TRPM4 (Q8TD43) variants and mutations
TRPM4 (also known as Q8TD43) is a human protein-coding gene encoding a transient receptor potential cation channel subfamily M member 4 protein. A calcium-activated channel that conducts monovalent cations and regulates membrane depolarization. Certain variants have been linked to progressive familial cardiac conduction disease. This analysis covers 1,917 TRPM4 variants and mutations. Of these, 98% have computational variant effect predictions. Disease context includes progressive familial heart block, erythrokeratodermia variabilis, and Abnormality of the cardiovascular system. Example TRPM4 variants include M1I, M1L, and M1T.
Variant analysis overview
- Gene: TRPM4
- Protein: Q8TD43
- UniProt accession: Q8TD43
- Organism: Homo sapiens
- Variants analyzed: 1917
- Variant scope: all variants
- Completed: 2026-10-09
Variant and mutation evidence
- Variant composition: 1,833 unspecified-consequence records; 96 missense variants; 56 synonymous variants; 2 in-frame deletions; 6 stop-gained variants; 3 splice-region variants; 12 frameshift variants; 5 substitution
- Prediction scores: 1,875 variants have prediction scores (98% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: progressive familial heart block, erythrokeratodermia variabilis, Abnormality of the cardiovascular system, Brugada syndrome, Prolonged QT interval, hypertrophic cardiomyopathy, cardiomyopathy, progressive familial heart block, type 1A, hereditary disease, sudden cardiac arrest, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy.
Protein structure and variant hotspots
- Protein features: 6 transmembrane segments; 13 binding sites; 3 post-translational modification sites.
- Structural context: 165 variants have structural context.
- PTM context: 7 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.
Diseases linked to TRPM4
Notable TRPM4 variants
Examples include M1I, M1L, M1T, M1V, V2A, V2L, V2M, V2V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs2514022995, ClinGen CA406787612, ClinVar RCV003380380, ESM-1b 1.00, AlphaMissense 0.38, Uncertain significance, Cardiovascular phenotype
- M1L (p.Met1Leu), rs969064041, ClinGen CA406787603, ClinVar RCV003380383, ESM-1b 0.45, AlphaMissense 0.17, Uncertain significance, Cardiovascular phenotype
- M1T (p.Met1Thr), rs2041541781, ClinGen CA406787607, ClinVar RCV002587998, ESM-1b 0.44, AlphaMissense 0.34, Uncertain significance, Progressive familial heart block type IB
- M1V (p.Met1Val), rs969064041, ClinGen CA309424812, ClinVar RCV001134313, ESM-1b 0.50, AlphaMissense 0.10, Uncertain significance, Progressive familial heart block type IB
- V2A (p.Val2Ala), gnomAD rs1340472576, REVEL 0.07, ESM-1b 0.00
- V2L (p.Val2Leu), TOPMed rs1326898712, gnomAD rs1326898712, REVEL 0.05, ESM-1b 0.00
- V2M (p.Val2Met), gnomAD 19-49157870-G-A, REVEL 0.10, ESM-1b 0.00
