TIGIT (Q495A1) variants and mutations
TIGIT (also known as Q495A1) is a human protein-coding gene encoding a t-cell immunoreceptor with Ig and ITIM domains protein. It suppresses T-cell and natural-killer-cell activity after binding ligands such as CD155 and competes with activating receptors for the same ligands. Persistent TIGIT signaling can contribute to immune exhaustion in tumors and chronic infection, making it an immune-checkpoint target. This analysis covers 655 TIGIT variants and mutations. Of these, 79% have computational variant effect predictions. Disease context includes non-small cell lung carcinoma, small cell lung carcinoma, and esophageal squamous cell carcinoma. Example TIGIT variants include M1L, M1V, and M1T.
Variant analysis overview
- Gene: TIGIT
- Protein: Q495A1
- UniProt accession: Q495A1
- Organism: Homo sapiens
- Variants analyzed: 655
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 358 unspecified-consequence records; 162 missense variants; 99 synonymous variants; 16 frameshift variants; 10 stop-gained variants; 1 in-frame insertions; 7 in-frame deletions; 2 splice-region variants; 1 substitution
- Prediction scores: 517 variants have prediction scores (79% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: non-small cell lung carcinoma, small cell lung carcinoma, esophageal squamous cell carcinoma, neurodegenerative disease, melanoma, hepatocellular carcinoma, cancer, gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, lung cancer, esophageal adenocarcinoma, cholelithiasis.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 1 domains; 3 post-translational modification sites.
- Structural context: 370 variants have structural context.
- PTM context: 9 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, MaveDB, LitVar.
Notable TIGIT variants
Examples include M1L, M1V, M1T, M1K, M1R, M1I, R2C, R2G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1L (p.Met1Leu), rs1261868555, gnomAD 3-114293885-A-C, CADD 2.34, SIFT 0.37
- M1V (p.Met1Val), rs1261868555, gnomAD 3-114293885-A-G, CADD 2.65, SIFT 0.81
- M1T (p.Met1Thr), gnomAD 3-114293886-T-C, CADD 6.92, SIFT 0.40
- M1K (p.Met1Lys), rs1429608897, gnomAD 3-114293886-T-A, CADD 6.42, SIFT 0.14
- M1R (p.Met1Arg), gnomAD 3-114293886-T-G, CADD 6.60, SIFT 0.16
- M1I (p.Met1Ile), gnomAD 3-114293887-G-T, CADD 9.50, SIFT 0.42
- R2C (p.Arg2Cys), rs977245811, ClinGen CA81660403, NCI-TCGA Cosmic COSV6732, ClinVar RCV004088397, REVEL 0.13, CADD 22.10, Uncertain significance, not specified
- R2G (p.Arg2Gly), TOPMed rs977245811, gnomAD rs977245811, REVEL 0.05, CADD 19.80, Uncertain significance
