MYBPC3 (Myosin-binding protein C, cardiac-type) variants and mutations
The associated protein is Myosin-binding protein C, cardiac-type. A cardiac thick-filament protein positioned in the cross-bridge region of striated muscle. It binds myosin and actin and helps tune contraction, while MYBPC3 variants are a leading genetic cause of hypertrophic cardiomyopathy. This CATVariant analysis covers 2,593 MYBPC3 variants and mutations. Disease context includes hypertrophic cardiomyopathy; this analysis is associated with hypertrophic cardiomyopathy. Available evidence includes missense variants, protein structure.
Variant analysis overview
- Gene: MYBPC3
- Protein: Myosin-binding protein C, cardiac-type
- UniProt accession: Q14896
- Organism: Homo sapiens
- Variants analyzed: 2593
- Variant scope: all variants
- Completed: 2026-05-15
Variant and mutation evidence
- Variant composition: 2,398 unspecified-consequence records; 8 frameshift variants; 1 stop retained variant; 1 stop lost; 70 missense variants; 98 synonymous variants; 3 splice-region variants; 10 in-frame deletions; 2 in-frame insertions; 2 stop-gained variants
- Prediction scores: 2,509 variants have prediction scores (97% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: hypertrophic cardiomyopathy, hypertrophic cardiomyopathy 4, left ventricular noncompaction 10, cardiomyopathy, cardiomyopathy, dilated, 1MM, Rare familial disorder with hypertrophic cardiomyopathy, dilated cardiomyopathy, familial hypertrophic cardiomyopathy, Abnormality of the cardiovascular system, hypertrophic cardiomyopathy 1, intrinsic cardiomyopathy, Left ventricular noncompaction cardiomyopathy.
Protein structure and variant hotspots
- Protein features: 10 domains; 4 binding sites; 10 post-translational modification sites.
- Structural context: 2,025 variants have structural context.
- PTM context: 24 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, PharmGKB, MaveDB, LitVar.
Notable MYBPC3 variants
Examples include M1?, M1I, M1L, P2R, P2T, P4L, P4S, G5R. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, rs397516045, ClinGen CA055236, NCI-TCGA Cosmic COSV5703, ClinVar RCV001313650, Likely pathogenic
- M1I (p.Met1Ile), rs397516045, ClinGen CA015014, ClinVar RCV000035622, ClinVar RCV000578781, ESM-1b 0.00, AlphaMissense 0.30, Conflicting interpretations, Cardiomyopathy; not provided; Hypertrophic cardiomyopathy
- M1L (p.Met1Leu), rs1461764618, ClinGen CA380342848, ClinVar RCV001915932, ClinVar RCV003150467, ESM-1b 0.00, AlphaMissense 0.14, Conflicting interpretations, Cardiovascular phenotype; Cardiomyopathy; Hypertrophic cardiomyopathy 4
- P2R (p.Pro2Arg), Ensembl rs2142870759, ESM-1b 0.00, AlphaMissense 0.17
- P2T (p.Pro2Thr), rs1565632363, ClinGen CA380342832, ClinVar RCV000712371, ClinVar RCV004649295, ESM-1b 0.00, AlphaMissense 0.12, Uncertain significance, not provided; Cardiovascular phenotype
- P4L (p.Pro4Leu), rs748689012, ClinGen CA043117, cosmic curated COSV57033, ClinVar RCV000774446, REVEL 0.10, ESM-1b 0.00, Uncertain significance, Cardiomyopathy; Cardiovascular phenotype; not provided
- P4S (p.Pro4Ser), rs1308785992, ClinGen CA380342797, ClinVar RCV001944963, ClinVar RCV005672780, REVEL 0.10, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy
- G5R (p.Gly5Arg), rs201278114, ClinGen CA010249, ClinVar RCV000148668, ClinVar RCV000151176, REVEL 0.19, ESM-1b 0.00, Benign, Hypertrophic cardiomyopathy
- G5W (p.Gly5Trp), rs201278114, ClinGen CA277841, ClinVar RCV000201920, ClinVar RCV001060982, REVEL 0.08, ESM-1b 0.38, Uncertain significance, Hypertrophic cardiomyopathy 1; Hypertrophic cardiomyopathy; Cardiovascular pheno
- K7T (p.Lys7Thr), rs1595851193, ClinGen CA380342752, ClinVar RCV005400748, Ensembl rs1595851193, REVEL 0.14, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype
- P8T (p.Pro8Thr), rs2095901975, ClinGen CA380342736, ClinVar RCV001219051, Ensembl rs2095901975, REVEL 0.03, ESM-1b 0.00, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy
- V9A (p.Val9Ala), rs1395620536, ClinGen CA380342076, ClinVar RCV001805418, ClinVar RCV004009129, REVEL 0.08, ESM-1b 0.00, Conflicting interpretations, Cardiomyopathy; Hypertrophic cardiomyopathy
