MSH2 (DNA mismatch repair protein Msh2) variants and mutations
MSH2 (also known as DNA mismatch repair protein Msh2) is a human protein-coding gene encoding a DNA mismatch repair protein. The protein forms mismatch-recognition complexes with MSH6 or MSH3 that detect base mismatches and insertion-deletion loops in DNA. This first step of mismatch repair helps preserve genome integrity, and inherited MSH2 variants are associated with Lynch syndrome. This analysis covers 4,452 MSH2 variants and mutations. Of these, 97% have computational variant effect predictions. Disease context includes Lynch syndrome, Constitutional mismatch repair deficiency syndrome, and Muir-Torre syndrome. Example MSH2 variants include M1L, M1R, and M1T.
Variant analysis overview
- Gene: MSH2
- Protein: DNA mismatch repair protein Msh2
- UniProt accession: P43246
- Organism: Homo sapiens
- Variants analyzed: 4452
- Variant scope: all variants
- Completed: 2026-05-29
Variant and mutation evidence
- Variant composition: 4,335 unspecified-consequence records; 73 synonymous variants; 2 in-frame deletions; 4 frameshift variants; 30 missense variants; 2 stop-gained variants; 2 splice-region variants; 1 splice acceptor variant; 1 protein altering variant; 2 substitution
- Prediction scores: 4,322 variants have prediction scores (97% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Lynch syndrome, Constitutional mismatch repair deficiency syndrome, Muir-Torre syndrome, mismatch repair cancer syndrome 1, colon carcinoma, hereditary nonpolyposis colon cancer, colonic neoplasm, malignant colon neoplasm, endometrial carcinoma, uterine corpus cancer, colorectal cancer, neoplasm.
Protein structure and variant hotspots
- Protein features: 1 binding sites; 8 post-translational modification sites.
- PTM context: 27 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, PharmGKB, MaveDB, LitVar.
Notable MSH2 variants
Examples include M1L, M1R, M1T, M1V, A2E, A2G, A2P, A2S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1L (p.Met1Leu), rs267607911, ClinGen CA019685, ClinVar RCV000076334, ClinVar RCV000160588, ESM-1b 1.00, AlphaMissense 0.28, Benign, Hereditary cancer-predisposing syndrome
- M1R (p.Met1Arg), rs876658825, ClinGen CA10577911, ClinVar RCV000220736, ClinVar RCV001853531, ESM-1b 1.00, AlphaMissense 0.83, Uncertain significance, Muir-Torré syndrome; Mismatch repair cancer syndrome 2; Lynch syndrome 1
- M1T (p.Met1Thr), rs876658825, ClinGen CA346728373, ClinVar RCV001881872, ClinVar RCV002440979, ESM-1b 1.00, AlphaMissense 0.86, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- M1V (p.Met1Val), rs267607911, ClinGen CA019692, ClinVar RCV000076335, ClinVar RCV000165763, ESM-1b 1.00, AlphaMissense 0.21, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- A2E (p.Ala2Glu), rs587778521, ClinGen CA021542, cosmic curated COSV10508, ClinVar RCV000165871, REVEL 0.55, ESM-1b 1.00, Uncertain significance, in LYNCH1
- A2G (p.Ala2Gly), cosmic curated COSV51878, TOPMed rs587778521, gnomAD rs587778521, ESM-1b 1.00, AlphaMissense 0.47, Uncertain significance, in LYNCH1
- A2P (p.Ala2Pro), ExAC rs63750466, TOPMed rs63750466, gnomAD rs63750466, REVEL 0.69, ESM-1b 1.00, Likely benign, in LYNCH1
