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Laboratory for Molecular Medicine

Genome Services

Clinical genome sequencing aims to end the diagnostic odyssey for individuals with rare genetic disorders and guide care for patients and their families.

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Diagnostic genome sequencing test

The genome sequencing test aims to end the diagnostic odyssey for individuals with rare genetic disorders, ultimately guiding clinical care for patients and their families. This test provides physicians with high quality genome sequencing, as well as unparalleled data interpretation. Results will be returned to the ordering physician in a concise report featuring an overall test result and in-depth phenotype-driven interpretation of known or plausible genetic causes of disease. Patients have the option to expand the report to include clinically actionable secondary findings (unrelated to the primary indication for testing).   

If you would like assistance in determining the appropriateness of genome sequencing for your patient, you may contact us by phone or submit pages two to three of our requisition form, along with your contact information, and we will contact you.

Diagnostic genome sequencing requisition form (triggers file download)

Testing is currently recommended for individuals with a suspected genetic disorder in whom traditional genetic testing has not yielded a result, despite a suspected genetic etiology. Genome sequencing may also be considered as a first-line testing strategy for conditions with a high degree of genetic heterogeneity for which panel-based testing is either limited or unavailable.

Genomic DNA extracted from blood or saliva are fragmented, adapter ligated, and barcoded. Library fragments are sequenced (2x150 base paired end) using Sequencing-By-Synthesis (SBS) chemistry and the Illumina NovaSeq sequencer with a minimum coverage of at least 20X for 90%. Sequence data are aligned to the GRCh38 assembly after discarding low quality sequences. Illumina's DRAGEN (Dynamic Read Analysis for GENomics) platform is used for demultiplexing, read mapping, genome alignment, read sorting, duplicate marking, and variant calling. Technical sensitivity of this assay is 99.10% (95% CI: 99.04-99.16%) and the positive predictive value is 99.39% (95% CI: 99.37-99.41%). All disease-associated variants on the report are confirmed via Sanger sequencing or another orthogonal technology.

Methodology for PGx if included: Genotype calls for specific genomic positions are identified using Illumina's DRAGEN (Dynamic Read Analysis for GENomics) platform. Diplotype, phenotype, and dosing information are generated using the Clinical Pharmacogenetics Implementation Consortium (CPIC®) and PharmGKB guidelines. The following pharmacogenomic variants are detected by this assay: CYP2C19: rs4244285, rs4986893, rs28399504, rs56337013, rs72552267, rs72558186, rs41291556, rs12248560, rs12769205; CYP2C9: rs1799853, rs1057910, rs28371686, rs9332131, rs7900194, rs28371685, rs72558187; CYP3A5: rs776746, rs10264272, rs41303343; CYP4F2: rs2108622; DPYD: rs3918290, rs55886062, rs67376798, rs72549309, rs115232898, rs1801266, rs78060119, rs56038477, rs72549303, rs1801268,rs75017182; IFNL3: rs12979860; NUDT15: rs116855232; SLCO1B1: rs4149056; TPMT: rs1800462, rs1800460, rs1142345, rs1800584; UGT1A1: rs4148323, rs35350960, rs3064744; VKORC1: rs9923231 (variant details). Additionally, variants in G6PD, RYR1, and CACNA1S associated with pharmacogenomic recommendations are reported, if identified.

Specific types of genetic variation, such as triplet repeat expansions, structural variation, and copy number events are currently not reliably detected by genome sequencing. Additionally, while genome sequencing covers about 95% of the genome; there are certain regions for which the assay may fail to adequately generate sequence information. Moreover, not all disease-associated genes have been identified and the clinical significance of variation in many genes is not well understood. Variant classification may change over time if more information becomes available. Gene-level coverage information for both tests is available and details regarding the coverage of genes associated with a specific indication can be determined upon request.

Requisition form

All samples must be accompanied with a completed requisition form. Please make sure any identifiers used on the specimen are provided on the paperwork. Consent page should be signed by a health care provider. Any incomplete or missing paperwork may delay the start of testing.

Ordering

Test code(s):

  • Genome sequencing 
  • Genome sequencing trio proband 
  • Genome sequencing trio auxiliary family member

Turnaround time: Reporting diagnostic genome sequencing is anticipated to be about 16 weeks, but it may vary depending on the complexity of the case and the volume of cases within the laboratory. Please contact us for current turnaround times.  

Specimen required:

  • 4-8 ml of whole blood collected in a lavender (K2EDTA/K3EDTA) top tube
    or
  • DNA sample (From CLIA certified lab): 5-10 µg extracted DNA at a concentration of 50 ng/µl in Tris-EDTA (TE) buffer with OD260/280 between 1.8-2.0

Billing information

The Laboratory for Molecular Medicine offers several billing options for our clients and their patients; however, we do not bill insurance companies and are unable to begin testing without accurate billing information.

CPT code:

  • Single diagnostic genome: 81425 
  • Trio diagnostic genome: 81425, 81426(2)

Price:

  • Single diagnostic genome: $1,900
  • Trio diagnostic genome: $2,800

Genomic screening test  

Genomic screening tests provide genomic information for individuals over 18 years of age who are interested in learning more about their health, reproductive and/or pharmacogenomic risks. This test provides high quality genome sequencing, as well as unparalleled data interpretation. Results will be returned to the ordering physician in a concise report.  Expanded Genomic Screening Test analyzes more than 3,500 genes with strong or definitive disease association and includes interpretations on pathogenic and likely pathogenic variants, carrier status variants, risk alleles, and PGx results. Complete genomic data is available in BAM or VCF files.  

