TNNI3 (Troponin I, cardiac muscle) variants and mutations
TNNI3 (also known as Troponin I, cardiac muscle) is a human protein-coding gene encoding a troponin I, cardiac muscle protein. It restrains cardiac actin-myosin interaction at low calcium and shifts position within the troponin complex when calcium binds, allowing contraction. Pathogenic variants can alter thin-filament calcium sensitivity and cause hypertrophic, restrictive, or dilated cardiomyopathy. This analysis covers 672 TNNI3 variants and mutations. Of these, 92% have computational variant effect predictions. Disease context includes hypertrophic cardiomyopathy, cardiomyopathy, familial restrictive, 1, and dilated cardiomyopathy 1FF. Example TNNI3 variants include M1I, M1V, and A2E.
Variant analysis overview
- Gene: TNNI3
- Protein: Troponin I, cardiac muscle
- UniProt accession: P19429
- Organism: Homo sapiens
- Variants analyzed: 672
- Variant scope: all variants
- Completed: 2026-08-10
Variant and mutation evidence
- Variant composition: 464 unspecified-consequence records; 1 stop retained variant; 90 synonymous variants; 94 missense variants; 7 stop-gained variants; 10 frameshift variants; 4 in-frame deletions; 1 in-frame insertions
- Prediction scores: 619 variants have prediction scores (92% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: hypertrophic cardiomyopathy, cardiomyopathy, familial restrictive, 1, dilated cardiomyopathy 1FF, dilated cardiomyopathy 2A, hypertrophic cardiomyopathy 7, familial isolated dilated cardiomyopathy, Rare familial disorder with hypertrophic cardiomyopathy, familial isolated restrictive cardiomyopathy, cardiomyopathy, Abnormality of the cardiovascular system, familial hypertrophic cardiomyopathy, dilated cardiomyopathy.
Protein structure and variant hotspots
- Protein features: 18 post-translational modification sites.
- PTM context: 69 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 TNNI3 variants
Examples include M1I, M1V, A2E, A2S, A2T, A2V, D3E, D3N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs1489475656, ClinGen CA407443564, ClinVar RCV001935570, MetaLR 0.80, MetaSVM 0.36, Uncertain significance, Hypertrophic cardiomyopathy
- M1V (p.Met1Val), rs397516341, ClinGen CA021351, ClinVar RCV000036273, ClinVar RCV001729362, MetaLR 0.80, MetaSVM 0.39, Uncertain significance, Hypertrophic cardiomyopathy
- A2E (p.Ala2Glu), NCI-TCGA Cosmic COSV1007, REVEL 0.33, MetaLR 0.82, Uncertain significance, Hypertrophic cardiomyopathy
- A2S (p.Ala2Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact., in CMD2A
- A2T (p.Ala2Thr), TOPMed rs2085744249
- A2V (p.Ala2Val), rs397516359, ClinGen CA022031, NCI-TCGA Cosmic COSV1007, REVEL 0.61, MetaLR 0.89, Conflicting interpretations, not specified; Cardiovascular phenotype; not provided
- D3E (p.Asp3Glu), rs2085744143, ClinGen CA407443515, ClinVar RCV003297327, Uncertain significance, Cardiovascular phenotype
- D3N (p.Asp3Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D3Y (p.Asp3Tyr), rs2085744165, ClinGen CA407443526, ClinVar RCV001219800, Ensembl rs2085744165, AlphaMissense 0.16, MetaLR 0.89, Uncertain significance, Hypertrophic cardiomyopathy
- G4A (p.Gly4Ala), gnomAD rs1351385449, REVEL 0.32, MetaLR 0.68, Likely benign
- G4E (p.Gly4Glu), rs1351385449, ClinGen CA407443505, ClinVar RCV001308925, ClinVar RCV002350559, REVEL 0.25, MetaLR 0.61, Conflicting interpretations, Hypertrophic cardiomyopathy; Cardiovascular phenotype
