NTHL1 (Endonuclease III-like protein 1) variants and mutations
NTHL1 (also known as Endonuclease III-like protein 1) is a human protein-coding gene encoding an endonuclease III-like protein 1 protein. It removes oxidized pyrimidines from DNA through base-excision repair and prevents accumulation of characteristic point mutations. Biallelic loss-of-function variants cause NTHL1 tumor syndrome with colorectal polyposis and increased risk of multiple malignancies. This analysis covers 1,074 NTHL1 variants and mutations. Of these, 82% have computational variant effect predictions. Disease context includes familial adenomatous polyposis 3, attenuated familial adenomatous polyposis, and cancer. Example NTHL1 variants include M1I, M1K, and M1L.
Variant analysis overview
- Gene: NTHL1
- Protein: Endonuclease III-like protein 1
- UniProt accession: P78549
- Organism: Homo sapiens
- Variants analyzed: 1074
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 917 unspecified-consequence records; 1 stop retained variant; 1 stop lost; 71 synonymous variants; 61 missense variants; 6 stop-gained variants; 2 in-frame deletions; 7 frameshift variants; 5 splice-region variants; 3 substitution
- Prediction scores: 876 variants have prediction scores (82% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: familial adenomatous polyposis 3, attenuated familial adenomatous polyposis, cancer, Inherited cancer-predisposing syndrome, hereditary neoplastic syndrome, NTHL1-deficiency tumor predisposition syndrome, colorectal cancer, breast carcinoma, prostate adenocarcinoma, head and neck squamous cell carcinoma, skin basal cell carcinoma, melanoma.
Protein structure and variant hotspots
- Protein features: 1 domains; 4 binding sites; 2 post-translational modification sites.
- Structural context: 96 variants have structural context.
- PTM context: 6 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, MaveDB, LitVar.
Notable NTHL1 variants
Examples include M1I, M1K, M1L, M1T, M1V, T2A, T2I, T2N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs2150958900, ClinGen CA394298719, ClinVar RCV002036346, ClinVar RCV005445582, MutPred 0.22, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- M1K (p.Met1Lys), rs764604281, ClinGen CA394298737, ClinVar RCV000812615, ClinVar RCV004028775, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- M1L (p.Met1Leu), rs1277993259, ClinGen CA394298742, ClinVar RCV001374070, ClinGen CA394298746, Uncertain significance, not provided
- M1T (p.Met1Thr), rs764604281, ClinGen CA027655, ClinVar RCV001245877, ClinVar RCV002436967, MutPred 0.28, Uncertain significance, Hereditary cancer-predisposing syndrome
- M1V (p.Met1Val), rs1277993259, ClinGen CA394298744, ClinVar RCV001227472, ClinVar RCV004944910, MutPred 0.27, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- T2A (p.Thr2Ala), TOPMed rs1346158495, gnomAD rs1346158495, CADD 7.11, PolyPhen-2 0.00, Uncertain significance
- T2I (p.Thr2Ile), rs1305523200, ClinGen CA394298704, ClinVar RCV001048330, ClinVar RCV004649423, CADD 0.69, PolyPhen-2 0.00, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided
- T2N (p.Thr2Asn), rs1305523200, ClinGen CA394298708, ClinVar RCV003714336, ClinVar RCV005445912, CADD 0.06, PolyPhen-2 0.00, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided
- T2P (p.Thr2Pro), rs1346158495, ClinGen CA394298715, ClinVar RCV002012638, ClinVar RCV002441174, CADD 10.90, PolyPhen-2 0.00, Uncertain significance, Familial adenomatous polyposis 3; Hereditary cancer-predisposing syndrome; not p
- T2S (p.Thr2Ser), gnomAD rs1305523200, CADD 0.07, PolyPhen-2 0.00, Uncertain significance, not provided
- A3P (p.Ala3Pro), rs753350404, ClinGen CA394298701, ClinVar RCV001363843, ClinVar RCV002322335, MutPred 0.18, Likely benign, Hereditary cancer-predisposing syndrome