- V2V (p.Val2Val), rs531997715, gnomAD 19-49157872-G-T, CADD 10.80
- V3A (p.Val3Ala), rs1600378229, ClinGen CA406787646, ClinVar RCV001988119, TOPMed rs1600378229, REVEL 0.09, ESM-1b 0.00, Uncertain significance, Progressive familial heart block type IB
- V3G (p.Val3Gly), TOPMed rs1600378229, gnomAD rs1600378229, REVEL 0.08, ESM-1b 0.00, Uncertain significance
- V3L (p.Val3Leu), gnomAD 19-49157873-G-T, REVEL 0.06, ESM-1b 0.00
- V3M (p.Val3Met), gnomAD 19-49157873-G-A, REVEL 0.08, ESM-1b 0.00
- V3V (p.Val3Val), gnomAD 19-49157875-G-T, CADD 2.46
- P4L (p.Pro4Leu), 1000Genomes rs1318656879, TOPMed rs1318656879, gnomAD rs1318656879, REVEL 0.12, ESM-1b 0.00, Uncertain significance
- P4R (p.Pro4Arg), rs1318656879, ClinGen CA406787663, ClinVar RCV000700318, ClinVar RCV001592896, REVEL 0.12, ESM-1b 0.00, Uncertain significance, Progressive familial heart block type IB; Erythrokeratodermia variabilis et prog
- P4S (p.Pro4Ser), rs1280227892, ClinGen CA406787655, ClinVar RCV002036852, ClinVar RCV005764579, REVEL 0.19, ESM-1b 0.00, Conflicting interpretations, Cardiovascular phenotype; not specified; Progressive familial heart block type I
- P4T (p.Pro4Thr), gnomAD rs1280227892, REVEL 0.16, ESM-1b 0.00, Uncertain significance
- P4Q (p.Pro4Gln), gnomAD 19-49157877-C-A, REVEL 0.15, ESM-1b 0.00
- P4P (p.Pro4Pro), gnomAD 19-49157878-G-C, CADD 4.73
- E5A (p.Glu5Ala), rs2041542552, ClinGen CA406787673, ClinVar RCV003608932, Ensembl rs2041542552, REVEL 0.09, ESM-1b 0.00, Uncertain significance, Progressive familial heart block type IB
- E5K (p.Glu5Lys), rs999572673, ClinGen CA309424822, ClinVar RCV001307890, ClinVar RCV003375202, REVEL 0.18, ESM-1b 0.00, Uncertain significance, Progressive familial heart block type IB; Cardiovascular phenotype
- E5Q (p.Glu5Gln), TOPMed rs999572673, gnomAD rs999572673, REVEL 0.16, ESM-1b 0.00, Uncertain significance, Progressive familial heart block type IB; Cardiovascular phenotype
- E5* (p.Glu5Ter), gnomAD 19-49157879-G-T, CADD 41.00
- E5V (p.Glu5Val), gnomAD 19-49157880-A-T, REVEL 0.26, ESM-1b 0.00
- E5G (p.Glu5Gly), gnomAD 19-49157880-A-G, REVEL 0.17, ESM-1b 0.00
- E5D (p.Glu5Asp), gnomAD 19-49157881-G-C, REVEL 0.20, ESM-1b 0.00
- E5E (p.Glu5Glu), gnomAD 19-49157881-G-A, CADD 14.60
- K6N (p.Lys6Asn), rs2122723185, ClinGen CA406787698, ClinVar RCV003301670, ESM-1b 0.28, AlphaMissense 0.51, Uncertain significance, Cardiovascular phenotype
- K6del (p.Lys6del), gnomAD 19-49157879-GAGA-, CADD 22.30
- K6* (p.Lys6Ter), gnomAD 19-49157882-A-T, CADD 42.00
- K6K (p.Lys6Lys), rs2122723185, gnomAD 19-49157884-G-A, CADD 14.80
- E7K (p.Glu7Lys), rs267607142, ClinGen CA250505, ClinVar RCV000003968, ClinVar RCV004532279, REVEL 0.49, ESM-1b 0.00, Likely pathogenic, TRPM4-related disorder
- E7* (p.Glu7Ter), gnomAD 19-49157885-G-T, CADD 42.00
- E7D (p.Glu7Asp), gnomAD 19-49157887-G-T, REVEL 0.22, ESM-1b 0.00
- E7E (p.Glu7Glu), rs1053465808, gnomAD 19-49157887-G-A, CADD 14.00
