TBX5 (T-box transcription factor TBX5) variants and mutations
TBX5 (also known as T-box transcription factor TBX5) is a human protein-coding gene encoding a t-box transcription factor protein. It directs upper-limb and cardiac developmental programs and later helps maintain cardiac conduction gene expression. Haploinsufficiency causes Holt-Oram syndrome, characterized by radial-ray limb abnormalities and congenital heart or conduction defects. This analysis covers 1,246 TBX5 variants and mutations. Of these, 66% have computational variant effect predictions. Disease context includes Holt-Oram syndrome, aortic valve disease 2, and atrial fibrillation. Example TBX5 variants include M1?, A2G, and A2T.
Variant analysis overview
- Gene: TBX5
- Protein: T-box transcription factor TBX5
- UniProt accession: Q99593
- Organism: Homo sapiens
- Variants analyzed: 1246
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 923 unspecified-consequence records; 8 frameshift variants; 156 synonymous variants; 147 missense variants; 3 stop-gained variants; 3 in-frame deletions; 2 in-frame insertions; 1 protein altering variant; 2 splice-region variants; 3 substitution
- Prediction scores: 825 variants have prediction scores (66% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Holt-Oram syndrome, aortic valve disease 2, atrial fibrillation, Abnormality of the cardiovascular system, Abnormality of the skeletal system, atrial flutter, cardiac arrhythmia, neurodegenerative disease, hypertensive disorder, heart disorder, Brugada syndrome, coronary atherosclerosis.
Protein structure and variant hotspots
- Protein features: 1 post-translational modification sites.
- PTM context: 2 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 TBX5 variants
Examples include M1?, A2G, A2T, D3E, D3G, D3N, A4G, A4S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA Cosmic COSV5986, cosmic curated COSV59863, Variant assessed as somatic; high impact.
- A2G (p.Ala2Gly), Ensembl rs2136424843
- A2T (p.Ala2Thr), rs1246421378, ClinGen CA386863702, ClinVar RCV002343050, gnomAD rs1246421378, REVEL 0.46, CADD 28.60, Uncertain significance, Cardiovascular phenotype
- D3E (p.Asp3Glu), Ensembl rs774750288, REVEL 0.38, CADD 23.30
- D3G (p.Asp3Gly), Ensembl rs1872012683
- D3N (p.Asp3Asn), rs1565943407, Ensembl rs1565943407, REVEL 0.27, CADD 22.80, Uncertain significance, not provided
- A4G (p.Ala4Gly), gnomAD rs1414031361, REVEL 0.21, CADD 18.50
- A4S (p.Ala4Ser), gnomAD rs1319312312, REVEL 0.24, CADD 18.50, Uncertain significance
- A4T (p.Ala4Thr), rs1319312312, ClinGen CA386863691, NCI-TCGA Cosmic COSV5985, cosmic curated COSV59859, REVEL 0.18, CADD 20.70, Uncertain significance, Aortic valve disease 2
- D5N (p.Asp5Asn), rs886048999, ClinGen CA10632086, ClinVar RCV000349562, ClinVar RCV004668891, AlphaMissense 0.12, MetaLR 0.47, Uncertain significance, Holt-Oram syndrome; Cardiovascular phenotype
- E6* (p.Glu6Ter), cosmic curated COSV59863
- E6D (p.Glu6Asp), NCI-TCGA TCGA novel, REVEL 0.20, CADD 18.10, Variant assessed as somatic; moderate impact.