- A3S (p.Ala3Ser), rs753350404, ClinGen CA027686, ClinVar RCV000798390, ClinVar RCV001019155, CADD 4.91, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- A3T (p.Ala3Thr), rs753350404, ClinGen CA394298702, ClinVar RCV000798868, ClinVar RCV002325530, CADD 5.06, PolyPhen-2 0.00, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not specified; not provided
- A3V (p.Ala3Val), rs2548332676, ClinGen CA394298681, ClinVar RCV003580018, ClinVar RCV005377418, CADD 13.30, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- L4* (p.Leu4Ter), rs1413587495, ClinGen CA394298671, ClinVar RCV001909047, ClinVar RCV003458235, CADD 13.70, Pathogenic
- L4F (p.Leu4Phe), rs2084530050, ClinGen CA394298665, ClinVar RCV001324475, Ensembl rs2084530050, CADD 3.45, PolyPhen-2 0.01, Uncertain significance, Hereditary cancer-predisposing syndrome
- L4S (p.Leu4Ser), Ensembl rs1413587495, CADD 7.64, PolyPhen-2 0.00, Pathogenic
- L4V (p.Leu4Val), rs2548332651, ClinGen CA394298674, ClinVar RCV003704375, Uncertain significance, not provided
- L4W (p.Leu4Trp), rs1413587495, ClinGen CA394298667, ClinVar RCV002455198, ClinVar RCV003099609, CADD 9.52, PolyPhen-2 0.00, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- S5C (p.Ser5Cys), ExAC rs760388875, gnomAD rs760388875
- S5N (p.Ser5Asn), rs750166500, ClinGen CA027717, ClinVar RCV001056296, ClinVar RCV002365712, CADD 10.20, PolyPhen-2 0.01, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- S5R (p.Ser5Arg), rs1596228346, ClinGen CA394298643, ClinVar RCV001055224, ClinVar RCV002374926, CADD 11.10, PolyPhen-2 0.04, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- S5T (p.Ser5Thr), rs750166500, ClinGen CA394298652, ClinVar RCV000807679, ClinVar RCV002257974, CADD 7.98, PolyPhen-2 0.01, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided
- A6E (p.Ala6Glu), rs767282292, ClinGen CA276766775, ClinVar RCV001213594, ClinVar RCV004033896, CADD 0.61, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- A6G (p.Ala6Gly), rs767282292, ClinGen CA394298632, ClinVar RCV001884701, ClinVar RCV004945772, MutPred 0.21, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- A6S (p.Ala6Ser), rs2150958724, ClinGen CA394298637, ClinVar RCV003302009, Ensembl rs2150958724, CADD 0.09, PolyPhen-2 0.02, Uncertain significance, Hereditary cancer-predisposing syndrome
- A6V (p.Ala6Val), rs767282292, ClinGen CA027730, ClinVar RCV001022036, ClinVar RCV001207339, CADD 2.40, PolyPhen-2 0.00, Conflicting interpretations, not provided; Hereditary cancer-predisposing syndrome
- R7G (p.Arg7Gly), rs2548332469, ClinGen CA394298629, ClinVar RCV002770370, ClinVar RCV005455604, CADD 22.40, PolyPhen-2 0.98, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- R7K (p.Arg7Lys), rs930166212, ClinGen CA394298624, ClinVar RCV001298868, ClinVar RCV002327643, CADD 20.10, PolyPhen-2 0.94, Likely benign, Hereditary cancer-predisposing syndrome
- R7S (p.Arg7Ser), rs762030002, ClinGen CA394298616, ClinVar RCV001208008, ClinVar RCV002256698, CADD 23.70, PolyPhen-2 0.98, Pathogenic/Likely pathogenic, Familial adenomatous polyposis 3
- R7T (p.Arg7Thr), rs2084528877, ClinGen CA2201989455, ClinVar RCV001338554, ClinVar RCV002329308, CADD 20.70, PolyPhen-2 0.98, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- M8I (p.Met8Ile), rs2548332297, ClinGen CA394298596, ClinVar RCV002340631, ClinVar RCV003708645, CADD 20.80, PolyPhen-2 0.00, Uncertain significance, not provided
- M8K (p.Met8Lys), ESP rs376966505, ExAC rs376966505, gnomAD rs376966505, CADD 21.10, PolyPhen-2 0.05
- M8L (p.Met8Leu), rs1596228289, ClinGen CA394298609, ClinVar RCV003063929, 1000Genomes rs1596228289, CADD 23.20, PolyPhen-2 0.00, Uncertain significance, not provided
- M8R (p.Met8Arg), ESP rs376966505, ExAC rs376966505, gnomAD rs376966505
- M8T (p.Met8Thr), rs376966505, ClinGen CA394298607, ClinVar RCV002716209, ClinVar RCV005685012, MutPred 0.39, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- M8V (p.Met8Val), rs1596228289, ClinGen CA394298614, ClinVar RCV001974043, 1000Genomes rs1596228289, MutPred 0.39, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- L9M (p.Leu9Met), rs1596228271, ClinGen CA394298592, ClinVar RCV001895464, Ensembl rs1596228271, CADD 4.12, PolyPhen-2 0.00, Uncertain significance, not provided