- Q8E (p.Gln8Glu), TOPMed rs893498576, REVEL 0.19, ESM-1b 0.00
- Q8L (p.Gln8Leu), rs1057522811, ClinGen CA16608288, ClinVar RCV000440150, ClinVar RCV002506057, REVEL 0.15, ESM-1b 0.00, Uncertain significance, Progressive familial heart block type IB; Erythrokeratodermia variabilis et prog
- Q8K (p.Gln8Lys), gnomAD 19-49157888-C-A, REVEL 0.17, ESM-1b 0.00
- Q8* (p.Gln8Ter), gnomAD 19-49157888-C-T, CADD 46.00
- Q8Q (p.Gln8Gln), rs2041543043, gnomAD 19-49157890-G-A, CADD 23.60
- S9G (p.Ser9Gly), rs774622226, ClinGen CA9568651, ClinVar RCV004522183, ExAC rs774622226, REVEL 0.49, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype
- S9T (p.Ser9Thr), gnomAD 19-49158193-G-C, REVEL 0.46, ESM-1b 0.00
- W10* (p.Trp10Ter), rs893456469, ClinGen CA309425005, ClinVar RCV001038669, TOPMed rs893456469, AlphaMissense 0.99, MetaLR 0.64, Uncertain significance
- W10C (p.Trp10Cys), rs893456469, ClinGen CA406787850, cosmic curated COSV53259, ClinVar RCV004277576, REVEL 0.80, ESM-1b 0.52, Uncertain significance, Cardiovascular phenotype
- W10L (p.Trp10Leu), gnomAD rs1434592140, ESM-1b 1.00, AlphaMissense 0.82
- W10R (p.Trp10Arg), Ensembl rs1600379463, REVEL 0.79, ESM-1b 1.00
- I11V (p.Ile11Val), rs1396348949, ClinGen CA406787852, ClinVar RCV002322949, ClinVar RCV006616669, REVEL 0.54, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype; Progressive familial heart block type IB
- P12R (p.Pro12Arg), ExAC rs760102851, gnomAD rs760102851, REVEL 0.56, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype
- K13R (p.Lys13Arg), rs767972673, ClinGen CA406787888, ClinVar RCV001922819, ClinVar RCV003303336, REVEL 0.22, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype; Progressive familial heart block type IB
- K13T (p.Lys13Thr), ExAC rs767972673, TOPMed rs767972673, gnomAD rs767972673, REVEL 0.44, ESM-1b 0.00, Uncertain significance
- K13N (p.Lys13Asn), gnomAD 19-49158206-G-C, REVEL 0.16, ESM-1b 0.00
- I14M (p.Ile14Met), gnomAD rs1160765003, REVEL 0.23, ESM-1b 0.00
- I14N (p.Ile14Asn), gnomAD 19-49158208-T-A, REVEL 0.44, ESM-1b 0.28
- F15L (p.Phe15Leu), rs1009277467, ClinGen CA309425015, NCI-TCGA Cosmic COSV5325, cosmic curated COSV53256, REVEL 0.32, ESM-1b 0.48, Uncertain significance, not provided; Progressive familial heart block type IB; Cardiovascular phenotype
- F15F (p.Phe15Phe), gnomAD 19-49158212-C-T, CADD 17.50
- K16E (p.Lys16Glu), TOPMed rs2041554005, REVEL 0.49, ESM-1b 0.40, Uncertain significance, Progressive familial heart block type IB
- K16N (p.Lys16Asn), rs776066828, ClinGen CA9568654, ClinVar RCV003083475, ExAC rs776066828, REVEL 0.38, ESM-1b 0.39, Uncertain significance, Progressive familial heart block type IB
- K16T (p.Lys16Thr), gnomAD 19-49158214-A-C, REVEL 0.40, ESM-1b 0.00
- K17E (p.Lys17Glu), rs2514024580, ClinGen CA406787952, ClinVar RCV004522198, ClinVar RCV005100598, ESM-1b 1.00, AlphaMissense 0.69, Uncertain significance, Progressive familial heart block type IB; Cardiovascular phenotype