- V9I (p.Val9Ile), rs1064793201, ClinGen CA380342716, ClinVar RCV001932493, Ensembl rs1064793201, ESM-1b 0.00, AlphaMissense 0.12, Uncertain significance, Hypertrophic cardiomyopathy
- V9L (p.Val9Leu), rs1064793201, ClinGen CA16619345, ClinVar RCV000486424, Ensembl rs1064793201, ESM-1b 0.00, AlphaMissense 0.23, Uncertain significance, not provided
- S10* (p.Ser10Ter), rs2495786759, ClinGen CA380342071, ClinVar RCV002435602, Pathogenic
- A11T (p.Ala11Thr), Ensembl rs1565631973, ESM-1b 0.06, AlphaMissense 0.13
- F12L (p.Phe12Leu), rs2495786749, ClinGen CA380342061, ClinVar RCV002966724, REVEL 0.70, ESM-1b 0.00, Uncertain significance, Hypertrophic cardiomyopathy
- F12S (p.Phe12Ser), rs1462884291, ClinGen CA380342058, ClinVar RCV002223494, ClinVar RCV002487024, REVEL 0.84, ESM-1b 1.00, Uncertain significance, not provided; Left ventricular noncompaction 10; Hypertrophic cardiomyopathy 4
- S13R (p.Ser13Arg), rs730880136, ClinGen CA015006, ClinVar RCV000157301, gnomAD rs730880136, REVEL 0.06, ESM-1b 0.21, Uncertain significance, Long QT syndrome
- K14R (p.Lys14Arg), rs779049126, ClinGen CA055355, ClinVar RCV000481305, ClinVar RCV000629011, REVEL 0.25, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype; not provided; Cardiomyopathy
- P16S (p.Pro16Ser), rs730880573, ClinGen CA015183, ClinVar RCV000158175, ClinVar RCV001352035, REVEL 0.36, ESM-1b 1.00, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy 4; Left ventricular noncom
- R17L (p.Arg17Leu), ESP rs374630007, ExAC rs374630007, TOPMed rs374630007, gnomAD rs374630007, REVEL 0.30, ESM-1b 0.63, Uncertain significance
- R17Q (p.Arg17Gln), rs374630007, ClinGen CA015360, cosmic curated COSV10940, ClinVar RCV000151174, REVEL 0.14, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype; not provided; Cardiomyopathy
- R17W (p.Arg17Trp), rs747857800, ClinGen CA055562, cosmic curated COSV99909, ClinVar RCV000520274, REVEL 0.39, ESM-1b 1.00, Uncertain significance, not specified; Hypertrophic cardiomyopathy; Cardiomyopathy
- S18* (p.Ser18Ter), rs1320775536, ClinGen CA380342022, ClinVar RCV003532650, ClinVar RCV004011513, CADD 36.00, Pathogenic
- S18L (p.Ser18Leu), rs1320775536, ClinGen CA380342020, ClinVar RCV003532649, TOPMed rs1320775536, REVEL 0.12, ESM-1b 1.00, Uncertain significance, Cardiomyopathy
- V19A (p.Val19Ala), rs1247917628, ClinGen CA380342015, ClinVar RCV001342408, gnomAD rs1247917628, REVEL 0.12, ESM-1b 0.00, Conflicting interpretations, Cardiomyopathy; Hypertrophic cardiomyopathy
- V19G (p.Val19Gly), rs1247917628, ClinGen CA380342014, ClinVar RCV001061006, gnomAD rs1247917628, ESM-1b 1.00, AlphaMissense 0.35, Uncertain significance, Hypertrophic cardiomyopathy
- E20G (p.Glu20Gly), NCI-TCGA TCGA novel, REVEL 0.28, ESM-1b 1.00, Variant assessed as somatic; moderate impact.
- V21A (p.Val21Ala), rs1362750360, ClinGen CA380342001, ClinVar RCV001524616, ClinVar RCV003748341, REVEL 0.13, ESM-1b 0.00, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy
- V21E (p.Val21Glu), rs1362750360, ClinGen CA380342002, ClinVar RCV004007967, ESM-1b 1.00, AlphaMissense 0.68, Uncertain significance, Hypertrophic cardiomyopathy
- V21G (p.Val21Gly), gnomAD rs1362750360, REVEL 0.52, ESM-1b 0.83, Uncertain significance
- A22T (p.Ala22Thr), Ensembl rs2095900988, REVEL 0.03, ESM-1b 0.00
- A22V (p.Ala22Val), rs2495786653, ClinGen CA380341996, ClinVar RCV004014352, REVEL 0.03, ESM-1b 0.00, Uncertain significance, Hypertrophic cardiomyopathy
- A23E (p.Ala23Glu), rs2495786633, ClinGen CA380341992, ClinVar RCV002362315, REVEL 0.03, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype
- A23P (p.Ala23Pro), rs758044508, ClinGen CA015694, ClinVar RCV001998141, ExAC rs758044508, REVEL 0.10, ESM-1b 0.00, Conflicting interpretations, Cardiomyopathy; Hypertrophic cardiomyopathy
- A23T (p.Ala23Thr), rs758044508, ClinGen CA056440, NCI-TCGA Cosmic COSV5703, cosmic curated COSV57033, REVEL 0.05, ESM-1b 0.00, Conflicting interpretations, Cardiovascular phenotype; not specified; Cardiomyopathy
- A23V (p.Ala23Val), NCI-TCGA Cosmic COSV9990, cosmic curated COSV99909, REVEL 0.02, ESM-1b 0.00, Variant assessed as somatic; moderate impact.