- E6K (p.Glu6Lys), rs145365553, ClinGen CA6809742, cosmic curated COSV59861, NCI-TCGA Cosmic COSV5986, REVEL 0.43, CADD 25.40, Benign/Likely benign, Cardiovascular phenotype; Aortic valve disease 2; not specified
- G7D (p.Gly7Asp), ExAC rs751312844, gnomAD rs751312844, REVEL 0.33, CADD 23.50
- G7R (p.Gly7Arg), TOPMed rs962421632, gnomAD rs962421632, REVEL 0.34, CADD 24.40, Uncertain significance, Cardiovascular phenotype
- F8S (p.Phe8Ser), ExAC rs766170094, TOPMed rs766170094, gnomAD rs766170094, REVEL 0.56, CADD 26.50, Uncertain significance, Cardiovascular phenotype
- G9D (p.Gly9Asp), rs2540477851, ClinGen CA386863658, ClinVar RCV002900247, NCI-TCGA TCGA novel, REVEL 0.31, CADD 25.50, Uncertain significance, Aortic valve disease 2
- G9R (p.Gly9Arg), Ensembl rs1017137525, Uncertain significance, Cardiovascular phenotype
- L10M (p.Leu10Met), cosmic curated COSV59863, gnomAD rs1406353614, REVEL 0.16, CADD 20.80
- L10P (p.Leu10Pro), TOPMed rs1872009251, Uncertain significance
- L10R (p.Leu10Arg), rs1872009251, ClinGen CA386863651, ClinVar RCV003532386, TOPMed rs1872009251, REVEL 0.46, CADD 31.00, Uncertain significance, Aortic valve disease 2
- A11E (p.Ala11Glu), TOPMed rs1382901395, REVEL 0.20, CADD 24.50, Uncertain significance, Cardiovascular phenotype
- A11S (p.Ala11Ser), TOPMed rs969971326
- A11T (p.Ala11Thr), TOPMed rs969971326
- A11V (p.Ala11Val), rs1382901395, NCI-TCGA Cosmic COSV5985, cosmic curated COSV59859, TOPMed rs1382901395, REVEL 0.24, CADD 24.90, Uncertain significance
- H12L (p.His12Leu), gnomAD rs1292676653
- T13K (p.Thr13Lys), rs763125466, ClinGen CA6809739, ClinVar RCV000617189, ClinVar RCV002483716, REVEL 0.44, CADD 23.30, Uncertain significance, Cardiovascular phenotype; Aortic valve disease 2; Holt-Oram syndrome
- T13M (p.Thr13Met), NCI-TCGA Cosmic COSV5986, cosmic curated COSV59861, REVEL 0.32, CADD 25.20, Variant assessed as somatic; moderate impact.
- T13S (p.Thr13Ser), rs1244677569, ClinGen CA386863635, ClinVar RCV003305470, TOPMed rs1244677569, REVEL 0.16, CADD 22.10, Uncertain significance, Cardiovascular phenotype
- P14L (p.Pro14Leu), Ensembl rs1565943367
- P14S (p.Pro14Ser), ExAC rs773397553, TOPMed rs773397553, gnomAD rs773397553, REVEL 0.59, CADD 28.50, Pathogenic
- P14T (p.Pro14Thr), rs773397553, ClinGen CA6809738, ClinVar RCV000515608, ExAC rs773397553, REVEL 0.65, CADD 27.90, Pathogenic, not provided
- P17A (p.Pro17Ala), gnomAD rs1430022884, REVEL 0.18, CADD 19.60
- P17T (p.Pro17Thr), NCI-TCGA Cosmic COSV5985, cosmic curated COSV59858, Variant assessed as somatic; moderate impact.