- G4R (p.Gly4Arg), rs1327794718, TOPMed rs1327794718, ClinGen CA407443510, ClinVar RCV001929719, AlphaMissense 0.13, MetaLR 0.60, Uncertain significance, Hypertrophic cardiomyopathy
- G4W (p.Gly4Trp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G4L (p.Gly4Leu), gnomAD 19-55156359-GCC-G, CADD 0.64
- G4G (p.Gly4Gly), gnomAD 19-55156359-G-A, CADD 7.72
- G4D (p.Gly4Asp), rs1330144062, gnomAD 19-55156360-C-T, CADD 1.24
- G4S (p.Gly4Ser), gnomAD 19-55156361-C-T, CADD 1.93
- S5G (p.Ser5Gly), rs2085740955, ClinGen CA407443418, ClinVar RCV001227637, ClinVar RCV004679014, AlphaMissense 0.06, MetaLR 0.32, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy
- S5R (p.Ser5Arg), rs989588363, ClinGen CA310150545, ClinVar RCV001182196, ClinVar RCV001305113, REVEL 0.23, MetaLR 0.31, Conflicting interpretations, Cardiomyopathy; Hypertrophic cardiomyopathy
- S6G (p.Ser6Gly), rs2515504344, ClinGen CA407443395, ClinVar RCV002406295, Likely benign, Cardiovascular phenotype
- D7H (p.Asp7His), rs1201960520, ClinGen CA407443378, ClinVar RCV000521742, TOPMed rs1201960520, REVEL 0.24, MetaLR 0.48, Uncertain significance, not provided
- D7N (p.Asp7Asn), rs1201960520, TOPMed rs1201960520, gnomAD rs1201960520, REVEL 0.19, MetaLR 0.38, Uncertain significance, Cardiomyopathy; Cardiovascular phenotype; Hypertrophic cardiomyopathy
- A8G (p.Ala8Gly), rs770640091, ClinGen CA407443348, ClinVar RCV004017183, AlphaMissense 0.10, MetaLR 0.26, Uncertain significance, Dilated cardiomyopathy 1FF
- A8V (p.Ala8Val), ExAC rs770640091, gnomAD rs770640091, REVEL 0.23, AlphaMissense 0.10
- A9T (p.Ala9Thr), TOPMed rs2085739039
- A9V (p.Ala9Val), rs771967539, ClinGen CA050955, ClinVar RCV003587288, ExAC rs771967539, REVEL 0.19, MetaLR 0.27, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy
- R10G (p.Arg10Gly), rs2085739021, ClinGen CA407443267, ClinVar RCV001184358, ClinVar RCV006557143, AlphaMissense 0.05, MetaLR 0.18, Conflicting interpretations, Cardiomyopathy; Hypertrophic cardiomyopathy
- R10S (p.Arg10Ser), rs2085738998, ClinGen CA407443247, ClinVar RCV001180476, ClinVar RCV004803469, REVEL 0.15, MetaLR 0.22, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy
- E11K (p.Glu11Lys), gnomAD rs1379665147, REVEL 0.10, MetaLR 0.34
- P12L (p.Pro12Leu), rs768052584, ClinGen CA051333, ClinVar RCV001185813, ClinVar RCV001876174, REVEL 0.21, MetaLR 0.34, Uncertain significance, Hypertrophic cardiomyopathy; Cardiovascular phenotype; Cardiomyopathy
- P12S (p.Pro12Ser), rs553214254, ClinGen CA051305, ClinVar RCV001175475, ClinVar RCV001182994, REVEL 0.09, MetaLR 0.23, Uncertain significance, not specified; Cardiomyopathy; Cardiovascular phenotype
- P12T (p.Pro12Thr), 1000Genomes rs553214254, ExAC rs553214254, gnomAD rs553214254, REVEL 0.13, MetaLR 0.29, Uncertain significance
- R13H (p.Arg13His), rs2085738889, ClinGen CA407443203, ClinVar RCV002278877, TOPMed rs2085738889, REVEL 0.20, MetaLR 0.29, Uncertain significance, not provided
- R13L (p.Arg13Leu), TOPMed rs2085738889, REVEL 0.22, MetaLR 0.28, Uncertain significance
- P14A (p.Pro14Ala), rs2085738832, ClinGen CA407443197, ClinVar RCV003749458, TOPMed rs2085738832, AlphaMissense 0.05, MetaLR 0.90, Uncertain significance, Hypertrophic cardiomyopathy
- P14S (p.Pro14Ser), NCI-TCGA Cosmic COSV6127, MetaLR 0.90, MetaSVM 0.99, Variant assessed as somatic; moderate impact.
