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IgVH Mutation Analysis Test

Last updated May 29, 2017

Approved by: Maulik P. Purohit MD MPH

The IgVH Mutation Analysis Test is a genetic test that detects abnormalities in the IgVH gene. It is used to diagnose CLL.

What are other Names for this Test? (Equivalent Terms)

  • Immunoglobulin Heavy-Chain Variable-Region Mutation Analysis Test

What is IgVH Mutation Analysis Test? (Background Information)

  • IgVH mutation refers to an alteration in the IgVH gene, which is associated with cancer of the white blood cells (leukemia). It is specifically associated with chronic lymphocytic leukemia (CLL), the most common type of leukemia in the Western world
  • The IgVH gene gives instructions for a protein that forms a part of a typical antibody called the heavy chain variable region
  • Antibodies are defense proteins made by specialized immune cells called B-lymphocytes, or “B-cells”. Rather, they are formed by plasma cells, which are further-specialized B-cells that serve as antibody-making factories
  • Antibodies are powerful defense proteins capable of recognizing a vast array of antigens by virtue of each antibody’s specificity. This specificity is conferred by the variable region of the antibody, so named because it is genetically shifty and thus varies from antibody to antibody. The heavy chain variable region is one such variable region important for antibody action
  • Alterations in the IgVH gene may result in antibodies with defective heavy chain variable regions, which is linked with CLL
  • The IgVH Mutation Analysis Test is a genetic test that detects abnormalities in the IgVH gene. It is used to diagnose CLL. It also aids in the treatment of CLL by guiding selection of therapeutic drugs, including disqualifying certain drugs from use

The molecular testing, in general, can be performed using a variety of methods. Some of these methods include:

  • In situ hybridization technique, such as fluorescence in situ hybridization (FISH)
  • Immunohistochemistry (IHC)
  • Next-generation sequencing (NGS)
  • Polymerase chain reaction (PCR)
  • Comparative genomic hybridization (CGH)
  • Karyotyping including spectral karyotyping
  • mRNA analysis
  • Tissue microarrays (TMAs)
  • Southern blot test
  • Northern blot test
  • Western blot test
  • Eastern blot test

The methodology used for the test may vary from one laboratory to another. 

Note: Molecular testing has limitations due to the molecular method and genetic mutational abnormalities being tested. This can affect the results on a case-by-case basis. Consultation with your healthcare provider will help in determining the right test and right molecular method, based on individual circumstances.

What are the Clinical Indications for performing the IgVH Mutation Analysis Test?

Following are the clinical indications for performing the IgVH Mutation Analysis Test: 

  • Enlarged, but painless, lymph nodes
  • Fatigue
  • Fever, night sweats
  • Pain in the upper left portion of the abdomen, which may be caused by an enlarged spleen
  • Weight loss
  • Frequent infections

In general, the molecular genetic testing is undertaken in the following situations: 

  • To assist (and in some cases, confirm) the initial diagnosis
  • To distinguish other tumors/conditions that have similar histological features, when examined by a pathologist under the microscope
  • To help in determining treatment options
  • To confirm recurrence of the tumor: Tumor recurrence can either be at the original tumor site, or at a distant location (away from the initial site)

How is the Specimen Collected for IgVH Mutation Analysis Test?

Following is the specimen collection process for IgVH Mutation Analysis Test

The specimen sample requirements may vary from lab to lab. Hence, it is important to contact the testing lab for exact specimen requirements, before initiating the testing process.

  • Sample on which the test is performed may include:
    • Fresh tumor tissue during biopsy
    • Formalin-fixed paraffin-embedded solid tumor tissue (FFPE tumor tissue), often referred to as paraffin block of the tumor
    • Unstained tissue slides
  • Process of obtaining the sample: As outlined by the laboratory testing facility
  • Preparation required: As outlined by the laboratory testing facility


  • In some cases, a different source of specimen (such as peripheral blood, bone marrow biopsy specimen, or other body fluids) may be acceptable to the laboratory performing the test
  • Occasionally, additional samples may be required to either repeat the test or to perform follow-up testing
  • Depending on the location of testing, it may take up to 2 weeks’ turnaround time, to obtain the test results
  • Many hospitals preserve the paraffin blocks for at least 7 years. In general, older paraffin blocks (over 5 years) may affect the detection of specific mutations, due to degradation of the tumor specimen over time

Cost of IgVH Mutation Analysis Test:

  • The cost of the test procedure depends on a variety of factors, such as the type of your health insurance, annual deductibles, co-pay requirements, out-of-network and in-network of your healthcare providers and healthcare facilities
  • In many cases, an estimate may be provided before the test is conducted. The final amount may depend upon the findings during the test procedure and post-operative care that is necessary (if any)

What is the Significance of the IgVH Mutation Analysis Test Result?

  • A mutation in the IgVH gene indicates a positive result for the IgVH Mutation Analysis Test. This may point to a diagnosis of chronic lymphocytic leukemia (CLL)

The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results in the context of the overall clinical scenario.

Additional and Relevant Useful Information:

  • Individuals with chronic lymphocytic leukemia, who also possess a mutation in IgVH, generally survive longer (approximately 15 years longer) than individuals with CLL lacking the IgVH mutation
  • Many laboratories may not have the capability to perform this test. Only highly-specialized labs with advanced facilities and testing procedures may perform this test

Certain medications that you may be currently taking may influence the outcome of the test. Hence, it is important to inform your healthcare provider, the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid unnecessary chances of a misdiagnosis.

What are some Useful Resources for Additional Information?

The following DoveMed website link is a useful resource for additional information:


Please visit our Laboratory Procedures Center for more physician-approved health information:


References and Information Sources used for the Article:

https://ghr.nlm.nih.gov/primer/testing/genetictesting (accessed on 05/10/2017)

https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5806a1.htm (accessed on 05/10/2017)

http://www.nature.com/gim/journal/v10/n5/full/gim200852a.html (accessed on 05/10/2017)

http://pediatrics.aappublications.org/content/106/6/1494 (accessed on 05/10/2017)

Chronic Lymphocytic Leukemia, IgVH Mutation Status. (n.d.). Retrieved from http://www.questdiagnostics.com/testcenter/testguide.action?dc=TH_IgVHMutation

IgVH Mutation Analysis | Integrated Oncology. (n.d.). Retrieved from http://www.integratedoncology.com/test-menu/igvh-mutation-analysis-/295c06f8-032d-4a8a-b4a3-790e55208b07

Lehninger, A. L., Nelson, D. L., & Cox, M. M. (2000). Lehninger principles of biochemistry. New York: Worth Publishers.

Lin, K. I., Tam, C. S., Keating, M. J., Wierda, W. G., O'Brien, S., Lerner, S., … Abruzzo, L. V. (2008). Relevance of the immunoglobulin VH somatic mutation status in patients with chronic lymphocytic leukemia treated with fludarabine, cyclophosphamide, and rituximab (FCR) or related chemoimmunotherapy regimens. Blood, 113(14), 3168-3171. doi:10.1182/blood-2008-10-184853

Symptoms and causes - Chronic lymphocytic leukemia - Mayo Clinic. (n.d.). Retrieved from http://www.mayoclinic.org/diseases-conditions/chronic-lymphocytic-leukemia/symptoms-causes/dxc-20200674

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Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: May 29, 2017
Last updated: May 29, 2017