- K17N (p.Lys17Asn), rs2514024591, ClinGen CA406787972, ClinVar RCV003039863, REVEL 0.61, ESM-1b 1.00, Uncertain significance, Progressive familial heart block type IB
- K18T (p.Lys18Thr), TOPMed rs2041554311, gnomAD rs2041554311, REVEL 0.39, ESM-1b 0.54
- K18del (p.Lys18del), rs1361734644, gnomAD 19-49158212-CAAG-, CADD 22.50
- T19A (p.Thr19Ala), TOPMed rs906300951, REVEL 0.08, ESM-1b 0.00
- T19S (p.Thr19Ser), gnomAD 19-49158223-C-G, REVEL 0.10, ESM-1b 0.00
- T19N (p.Thr19Asn), gnomAD 19-49158223-C-A, REVEL 0.18, ESM-1b 0.00
- T19T (p.Thr19Thr), gnomAD 19-49158224-C-G, CADD 8.60
- C20S (p.Cys20Ser), rs864622643, ClinGen CA349108, ClinVar RCV000204919, ClinVar RCV000786236, REVEL 0.89, ESM-1b 1.00, Uncertain significance, not provided; Progressive familial heart block type IB
- C20F (p.Cys20Phe), gnomAD 19-49158226-G-T, REVEL 0.89, ESM-1b 1.00
- C20C (p.Cys20Cys), rs1306247621, gnomAD 19-49158227-C-T, CADD 14.30
- T21M (p.Thr21Met), rs1399916515, ClinGen CA406788030, cosmic curated COSV53256, ClinVar RCV001205894, REVEL 0.41, ESM-1b 0.51, Uncertain significance, Cardiovascular phenotype; Progressive familial heart block type IB
- T21R (p.Thr21Arg), gnomAD 19-49158227-CA-C, CADD 27.30
- T21K (p.Thr21Lys), gnomAD 19-49158229-C-A, REVEL 0.61, ESM-1b 0.05
- T22M (p.Thr22Met), rs1600379607, ClinGen CA406788043, cosmic curated COSV53258, ClinVar RCV001043152, REVEL 0.43, ESM-1b 0.00, Uncertain significance, Progressive familial heart block type IB
- T22T (p.Thr22Thr), rs1003340287, gnomAD 19-49158233-G-T, CADD 9.83
- F23L (p.Phe23Leu), rs760887443, ClinGen CA9568655, ClinVar RCV002012074, ClinVar RCV006558099, REVEL 0.84, ESM-1b 1.00, Uncertain significance, not provided; Cardiovascular phenotype; Progressive familial heart block type IB
- F23F (p.Phe23Phe), gnomAD 19-49158236-C-T, CADD 15.60
- I24T (p.Ile24Thr), Ensembl rs1568450327, REVEL 0.42, ESM-1b 0.00
- I24S (p.Ile24Ser), gnomAD 19-49158236-CAT-C, CADD 26.10
- I24I (p.Ile24Ile), gnomAD 19-49158239-A-C, CADD 14.90
- V25G (p.Val25Gly), Ensembl rs2041554868, REVEL 0.07, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype
- V25I (p.Val25Ile), Ensembl rs2122725747, REVEL 0.13, ESM-1b 0.00
- V25A (p.Val25Ala), gnomAD 19-49158241-T-C, REVEL 0.03, ESM-1b 0.00
- D26A (p.Asp26Ala), gnomAD 19-49158244-A-C, REVEL 0.25, ESM-1b 0.00
- S27P (p.Ser27Pro), gnomAD 19-49158246-T-C, REVEL 0.05, ESM-1b 0.00
- S27F (p.Ser27Phe), gnomAD 19-49158247-C-T, REVEL 0.03, ESM-1b 0.27
- S27S (p.Ser27Ser), rs372942488, gnomAD 19-49158248-C-T, CADD 11.00
- T28I (p.Thr28Ile), rs1368982955, ClinGen CA406788124, ClinVar RCV002735227, ClinVar RCV004765555, REVEL 0.05, ESM-1b 0.47, Uncertain significance, Progressive familial heart block type IB; not provided
