Genetic Renal Panel v8 - Clinical Genetic Test - GTR

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Genetic Renal Panel v8

Clinical Genetic Test

offered by

Molecular Otolaryngology and Renal Research Laboratories

View lab's test page

GTR Test Accession: GTR000512537.11

HEMATOLOGYINHERITED DISEASEIMMUNOLOGY ... View more

Last updated in GTR: 2024-01-10

Last annual review date for the lab: 2024-01-11

At a Glance

Test purpose:

Diagnosis; Mutation Confirmation; Recurrence; ...

Conditions (21):

Thrombotic microangiopathy; Anemia, nonspherocytic hemolytic, due to G6PD deficiency; Atypical hemolytic-uremic syndrome; ...

Genes (17):

ADAMTS13 (9q34.2), C3 (19p13.3), CD46 (1q32.2), CFB (6p21.33), CFH (1q31.3), ...

Methods (2):

Molecular Genetics - Deletion/duplication analysis: Multiplex Ligation-dependent Probe Amplification (MLPA); ...

Target population:

The 13 genes included on the Genetic Renal Panel v8 …

Clinical validity:

Not provided

Clinical utility:

Establish or confirm diagnosis

Ordering Information

Offered by:

Molecular Otolaryngology and Renal Research Laboratories
View lab's website
View lab's test page

Test short name:

Genetic Renal Panel

Specimen Source:

Isolated DNA
Peripheral (whole) blood
View specimen requirements

Who can order:

Genetic Counselor
Health Care Provider
Licensed Physician
Nurse Practitioner
Physician Assistant

Test Order Code:

GRP08
View other test codes

CPT codes:

81405
81479

**AMA CPT codes notice

Lab contact:

Jori Hendon, BA, Administrator
jori-hendon@uiowa.edu
319-335-6653
Amy Weaver, Administrator
amy-weaver@uiowa.edu
319-335-6623

Contact Policy:

Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.

How to Order:

Sample types accepted include: 3-5 cc EDTA whole blood; 5 μg DNA, resuspended in at least 50 ul of DNA Elution Buffer; Saliva (DNA Genotek, ORAGene Discover, OGR-500); or Buccal Swabs, at least 4 (DNA Genotek, OraCollect, OCD-100). Samples can be received Monday - Friday (no weekend or holiday deliveries), …

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Order URL

Test service:

Clinical Testing/Confirmation of Mutations Identified Previously
Comment: Includes next-generation sequencing and copy number variation studies via MLPA methodology (deletion/duplication studies).

Test additional service:

Custom mutation-specific/Carrier testing

Test development:

Test developed by laboratory (no manufacturer test name)

Informed consent required:

Based on applicable state law

Test strategy:

Genetic Renal Panel simultaneously screens all genes known to be associated with various TMAs. This comprehensive approach decreases cost and waiting time for test results. The Genetic Renal Panel uses custom-targeted sequence capture for DNA enrichment followed by massively parallel DNA sequencing. Data analysis to identify causative variants is completed … View more

View citations (1)

Bu F, Borsa NG, Jones MB, Takanami E, Nishimura C, Hauer JJ, Azaiez H, Black-Ziegelbein EA, Meyer NC, Kolbe DL, Li Y, Frees K, Schnieders MJ, Thomas C, Nester C, Smith RJ. High-Throughput Genetic Testing for Thrombotic Microangiopathies and C3 Glomerulopathies. J Am Soc Nephrol. 2016;27(4):1245-53. doi:10.1681/ASN.2015040385. Epub 2015 Aug 17. PMID: 26283675.

Pre-test genetic counseling required:

Decline to answer

Post-test genetic counseling required:

Decline to answer

Conditions

Total conditions: 21

Condition/Phenotype	Identifier

Test Targets

Genes

Total genes: 17

Gene	Associated Condition	Germline or Somatic	Allele (Lab-provided)	Variant in NCBI

Methodology

Total methods: 2

Method Category

Test method

Instrument

Deletion/duplication analysis

Multiplex Ligation-dependent Probe Amplification (MLPA)

MRC Holland custom probe mix

Sequence analysis of the entire coding region

Next-Generation (NGS)/Massively parallel sequencing (MPS)

Agilent SureSelect

Clinical Information

Test purpose:

Diagnosis; Mutation Confirmation; Recurrence; Risk Assessment; Therapeutic management

Clinical utility:

Establish or confirm diagnosis

View citations (1)

https://morl.lab.uiowa.edu/clinical-diagnostic-services/clinical-renal-diagnostic-division/genetic-renal-panel-testing-0

Target population:

The 13 genes included on the Genetic Renal Panel v8 platform – CFH, CFI, MCP (CD46), CFB, CFHR5, C3, THBD, DGKE, PLG, ADAMTS13, MMACHC, G6PD and WT1 – are implicated in the thrombotic microangiopathies (TMA), which include complement-mediated Hemolytic Uremic Syndrome (aHUS), Upshaw-Schulman syndrome (a hereditary form of Thrombotic Thrombocytopenic … View more

View citations (15)