- A2S (p.Ala2Ser), ExAC rs63750466, TOPMed rs63750466, gnomAD rs63750466, REVEL 0.56, ESM-1b 0.24, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- A2T (p.Ala2Thr), rs63750466, ClinGen CA021232, ClinVar RCV000034558, ClinVar RCV000076617, REVEL 0.84, ESM-1b 1.00, Benign, in LYNCH1
- A2V (p.Ala2Val), rs587778521, ClinGen CA021548, cosmic curated COSV10585, ClinVar RCV000121557, REVEL 0.68, ESM-1b 1.00, Benign, in LYNCH1
- A2A (p.Ala2Ala), rs368270856, gnomAD 2-47403197-G-A, CADD 14.40
- V3A (p.Val3Ala), Ensembl rs1573422534, ESM-1b 0.00, AlphaMissense 0.54, Uncertain significance
- V3E (p.Val3Glu), Ensembl rs1573422534, REVEL 0.60, ESM-1b 0.19, Uncertain significance
- V3G (p.Val3Gly), rs1573422534, ClinGen CA346728410, ClinVar RCV003988390, Ensembl rs1573422534, REVEL 0.59, ESM-1b 0.53, Uncertain significance, not specified
- V3L (p.Val3Leu), rs1257347271, ClinGen CA346728406, ClinVar RCV000774955, ClinVar RCV000781996, REVEL 0.37, ESM-1b 0.00, Likely benign, Lynch syndrome
- V3M (p.Val3Met), rs1257347271, ClinGen CA346728404, ClinVar RCV000706952, ClinVar RCV000776681, REVEL 0.48, ESM-1b 0.60, Conflicting interpretations, Lynch syndrome; Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer
- V3V (p.Val3Val), rs2103866120, gnomAD 2-47403200-G-A, CADD 12.40
- Q4* (p.Gln4Ter), rs878853797, ClinGen CA346728415, cosmic curated COSV51878, ClinVar RCV000701344, AlphaMissense 0.24, MetaLR 0.79, Pathogenic
- Q4E (p.Gln4Glu), rs878853797, ClinGen CA346728414, ClinVar RCV004522919, TOPMed rs878853797, ESM-1b 0.00, AlphaMissense 0.24, Uncertain significance, Hereditary cancer-predisposing syndrome
- Q4H (p.Gln4His), rs878853800, ClinGen CA346728424, ClinVar RCV000758584, TOPMed rs878853800, REVEL 0.62, ESM-1b 1.00, Likely benign, Lynch syndrome
- Q4K (p.Gln4Lys), rs878853797, ClinGen CA10581987, ClinVar RCV000227770, ClinVar RCV000480195, REVEL 0.51, ESM-1b 0.00, Pathogenic
- Q4L (p.Gln4Leu), rs754562075, ClinGen CA027207, ClinVar RCV000219790, ClinVar RCV000235807, REVEL 0.72, ESM-1b 1.00, Likely benign
- Q4P (p.Gln4Pro), rs1553348689, ClinGen CA658655649, ClinVar RCV000570258, ClinVar RCV001858305, ESM-1b 1.00, AlphaMissense 0.21, Conflicting interpretations, not provided; Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis c
- Q4R (p.Gln4Arg), ExAC rs754562075, TOPMed rs754562075, gnomAD rs754562075, REVEL 0.63, ESM-1b 0.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- Q4Q (p.Gln4Gln), rs878853800, gnomAD 2-47403203-G-A, CADD 11.60
- P5A (p.Pro5Ala), rs1573422612, ClinGen CA346728427, ClinVar RCV001923634, ClinVar RCV005370039, REVEL 0.52, ESM-1b 1.00, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- P5L (p.Pro5Leu), rs56170584, ClinGen CA018467, ClinVar RCV000160589, ClinVar RCV000559215, REVEL 0.71, ESM-1b 1.00, Benign
- P5Q (p.Pro5Gln), rs56170584, ClinGen CA018457, ClinVar RCV000076178, ClinVar RCV000165088, REVEL 0.83, ESM-1b 1.00, Benign
- P5R (p.Pro5Arg), rs56170584, ClinGen CA346728432, cosmic curated COSV99028, ClinVar RCV000546654, REVEL 0.79, ESM-1b 1.00, Benign
- P5S (p.Pro5Ser), rs1573422612, ClinGen CA346728429, ClinVar RCV000804405, ClinVar RCV001011368, REVEL 0.59, ESM-1b 1.00, Uncertain significance, not provided; Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-pr