- S25C (p.Ser25Cys), rs749970304, ClinGen CA056566, ClinVar RCV000774401, ClinVar RCV003133586, REVEL 0.14, ESM-1b 0.28, Uncertain significance, Cardiomyopathy; not provided; Hypertrophic cardiomyopathy
- S25N (p.Ser25Asn), rs371140684, ClinGen CA015780, ClinVar RCV000151173, ClinVar RCV000314127, REVEL 0.08, ESM-1b 0.00, Conflicting interpretations, Cardiovascular phenotype; Left ventricular noncompaction 10; Hypertrophic cardio
- P26S (p.Pro26Ser), rs2495786604, ClinGen CA380341975, ClinVar RCV003077405, ClinVar RCV003533347, REVEL 0.04, ESM-1b 0.00, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy
- V28G (p.Val28Gly), gnomAD rs1388702628, REVEL 0.19, ESM-1b 1.00
- V28M (p.Val28Met), rs776834755, ClinGen CA057025, NCI-TCGA Cosmic COSV9990, cosmic curated COSV99908, REVEL 0.18, ESM-1b 1.00, Benign/Likely benign, Cardiovascular phenotype; Hypertrophic cardiomyopathy 4; Left ventricular noncom
- F29C (p.Phe29Cys), TOPMed rs2095900955, ESM-1b 1.00, AlphaMissense 0.99, Uncertain significance
- F29S (p.Phe29Ser), rs2095900955, ClinGen CA380341956, ClinVar RCV001181746, TOPMed rs2095900955, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, Cardiomyopathy
- E30K (p.Glu30Lys), rs761079937, ClinGen CA016004, NCI-TCGA Cosmic COSV5703, cosmic curated COSV57030, REVEL 0.30, ESM-1b 1.00, Uncertain significance, Cardiovascular phenotype; not provided; Cardiomyopathy
- E30Q (p.Glu30Gln), rs761079937, ClinGen CA380341952, ClinVar RCV004016348, REVEL 0.30, ESM-1b 0.51, Uncertain significance, Hypertrophic cardiomyopathy
- A31T (p.Ala31Thr), rs536744834, ClinGen CA057465, ClinVar RCV004009847, 1000Genomes rs536744834, REVEL 0.36, ESM-1b 0.32, Uncertain significance, Hypertrophic cardiomyopathy
- E32K (p.Glu32Lys), rs730880575, ClinGen CA016177, ClinVar RCV000223809, ClinVar RCV000473946, REVEL 0.45, ESM-1b 1.00, Conflicting interpretations, Cardiovascular phenotype; not specified; Cardiomyopathy
- E32Q (p.Glu32Gln), rs730880575, ClinGen CA057616, ClinVar RCV002734775, ClinVar RCV004983097, REVEL 0.29, ESM-1b 0.78, Uncertain significance, Hypertrophic cardiomyopathy; Cardiovascular phenotype
- T33A (p.Thr33Ala), rs1265723882, ClinGen CA380341934, ClinVar RCV000560452, ClinVar RCV003159716, REVEL 0.47, ESM-1b 0.00, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy; Cardiovascular phenotype
- T33I (p.Thr33Ile), rs2095900926, ClinGen CA380341930, ClinVar RCV002774930, ClinVar RCV005401984, REVEL 0.43, ESM-1b 0.00, Uncertain significance, Hypertrophic cardiomyopathy; Cardiomyopathy
- E34A (p.Glu34Ala), Ensembl rs2095900921, ESM-1b 0.00, AlphaMissense 0.22
- E34K (p.Glu34Lys), NCI-TCGA Cosmic COSV5702, cosmic curated COSV57028, ESM-1b 0.00, AlphaMissense 0.32, Variant assessed as somatic; moderate impact.
- E34Q (p.Glu34Gln), rs2095900924, ClinGen CA380341928, ClinVar RCV003301256, ClinVar RCV005102716, ESM-1b 0.00, AlphaMissense 0.23, Uncertain significance, Hypertrophic cardiomyopathy; Cardiovascular phenotype
- R35L (p.Arg35Leu), rs397515885, ClinGen CA380341918, ClinVar RCV002401165, REVEL 0.39, ESM-1b 1.00, Uncertain significance, Cardiovascular phenotype
- R35Q (p.Arg35Gln), rs397515885, ClinGen CA009727, ClinVar RCV000459433, ClinVar RCV000766304, REVEL 0.68, ESM-1b 0.23, Conflicting interpretations, Cardiovascular phenotype; Hypertrophic cardiomyopathy 4; Left ventricular noncom
- R35W (p.Arg35Trp), rs727504249, ClinGen CA009726, ClinVar RCV001183966, ClinVar RCV001367394, REVEL 0.56, ESM-1b 1.00, Uncertain significance, Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10; Cardiovascular
- A36E (p.Ala36Glu), rs376646845, ClinGen CA042282, ClinVar RCV001178622, ClinVar RCV001216981, REVEL 0.08, ESM-1b 0.00, Uncertain significance, Hypertrophic cardiomyopathy; Cardiomyopathy; Cardiovascular phenotype
- A36T (p.Ala36Thr), cosmic curated COSV10584, Ensembl rs1595850720, REVEL 0.03, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy
- G37E (p.Gly37Glu), rs1085307653, ClinGen CA380341909, ClinVar RCV000489464, ClinVar RCV005090999, ESM-1b 0.92, AlphaMissense 0.28, Uncertain significance, Hypertrophic cardiomyopathy; not provided; Cardiomyopathy
- G37R (p.Gly37Arg), rs2142869753, ClinGen CA380341912, ClinVar RCV001526245, Ensembl rs2142869753, REVEL 0.43, ESM-1b 1.00, Uncertain significance, Cardiomyopathy
- V38A (p.Val38Ala), Ensembl rs1595850711, ESM-1b 0.00, AlphaMissense 0.30, Uncertain significance
- V38G (p.Val38Gly), rs1595850711, ClinGen CA380341902, ClinVar RCV001986269, Ensembl rs1595850711, ESM-1b 0.77, AlphaMissense 0.28, Uncertain significance, Hypertrophic cardiomyopathy
- V38M (p.Val38Met), rs1299024877, ClinGen CA380341906, ClinVar RCV001319830, ClinVar RCV001525303, REVEL 0.06, ESM-1b 0.39, Uncertain significance, Cardiovascular phenotype; not specified; not provided
- K39N (p.Lys39Asn), rs747965077, NCI-TCGA Cosmic COSV9990, cosmic curated COSV99909, ExAC rs747965077, REVEL 0.27, ESM-1b 0.00, Variant assessed as somatic; moderate impact.