- A17V (p.Ala17Val), TOPMed rs2085738776, REVEL 0.16, MetaLR 0.37
- P18A (p.Pro18Ala), rs779416591, ClinGen CA407443129, ClinVar RCV001180213, ExAC rs779416591, REVEL 0.34, MetaLR 0.81, Uncertain significance, Cardiomyopathy
- P18S (p.Pro18Ser), ExAC rs779416591, TOPMed rs779416591, gnomAD rs779416591, REVEL 0.35, MetaLR 0.87, Uncertain significance
- P18T (p.Pro18Thr), rs779416591, ClinGen CA051703, ClinVar RCV001858852, ExAC rs779416591, REVEL 0.36, MetaLR 0.87, Uncertain significance, Hypertrophic cardiomyopathy
- I19L (p.Ile19Leu), rs755862334, ClinGen CA407443121, ClinVar RCV001804613, ClinVar RCV002343868, REVEL 0.26, MetaLR 0.22, Uncertain significance, Cardiomyopathy; Cardiovascular phenotype; Hypertrophic cardiomyopathy
- I19M (p.Ile19Met), ExAC rs778133452, TOPMed rs778133452, gnomAD rs778133452, REVEL 0.22, MetaLR 0.34, Likely benign
- I19N (p.Ile19Asn), Ensembl rs894238478
- I19T (p.Ile19Thr), NCI-TCGA Cosmic COSV6127, MetaLR 0.31, MetaSVM -0.82, Variant assessed as somatic; moderate impact.
- I19V (p.Ile19Val), rs755862334, ClinGen CA051852, ClinVar RCV000694571, ClinVar RCV001191348, REVEL 0.28, MetaLR 0.20, Conflicting interpretations, Cardiomyopathy; Hypertrophic cardiomyopathy
- R20S (p.Arg20Ser), rs2515503781, ClinGen CA407443100, ClinVar RCV003587997, Uncertain significance, Hypertrophic cardiomyopathy
- R21C (p.Arg21Cys), rs267607128, ClinGen CA022092, ClinVar RCV000013247, ClinVar RCV001851817, REVEL 0.63, MetaLR 0.83, Pathogenic, Cardiovascular phenotype; Hypertrophic cardiomyopathy
- R21H (p.Arg21His), NCI-TCGA Cosmic COSV6127, REVEL 0.42, MetaLR 0.83, Uncertain significance, Hypertrophic cardiomyopathy
- R21S (p.Arg21Ser), rs267607128, ClinGen CA407443093, ClinVar RCV000809848, Ensembl rs267607128, REVEL 0.47, MetaLR 0.74, Uncertain significance, Hypertrophic cardiomyopathy
- R22G (p.Arg22Gly), rs2085738602, ClinGen CA407443080, ClinVar RCV001170845, ClinVar RCV002557471, AlphaMissense 0.35, MetaLR 0.55, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy
- R22H (p.Arg22His), rs397516360, ClinGen CA022115, ClinVar RCV000036310, ClinVar RCV000808735, REVEL 0.34, MetaLR 0.56, Uncertain significance, not specified; Hypertrophic cardiomyopathy
- R22L (p.Arg22Leu), rs397516360, ClinGen CA407443073, ClinVar RCV000628892, ClinVar RCV006367163, REVEL 0.38, MetaLR 0.52, Uncertain significance, Hypertrophic cardiomyopathy; Cardiovascular phenotype
- S23P (p.Ser23Pro), rs1555864374, ClinGen CA407443069, ClinVar RCV000546206, ClinVar RCV000786226, AlphaMissense 0.53, MetaLR 0.78, Uncertain significance, Hypertrophic cardiomyopathy; not provided
- S23S (p.Ser23Ser), rs796760216, []
- S24F (p.Ser24Phe), rs1056846497, ClinGen CA310150385, ClinVar RCV001190554, ClinVar RCV004803542, REVEL 0.48, MetaLR 0.82, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy
- S24T (p.Ser24Thr), rs2085738488, ClinGen CA407443054, ClinVar RCV001306062, ClinVar RCV005403022, AlphaMissense 0.28, MetaLR 0.80, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy
- N25D (p.Asn25Asp), rs2085738407, ClinGen CA407443033, ClinVar RCV001181194, Ensembl rs2085738407, AlphaMissense 0.57, MetaLR 0.74, Uncertain significance, Cardiomyopathy
- N25I (p.Asn25Ile), rs1555864368, ClinGen CA407443023, ClinVar RCV001180969, Ensembl rs1555864368, AlphaMissense 0.16, MetaLR 0.65, Uncertain significance, Cardiomyopathy
- N25K (p.Asn25Lys), rs1568859781, ClinGen CA407443015, ClinVar RCV000774299, Ensembl rs1568859781, REVEL 0.42, MetaLR 0.70, Uncertain significance, Cardiomyopathy