- L9P (p.Leu9Pro), rs1596228259, ClinGen CA394298585, ClinVar RCV001023546, ClinVar RCV001766854, CADD 19.60, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- L9R (p.Leu9Arg), rs1596228259, ClinGen CA394298583, ClinVar RCV001360416, Ensembl rs1596228259, MutPred 0.41, Uncertain significance, not provided
- L9V (p.Leu9Val), rs1596228271, ClinGen CA394298590, ClinVar RCV000802597, Ensembl rs1596228271, MutPred 0.28, Uncertain significance, not provided
- T10I (p.Thr10Ile), rs370539291, ClinGen CA027763, ClinVar RCV001933063, ClinVar RCV002344032, CADD 22.90, PolyPhen-2 0.83, Uncertain significance, Familial adenomatous polyposis 3; Hereditary cancer-predisposing syndrome; not p
- T10P (p.Thr10Pro), rs2150958551, ClinGen CA394298580, ClinVar RCV002344572, MutPred 0.29, Uncertain significance, Hereditary cancer-predisposing syndrome
- T10S (p.Thr10Ser), Ensembl rs2150958551, CADD 22.30, PolyPhen-2 0.58, Conflicting interpretations, Familial adenomatous polyposis 3; Hereditary cancer-predisposing syndrome; not s
- R11G (p.Arg11Gly), rs549760347, ClinGen CA394298565, ClinVar RCV000819128, ClinVar RCV002345886, CADD 24.50, PolyPhen-2 0.74, Uncertain significance, Hereditary cancer-predisposing syndrome
- R11L (p.Arg11Leu), rs372992221, ClinGen CA394298564, ClinVar RCV001037470, ClinVar RCV004944782, CADD 23.80, PolyPhen-2 0.05, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- R11P (p.Arg11Pro), rs372992221, ClinGen CA394298563, ClinVar RCV001323980, ClinVar RCV002350597, CADD 26.70, PolyPhen-2 0.88, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- R11Q (p.Arg11Gln), rs372992221, ClinGen CA027789, ClinVar RCV000792050, ClinVar RCV001024430, CADD 25.90, PolyPhen-2 0.73, Uncertain significance, not provided; Familial adenomatous polyposis 3; Hereditary cancer-predisposing s
- R11W (p.Arg11Trp), rs549760347, ClinGen CA027783, ClinVar RCV000823099, ClinVar RCV001024310, CADD 25.80, PolyPhen-2 0.92, Uncertain significance, not provided
- S12C (p.Ser12Cys), Ensembl rs2150958482, CADD 21.30, PolyPhen-2 0.13
- S12I (p.Ser12Ile), rs2150958467, ClinGen CA394298556, ClinVar RCV002811976, CADD 18.20, PolyPhen-2 0.04, Uncertain significance, not provided
- S12N (p.Ser12Asn), rs2150958467, ClinGen CA394298558, ClinVar RCV002015880, Ensembl rs2150958467, MutPred 0.24, Uncertain significance, not provided
- S12R (p.Ser12Arg), rs1216311147, ClinGen CA394298555, ClinVar RCV002657865, ClinGen CA394298554, CADD 15.10, PolyPhen-2 0.00, Uncertain significance, not provided
- R13G (p.Arg13Gly), rs3087469, ClinGen CA394298553, ClinVar RCV003858505, MutPred 0.14, Uncertain significance, not provided
- R13L (p.Arg13Leu), rs2084526654, ClinGen CA394298552, ClinVar RCV002259248, TOPMed rs2084526654, MutPred 0.28, Uncertain significance, Hereditary cancer-predisposing syndrome
- R13P (p.Arg13Pro), rs2084526654, ClinGen CA394298550, ClinVar RCV003302014, CADD 17.00, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- R13Q (p.Arg13Gln), rs2084526654, ClinGen CA394298551, ClinVar RCV002706313, ClinVar RCV005382460, CADD 15.80, PolyPhen-2 0.00, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- R13W (p.Arg13Trp), rs3087469, ClinGen CA027813, ClinVar RCV000802855, ClinVar RCV001024999, CADD 20.80, PolyPhen-2 0.00, Conflicting interpretations, Familial adenomatous polyposis 3; Hereditary cancer-predisposing syndrome; not p
- S14G (p.Ser14Gly), rs1596228177, ClinGen CA394298548, ClinVar RCV001025341, ClinVar RCV005093260, CADD 21.90, PolyPhen-2 0.14, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- S14I (p.Ser14Ile), rs746090969, ClinGen CA394298539, ClinVar RCV003016833, ExAC rs746090969, CADD 22.40, PolyPhen-2 0.35, Uncertain significance, not provided
- S14N (p.Ser14Asn), rs746090969, ClinGen CA027818, ClinVar RCV001057848, ClinVar RCV002374937, CADD 21.70, PolyPhen-2 0.19, Uncertain significance, Familial adenomatous polyposis 3; Hereditary cancer-predisposing syndrome; not s
