KidneySeq™ Version 3

PDF iconKidneySeq Version 3 Brochure for Healthcare Providers.pdf

About this Test

KidneySeqTM Version is a test panel of PDF iconKidneySeq v3 Gene List causally related to over 120 renal diseases offered by the Iowa Institute of Human Genetics (IIHG) to physicians as a test in the diagnosis and management of patients. 

KidneySeqTM testing options

  • Comprehensive testing (264 genes)
  • CAKUT (44 genes)
  • Ciliopathies/tubulointerstitial diseases (79 genes)
  • Disorders of tubular ion transport (67 genes)
  • Glomerulopathies (67 genes)
  • Nephrolithiasis/nephrocalcinosis (35 genes)

Indications for testing 

This test is appropriate to validate a likely genetic renal diagnosis, when there are several genetic renal possibilities or when there is uncertainty as to the genetic renal diagnosis. It should also be considered as part of the transplant evaluation of recipients especially when living-related donation is planned. For a complete list of genes and diseases included in KidneySeqTM screen, PDF iconKidneySeq v3 Gene List.

  • Establishing a possible cause in patients presenting with atypical renal diseases.
  • Screening potential living related donors at risk for genetic renal disease.
  • Testing for specific genetic renal diseases including, but not limited to: 
    • CAKUT: Branchio-oto-renal syndrome, common CAKUT, renal hypo-dysplasia, and vesicoureteral reflux
    • Ciliopathies/tubulointerstitial diseases: polycystic kidney disease (AR and AD), Bardet-Biedl syndrome, Joubert syndrome, and orofaciodigital syndrome.
    • Disorders of tubular ion transport: Bartter syndrome, nephrogenic diabetes insipidus, primary aldosteronism, and SESAME syndrome
    • Glomerulopathies: Alport syndrome, focal segmental glomerulosclerosis, Denys-Drash syndrome, and nephrotic syndrome.
    • Nephrolithiasis/nephrocalcinosis: cystinuria, Dent disease, renal tubular acidosis
    • Comprehensive testing includes all of the above categories and other diseases such as: Okihiro syndrome, Pallister-Hall syndrome, Rubinstein-Taybi syndrome, and Smith-Lemli-Optiz syndrome

How to Order KidneySeqTM

  1. This test must be ordered by a health care provider. Please note patients are not permitted to order the test.
  2. Complete the PDF iconrequisition form:
  • UIHC health care providers should complete a PDF iconrequisition form and place a test order as a Miscellaneous Test in Epic - titled 'KidneySeq Test'. This is a send out test.
  • Health care providers outside of the University of Iowa Hospitals and Clinics may order the test by mailing the completed PDF iconrequisition form and sample to the address listed below.
  1. See Specimen Type of sample collection information.
  2. After collection, samples should be stored and shipped at room temperature.
  3. Delivery: will receive Monday-Friday. The IIHG does not receive samples on weekends or US holidays.

IIHG Clinical Diagnostic Division

285 Newton Road, 5292 CBRB

Iowa City, IA 52242


Specimen Type

*All samples must be labeled with the patient's name, date of birth, and date of collection.

  • ~6mL EDTA whole blood in lavender EDTA tube (3mL pediatric minimum).

OR

  • 10ug DNA (A260/A280 1.8-2) resuspended in 0.1mM EDTA (10mM Tris HCl, 0.1mM EDTA, pH 8, Teknova Cat# T0220)

After collection, samples should be stored and shipped at room temperature for delivery Monday-Friday. The IIHG does not receive samples on weekends or US holidays.

Please note: If insufficient quality or quantity of DNA is obtained, an additional sample will be requested. Incorrect handling or shipping can result in insufficient DNA quality or quantity


Turnaround Time

  • ~12 weeks after receipt of sample and test requisition at the IIHG lab.

Cost, Billing, and CPT Codes

Cost, Billing, and CPT Codes 

Your institution will be billed for this test. The IIHG will NOT submit to insurance or bill patients directly. Insurance may, or may not, cover this test. Please check with the patient's insurance provider for current coverage.
The IIHG accepts institutional billing, Visa and MasterCard.
KidneySeq™:

  • Comprehensive testing:
    • $2250
    • 81404, 81405, 81406, 81407, 81408, 81479
  • CAKUT:
    • $2000
    • 81405, 81406, 81407, 81479
  • Ciliopathies/tubulointerstitial diseases:
    • $2000
    • 81404, 81405, 81406, 81407, 81408, 81479
  • Disorders of tubular ion transport:
    • $2000
    • 81404, 81405, 81406, 81407, 81479
  • Glomerulopathies:
    • $2000
    • 81404, 81405, 81406, 81407, 81408, 81479
  • Nephrolithiasis/nephrosclerosis:
    • $2000
    • 81404, 81405, 81406, 81407, 81479
  • Familial testing: contact laboratory

*Please note: billing information must be complete before samples will be processed.  