- N25S (p.Asn25Ser), rs1555864368, ClinGen CA407443029, ClinVar RCV003443297, Ensembl rs1555864368, REVEL 0.37, AlphaMissense 0.16, Uncertain significance, not provided
- N25T (p.Asn25Thr), rs1555864368, ClinGen CA407443026, ClinVar RCV000628900, Ensembl rs1555864368, AlphaMissense 0.16, MetaLR 0.65, Uncertain significance, Hypertrophic cardiomyopathy
- Y26* (p.Tyr26Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- Y26C (p.Tyr26Cys), rs2147285958, ClinGen CA407442995, ClinVar RCV002010616, Ensembl rs2147285958, AlphaMissense 0.80, MetaLR 0.83, Uncertain significance, Hypertrophic cardiomyopathy
- R27C (p.Arg27Cys), rs1555864366, ClinGen CA407442981, ClinVar RCV001036946, ClinVar RCV002259377, REVEL 0.65, MetaLR 0.78, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy
- R27G (p.Arg27Gly), rs1555864366, ClinGen CA407442984, ClinVar RCV000606248, ClinVar RCV000800634, CADD 0.57, Uncertain significance, Cardiovascular phenotype; not specified; Hypertrophic cardiomyopathy
- R27H (p.Arg27His), rs2147285955, ClinGen CA407442976, NCI-TCGA Cosmic COSV6127, ClinVar RCV002298146, REVEL 0.54, MetaLR 0.76, Uncertain significance, Hypertrophic cardiomyopathy
- R27P (p.Arg27Pro), rs2147285955, ClinGen CA407442973, ClinVar RCV001907930, ClinVar RCV002422937, CADD 0.80, Uncertain significance, Hypertrophic cardiomyopathy; Cardiovascular phenotype
- R27R (p.Arg27Arg), gnomAD 19-55156365-C-T, CADD 3.60
- A28S (p.Ala28Ser), rs2147285950, ClinGen CA407442966, ClinVar RCV003533541, ClinVar RCV004804652, REVEL 0.23, MetaLR 0.20, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy
- A28T (p.Ala28Thr), rs2147285950, ClinGen CA407442964, ClinVar RCV002037156, NCI-TCGA TCGA novel, REVEL 0.29, MetaLR 0.42, Uncertain significance, Hypertrophic cardiomyopathy
- A28V (p.Ala28Val), rs1194177269, ClinGen CA407442955, ClinVar RCV003749975, TOPMed rs1194177269, REVEL 0.29, MetaLR 0.53, Uncertain significance, Hypertrophic cardiomyopathy
- Y29C (p.Tyr29Cys), rs2085738286, ClinGen CA407442943, ClinVar RCV001344454, Ensembl rs2085738286, AlphaMissense 0.49, MetaLR 0.83, Uncertain significance, Hypertrophic cardiomyopathy
- Y29D (p.Tyr29Asp), rs727503510, ClinGen CA022127, ClinVar RCV000152092, ClinVar RCV003998232, AlphaMissense 0.75, MetaLR 0.72, Uncertain significance, not specified; Hypertrophic cardiomyopathy
- Y29H (p.Tyr29His), NCI-TCGA Cosmic COSV6127, Variant assessed as somatic; moderate impact.
- Y29S (p.Tyr29Ser), Ensembl rs2085738286, MetaLR 0.83, MetaSVM 0.79, Uncertain significance, Hypertrophic cardiomyopathy
- A30T (p.Ala30Thr), rs796104366, ClinGen CA10587918, ClinVar RCV000246508, ClinVar RCV000493547, REVEL 0.40, MetaLR 0.64, Uncertain significance, Cardiovascular phenotype; not specified; not provided
- A30V (p.Ala30Val), Ensembl rs867738263, REVEL 0.39, MetaLR 0.61
- A30D (p.Ala30Asp), gnomAD 19-55156354-G-T, CADD 6.67
- A30S (p.Ala30Ser), rs1599911228, gnomAD 19-55156355-C-A, CADD 4.28
- T31A (p.Thr31Ala), rs1298916040, ClinGen CA407442920, ClinVar RCV001524401, ClinVar RCV004804211, AlphaMissense 0.15, MetaLR 0.47, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy
- T31M (p.Thr31Met), rs201928445, ClinGen CA052001, ClinVar RCV000774233, ClinVar RCV000812844, REVEL 0.38, MetaLR 0.55, Uncertain significance, Cardiovascular phenotype; not provided; Cardiomyopathy
- T31P (p.Thr31Pro), gnomAD rs1298916040, REVEL 0.44, AlphaMissense 0.15, Uncertain significance