- S14R (p.Ser14Arg), rs898348644, ClinGen CA394298534, ClinVar RCV001054556, TOPMed rs898348644, CADD 19.80, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- L15P (p.Leu15Pro), rs781328762, ClinGen CA027827, ClinVar RCV000822008, ClinVar RCV001025785, CADD 16.90, PolyPhen-2 0.10, Uncertain significance, Familial adenomatous polyposis 3; Hereditary cancer-predisposing syndrome; not p
- L15R (p.Leu15Arg), ExAC rs781328762, TOPMed rs781328762, gnomAD rs781328762, Uncertain significance
- L15V (p.Leu15Val), rs931865828, ClinGen CA276766738, ClinVar RCV000802537, ClinVar RCV002360957, CADD 18.20, PolyPhen-2 0.01, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Familial adenomatous poly
- G16A (p.Gly16Ala), rs747325774, ClinGen CA027845, ClinVar RCV000795884, ClinVar RCV002370084, CADD 6.18, PolyPhen-2 0.00, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided
- G16E (p.Gly16Glu), rs747325774, ClinGen CA027835, ClinVar RCV003550121, ExAC rs747325774, CADD 9.22, PolyPhen-2 0.00, Uncertain significance, not provided
- G16R (p.Gly16Arg), rs1271271380, ClinGen CA394298518, ClinVar RCV000818618, ClinVar RCV001294000, CADD 10.80, PolyPhen-2 0.06, Uncertain significance, Familial adenomatous polyposis 3; Hereditary cancer-predisposing syndrome; not p
- P17H (p.Pro17His), rs1343729377, ClinGen CA394298499, ClinVar RCV000799812, ClinVar RCV002388469, CADD 14.70, PolyPhen-2 0.20, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- P17L (p.Pro17Leu), rs1343729377, ClinGen CA394298494, ClinVar RCV002391614, ClinVar RCV003776400, CADD 10.60, PolyPhen-2 0.03, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- P17R (p.Pro17Arg), rs1343729377, ClinGen CA394298496, ClinVar RCV003735966, ClinVar RCV004943224, CADD 7.83, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- P17S (p.Pro17Ser), rs1173561620, ClinGen CA394298502, ClinVar RCV003694056, TOPMed rs1173561620, CADD 7.28, PolyPhen-2 0.00, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- G18E (p.Gly18Glu), rs1406320674, ClinGen CA394298480, ClinVar RCV003078293, ClinVar RCV003274215, CADD 12.30, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- G18R (p.Gly18Arg), rs1456331577, ClinGen CA394298491, ClinVar RCV001239786, TOPMed rs1456331577, CADD 8.03, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- G18W (p.Gly18Trp), rs1456331577, ClinGen CA394298486, ClinVar RCV002036370, ClinVar RCV005445583, CADD 20.30, PolyPhen-2 0.47, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- A19S (p.Ala19Ser), Ensembl rs2150958171, CADD 2.18, PolyPhen-2 0.00, Uncertain significance
- A19T (p.Ala19Thr), rs2150958171, ClinGen CA394298472, ClinVar RCV001986125, ClinVar RCV004045331, CADD 4.80, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- A19V (p.Ala19Val), rs2084523141, ClinGen CA394298463, ClinVar RCV003057722, Ensembl rs2084523141, CADD 5.70, PolyPhen-2 0.00, Uncertain significance, not provided
- G20A (p.Gly20Ala), TOPMed rs1430939825, gnomAD rs1430939825, CADD 8.94, PolyPhen-2 0.00, Uncertain significance
- G20E (p.Gly20Glu), rs1430939825, ClinGen CA394298453, ClinVar RCV000808918, ClinVar RCV002440734, CADD 13.30, PolyPhen-2 0.04, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- G20R (p.Gly20Arg), rs529997128, ClinGen CA394298460, ClinVar RCV000809021, ClinVar RCV001027384, CADD 3.32, PolyPhen-2 0.00, Uncertain significance, not provided
- G20V (p.Gly20Val), TOPMed rs1430939825, gnomAD rs1430939825, CADD 12.60, PolyPhen-2 0.06, Uncertain significance, not provided
- P21L (p.Pro21Leu), rs753200685, ClinGen CA394298440, ClinVar RCV000808163, ClinVar RCV003362963, CADD 10.70, PolyPhen-2 0.00, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- P21Q (p.Pro21Gln), rs753200685, ClinGen CA027874, ClinVar RCV000813233, ClinVar RCV004649338, CADD 9.76, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- P21R (p.Pro21Arg), rs753200685, ClinGen CA394298436, ClinVar RCV001939838, ClinVar RCV004945786, MutPred 0.16, Conflicting interpretations, not provided; Hereditary cancer-predisposing syndrome
