Table 1.
Phenotypic Evaluation for polyposis and/or colorectal cancer for syndromic and non-syndromic genes found on clinically available testing panels
| Gene | Disease Entity Curated (Inheritance) |
Disease MIM ID, Orphanet ID |
Phenotype(s) of Curation Focus |
Classification | aNotes |
|---|---|---|---|---|---|
| APC | Familial Adenomatous Polyposis (AD) | MIM:175100, ORPHA:247806 | Adenomatous polyps and Colorectal cancer | Definitive (12 GE, 6 EE, r/t) | |
| ATM | Colorectal cancer Susceptibility (AD) | MIM:N/A, ORPHA: 443909 | Colorectal cancer | Moderate (5 GE, 2 EE) | |
| AXIN2 | Oligodontia-colorectal cancer syndrome (AD) | MIM:608615, ORPHA:401911 | Hyperplastic polyps, Adenomatous polyps, Colorectal cancer | Moderate (8.5 GE, 2.5 EE) | |
| BLM | Colorectal cancer/Polyposis Susceptbility (AD) | MIM:N/A, ORPHA:N/A | Adenomatous polyps, Colorectal cancer | Definitive (8.3 GE, 6 EE, r/t) | |
| BMPR1A | Juvenile Polyposis Syndrome (AD) | MIM:174900, ORPHA:329971 | Hamartomatous polyps | Definitive (12 GE, 4.5 EE, r/t) | |
| CHEK2 | Colorectal cancer Susceptibility (AD) | MIM:604373, ORPHA: 443909 | Colorectal cancer | Limited (3.25 GE, 2.5 EE) | |
| ENG | Colorectal cancer/Polyposis Susceptibility (AD) | MIM:N/A, ORPHA:329971 | Hamartomatous polyps, Hyperplastic polyps, Adenomatous polyps, Colorectal cancer | Limited (0.2 GE, 1 EE) | |
| EPCAM | Lynch Syndrome (AD) | MIM:613244, ORPHA:144 | Colorectal cancer | Definitive (12 GE, 4 EE, r/t) | GE consists of probands with 3’UTR deletions/ exonic deletions at 3’ end of EPCAM, PMID: 19098912, 19177550 |
| GALNT12 | Colorectal cancer Susceptibility (AD) | MIM:608812, ORPHA: 443909 | Colorectal cancer | Limited (4 GE, 0.5 EE) | |
| GREM1 | Hereditary Mixed Polyposis Syndrome (AD) | MIM:601228, ORPHA:157794 | Hamartomatous polyps Adenomatous polyps Colorectal cancer | Strong (8.5 GE, 6 EE) | GE consists of probands with a single tandem duplication upstream of GREM1, PMID: 22561515 |
| MLH1 | Lynch Syndrome (AD) | MIM:609310, ORPHA:144 | Colorectal cancer | Definitive (12 GE, 6 EE, r/t) | |
| MLH3 | Colorectal cancer Susceptibility (AD) | MIM:614385, ORPHA: 443909 | Colorectal cancer | Moderate (5 GE, 5 EE) | |
| MSH2 | Lynch Syndrome (AD) | MIM:120435, ORPHA:144 | Colorectal cancer | Definitive (12 GE, 6 EE, r/t) | |
| MSH6 | Lynch Syndrome (AD) | MIM:614350, ORPHA:144 | Colorectal cancer | Definitive (12 GE, 6 EE, r/t) | |
| MUTYH | Colorectal cancer Susceptibility (AD) | MIM:N/A, ORPHA: 247798 | Colorectal cancer | Moderate (7 GE, 4.5 EE) | GE consists of case-level and case-control data in MUTYH monoallelic carriers |
| MUTYH | MUTYH associated Polyposis (AR) | MIM:608456, ORPHA:247798 | Adenomatous polyps, Colorectal cancer | Definitive (12 GE, 6 EE, r/t) | |
| PALB2 | Colorectal cancer Susceptibility (AD) | MIM:N/A ORPHA: 443909 | Colorectal cancer | Limited (5.2 GE, 0.5 EE) | |
| PMS1 | Lynch Syndrome (AD) | MIM:N/A, ORPHA:144 | Colorectal cancer | Refuted | |
| PMS2 | Lynch Syndrome (AD) | MIM:614337, ORPHA:144 | Colorectal cancer | Definitive (12 GE, 3 EE, r/t) | |
| POLD1 | Colorectal cancer/Polyposis Susceptbility (AD) | MIM:612591, ORPHA:447877 | Adenomatous polyps, Colorectal cancer | Definitive (8.5 GE, 5.5 EE, r/t) | GE consists of probands with missense substitutions in the exonuclease domain, PMID: 23263490 |
| POLE | Colorectal cancer/Polyposis Susceptbility (AD) | MIM:615083, ORPHA:447877 | Adenomatous polyps, Colorectal cancer | Definitive (12 GE, 3 EE, r/t) | GE consists of probands with missense substitutions in the exonuclease domain, PMID: 23263490 |
| PTEN | PTEN Hamartoma Tumor Syndrome (AD) | MIM:601728, ORPHA:306498 | Hamartomatous polyps, Hyperplastic polyps, Adenomatous polyps | Definitive (12 GE, 6 EE, r/t) | |
| SMAD4 | Juvenile Polyposis Syndrome (AD) | MIM:174900, ORPHA:329971 | Hamartomatous polyps | Definitive (12 GE, 6 EE, r/t) | |
| STK11 | Peutz-Jeghers Syndrome (AD) | MIM:175200, ORPHA:2869 | Hamartomatous polyps, Colorectal cancer | Definitive (12 GE, 6 EE, r/t) |
Abbreviations- AD: Autosomal Dominant, AR: Autosomal Recessive, r/t: replicated over time, N/A: Not Applicable, MIM: Mendelian Inheritance in Man, ORPHA:Orphanet identifier. GE: Genetic Evidence, EE: Experimental Evidence, PMID: PubMed identifier.
a
These notes serve as an explanation for the asterisks in Figure 1.