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Table 5 In silico analysis of the MLH1, MSH2 and MSH6 variants

From: Prevalence and spectrum of MLH1, MSH2, and MSH6 pathogenic germline variants in Pakistani colorectal cancer patients

Gene Coding variants In silico predictions  
AlignGVGD PolyPhen2 SIFT MutPred SNPs&GO PhD-SNP SNAP Consensusa
MLH1 c.1913G > T (G638 L) C15 Probably damaging Deleterious Benign Neutral Neutral Neutral B (3/7)
c.1919C > T (P640L) C65 Probably damaging Deleterious Deleterious Disease Disease Disease LP (7/7)
MSH2 c.944G > T (G315 V) C0 Benign Deleterious Benign Neutral Neutral Neutral B (1/7)
c.1074G > C (E358D) C35 Possibly damaging Tolerated Benign Neutral Disease Neutral B (3/7)
c.2120G > A (C707Y) C0 Probably damaging Damaging Benign Disease Disease Disease LP (5/7)
MSH6 c.3151G > A (V1051I) C0 Benign Tolerated Benign Neutral Neutral Neutral B (0/7)
Noncoding variants Splice-site predictions  
SpliceSiteFinder-like MaxEntScan NNSPLICE GeneSplicer HumanSpliceSite Finder Consensusb, c
MLH1 c.116 + 3A > T D (75.7 → 0) D (8.6 → 2.4) D (0.9 → 0) D (5.5 → 0) NE LP (4/5)
c.116 + 4C > A NE NE NE NE NE B (0/5)
c.1990-26 T > C NE NE NE NE NE B (0/5)
MSH2 c.2006-36_2006-33dup NE NE NE NE NE B (0/5)
MSH6 c.457 + 50 T > A NE NE NE NE NE B (0/5)
c.3556 + 170del NE NE NE NE NE B (0/5)
c.4001 + 26A > G NE D (0 → 2.9) NE NE D (0 → 71.4) B (2/5)
  1. B Benign, D Donor, LP Likely pathogenic, NE No effect
  2. aThe variant is considered as likely pathogenic by five of the seven protein function prediction algorithms
  3. b The variant is considered as likely pathogenic by four of the five splice-site prediction algorithms
  4. c > 20% change in score (i.e., a wild-type splice-site score decreases and/or a cryptic splice-site score increases) is considered as significant
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Hereditary Cancer in Clinical Practice

ISSN: 1897-4287