The Pediatric Neurology Region of Interest is designed to give Providers what they want: the power of an exome with the focus of a panel. This test is built on the Claritas Clinical Exome platform, which offers a number of advantages over other exome-based testing strategies:
- Providers select gene lists based on the patient’s phenotype. This important contribution from the ordering provider helps guide the analysis, giving additional strength to the results interpretation step.
- If no diagnostic finding is reported in the Region of Interest test, ordering providers can choose to order an expanded interpretation of the whole exome data (test code N0527).
- Providers can request raw data via VCF or BAM files, or access to their patient’s exome data via the WuXi NextCODE platform, which is provided for 3 months without additional fees.
Providers ordering the Pediatric Neurology Region of Interest test can select from the following gene lists:
Neuromuscular Disorders- 556 genes
Movement Disorders- 522 genes
Epilepsy/Seizures- 455 genes
Brain Malformations- 414 genes
Developmental Delay/Intellectual Disability- 340 genes
Hereditary peripheral neuropathy- 271 genes
Leukodystrophy/Encephalopathy- 236 genes
Autism- 196 genes
Providers typically select 1-3 gene lists. If all phenotypes are relevant to the patient, we recommend ordering the Claritas Clinical Exome (Trio: N0560. Proband only: N0889). See the gene lists separated by phenotype here. Providers also may order a companion deletion/duplication analysis to increase the power of the assay.
Results are reported back in two phases. The Rapid Report includes orthogonally-confirmed, known and previously-observed pathogenic or likely pathogenic variants. This report is available within 5 weeks. The Complete Report adds variants of unknown significance, any remaining relevant variants that require Sanger-confirmation, and results from the deletion/duplication analysis, if ordered. The Complete Report is available in an additional 8 weeks after the Rapid Report. In case of a non-diagnostic finding, ordering providers have the option to go beyond the Region of Interest test after receiving the Complete Report, by ordering an Expansion to the Claritas Clinical Exome (Test Code N0527). A new sample will not need to be submitted. Interpretation will be provided in a new report that will be available in 12-14 weeks.
- Orthogonally-confirmed variants demonstrate high specificity (PPV~99.998%)
- Orthogonal approach using Illumina NextSeq with simultaneous confirmation of 95% of variants on the LIFE Ion Proton
- Remaining 5% of variants are Sanger sequenced so that all reported variants are confirmed
- Mean coverage of >100x for both the Illumina NextSeq and LIFE Ion Proton
- Protein coding sequences and 10 bp of adjacent intronic sequences are analyzed
- This assay detects SNVs, insertions, and deletions less than 10 bp
- As deletions or duplications >5 base pairs are not always detected by this assay, a companion deletion/duplication analysis with up to single exon resolution is available (Test Code C0598). This increases the detection ability for clinically relevant results.
Increase the power of the assay:
- Add companion deletion/duplication testing (Test Code C0598)
- If no diagnostic findings are reported in the ROI, providers can order an expanded interpretation of the whole clinical exome (Test Code N0527)
- This entry is for the Trio which includes testing of the Proband and biological parents. See Test Code N0883 for the Proband Only Order.
- The ROI includes analysis of the ACMG56 genes (a list of 56 genes recommended by the American College of Genetics and Genomics, variants that can lead to health issues and have evidence-based management and/or treatment plans) only to the extent that they are in the gene lists being ordered. However, if a provider orders the Expansion into the Claritas Clinical Exome after the initial analysis, the ACMG56 genes will be examined. Providers who request the Expansion into the Claritas Clinical Exome should discuss the ACMG56 with the patient. More information about the ACMG56 is available in the Claritas Clinical Exome Informed Consent Guide. It is Claritas policy to report on the ACMG56 in the patient unless the patient opts out. 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 the ACMG56 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 the ACMG56.
- A list of genes on the Pediatric Neurology Region of Interest divided by phenotype can be reviewed here.
Additional Service Highlights
- Providers may request a review of variant classification at any time.
- Providers may access the Interpretative Genomics Service at Boston Childrens Hospital, which provides consultation with experts in genes and/or phenotypes. Please contact [email protected] for more information.
- Claritas Genomics will release raw data files or provide access to exome data via NextCODE to authorized health care providers. Review Data Return Program details here.