Table 2.
Novel MSH6 variants identified in this study.
| Family | ID | Mutation | Protein Effect | In Silico Analysis | Frequency in Healthy Controls | Phenotype MSI | Segregation Analysis in Affected Subjects | ||
|---|---|---|---|---|---|---|---|---|---|
| PolyPhen (Score) | SIFT (Score) | HSF | |||||||
| 31 | 808 | Ex2 c.261 -46 A>G | ND | ND | +3’ss; +BP |
0/100 | AM−; ND |
ND | |
| 33 | 409 | Ex2 c.457+33_+34insGTGT | ND | ND | +3’ss × 2; +ESE |
0/100 | AM−; MSI-L |
3/3 | |
| 10 | 9529 | Ex2 c.457 +50 T>A | ND | ND | +3’ss | 0/100 | AM+; MSI-H |
ND | |
| 34 | 410 | Ex4 c.990 A>T | p. = (Ser) | ND | ND | −SRp55; −EIE |
0/100 | AM+; MSI-H |
ND |
| 26 | 210 | Ex4 c.1395 A>T | p. = (Ala) | ND | ND | −SRp55; +ESS × 2; +ESR |
2/100 | AM+; MSI-H |
1/2 |
| 102 | 1454 | Ex4 c.2049_2050insAGT | p.Ala683_Leu684insSer | ND | ND | +3’ss × 2; +BP |
0/100 | AM−; MSI-H |
2/2 |
| 26 | 210 | Ex4 c.2941 A>G | p.Ile981Val | Benign (0.181) | Tolerated (1) | +3’ss; +ESE × 2; −EIE × 2; +ESS; +9G8; +ESR |
0/100 | AM+; MSI-H |
2/2 |
| 21 | 105 | Ex5 c.3296_97delTT | p.Ile1099delinsAsnfs*8 | ND | ND | ND | 0/100 | AM+; MSI-H |
1/4 |
| 18 | 013 | Ex7 c.3639 T>A | p.Asp1214Glu | Probably damaging (1) | Damaging (0) | +3’ss × 2; +ESE × 5; +EIE; +Tra2β; −IIE × 3; +ESR |
0/100 | AM+; ND |
ND |
ID: identification number patient; AM: Amsterdam Criteria; MSI-L/H: low/high microsatellite instability; ND: not done; motifs identified (+) or broken (−) by HSF (Human Splicing Finder): 3’ss, acceptor cryptic splice site; BP: branch point; ESE: exonic splicing enhancer; EIE: exon identity element; ESS: exonic splicing silencer; ESR: exonic splicing regulatory; IIE: intron identity element; SRp55, 9G8 and Tra2β: splicing enhancer proteins; SIFT: Sorting Intolerant From Tolerant. When multiple adjacent sites were predicted, the number of sites is indicated: ×2 means that two adjacent sites were modified by the mutation.