- D18E (p.Asp18Glu), rs1479545982, ClinGen CA386863602, ClinVar RCV000690141, ClinVar RCV001112941, REVEL 0.21, CADD 0.52, Uncertain significance, Holt-Oram syndrome; Aortic valve disease 2
- D18H (p.Asp18His), TOPMed rs1196700597, gnomAD rs1196700597, REVEL 0.22, CADD 24.00
- A19G (p.Ala19Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A19P (p.Ala19Pro), cosmic curated COSV59862, REVEL 0.14, CADD 13.40
- A19S (p.Ala19Ser), rs200461617, ClinGen CA6809736, ClinVar RCV000244681, ClinVar RCV000292317, REVEL 0.14, CADD 6.50, Conflicting interpretations, Cardiovascular phenotype; not specified; not provided
- A19T (p.Ala19Thr), cosmic curated COSV10009, 1000Genomes rs200461617, ESP rs200461617, ExAC rs200461617, REVEL 0.13, CADD 11.40, Uncertain significance, Cardiovascular phenotype
- D21N (p.Asp21Asn), Ensembl rs1872004761
- L22R (p.Leu22Arg), TOPMed rs1444078249, gnomAD rs1444078249, REVEL 0.26, CADD 24.70
- P23H (p.Pro23His), rs141609745, ClinGen CA6809732, ClinVar RCV000332226, ClinVar RCV000621936, REVEL 0.24, CADD 23.20, Conflicting interpretations, Aortic valve disease 2; Cardiovascular phenotype; Holt-Oram syndrome
- P23L (p.Pro23Leu), 1000Genomes rs141609745, ESP rs141609745, ExAC rs141609745, TOPMed rs141609745, REVEL 0.19, CADD 23.40, Likely benign
- C24F (p.Cys24Phe), ExAC rs772587337, gnomAD rs772587337, REVEL 0.25, CADD 23.70
- D25N (p.Asp25Asn), cosmic curated COSV59858, REVEL 0.28, CADD 24.50
- D25V (p.Asp25Val), cosmic curated COSV10009
- D25Y (p.Asp25Tyr), rs148195311, ClinGen CA6809729, ClinVar RCV002384874, ClinVar RCV005097109, REVEL 0.39, CADD 27.50, Uncertain significance, Cardiovascular phenotype; Aortic valve disease 2
- S26L (p.Ser26Leu), rs1085307848, ClinGen CA386863551, cosmic curated COSV59859, ClinVar RCV000489172, REVEL 0.12, CADD 22.30, Conflicting interpretations, Cardiovascular phenotype; Holt-Oram syndrome; not provided
- S26W (p.Ser26Trp), TOPMed rs1085307848, gnomAD rs1085307848, Uncertain significance
- P28H (p.Pro28His), ExAC rs755790672, gnomAD rs755790672
- P28L (p.Pro28Leu), ExAC rs755790672, gnomAD rs755790672, REVEL 0.21, CADD 23.20
- P28T (p.Pro28Thr), cosmic curated COSV59863, Ensembl rs896460617
- E29K (p.Glu29Lys), TOPMed rs1224983589, gnomAD rs1224983589, REVEL 0.25, CADD 23.30
- E29Q (p.Glu29Gln), TOPMed rs1224983589, gnomAD rs1224983589
- S30G (p.Ser30Gly), rs2540477713, ClinGen CA386863529, ClinVar RCV002376038, Uncertain significance, Cardiovascular phenotype
- S30I (p.Ser30Ile), NCI-TCGA Cosmic COSV5986, Variant assessed as somatic; moderate impact.
- S30N (p.Ser30Asn), NCI-TCGA Cosmic COSV5986, cosmic curated COSV59861, Variant assessed as somatic; moderate impact.
- S30R (p.Ser30Arg), rs1872000801, ClinGen CA386863524, ClinVar RCV003648973, REVEL 0.12, CADD 12.70, Uncertain significance, Aortic valve disease 2
- A31P (p.Ala31Pro), gnomAD rs1300164371, REVEL 0.18, CADD 9.01
- A31S (p.Ala31Ser), cosmic curated COSV59863, gnomAD rs1300164371, REVEL 0.19, CADD 4.25
- A31T (p.Ala31Thr), cosmic curated COSV10009
- A31V (p.Ala31Val), rs1214991478, ClinGen CA386863519, cosmic curated COSV10738, ClinVar RCV002371524, AlphaMissense 0.06, MetaLR 0.34, Uncertain significance, Cardiovascular phenotype
- L32H (p.Leu32His), TOPMed rs1871999364, REVEL 0.42, CADD 23.20
- L32P (p.Leu32Pro), NCI-TCGA TCGA novel, REVEL 0.16, CADD 23.10, Variant assessed as somatic; moderate impact.
