Table 1.
Summary of Functional Assay in Present Study and In Silico Prediction, Functional Assay in Previous Studies, Clinical Information
| Variations | Nucleotide changea | Functional assay (fold to wild type)b | Protein levelc | SIFT (score)d | Polyphen-2 (score)e | Glycosylase assay | Previous rifampicin assay | Detected population (frequency of report) | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| p.P18L | c.53C>T | 26.0 | (2.7) | 0.96 | T | (0.50) | B | (0.028) | NE | NE | FAP (1), MP (5), sporadic CRC(6), LC (1), HC (3) |
| p.V22M | c.64G>A | 12.0 | (1.2) | 1.00 | A | (0.00) | B | (0.185) | Proficient | NE | FAP, sporadic CRC, HC (allele frequency = 13%) |
| p.G25D | c.74G>A | 5.00 | (0.5) | 0.82 | A | (0.43) | B | (0.335) | NE | NE | FAP (1), MP (5), sporadic CRC(6), LC (1), HC (3) |
| p.W103R | c.265A>G | 47.0 | (4.9) | 0.89 | A | (0.00) | D (++) | (1.000) | NE | NE | Sporadic HCC (4), HC |
| p.D105N | c.271C>T | 8.67 | (0.9) | 0.84 | A | (0.00) | D (++) | (0.802) | NE | NE | MP (1), sporadic CRC (1) |
| p.Y128H | c.340T>C | 34.7 | (3.6) | 1.17 | A | (0.00) | D (++) | (1.000) | NE | NE | AFAP (1) |
| p.W131R | c.349T>A | 75.3 | (7.8) | 1.22 | A | (0.00) | D (++) | (1.000) | NE | NE | FAP (1) |
| p.P157L | c.428G>A | 31.3 | (3.2) | 0.83 | A | (0.00) | D (++) | (1.000) | NE | NE | AFAP (1) |
| p.Y179C | c.494A>G | 46.7 | (4.8) | 1.17 | A | (0.00) | D (++) | (1.000) | Deficient | Deficient | Common variant in FAP, AFAP |
| p.R182C | c.502G>A | 85.3 | (8.8) | 0.67 | A | (0.00) | D (++) | (1.000) | Deficient | NE | MP (1), sporadic CRC (1) |
| p.R182H | c.503G>A | 63.0 | (6.5) | 1.31 | A | (0.00) | D (++) | (1.000) | NE | NE | AFAP (4) |
| p.R185Q | c.512C>T | 50.7 | (5.2) | 1.10 | T | (0.13) | D (++) | (0.977) | NE | NE | AFAP (1) |
| p.G189E | c.524C>T | 24.5 | (2.5) | 0.77 | A | (0.00) | D (++) | (1.000) | NE | NE | AFAP (1) |
| p.I223V | c.625A>G | 11.0 | (1.1) | 0.71 | T | (0.06) | D (++) | (0.958) | Partially active | NE | FAP (1), MP (1) |
| p.A227V | c.638C>T | 17.5 | (1.8) | 1.08 | A | (0.01) | D (++) | (0.999) | NE | NE | HC (1) |
| p.V234M | c.658G>A | 22.3 | (2.3) | 0.73 | A | (0.01) | D (+) | (0.815) | NE | NE | Familial CRC (1) |
| p.R241W | c.679C>T | 40.7 | (4.2) | 0.76 | A | (0.00) | D (++) | (1.000) | Deficient | Deficient | Sporadic CRC or HC (1) |
| p.R245C | c.691C>T | 40.7 | (4.2) | 0.91 | A | (0.00) | D (++) | (1.000) | NE | NE | MP (2) |
| p.R245H | c.692G>A | 69.5 | (7.0) | 0.58 | A | (0.00) | D (++) | (1.000) | Deficient | NE | FAP (5), AFAP (1) |
| p.V246F | c.694G>T | 11.7 | (1.2) | 1.19 | A | (0.02) | B | (0.143) | Deficient | Slightly deficient | FAP (3), sporadic CRC or HC (1) |
| p.R274W | c.778C>T | 55.0 | (5.7) | 0.55 | A | (0.00) | D (++) | (0.999) | NE | NE | FAP (1), AFAP (1) |
| p.G286E | c.815G>A | 5.00 | (0.5) | 1.24 | A | (0.00) | D (++) | (1.000) | Deficient | NE | FAP (1), MP (1) |
| p.C290W | c.828T>G | 51.0 | (5.3) | 0.87 | A | (0.00) | D (++) | (1.000) | NE | NE | Sporadic LC (1), HC (1) |
| p.P295L | c.842C>T | 55.5 | (5.7) | 0.42 | A | (0.00) | D (++) | (1.000) | Deficient | NE | FAP or AFAP (7), MP (3) |
| p.R309C | c.883C>T | 27.7 | (2.9) | 0.52 | T | (0.11) | B | (0.012) | Proficient | NE | AFAP (2), MP (2) |
| p.Q338H | c.972G>C | 6.67 | (0.7) | 0.83 | T | (0.14) | B | (0.343) | Proficient | Proficient | FAP, sporadic CRC, HC (allele frequency = 30%) |