- P21S (p.Pro21Ser), rs2084522305, ClinGen CA394298443, ClinVar RCV001313344, ClinVar RCV002447327, CADD 7.35, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- P21T (p.Pro21Thr), 1000Genomes rs2084522305, CADD 7.77, PolyPhen-2 0.02, Uncertain significance
- R22G (p.Arg22Gly), TOPMed rs2084521791, Uncertain significance
- R22L (p.Arg22Leu), rs779612126, ClinGen CA027877, ClinVar RCV001969756, ClinVar RCV003289281, CADD 13.40, PolyPhen-2 0.05, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- R22P (p.Arg22Pro), ExAC rs779612126, TOPMed rs779612126, gnomAD rs779612126, CADD 15.00, PolyPhen-2 0.24, Uncertain significance, Hereditary cancer-predisposing syndrome
- R22Q (p.Arg22Gln), rs779612126, ClinGen CA394298427, ClinVar RCV003494159, ClinVar RCV005100346, CADD 13.20, PolyPhen-2 0.00, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome; not specified
- R22W (p.Arg22Trp), rs2084521791, ClinGen CA394298430, ClinVar RCV001064256, ClinVar RCV002374965, CADD 12.40, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- G23E (p.Gly23Glu), rs749963973, ClinGen CA394298410, ClinVar RCV000819939, ClinVar RCV002372336, CADD 7.99, PolyPhen-2 0.20, Uncertain significance, Familial adenomatous polyposis 3; Hereditary cancer-predisposing syndrome; not p
- G23R (p.Gly23Arg), Ensembl rs2084521094, CADD 3.60, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- G23V (p.Gly23Val), rs749963973, ClinGen CA027909, ClinVar RCV001049217, ClinVar RCV002374897, CADD 10.90, PolyPhen-2 0.20, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- C24F (p.Cys24Phe), rs1034291686, ClinGen CA394298389, ClinVar RCV001346801, ClinVar RCV005372662, CADD 2.33, PolyPhen-2 0.01, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- C24G (p.Cys24Gly), rs1596227962, ClinGen CA394298399, ClinVar RCV003083446, ClinVar RCV006411784, MutPred 0.23, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided
- C24R (p.Cys24Arg), rs1596227962, ClinGen CA394298401, ClinVar RCV002374146, CADD 2.81, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- C24S (p.Cys24Ser), Ensembl rs1596227962, Uncertain significance
- C24W (p.Cys24Trp), TOPMed rs1265227121, gnomAD rs1265227121, Uncertain significance, Hereditary cancer-predisposing syndrome
- C24Y (p.Cys24Tyr), rs1034291686, ClinGen CA276766673, ClinVar RCV000824649, ClinVar RCV001019545, CADD 0.90, PolyPhen-2 0.03, Conflicting interpretations, not provided; NTHL1-related disorder; Hereditary cancer-predisposing syndrome
- R25G (p.Arg25Gly), rs369039003, ClinGen CA027938, ClinVar RCV001900476, ClinVar RCV002370417, CADD 2.44, PolyPhen-2 0.00, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided
- R25K (p.Arg25Lys), rs2302172, ClinGen CA027945, ClinVar RCV000879706, ClinVar RCV001019876, CADD 7.62, PolyPhen-2 0.00, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not specified; not provided
- R25M (p.Arg25Met), rs2302172, ClinGen CA394298372, ClinVar RCV001224653, 1000Genomes rs2302172, CADD 14.70, PolyPhen-2 0.10, Uncertain significance, not provided
- R25S (p.Arg25Ser), rs1274325491, ClinGen CA394298368, ClinVar RCV001978836, TOPMed rs1274325491, CADD 14.30, PolyPhen-2 0.01, Uncertain significance, not provided
- R25W (p.Arg25Trp), rs369039003, ClinGen CA394298379, ClinVar RCV000810751, ClinVar RCV002381801, CADD 14.60, PolyPhen-2 0.13, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- E26D (p.Glu26Asp), rs2084518192, ClinGen CA394298348, ClinVar RCV001208148, Ensembl rs2084518192, CADD 9.31, PolyPhen-2 0.00, Uncertain significance, not provided
- E26G (p.Glu26Gly), rs763847748, ClinGen CA394298354, ClinVar RCV002304707, ClinVar RCV005382411, MutPred 0.17, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- E26K (p.Glu26Lys), Ensembl rs1567376138
- E26V (p.Glu26Val), ExAC rs763847748, gnomAD rs763847748, CADD 21.90, PolyPhen-2 0.21, Uncertain significance, not provided