- G33R (p.Gly33Arg), cosmic curated COSV10009, ExAC rs751532982, TOPMed rs751532982, gnomAD rs751532982, REVEL 0.22, CADD 23.10, Variant assessed as somatic; moderate impact.
- G33W (p.Gly33Trp), rs751532982, NCI-TCGA Cosmic COSV1000, ExAC rs751532982, TOPMed rs751532982, REVEL 0.55, CADD 28.80, Uncertain significance, Cardiovascular phenotype
- A34D (p.Ala34Asp), rs761952835, ClinGen CA6809720, cosmic curated COSV59858, ClinVar RCV001768833, REVEL 0.17, CADD 23.00, Uncertain significance, Aortic valve disease 2; Cardiovascular phenotype; not provided
- A34P (p.Ala34Pro), NCI-TCGA Cosmic COSV5985, cosmic curated COSV59859, Variant assessed as somatic; high impact.
- A34S (p.Ala34Ser), rs368311885, ClinGen CA6809721, ClinVar RCV001301593, ClinVar RCV002437022, REVEL 0.19, CADD 19.10, Conflicting interpretations, Cardiovascular phenotype; Aortic valve disease 2
- A34T (p.Ala34Thr), 1000Genomes rs368311885, ESP rs368311885, ExAC rs368311885, TOPMed rs368311885, REVEL 0.20, CADD 20.60, Uncertain significance, Cardiovascular phenotype
- A34V (p.Ala34Val), rs761952835, ClinGen CA6809719, cosmic curated COSV10644, ClinVar RCV001872339, REVEL 0.18, CADD 22.90, Conflicting interpretations, Aortic valve disease 2; Cardiovascular phenotype
- P35A (p.Pro35Ala), TOPMed rs1309984671, gnomAD rs1309984671, REVEL 0.10, CADD 19.40
- P35H (p.Pro35His), rs776705102, ClinGen CA6809718, ClinVar RCV002400995, ClinVar RCV006470945, REVEL 0.31, AlphaMissense 0.07, Uncertain significance, Cardiovascular phenotype; Aortic valve disease 2
- P35L (p.Pro35Leu), rs776705102, ExAC rs776705102, TOPMed rs776705102, gnomAD rs776705102, AlphaMissense 0.07, MetaLR 0.43, Conflicting interpretations, Cardiovascular phenotype; Aortic valve disease 2
- P35S (p.Pro35Ser), NCI-TCGA Cosmic COSV5986, cosmic curated COSV59864, Likely pathogenic, Holt-Oram syndrome
- S36R (p.Ser36Arg), cosmic curated COSV10590, gnomAD rs1430688195, REVEL 0.34, CADD 24.90
- S36T (p.Ser36Thr), gnomAD rs1171372107, REVEL 0.18, CADD 22.10
- S38P (p.Ser38Pro), cosmic curated COSV59863, REVEL 0.15, CADD 23.00
- P39L (p.Pro39Leu), TOPMed rs1028816896, gnomAD rs1028816896, REVEL 0.49, CADD 26.10
- P39S (p.Pro39Ser), rs145703644, ClinGen CA6809716, ClinVar RCV002373228, ClinVar RCV003094446, REVEL 0.30, CADD 26.60, Likely benign, Aortic valve disease 2; Cardiovascular phenotype
- S40* (p.Ser40Ter), rs903933027, ClinGen CA386863471, ClinVar RCV000782330, Ensembl rs903933027, AlphaMissense 0.07, MetaLR 0.46, Pathogenic
- S40L (p.Ser40Leu), NCI-TCGA Cosmic COSV5985, cosmic curated COSV59858, Ensembl rs903933027, Pathogenic
- S40P (p.Ser40Pro), Ensembl rs2136424437
- S40W (p.Ser40Trp), rs903933027, ClinGen CA244132190, NCI-TCGA Cosmic COSV5985, ClinVar RCV002346778, AlphaMissense 0.07, MetaLR 0.46, Uncertain significance, Cardiovascular phenotype
- S41F (p.Ser41Phe), cosmic curated COSV59859
- P42A (p.Pro42Ala), cosmic curated COSV10511
- P42L (p.Pro42Leu), rs759976245, ClinGen CA6809714, ClinVar RCV001450648, ClinVar RCV002432252, REVEL 0.42, CADD 31.00, Conflicting interpretations, Aortic valve disease 2; Cardiovascular phenotype
- P42S (p.Pro42Ser), gnomAD rs1205091445, REVEL 0.39, CADD 26.90
- A44V (p.Ala44Val), rs1255070392, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10009, gnomAD rs1255070392, REVEL 0.31, CADD 23.80, Variant assessed as somatic; moderate impact.