- R2H (p.Arg2His), rs138322602, ESP rs138322602, ExAC rs138322602, TOPMed rs138322602, REVEL 0.04, CADD 5.75, Uncertain significance, not specified
- R2L (p.Arg2Leu), ESP rs138322602, ExAC rs138322602, TOPMed rs138322602, gnomAD rs138322602, REVEL 0.05, CADD 8.00, Uncertain significance
- R2P (p.Arg2Pro), ESP rs138322602, ExAC rs138322602, TOPMed rs138322602, gnomAD rs138322602, REVEL 0.14, CADD 13.90, Uncertain significance
- R2S (p.Arg2Ser), rs977245811, NCI-TCGA Cosmic COSV6732, cosmic curated COSV67329, TOPMed rs977245811, REVEL 0.05, CADD 15.30, Uncertain significance
- R2R (p.Arg2Arg), gnomAD 3-114294067-C-T, CADD 7.93
- W3* (p.Trp3Ter), gnomAD rs938517138, CADD 36.00
- W3G (p.Trp3Gly), gnomAD rs1421141599
- W3R (p.Trp3Arg), gnomAD rs1421141599
- W3L (p.Trp3Leu), gnomAD 3-114294069-G-T, REVEL 0.24, MetaLR 0.19
- W3S (p.Trp3Ser), gnomAD 3-114294069-G-C, REVEL 0.26, MetaLR 0.19
- W3C (p.Trp3Cys), gnomAD 3-114294070-G-T, REVEL 0.07, MetaLR 0.17
- C4G (p.Cys4Gly), gnomAD rs1360039945, REVEL 0.15, CADD 21.60
- C4Y (p.Cys4Tyr), gnomAD rs1425212224, REVEL 0.07, CADD 12.60
- C4R (p.Cys4Arg), rs765063281, gnomAD 3-114293915-T-C, CADD 3.07, SIFT 0.07
- C4F (p.Cys4Phe), gnomAD 3-114293916-G-T, CADD 2.15, SIFT 0.08
- C4W (p.Cys4Trp), rs1362806561, gnomAD 3-114293917-T-G, CADD 7.20, SIFT 0.02
- C4C (p.Cys4Cys), gnomAD 3-114293917-T-C, CADD 7.51
- C4* (p.Cys4Ter), gnomAD 3-114294073-T-A, CADD 32.00
- L5F (p.Leu5Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L5P (p.Leu5Pro), TOPMed rs1363645948, gnomAD rs1363645948, REVEL 0.39, CADD 24.40
- L5R (p.Leu5Arg), TOPMed rs1363645948, gnomAD rs1363645948, REVEL 0.27, CADD 23.70
- L5I (p.Leu5Ile), gnomAD 3-114294074-C-A, REVEL 0.05, MetaLR 0.10
- L5L (p.Leu5Leu), gnomAD 3-114294076-C-T, CADD 7.04
- L6I (p.Leu6Ile), gnomAD 3-114294077-C-A, REVEL 0.06, MetaLR 0.16
- L6L (p.Leu6Leu), rs2078437922, gnomAD 3-114294079-C-A, CADD 8.04
- L7P (p.Leu7Pro), gnomAD rs1435416102, REVEL 0.42, CADD 25.00
- L7del (p.Leu7del), rs775454485, gnomAD 3-114294073-TCTC-, CADD 14.80
- L7V (p.Leu7Val), gnomAD 3-114294080-C-G, REVEL 0.08, MetaLR 0.20
- L7M (p.Leu7Met), gnomAD 3-114294080-C-A, REVEL 0.14, MetaLR 0.29
- L7L (p.Leu7Leu), rs1017370946, gnomAD 3-114294082-G-A, CADD 13.20
- I8F (p.Ile8Phe), ESP rs149574739, gnomAD rs149574739, REVEL 0.05, CADD 22.30
- I8V (p.Ile8Val), ESP rs149574739, gnomAD rs149574739, REVEL 0.05, CADD 16.50
- I8T (p.Ile8Thr), gnomAD 3-114294084-T-C, REVEL 0.12, MetaLR 0.11
- I8I (p.Ile8Ile), gnomAD 3-114294085-C-T, CADD 11.00