- K39R (p.Lys39Arg), gnomAD rs1385174534, ESM-1b 0.00, AlphaMissense 0.13
- V40M (p.Val40Met), rs780085131, ClinGen CA043085, ClinVar RCV001221257, ClinVar RCV002339585, REVEL 0.63, ESM-1b 1.00, Uncertain significance, Hypertrophic cardiomyopathy; not provided; Cardiovascular phenotype
- R41C (p.Arg41Cys), rs373638535, ClinGen CA009878, NCI-TCGA Cosmic COSV9990, cosmic curated COSV99908, REVEL 0.40, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype; Left ventricular noncompaction 10; Hypertrophic cardio
- R41H (p.Arg41His), rs764849803, ClinGen CA043924, ClinVar RCV000234241, ClinVar RCV001184028, REVEL 0.23, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype; Left ventricular noncompaction 10; Hypertrophic cardio
- R41L (p.Arg41Leu), rs764849803, ClinGen CA380341886, ClinVar RCV003150781, REVEL 0.22, ESM-1b 0.00, Uncertain significance, Cardiomyopathy
- R41S (p.Arg41Ser), TOPMed rs1327610051, REVEL 0.16, CADD 24.30, Uncertain significance
- W42* (p.Trp42Ter), Ensembl rs1384247644, CADD 36.00
- W42L (p.Trp42Leu), Ensembl rs2142869700, ESM-1b 1.00, AlphaMissense 0.95
- W42R (p.Trp42Arg), rs1335468052, ClinGen CA380341884, ClinVar RCV001772386, ClinVar RCV002538807, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, Hypertrophic cardiomyopathy
- Q43* (p.Gln43Ter), rs892087411, NCI-TCGA Cosmic COSV5703, cosmic curated COSV57034, TOPMed rs892087411, Variant assessed as somatic; high impact.
- R44C (p.Arg44Cys), rs557439091, ClinGen CA044213, ClinVar RCV001180941, ClinVar RCV001751322, REVEL 0.10, ESM-1b 1.00, Uncertain significance, Hypertrophic cardiomyopathy; Cardiomyopathy; not provided
- R44H (p.Arg44His), rs369205562, ClinGen CA010081, ClinVar RCV000158188, ClinVar RCV000699945, REVEL 0.23, ESM-1b 1.00, Uncertain significance, Cardiovascular phenotype; not provided; Cardiomyopathy
- G45R (p.Gly45Arg), rs775837337, ClinGen CA044401, NCI-TCGA Cosmic COSV5702, cosmic curated COSV57026, REVEL 0.11, ESM-1b 0.48, Uncertain significance, Cardiovascular phenotype; Left ventricular noncompaction 10; Hypertrophic cardio
- G46D (p.Gly46Asp), rs2095900834, ClinGen CA380341857, ClinVar RCV003168178, ClinVar RCV004808450, REVEL 0.33, ESM-1b 0.25, Uncertain significance, Hypertrophic cardiomyopathy; Cardiovascular phenotype
- S47G (p.Ser47Gly), rs1267396024, ClinGen CA380341854, ClinVar RCV001184625, gnomAD rs1267396024, REVEL 0.14, ESM-1b 0.00, Uncertain significance, Cardiomyopathy
- S47N (p.Ser47Asn), rs1565631851, ClinGen CA380341851, ClinVar RCV001301504, ClinVar RCV004651551, REVEL 0.13, ESM-1b 0.00, Uncertain significance, Hypertrophic cardiomyopathy; Cardiovascular phenotype
- S47R (p.Ser47Arg), gnomAD rs1267396024, REVEL 0.09, ESM-1b 0.00, Uncertain significance
- I49* (p.Ile49Ter), Ensembl rs869025462, Likely pathogenic
- I49F (p.Ile49Phe), rs760058908, ClinGen CA045280, ClinVar RCV000770385, ClinVar RCV004807130, REVEL 0.54, ESM-1b 1.00, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy
- I49M (p.Ile49Met), rs774273586, ClinGen CA221708845, ClinVar RCV001189866, ClinVar RCV005093993, ESM-1b 1.00, AlphaMissense 0.53, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy
- I49V (p.Ile49Val), rs760058908, ClinGen CA380341838, ClinVar RCV002394771, REVEL 0.29, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy
- S50G (p.Ser50Gly), rs373164247, ClinGen CA010476, ClinVar RCV000035404, ClinVar RCV000770384, REVEL 0.07, ESM-1b 0.26, Conflicting interpretations, Cardiovascular phenotype; not specified; not provided