| p.Q338R | c.971T>C | 12.5 | (1.3) | 0.93 | T | (0.52) | B | (0.039) | NE | NE | HNPCC (-like) family (1) |
| p.P380T | c.1096G>T | 18.0 | (1.9) | 0.64 | T | (0.59) | B | (0.004) | NE | NE | FAP (1) |
| p.L388P | c.1121A>G | 69.5 | (7.2) | 0.40 | A | (0.00) | D (++) | (1.000) | Deficient | NE | AFAP (1), MP (2) |
| p.G396D | c.1145G>A | 16.3 | (1.7) | 1.30 | A | (0.00) | D (++) | (1.000) | Partially active | Deficient | Common variant in FAP, AFAP |
| p.P405L | c.1172G>A | 101 | (10.4) | 0.96 | A | (0.00) | D (++) | (1.000) | Deficient | Deficient | FAP (9), AFAP (10), MP (5), CRC (4) |
| p.P405S | c.1172G>A | 32.3 | (3.3) | 0.71 | A | (0.00) | D (++) | (0.999) | NE | NE | GC (1) |
| p.Q414R | c.1199A>G | 12.0 | (1.2) | 1.31 | T | (0.27) | B | (0.000) | NE | NE | GC (1) |
| p.L420M | c.1216G>T | 7.00 | (0.7) | 0.91 | T | (0.14) | B | (0.180) | NE | NE | FAP (1), MP (1), HNPCC (-like) family (1) |
| p.R426C | c.1234C>T | 10.7 | (1.1) | 0.72 | T | (0.05) | B | (0.000) | NE | NE | FAP (1), FAP or AFAP (1), HC (1) |
| p.R437P | c.1268C>G | 21.5 | (2.2) | 0.57 | T | (0.08) | B | (0.445) | NE | NE | Sporadic CRC (1), sporadic CRC or HC (1) |
| p.R437Q | c.1268C>T | 10.0 | (1.0) | 1.51 | T | (1.00) | B | (0.001) | NE | NE | Sporadic CRC (1), sporadic CRC or HC (1) |
| p.A473D | c.1378C>A | 54.0 | (5.6) | 0.93 | T | (0.20) | D (++) | (0.863) | Deficient | NE | FAP (2) |
| p.A473T | c.1375G>A | 12.0 | (1.2) | 0.56 | T | (0.44) | B | (0.139) | NE | NE | MP (1) |
| p.A489T | c.1423G>A | 32.0 | (3.3) | 1.07 | A | (0.01) | D (++) | (0.973) | NE | NE | AFAP (1) |
| p.V493F | c.1435G>T | 37.0 | (3.8) | 1.26 | A | (0.00) | D (+) | (0.73) | NE | NE | FAP or AFAP (1), sporadic CRC (2), HC (1) |
| p.G503E | c.1466G>A | 18.5 | (1.9) | 0.67 | T | (0.08) | B | (0.404) | NE | NE | HC (dbSNP) |
| p.S515F | c.1502C>T | 9.67 | (1.0) | 1.32 | A | (0.05) | B | (0.003) | Proficient | NE | FAP, sporadic CRC, HC (allele frequency = 3%) |
| p.P516L | c.1505C>T | 10.0 | (1.0) | 1.20 | T | (0.47) | B | (0.017) | NE | NE | HC (1) |
| p.L529M | c.1543C>A | 5.50 | (0.6) | 1.10 | T | (0.11) | D (++) | (0.915) | NE | NE | HC (dbSNP) |
| p.R534Q | c.1559G>A | 6.00 | (0.6) | 1.15 | T | (0.33) | B | (0.032) | NE | NE | Sporadic CRC (1), LC or HC (1) |
| p.E480del | c.1395_1397delGGA | 40.5 | (4.2) | 0.84 | NA | NA | Deficient | NE | FAP (6), AFAP, sporadic CRC | ||
a
The reference sequence for the MUTYH gene-encoding type 2 protein is accession number NM_001048171.1. For cDNA numbering: nucleotide numbering uses +1 as the A of the ATG translation initiation codon in the reference sequence, with the initiation codon as codon 1.
b
Indicated numbers are rifampicin-resistant rate (/108) in MutY-deficient E. coli.
c
Indicated numbers are band intensity of western blotting normalized by actin control.
d
Prediction by SIFT algorism.
e
Prediction by Polyphen-2 algorism.
T, tolerated; A, affect protein function; NA, not analyzed; NE, not examined; FAP, familial adenomatous polyposis; B, benign, D(+), possibly damaging, D(++), probably damaging; AFAP, attenuated FAP; MP, multiple polyps; CRC, colorectal cancer; GC, gastric cancer; LC, lung cancer; HCC, hepatocellular carcinoma; HC, healthy control; dbSNP, data base of single-nucleotide polymorphism.