- A45T (p.Ala45Thr), rs942514260, ClinGen CA244132183, ClinVar RCV002387674, TOPMed rs942514260, REVEL 0.29, CADD 23.00, Uncertain significance, Cardiovascular phenotype
- T47S (p.Thr47Ser), rs2540477528, ClinGen CA386863427, ClinVar RCV002389459, Uncertain significance, Cardiovascular phenotype
- Q48* (p.Gln48Ter), rs863223777, ClinGen CA325146, ClinVar RCV000200559, ClinVar RCV001390030, Pathogenic
- Q49=, rs1227377137, NCI-TCGA Cosmic COSV5986, Variant assessed as somatic; low impact., in HOS
- Q49K (p.Gln49Lys), rs104894383, ClinGen CA254302, ClinVar RCV000008461, UniProt VAR 015381, REVEL 0.51, CADD 27.50, Pathogenic, Holt-Oram syndrome
- G50C (p.Gly50Cys), cosmic curated COSV59859
- M51I (p.Met51Ile), ExAC rs746504712, gnomAD rs746504712
- E52* (p.Glu52Ter), rs1208004863, ClinGen CA386863317, ClinVar RCV001035895, gnomAD rs1208004863, AlphaMissense 0.56, MetaLR 0.70, Pathogenic
- E52D (p.Glu52Asp), gnomAD rs771883815, REVEL 0.30, CADD 22.40, Likely benign
- E52Q (p.Glu52Gln), gnomAD rs1208004863, REVEL 0.41, AlphaMissense 0.56, Pathogenic
- G53E (p.Gly53Glu), rs369919453, ClinGen CA6809689, cosmic curated COSV10511, ClinVar RCV003649055, REVEL 0.49, CADD 25.70, Uncertain significance, Aortic valve disease 2; Cardiovascular phenotype
- G53R (p.Gly53Arg), rs779550194, ClinGen CA6809690, cosmic curated COSV10463, ClinVar RCV002405768, REVEL 0.60, CADD 26.60, Uncertain significance, Cardiovascular phenotype
- I54M (p.Ile54Met), NCI-TCGA Cosmic COSV1000, cosmic curated COSV10009, Variant assessed as somatic; moderate impact., in HOS
- I54T (p.Ile54Thr), rs104894384, ClinGen CA254304, ClinVar RCV000008462, UniProt VAR 015382, AlphaMissense 0.88, MetaLR 0.58, Pathogenic, Holt-Oram syndrome
- I54V (p.Ile54Val), ESP rs145890934, TOPMed rs145890934, gnomAD rs145890934, REVEL 0.25, CADD 22.50
- V56A (p.Val56Ala), cosmic curated COSV59858
- V56E (p.Val56Glu), rs1287994219, ClinGen CA386863261, ClinVar RCV002414531, gnomAD rs1287994219, REVEL 0.96, CADD 31.00, Uncertain significance, Cardiovascular phenotype
- V56L (p.Val56Leu), TOPMed rs1327141955, gnomAD rs1327141955, REVEL 0.83, CADD 24.10
- F57I (p.Phe57Ile), 1000Genomes rs562706670, ExAC rs562706670, gnomAD rs562706670, REVEL 0.27, CADD 22.90
- L58F (p.Leu58Phe), NCI-TCGA Cosmic COSV5986, cosmic curated COSV59865, Variant assessed as somatic; moderate impact.