- E27D (p.Glu27Asp), rs1596227883, ClinGen CA394298338, ClinVar RCV000820565, ClinVar RCV002397717, CADD 4.01, PolyPhen-2 0.00, Uncertain significance, not provided
- E27G (p.Glu27Gly), rs762937286, ClinGen CA027380, ClinVar RCV001054038, ClinVar RCV003160427, CADD 22.80, PolyPhen-2 0.04, Conflicting interpretations, Familial adenomatous polyposis 3; Hereditary cancer-predisposing syndrome; not p
- E27K (p.Glu27Lys), rs2084517936, ClinGen CA394298346, ClinVar RCV002389650, ClinVar RCV003095230, CADD 13.40, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- E27Q (p.Glu27Gln), rs2084517936, ClinGen CA394298345, ClinVar RCV001297281, ClinVar RCV003365303, MutPred 0.20, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- E27V (p.Glu27Val), ExAC rs762937286, gnomAD rs762937286, Uncertain significance
- P28A (p.Pro28Ala), rs1056290046, ClinGen CA394298335, ClinVar RCV001917231, TOPMed rs1056290046, MutPred 0.20, Uncertain significance, not provided
- P28S (p.Pro28Ser), rs1056290046, ClinGen CA276766665, ClinVar RCV001017193, ClinVar RCV002279708, CADD 8.91, PolyPhen-2 0.02, Conflicting interpretations, not provided; Hereditary cancer-predisposing syndrome
- P28T (p.Pro28Thr), rs1056290046, ClinGen CA394298336, ClinVar RCV003104727, ClinVar RCV003162124, CADD 8.43, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- G29E (p.Gly29Glu), rs1453838226, NCI-TCGA Cosmic COSV9952, gnomAD rs1453838226, CADD 1.50, PolyPhen-2 0.00, Variant assessed as somatic; moderate impact.
- G29R (p.Gly29Arg), rs1161055704, ClinGen CA394298330, ClinVar RCV001298665, TOPMed rs1161055704, CADD 10.20, PolyPhen-2 0.01, Uncertain significance, not provided
- P30A (p.Pro30Ala), rs541004726, ClinGen CA027398, ClinVar RCV001054452, ClinVar RCV002320298, CADD 16.30, PolyPhen-2 0.04, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- P30L (p.Pro30Leu), rs759555861, ClinGen CA276766637, ClinVar RCV001368551, ClinVar RCV002456572, CADD 15.80, PolyPhen-2 0.06, Uncertain significance, Familial adenomatous polyposis 3; Hereditary cancer-predisposing syndrome; not p
- P30R (p.Pro30Arg), rs759555861, ClinGen CA027403, ClinVar RCV000809382, ClinVar RCV001009990, CADD 10.40, PolyPhen-2 0.01, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- P30S (p.Pro30Ser), rs541004726, ClinGen CA394298324, ClinVar RCV001056021, 1000Genomes rs541004726, CADD 16.50, PolyPhen-2 0.01, Uncertain significance, not provided
- L31F (p.Leu31Phe), rs1259870849, ClinGen CA394298322, ClinVar RCV000815980, ClinVar RCV002257982, CADD 12.20, PolyPhen-2 0.11, Conflicting interpretations, not provided; Familial adenomatous polyposis 3; Hereditary cancer-predisposing s
- L31P (p.Leu31Pro), rs776714028, ClinGen CA027420, ClinVar RCV003731329, ClinVar RCV006411933, CADD 6.62, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- R32G (p.Arg32Gly), rs1285624591, ClinGen CA394298312, ClinVar RCV001238757, ClinVar RCV002339660, MutPred 0.25, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- R32Q (p.Arg32Gln), rs1411639953, ClinGen CA394298309, ClinVar RCV000811166, ClinVar RCV004028719, CADD 8.25, PolyPhen-2 0.00, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- R32W (p.Arg32Trp), rs1285624591, ClinGen CA394298310, ClinVar RCV001304317, ClinVar RCV002341606, CADD 13.30, PolyPhen-2 0.00, Conflicting interpretations, not provided; Familial adenomatous polyposis 3; Hereditary cancer-predisposing s
- R33G (p.Arg33Gly), rs2548331011, ClinGen CA394298302, ClinVar RCV002299271, CADD 21.50, PolyPhen-2 0.01, Uncertain significance, not provided
- R33K (p.Arg33Lys), rs1421779919, ClinGen CA394298298, ClinVar RCV001318948, ClinVar RCV002375416, CADD 3.97, PolyPhen-2 0.00, Uncertain significance, Familial adenomatous polyposis 3; Hereditary cancer-predisposing syndrome; not p
- R34K (p.Arg34Lys), rs1388213392, ClinGen CA394298281, ClinVar RCV001010595, gnomAD rs1388213392, CADD 8.71, PolyPhen-2 0.01, Likely benign, Hereditary cancer-predisposing syndrome