- T31R (p.Thr31Arg), rs201928445, ClinGen CA407442911, ClinVar RCV003029658, REVEL 0.49, MetaLR 0.59, Uncertain significance, Hypertrophic cardiomyopathy
- E32G (p.Glu32Gly), rs2515503663, ClinGen CA407442900, ClinVar RCV003384115, REVEL 0.57, MetaLR 0.79, Uncertain significance, Cardiovascular phenotype
- E32Q (p.Glu32Gln), gnomAD rs1325580070, REVEL 0.39, MetaLR 0.85
- P33L (p.Pro33Leu), rs2147285907, ClinGen CA407442871, ClinVar RCV002014492, Ensembl rs2147285907, REVEL 0.55, AlphaMissense 0.39, Uncertain significance, Hypertrophic cardiomyopathy
- P33Q (p.Pro33Gln), rs2147285907, ClinGen CA407442876, ClinVar RCV001372354, Ensembl rs2147285907, REVEL 0.49, AlphaMissense 0.39, Uncertain significance, Hypertrophic cardiomyopathy
- P33R (p.Pro33Arg), rs2147285907, ClinGen CA407442875, ClinVar RCV004008018, AlphaMissense 0.39, MetaLR 0.85, Uncertain significance, Hypertrophic cardiomyopathy
- P33S (p.Pro33Ser), gnomAD rs1379608043, REVEL 0.45, MetaLR 0.76, Uncertain significance
- P33T (p.Pro33Thr), rs1379608043, ClinGen CA407442886, ClinVar RCV001772780, gnomAD rs1379608043, REVEL 0.57, MetaLR 0.81, Uncertain significance, not provided
- P33H (p.Pro33His), gnomAD 19-55156342-G-T, CADD 9.66
- H34L (p.His34Leu), ExAC rs759949951, gnomAD rs759949951, REVEL 0.51, MetaLR 0.73
- H34Q (p.His34Gln), TOPMed rs2085737900, REVEL 0.41, MetaLR 0.64, Uncertain significance, Hypertrophic cardiomyopathy
- A35D (p.Ala35Asp), rs1190447904, ClinGen CA407442831, ClinVar RCV001133669, ClinVar RCV001133670, REVEL 0.48, MetaLR 0.70, Uncertain significance, Dilated cardiomyopathy 2A; Cardiomyopathy, familial restrictive, 1; Hypertrophic
- A35T (p.Ala35Thr), rs1408482066, ClinGen CA407442842, ClinVar RCV001943658, gnomAD rs1408482066, REVEL 0.38, MetaLR 0.71, Uncertain significance, Hypertrophic cardiomyopathy
- A35V (p.Ala35Val), rs1190447904, ClinGen CA407442832, ClinVar RCV000556107, ClinVar RCV001191186, REVEL 0.37, MetaLR 0.66, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy 7; Dilated cardiomyopathy
- K36Q (p.Lys36Gln), rs267607130, ClinGen CA021239, ClinVar RCV000013243, UniProt VAR 063548, AlphaMissense 0.18, MetaLR 0.78, Pathogenic, Dilated cardiomyopathy 1FF
- K36R (p.Lys36Arg), rs886039441, ClinGen CA407442813, ClinVar RCV002017123, Ensembl rs886039441, AlphaMissense 0.45, MetaLR 0.80, Uncertain significance, Hypertrophic cardiomyopathy
- K36T (p.Lys36Thr), rs886039441, ClinGen CA10588688, ClinVar RCV000255623, Ensembl rs886039441, AlphaMissense 0.45, MetaLR 0.80, Uncertain significance, not provided
- K38N (p.Lys38Asn), rs730881066, ClinGen CA021251, ClinVar RCV000159209, ClinVar RCV001525777, REVEL 0.59, MetaLR 0.94, Conflicting interpretations, Cardiovascular phenotype; not provided; Cardiomyopathy
- S39C (p.Ser39Cys), rs2085732731, ClinGen CA407442483, ClinVar RCV001184655, ClinVar RCV001876150, REVEL 0.34, MetaLR 0.81, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy
- S39P (p.Ser39Pro), rs1568859416, ClinGen CA407442488, ClinVar RCV002375438, ClinVar RCV003094454, REVEL 0.48, MetaLR 0.73, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy
- S39S (p.Ser39Ser), gnomAD 19-55156350-G-A, CADD 7.65
- S39Y (p.Ser39Tyr), gnomAD 19-55156351-G-T, CADD 2.94
- K40M (p.Lys40Met), rs2515502447, ClinGen CA407442468, ClinVar RCV002344683, ClinVar RCV005096766, REVEL 0.79, MetaLR 0.89, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy
- K40R (p.Lys40Arg), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10078, MetaLR 0.88, MetaSVM 0.93, Variant assessed as somatic; moderate impact.
