For the tumor spectrum, multiple tumor manifestations in a single patient were individually considered. ∗Endometrial cancer (N=27), stomach cancer (N=13), ovary cancer (N=7), bladder cancer (N=4), small intestinal cancer (N=4), cervical cancer (N=3), breast cancer (N=3), glioblastoma (N=2), lung cancer (N=2), esophageal cancer (N=1), pheochromocytoma (N₌1), and skin cancer (N₌1);

^† The tumor spectrum of family members from 164 cases was as follows: CRC (N=240), stomach cancer (N=28), hepatobiliary cancer (N=22), EC (N=18), lung cancer (N=10), pancreatic cancer (N=7), urinary cancer (N=5), ovary cancer (N=5), breast cancer (N=4), skin cancer (N=2), hematologic cancer (N=2), thyroid cancer (N=2), cervical cancer (N=2), brain cancer (N₌1), prostate cancer (N₌1), small intestinal cancer (N₌1), and pharyngeal cancer (N=1);

^‡ Immunohistochemistry and the microsatellite instability assessments were described as the number/total number available.

Abbreviations: NT, nucleotide; AA, amino acid; dbSNP, database of single nucleotide polymorphisms, v150; HGMD, human gene mutation database (professional version, updated in March 2017); InSiGHT, International Society of Gastrointestinal Hereditary Tumors (updated in August 2017 and accessed on January, 2018); ACMG, American College of Medical Genetics and Genomics; DM, disease-causing mutation; NA, not applicable; P, pathogenic; LP, likely pathogenic.

^∗ MLH1 (NM_000249.2), MSH2 (NM_000251.1), and MSH6 (NM_000179.2);

^† Alterations at the amino acid level were deduced from nucleotide alterations in the case of experimental evidence and were filled based on predicted protein sequences in parentheses; ^‡ Allele frequency of SNPs: rs147542208 (0.000200000 from 1000GP, 0.00002486 from ExAC, 0.000909091 from KRGDB databases), rs63749932 (0.000008244 from ExAC), rs267608087 (0.000057680 from ExAC); ^§ The status of variants was evaluated based on the curated data from InSiGHT, HGMD, and ClinVar (accessed in January 2018) databases; ^¶ The criteria were applied as follows: PVS1 (nonsense variants, splicing variants and frameshift variants), PS3 (functional evidences by splicing/transcript expression, MMR activity, sub-cellular localization, subunit interaction, protein expression, and stability data from the curated data in In-SiGHT, available at http://insight-group.org/variants/database/ accessed on January, 2018), PM2 (allele frequency less than 0.01 or absent from the databases including the 1000 Genomes Project, Exome Sequencing Project, Exome Aggregation Consortium, or the Korean Reference Genome Database, available at 1000GP, http://browser.1000genomes.org/index.html, http://evs.gs.washington.edu/EVS/, http://exac.broadinstitute.org/, http://152.99.75.168/ KRGDB/, respectively), PP1 (co-segregation data from the curated data in InSiGHT), PP3 (evidence supporting “deleterious” or “damaging” effects was higher than 3 using the in silico tools: functional effects of missense variants were predicted by sorting intolerant from tolerant (SIFT), polymorphism phenotyping-2 (PolyPhen), LRT, FATHMM, MutationTaster, MutationAssesor, and Genomic Evolutionary Rate Profiling (GERP) score), PP5 (a “disease-causing mutation” in the human gene mutation database (HGMD professional, updated on March, 2017, a “pathogenic” mutation in ClinVar (available at http://www.ncbi.nlm.nih.gov/clinvar/ accessed on January, 2018), a “class 4 or class 5 in InSiGHT and Leiden Open Variation Database (LOVD v3.0 Build 19 http://www.lovd.nl/3.0/home), or variants reported from previous studies) [18, 24, 29-31]; ^ll This pathogenic variant (c.677G> A) is predicted to be a nucleotide substitution at the coding DNA level. However, protein and RNA-based functional studies have consistently found that this variant results in the skipping of exon 8. This variant was classified as a frameshift variant [26-28];

^∗∗ This variant (c.1333C> T) was reported in the previous study [35].

Abbreviations: MLPA, multiplex ligation-dependent probe amplification; LS, Lynch syndrome; SSCP, single strand conformation polymorphism; DGGE, denaturing gradient gel electrophoresis; DHPLC, denaturing high perfor-mance liquid chromatography; NA, not applicable.

Abbreviations: NT, nucleotide; AA, amino acid; 1000GP, 1000 Genomes Project; ESP, Exome Sequencing Project; ExAC, Exome Aggregation Consortium; KRGDB, Korean Reference Genome Database; SIFT, sorting intolerant from tolerant; PolyPhen, polymorphism phenotyping-2; GERP, Genomic Evolutionary Rate Profiling; A, Absent; D, damaging (in PolyPhen)/deleterious (in SIFT, LRT, and FATHMM)/disease-causing (in MutationTaster); P, possibly or probably damaging (in PolyPhen); H, high (functional); M, medium (functional); N, neutral (nonfunctional); L, low(nonfunctional); T, tolerated (in SIFT and FATHMM).

Abbreviation: NA, not applicable.

^∗ Positive for genetic alterations vs. negative for genetic alterations;

^† Immunohistochemistry and the microsatellite instability assessments were described as the number/total number available.