Genetic variants in C5 and poor response to eculizumab. Nishimura J, et al. N Engl J Med. 2014;370(7):632-9. doi:10.1056/NEJMoa1311084. PMID: 24521109.
Rodríguez de Córdoba S, Hidalgo MS, Pinto S, Tortajada A. Genetics of atypical hemolytic uremic syndrome (aHUS). Semin Thromb Hemost. 2014;40(4):422-30. doi:10.1055/s-0034-1375296. Epub 2014 May 05. PMID: 24799305.
Nester CM, Barbour T, de Cordoba SR, Dragon-Durey MA, Fremeaux-Bacchi V, Goodship TH, Kavanagh D, Noris M, Pickering M, Sanchez-Corral P, Skerka C, Zipfel P, Smith RJ. Atypical aHUS: State of the art. Mol Immunol. 2015;67(1):31-42. doi:10.1016/j.molimm.2015.03.246. Epub 2015 Apr 03. PMID: 25843230.
Managing atypical hemolytic uremic syndrome: chapter 2. Nester CM, et al. Kidney Int. 2015;87(5):882-4. doi:10.1038/ki.2015.60. PMID: 25951068.
Bu F, Borsa NG, Jones MB, Takanami E, Nishimura C, Hauer JJ, Azaiez H, Black-Ziegelbein EA, Meyer NC, Kolbe DL, Li Y, Frees K, Schnieders MJ, Thomas C, Nester C, Smith RJ. High-Throughput Genetic Testing for Thrombotic Microangiopathies and C3 Glomerulopathies. J Am Soc Nephrol. 2016;27(4):1245-53. doi:10.1681/ASN.2015040385. Epub 2015 Aug 17. PMID: 26283675.
Muff-Luett M, Nester CM. The Genetics of Ultra-Rare Renal Disease. J Pediatr Genet. 2016;5(1):33-42. doi:10.1055/s-0036-1572515. Epub 2016 Feb 23. PMID: 27617140.
Goodship TH, Cook HT, Fakhouri F, Fervenza FC, Frémeaux-Bacchi V, Kavanagh D, Nester CM, Noris M, Pickering MC, Rodríguez de Córdoba S, Roumenina LT, Sethi S, Smith RJ, . Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference. Kidney Int. 2017;91(3):539-551. doi:10.1016/j.kint.2016.10.005. Epub 2016 Dec 16. PMID: 27989322.
Alge JL, Wenderfer SE, Hicks J, Bekheirnia MR, Schady DA, Kain JS, Braun MC. Hemolytic uremic syndrome as the presenting manifestation of WT1 mutation and Denys-Drash syndrome: a case report. BMC Nephrol. 2017;18(1):243. doi:10.1186/s12882-017-0643-1. Epub 2017 Jul 18. PMID: 28720077.
Walsh PR, Johnson S, Brocklebank V, Salvatore J, Christian M, Kavanagh D. Glucose-6-Phosphate Dehydrogenase Deficiency Mimicking Atypical Hemolytic Uremic Syndrome. Am J Kidney Dis. 2018;71(2):287-290. doi:10.1053/j.ajkd.2017.08.007. Epub 2017 Dec 13. PMID: 29248304.
Osborne AJ, Breno M, Borsa NG, Bu F, Frémeaux-Bacchi V, Gale DP, van den Heuvel LP, Kavanagh D, Noris M, Pinto S, Rallapalli PM, Remuzzi G, Rodríguez de Cordoba S, Ruiz A, Smith RJH, Vieira-Martins P, Volokhina E, Wilson V, Goodship THJ, Perkins SJ. Statistical Validation of Rare Complement Variants Provides Insights into the Molecular Basis of Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy. J Immunol. 2018;200(7):2464-2478. doi:10.4049/jimmunol.1701695. Epub 2018 Mar 02. PMID: 29500241.
Goicoechea de Jorge E, López Lera A, Bayarri-Olmos R, Yebenes H, Lopez-Trascasa M, Rodríguez de Córdoba S. Common and rare genetic variants of complement components in human disease. Mol Immunol. 2018;102:42-57. doi:10.1016/j.molimm.2018.06.011. Epub 2018 Jun 18. PMID: 29914697.
Bu F, Zhang Y, Wang K, Borsa NG, Jones MB, Taylor AO, Takanami E, Meyer NC, Frees K, Thomas CP, Nester C, Smith RJH. Genetic Analysis of 400 Patients Refines Understanding and Implicates a New Gene in Atypical Hemolytic Uremic Syndrome. J Am Soc Nephrol. 2018;29(12):2809-2819. doi:10.1681/ASN.2018070759. Epub 2018 Oct 30. PMID: 30377230.
C3 glomerulopathy - understanding a rare complement-driven renal disease. Smith RJH, et al. Nat Rev Nephrol. 2019;15(3):129-143. doi:10.1038/s41581-018-0107-2. PMID: 30692664.
Sabry W, Elemary M, Burnouf T, Seghatchian J, Goubran H. Vitamin B12 deficiency and metabolism-mediated thrombotic microangiopathy (MM-TMA). Transfus Apher Sci. 2020;59(1):102717. doi:10.1016/j.transci.2019.102717. Epub 2019 Dec 31. PMID: 31902683.
Zhang Y, Ghiringhelli Borsa N, Shao D, Dopler A, Jones MB, Meyer NC, Pitcher GR, Taylor AO, Nester CM, Schmidt CQ, Smith RJH. Factor H Autoantibodies and Complement-Mediated Diseases. Front Immunol. 2020;11:607211. doi:10.3389/fimmu.2020.607211. Epub 2020 Dec 15. PMID: 33384694.

