MUTYH Associated Polyposis (MAP) Syndrome via the MUTYH 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 | |
|---|---|---|---|---|---|
| 7505 | MUTYH | 81406 | 81406,81479 | $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
MUTYH-associated polyposis (MAP) (OMIM 608456) is an autosomal recessive condition of familial adenomatous polyposis (FAP) (OMIM 175100) caused exclusively by variants in the MUTYH gene (OMIM 604933) (Al-Tassan et al. Nat Genet 30:227-232, 2002; Sieber et al. New Eng J Med 348:791-799, 2003). Individuals with MAP typically present by age 55 with multiple (between 10 and 1000) colorectal adenomas, some of which have or will become colorectal tumors (Poulsen & Bisgaard Curr Genomics 9:420-435, 2008). The MUTYH gene encodes a vital component of the base excision repair (BER) system, which protects DNA from oxidative damage and the misincorporation of adenines opposite guanines during DNA replication (Lu et al. Front Biosci 11:3062-3080, 2006). As such, the molecular profile of colorectal adenomas and carcinomas taken from MAP patients includes G:C → T:A transversions in the adenomatous polyposis coli (APC) and K-ras tumor suppressor (KRAS) genes, among others (Lipton et al. Cancer Res 63:7595-7599, 2003; Jones et al. Br J Cancer 90:1591-1593, 2004).
Genetics
To date, about 100 pathogenic variants have been reported in the MUTYH gene, nearly all (~99%) of which are single nucleotide variations, small insertions or deletions, or splice-site variants (www.insight-group.org, www.hgmd.org). While MUTYH-associated polyposis (MAP) occurs in patients from various ethnic groups, specific MUTYH variants are found in different populations. In European and North American MAP populations, two missense variants, p.Tyr179Cys and p.Gly396Asp, are most common; both homozygous and compound heterozygous variants contribute to the disease (Jones et al. Hum Mol Genet 11:2961-2967, 2002). In Asian MAP populations, common variants include the missense variant p.Arg245Cys, splice-site variant c.934-2A>G, and p.Glu480* nonsense variant; in these cases only homozygous variants have been reported to contribute to disease (Tao et al. Carcinogenesis 25:1859-1866, 2004; Miyaki et al. Mutat Res 578:430-433, 2005). The penetrance of colorectal cancer (CRC) for biallelic carriers of MUTYH variants is nearly 100% by the age of 60 (Farrington et al. Am J Hum Genet 77:112-119, 2005).
Clinical Sensitivity - Sequencing with CNV PG-Select
By definition, all MAP patients have biallelic germline variants in MUTYH. However, variants in MUTYH are also found in ~25% of patients initially diagnosed with familial adenomatous polyposis (FAP) (Sampson et al. Lancet 362:39-41, 2003). Clinical sensitivity for MUTYH deletions/duplications is not currently known.
Testing Strategy
This test provides full coverage of all coding exons of the MUTYH 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 multiple colorectal adenomas–especially if no germline APC variants have been identified or with recessive inheritance of colorectal adenomatous polyposis as suggested by family history. Relatives, particularly siblings, of patients with a verified MUTYH germline variant are also candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in MUTYH. 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 multiple colorectal adenomas–especially if no germline APC variants have been identified or with recessive inheritance of colorectal adenomatous polyposis as suggested by family history. Relatives, particularly siblings, of patients with a verified MUTYH germline variant are also candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in MUTYH. 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 |
|---|---|
| MUTYH | 604933 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Myh-Associated Polyposis | AR | 608456 |
Related Test
| Name |
|---|
| Hereditary Endometrial Cancer Panel |
Citations
- Al-Tassan N, Chmiel NH, Maynard J, Fleming N, Livingston AL, Williams GT, Hodges AK, Davies DR, David SS, Sampson JR, Cheadle JP. 2002. Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors. Nat. Genet. 30: 227–232. PubMed ID: 11818965
- Farrington SM, Tenesa A, Barnetson R, Wiltshire A, Prendergast J, Porteous M, Campbell H, Dunlop MG. 2005. Germline susceptibility to colorectal cancer due to base-excision repair gene defects. The American Journal of Human Genetics 77: 112–119. PubMed ID: 15931596
- Human Gene Mutation Database (Bio-base).
- International Society for Gastrointestinal Hereditary Tumors.
- Jones S, Emmerson P, Maynard J, Best JM, Jordan S, Williams GT, Sampson JR, Cheadle JP. 2002. Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G: C→ T: A mutations. Human Molecular Genetics 11: 2961–2967. PubMed ID: 12393807
- Jones S, Lambert S, Williams GT, Best JM, Sampson JR, Cheadle JP. 2004. Increased frequency of the k-ras G12C mutation in MYH polyposis colorectal adenomas. British Journal of Cancer 90: 1591–1593. PubMed ID: 15083190
- Lipton L, Halford SE, Johnson V, Novelli MR, Jones A, Cummings C, Barclay E, Sieber O, Sadat A, Bisgaard M-L. 2003. Carcinogenesis in MYH-associated polyposis follows a distinct genetic pathway. Cancer research 63: 7595–7599. PubMed ID: 14633673
- Lu A-L, Bai H, Shi G, Chang D-Y. 2006. MutY and MutY homologs (MYH) in genome maintenance. Front. Biosci. 11: 3062–3080. PubMed ID: 16720376
- Miyaki M, Iijima T, Yamaguchi T, Hishima T, Tamura K, Utsunomiya J, Mori T. 2005. Germline mutations of the MYH gene in Japanese patients with multiple colorectal adenomas. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 578: 430–433. PubMed ID: 15890374
- Poulsen MLM, Bisgaard ML. 2008. MUTYH Associated Polyposis (MAP). Curr. Genomics 9: 420–435. PubMed ID: 19506731
- Sampson JR, Dolwani S, Jones S, Eccles D, Ellis A, Evans DG, Frayling I, Jordan S, Maher ER, Mak T. 2003. Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH. The Lancet 362: 39–41. PubMed ID: 12853198
- Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, Bisgaard M-L, Orntoft TF, Aaltonen LA, Hodgson SV. 2003. Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. New England Journal of Medicine 348: 791–799. PubMed ID: 12606733
- Tao H. 2004. A novel splice-site variant of the base excision repair gene MYH is associated with production of an aberrant mRNA transcript encoding a truncated MYH protein not localized in the nucleus. Carcinogenesis 25: 1859–1866. PubMed ID: 15180946
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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