- W9R (p.Trp9Arg), gnomAD rs1221754538, REVEL 0.60, CADD 27.70
- W9G (p.Trp9Gly), gnomAD 3-114294086-T-G, REVEL 0.61, MetaLR 0.37
- W9* (p.Trp9Ter), gnomAD 3-114294087-G-A, CADD 37.00
- W9L (p.Trp9Leu), gnomAD 3-114294087-G-T, REVEL 0.44, MetaLR 0.38
- W9C (p.Trp9Cys), gnomAD 3-114294088-G-T, REVEL 0.57, MetaLR 0.38
- A10D (p.Ala10Asp), TOPMed rs1161667590, gnomAD rs1161667590, REVEL 0.18, CADD 23.80
- A10S (p.Ala10Ser), gnomAD 3-114293864-G-T, CADD 13.10, SIFT 0.01
- A10T (p.Ala10Thr), gnomAD 3-114293864-G-A, CADD 13.50, SIFT 0.04
- A10A (p.Ala10Ala), rs1318123804, gnomAD 3-114293866-C-T, CADD 11.20
- A10V (p.Ala10Val), gnomAD 3-114293877-C-T, CADD 13.60, SIFT 0.01
- A10G (p.Ala10Gly), gnomAD 3-114294090-C-G, REVEL 0.09, MetaLR 0.15
- Q11P (p.Gln11Pro), TOPMed rs894398089, gnomAD rs894398089, REVEL 0.24, CADD 24.10
- Q11* (p.Gln11Ter), rs981665642, gnomAD 3-114293888-C-T, CADD 5.34
- Q11K (p.Gln11Lys), gnomAD 3-114293888-C-A, CADD 4.67, SIFT 0.25
- Q11R (p.Gln11Arg), rs2107945851, gnomAD 3-114293889-A-G, CADD 4.14, SIFT 0.17
- Q11H (p.Gln11His), gnomAD 3-114293890-G-C, CADD 10.20, SIFT 0.31
- Q11Q (p.Gln11Gln), rs1173238936, gnomAD 3-114293890-G-A, CADD 10.50
- G12R (p.Gly12Arg), cosmic curated COSV10104, REVEL 0.37, CADD 24.20
- G12W (p.Gly12Trp), gnomAD 3-114294095-G-T, REVEL 0.23, MetaLR 0.25
- G12V (p.Gly12Val), gnomAD 3-114294096-G-T, REVEL 0.04, MetaLR 0.11
- G12G (p.Gly12Gly), rs201739271, gnomAD 3-114294097-G-T, CADD 7.26
- L13F (p.Leu13Phe), gnomAD 3-114293905-G-T, CADD 5.22, SIFT 0.12
- L13* (p.Leu13Ter), rs2107946070, gnomAD 3-114294093-AG-A, CADD 24.70
- L13L (p.Leu13Leu), rs144225399, gnomAD 3-114294098-C-T, CADD 11.90
- L13M (p.Leu13Met), gnomAD 3-114294098-C-A, REVEL 0.28, MetaLR 0.30
- L13P (p.Leu13Pro), gnomAD 3-114294099-T-C, REVEL 0.61, MetaLR 0.32
- R14G (p.Arg14Gly), TOPMed rs2078438130, REVEL 0.04, CADD 22.00
- R14K (p.Arg14Lys), rs1037690852, ClinGen CA81660457, ClinVar RCV004074678, TOPMed rs1037690852, REVEL 0.07, CADD 12.30, Uncertain significance, not specified
- R14S (p.Arg14Ser), ExAC rs771830740, gnomAD rs771830740, REVEL 0.08, CADD 15.30
- R14M (p.Arg14Met), rs1431949855, gnomAD 3-114293973-G-T, CADD 8.26, SIFT 0.13
- R14W (p.Arg14Trp), gnomAD 3-114294101-A-T, REVEL 0.16, MetaLR 0.13
- R14R (p.Arg14Arg), gnomAD 3-114294103-G-A, CADD 6.86
- Q15P (p.Gln15Pro), gnomAD rs1481730480, REVEL 0.27, CADD 24.20
- Q15R (p.Gln15Arg), gnomAD rs1481730480, REVEL 0.24, CADD 24.00
- Q15* (p.Gln15Ter), gnomAD 3-114294104-C-T, CADD 38.00
- Q15K (p.Gln15Lys), gnomAD 3-114294104-C-A, REVEL 0.12, MetaLR 0.10