- I41M (p.Ile41Met), rs1311862702, ClinGen CA407442444, ClinVar RCV002004966, ClinVar RCV003136366, AlphaMissense 0.53, MetaLR 0.74, Uncertain significance, Hypertrophic cardiomyopathy; not provided
- I41N (p.Ile41Asn), rs2085732683, ClinGen CA407442446, ClinVar RCV001178001, ClinVar RCV004006431, REVEL 0.90, MetaLR 0.88, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy
- I41V (p.Ile41Val), rs2515502445, ClinGen CA407442462, ClinVar RCV003017469, ClinVar RCV006546237, REVEL 0.55, MetaLR 0.81, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy
- S42C (p.Ser42Cys), TOPMed rs2085732640, REVEL 0.64, MetaLR 0.79, Uncertain significance
- S42F (p.Ser42Phe), rs2085732640, ClinGen CA407442426, ClinVar RCV001203526, ClinVar RCV001799048, REVEL 0.72, MetaLR 0.81, Uncertain significance, Cardiovascular phenotype; Cardiomyopathy; Hypertrophic cardiomyopathy
- S42P (p.Ser42Pro), rs2515502440, ClinGen CA407442439, ClinVar RCV003314308, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy 7
- A43G (p.Ala43Gly), rs2085732607, ClinGen CA407442414, ClinVar RCV001305951, Ensembl rs2085732607, AlphaMissense 0.60, MetaLR 0.88, Uncertain significance, Hypertrophic cardiomyopathy
- A43S (p.Ala43Ser), rs727505023, ClinGen CA021272, ClinVar RCV000156448, ClinVar RCV004019879, REVEL 0.39, MetaLR 0.79, Uncertain significance, Cardiovascular phenotype; not specified
- A43T (p.Ala43Thr), rs727505023, ClinGen CA407442424, ClinVar RCV001810382, ClinVar RCV003748364, REVEL 0.45, MetaLR 0.85, Conflicting interpretations, Hypertrophic cardiomyopathy; not provided
- S44A (p.Ser44Ala), rs2147285302, ClinGen CA407442410, ClinVar RCV002246776, Ensembl rs2147285302, AlphaMissense 0.23, MetaLR 0.85, Pathogenic, Cardiomyopathy, familial restrictive, 1
- S44L (p.Ser44Leu), rs730881085, ClinGen CA407442404, ClinVar RCV004525332, REVEL 0.68, AlphaMissense 0.89, Uncertain significance, Cardiovascular phenotype
- S44T (p.Ser44Thr), rs2147285302, ClinGen CA407442413, ClinVar RCV002385420, AlphaMissense 0.23, MetaLR 0.85, Uncertain significance, Cardiovascular phenotype
- S44W (p.Ser44Trp), rs730881085, ClinGen CA021278, ClinVar RCV000159256, ClinVar RCV001058132, AlphaMissense 0.89, MetaLR 0.90, Conflicting interpretations, Cardiovascular phenotype; not provided; Hypertrophic cardiomyopathy
- S44R (p.Ser44Arg), rs772695512, gnomAD 19-55156281-G-T, CADD 15.20
- S44N (p.Ser44Asn), rs1276999572, gnomAD 19-55156282-C-T, CADD 13.40
- R45K (p.Arg45Lys), rs2147285293, ClinGen CA407442396, ClinVar RCV002008882, ClinVar RCV004045241, AlphaMissense 0.80, MetaLR 0.91, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy
- R45Q (p.Arg45Gln), rs2147284967, gnomAD 19-55156288-C-T, CADD 6.76
- R45L (p.Arg45Leu), gnomAD 19-55156288-C-A, CADD 6.30
- K46* (p.Lys46Ter), rs2085732554, ClinGen CA407442383, ClinVar RCV001189336, Ensembl rs2085732554, Uncertain significance
- K46I (p.Lys46Ile), rs2147285289, ClinGen CA407442374, ClinVar RCV001367875, Ensembl rs2147285289, AlphaMissense 0.97, MetaLR 0.93, Uncertain significance, Hypertrophic cardiomyopathy
- K46R (p.Lys46Arg), gnomAD 19-55156306-T-C, CADD 14.20
- L47R (p.Leu47Arg), rs1438878332, gnomAD 19-55156330-A-C, CADD 12.80