- P5T (p.Pro5Thr), rs1573422612, ClinGen CA346728430, ClinVar RCV002389234, Ensembl rs1573422612, REVEL 0.74, ESM-1b 1.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- P5P (p.Pro5Pro), rs758054171, gnomAD 2-47403206-G-T, CADD 8.86
- K6* (p.Lys6Ter), ExAC rs777351049, gnomAD rs777351049, Benign
- K6E (p.Lys6Glu), rs777351049, ClinGen CA030563, ClinVar RCV000538201, ClinVar RCV000562322, REVEL 0.52, ESM-1b 1.00, Benign
- K6M (p.Lys6Met), Ensembl rs1672230236, REVEL 0.60, ESM-1b 1.00, Uncertain significance
- K6N (p.Lys6Asn), rs146017810, ClinGen CA346728447, ClinVar RCV001947295, ClinVar RCV003164181, REVEL 0.47, ESM-1b 1.00, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- K6R (p.Lys6Arg), rs1672230236, ClinGen CA346728442, ClinVar RCV002407866, ClinVar RCV003097251, REVEL 0.52, ESM-1b 0.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- E7* (p.Glu7Ter), rs375561490, ClinGen CA346728451, ClinVar RCV001014004, ClinVar RCV004588466, CADD 43.00, Pathogenic
- E7A (p.Glu7Ala), rs530071578, ClinGen CA46666467, ClinVar RCV000580313, ClinVar RCV000698385, REVEL 0.38, ESM-1b 1.00, Uncertain significance
- E7D (p.Glu7Asp), Ensembl rs1060504423, REVEL 0.48, ESM-1b 1.00, Likely benign, Hereditary cancer-predisposing syndrome
- E7G (p.Glu7Gly), rs530071578, ClinGen CA16610839, ClinVar RCV000461641, ClinVar RCV000567075, REVEL 0.41, ESM-1b 1.00, Uncertain significance
- E7K (p.Glu7Lys), rs375561490, ClinGen CA46666445, ClinVar RCV001189020, ClinVar RCV001321132, REVEL 0.43, ESM-1b 1.00, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- E7Q (p.Glu7Gln), rs375561490, ClinGen CA346728450, ClinVar RCV000561430, ClinVar RCV002528990, REVEL 0.38, ESM-1b 0.00, Pathogenic
- E7V (p.Glu7Val), rs530071578, ClinGen CA346728457, ClinVar RCV001307185, 1000Genomes rs530071578, REVEL 0.55, ESM-1b 1.00, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- T8A (p.Thr8Ala), rs876660332, ClinGen CA346728464, cosmic curated COSV51883, ClinVar RCV003759329, ESM-1b 1.00, AlphaMissense 0.07, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Lynch syndrome
- T8K (p.Thr8Lys), rs17217716, ClinGen CA346728466, ClinVar RCV001038223, ClinVar RCV002454276, REVEL 0.41, ESM-1b 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- T8M (p.Thr8Met), rs17217716, ClinGen CA020551, cosmic curated COSV51875, ClinVar RCV000076466, REVEL 0.57, ESM-1b 1.00, Benign
- T8P (p.Thr8Pro), TOPMed rs876660332, ESM-1b 1.00, AlphaMissense 0.11, Uncertain significance, Hereditary cancer-predisposing syndrome
- T8R (p.Thr8Arg), rs17217716, ClinGen CA16610971, ClinVar RCV000460417, ClinVar RCV000564460, REVEL 0.52, ESM-1b 1.00, Benign
- T8S (p.Thr8Ser), rs876660332, ClinGen CA10577912, ClinVar RCV000218068, ClinVar RCV002515713, ESM-1b 1.00, AlphaMissense 0.07, Likely benign
- p.Thr8 Glu12del, rs1184949521, gnomAD 2-47403208-AGGAGA, CADD 22.50
- T8T (p.Thr8Thr), rs1166025357, gnomAD 2-47403215-G-A, CADD 13.50
- L9M (p.Leu9Met), rs1672231681, ClinGen CA346728467, ClinVar RCV001178769, Ensembl rs1672231681, REVEL 0.53, ESM-1b 1.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- L9P (p.Leu9Pro), rs1573422744, ClinGen CA346728473, ClinVar RCV002428998, ClinVar RCV004999762, REVEL 0.86, ESM-1b 1.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- L9Q (p.Leu9Gln), Ensembl rs1573422744, ESM-1b 1.00, AlphaMissense 0.29, Likely benign