- S50N (p.Ser50Asn), rs2142869623, ClinGen CA380341831, ClinVar RCV001703350, Ensembl rs2142869623, ESM-1b 1.00, AlphaMissense 0.31, Uncertain significance, not provided
- S50R (p.Ser50Arg), rs368918487, ClinGen CA16613591, ClinVar RCV000470523, ClinVar RCV000619458, REVEL 0.07, ESM-1b 0.00, Uncertain significance, not provided; Hypertrophic cardiomyopathy
- A51G (p.Ala51Gly), ExAC rs746738538, gnomAD rs746738538, REVEL 0.10, ESM-1b 0.00
- A51S (p.Ala51Ser), rs534282225, ClinGen CA010559, ClinVar RCV000172017, ClinVar RCV001063574, REVEL 0.05, ESM-1b 0.00, Conflicting interpretations, Cardiovascular phenotype; Cardiomyopathy; not provided
- A51T (p.Ala51Thr), rs534282225, ClinGen CA045598, ClinVar RCV000487308, ClinVar RCV001184827, REVEL 0.07, ESM-1b 0.00, Conflicting interpretations, Cardiovascular phenotype; Hypertrophic cardiomyopathy; Cardiomyopathy
- A51V (p.Ala51Val), ExAC rs746738538, gnomAD rs746738538, REVEL 0.15, ESM-1b 0.00
- S52C (p.Ser52Cys), rs2095900771, ClinGen CA380341822, ClinVar RCV001044193, ClinVar RCV001772241, ESM-1b 1.00, AlphaMissense 0.43, Uncertain significance, not provided; Cardiovascular phenotype; Hypertrophic cardiomyopathy
- Y55* (p.Tyr55Ter), rs780012957, ClinGen CA380341793, ClinVar RCV003747867, ClinGen CA380341794, Pathogenic
- Y55C (p.Tyr55Cys), rs2495786214, ClinGen CA380341796, ClinVar RCV002297125, ESM-1b 1.00, AlphaMissense 0.94, Uncertain significance, Hypertrophic cardiomyopathy
- G56D (p.Gly56Asp), NCI-TCGA TCGA novel, Ensembl rs2142869589, REVEL 0.04, ESM-1b 0.00, Variant assessed as somatic; moderate impact.
- G56S (p.Gly56Ser), rs397515918, ClinGen CA010889, cosmic curated COSV57034, ClinVar RCV000035425, REVEL 0.03, ESM-1b 0.00, Conflicting interpretations, not specified; not provided; Cardiomyopathy
- L57P (p.Leu57Pro), gnomAD rs1307586978, REVEL 0.50, ESM-1b 0.18
- T59A (p.Thr59Ala), rs121909375, ClinGen CA011043, ClinVar RCV000009145, UniProt VAR 029391, ESM-1b 0.00, AlphaMissense 0.10, Pathogenic, Hypertrophic cardiomyopathy 4
- E60* (p.Glu60Ter), rs1410935154, ClinGen CA380341769, ClinVar RCV001924140, ClinVar RCV005868454, CADD 33.00, Pathogenic
- E60D (p.Glu60Asp), rs1399076195, ClinGen CA380341765, ClinVar RCV004014676, gnomAD rs1399076195, REVEL 0.02, ESM-1b 0.00, Uncertain significance, Hypertrophic cardiomyopathy
- E60G (p.Glu60Gly), rs2495786167, ClinGen CA380341767, ClinVar RCV004008150, REVEL 0.41, ESM-1b 1.00, Uncertain significance, Hypertrophic cardiomyopathy
- E60K (p.Glu60Lys), gnomAD rs1410935154, ESM-1b 0.00, AlphaMissense 0.25, Pathogenic
- G61D (p.Gly61Asp), Ensembl rs546345474, REVEL 0.41, ESM-1b 1.00, Uncertain significance, Hypertrophic cardiomyopathy
- G61R (p.Gly61Arg), Ensembl rs1595850639, ESM-1b 1.00, AlphaMissense 0.59
- T62A (p.Thr62Ala), rs377225516, ClinGen CA380341757, ClinVar RCV004014084, ESM-1b 0.00, AlphaMissense 0.14, Uncertain significance, Hypertrophic cardiomyopathy
- T62P (p.Thr62Pro), rs377225516, ClinGen CA011327, ClinVar RCV000035444, ClinVar RCV000148667, REVEL 0.33, ESM-1b 0.00, Conflicting interpretations, Left ventricular noncompaction 10; Cardiovascular phenotype; Hypertrophic cardio
- R63G (p.Arg63Gly), rs373315466, ClinGen CA380341753, ClinVar RCV001993985, 1000Genomes rs373315466, ESM-1b 1.00, AlphaMissense 0.45, Uncertain significance, Hypertrophic cardiomyopathy
- R63L (p.Arg63Leu), NCI-TCGA TCGA novel, REVEL 0.31, ESM-1b 0.00, Variant assessed as somatic; moderate impact.
