ACTC1 (Actin, alpha cardiac muscle 1) variants and mutations
ACTC1 (also known as Actin, alpha cardiac muscle 1) is a human protein-coding gene encoding an actin, alpha cardiac muscle 1 protein. Its cardiac alpha-actin filaments form the core of the sarcomeric thin filament and provide the track against which myosin generates force. Pathogenic variants can cause hypertrophic or dilated cardiomyopathy and selected congenital heart defects. This analysis covers 684 ACTC1 variants and mutations. Of these, 83% have computational variant effect predictions. Disease context includes hypertrophic cardiomyopathy, atrial septal defect 5, and left ventricular noncompaction. Example ACTC1 variants include M1L, M1T, and M1V.
Variant analysis overview
- Gene: ACTC1
- Protein: Actin, alpha cardiac muscle 1
- UniProt accession: P68032
- Organism: Homo sapiens
- Variants analyzed: 684
- Variant scope: all variants
- Completed: 2026-08-10
Variant and mutation evidence
- Variant composition: 465 unspecified-consequence records; 150 synonymous variants; 53 missense variants; 9 frameshift variants; 3 stop-gained variants; 2 splice-region variants; 1 in-frame deletions; 1 substitution
- Prediction scores: 568 variants have prediction scores (83% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: hypertrophic cardiomyopathy, atrial septal defect 5, left ventricular noncompaction, hypertrophic cardiomyopathy 11, familial isolated dilated cardiomyopathy, left ventricular noncompaction 4, atrial septal defect, Abnormality of the cardiovascular system, Left ventricular noncompaction cardiomyopathy, cardiomyopathy, Rare familial disorder with hypertrophic cardiomyopathy, familial hypertrophic cardiomyopathy.
Protein structure and variant hotspots
- Protein features: 5 post-translational modification sites.
- PTM context: 5 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 ACTC1 variants
Examples include M1L, M1T, M1V, C2Y, D3E, D3H, D4E, D4H. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1L (p.Met1Leu), rs1891784379, ClinGen CA391633546, ClinVar RCV003380020, MetaLR 0.70, MetaSVM 0.30, Uncertain significance, Cardiovascular phenotype
- M1T (p.Met1Thr), rs781220417, ClinGen CA041583, ClinVar RCV001241829, MetaLR 0.75, MetaSVM 0.44, Likely benign, not provided
- M1V (p.Met1Val), rs1891784379, ClinGen CA391633548, ClinVar RCV003802232, MetaLR 0.70, MetaSVM 0.30, Uncertain significance, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- C2Y (p.Cys2Tyr), rs1469206760, ClinGen CA391633527, ClinVar RCV001207253, ClinVar RCV003532894, REVEL 0.56, MetaLR 0.59, Uncertain significance, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- D3E (p.Asp3Glu), 1000Genomes rs535623090, gnomAD rs535623090, REVEL 0.42, MetaLR 0.64, Likely benign
- D3H (p.Asp3His), rs397517069, ClinGen CA019928, ClinVar RCV000038338, Ensembl rs397517069, AlphaMissense 0.59, MetaLR 0.75, Uncertain significance, not specified
- D4E (p.Asp4Glu), rs768526036, ClinGen CA391633489, ClinVar RCV000648298, ExAC rs768526036, REVEL 0.48, MetaLR 0.63, Uncertain significance, Atrial septal defect 5; Dilated cardiomyopathy 1R; Hypertrophic cardiomyopathy 1
- D4H (p.Asp4His), rs730880408, ClinGen CA019643, ClinVar RCV000157803, ClinVar RCV000821482, REVEL 0.61, MetaLR 0.85, Uncertain significance, Atrial septal defect 5; Dilated cardiomyopathy 1R; Hypertrophic cardiomyopathy 1
- D4N (p.Asp4Asn), rs730880408, ClinGen CA391633500, ClinVar RCV000648302, ClinVar RCV002424493, REVEL 0.38, MetaLR 0.77, Uncertain significance, Atrial septal defect 5; Dilated cardiomyopathy 1R; Hypertrophic cardiomyopathy 1
- D4Y (p.Asp4Tyr), gnomAD rs730880408, REVEL 0.65, MetaLR 0.85, Uncertain significance
- E5G (p.Glu5Gly), NCI-TCGA TCGA novel, MetaLR 0.83, MetaSVM 0.74, Variant assessed as somatic; moderate impact.