- L9R (p.Leu9Arg), rs1573422744, ClinGen CA346728475, ClinVar RCV000817588, ClinVar RCV003307535, ESM-1b 1.00, AlphaMissense 0.31, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- L9V (p.Leu9Val), rs1672231681, ClinGen CA346728469, ClinVar RCV001323925, ClinVar RCV004570786, ESM-1b 1.00, AlphaMissense 0.15, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- L9L (p.Leu9Leu), gnomAD 2-47403218-G-T, CADD 13.50
- Q10* (p.Gln10Ter), rs63751099, ClinGen CA020976, ClinVar RCV000076557, ClinVar RCV000804938, CADD 43.00, Pathogenic
- Q10E (p.Gln10Glu), Ensembl rs63751099, ESM-1b 0.00, AlphaMissense 0.15, Likely benign, Hereditary cancer-predisposing syndrome
- Q10H (p.Gln10His), rs786203228, gnomAD rs786203228, ClinGen CA021004, ClinVar RCV000166449, REVEL 0.49, ESM-1b 0.00, Benign
- Q10K (p.Gln10Lys), rs63751099, ClinGen CA020973, ClinVar RCV000034557, ClinVar RCV002433492, REVEL 0.45, ESM-1b 0.00, Pathogenic
- Q10L (p.Gln10Leu), Ensembl rs1573422771, ESM-1b 0.40, AlphaMissense 0.12, Uncertain significance
- Q10P (p.Gln10Pro), rs1573422771, ClinGen CA346728481, ClinVar RCV001017894, Ensembl rs1573422771, ESM-1b 0.00, AlphaMissense 0.07, Conflicting interpretations, not provided; Hereditary nonpolyposis colorectal neoplasms
- Q10R (p.Gln10Arg), Ensembl rs1573422771, REVEL 0.48, ESM-1b 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- Q10Q (p.Gln10Gln), rs786203228, gnomAD 2-47403221-G-A, CADD 13.80
- L11* (p.Leu11Ter), rs2103868483, ClinGen CA346728494, ClinVar RCV003450107, Ensembl rs2103868483, CADD 44.00, Pathogenic
- L11F (p.Leu11Phe), Ensembl rs2103868565, ESM-1b 1.00, AlphaMissense 0.18, Likely benign
- L11M (p.Leu11Met), Ensembl rs2103868361, REVEL 0.31, ESM-1b 0.00, Uncertain significance
- L11S (p.Leu11Ser), rs2103868483, ClinGen CA346728496, ClinVar RCV002000962, Ensembl rs2103868483, REVEL 0.73, ESM-1b 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- L11V (p.Leu11Val), rs2103868361, ClinGen CA346728491, ClinVar RCV002322972, NCI-TCGA TCGA novel, ESM-1b 0.61, AlphaMissense 0.11, Uncertain significance, Hereditary cancer-predisposing syndrome
- L11W (p.Leu11Trp), Ensembl rs2103868483, ESM-1b 1.00, AlphaMissense 0.35, Pathogenic
- L11L (p.Leu11Leu), gnomAD 2-47403222-T-C, CADD 13.70
- E12* (p.Glu12Ter), rs917968387, ClinGen CA346728508, ClinVar RCV001295935, ClinVar RCV003449847, AlphaMissense 0.49, MetaLR 0.60, Pathogenic
- E12A (p.Glu12Ala), rs1553348722, ClinGen CA346728510, ClinVar RCV000530789, ClinVar RCV003362822, ESM-1b 1.00, AlphaMissense 0.48, Likely benign
- E12D (p.Glu12Asp), rs1558451303, ClinGen CA346728515, ClinVar RCV000690765, ClinVar RCV003323690, REVEL 0.37, ESM-1b 0.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Lynch syndrome; Hereditary cancer
- E12K (p.Glu12Lys), Ensembl rs917968387, ESM-1b 0.65, AlphaMissense 0.88, Pathogenic
- E12Q (p.Glu12Gln), rs917968387, ClinGen CA46666533, ClinVar RCV000574098, ClinVar RCV000818613, ESM-1b 1.00, AlphaMissense 0.49, Pathogenic
- E12G (p.Glu12Gly), rs63750614, gnomAD 2-47403223-T-TG, CADD 33.00