- R34S (p.Arg34Ser), rs527315265, ClinGen CA027426, ClinVar RCV000802631, ClinVar RCV001010673, CADD 11.10, PolyPhen-2 0.00, Conflicting interpretations, Familial adenomatous polyposis 3; not provided; Hereditary cancer-predisposing s
- E35D (p.Glu35Asp), rs1596227700, ClinGen CA394298259, ClinVar RCV000806754, ClinVar RCV003325217, CADD 2.67, PolyPhen-2 0.12, Conflicting interpretations, Familial adenomatous polyposis 3; not provided; Hereditary cancer-predisposing s
- E35G (p.Glu35Gly), rs778185523, ClinGen CA027443, ClinVar RCV001037901, ClinVar RCV002379490, CADD 22.90, PolyPhen-2 0.00, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided
- E35K (p.Glu35Lys), rs747272786, ClinGen CA394298270, ClinVar RCV001972336, ClinVar RCV004641816, CADD 20.10, PolyPhen-2 0.01, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- E35Q (p.Glu35Gln), rs747272786, ClinGen CA027431, ClinVar RCV000807595, ClinVar RCV001010720, CADD 15.40, PolyPhen-2 0.18, Conflicting interpretations, not provided; Familial adenomatous polyposis 3; Hereditary cancer-predisposing s
- A36D (p.Ala36Asp), rs772384035, ClinGen CA394298249, ClinVar RCV001890964, ExAC rs772384035, CADD 15.30, PolyPhen-2 0.16, Uncertain significance, not provided
- A36G (p.Ala36Gly), rs772384035, ClinGen CA027458, ClinVar RCV001994282, ClinVar RCV003170357, CADD 20.40, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- A36S (p.Ala36Ser), rs2150957402, ClinGen CA394298252, ClinVar RCV002258604, Ensembl rs2150957402, CADD 10.90, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- A36T (p.Ala36Thr), rs2150957402, ClinGen CA394298255, ClinVar RCV003562127, ClinVar RCV006425082, CADD 14.20, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- A37T (p.Ala37Thr), rs564610639, ClinGen CA027474, ClinVar RCV002387679, ClinVar RCV003738237, CADD 21.60, PolyPhen-2 0.99, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- A37V (p.Ala37Val), rs1482983792, ClinGen CA394298237, ClinVar RCV001312444, ClinVar RCV002384386, CADD 24.30, PolyPhen-2 0.99, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided
- A38G (p.Ala38Gly), rs202082304, ClinGen CA394298220, ClinVar RCV001343324, 1000Genomes rs202082304, MutPred 0.21, Uncertain significance, not provided
- A38T (p.Ala38Thr), Ensembl rs2150957299, CADD 16.00, PolyPhen-2 0.28, Likely benign, Hereditary cancer-predisposing syndrome
- A38V (p.Ala38Val), rs202082304, ClinGen CA027490, ClinVar RCV000961022, ClinVar RCV001011260, CADD 33.00, PolyPhen-2 0.29, Conflicting interpretations, not specified; Inherited polyposis and early onset colorectal cancer - germline
- E39A (p.Glu39Ala), rs2084387796, ClinGen CA394298119, ClinVar RCV001054585, Ensembl rs2084387796, MutPred 0.26, Uncertain significance, not provided
- E39D (p.Glu39Asp), rs2548321780, ClinGen CA394298113, ClinVar RCV002391769, Uncertain significance, Hereditary cancer-predisposing syndrome
- E39Q (p.Glu39Gln), rs1274541982, ClinGen CA394298213, ClinVar RCV001922570, ClinVar RCV002388792, CADD 36.00, PolyPhen-2 0.83, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- A40G (p.Ala40Gly), rs375615004, ClinGen CA394298101, ClinVar RCV004516043, ESP rs375615004, MutPred 0.27, Likely benign, Hereditary cancer-predisposing syndrome
- A40S (p.Ala40Ser), rs2084387662, ClinGen CA394298103, ClinVar RCV001202275, Ensembl rs2084387662, MutPred 0.25, Uncertain significance, not provided
- A40V (p.Ala40Val), rs375615004, ClinGen CA7828361, ClinVar RCV000809621, ClinVar RCV001011586, CADD 5.87, PolyPhen-2 0.02, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome; not specified
- R41S (p.Arg41Ser), rs2084387412, ClinGen CA394298086, ClinVar RCV001218029, Ensembl rs2084387412, CADD 10.60, PolyPhen-2 0.00, Uncertain significance, not provided
- K42N (p.Lys42Asn), rs1015408170, ClinGen CA276765721, ClinVar RCV000803402, ClinVar RCV002388499, CADD 15.80, PolyPhen-2 0.06, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- S43G (p.Ser43Gly), gnomAD rs1209679396, CADD 6.18, PolyPhen-2 0.03