- Q15L (p.Gln15Leu), gnomAD 3-114294105-A-T, REVEL 0.22, MetaLR 0.15
- Q15H (p.Gln15His), gnomAD 3-114294106-G-T, REVEL 0.12, MetaLR 0.18
- A16P (p.Ala16Pro), ExAC rs777596601, TOPMed rs777596601, gnomAD rs777596601, REVEL 0.35, CADD 23.40
- A16S (p.Ala16Ser), ExAC rs777596601, TOPMed rs777596601, gnomAD rs777596601, REVEL 0.03, CADD 20.50
- A16T (p.Ala16Thr), gnomAD 3-114294107-G-A, REVEL 0.01, MetaLR 0.12
- A16D (p.Ala16Asp), gnomAD 3-114294108-C-A, REVEL 0.26, MetaLR 0.16
- A16V (p.Ala16Val), gnomAD 3-114294108-C-T, REVEL 0.04, MetaLR 0.14
- A16A (p.Ala16Ala), gnomAD 3-114294109-T-C, CADD 6.33
- P17H (p.Pro17His), Ensembl rs897902406, REVEL 0.03, CADD 5.21
- P17S (p.Pro17Ser), cosmic curated COSV10104, Ensembl rs2078438298, REVEL 0.01, CADD 0.20
- P17A (p.Pro17Ala), rs1352999409, gnomAD 3-114293882-C-G, CADD 0.20, SIFT 0.07
- P17T (p.Pro17Thr), gnomAD 3-114293882-C-A, CADD 0.19, SIFT 0.00
- P17L (p.Pro17Leu), gnomAD 3-114294111-C-T, REVEL 0.04, MetaLR 0.07
- P17P (p.Pro17Pro), gnomAD 3-114294112-C-A, CADD 4.35
- L18P (p.Leu18Pro), Ensembl rs1576134457, REVEL 0.37, CADD 21.50
- L18V (p.Leu18Val), gnomAD 3-114293912-T-G, CADD 6.70, SIFT 0.02
- L18L (p.Leu18Leu), rs759191414, gnomAD 3-114293914-A-G, CADD 4.30
- p.Leu28dup, gnomAD 3-114293941-A-ACT, CADD 1.69
- L18I (p.Leu18Ile), gnomAD 3-114293942-C-A, CADD 2.70, SIFT 0.08
- L18F (p.Leu18Phe), rs1202694984, gnomAD 3-114293942-C-T, CADD 3.37, SIFT 0.09
- L18S (p.Leu18Ser), gnomAD 3-114294109-TC-T, CADD 11.80
- L18H (p.Leu18His), gnomAD 3-114294114-T-A, REVEL 0.20, MetaLR 0.25
- A19G (p.Ala19Gly), TOPMed rs2078438424, gnomAD rs2078438424, REVEL 0.03, CADD 8.53
- A19T (p.Ala19Thr), rs377262337, ClinGen CA2550946, ClinVar RCV004303227, ESP rs377262337, REVEL 0.03, CADD 0.09, Likely benign, not specified
- A19S (p.Ala19Ser), gnomAD 3-114293936-G-T, CADD 11.50, SIFT 0.09
- A19D (p.Ala19Asp), gnomAD 3-114293937-C-A, CADD 13.60, SIFT 0.01
- A19A (p.Ala19Ala), rs767774354, gnomAD 3-114293938-C-T, CADD 10.40
- A19V (p.Ala19Val), gnomAD 3-114294117-C-T, REVEL 0.04, MetaLR 0.07
- S20L (p.Ser20Leu), rs1322095400, gnomAD 3-114294116-G-GC, CADD 20.20
- S20T (p.Ser20Thr), gnomAD 3-114294119-T-A, REVEL 0.02, MetaLR 0.07
- S20A (p.Ser20Ala), gnomAD 3-114294119-T-G, REVEL 0.02, MetaLR 0.06
- S20P (p.Ser20Pro), gnomAD 3-114294119-T-C, REVEL 0.16, MetaLR 0.09
- S20* (p.Ser20Ter), gnomAD 3-114294120-C-A, CADD 35.00
- S20S (p.Ser20Ser), gnomAD 3-114294121-A-G, CADD 22.40
- G21E (p.Gly21Glu), NCI-TCGA Cosmic COSV6732, cosmic curated COSV67328, REVEL 0.04, CADD 21.20, Variant assessed as somatic; moderate impact.