- E6D (p.Glu6Asp), rs1891783715, ClinGen CA391633458, NCI-TCGA Cosmic COSV9929, ClinVar RCV002408240, REVEL 0.47, MetaLR 0.81, Uncertain significance, Cardiovascular phenotype
- T7N (p.Thr7Asn), rs2504185703, ClinGen CA391633450, NCI-TCGA Cosmic COSV9929, ClinVar RCV004016058, Uncertain significance, Hypertrophic cardiomyopathy
- T7S (p.Thr7Ser), rs746748461, ClinGen CA041208, ClinVar RCV001177947, ClinVar RCV003769916, REVEL 0.46, MetaLR 0.56, Uncertain significance, Cardiomyopathy; Atrial septal defect 5; Dilated cardiomyopathy 1R
- T8A (p.Thr8Ala), rs730880390, ClinGen CA019702, ClinVar RCV000157775, ClinVar RCV001319568, AlphaMissense 0.14, MetaLR 0.79, Uncertain significance, Cardiovascular phenotype; Atrial septal defect 5; Dilated cardiomyopathy 1R
- T8I (p.Thr8Ile), NCI-TCGA Cosmic COSV9929, MetaLR 0.92, MetaSVM 1.06, Variant assessed as somatic; moderate impact.
- T8S (p.Thr8Ser), ExAC rs780088008, gnomAD rs780088008, REVEL 0.55, MetaLR 0.80, Uncertain significance, Cardiomyopathy
- A9T (p.Ala9Thr), NCI-TCGA Cosmic COSV5175, Uncertain significance, not provided
- L10M (p.Leu10Met), rs397517057, ClinGen CA019732, ClinVar RCV000043641, ClinVar RCV000251618, REVEL 0.77, MetaLR 0.95, Conflicting interpretations, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- V11L (p.Val11Leu), rs1794699355, ClinGen CA391633409, ClinVar RCV003801211, AlphaMissense 1.00, MetaLR 0.98, Uncertain significance, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- V11M (p.Val11Met), TOPMed rs1794699355
- C12Y (p.Cys12Tyr), rs2504185646, ClinGen CA391633395, ClinVar RCV004015992, Uncertain significance, Hypertrophic cardiomyopathy
- N14D (p.Asn14Asp), rs2504185639, ClinGen CA391633370, ClinVar RCV003815494, Uncertain significance, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- G15C (p.Gly15Cys), NCI-TCGA Cosmic COSV9929, Variant assessed as somatic; moderate impact.
- G15R (p.Gly15Arg), rs2504185628, ClinGen CA391633353, ClinVar RCV003803554, Uncertain significance, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- S16C (p.Ser16Cys), Ensembl rs1891782816
- L18M (p.Leu18Met), rs2504185604, ClinGen CA391633318, ClinVar RCV003017463, Uncertain significance, Atrial septal defect 5; Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1
- A21T (p.Ala21Thr), rs1270508243, ClinGen CA391633280, ClinVar RCV002900643, ClinVar RCV003167924, REVEL 0.90, MetaLR 0.97, Uncertain significance, Cardiovascular phenotype; Atrial septal defect 5; Hypertrophic cardiomyopathy 11
- A21V (p.Ala21Val), rs1060502823, ClinGen CA16614451, ClinVar RCV000468585, Ensembl rs1060502823, AlphaMissense 0.89, MetaLR 0.92, Uncertain significance, Atrial septal defect 5; Dilated cardiomyopathy 1R; Hypertrophic cardiomyopathy 1
- G22S (p.Gly22Ser), NCI-TCGA Cosmic COSV5175, Variant assessed as somatic; moderate impact.
- F23I (p.Phe23Ile), NCI-TCGA Cosmic COSV9929, Variant assessed as somatic; moderate impact.
- F23L (p.Phe23Leu), rs193922681, ClinGen CA019869, ClinVar RCV000029294, ClinVar RCV001342095, AlphaMissense 1.00, MetaLR 0.89, Uncertain significance, Cardiovascular phenotype
- G25S (p.Gly25Ser), TOPMed rs1891781693, REVEL 0.94, MetaLR 0.95
- G25V (p.Gly25Val), NCI-TCGA Cosmic COSV5175, MetaLR 0.97, MetaSVM 1.07, Variant assessed as somatic; moderate impact.
