Mutyh-associated polyposis: genes and variants
Explore variant evidence for Mutyh-associated polyposis across 5 analyzed proteins (MUTYH, APC, NTHL1, MSH3, TSC2). Linked ClinVar records include 32 pathogenic or likely pathogenic variants, 2,775 variants of uncertain significance and 581 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Mutyh-associated polyposis
MUTYH: Adenine DNA glycosylase
It removes adenines incorrectly paired with oxidized guanine, preventing characteristic G:C-to-T:A mutations during base-excision repair. Biallelic loss-of-function variants cause MUTYH-associated polyposis and substantially increase colorectal-cancer risk.
27 ClinVar pathogenic / likely pathogenic and 995 uncertain variants in MUTYH have source records linked to Mutyh-associated polyposis. Association strength is not clinical gene validity.
APC: Adenomatous polyposis coli protein
A tumor-suppressor protein that promotes the removal of beta-catenin and helps keep Wnt signaling under control. It also organizes microtubules and actin in the cell, and inherited APC disruption is strongly associated with familial adenomatous polyposis and colorectal tumor risk.
4 ClinVar pathogenic / likely pathogenic and 2,091 uncertain variants in APC have source records linked to Mutyh-associated polyposis. Association strength is not clinical gene validity.
NTHL1: Endonuclease III-like protein 1
It removes oxidized pyrimidines from DNA through base-excision repair and prevents accumulation of characteristic point mutations. Biallelic loss-of-function variants cause NTHL1 tumor syndrome with colorectal polyposis and increased risk of multiple malignancies.
1 ClinVar pathogenic / likely pathogenic and 154 uncertain variants in NTHL1 have source records linked to Mutyh-associated polyposis. Association strength is not clinical gene validity.
MSH3: DNA mismatch repair protein Msh3
Together with MSH2, it recognizes larger insertion-deletion loops and certain DNA secondary structures during mismatch repair. Variation can modify the behavior of repeat-expansion disorders, while biallelic loss has been associated with a recessive adenomatous-polyposis phenotype.
0 ClinVar pathogenic / likely pathogenic and 115 uncertain variants in MSH3 have source records linked to Mutyh-associated polyposis. Association strength is not clinical gene validity.
TSC2: Tuberin
Together with TSC1, it inactivates RHEB and restrains mTORC1 when growth conditions are unfavorable. Loss-of-function variants cause tuberous sclerosis complex with hamartomas and tumors affecting the brain, kidneys, skin, heart, lungs, and other organs.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in TSC2 have source records linked to Mutyh-associated polyposis. Association strength is not clinical gene validity.
Weakly linked (only a few uncertain records): VDR.
ClinVar pathogenic and likely pathogenic variants linked to Mutyh-associated polyposis
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| MUTYH R242C | 242 | Pathogenic / likely pathogenic (★★) | |
| MUTYH R242H | 242 | Pathogenic / likely pathogenic (★★) | |
| MUTYH R106P | 106 | Pathogenic / likely pathogenic (★★) | |
| MUTYH R106G | 106 | Pathogenic / likely pathogenic (★★) | |
| MUTYH R106W | 106 | Pathogenic / likely pathogenic (★★) | |
| MUTYH L108P | 108 | Pathogenic / likely pathogenic (★★) | |
| MUTYH R244G | 244 | Pathogenic / likely pathogenic (★★) | |
| MUTYH L98P | 98 | Pathogenic / likely pathogenic (★★) | |
| MUTYH W128R | 128 | Pathogenic / likely pathogenic (★★) | |
| MUTYH R179H | 179 | Pathogenic / likely pathogenic (★★) | |
| MUTYH G180D | 180 | Pathogenic / likely pathogenic (★★) | |
| MUTYH V212M | 212 | Pathogenic / likely pathogenic (★★) | |
| MUTYH N235S | 235 | Pathogenic / likely pathogenic (★★) | |
| MUTYH R238W | 238 | Pathogenic / likely pathogenic (★★) | |
| MUTYH V243F | 243 | Pathogenic / likely pathogenic (★★) | |
| MUTYH G273E | 273 | Pathogenic / likely pathogenic (★★) | |
| MUTYH M280V | 280 | Pathogenic / likely pathogenic (★★) | |
| MUTYH G283E | 283 | Pathogenic / likely pathogenic (★★) | |
| MUTYH P292L | 292 | Pathogenic / likely pathogenic (★★) | |
| MUTYH L385P | 385 | Nudix hydrolase | Pathogenic / likely pathogenic (★★) |
| NTHL1 R7S | 7 | Pathogenic / likely pathogenic (★★) | |
| MUTYH M1V | 1 | Pathogenic / likely pathogenic (★★) | |
| MUTYH V72M | 72 | Pathogenic / likely pathogenic (★★) | |
| MUTYH P154L | 154 | Pathogenic / likely pathogenic (★★) | |
| MUTYH P402L | 402 | Nudix hydrolase | Pathogenic / likely pathogenic (★★) |
| MUTYH M15V | 15 | Pathogenic / likely pathogenic (★★) | |
| MUTYH R271W | 271 | Pathogenic / likely pathogenic (★★) | |
| APC N1012K | 1012 | Responsible for down-regulation through a proces | Pathogenic / likely pathogenic (★) |
| APC S1385N | 1385 | Pathogenic / likely pathogenic (★) | |
| APC S1403N | 1403 | Pathogenic / likely pathogenic (★) | |
| APC S1421N | 1421 | Pathogenic / likely pathogenic (★) | |
| MUTYH H82D | 82 | Pathogenic / likely pathogenic (★) |
Which prediction tools work for Mutyh-associated polyposis
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- AlphaMissense: 88 out of 100
- MetaLR: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 85 out of 100
- MutPred2: 85 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 84 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 84 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- EVE: 84 out of 100
Same protein, different disease
- Ovarian cancer also has ClinVar records linked to APC variants; they fall mostly in different places as the Mutyh-associated polyposis variants (4 pathogenic / likely pathogenic).
Diseases related to Mutyh-associated polyposis
- Colorectal cancer, also linked to APC, MUTYH and NTHL1
- Ovarian cancer, also linked to APC and TSC2
- Gastric cancer, also linked to APC and MUTYH
- Colon carcinoma, also linked to APC and MUTYH
- Hepatocellular carcinoma, also linked to APC and TSC2
- Inherited polyposis and early onset colorectal cancer - germline testing, also linked to MUTYH and NTHL1
- Classic or attenuated familial adenomatous polyposis, also linked to APC and MUTYH
- Tuberous sclerosis, also linked to TSC2
- Isolated focal cortical dysplasia type II, also linked to TSC2
- Pilomatrixoma, also linked to MUTYH
- Endometrial carcinoma, also linked to MSH3
- Desmoid disease, hereditary, also linked to APC
Frequently asked questions
Which genes have records linked to Mutyh-associated polyposis?
This view contains 5 analyzed proteins: MUTYH, APC, NTHL1, MSH3, TSC2. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 32 pathogenic or likely pathogenic variants, 2,775 variants of uncertain significance and 581 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 3,578 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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