- L58P (p.Leu58Pro), TOPMed rs1322050108, gnomAD rs1322050108, REVEL 0.98, CADD 32.00
- H59Y (p.His59Tyr), cosmic curated COSV59861, REVEL 0.75, CADD 27.50
- E60* (p.Glu60Ter), rs1064794030, ClinGen CA16619437, ClinVar RCV000486016, Ensembl rs1064794030, Pathogenic
- E60K (p.Glu60Lys), NCI-TCGA Cosmic COSV1000, cosmic curated COSV10009, Variant assessed as somatic; moderate impact.
- R61* (p.Arg61Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- R61I (p.Arg61Ile), NCI-TCGA Cosmic COSV5986, Variant assessed as somatic; moderate impact.
- R61K (p.Arg61Lys), rs1386360765, ClinGen CA386863198, cosmic curated COSV59865, ClinVar RCV002410516, REVEL 0.29, CADD 17.60, Uncertain significance, Cardiovascular phenotype
- R61S (p.Arg61Ser), ExAC rs777853147, gnomAD rs777853147, REVEL 0.59, CADD 21.50
- E62* (p.Glu62Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E62K (p.Glu62Lys), ExAC rs756464860, gnomAD rs756464860, REVEL 0.78, CADD 24.80, Uncertain significance, Cardiovascular phenotype
- L63R (p.Leu63Arg), rs2540475324, ClinGen CA386863172, ClinVar RCV003028279, Uncertain significance, Aortic valve disease 2
- W64* (p.Trp64Ter), rs1555226581, ClinGen CA386863160, ClinVar RCV001193147, ClinVar RCV001268738, AlphaMissense 1.00, MetaLR 0.93, Pathogenic
- W64C (p.Trp64Cys), rs1555226581, ClinGen CA386863156, ClinVar RCV000585449, Ensembl rs1555226581, REVEL 0.93, AlphaMissense 1.00, Uncertain significance, not provided
- W64R (p.Trp64Arg), cosmic curated COSV10811
- L65P (p.Leu65Pro), rs2540475317, ClinGen CA386863148, ClinVar RCV003235836, Uncertain significance, not provided
- K66I (p.Lys66Ile), rs1457871803, ClinGen CA386863134, ClinVar RCV004474328, TOPMed rs1457871803, AlphaMissense 0.92, MetaLR 0.77, Uncertain significance, Cardiovascular phenotype
- H68Y (p.His68Tyr), cosmic curated COSV10511
- E69* (p.Glu69Ter), rs104894377, ClinGen CA254295, NCI-TCGA Cosmic COSV5985, ClinVar RCV000008456, AlphaMissense 0.56, MetaLR 0.45, Pathogenic
- E69D (p.Glu69Asp), rs760082444, ClinGen CA6809680, ClinVar RCV002422265, ExAC rs760082444, REVEL 0.29, CADD 21.40, Uncertain significance, Cardiovascular phenotype
- E69K (p.Glu69Lys), NCI-TCGA Cosmic COSV5985, cosmic curated COSV59858, Ensembl rs104894377, Pathogenic
- E69Q (p.Glu69Gln), cosmic curated COSV10738, REVEL 0.46, CADD 23.00
- V70M (p.Val70Met), rs1378993147, ClinGen CA386863086, ClinVar RCV002424025, ClinVar RCV005097936, REVEL 0.56, CADD 24.00, Uncertain significance, Aortic valve disease 2; Cardiovascular phenotype
- G71A (p.Gly71Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- T72K (p.Thr72Lys), TOPMed rs863223779
- T72M (p.Thr72Met), TOPMed rs863223779, REVEL 0.95, CADD 31.00
- E73Q (p.Glu73Gln), rs2540475270, ClinGen CA386863046, ClinVar RCV003648289, Likely pathogenic, Aortic valve disease 2
- M74V (p.Met74Val), rs1555226577, Ensembl rs1555226577, AlphaMissense 1.00, MetaLR 0.81, Variant assessed as somatic; moderate impact.