- E12E (p.Glu12Glu), rs1558451303, gnomAD 2-47403227-G-A, CADD 12.80
- S13C (p.Ser13Cys), Ensembl rs2103868921, ESM-1b 1.00, AlphaMissense 0.20, Likely benign, not specified
- S13G (p.Ser13Gly), Ensembl rs2103868921, REVEL 0.41, ESM-1b 0.00, Uncertain significance, in CRC
- S13I (p.Ser13Ile), rs63749907, UniProt VAR 043736, TOPMed rs63749907, gnomAD rs63749907, REVEL 0.55, ESM-1b 1.00, Benign, in CRC
- S13N (p.Ser13Asn), rs63749907, ClinGen CA10584201, ClinVar RCV000235367, ClinVar RCV000572196, REVEL 0.30, ESM-1b 0.00, Benign, in CRC
- S13R (p.Ser13Arg), rs1060502015, ClinGen CA16610974, ClinVar RCV000471952, ClinVar RCV000574312, REVEL 0.60, ESM-1b 0.17, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- S13T (p.Ser13Thr), gnomAD 2-47403229-G-C, REVEL 0.33, ESM-1b 0.00
- S13S (p.Ser13Ser), rs1060502015, gnomAD 2-47403230-C-T, CADD 15.50
- A14G (p.Ala14Gly), Ensembl rs1672233353, REVEL 0.34, ESM-1b 0.00
- A14T (p.Ala14Thr), rs876658277, ClinGen CA10577913, ClinVar RCV000216179, ClinVar RCV000558623, REVEL 0.29, ESM-1b 0.00, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- A14V (p.Ala14Val), Ensembl rs1672233353, REVEL 0.33, ESM-1b 0.47, Likely benign, Hereditary cancer-predisposing syndrome
- A14S (p.Ala14Ser), gnomAD 2-47403231-G-T, REVEL 0.32, ESM-1b 0.00
- A14A (p.Ala14Ala), rs374396150, gnomAD 2-47403233-G-T, CADD 14.50
- A15G (p.Ala15Gly), ExAC rs776671839, gnomAD rs776671839, REVEL 0.52, ESM-1b 0.00, Uncertain significance
- A15P (p.Ala15Pro), TOPMed rs1183892581, gnomAD rs1183892581, REVEL 0.69, ESM-1b 1.00, Likely benign, Hereditary cancer-predisposing syndrome
- A15T (p.Ala15Thr), rs1183892581, ClinGen CA346728542, ClinVar RCV000630170, ClinVar RCV001764503, REVEL 0.45, ESM-1b 0.41, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Lynch syndrome 1
- A15V (p.Ala15Val), rs776671839, ClinGen CA346728545, ClinVar RCV001190993, ClinVar RCV003770150, REVEL 0.54, ESM-1b 0.48, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- A15S (p.Ala15Ser), gnomAD 2-47403234-G-T, REVEL 0.35, ESM-1b 0.00
- A15A (p.Ala15Ala), rs876659170, gnomAD 2-47403236-C-G, CADD 14.20
- E16A (p.Glu16Ala), rs745771647, ClinGen CA038939, cosmic curated COSV51884, ClinVar RCV000484013, REVEL 0.82, ESM-1b 1.00, Likely benign
- E16D (p.Glu16Asp), rs1060502036, ClinGen CA16610768, ClinVar RCV000469251, ClinVar RCV000581112, REVEL 0.69, ESM-1b 1.00, Likely benign
- E16G (p.Glu16Gly), ExAC rs745771647, gnomAD rs745771647, ESM-1b 1.00, AlphaMissense 0.48, Likely benign
- E16V (p.Glu16Val), ExAC rs745771647, gnomAD rs745771647, REVEL 0.90, ESM-1b 1.00, Likely benign
- E16* (p.Glu16Ter), gnomAD 2-47403237-G-T, CADD 44.00
- E16K (p.Glu16Lys), gnomAD 2-47403237-G-A, REVEL 0.88, ESM-1b 1.00
- V17A (p.Val17Ala), cosmic curated COSV51880, ExAC rs769731040, gnomAD rs769731040, ESM-1b 0.00, AlphaMissense 0.06, Uncertain significance, in gastric cancer
- V17D (p.Val17Asp), ExAC rs769731040, gnomAD rs769731040, REVEL 0.46, ESM-1b 1.00, Uncertain significance, in gastric cancer
- V17F (p.Val17Phe), rs63750966, ClinGen CA021228, ClinVar RCV000985812, ClinVar RCV001212396, REVEL 0.33, ESM-1b 1.00, Likely benign, in gastric cancer
- V17G (p.Val17Gly), ExAC rs769731040, gnomAD rs769731040, REVEL 0.43, ESM-1b 0.74, Uncertain significance, in gastric cancer
