ExomePLUS - Renal Disease Available Tests

• ExomePLUS - Cystic & Dysplasia/Agenesis
  • MUC1 Cytosine Duplication Analysis*
  • NPHP1 Copy Number Analysis*
• ExomePLUS - Electrolyte & Kidney Stone
  • CTNS Copy Number Analysis*
• ExomePLUS - Proteinuria/FSGS & Hematuria

*Available at additional charge

Background

Two stage analysis leverages the combined power of both exome and targeted panel sequencing.

• Stage 1: Targeted, phenotype-guided gene panel analysis 

  • Guaranteed 100% coverage of phenotype guided gene panels including established disease genes that meet ClinGen criteria for definitive or strong disease association

  • Deep result interpretation (reports include variants classified as pathogenic, likely pathogenic, VUS, and likely benign)

• Stage 2: Expanded Analysis 

  • Automatic reflex to the rest of the exome at no additional cost when the targeted analysis is negative or inconclusive

  • Reports include variants classified as pathogenic and likely pathogenic

• Incidental Findings

  • Patient can choose whether to receive incidental findings in genes recommended by the American College of Medical Genetics (https://www.ncbi.nlm.nih.gov/clinvar/docs/acmg/)

• Pharmacogenomics (PGx)

  • Report includes variants in genes known to influence metabolism of drugs commonly prescribed for targeted phenotypes

Requirements, Pricing and TAT

Requirements

1. ExomePLUS Renal Disease Sequencing Requisition Form, completed and sent with specimen
2. Acceptable Specimens:
   • 7mL of whole blood collected in a lavender (K₂EDTA/K₃EDTA) top tube
     OR
   • DNA sample: 5–10 µg extracted DNA at a concentration of 50 ng/µl in Tris-EDTA (TE) buffer with OD_260/280 between 1.8–2.0

Methodology

Exome sequence is generated from genomic DNA that is fragmented, barcoded, and subjected to solution phase hybridization capture (Agilent SureSelect Clinical Research Exome) followed by sequencing on the Illumina HiSeq 2500 instrument at an average target coverage of 125X with a minimum of 93% of bases covered at least 15X. Sanger sequencing is used to fill in missing data in ClinGen curated phenotype guided gene panels . Reads are aligned to the NCBI reference sequence (GRCh37), using the Burrows-Wheeler Aligner (BWA), and variant calls are made using the Genomic Analysis Tool Kit (GATK). Variant calls are filtered using validated, laboratory developed protocols and variant interpretation is performed using our laboratory’s classification rules.

Limitations

Specific types of genetic variation, such as triplet repeat expansions, translocations, large copy number events, and mitochondrial variation are currently not reliably detected by Exome Sequencing. Because Exome Sequencing only covers the coding regions of the genome, any genetic changes residing outside of the targeted region will not be detected. Full coverage for genes outside the phenotype guided panels cannot be guaranteed. Gene-level coverage information is available online.

For additional questions, you also may visit our Frequently Asked Questions page.