- T77N (p.Thr77Asn), TOPMed rs1871832255, gnomAD rs1871832255, REVEL 0.87, CADD 27.90
- K78R (p.Lys78Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A79P (p.Ala79Pro), Ensembl rs1871831635
- A79T (p.Ala79Thr), cosmic curated COSV10009, REVEL 0.51, CADD 26.50
- A79V (p.Ala79Val), ExAC rs763219727, REVEL 0.65, CADD 27.10
- G80E (p.Gly80Glu), rs1871830806, ClinGen CA386862962, ClinVar RCV001067927, ClinVar RCV001759841, AlphaMissense 1.00, MetaLR 0.95, Conflicting interpretations, not provided; Aortic valve disease 2
- G80R (p.Gly80Arg), rs104894381, ClinGen CA254300, ClinVar RCV000008458, UniProt VAR 009701, AlphaMissense 1.00, MetaLR 0.94, Pathogenic, Holt-Oram syndrome
- R81K (p.Arg81Lys), rs2540475204, ClinGen CA386862959, ClinVar RCV003648283, Uncertain significance, Aortic valve disease 2
- R81M (p.Arg81Met), rs2540475204, ClinGen CA386862957, ClinVar RCV003984874, Uncertain significance, Holt-Oram syndrome
- R82Q (p.Arg82Gln), NCI-TCGA Cosmic COSV5986, cosmic curated COSV59865, REVEL 0.90, CADD 33.00, Variant assessed as somatic; moderate impact.
- R82W (p.Arg82Trp), Ensembl rs1871673360, Benign
- M83I (p.Met83Ile), rs1871672543, ClinGen CA386862926, ClinVar RCV002794922, Ensembl rs1871672543, AlphaMissense 0.99, MetaLR 0.82, Uncertain significance, Aortic valve disease 2
- M83L (p.Met83Leu), cosmic curated COSV59861, REVEL 0.90, CADD 29.10
- F84L (p.Phe84Leu), rs1131691460, ClinGen CA386862921, ClinVar RCV000493054, Ensembl rs1131691460, AlphaMissense 1.00, MetaLR 0.91, Pathogenic, Aortic valve disease 2
- P85L (p.Pro85Leu), rs1565941576, ClinGen CA386862897, ClinVar RCV000782342, ClinVar RCV006342541, AlphaMissense 1.00, MetaLR 0.96, Conflicting interpretations, Cardiovascular phenotype; Aortic valve disease 2
- P85S (p.Pro85Ser), rs1565941579, ClinGen CA386862904, ClinVar RCV000782306, Ensembl rs1565941579, AlphaMissense 1.00, MetaLR 0.96, Likely pathogenic, Holt-Oram syndrome
- P85T (p.Pro85Thr), rs1565941579, ClinGen CA386862907, ClinVar RCV000824680, Ensembl rs1565941579, AlphaMissense 1.00, MetaLR 0.96, Likely pathogenic, Clubbing of fingers; Blue nevus; Radial ray deficiency
- Y87* (p.Tyr87Ter), rs767197919, ClinGen CA386862869, ClinVar RCV003153142, ClinVar RCV006342922, Pathogenic
- Y87C (p.Tyr87Cys), rs886039131, ClinGen CA10587737, ClinVar RCV000245821, ClinVar RCV001364631, REVEL 0.61, CADD 26.90, Uncertain significance, Cardiovascular phenotype; Aortic valve disease 2
- K88* (p.Lys88Ter), rs2136418232, ClinGen CA386862861, ClinVar RCV001530478, Ensembl rs2136418232, Pathogenic
- V89L (p.Val89Leu), NCI-TCGA TCGA novel, gnomAD rs778885169, REVEL 0.89, CADD 26.40, Variant assessed as somatic; moderate impact.