- G21* (p.Gly21Ter), gnomAD 3-114294122-G-T, CADD 49.00, SIFT 0.05
- M22T (p.Met22Thr), cosmic curated COSV10530
- M23L (p.Met23Leu), TOPMed rs1467777402
- M23T (p.Met23Thr), Ensembl rs2078447526, CADD 5.12
- M23I (p.Met23Ile), rs573563746, gnomAD 3-114293929-G-A, CADD 10.50, SIFT 1.00
- T24I (p.Thr24Ile), Ensembl rs2107947001, REVEL 0.09, CADD 18.90
- T24K (p.Thr24Lys), gnomAD 3-114293907-C-A, CADD 1.06, SIFT 0.44
- T24A (p.Thr24Ala), gnomAD 3-114293909-A-G, CADD 3.26, SIFT 0.72
- T24N (p.Thr24Asn), gnomAD 3-114293910-C-A, CADD 2.21, SIFT 0.28
- T24S (p.Thr24Ser), rs866543667, gnomAD 3-114293910-C-G, CADD 2.38, SIFT 0.53
- G25D (p.Gly25Asp), TOPMed rs1169726816, gnomAD rs1169726816, REVEL 0.37, CADD 21.90
- G25G (p.Gly25Gly), rs373334849, gnomAD 3-114295558-C-T, CADD 5.39
- T26T (p.Thr26Thr), rs2078447590, gnomAD 3-114295561-A-G, CADD 0.20
- I27M (p.Ile27Met), ExAC rs768453703, gnomAD rs768453703, REVEL 0.11, CADD 13.00
- I27T (p.Ile27Thr), ExAC rs749016800, gnomAD rs749016800, REVEL 0.39, CADD 22.80, Uncertain significance, not specified
- I27V (p.Ile27Val), ExAC rs775439016, gnomAD rs775439016, REVEL 0.01, CADD 1.82
- E28K (p.Glu28Lys), NCI-TCGA Cosmic COSV6732, cosmic curated COSV67329, Variant assessed as somatic; moderate impact.
- E28E (p.Glu28Glu), gnomAD 3-114295567-A-G, CADD 1.16
- T30K (p.Thr30Lys), 1000Genomes rs376892258, ESP rs376892258, ExAC rs376892258, TOPMed rs376892258, REVEL 0.05, CADD 0.00, Likely benign
- T30M (p.Thr30Met), rs376892258, ClinGen CA2550968, NCI-TCGA Cosmic COSV6732, cosmic curated COSV67328, REVEL 0.05, CADD 0.00, Likely benign, not specified
- T30I (p.Thr30Ile), gnomAD 3-114293958-C-T, CADD 12.20, SIFT 0.04
- T30T (p.Thr30Thr), gnomAD 3-114293959-C-A, CADD 10.50
- G31E (p.Gly31Glu), ExAC rs759559781, gnomAD rs759559781, REVEL 0.17, CADD 22.20
- G31R (p.Gly31Arg), ExAC rs776752435, TOPMed rs776752435, gnomAD rs776752435, REVEL 0.15, CADD 21.50
- G31W (p.Gly31Trp), ExAC rs776752435, TOPMed rs776752435, gnomAD rs776752435, REVEL 0.29, CADD 23.70
- G31C (p.Gly31Cys), gnomAD 3-114293945-G-T, CADD 2.37, SIFT 0.05
- G31D (p.Gly31Asp), gnomAD 3-114293946-G-A, CADD 5.45, SIFT 0.10
- G31G (p.Gly31Gly), rs914984512, gnomAD 3-114293947-T-C, CADD 14.50
- N32K (p.Asn32Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- N32T (p.Asn32Thr), gnomAD rs1324498331, REVEL 0.20, CADD 22.80
- N32Y (p.Asn32Tyr), Ensembl rs2078447792
- N32N (p.Asn32Asn), rs1383836313, gnomAD 3-114293926-T-C, CADD 8.32
- I33M (p.Ile33Met), rs200039145, ClinGen CA2550974, ClinVar RCV004204047, ESP rs200039145, REVEL 0.24, CADD 20.20, Uncertain significance, not specified
- I33V (p.Ile33Val), rs13098836, cosmic curated COSV10530, UniProt VAR 056079, 1000Genomes rs13098836, REVEL 0.05, CADD 1.97
- I33T (p.Ile33Thr), gnomAD 3-114295581-T-C, REVEL 0.39, MetaLR 0.33
- S34F (p.Ser34Phe), rs1441981882, NCI-TCGA Cosmic COSV6732, cosmic curated COSV67329, TOPMed rs1441981882, REVEL 0.37, CADD 24.00, Variant assessed as somatic; moderate impact.
