CHOP Medical Exome Reanalysis should be considered for individuals who have had the CHOP Medical Exome signed out more than one year prior to ordering the reanalysis and/or has a significantly different indication for study compared to the initial exome analysis (e.g. a newly emerging phenotype). Typically, a new specimen will not be required for the CHOP Medical Exome Reanalysis test, as the laboratory should already have the patient’s exome sequencing data as well as stored DNA. Rarely, the lab will need a new specimen to perform confirmation of identity testing.
1) originally provided consent for testing before 12/8/2020 or
2) wants secondary findings.
(A new consent form is not required for family members who consented to the original analysis on or after 12/8/20, unless they want to receive secondary findings.) Please contact the lab if a relevant family member included in the original analysis that was ordered before 12/8/20 is no longer available to provide consent. The completed form(s) should be uploaded into the electronic medical record of the individual for whom the form was completed.
Clinical History: Please provide a detailed clinical history as the analysis is partially phenotype-driven. NOTE: The clinical indication entered on the Epic order/requisition form guides the phenotype to target for analysis and reporting and the indication will appear on the report. Please be certain to include all key clinical features that should be used for the analysis and avoid abbreviations. Genes of interest (≤10) may also be entered on the Epic order/requisition form to help focus the lab’s analysis.
Familial Member Samples: Please see below for information regarding ordering testing on family members. If not submitted as part of the proband’s original exome analysis, submission of new parental and/or similarly affected family members via the order for Exome, Family Member is highly recommended. For more information contact the lab at 267-426-1447 or by sending an email to DGDGeneticCounselor@chop.edu.
Unacceptable Conditions
N/A
Storage/Transport Temperature
N/A
Volume Required
N/A
Minimum Required
N/A
Phlebotomy Draw
No
Clinical Features
Utilizing a combined variant and phenotype-driven analysis, the CHOP Medical Exome Reanalysis focuses on identifying and reporting sequence and copy number variants that are highly likely to underlie the patient’s reason for study based on our current understanding of Mendelian genetic disorders. The test does not target variants contributing to disorders with multifactorial inheritance. It is an appropriate clinical test for patients with a complex presentation or those that do not have a clear clinical diagnosis, as well as for patients with phenotypes that could be caused by one of several different genes. It is also a useful diagnostic test for disorders in which a gene or genes have been implicated but for which no targeted clinical diagnostic test is available.
Ordering Recommendations
A reanalysis of CHOP Medical Exome data can be ordered for anyone who has previously had a CHOP Medical Exome analysis. This option is typically recommended if it has been more than a year since the original analysis and/or the patient has developed additional symptoms/features.
Exome Reanalysis for exomes ordered before February 8, 2023 (v1, v2, and v3) will not be available on the Exome v4 bioinformatic pipeline. Exome reanalysis for exomes ordered before February 8, 2023 (v1, v2, and v3) will utilize the Exome v3 bioinformatic pipeline. Exome reanalysis for exomes ordered after February 8, 2023 (v4) will utilize the Exome v4 pipeline. The ordering process is the same regardless of date of original exome.
What to order for Family Members being included in the patient’s (proband’s) exome reanalysis:
Order Exome DNA Extract for a family member who is not undergoing exome analysis but wants to submit a sample for Sanger analysis. New family members (who were not submitted with the patient’s original CHOP Medical Exome) can only be submitted for Sanger sequencing (via the Exome DNA Extract order). They cannot undergo full exome analysis as a part of the proband’s reanalysis.
Order Exome Reanalysis, Family Member for family members who were included in the patient’s original CHOP Medical Exome analysis and are now undergoing reanalysis of existing exome data to directly assist in interpretation of the patient's exome sequencing data (typically parents and/or an affected sibling). The test order should be placed in the family member’s medical record, not the patient’s medical record.
Genomic DNA is extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing is performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis are based on the GRCh38 reference sequence. Sequencing data is processed using the Dragen pipeline (Illumina) to call both sequencing and copy number variants. Whole genome sequencing has uniform coverage with a minimum read depth of 20X for at least 90% of the genome. For re-analysis or reflex testing, sequencing data is generated using the methods above.
Expedited testing is available on request. Please contact DGDgeneticcounselor@chop.edu to inquire about process.
CPT Codes
Proband CHOP Medical Exome Reanalysis: 81417
For each new family member submitted for exome reanalysis, please authorize one unit of 81416. There is no additional code/charge for family members who were submitted for exome sequencing as part of the original CHOP Medical Exome.
