consent signature page on the requisition form for more details. Note that if the proband opts out, the parent samples will not be evaluated for these genes.
  4. CCE companion high resolution deletion/duplication analysis (Test Code C0164) is available at additional charge.
  5. Mitochondrial DNA is available at no additional charge.
  6. Providers whose patients require quicker results may order phenotypically-driven, exome-based Regions of Interest where results are returned in 8 – 11 weeks (See the test menu for a complete listing of ROIs). 

Additional Service Highlights

  1. Reanalysis of a patient’s case is available and performed at no additional cost when the request is made within 2 years of the date the report was issued.
  2. Review of variant classification is available on request at any time.
  3. The Interpretative Genomics Service at Boston Children’s Hospital, which provides consultation with clinical and research experts in genes and/or phenotypes is available to all patients and providers. Contact [email protected] for more information.
  4. Raw data files or access to exome data via NextCODE is available to all authorized health care providers. Review Data Return Program details here.