- L47P (p.Leu47Pro), gnomAD 19-55156330-A-G, CADD 13.40
- L47F (p.Leu47Phe), rs786204398, gnomAD 19-55156340-G-A, CADD 8.86
- L47I (p.Leu47Ile), gnomAD 19-55156340-G-T, CADD 12.70
- L47V (p.Leu47Val), rs1013144337, gnomAD 19-55156349-G-C, CADD 1.50
- L47H (p.Leu47His), gnomAD 19-55156349-GGGAA, CADD 5.17
- Q48* (p.Gln48Ter), gnomAD rs1384960650, CADD 46.00
- Q48H (p.Gln48His), Ensembl rs866918068, REVEL 0.46, MetaLR 0.61
- Q48L (p.Gln48Leu), 1000Genomes rs200720341, ExAC rs200720341, gnomAD rs200720341, REVEL 0.33, MetaLR 0.48, Uncertain significance
- Q48P (p.Gln48Pro), rs200720341, ClinGen CA050324, ClinVar RCV000253227, ClinVar RCV000656735, REVEL 0.75, MetaLR 0.77, Uncertain significance, Hypertrophic cardiomyopathy; not provided; Cardiomyopathy
- Q48R (p.Gln48Arg), 1000Genomes rs200720341, ExAC rs200720341, gnomAD rs200720341, REVEL 0.61, MetaLR 0.73, Uncertain significance
- L49Q (p.Leu49Gln), rs1397663689, ClinGen CA407442355, ClinVar RCV003172081, ClinVar RCV004009636, REVEL 0.92, MetaLR 0.91, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy
- L49V (p.Leu49Val), gnomAD rs1445843881, REVEL 0.78, MetaLR 0.89, Uncertain significance, Cardiomyopathy
- T51A (p.Thr51Ala), rs2515501787, ClinGen CA407442124, ClinVar RCV002392389, Uncertain significance, Cardiovascular phenotype
- T51I (p.Thr51Ile), rs1366283106, ClinGen CA407442118, ClinVar RCV001189767, ClinVar RCV005762196, REVEL 0.57, MetaLR 0.59, Uncertain significance, Cardiovascular phenotype; Cardiomyopathy
- T51N (p.Thr51Asn), gnomAD 19-55156331-G-T, REVEL 0.43, MetaLR 0.62
- L52P (p.Leu52Pro), rs2147285030, ClinGen CA407442102, ClinVar RCV002050686, Ensembl rs2147285030, REVEL 0.87, MetaLR 0.92, Uncertain significance, Hypertrophic cardiomyopathy
- L52V (p.Leu52Val), rs2147285032, ClinGen CA407442106, ClinVar RCV001871530, Ensembl rs2147285032, AlphaMissense 0.16, MetaLR 0.89, Uncertain significance, Hypertrophic cardiomyopathy
- L52M (p.Leu52Met), gnomAD 19-55156329-G-T, REVEL 0.70, MetaLR 0.92
- L53G (p.Leu53Gly), rs2515501775, ClinGen CA2740096977, ClinVar RCV003837696, Uncertain significance, Hypertrophic cardiomyopathy
- L53R (p.Leu53Arg), ExAC rs762589736, TOPMed rs762589736, gnomAD rs762589736
- L53V (p.Leu53Val), ExAC rs763981651, TOPMed rs763981651, gnomAD rs763981651, Likely benign
- L53P (p.Leu53Pro), gnomAD 19-55156325-A-G, REVEL 0.93, MetaLR 0.86
- L53L (p.Leu53Leu), rs763981651, gnomAD 19-55156326-G-A, CADD 15.50
- L54del (p.Leu54del), gnomAD 19-55156319-TGCA-, CADD 22.80
- L54L (p.Leu54Leu), rs1555864068, gnomAD 19-55156323-G-A, CADD 16.30
- Q55P (p.Gln55Pro), rs775512887, ClinGen CA050551, ClinVar RCV000704620, ClinVar RCV001185161, REVEL 0.80, MetaLR 0.85, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy; Cardiomyopathy
- I56M (p.Ile56Met), rs727503509, ClinGen CA021335, ClinVar RCV000152090, ClinVar RCV001850073, REVEL 0.29, MetaLR 0.57, Uncertain significance, Cardiovascular phenotype; not specified; Hypertrophic cardiomyopathy
- I56T (p.Ile56Thr), rs545441942, ClinGen CA021328, ClinVar RCV000798666, ClinVar RCV002483314, REVEL 0.56, MetaLR 0.77, Uncertain significance, Cardiovascular phenotype; Cardiomyopathy, familial restrictive, 1; Hypertrophic