- D29G (p.Asp29Gly), rs2514024721, ClinGen CA406788133, ClinVar RCV003063818, ESM-1b 0.00, AlphaMissense 0.16, Uncertain significance, Progressive familial heart block type IB
- D29H (p.Asp29His), rs2041555070, ClinGen CA406788128, ClinVar RCV003609423, TOPMed rs2041555070, REVEL 0.44, ESM-1b 0.00, Uncertain significance, Progressive familial heart block type IB
- D29N (p.Asp29Asn), gnomAD 19-49158252-G-A, REVEL 0.32, ESM-1b 0.00
- P30L (p.Pro30Leu), rs200868666, ClinGen CA9568657, ClinVar RCV003816074, 1000Genomes rs200868666, REVEL 0.12, ESM-1b 0.00, Uncertain significance, Progressive familial heart block type IB
- P30S (p.Pro30Ser), gnomAD rs1231819815, REVEL 0.02, ESM-1b 0.00
- P30P (p.Pro30Pro), gnomAD 19-49158257-G-A, CADD 7.54
- G31R (p.Gly31Arg), Ensembl rs967873202, REVEL 0.27, ESM-1b 0.00
- G32A (p.Gly32Ala), ExAC rs772015839, gnomAD rs772015839, REVEL 0.13, ESM-1b 0.00
- G32R (p.Gly32Arg), rs1216651490, ClinGen CA406789292, ClinVar RCV002374134, TOPMed rs1216651490, REVEL 0.18, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype
- G32W (p.Gly32Trp), gnomAD 19-49166042-G-T, REVEL 0.27, ESM-1b 0.00
- G32E (p.Gly32Glu), gnomAD 19-49166043-G-A, REVEL 0.15, ESM-1b 0.00
- G32G (p.Gly32Gly), rs1967160337, gnomAD 19-49166044-G-A, CADD 9.79
- T33T (p.Thr33Thr), rs765230099, gnomAD 19-49166047-C-T, CADD 10.80
- L34W (p.Leu34Trp), rs1568456560, ClinGen CA406789326, ClinVar RCV002298368, Ensembl rs1568456560, REVEL 0.18, ESM-1b 1.00, Uncertain significance, Progressive familial heart block type IB
- L34M (p.Leu34Met), gnomAD 19-49166048-T-A, REVEL 0.23, ESM-1b 0.43
- L34L (p.Leu34Leu), rs780231602, gnomAD 19-49166048-T-C, CADD 8.18
- L34S (p.Leu34Ser), gnomAD 19-49166049-T-C, REVEL 0.47, ESM-1b 1.00
- C35Y (p.Cys35Tyr), gnomAD 19-49166052-G-A, REVEL 0.79, ESM-1b 1.00
- C35F (p.Cys35Phe), gnomAD 19-49166052-G-T, REVEL 0.79, ESM-1b 1.00
- C35C (p.Cys35Cys), gnomAD 19-49166053-C-T, CADD 14.40
- C35* (p.Cys35Ter), gnomAD 19-49166053-C-A, CADD 39.00
- Q36* (p.Gln36Ter), Ensembl rs867521515, CADD 40.00
- Q36H (p.Gln36His), ExAC rs747457887, gnomAD rs747457887, REVEL 0.24, ESM-1b 0.00, Uncertain significance, Progressive familial heart block type IB
- Q36K (p.Gln36Lys), gnomAD 19-49166054-C-A, REVEL 0.23, ESM-1b 0.83
- Q36R (p.Gln36Arg), gnomAD 19-49166055-A-G, REVEL 0.26, ESM-1b 0.00
- Q36Q (p.Gln36Gln), rs747457887, gnomAD 19-49166056-G-A, CADD 11.50
- C37F (p.Cys37Phe), Ensembl rs1967161146, REVEL 0.78, ESM-1b 1.00
- C37V (p.Cys37Val), gnomAD 19-49166054-C-CA, CADD 31.00
- C37Y (p.Cys37Tyr), gnomAD 19-49166058-G-A, REVEL 0.78, ESM-1b 1.00
- C37S (p.Cys37Ser), gnomAD 19-49166058-G-C, REVEL 0.80, ESM-1b 1.00
- C37C (p.Cys37Cys), gnomAD 19-49166059-T-C, CADD 10.30
- G38R (p.Gly38Arg), TOPMed rs1283660220, gnomAD rs1283660220, REVEL 0.76, ESM-1b 1.00
- G38T (p.Gly38Thr), NCI-TCGA Cosmic COSV5325, cosmic curated COSV53256, Variant assessed as somatic; moderate impact.