Collection
Collect
CHOP Medical Exome Reanalysis should be considered for individuals who have had the CHOP Medical Exome signed out more than one year prior to ordering the reanalysis and/or has a significantly different indication for study compared to the initial exome analysis (e.g. a newly emerging phenotype). Typically, a new specimen will not be required for the CHOP Medical Exome Reanalysis test, as the laboratory should already have the patient’s exome sequencing data as well as stored DNA. Rarely, the lab will need a new specimen to perform confirmation of identity testing.
1) originally provided consent for testing before 12/8/2020 or
2) wants secondary findings.
(A new consent form is not required for family members who consented to the original analysis on or after 12/8/20, unless they want to receive secondary findings.) Please contact the lab if a relevant family member included in the original analysis that was ordered before 12/8/20 is no longer available to provide consent. The completed form(s) should be uploaded into the electronic medical record of the individual for whom the form was completed.
Clinical History: Please provide a detailed clinical history as the analysis is partially phenotype-driven. NOTE: The clinical indication entered on the Epic order/requisition form guides the phenotype to target for analysis and reporting and the indication will appear on the report. Please be certain to include all key clinical features that should be used for the analysis and avoid abbreviations. Genes of interest (≤10) may also be entered on the Epic order/requisition form to help focus the lab’s analysis.
Familial Member Samples: Please see below for information regarding ordering testing on family members. If not submitted as part of the proband’s original exome analysis, submission of new parental and/or similarly affected family members via the order for Exome, Family Member is highly recommended. For more information contact the lab at 267-426-1447 or by sending an email to DGDGeneticCounselor@chop.edu.
Unacceptable Conditions
N/A
Storage/Transport Temperature
N/A
Volume Required
N/A
Minimum Required
N/A
Phlebotomy Draw
No
Ordering
Clinical Features
Utilizing a combined variant and phenotype-driven analysis, the CHOP Medical Exome Reanalysis focuses on identifying and reporting sequence and copy number variants that are highly likely to underlie the patient’s reason for study based on our current understanding of Mendelian genetic disorders. The test does not target variants contributing to disorders with multifactorial inheritance. It is an appropriate clinical test for patients with a complex presentation or those that do not have a clear clinical diagnosis, as well as for patients with phenotypes that could be caused by one of several different genes. It is also a useful diagnostic test for disorders in which a gene or genes have been implicated but for which no targeted clinical diagnostic test is available.
Ordering Recommendations
A reanalysis of CHOP Medical Exome data can be ordered for anyone who has previously had a CHOP Medical Exome analysis. This option is typically recommended if it has been more than a year since the original analysis and/or the patient has developed additional symptoms/features.
Exome Reanalysis for exomes ordered before February 8, 2023 (v1, v2, and v3) will not be available on the Exome v4 bioinformatic pipeline. Exome reanalysis for exomes ordered before February 8, 2023 (v1, v2, and v3) will utilize the Exome v3 bioinformatic pipeline. Exome reanalysis for exomes ordered after February 8, 2023 (v4) will utilize the Exome v4 pipeline. The ordering process is the same regardless of date of original exome.
What to order for Family Members being included in the patient’s (proband’s) exome reanalysis:
Order Exome DNA Extract for a family member who is not undergoing exome analysis but wants to submit a sample for Sanger analysis. New family members (who were not submitted with the patient’s original CHOP Medical Exome) can only be submitted for Sanger sequencing (via the Exome DNA Extract order). They cannot undergo full exome analysis as a part of the proband’s reanalysis.
Order Exome Reanalysis, Family Member for family members who were included in the patient’s original CHOP Medical Exome analysis and are now undergoing reanalysis of existing exome data to directly assist in interpretation of the patient's exome sequencing data (typically parents and/or an affected sibling). The test order should be placed in the family member’s medical record, not the patient’s medical record.
Genomic DNA is extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing is performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis are based on the GRCh38 reference sequence. Sequencing data is processed using the Dragen pipeline (Illumina) to call both sequencing and copy number variants. Whole genome sequencing has uniform coverage with a minimum read depth of 20X for at least 90% of the genome. For re-analysis or reflex testing, sequencing data is generated using the methods above.
Expedited testing is available on request. Please contact DGDgeneticcounselor@chop.edu to inquire about process.
Result Interpretation
Administrative
CPT Codes
Proband CHOP Medical Exome Reanalysis: 81417
For each new family member submitted for exome reanalysis, please authorize one unit of 81416. There is no additional code/charge for family members who were submitted for exome sequencing as part of the original CHOP Medical Exome.