- V89M (p.Val89Met), gnomAD rs778885169, Uncertain significance, Aortic valve disease 2
- K90R (p.Lys90Arg), gnomAD rs1400168801, REVEL 0.52, CADD 26.80, Uncertain significance, Cardiovascular phenotype
- V91A (p.Val91Ala), TOPMed rs775593443, gnomAD rs775593443, REVEL 0.73, CADD 27.40
- V91M (p.Val91Met), gnomAD rs1473835296, REVEL 0.74, CADD 27.10
- T92A (p.Thr92Ala), gnomAD rs1187125731, REVEL 0.31, CADD 23.70
- T92K (p.Thr92Lys), NCI-TCGA Cosmic COSV5985, cosmic curated COSV59858, NCI-TCGA Cosmic COSV5986, Variant assessed as somatic; moderate impact.
- T92M (p.Thr92Met), NCI-TCGA Cosmic COSV5985, NCI-TCGA Cosmic COSV5986, cosmic curated COSV59860, REVEL 0.67, CADD 28.50, Variant assessed as somatic; moderate impact.
- G93A (p.Gly93Ala), cosmic curated COSV59863
- G93C (p.Gly93Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G93D (p.Gly93Asp), TOPMed rs890394778, gnomAD rs890394778, REVEL 0.94, CADD 27.60
- G93S (p.Gly93Ser), ExAC rs770717773, TOPMed rs770717773, gnomAD rs770717773, REVEL 0.97, CADD 27.50, Uncertain significance, Holt-Oram syndrome
- G93V (p.Gly93Val), TOPMed rs890394778, gnomAD rs890394778, REVEL 0.94, CADD 27.30, Uncertain significance, Aortic valve disease 2
- N95H (p.Asn95His), Ensembl rs1593881366
- P96H (p.Pro96His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P96S (p.Pro96Ser), rs1203503352, ClinGen CA386862770, cosmic curated COSV10511, ClinVar RCV002917489, REVEL 0.83, CADD 28.30, Uncertain significance, Aortic valve disease 2; Cardiovascular phenotype
- K97E (p.Lys97Glu), rs749255660, ClinGen CA6809648, ClinVar RCV002438009, ExAC rs749255660, REVEL 0.68, CADD 25.60, Uncertain significance, Cardiovascular phenotype
- T98K (p.Thr98Lys), ExAC rs772844823, TOPMed rs772844823, gnomAD rs772844823, REVEL 0.70, CADD 29.30, Uncertain significance
- T98M (p.Thr98Met), rs772844823, ClinGen CA244128692, cosmic curated COSV59866, ClinVar RCV001303559, REVEL 0.77, CADD 29.70, Uncertain significance, Cardiovascular phenotype; Aortic valve disease 2
- T98R (p.Thr98Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- K99* (p.Lys99Ter), rs1565941529, ClinGen CA386862732, ClinVar RCV000782328, Ensembl rs1565941529, Pathogenic
- K99E (p.Lys99Glu), rs1565941529, ClinGen CA386862733, ClinVar RCV002467256, Uncertain significance, not provided
- K99N (p.Lys99Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
Public TBX5 analysis runs
- TBX5 analysis run — TBX5 (1,246 variants) — completed 2026-08-22