- R63Q (p.Arg63Gln), rs549239819, ClinGen CA011393, ClinVar RCV000802262, ClinVar RCV001178564, REVEL 0.12, ESM-1b 0.93, Conflicting interpretations, Cardiovascular phenotype; Left ventricular noncompaction 10; Hypertrophic cardio
- R63W (p.Arg63Trp), rs373315466, ClinGen CA047089, ClinVar RCV000429655, ClinVar RCV000800606, REVEL 0.43, ESM-1b 1.00, Uncertain significance, Cardiomyopathy; not provided; Cardiovascular phenotype
- H64R (p.His64Arg), rs1250637243, ClinGen CA380341746, ClinVar RCV004008248, gnomAD rs1250637243, REVEL 0.44, ESM-1b 1.00, Uncertain significance, Hypertrophic cardiomyopathy
- T65K (p.Thr65Lys), ExAC rs753300898, TOPMed rs753300898, gnomAD rs753300898, REVEL 0.39, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype
- T65M (p.Thr65Met), rs753300898, ClinGen CA047700, NCI-TCGA Cosmic COSV5703, cosmic curated COSV57030, REVEL 0.35, ESM-1b 0.85, Conflicting interpretations, Hypertrophic cardiomyopathy; Cardiovascular phenotype; not specified
- T65S (p.Thr65Ser), gnomAD rs1182438503, REVEL 0.18, ESM-1b 0.00
- V68A (p.Val68Ala), rs2095900715, ClinGen CA380341722, ClinVar RCV001186076, ClinVar RCV004033358, ESM-1b 1.00, AlphaMissense 0.88, Uncertain significance, Cardiomyopathy; Cardiovascular phenotype
- V68M (p.Val68Met), rs1199851911, ClinGen CA380341726, ClinVar RCV000770383, ClinVar RCV001346659, REVEL 0.35, ESM-1b 1.00, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy
- R69P (p.Arg69Pro), rs397515945, ClinGen CA380341718, ClinVar RCV002922943, ESM-1b 1.00, AlphaMissense 0.69, Uncertain significance, Hypertrophic cardiomyopathy
- R69Q (p.Arg69Gln), rs397515945, ClinGen CA011710, ClinVar RCV000035462, ClinVar RCV000208106, REVEL 0.05, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype; Cardiomyopathy; Hypertrophic cardiomyopathy
- R69W (p.Arg69Trp), rs1173357672, ClinGen CA380341719, ClinVar RCV000628843, TOPMed rs1173357672, REVEL 0.34, ESM-1b 1.00, Uncertain significance, Hypertrophic cardiomyopathy; Cardiomyopathy
- E70* (p.Glu70Ter), rs11570045, ClinGen CA221708712, ClinVar RCV000494482, Ensembl rs11570045, CADD 36.00, Likely pathogenic
- E70A (p.Glu70Ala), rs2142869503, ClinGen CA380341714, ClinVar RCV002297601, ESM-1b 0.00, AlphaMissense 0.24, Uncertain significance, Hypertrophic cardiomyopathy
- E70D (p.Glu70Asp), rs1225434780, ClinGen CA380341711, ClinVar RCV001035659, ClinVar RCV002416328, REVEL 0.01, ESM-1b 0.00, Conflicting interpretations, Cardiomyopathy; Hypertrophic cardiomyopathy; Cardiovascular phenotype
- E70G (p.Glu70Gly), rs2142869503, ClinGen CA380341713, ClinVar RCV001972975, Ensembl rs2142869503, ESM-1b 0.00, AlphaMissense 0.23, Uncertain significance, Hypertrophic cardiomyopathy
- V71M (p.Val71Met), Ensembl rs2095900693, REVEL 0.34, ESM-1b 1.00
- G72D (p.Gly72Asp), rs1018066429, Ensembl rs1018066429, REVEL 0.03, ESM-1b 1.00, Variant assessed as somatic; moderate impact.