- V17I (p.Val17Ile), rs63750966, ClinGen CA346728561, cosmic curated COSV51883, ClinVar RCV000584099, REVEL 0.27, ESM-1b 0.00, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Lynch syndrome 1; Hereditary nonpolypos
- V17L (p.Val17Leu), rs63750966, ClinGen CA346728564, ClinVar RCV000629710, ClinVar RCV003162789, REVEL 0.29, ESM-1b 0.00, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- V17V (p.Val17Val), rs397515879, gnomAD 2-47403242-C-T, CADD 12.90
- G18A (p.Gly18Ala), rs1200418561, ClinGen CA346728580, ClinVar RCV003350728, gnomAD rs1200418561, ESM-1b 1.00, AlphaMissense 0.22, Likely benign, Hereditary cancer-predisposing syndrome
- G18D (p.Gly18Asp), rs1200418561, ClinGen CA346728579, ClinVar RCV000758585, gnomAD rs1200418561, REVEL 0.79, ESM-1b 1.00, Uncertain significance, Lynch syndrome
- G18C (p.Gly18Cys), gnomAD 2-47403243-G-T, REVEL 0.88, ESM-1b 1.00
- G18V (p.Gly18Val), gnomAD 2-47403244-G-T, REVEL 0.83, ESM-1b 1.00
- G18G (p.Gly18Gly), rs63750777, gnomAD 2-47403245-C-T, CADD 15.20
- F19C (p.Phe19Cys), TOPMed rs1320061495, ESM-1b 1.00, AlphaMissense 0.98, Likely benign
- F19I (p.Phe19Ile), 1000Genomes rs141711342, ESP rs141711342, ExAC rs141711342, TOPMed rs141711342, ESM-1b 1.00, AlphaMissense 0.93, Benign
- F19L (p.Phe19Leu), rs141711342, ClinGen CA021396, ClinVar RCV000160635, ClinVar RCV000409531, REVEL 0.93, ESM-1b 1.00, Benign, Lynch syndrome 1
- F19S (p.Phe19Ser), rs1320061495, ClinGen CA346728591, cosmic curated COSV51884, ClinVar RCV000805682, ESM-1b 1.00, AlphaMissense 0.99, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- F19V (p.Phe19Val), rs141711342, ClinGen CA16617545, ClinVar RCV000486701, ClinVar RCV000695062, ESM-1b 1.00, AlphaMissense 0.99, Likely benign, Hereditary cancer-predisposing syndrome
- F19F (p.Phe19Phe), rs764466720, gnomAD 2-47403248-C-T, CADD 14.60
- V20A (p.Val20Ala), rs2103870459, ClinGen CA346728609, ClinVar RCV003350721, Ensembl rs2103870459, ESM-1b 1.00, AlphaMissense 0.39, Uncertain significance, Hereditary cancer-predisposing syndrome
- V20E (p.Val20Glu), Ensembl rs2103870459, ESM-1b 1.00, AlphaMissense 0.81, Uncertain significance
- V20G (p.Val20Gly), Ensembl rs2103870459, REVEL 0.88, ESM-1b 1.00, Uncertain significance
- V20L (p.Val20Leu), rs1198168331, ClinGen CA346728605, ClinVar RCV001024669, ClinVar RCV005093249, REVEL 0.30, ESM-1b 0.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- V20M (p.Val20Met), rs1198168331, ClinGen CA346728601, ClinVar RCV000580093, ClinVar RCV001359880, REVEL 0.58, ESM-1b 1.00, Uncertain significance
- V20V (p.Val20Val), rs368874228, gnomAD 2-47403251-G-A, CADD 13.90
- R21C (p.Arg21Cys), rs774708147, ClinGen CA346728615, ClinVar RCV000561569, ExAC rs774708147, REVEL 0.73, ESM-1b 1.00, Likely benign
- R21G (p.Arg21Gly), rs774708147, ClinGen CA039498, ClinVar RCV003182949, ExAC rs774708147, ESM-1b 0.73, AlphaMissense 0.50, Likely benign, Hereditary cancer-predisposing syndrome
- R21H (p.Arg21His), rs730881760, ClinGen CA021613, ClinVar RCV000160594, ClinVar RCV000539963, REVEL 0.72, ESM-1b 1.00, Likely benign
- R21L (p.Arg21Leu), rs730881760, ClinGen CA16617546, ClinVar RCV000485060, ClinVar RCV000552453, REVEL 0.80, ESM-1b 1.00, Likely benign