- G38W (p.Gly38Trp), gnomAD 19-49166060-G-T, REVEL 0.79, ESM-1b 1.00
- G38V (p.Gly38Val), gnomAD 19-49166061-G-T, REVEL 0.80, ESM-1b 1.00
- G38E (p.Gly38Glu), gnomAD 19-49166061-G-A, REVEL 0.79, ESM-1b 1.00
- G38G (p.Gly38Gly), gnomAD 19-49166062-G-T, CADD 10.30
- R39C (p.Arg39Cys), rs865920466, ClinGen CA309429451, ClinVar RCV003854091, Ensembl rs865920466, REVEL 0.14, ESM-1b 1.00, Uncertain significance, Progressive familial heart block type IB
- R39H (p.Arg39His), rs1202949892, ClinGen CA406789385, cosmic curated COSV53261, ClinVar RCV003380386, REVEL 0.06, ESM-1b 0.93, Uncertain significance, Cardiovascular phenotype
- R39A (p.Arg39Ala), gnomAD 19-49166059-TG-T, CADD 33.00
- R39S (p.Arg39Ser), gnomAD 19-49166063-C-A, REVEL 0.14, ESM-1b 1.00
- R39L (p.Arg39Leu), gnomAD 19-49166064-G-T, REVEL 0.05, ESM-1b 0.16
- R39R (p.Arg39Arg), rs769272338, gnomAD 19-49166065-C-G, CADD 1.52
- P40L (p.Pro40Leu), rs777131422, ClinGen CA9568696, ClinVar RCV003817474, ExAC rs777131422, REVEL 0.12, ESM-1b 0.00, Uncertain significance, Progressive familial heart block type IB
- P40T (p.Pro40Thr), gnomAD 19-49166066-C-A, REVEL 0.09, ESM-1b 0.76
- P40S (p.Pro40Ser), gnomAD 19-49166066-C-T, REVEL 0.13, ESM-1b 0.22
- P40H (p.Pro40His), gnomAD 19-49166067-C-A, REVEL 0.24, ESM-1b 0.99
- P40P (p.Pro40Pro), gnomAD 19-49166068-C-A, CADD 4.75
- R41Q (p.Arg41Gln), cosmic curated COSV53263, gnomAD rs1255971986, REVEL 0.18, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype
- R41W (p.Arg41Trp), rs1028746202, ClinGen CA309429461, ClinVar RCV002026710, ClinVar RCV002361404, REVEL 0.23, ESM-1b 0.48, Uncertain significance, Cardiovascular phenotype; Progressive familial heart block type IB
- R41G (p.Arg41Gly), gnomAD 19-49166064-GC-G, CADD 8.85
- R41R (p.Arg41Arg), gnomAD 19-49166069-C-A, CADD 7.42
- R41L (p.Arg41Leu), gnomAD 19-49166070-G-T, REVEL 0.14, ESM-1b 0.00
- T42A (p.Thr42Ala), rs762111515, ClinGen CA9568697, ClinVar RCV003380390, ClinVar RCV006472582, REVEL 0.02, ESM-1b 0.00, Uncertain significance, Progressive familial heart block type IB; Cardiovascular phenotype
- T42I (p.Thr42Ile), rs770169566, ClinGen CA9568698, ClinVar RCV003610533, ExAC rs770169566, REVEL 0.03, ESM-1b 0.39, Uncertain significance, Progressive familial heart block type IB
- T42P (p.Thr42Pro), ExAC rs762111515, TOPMed rs762111515, gnomAD rs762111515, REVEL 0.04, ESM-1b 0.00, Uncertain significance
- T42N (p.Thr42Asn), gnomAD 19-49166073-C-A, REVEL 0.01, ESM-1b 0.00
- T42T (p.Thr42Thr), rs1401034530, gnomAD 19-49166074-C-T, CADD 0.75
- A43S (p.Ala43Ser), 1000Genomes rs112149155, ESP rs112149155, ExAC rs112149155, TOPMed rs112149155, REVEL 0.04, ESM-1b 0.00, Uncertain significance
- A43T (p.Ala43Thr), rs112149155, ClinGen CA9568699, ClinVar RCV000645469, ClinVar RCV002369709, REVEL 0.01, ESM-1b 0.00, Uncertain significance, Progressive familial heart block type IB; Erythrokeratodermia variabilis et prog
- A43V (p.Ala43Val), gnomAD 19-49166076-C-T, REVEL 0.02, ESM-1b 0.00