Variant Interpretation:

What is the protocol for interpreting a variation as a VUS?
All testing results for your patient (Functional, Biomarker and Genetic) are reviewed at our weekly multidisciplinary Renal Team meeting. At this meeting, a group of physicians, bioinformaticians, graduate students, post-doctoral fellows, medical students, medical residents, and scientists discuss and interpret each patient’s results in the context of a wide-array of … All testing results for your patient (Functional, Biomarker and Genetic) are reviewed at our weekly multidisciplinary Renal Team meeting. At this meeting, a group of physicians, bioinformaticians, graduate students, post-doctoral fellows, medical students, medical residents, and scientists discuss and interpret each patient’s results in the context of a wide-array of information including: Clinical information provided by healthcare provider Including diagnosis, hematologic parameters, treatment methods, family history and clinical history Biopsy reports Biomarker results Functional results Genetic findings (NGS and MLPA) Each variant is discussed in the context of the above information to determine whether it may be contributing as a disease-driver or disease risk-factor. An easy-to-interpret report is then generated that includes both Genetic Renal Panel results and MLPA results, which is sent to the healthcare provider within three weeks of the date the sample was received. Additionally, a preliminary report for functional testing including biomarker and functional results is sent within two weeks of the sample received date. A final report will be sent within one month of the sample received date. This meeting provides the unique opportunity for a team of experts in the field of ultra-rare renal diseases to interpret results accurately and efficiently to help healthcare providers in the clinical setting. This meeting facilitates the relationship between the healthcare provider and the laboratory. Finally, this meeting facilitates the relationship between the healthcare provider and the laboratory. Additionally, this liaison helps research to be translated into results and vice versa. As the only translational research to clinical laboratory, if clinical results do not explain a patient’s disease, a research invitation may be sent to a patient inviting them to participate in research studies designed to understand these ultra-rare renal diseases. As always, if any questions arise regarding the results provided please reach out to our Clinical Team at morl@uiowa.edu or (319)335-6653. View more

Will the lab re-contact the ordering physician if variant interpretation changes?
Not provided. Healthcare providers are invited to contact the MORL for reinterpretation of previously tested patients in the MORL for an updated interpretation of previously reported variants.

Research:

Is research allowed on the sample after clinical testing is complete?
Review for research participation may be requested for review and will require patient demographic, clinical history, biopsy, and any functional and biomarker testing previously performed. Requests are evaluated in the scope of research currently being performed in the MORL.

Recommended fields not provided:

Clinical validity, Are family members with defined clinical status recruited to assess significance of VUS without charge?, Will the lab re-contact the ordering physician if variant interpretation changes?, Sample negative report, Sample positive report

Technical Information

Test Procedure:

targeted enrichment and massively parallel sequencing

Test Platform:

None/not applicable

Test Confirmation:

We have shown experimentally variants with QD >10 do not require Sanger sequencing validation (PMID: 21078986). In cases where the QD is between 5 and 10 and/or the zygosity status is indeterminate, Sanger confirmation is performed. Quality control testing to detect specimen mislabeling or sample contamination (sample integrity check) is … View more

Test Comments:

This assay is designed to amplify a panel of complement-mediated disease/TMA mimic-causing genes:CFH, CFI, MCP(CD46), CFB, CFHR5, C3, THBD, DGKE, PLG, ADAMTS13, MMACHC, G6PD, WT1and C5 p.Arg885. Other genes are not detected with this assay. Deep intronic or regulatory region variants and some copy number variations are not detected with … View more

Availability:

Tests performed
Interpretation performed in-house
Report generated in-house
Specimen preparation performed both in-house and at an outside lab
Wet lab work performed in-house

Test performance comments
DNA isolation from whole blood may be performed at the ordering healthcare provider's institution and/or applicable send out labs.

Analytical Validity:

Sensitivity greater than 99%.

Assay limitations:

Proficiency testing (PT):

Is proficiency testing performed for this test?
Yes

Method used for proficiency testing:
Intra-Laboratory

Description of PT method:
The MORL does intra-laboratory proficiency testing on a biannual basis.

VUS:

Laboratory's policy on reporting novel variations
The results report will provide a summary of all gene/variant information identified in the targeted genes and includes any further testing recommendations including genetic counseling and clinical correlation.

Recommended fields not provided:

Citations to support assay limitations, Description of internal test validation method, Citations for Analytical validity, PT Provider, Major CAP category, CAP category, CAP test list

Regulatory Approval

FDA Review:

Category: FDA exercises enforcement discretion

Additional Information

Reviews:

PubMed Clinical Queries

Clinical resources:

Consumer resources:

IMPORTANT NOTE: NIH does not independently verify information submitted to GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.