Lab Test

Chronic Lymphocytic Leukemia (CLL) IgHV Mutational Status

CLL IgHV Mutational Status, Immunoglobulin Heavy Chain Gene

Test Codes

EPIC: LAB7815, Beaker: GIGHV


Molecular Pathology


Sample should be drawn as early in the day as possible so the specimen can be delivered to the Laboratory the same day.

Specimen Collection Criteria

Collect: One of the following specimen types, as described below:

  1. Blood: 10.0 mL whole blood in Lavender-top EDTA tubes. Invert several times to mix blood. (Minimum: 3.0 mL) 
  2. Bone Marrow: 1.0 mL bone marrow in a Lavender-top EDTA tube. Invert several times to mix bone marrow. 
  • All specimen types should be sent to the Laboratory immediately for processing. 
  • DNA will be assessed for quality. If it is deemed unacceptable, testing will be cancelled with client notification. 
The specimen must be accompanied by a completed requisition and must contain the patient name, hospital and visit number, date of birth, collection date, ordering physician, and source of specimen.

Physician Office/Draw Specimen Preparation

Do not freeze specimens. Maintain specimens at room temperature (20-26°C or 68-78.8°F) and transport to the Laboratory within 4-6 hours of collection.

Preparation for Courier Transport

Transport: Blood and bone marrow refrigerated (2-8°C or 36-46°F).

Rejection Criteria

  • Frozen specimens. 
  • Unlabeled tubes. 
  • Specimens collected in heparin (Green-top), clot tubes (Red-top), or SST tubes. 

In-Lab Processing

Do not freeze specimens. Maintain specimen refrigerated (2-8°C or 36-46°F) prior to testing. 


Specimen Stability for Testing:

Room Temperature (20-26°C or 68-78.8°F): 72 hours
Refrigerated (2-8°C or 36-46°F): 7 days
Frozen (-20°C/-4°F or below): Unacceptable

Specimen Storage in Department Prior to Disposal:

Refrigerated (2-8°C or 36-46°F): 7 days

Extracted DNA may be available for additional testing if clinically indicated. Contact the Molecular Pathology Laboratory for verification.


Royal Oak Molecular Pathology Laboratory


Once per week.
Results available within 21 days.

Reference Range


Test Methodology

IGHV somatic hypermutation testing is performed on genomic DNA isolated from a peripheral blood or bone marrow specimen. DNA is PCR amplified with 5’ Leader and 3’ IGHJ primers and analyzed by capillary electrophoresis. The resultant amplified product is sequenced bidirectionally using Sanger methodology. DNA Sequences of IGHV rearrangements are subjected to bioinformatics analysis with IgBLAST ( to determine the percent sequence homology with germline IGHV sequences.


IGHV mutational status defined as: MUTATED; ≤97%, UNMUTATED; ≥98%, and BORDERLINE; >97% and <97.9% identity with germline reference sequence gene, respectively. An Indeterminate IGHV mutational status reflects either a non-productive clone or a polyclonal process.


  1. Chia P, et al. ERIC recommendations on IGHV gene mutational status analysis in chronic lymphocytic leukemia. Leukemia (2007) 21, 1-3.
  2. Vardi  A, et al. Immunogenetic studies of chronic lymphocytic leukemia: Revelations and Speculations about Ontogeny and Clinical Evolution. Cancer Res (2014) 74(16); 4211-4216.
  3. Rosenquist R, et al. Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: updated ERIC recommendations. Leukemia (2017) 31, 1477-1481.

Clinical Utility

  • IgHV Somatic Mutational status analysis is used as a prognostic indicator in CLL. 
  • The test is recommended for risk stratification of CLL patients. 

Guidelines for Cytogenetic Molecular Follow-Up Testing of Hematopoietic Malignancy

CPT Codes

81263 – IGH (immunoglobulin heavy chain locus) (eg, leukemia and lymphoma, B-cell), variable region somatic mutation analysis.


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