- A43D (p.Ala43Asp), gnomAD 19-49166076-C-A, REVEL 0.03, ESM-1b 0.00
- A43A (p.Ala43Ala), gnomAD 19-49166077-C-T, CADD 2.95
- H44N (p.His44Asn), gnomAD rs1408421722, ESM-1b 1.00, AlphaMissense 0.87
- H44P (p.His44Pro), Ensembl rs1600400452, REVEL 0.71, ESM-1b 1.00, Uncertain significance
- H44R (p.His44Arg), rs1600400452, ClinGen CA406789413, ClinVar RCV001237168, Ensembl rs1600400452, REVEL 0.65, ESM-1b 1.00, Uncertain significance, Progressive familial heart block type IB
- H44Y (p.His44Tyr), gnomAD 19-49166078-C-T, REVEL 0.51, ESM-1b 1.00
- H44Q (p.His44Gln), gnomAD 19-49166080-C-A, REVEL 0.43, ESM-1b 1.00
- H44H (p.His44His), rs1168125244, gnomAD 19-49166080-C-T, CADD 6.35
- P45S (p.Pro45Ser), ExAC rs765781527, TOPMed rs765781527, gnomAD rs765781527, REVEL 0.09, ESM-1b 0.00
- P45T (p.Pro45Thr), ExAC rs765781527, TOPMed rs765781527, gnomAD rs765781527, REVEL 0.12, ESM-1b 0.00
- P45A (p.Pro45Ala), gnomAD 19-49166081-C-G, REVEL 0.11, ESM-1b 0.00
- P45H (p.Pro45His), gnomAD 19-49166082-C-A, REVEL 0.17, ESM-1b 0.00
- P45P (p.Pro45Pro), rs1448432872, gnomAD 19-49166083-C-T, CADD 0.09
- A46S (p.Ala46Ser), rs751134895, ClinGen CA10648961, ClinVar RCV000366846, ExAC rs751134895, REVEL 0.10, ESM-1b 0.00, Uncertain significance, Progressive familial heart block type IB
- A46T (p.Ala46Thr), rs751134895, ClinGen CA9568702, ClinVar RCV003609384, ClinVar RCV006347745, REVEL 0.11, ESM-1b 0.00, Uncertain significance, Progressive familial heart block type IB; Cardiovascular phenotype
- A46Q (p.Ala46Gln), gnomAD 19-49166079-AC-A, CADD 23.00
- A46A (p.Ala46Ala), rs1353425281, gnomAD 19-49166086-A-C, CADD 0.37
- V47A (p.Val47Ala), Ensembl rs1967163999, REVEL 0.45, ESM-1b 0.22
- V47M (p.Val47Met), gnomAD 19-49166087-G-A, REVEL 0.31, ESM-1b 0.81
- V47V (p.Val47Val), rs1401313822, gnomAD 19-49166089-G-C, CADD 6.74
- A48S (p.Ala48Ser), gnomAD 19-49166090-G-T, REVEL 0.52, ESM-1b 0.00
- A48T (p.Ala48Thr), gnomAD 19-49166090-G-A, REVEL 0.44, ESM-1b 0.00
- A48D (p.Ala48Asp), gnomAD 19-49166091-C-A, REVEL 0.58, ESM-1b 0.00
- A48V (p.Ala48Val), gnomAD 19-49166091-C-T, REVEL 0.52, ESM-1b 0.00
- A48A (p.Ala48Ala), rs759383683, gnomAD 19-49166092-C-T, CADD 3.00
- M49L (p.Met49Leu), rs932987690, ClinGen CA406789440, ClinVar RCV002394769, ESM-1b 0.00, AlphaMissense 0.05, Uncertain significance, Cardiovascular phenotype
- M49V (p.Met49Val), TOPMed rs932987690, REVEL 0.10, ESM-1b 0.00, Uncertain significance
- M49P (p.Met49Pro), gnomAD 19-49166089-G-GGC, CADD 25.90
- E50K (p.Glu50Lys), Ensembl rs1967164464, REVEL 0.26, ESM-1b 0.00, Uncertain significance, Progressive familial heart block type IB
- E50D (p.Glu50Asp), gnomAD 19-49166098-G-C, REVEL 0.06, ESM-1b 0.00
- D51N (p.Asp51Asn), gnomAD 19-49166099-G-A, REVEL 0.22, ESM-1b 1.00
- D51G (p.Asp51Gly), gnomAD 19-49166100-A-G, REVEL 0.29, ESM-1b 1.00
Public TRPM4 analysis runs
- TRPM4 analysis run — TRPM4 (1,917 variants) — completed 2026-10-09