Methodology

Traditionally, genetic testing involved sequentially or simultaneously screening individual genes which was expensive and time consuming. By contrast, KidneySeqTM, a genetic renal disease panel at the University of Iowa contains over 260 disease genes on a single platform that are simultaneously screened using targeted genomic enrichment and massively parallel sequencing. High throughout screening is efficient, accurate and relatively inexpensive.  

  • Agilent SureSelect Custom Capture Panel 
  • Massively parallel sequencing 
  • Custom data analysis pipeline 
  • Sanger sequence validation

Resources

The IIHG can help:

  • Determine whether testing is appropriate for your patient 
  • Interpretation of results
  • For questions, please contact us at iihg@uiowa.edu or 319-335-3688
  • If you would like an appointment or refer a patient to our UIHC Rare Kidney Disease Clinic, click here.  

Interpretation of Results

  • All results are discussed in our disciplinary IIHG KidneySeqTM Meeting. The goal of this meeting is to integrate clinical information and sequencing data to identify the most likely genetic cause of kidney disease (if any) in your patient. All variants are discussed by physicians, a genetic counselor, bioinformaticians, and scientists who provided expert contextual interpretation of genetic variants. 
  • After the IIHG KidneySeqTM team meets a result report is generated and sent back to the referring physician. 
  • The IIHG Clinical Diagnostics laboratory utilizes the ACMG Recommendations for standards for interpretation of sequencing variations (Richards et al. Genetics in Medicine (2015) 17:405-42). 

Incidental and Secondary Findings

  • Incidental findings are variants in genes associated with the patient's primary condition that are predicted/expected to cause symptoms but differ from the  indication for testing. For example, if the patient is being tested for genetic causes of kidney disease and a variant is identified in a gene that is known to cause kidney disease, however,  the specific variant is predicted/expected to cause infertility not kidney disease. This variant is called an "incidental finding.” It is not possible to predict the symptoms associated with all incidental findings. 
  • Secondary findings are findings unrelated to the patient's primary condition. These genes are not analyzed and therefore no secondary findings are reported. 

Data Storage

The volume of data generated from this test is large. Below is a description of the files the IIHG will keep. 

  • Fastq and vcf files are kept for six years
  • The final report is kept for a minimum of 20 years

Technical Limitations 

  • KidneySeqTM is a targeted capture platform which does not capture the entire exome. Regions not captured by the panel will not be analyzed.        
    • Please note, it is important to understand the absence of a reportable variant in a given gene does not mean there are not pathogenic variants in that gene.
  • The variant causing the patient's symptoms may not be detected because: some types of variants are very difficult to identify; and it may not be included in the sequenced/studied region. Typically, single nucleotide variations (SNV), and small insertions or deletions (indels) can be detected. Examples of genomic variations that are not reliably detected include: 
    • Trinucleotide repeats
    • Genomic rearrangements 
    • Large deletions, duplications, and insertions 
    • Copy Number Variants (CNV)
    • Regulatory variants 
    • Non-coding RNA 
    • Gain-of-splice site variants 
    • Multi-gene contributions 
    • Un-annotated or under-annotated genes 
    • Epigenetic/chromatin variations 
    • Mutations involved in tri-allelic inheritance 
    • Mitochondrial genome mutations 
    • Mutations in genes with pseudogenes
  • The test cannot predict disease onset or severity. 
  • If a variant is identified, it may not be recognized as disease-causing because the understanding of the genome is not complete and it is not possible to predict with 100% accuracy the effect of all variants. 
  • Interpretation of results is based on the current understanding of the human genome and human health and disease. The test may detect variants of uncertain clinical significance. Efforts will be made to limit these types of results. 
  • The results may be unclear and testing of other family members may be necessary to interpret the patient's test results, however, this testing would require the patient's approval and the consent of their family members. 
  • The ability to identify the variant responsible for the condition is highly dependent on the clinical information provided to the laboratory by the ordering physician.