HNPCC/Lynch Syndrome (MLH1) Sequencing and Deletion/Duplication
Ordering Recommendation

Detect germline MLH1 variants. Use in MMR-deficient carcinoma with suggestive IHC results (loss of MLH1 and PMS2 proteins), negative for the BRAF codon 600 pathogenic variant, and normal MLH1 methylation studies.

Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification
28-35 days
New York DOH Approval Status
This test is New York DOH approved.
Specimen Required
Patient Preparation
Lavender (EDTA), pink (K2EDTA), or yellow (ACD solution A or B). 
Specimen Preparation
Transport 3 mL whole blood. (Min: 1 mL) 
Storage/Transport Temperature
Unacceptable Conditions
Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable 
Reference Interval
Available Separately
Reference Interval
NoMLH1 SequencingBy report
NoMLHI Deletion/DuplicationBy report

Interpretive Data
Background Information for HNPCC/Lynch Syndrome (MLH1) Sequencing and Deletion/Duplication:
Characteristics: Increased risk of colorectal and extra-colonic cancers including endometrial, renal pelvis, ureter, ovary, stomach, small intestine, and hepatobiliary tract.
Incidence: 1-2 percent of colorectal cancer is due to mismatch repair gene mutations.
Inheritance: Autosomal dominant
Penetrance of MLH1 Mutations: 80 percent lifetime risk of colorectal cancer; 20-60 percent risk for endometrial cancer.
Cause: Pathogenic germline MLH1, MSH2, MSH6, and PMS2 gene mutations.
Gene Tested: MLH1
Clinical Sensitivity: Approximately 45 percent of Lynch syndrome is due to MLH1 mutations.
Methodology: Bidirectional sequencing of MLH1 coding regions and intron-exon boundaries; multiplex ligation-dependent probe amplification (MLPA) to detect large MLH1 exonic deletions.Analytical Sensitivity & Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. The breakpoints of large deletions/duplications will not be determined. Regulatory region mutations, deep intronic mutations and mutations in genes other than MLH1 will not be detected.

Compliance Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Hotline History
Component Test Code*Component Chart NameLOINC
0051651Lynch Syndrome (MLH1) Interpretation
2001365MLH1 FGA Specimen
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
  • MLH1gene testing
  • hMLH1genotyping
  • Hypermethylation
  • MLH1 genotyping
  • MLH1 Full Gene Analysis
  • MLH1 Hypermethylation
  • MLH1germline assay