- G72S (p.Gly72Ser), gnomAD rs1327146767, REVEL 0.04, ESM-1b 0.00
- P73L (p.Pro73Leu), TOPMed rs1443164591, gnomAD rs1443164591, REVEL 0.11, ESM-1b 0.00
- A74D (p.Ala74Asp), TOPMed rs1215945374, gnomAD rs1215945374, REVEL 0.07, ESM-1b 0.16
- A74T (p.Ala74Thr), rs1555123744, ClinGen CA380341692, ClinVar RCV000544448, Ensembl rs1555123744, REVEL 0.05, ESM-1b 0.00, Uncertain significance, Hypertrophic cardiomyopathy
- D75E (p.Asp75Glu), rs1395765226, ClinGen CA380341680, ClinVar RCV002049921, gnomAD rs1395765226, REVEL 0.64, ESM-1b 1.00, Uncertain significance, Hypertrophic cardiomyopathy
- D75N (p.Asp75Asn), rs375471260, ClinGen CA011926, ClinVar RCV000148688, ClinVar RCV000154385, REVEL 0.65, ESM-1b 1.00, Uncertain significance, not specified; Cardiomyopathy; not provided
- D75Y (p.Asp75Tyr), rs375471260, ClinGen CA380341685, ClinVar RCV004015720, ESP rs375471260, REVEL 0.84, ESM-1b 1.00, Uncertain significance, Hypertrophic cardiomyopathy
- Q76* (p.Gln76Ter), rs1383067193, ClinGen CA380341677, ClinVar RCV003333608, ClinVar RCV003333609, Pathogenic
- Q76L (p.Gln76Leu), rs2495785929, ClinGen CA380341676, ClinVar RCV004015108, ClinVar RCV004987167, ESM-1b 1.00, AlphaMissense 0.43, Uncertain significance, Hypertrophic cardiomyopathy; Cardiovascular phenotype
- Q76R (p.Gln76Arg), rs2495785929, ClinGen CA380341674, ClinVar RCV002672181, REVEL 0.23, ESM-1b 0.00, Uncertain significance, Hypertrophic cardiomyopathy; Cardiomyopathy
- G77* (p.Gly77Ter), rs869025459, ClinGen CA351921, ClinVar RCV000208292, ClinVar RCV003152695, CADD 35.00, Pathogenic
- G77E (p.Gly77Glu), rs730880580, ClinGen CA012059, ClinVar RCV000158199, ClinVar RCV003998348, ESM-1b 1.00, AlphaMissense 0.68, Conflicting interpretations, not provided; Hypertrophic cardiomyopathy
- G77V (p.Gly77Val), rs730880580, ClinGen CA380341668, ClinVar RCV004012936, ClinVar RCV004987160, REVEL 0.28, ESM-1b 1.00, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy
- S78Y (p.Ser78Tyr), NCI-TCGA TCGA novel, ESM-1b 1.00, AlphaMissense 0.38, Variant assessed as somatic; moderate impact.
- Y79* (p.Tyr79Ter), rs730880698, ClinGen CA012155, ClinVar RCV000158452, ClinVar RCV000219427, CADD 28.70, Pathogenic
- Y79C (p.Tyr79Cys), rs2095900637, ClinGen CA380341658, ClinVar RCV001179168, Ensembl rs2095900637, ESM-1b 1.00, AlphaMissense 0.96, Uncertain significance, Cardiomyopathy
- Y79N (p.Tyr79Asn), rs730880581, ClinGen CA012128, ClinVar RCV000158200, Ensembl rs730880581, ESM-1b 1.00, AlphaMissense 0.99, Likely pathogenic, not provided
- A80G (p.Ala80Gly), rs1410583905, ClinGen CA380341640, ClinVar RCV000700176, TOPMed rs1410583905, REVEL 0.32, ESM-1b 0.00, Uncertain significance, Hypertrophic cardiomyopathy
- A80P (p.Ala80Pro), rs730880700, ClinGen CA380341646, ClinVar RCV001805589, ExAC rs730880700, ESM-1b 1.00, AlphaMissense 0.99, Uncertain significance, Cardiomyopathy
- A80S (p.Ala80Ser), rs730880700, ClinGen CA221708620, ClinVar RCV001190059, ClinVar RCV001786449, REVEL 0.22, ESM-1b 0.00, Uncertain significance, Cardiomyopathy; Cardiovascular phenotype; not provided
- A80T (p.Ala80Thr), rs730880700, ClinGen CA012189, ClinVar RCV000158454, ClinVar RCV001181610, REVEL 0.28, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype; not provided; Hypertrophic cardiomyopathy 4
- V81F (p.Val81Phe), rs999833111, ClinGen CA221708602, ClinVar RCV001182750, ClinVar RCV001297131, REVEL 0.23, ESM-1b 1.00, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy; Cardiomyopathy
- V81L (p.Val81Leu), rs999833111, ClinGen CA380341630, ClinVar RCV001884173, TOPMed rs999833111, REVEL 0.20, ESM-1b 0.00, Uncertain significance, Hypertrophic cardiomyopathy
- I82T (p.Ile82Thr), rs2142869399, ClinGen CA380341612, ClinVar RCV002015873, Ensembl rs2142869399, REVEL 0.47, ESM-1b 0.00, Uncertain significance, Hypertrophic cardiomyopathy
- I82V (p.Ile82Val), rs1470947124, ClinGen CA380341617, ClinVar RCV001804477, TOPMed rs1470947124, REVEL 0.20, ESM-1b 0.00, Uncertain significance, Hypertrophic cardiomyopathy; Cardiomyopathy
- A83T (p.Ala83Thr), gnomAD rs1186618936, REVEL 0.58, ESM-1b 0.26
- G84A (p.Gly84Ala), rs569824900, ClinGen CA380341580, ClinVar RCV002433036, ESM-1b 1.00, AlphaMissense 0.34, Uncertain significance, Cardiovascular phenotype
- G84D (p.Gly84Asp), rs569824900, ClinGen CA050305, ClinVar RCV000988557, ClinVar RCV001179873, REVEL 0.61, ESM-1b 0.05, Uncertain significance, Hypertrophic cardiomyopathy 4; Hypertrophic cardiomyopathy; Cardiomyopathy
- S85F (p.Ser85Phe), gnomAD rs1280347352, REVEL 0.40, ESM-1b 1.00, Uncertain significance, Hypertrophic cardiomyopathy
- S86C (p.Ser86Cys), ExAC rs772057451, REVEL 0.45, ESM-1b 0.38
- S86T (p.Ser86Thr), gnomAD rs1463632321, REVEL 0.28, ESM-1b 0.00
- K87N (p.Lys87Asn), NCI-TCGA TCGA novel, REVEL 0.29, ESM-1b 0.94, Variant assessed as somatic; moderate impact.