If you would like assistance in determining the appropriateness of genomic screening for you or your patient, you may contact us by phone or submit pages two to three of our requisition form, along with your contact information, and we will contact you. 

Genomic screening requisition form (triggers file download)

These tests are intended as screening for healthy adults over 18 years of age who are interested in learning more about their genomic variants and implications that information may have on health and reproductive risks. These tests are not intended to be utilized for diagnostic purposes and will not include patient-specific analysis for specific diseases or conditions. We offer diagnostic genome services for that purpose. 

Genomic DNA extracted from blood or saliva are fragmented, adapter ligated, and barcoded. Library fragments are sequenced (2x150 base paired end) using Sequencing-By-Synthesis (SBS) chemistry and the Illumina NovaSeq sequencer with a minimum coverage of at least 20X for 90%. Sequence data are aligned to the GRCh38 assembly after discarding low quality sequences. Illumina's DRAGEN (Dynamic Read Analysis for GENomics) platform is used for demultiplexing, read mapping, genome alignment, read sorting, duplicate marking, and variant calling. Technical sensitivity of this assay is 99.10% (95% CI: 99.04-99.16%) and the positive predictive value is 99.39% (95% CI: 99.37-99.41%). All disease-associated variants on the report are confirmed via Sanger sequencing or another orthogonal technology.

Variants are subsequently filtered to identify:

  • Variants previously classified by our laboratory as pathogenic or likely pathogenic
  • Variants classified as disease causing mutations in public databases that have a minor allele frequency less than 5.0% in the Genome Aggregation Database
  • Nonsense, frameshift, and plus or minus 1,2 splice-site variants in disease-associated genes with a minor allele frequency ≤1.0% in gnomAD
  • Curated established and likely risk alleles with an odds-ratio of at least 2-4

The evidence for disease-causality is then evaluated for each variant identified from the filtering strategies listed above and variants are classified based on ACMG/AMP criteria (Richards et al. 2015) with ClinGen rule specifications, or our internal framework for classification of risk alleles.

Variants are reported according to HGVS nomenclature. Only those variants with evidence for causing or contributing to disease are reported. All disease-associated variants on this report are confirmed via Sanger sequencing or another orthogonal technology. Please contact the laboratory for additional information.

PGx: Genotype calls for specific genomic positions are identified using Illumina's DRAGEN (Dynamic Read Analysis for GENomics) platform. Diplotype, phenotype, and dosing information are generated using the Clinical Pharmacogenetics Implementation Consortium (CPIC®) and PharmGKB guidelines. The following pharmacogenomic variants are detected by this assay: CYP2C19: rs4244285, rs4986893, rs28399504, rs56337013, rs72552267, rs72558186, rs41291556, rs12248560, rs12769205; CYP2C9: rs1799853, rs1057910, rs28371686, rs9332131, rs7900194, rs28371685, rs72558187; CYP3A5: rs776746, rs10264272, rs41303343; CYP4F2: rs2108622; DPYD: rs3918290, rs55886062, rs67376798, rs72549309, rs115232898, rs1801266, rs78060119, rs56038477, rs72549303, rs1801268,rs75017182; IFNL3: rs12979860; NUDT15: rs116855232; SLCO1B1: rs4149056; TPMT: rs1800462, rs1800460, rs1142345, rs1800584; UGT1A1: rs4148323, rs35350960, rs3064744; VKORC1: rs9923231 (variant details). Additionally, variants in G6PD, RYR1, and CACNA1S associated with pharmacogenomic recommendations are reported, if identified.

Specific types of genetic variation—such as triplet repeat expansions, structural variation, regions with high homology, and copy number events—are currently not reliably detected by genome sequencing. Additionally, while genome sequencing adequately covers about 95% of the genome; there are certain regions for which the assay may fail to sufficiently generate sequence information. Moreover, not all disease-associated genes have been identified and the clinical significance of variation in many genes is not well understood. Variant interpretation may change over time if more information becomes available. Gene-level coverage information and details regarding the coverage of genes associated with a specific indication can be determined upon request. Email LMM@partners.org for more information.

Requisition form

All samples must be accompanied with a completed requisition form. Please make sure any identifiers used on the specimen are provided on the paperwork. Consent page should be signed by a health care provider. Any incomplete or missing paperwork may delay the start of testing.

Ordering

Test name: Expanded genome screening

Turnaround time: Reporting genome sequencing is anticipated to take about 10-12 weeks, but it may vary depending on the complexity of the case and the volume of cases within the laboratory. Please contact us for current turnaround times.

Specimen required:

  • 4-8 ml of whole blood collected in a lavender (K2EDTA/K3EDTA) top tube
    or 
  • DNA sample (From CLIA certified lab): 5-10 µg extracted DNA at a concentration of 50 ng/µl in Tris-EDTA (TE) buffer with OD260/280 between 1.8-2.0

Billing information

The Laboratory for Molecular Medicine offers several billing options for our clients and their patients; however, we do not bill insurance companies and are unable to begin testing without accurate billing information.

  • Price: $1,500

Mass General Brigham Personalized Medicine

We offer whole genome and exome sequencing to help detect disease risks and improve the accuracy of diagnoses. Improvements in detection can lead to more targeted, effective, and sometimes preventative care.

Contact us Laboratory for Molecular Medicine Biobank Genomics Core
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