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Table 2 MLH1, MSH2 and MSH6 germline variants in Pakistani study participants

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

Gene Location Nucleotide changea Amino acid change Variant type SNP linkb Classification Prevalence N (%) Previously described
HNPCC/suspected-HNPCC cases (N = 29) non-HNPCC cases (N = 183) Healthy controls (N = 100)
MLH1
  Exon 1 c.67delG p.E23Kfs*13 Frameshift P 1 (3.4) 0 Yes
Exon 12 c.1358dup p.T455Dfs*24 Frameshift P 2 (6.9) 0 Yes
Exon 15 c.1672G > T p.E558* Nonsense P 1 (3.4) 0 Yes
Exon 18 c.2041G > A p.A681T Missense rs63750217 P 1 (3.4) 1 (0.6) Yes
Intron 1 c.116 + 3A > T Intronic LPc 0 1 (0.6) 0 No
Exon 8 c.655A > G p.I219V Missense rs1799977 B 2 (6.9) Yes
Exon 17 c.1913G > T p.G638 L Missense Bc 0 2 (1.1) No
Exon 17 c.1919C > T p.P640L Missense LPc 6 (20.7) 2 (1.1) Yes
Exon 17 c.1959G > T p.L653 L Silent rs1800146 B 0 1 (0.6) Yes
Intron 1 c.116 + 4C > A Intronic Bc 0 1 (0.6) No
Intron 13 c.1558 + 14G > A Intronic rs41562513 B 1 (3.4) Yes
Intron 14 c.1668-19A > G Intronic rs9876116 B 8 (27.6) 55 (30.1) Yes
Intron 17 c.1990-26 T > C Intronic Bc 0 2 (1.1) No
MSH2
  Exon 12 c.1861C > T p.R621* Nonsense P 1 (3.4) 0 Yes
Exon 16 c.2656G > T p.E886* Nonsense P 1 (3.4) 0 0 Yesd
Intron 5 c.943-1G > C p.G315Ifs*12 Splice site LP 3 (10.4) 0 Yes
Exon 13 c.2120G > A p.C707Y Missense LPc 1 (3.4) 2 (1.1) 2 (2) No
Exon 6 c.984C > T p.A328A Silent LB 2 (6.9) 0 Yes
Exon 6 c.944G > T p.G315 V Missense rs202026056 Bc 0 1 (0.6) Yes
Exon 6 c.965G > A p.G322D Missense rs4987188 B 1 (3.4) 10 (5.5) Yes
Exon 6 c.1074G > C p.E358D Missense Bc 0 1 (0.6) No
Exon 12 c.1786_1788delAAT p.N596del In-frame deletion P 0 1 (0.6) Yes
Exon 13 c.2205C > T p.I735I Silent rs533553381 B 0 5 (2.7) Yes
Intron 1 c.211 + 9C > G Intronic rs2303426 LB 12 (41.4) Yes
Intron 9 c.1511-9A > T Intronic rs12998837 B 2 (6.9) Yes
Intron 10 c.1661 + 12G > A Intronic rs3732183 B 13 (44.8) Yes
Intron 12 c.2006-6 T > C Intronic rs2303428 B 1 (3.4) 37 (20.2) Yes
Intron 12 c.2006-36_2006-33dup Intronic rs587779126 Bc 0 5 (2.7) Yes
MSH6
  Exon 3 c.540 T > C p.D180D Silent rs1800935 B 1 (3.4) Yes
Exon 4A c.642C > T p.Y214Y Silent rs1800937 B 1 (3.4) Yes
Exon 4G c.3151G > A p.V1051I Missense Bc 1 (3.4) Yes
Exon 5 c.3306 T > A p.T1102 T Silent rs2020910 B 1 (3.4) Yes
Intron 2 c.457 + 13A > G Intronic rs1800933 LB 1 (3.4) Yes
Intron 2 c.457 + 50 T > A Intronic Bc 3 (10.3) No
Intron 2 c.457 + 52 T > A Intronic rs3136282 B 23 (79.3) Yes
Intron 4 c.3172 + 20 T > C Intronic rs3136335 B 2 (6.9) Yes
Intron 5 c.3438 + 14A > T Intronic rs2020911 B 15 (51.7) Yes
Intron 6 c.3556 + 146G > A Intronic rs7562048 B 1 (3.4) Yes
Intron 6 c.3556 + 160 T > C Intronic rs56320267 B 1 (3.4) Yes
Intron 6 c.3556 + 170delT Intronic Bc 1 (3.4) No
Intron 6 c.3557–4 dupT Intronic B 1 (3.4) Yes
Intron 6 c.3557-40 T > A Intronic rs189436849 LB 1 (3.4) Yes
Intron 9 c.4001 + 26A > G Intronic Bc 1 (3.4) No
  1. B Benign, LB Likely benign, LP Likely pathogenic. P Pathogenic
  2. aNomenclature follows Human Genome Variation Society (HGVS) (http://www.hgvs.org). Numbering start at the first A of the first coding ATG of NCBI reference sequences
  3. NM_000249.3(MLH1), NM_000251.2 (MSH2) and NM_000179.2 (MSH6)
  4. bLink to NCBI SNP database (http://ncbi.nlm.nih.gov/projects/SNP/)
  5. cClassification of the alterations is based on in silico analyses
  6. dPreviously reported in Pakistani population [28]