- V88D (p.Val88Asp), rs730880583, ClinGen CA012782, ClinVar RCV000158204, ClinVar RCV001857563, REVEL 0.51, ESM-1b 1.00, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy; not provided
- F90L (p.Phe90Leu), rs367990952, ClinGen CA012859, ClinVar RCV000171196, ESP rs367990952, REVEL 0.34, ESM-1b 1.00, Uncertain significance, Cardiomyopathy
- D91H (p.Asp91His), rs778851720, ClinGen CA380341492, ClinVar RCV004007982, ESM-1b 0.00, AlphaMissense 0.53, Uncertain significance, Hypertrophic cardiomyopathy
- D91N (p.Asp91Asn), rs778851720, ClinGen CA051307, ClinVar RCV000823877, ClinVar RCV001814243, REVEL 0.19, ESM-1b 0.00, Uncertain significance, Hypertrophic cardiomyopathy; Cardiovascular phenotype; Left ventricular noncompa
- D91Y (p.Asp91Tyr), ExAC rs778851720, TOPMed rs778851720, gnomAD rs778851720, REVEL 0.32, ESM-1b 0.97, Uncertain significance
- V94F (p.Val94Phe), rs770777166, ClinGen CA051564, ClinVar RCV001170430, ClinVar RCV001859103, REVEL 0.58, ESM-1b 1.00, Uncertain significance, Hypertrophic cardiomyopathy; Cardiomyopathy
- I95L (p.Ile95Leu), rs549758428, ClinGen CA051645, ClinVar RCV001103398, ClinVar RCV001105313, REVEL 0.02, ESM-1b 0.00, Uncertain significance, Hypertrophic cardiomyopathy
- I95T (p.Ile95Thr), rs727504945, ClinGen CA013055, ClinVar RCV000156346, ClinVar RCV000766605, REVEL 0.02, ESM-1b 0.00, Conflicting interpretations, not specified; not provided; Cardiomyopathy
- I95V (p.Ile95Val), 1000Genomes rs549758428, ExAC rs549758428, TOPMed rs549758428, gnomAD rs549758428, REVEL 0.02, ESM-1b 0.00, Likely benign
- E96G (p.Glu96Gly), ExAC rs777170653, gnomAD rs777170653, REVEL 0.16, ESM-1b 0.00
- E96K (p.Glu96Lys), NCI-TCGA TCGA novel, ESM-1b 0.68, AlphaMissense 0.23, Variant assessed as somatic; moderate impact.
- E96Q (p.Glu96Gln), rs1011673088, ClinGen CA221708491, ClinVar RCV001190120, ClinVar RCV002560075, REVEL 0.06, ESM-1b 0.84, Uncertain significance, Hypertrophic cardiomyopathy; Cardiomyopathy
- E96V (p.Glu96Val), ExAC rs777170653, gnomAD rs777170653, REVEL 0.31, ESM-1b 0.80
- A97S (p.Ala97Ser), rs2095900531, ClinGen CA380341399, ClinVar RCV001200342, ClinVar RCV003486964, REVEL 0.03, ESM-1b 0.00, Uncertain significance, not provided; Cardiomyopathy
- A97V (p.Ala97Val), rs397515993, ClinGen CA013180, ClinVar RCV000035541, ClinVar RCV000705202, REVEL 0.10, ESM-1b 0.00, Conflicting interpretations, not specified; not provided; Hypertrophic cardiomyopathy
- E98* (p.Glu98Ter), rs868819340, ClinGen CA221708458, ClinVar RCV000628982, Ensembl rs868819340, CADD 45.00, Pathogenic
- E98G (p.Glu98Gly), rs2495783963, ClinGen CA380341245, ClinVar RCV002440141, REVEL 0.06, ESM-1b 0.00, Uncertain significance, Cardiovascular phenotype
- E98Q (p.Glu98Gln), rs868819340, ClinGen CA16613414, ClinVar RCV000468949, ClinVar RCV001549952, ESM-1b 0.00, AlphaMissense 0.15, Uncertain significance, Hypertrophic cardiomyopathy; not provided; Cardiovascular phenotype
- K99T (p.Lys99Thr), rs1555123639, ClinGen CA380341219, ClinVar RCV000614279, ClinVar RCV001046923, REVEL 0.05, ESM-1b 0.00, Uncertain significance, Hypertrophic cardiomyopathy; not specified
- A100V (p.Ala100Val), TOPMed rs2095899790, REVEL 0.07, ESM-1b 0.00
Public MYBPC3 analysis runs
- MYBPC3 analysis run — MYBPC3 (2,593 variants) — completed 2026-05-15