Lynch Syndrome via the MLH1 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 4699 | MLH1 | 81292 | 81292,81294 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
Turnaround Time
3 weeks on average for standard orders or 2 weeks on average for STAT orders.
Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
Clinical Features
Lynch syndrome (OMIM 120435), also called hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited cancer syndrome caused by germline variants in DNA mismatch repair (MMR) genes. MMR genes are responsible for repairing small sequence errors, or mismatches, during DNA replication. Variants in a single mismatch repair gene can cause widespread genomic instability characterized by the expansion or contraction of short tandem repeat sequences (microsatellites) (reviewed by Grady & Carethers in Gastroenterology 135:1079-1099, 2008). This phenomenon of microsatellite instability (MSI) leads to somatic variants in oncogenes or tumor suppressor genes, including TGFBR2 and NF1 among others (Wang et al. Hum. Genet. 112:117-123, 2003). As a result, Lynch syndrome is marked by early onset and high lifetime risk of cancer, particularly in the right colon but also in the endometrium, ovary, stomach, bile duct, kidney, bladder, ureter, and brain (Jang & Chung, Gut and Liver 4:151-160, 2010). Clinical hallmarks of Lynch syndrome, as delineated by the Amsterdam criteria, include heritable colorectal (Type I) or extracolonic (Type II) cancer, present in at least three relatives over at least two consecutive generations, with an onset of cancer before the age of 50 in at least one case and pathological MSI within tumors (Vasen et al. Gastroenterology 116:1453-1456, 1999).
Genetics
Lynch syndrome is an autosomal dominant disease caused by germline variants in one of five described MMR genes: MLH1, MSH2, MSH6, PMS2 and EPCAM (Idos and Valle. 2021. PubMed ID: 20301390). More than 400 pathogenic variations have been reported in the MLH1 gene (OMIM 120436), most (~90%) of which are single nucleotide substitutions, small insertions or deletions, or splice-site variants (Human Gene Mutation Database, www.hgmd.cf.ac.uk; www.insight-group.org).
Clinical Sensitivity - Sequencing with CNV PG-Select
Depending on the clinical criteria used to make a diagnosis (i.e. Amsterdam or “Revised Bethesda”), 30-50% of Lynch patients have a detectable MLH1 variant (Syngal et al., J. Med. Genet 37:641-645, 2000).
Testing Strategy
This test provides full coverage of all coding exons of the MLH1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Candidates for this test are patients with a Lynch syndrome diagnosis, and relatives of patients who have a verified MLH1 variant. This test is specifically designed for heritable germline variants and is not appropriate for the detection of somatic variants in tumor tissue.
Candidates for this test are patients with a Lynch syndrome diagnosis, and relatives of patients who have a verified MLH1 variant. This test is specifically designed for heritable germline variants and is not appropriate for the detection of somatic variants in tumor tissue.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| MLH1 | 120436 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Lynch Syndrome II | 609310 |
Related Tests
Citations
- Grady WM, Carethers JM. 2008. Genomic and Epigenetic Instability in Colorectal Cancer Pathogenesis. Gastroenterology 135: 1079–1099. PubMed ID: 18773902
- Idos and Valle. 2021. PubMed ID: 20301390
- International Society for Gastrointestinal Hereditary Tumours..
- Jang E, Chung DC. 2010. Hereditary Colon Cancer: Lynch Syndrome. Gut and Liver 4: 151. PubMed ID: 20559516
- Syngal S, Fox EA, Eng C, Kolodner RD, Garber JE. 2000. Sensitivity and specificity of clinical criteria for hereditary non-polyposis colorectal cancer associated mutations inMSH2 and MLH1. Journal of medical genetics 37: 641–645. PubMed ID: 10978352
- Vasen HF, Watson P, Mecklin J-P, Lynch HT. 1999. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology 116: 1453–1456. PubMed ID: 10348829
- Wang Q, Montmain G, Ruano E, Upadhyaya M, Dudley S, Liskay MR, Thibodeau SN, Puisieux A. 2003. Neurofibromatosis type 1 gene as a mutational target in a mismatch repair-deficient cell type. Human genetics 112: 117–123. PubMed ID: 12522551
Ordering/Specimens
Ordering Options
We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.
myPrevent - Online Ordering
- The test can be added to your online orders in the Summary and Pricing section.
- Once the test has been added log in to myPrevent to fill out an online requisition form.
- PGnome sequencing panels can be ordered via the myPrevent portal only at this time.
Requisition Form
- A completed requisition form must accompany all specimens.
- Billing information along with specimen and shipping instructions are within the requisition form.
- All testing must be ordered by a qualified healthcare provider.
For Requisition Forms, visit our Forms page
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
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ORDER OPTIONS
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2) Select Additional Test Options
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