Table 3.
Variants of unclassified significance and in silico prediction in South American Lynch syndrome families
| Country | Gene | Nucleotide | Consequence | Exon |
Polyphen |
SIFT |
MAP_MMR |
P-mut |
PON-MMR |
|||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Score | Classification | Score | Classification | Score | Classification | Score | Classification | Score | Classification | |||||
| Uruguay |
MLH1 |
c.289 T > G |
p.Y97D |
3 |
0.999 |
Probably damaging |
0 |
Damaging |
10.51 |
Damaging |
0.7266 |
Pathological |
0.83 |
Pathogenic |
| Argentina |
MLH1 |
c.336 T > A |
p.H112Q |
4 |
1 |
Probably damaging |
0.03 |
Damaging |
2.430 |
Neutral |
NA |
NA |
0.61 |
VUS |
| Colombia |
MLH1 |
c.421C > G |
p.P141A |
5 |
0.329 |
Benign |
0.05 |
Damaging |
3.15 |
Borderline deleterious |
0.4928 |
Neutral |
0.48 |
VUS |
| Chile |
MLH1 |
c.794G > C |
p.R265P |
10 |
1 |
Probably damaging |
0 |
Damaging |
38.09 |
Damaging |
0.7623 |
Pathological |
0.83 |
Pathogenic |
| Brazil |
MLH1 |
c.1013A > G |
p.N338S |
11 |
0.506 |
Possibly Damaging |
0.05 |
Damaging |
2.78 |
Neutral |
0.2551 |
Neutral |
0.38 |
VUS |
| Colombia |
MLH1 |
c.1558 + 14G > A |
|
13 |
NA |
NA |
NA |
NA |
NA |
NA |
NA |
NA |
NA |
NA |
| Argentina |
MLH1 |
c.1724G > A |
p.R575K |
15 |
0.001 |
Benign |
0.40 |
Tolerated |
1.490 |
Neutral |
NA |
NA |
0.15 |
Neutral |
| Brazil |
MLH1 |
c.1853A > C |
p.K618T |
16 |
0.997 |
Probably damaging |
0.02 |
Damaging |
5.11 |
Damaging |
0.7802 |
Pathological |
0.67 |
VUS |
| Colombia |
MLH1 |
c.1918C > T |
p.P640T |
17 |
1 |
Probably damaging |
0 |
Damaging |
17.77 |
Damaging |
0.6534 |
Pathological |
0.83 |
Pathogenic |
| Brazil |
MLH1 |
c.2252_2253dupAA |
p.V752Kfs*26 |
19 |
NA |
NA |
NA |
NA |
NA |
NA |
NA |
NA |
NA |
NA |
| Brazil | MSH2 | c.2187G > T | p.M729I | 13 | 2.293 | Probably damaging | 0 | Damaging | 21.99 | Damaging | 0.1988 | Neutral | 0.71 | VUS |
MLH1 (MIM#120436), MSH2 (MIM#609309), NA: not applicable, VUS: variants of unclassified significance, If SIFT score <0.05 then the aminoacid (AA) substitution is predicted to affect protein function, if PolyPhen score >0.5 then the AA substitution is predicted to affect protein function, if MAPP-MMR score >4.55 then the AA substitution is predicted to affect protein function, If P-mut score > 0.5, the AA substitution is classified as pathological, if PON-MMR score >0.7615, the AA substitution is classified as pathogenic.