Table 3.

Genotype-Phenotype Correlations in APC-Associated Conditions

PhenotypeLocation/Type of APC Pathogenic VariantCommentsReference(s)
FAP (classic form) Whole-gene deletion Quadri et al [2015]
Attenuated FAP
  • 5' end (codons 1-233) 1
  • Distal 3' end (1300-2843; esp 3' of codon 1585)
  • Exon 9 (codons 311-412)
Extraintestinal manifestations (e.g., CHRPE, desmoid tumors) are rare.Sieber et al [2006], Anele et al [2022]
GAPPS APC promoter 1B
Somatic mosaicism Codons 1286-1513 (most common)Colon phenotype:
  • 65% attenuated FAP
  • 30% FAP
  • 5% no adenomas
Friedl & Aretz [2005], Hes et al [2008], Jansen & Goel [2020]
Brain tumors Codons 697-1224
  • 3x ↑ risk brain tumor
  • 13x ↑ risk medulloblastoma
 Attard et al [2007]
CHRPE Codons 148-2043 Burger et al [2011]
Codons 311-1444See footnote 2.
Whole-gene deletion Aretz et al [2005]
Desmoids Codons 1395-1493Odds ratio: 4.37 Sinha et al [2011]
5' of codon 400Incidence: 14.9% Church et al [2015]
Codons 401-1400Incidence: 23.3%
3' of codon 1400Incidence: 37.1%
Duodenal adenomas Codons 976-10674x ↑ risk Bertario et al [2003]
Epidermoid cysts Codons 457-1493 Dinarvand et al [2019]
Osteomas Codons 767-1578
Profuse polyposis Codons 1250-1464Average of 5,000 polyps D'Elia et al [2018]
Thyroid cancer 5' end (codon 1061 or proximal to codon 938) Chenbhanich et al [2019]

CHRPE = congenital hypertrophy of the retinal pigment epithelium; FAP = familial adenomatous polyposis; GAPPS = gastric adenocarcinoma and proximal polyposis of the stomach

1.

Variants 5' of codon 233 are the most commonly described variants associated with attenuated FAP [Knudsen et al 2003].

2.

Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020]

From: APC-Associated Polyposis Conditions

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