- R21P (p.Arg21Pro), rs730881760, ClinGen CA346728619, ClinVar RCV001219934, ClinVar RCV005055157, ESM-1b 1.00, AlphaMissense 0.88, Uncertain significance, Lynch syndrome 1; Hereditary nonpolyposis colorectal neoplasms
- R21S (p.Arg21Ser), gnomAD 2-47403252-C-A, REVEL 0.36, ESM-1b 0.86
- R21R (p.Arg21Arg), rs1060504419, gnomAD 2-47403254-C-T, CADD 13.70
- F22I (p.Phe22Ile), rs1189127007, ClinGen CA346728621, ClinVar RCV000708824, ClinVar RCV001052926, REVEL 0.81, ESM-1b 1.00, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Lynch syndrome; Hereditary nonpolyposis
- F22L (p.Phe22Leu), rs200632093, ClinGen CA021716, cosmic curated COSV51876, ClinVar RCV000132460, REVEL 0.86, ESM-1b 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- F22Y (p.Phe22Tyr), Ensembl rs2103870946, REVEL 0.71, ESM-1b 1.00
- F22F (p.Phe22Phe), rs200632093, gnomAD 2-47403257-C-T, CADD 15.90
- F23C (p.Phe23Cys), Ensembl rs2103871125, ESM-1b 1.00, AlphaMissense 0.33
- F23I (p.Phe23Ile), 1000Genomes rs372619120, ExAC rs372619120, TOPMed rs372619120, gnomAD rs372619120, REVEL 0.57, ESM-1b 1.00, Benign
- F23L (p.Phe23Leu), Ensembl rs2103871174, REVEL 0.48, ESM-1b 1.00, Benign
- F23F (p.Phe23Phe), gnomAD 2-47403260-T-C, CADD 14.60
- Q24* (p.Gln24Ter), rs587779976, ClinGen CA022076, cosmic curated COSV10940, ClinVar RCV000115541, CADD 40.00, Pathogenic
- Q24E (p.Gln24Glu), rs587779976, ClinGen CA346728646, ClinVar RCV000560638, ClinVar RCV000777268, REVEL 0.25, ESM-1b 1.00, Pathogenic
- Q24H (p.Gln24His), rs1064794928, ClinGen CA16617547, ClinVar RCV000479166, ClinVar RCV000569588, REVEL 0.41, ESM-1b 0.00, Likely benign
- Q24L (p.Gln24Leu), Ensembl rs1672236653, REVEL 0.30, ESM-1b 0.00, Uncertain significance
- Q24R (p.Gln24Arg), rs1672236653, ClinGen CA346728651, ClinVar RCV001179994, Ensembl rs1672236653, REVEL 0.33, ESM-1b 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- Q24K (p.Gln24Lys), gnomAD 2-47403261-C-A, REVEL 0.35, ESM-1b 0.00
- Q24Q (p.Gln24Gln), rs1064794928, gnomAD 2-47403263-G-A, CADD 13.40
- G25C (p.Gly25Cys), rs746259256, ClinGen CA022143, cosmic curated COSV10956, ClinVar RCV000165126, ESM-1b 0.00, AlphaMissense 0.16, Uncertain significance
- G25D (p.Gly25Asp), rs767747378, ClinGen CA022180, ClinVar RCV000164134, ClinVar RCV000525136, REVEL 0.45, ESM-1b 1.00, Benign
- G25S (p.Gly25Ser), TOPMed rs746259256, REVEL 0.34, ESM-1b 0.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- G25A (p.Gly25Ala), gnomAD 2-47403265-G-C, REVEL 0.24, ESM-1b 0.00
- G25G (p.Gly25Gly), rs1465620610, gnomAD 2-47403266-C-T, CADD 16.50
- M26I (p.Met26Ile), rs1672237717, ClinGen CA346728677, ClinVar RCV004505566, ClinVar RCV005632673, REVEL 0.58, ESM-1b 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; not provided; Hereditary cancer-pr
- M26K (p.Met26Lys), rs1573423213, ClinGen CA346728667, ClinVar RCV003032999, ClinVar RCV005662562, ESM-1b 1.00, AlphaMissense 0.91, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- M26L (p.Met26Leu), rs876660371, Ensembl rs876660371, ClinGen CA10577915, ClinVar RCV000214711, REVEL 0.33, ESM-1b 0.00, Likely benign
- M26R (p.Met26Arg), Ensembl rs1573423213, ESM-1b 1.00, AlphaMissense 0.89, Likely benign