- I56V (p.Ile56Val), rs765219322, ClinGen CA050564, ClinVar RCV001981121, ExAC rs765219322, AlphaMissense 0.10, MetaLR 0.58, Uncertain significance, Hypertrophic cardiomyopathy
- A57G (p.Ala57Gly), TOPMed rs1300290294, CADD 8.47
- A57E (p.Ala57Glu), rs201422579, gnomAD 19-55156276-G-T, CADD 7.29
- A57T (p.Ala57Thr), gnomAD 19-55156314-C-T, REVEL 0.81, MetaLR 0.96
- K58R (p.Lys58Arg), rs878853955, ClinGen CA10583865, ClinVar RCV000226371, ClinVar RCV000253395, AlphaMissense 0.09, MetaLR 0.74, Conflicting interpretations, Cardiovascular phenotype; not specified; not provided
- K58T (p.Lys58Thr), rs878853955, ClinGen CA407441988, ClinVar RCV001181753, Ensembl rs878853955, AlphaMissense 0.09, MetaLR 0.74, Uncertain significance, Cardiomyopathy
- Q59* (p.Gln59Ter), rs2085729446, ClinGen CA407441981, ClinVar RCV003231888, AlphaMissense 0.08, MetaLR 0.24, Uncertain significance
- Q59E (p.Gln59Glu), rs2085729446, ClinGen CA407441982, ClinVar RCV001182605, Ensembl rs2085729446, REVEL 0.20, AlphaMissense 0.08, Uncertain significance, Cardiomyopathy
- Q59K (p.Gln59Lys), gnomAD 19-55156308-G-T, REVEL 0.20, MetaLR 0.52
- E60D (p.Glu60Asp), gnomAD rs1487255292
- E60G (p.Glu60Gly), rs2085729410, ClinGen CA407441961, ClinVar RCV001189077, Ensembl rs2085729410, AlphaMissense 0.28, MetaLR 0.87, Uncertain significance, Cardiomyopathy
- E60Q (p.Glu60Gln), ExAC rs776162352, gnomAD rs776162352, REVEL 0.66, MetaLR 0.89, Uncertain significance, Cardiovascular phenotype
- L61M (p.Leu61Met), gnomAD 19-55156302-G-T, REVEL 0.35, MetaLR 0.67
- E62* (p.Glu62Ter), rs1357844466, ClinGen CA407441936, ClinVar RCV004545966, ClinVar RCV004587646, AlphaMissense 0.27, MetaLR 0.78, Likely pathogenic
- E62G (p.Glu62Gly), Ensembl rs2085729352, REVEL 0.85, MetaLR 0.90, Uncertain significance, Hypertrophic cardiomyopathy 7
- E62K (p.Glu62Lys), rs1357844466, ClinGen CA407441938, ClinVar RCV000530156, ClinVar RCV000786225, AlphaMissense 0.27, MetaLR 0.78, Uncertain significance, Hypertrophic cardiomyopathy; not provided
- R63* (p.Arg63Ter), rs1286340820, ClinGen CA407441923, ClinVar RCV003749272, gnomAD rs1286340820, CADD 40.00, Pathogenic
- R63Q (p.Arg63Gln), rs1205435733, ClinGen CA407441922, ClinVar RCV004015271, ClinVar RCV006551096, REVEL 0.28, MetaLR 0.41, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy
- R63P (p.Arg63Pro), gnomAD 19-55156295-C-G, REVEL 0.64, MetaLR 0.74
- E64* (p.Glu64Ter), rs1245885836, ClinGen CA407441911, ClinVar RCV000628965, TOPMed rs1245885836, AlphaMissense 0.30, Pathogenic
- E64D (p.Glu64Asp), TOPMed rs2085729289
- E64Q (p.Glu64Gln), rs1245885836, ClinGen CA407441912, ClinVar RCV003288343, ClinVar RCV003748483, AlphaMissense 0.30, Uncertain significance, Hypertrophic cardiomyopathy; Cardiovascular phenotype
- A65T (p.Ala65Thr), Ensembl rs2085729273
- A65V (p.Ala65Val), rs1057518784, ClinGen CA16043560, ClinVar RCV000415365, ClinVar RCV001183815, REVEL 0.47, MetaLR 0.59, Uncertain significance, Primary dilated cardiomyopathy; Hypertrophic cardiomyopathy; Cardiovascular phen
Public TNNI3 analysis runs
- TNNI3 analysis run — TNNI3 (672 variants) — completed 2026-08-10