MLH1/MSH2/MSH6/PMS2 Comprehensive Analysis

CPT: 81292; 81295; 81298; 81317
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Test Details


  • Lynch Syndrome

Test Includes

This comprehensive test includes both Sanger sequencing and deletion/duplication analysis by MLPA of the MLH1, MSH2, MSH6, and PMS2 genes. The sequencing portion of this test covers all coding nucleotides plus at least two and typically 20 flanking intronic nucleotides upstream and downstream of each coding exon, covering the conserved donor and acceptor splice sites, as well as typically 20 flanking nucleotides in the 5' and 3' UTR. The deletion/duplication analysis can detect single exon, multi-exon, and full gene deletions or duplications.


Can confirm a clinical diagnosis of HNPCC and allow early diagnosis in family members, guiding preventive measures. Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal-dominant, genetically heterogeneous syndrome caused by heterozygous mutations in mismatch repair genes (MMR). HNPCC is estimated to account for 4% to 6% of colorectal cancer and is characterized by early onset, a predominant proximal location of colon cancer, multiple primary cancers, and significantly improved survival when compared stage for stage to sporadic colon cancer survival rates. HNPCC has been linked to mutations in the genes MLH1, MSH2, PMS2, MSH6, and EPCAM. Genetic testing can confirm the diagnosis of HNPCC and can also identify presymptomatic individuals among the patient's relatives.


Sequencing cannot detect variants in regions not covered by this analysis, such as variants in noncoding or deep intronic regions and may not reliably detect changes in repetitive elements, such as microsatellite repeats. Sequence analysis may also be affected by allele drop-out due to the presence of a rare variant under a primer site. MLPA is designed to detect single exon, multi-exon, and full gene deletions or duplications. MLPA may not detect certain genomic rearrangements, such as translocations, inversions, or some partial exon rearrangements. This assay cannot determine exact breakpoints of deletions or duplications detected. Mosaic variants are not reliably detected by either sequencing or MLPA. These analyses also cannot determine whether two or more heterozygous changes are located on the same or different chromosomes. Due to the presence of the pseudogene PMS2CL, which has not been associated with Lynch syndrome, this assay cannot determine the location, ie, in PMS2 or PMS2CL, of any large deletions or duplications of exons 12 to 15 of the PMS2 gene detected by deletion/duplication analysis.

This test was developed, and its performance characteristics determined, by LabCorp. It has not been cleared or approved by the US Food and Drug Administration (FDA).


DNA sequencing and multiplex ligation-dependent probe amplification (MLPA)

Specimen Requirements


Whole blood


7 mL

Minimum Volume

4 mL


Lavender-top (EDTA) tube

Storage Instructions

Maintain specimen at room temperature.

Causes for Rejection

Container broken or leaking; container not labeled; improper anticoagulant

Clinical Information


Evans JT, Vana J, Aronoff BL, Baker HW, Murphy GP. Management and survival of carcinoma of the colon: Results of a national survey of the American College of Surgeons. Ann Surg. 1978 Dec; 188(6):716-720. 736649
Hutter P, Wijnen J, Rey-Berthod C, et al. An MLH1 haplotype is over-represented on chromosomes carrying an HNPCC predisposing mutation in MLH1.J Med Genet. 2002 May; 39(5): 323-327. 12011148
Kohlmann W, Gruber SB. Lynch syndrome. In: Pagon RA, Adam MP, Ardinger HH, et al, eds. GeneReviews®. 2004 Feb 5; Seattle, Wash: University of Washington;1993-2014. Available at: Accessed July 26, 2014. 20301390
Online Mendelian Inheritance in Man (OMIM™). Colorectal cancer, hereditary nonpolyposis, type 8; HNPCC8. Baltimore, Md: Johns Hopkins University; Last updated February 4, 2010. Available at: Accessed August 2, 2010.
Online Mendelian Inheritance in Man (OMIM™). Lynch syndrome I. Baltimore, Md: Johns Hopkins University; Last updated June 4, 2010. Available at: Accessed July 26, 2010.
Online Mendelian Inheritance in Man (OMIM™). MutL, E coli, homolog of, 1; MLH1. Baltimore, Md: Johns Hopkins University; Last updated June 7, 2010. Available at: Accessed July 28, 2010.
Online Mendelian Inheritance in Man (OMIM™). MutS, E coli, homolog of, 2; MSH2. Baltimore, Md: Johns Hopkins University; Last updated February 5, 2010. Available at: Accessed July 28, 2010.
Online Mendelian Inheritance in Man (OMIM™). Postmeiotic segregation increased, S cerevisiae, 2; PMS2. Baltimore, Md: Johns Hopkins University; Last updated September 21, 2009. Available at: Accessed July 26, 2010.


Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
511700 MLH1/MSH2/MSH6/PMS2 Comp 511699 Specimen Type 31208-2
511700 MLH1/MSH2/MSH6/PMS2 Comp 511698 Result 79570-8
511700 MLH1/MSH2/MSH6/PMS2 Comp 511697 Director Review 72486-4
511700 MLH1/MSH2/MSH6/PMS2 Comp 511696 Tracking N/A
511700 MLH1/MSH2/MSH6/PMS2 Comp 511701 Putaway N/A
Reflex Table for Result
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 511775 Deletion/Duplication 511775 Deletion/Duplication Pending

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