- M26T (p.Met26Thr), rs1573423213, ClinGen CA346728671, cosmic curated COSV51875, ClinVar RCV001026826, ESM-1b 1.00, AlphaMissense 0.91, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- M26V (p.Met26Val), rs876660371, ClinGen CA346728663, ClinVar RCV000630093, Ensembl rs876660371, ESM-1b 1.00, AlphaMissense 0.37, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- P27A (p.Pro27Ala), rs878853826, ClinGen CA346728680, ClinVar RCV000820927, ClinVar RCV004944221, ESM-1b 1.00, AlphaMissense 0.12, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- P27L (p.Pro27Leu), rs750746034, ClinGen CA022338, ClinVar RCV000164692, ClinVar RCV000228123, REVEL 0.68, ESM-1b 1.00, Likely benign
- P27R (p.Pro27Arg), rs750746034, ClinGen CA040707, ClinVar RCV000688502, ClinVar RCV001771940, REVEL 0.76, ESM-1b 1.00, Conflicting interpretations, not provided; Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-pr
- P27S (p.Pro27Ser), rs878853826, ClinGen CA346728682, cosmic curated COSV51875, ClinVar RCV001027033, REVEL 0.60, ESM-1b 1.00, Conflicting interpretations, not specified; MSH2-related disorder; Hereditary nonpolyposis colorectal neoplas
- P27T (p.Pro27Thr), rs878853826, ClinGen CA10581989, ClinVar RCV000226454, ClinVar RCV000664273, REVEL 0.74, ESM-1b 1.00, Likely benign
- P27Q (p.Pro27Gln), gnomAD 2-47403271-C-A, REVEL 0.69, ESM-1b 1.00
- P27P (p.Pro27Pro), rs1553348766, gnomAD 2-47403272-G-A, CADD 15.10
- E28* (p.Glu28Ter), rs63751246, ClinGen CA022387, ClinVar RCV000076730, ClinVar RCV000491146, AlphaMissense 0.30, MetaLR 0.65, Pathogenic
- E28D (p.Glu28Asp), rs752220575, ExAC rs752220575, TOPMed rs752220575, gnomAD rs752220575, ESM-1b 0.41, AlphaMissense 0.11, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- E28K (p.Glu28Lys), rs63751246, ClinGen CA040832, ClinVar RCV001230131, ClinVar RCV002429983, REVEL 0.68, ESM-1b 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- E28Q (p.Glu28Gln), gnomAD 2-47403273-G-C, REVEL 0.52, ESM-1b 0.87
- E28E (p.Glu28Glu), rs752220575, gnomAD 2-47403275-G-A, AlphaMissense 0.11, MetaLR 0.50
- K29* (p.Lys29Ter), rs1060502001, ClinGen CA16610843, ClinVar RCV000467909, ClinVar RCV004017628, AlphaMissense 0.95, MetaLR 0.79, Pathogenic
- K29E (p.Lys29Glu), rs1060502001, ClinGen CA346728707, ClinVar RCV001035991, Ensembl rs1060502001, ESM-1b 1.00, AlphaMissense 0.95, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- K29M (p.Lys29Met), Ensembl rs2103872428, ESM-1b 1.00, AlphaMissense 0.89, Likely benign
- K29N (p.Lys29Asn), rs1573423284, ClinGen CA346728716, ClinVar RCV001018367, ClinVar RCV001322238, REVEL 0.68, ESM-1b 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- K29R (p.Lys29Arg), rs2103872428, ClinGen CA346728711, ClinVar RCV003182943, Ensembl rs2103872428, ESM-1b 0.89, AlphaMissense 0.30, Likely benign, Hereditary cancer-predisposing syndrome
- P30L (p.Pro30Leu), rs757892928, ClinGen CA022507, ClinVar RCV000164508, ClinVar RCV000233615, REVEL 0.77, ESM-1b 1.00, Benign
- P30Q (p.Pro30Gln), ExAC rs757892928, gnomAD rs757892928, REVEL 0.77, ESM-1b 1.00, Uncertain significance, not provided
Public MSH2 analysis runs
- MSH2 analysis run — MSH2 (4,452 variants) — completed 2026-05-29
- MSH2 analysis run — MSH2 (4,452 variants) — completed 2026-05-15