Lynch Syndrome via the MSH2 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture ProbesTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
4863 | MSH2 | 81295 | 81295,81297 | $990 | Order Options and Pricing |
Pricing Comments
This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
Testing run on PG-Select capture probes does not include exome-wide CNV analysis. Reflex is available to PGxome or an exome-based panel, or you can use this gene list to create a custom panel (click here).
Click here for costs to reflex to whole PGxome.
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, also called Hereditary Nonpolyposis Colorectal Cancer (HNPCC), is an inherited cancer syndrome caused by germline pathogenic variants in DNA mismatch repair (MMR) genes. MMR genes encode proteins that repair small sequence errors, or mismatches, during DNA replication. Pathogenic variants in a single mismatch repair gene can cause widespread genomic instability characterized by the expansion or contraction of short tandem repeat sequences, or microsatellites (Grady and Carethers. 2008. PubMed ID: 18773902). This phenomenon of microsatellite instability (MSI) leads to somatic mutations in oncogenes and/or tumor suppressor genes, including TGFβIIR and NF1 among others (Wang et al. 2003. PubMed ID: 12522551). 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 and Chung. 2010. PubMed ID: 20559516). 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. 1999. PubMed ID: 10348829).
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 500 pathogenic variants have been reported in the MSH2 gene, half of which are single nucleotide substitutions, small insertions/deletions or splice site mutations (Human Gene Mutation Database, www.hgmd.cf.ac.uk; www.insight-group.org). The other half are large deletions and not detectable by sequencing. In particular, a deletion of exons 1-6 is found in many North American families, but not found in European or Australian patients (Lynch et al. 2004. PubMed ID: 14871915). A germline inversion of exons 1-7 in MSH2 has been reported in fourteen individuals from eleven un-related families clinically presenting with Lynch syndrome associated phenotypes including colorectal, endometrial, gastric, and ovarian cancer (Wagner et al. 2002. PubMed ID: 12203789; Rhees et al. 2013. PubMed ID: 24114314; Mork et al. 2016. PubMed ID: 28004223).
Clinical Sensitivity - Sequencing with CNV PG-Select
Depending on the clinical criteria used to make a diagnosis (Amsterdam or “Revised Bethesda”), 15-20% of Lynch patients have a detectable MSH2 pathogenic variant (Syngal et al. 2000. PubMed ID: 10978352).
Testing Strategy
This test provides full coverage of all coding exons of the MSH2 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing. It also includes testing for the inversion of exons 1-7 in MSH2.
Indications for Test
Candidates for this test are patients with a Lynch Syndrome diagnosis, and relatives of patients who have a verified MSH2 pathogenic variant. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
Candidates for this test are patients with a Lynch Syndrome diagnosis, and relatives of patients who have a verified MSH2 pathogenic variant. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
Gene
Official Gene Symbol | OMIM ID |
---|---|
MSH2 | 609309 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Disease
Name | Inheritance | OMIM ID |
---|---|---|
Lynch Syndrome I | AD | 120435 |
Related Tests
Citations 
- Grady and Carethers. 2008. PubMed ID: 18773902
- Human Gene Mutation Database.
- Idos and Valle. 2021. PubMed ID: 20301390
- International Society for Gastrointestinal Hereditary Tumours..
- Jang and Chung. 2010. PubMed ID: 20559516
- Lynch et al. 2004. PubMed ID: 14871915
- Mork et al. 2016. PubMed ID: 28004223
- Rhees et al. 2013. PubMed ID: 24114314
- Syngal et al. 2000. PubMed ID: 10978352
- Vasen et al. 1999. PubMed ID: 10348829
- Wagner et al. 2002. PubMed ID: 12203789
- Wang et al. 2003. 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
Specimen Types
Specimen Requirements and Shipping Details
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
STAT and Prenatal Test Options are not available with Patient Plus.
No Additional Test Options are available for this test.