- S34Y (p.Ser34Tyr), gnomAD 3-114293952-C-A, CADD 12.90, SIFT 0.01
- S34S (p.Ser34Ser), rs750456045, gnomAD 3-114293953-C-T, CADD 9.79
- S34P (p.Ser34Pro), rs1200542845, gnomAD 3-114293966-T-C, CADD 2.91, SIFT 0.97
- A35S (p.Ala35Ser), gnomAD rs1193996002, REVEL 0.42, CADD 23.80
- A35V (p.Ala35Val), cosmic curated COSV10972
- A35A (p.Ala35Ala), rs2078447951, gnomAD 3-114295588-A-C, CADD 5.93
- E36K (p.Glu36Lys), rs142063959, ClinGen CA2550975, cosmic curated COSV67329, ClinVar RCV004190556, REVEL 0.17, CADD 13.40, Likely benign, not specified
- K37N (p.Lys37Asn), TOPMed rs2078447984, REVEL 0.12, CADD 22.60
- K37F (p.Lys37Phe), rs1223849992, gnomAD 3-114293937-CCAAA, CADD 8.71
- K37Q (p.Lys37Gln), gnomAD 3-114293939-A-C, CADD 9.94, SIFT 0.06
- K37K (p.Lys37Lys), rs1320932393, gnomAD 3-114293941-A-G, CADD 0.24
- G38D (p.Gly38Asp), Ensembl rs752473184, REVEL 0.71, CADD 24.30
- G38V (p.Gly38Val), Ensembl rs752473184
- G39D (p.Gly39Asp), TOPMed rs1428691057, REVEL 0.09, CADD 17.00
- G39S (p.Gly39Ser), NCI-TCGA Cosmic COSV6732, cosmic curated COSV67329, Variant assessed as somatic; moderate impact.
- G39A (p.Gly39Ala), rs1560030422, gnomAD 3-114294001-CG-C, CADD 1.08
- G39C (p.Gly39Cys), gnomAD 3-114295598-G-T, REVEL 0.27, MetaLR 0.22
- S40F (p.Ser40Phe), gnomAD rs1474404755, REVEL 0.63, CADD 24.40
- S40T (p.Ser40Thr), NCI-TCGA TCGA novel, CADD 9.57, Variant assessed as somatic; moderate impact.
- S40G (p.Ser40Gly), gnomAD 3-114293978-A-G, CADD 0.39, SIFT 0.20
- S40N (p.Ser40Asn), rs933863885, gnomAD 3-114293979-G-A, CADD 9.95, SIFT 0.03
- S40R (p.Ser40Arg), rs2078437128, gnomAD 3-114293980-T-G, CADD 5.17, SIFT 0.01
- S40S (p.Ser40Ser), gnomAD 3-114293980-T-C, CADD 5.52
- I41V (p.Ile41Val), gnomAD rs1192629675, REVEL 0.12, CADD 11.20
- I42del (p.Ile42del), gnomAD 3-114295603-TATC-, CADD 15.50
- I42T (p.Ile42Thr), gnomAD 3-114295608-T-C, REVEL 0.19, MetaLR 0.03
- I42I (p.Ile42Ile), gnomAD 3-114295609-C-T, CADD 7.04
- L43F (p.Leu43Phe), gnomAD rs1429798923, REVEL 0.61, CADD 17.90
- L43Y (p.Leu43Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- L43I (p.Leu43Ile), gnomAD 3-114293975-C-A, CADD 7.44, SIFT 0.18
- L43L (p.Leu43Leu), rs902381221, gnomAD 3-114293977-C-T, CADD 0.68
Public TIGIT analysis runs
- TIGIT analysis run — TIGIT (655 variants) — completed 2026-08-21