- S43R (p.Ser43Arg), rs1004057524, ClinGen CA394298056, ClinVar RCV001324518, TOPMed rs1004057524, CADD 7.17, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- H44D (p.His44Asp), rs374988261, ClinGen CA276765719, ClinVar RCV001012077, ClinVar RCV001040110, CADD 8.04, PolyPhen-2 0.00, Conflicting interpretations, not specified; not provided; Hereditary cancer-predisposing syndrome
- H44N (p.His44Asn), rs374988261, ClinGen CA394298053, ClinVar RCV003026779, Uncertain significance, not provided
- H44P (p.His44Pro), rs923173693, ClinGen CA394298045, ClinVar RCV002405372, MutPred 0.27, Uncertain significance, Hereditary cancer-predisposing syndrome
- H44Q (p.His44Gln), rs2150947647, ClinGen CA394298044, ClinVar RCV003713140, CADD 7.11, PolyPhen-2 0.03, Uncertain significance, not provided
- H44R (p.His44Arg), rs923173693, ClinGen CA276765716, ClinVar RCV001221499, ClinVar RCV002402677, CADD 0.48, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- H44Y (p.His44Tyr), rs374988261, ClinGen CA394298050, ClinVar RCV001344144, ClinVar RCV005385052, MutPred 0.19, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- S45G (p.Ser45Gly), rs2548321618, ClinGen CA394298037, ClinVar RCV002953944, CADD 0.18, PolyPhen-2 0.00, Uncertain significance, not provided
- S45I (p.Ser45Ile), Ensembl rs1567372419, CADD 4.89, PolyPhen-2 0.02, Uncertain significance
- S45N (p.Ser45Asn), rs1567372419, ClinGen CA394298035, ClinVar RCV003559985, ClinVar RCV004943101, MutPred 0.23, Conflicting interpretations, not provided; Hereditary cancer-predisposing syndrome
- S45R (p.Ser45Arg), rs2150947604, ClinGen CA394298026, ClinVar RCV003558122, ClinVar RCV004636779, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- S45T (p.Ser45Thr), Ensembl rs1567372419, Uncertain significance
- P46L (p.Pro46Leu), rs2150947574, ClinGen CA394298013, ClinVar RCV001355289, Ensembl rs2150947574, MutPred 0.18, Uncertain significance, not provided
- P46S (p.Pro46Ser), rs2150947586, ClinGen CA394298024, NCI-TCGA Cosmic COSV9952, ClinVar RCV001756795, Uncertain significance, not provided; Familial adenomatous polyposis 3
- P46T (p.Pro46Thr), rs2150947586, ClinGen CA394298022, ClinVar RCV002394810, MutPred 0.19, Uncertain significance, Hereditary cancer-predisposing syndrome
- V47G (p.Val47Gly), Ensembl rs2150947537
- V47L (p.Val47Leu), rs1210160367, ClinGen CA394298006, ClinVar RCV002394922, MutPred 0.16, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided
- V47M (p.Val47Met), rs1210160367, ClinGen CA394298008, ClinVar RCV000804043, ClinVar RCV002255529, CADD 0.02, PolyPhen-2 0.01, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- K48E (p.Lys48Glu), rs2150947503, ClinGen CA394297995, ClinVar RCV002011047, ClinVar RCV002398088, CADD 12.60, PolyPhen-2 0.04, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- K48R (p.Lys48Arg), rs2084385937, ClinGen CA394297989, ClinVar RCV001325137, Ensembl rs2084385937, CADD 4.99, PolyPhen-2 0.00, Uncertain significance, not provided
- R49C (p.Arg49Cys), rs371105614, ClinGen CA276765709, ClinVar RCV000809525, ClinVar RCV002397662, CADD 21.40, PolyPhen-2 0.52, Conflicting interpretations, not provided; Hereditary cancer-predisposing syndrome; Familial adenomatous poly
- R49H (p.Arg49His), rs566254536, ClinGen CA276765708, ClinVar RCV000806226, ClinVar RCV002257970, CADD 0.98, PolyPhen-2 0.00, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided
- P50A (p.Pro50Ala), Ensembl rs2150947428
- P50L (p.Pro50Leu), rs139165943, ClinGen CA7828357, ClinVar RCV000794648, ClinVar RCV001012937, CADD 0.07, PolyPhen-2 0.04, Conflicting interpretations, Familial adenomatous polyposis 3; Hereditary cancer-predisposing syndrome; not p
- P50S (p.Pro50Ser), rs2150947428, ClinGen CA394297964, ClinVar RCV002399169, MutPred 0.21, Uncertain significance, Hereditary cancer-predisposing syndrome
Public NTHL1 analysis runs
- NTHL1 analysis run — NTHL1 (1,074 variants) — completed 2026-08-19