- D26E (p.Asp26Glu), rs1439528781, ClinGen CA391633210, ClinVar RCV004017177, Uncertain significance, Hypertrophic cardiomyopathy
- D26N (p.Asp26Asn), rs727504399, ClinGen CA019909, NCI-TCGA Cosmic COSV5175, ClinVar RCV000154575, REVEL 0.74, MetaLR 0.92, Conflicting interpretations, Atrial septal defect 5; Dilated cardiomyopathy 1R; Hypertrophic cardiomyopathy 1
- D27E (p.Asp27Glu), rs753552901, ClinGen CA391633194, ClinVar RCV003141176, Uncertain significance, not provided
- A28T (p.Ala28Thr), rs2504185511, ClinGen CA391633190, ClinVar RCV002900405, NCI-TCGA TCGA novel, Conflicting interpretations, Atrial septal defect 5; Dilated cardiomyopathy 1R; Hypertrophic cardiomyopathy 1
- A28V (p.Ala28Val), rs397517072, ClinGen CA019957, NCI-TCGA Cosmic COSV5175, ClinVar RCV000043642, REVEL 0.80, MetaLR 0.80, Uncertain significance, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- R30C (p.Arg30Cys), NCI-TCGA Cosmic COSV5175, Variant assessed as somatic; moderate impact.
- R30S (p.Arg30Ser), Ensembl rs1595761997
- A31T (p.Ala31Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A31V (p.Ala31Val), rs2504185480, ClinGen CA391633146, ClinVar RCV003784865, Uncertain significance, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- V32A (p.Val32Ala), NCI-TCGA Cosmic COSV5175, Variant assessed as somatic; moderate impact.
- V32I (p.Val32Ile), rs1555419003, ClinGen CA391633142, ClinVar RCV000648299, Ensembl rs1555419003, AlphaMissense 0.40, MetaLR 0.69, Uncertain significance, Atrial septal defect 5; Dilated cardiomyopathy 1R; Hypertrophic cardiomyopathy 1
- V32L (p.Val32Leu), rs1555419003, ClinGen CA391633144, ClinVar RCV002988724, AlphaMissense 0.40, MetaLR 0.69, Uncertain significance, Dilated cardiomyopathy 1R; Atrial septal defect 5; Hypertrophic cardiomyopathy 1
- P34L (p.Pro34Leu), rs1373760624, ClinGen CA391633107, ClinVar RCV000678695, TOPMed rs1373760624, REVEL 0.97, AlphaMissense 0.98, Uncertain significance, Left ventricular dilatation
- P34Q (p.Pro34Gln), rs1373760624, ClinGen CA391633111, ClinVar RCV001039657, TOPMed rs1373760624, AlphaMissense 0.98, MetaLR 0.96, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy
- P34R (p.Pro34Arg), rs1373760624, ClinGen CA391633109, ClinVar RCV001341397, ClinVar RCV002368125, REVEL 0.97, AlphaMissense 0.98, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy
- P34S (p.Pro34Ser), rs1451590510, NCI-TCGA Cosmic COSV9929, gnomAD rs1451590510, AlphaMissense 0.90, MetaLR 0.93, Variant assessed as somatic; moderate impact.
- S35A (p.Ser35Ala), rs1595761987, ClinGen CA391633101, ClinVar RCV000795462, Ensembl rs1595761987, AlphaMissense 0.23, MetaLR 0.94, Uncertain significance, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- S35P (p.Ser35Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I36M (p.Ile36Met), rs1457769757, ClinGen CA391633083, ClinVar RCV003794027, ClinVar RCV004006036, Uncertain significance, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- I36V (p.Ile36Val), ExAC rs759988070, gnomAD rs759988070, REVEL 0.59, MetaLR 0.63
- V37A (p.Val37Ala), gnomAD rs1156953978, REVEL 0.93, MetaLR 0.94
- V37M (p.Val37Met), rs1407311947, NCI-TCGA Cosmic COSV5176, gnomAD rs1407311947, REVEL 0.92, MetaLR 0.93, Uncertain significance, Atrial septal defect 5; Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1
- G38S (p.Gly38Ser), Ensembl rs2140433187
- R39C (p.Arg39Cys), NCI-TCGA Cosmic COSV5175, Ensembl rs2140433184, Variant assessed as somatic; moderate impact.
- R39H (p.Arg39His), rs2504185412, NCI-TCGA Cosmic COSV5176, ClinVar RCV004558097, Likely benign, EBV-positive nodal T- and NK-cell lymphoma
- R41Q (p.Arg41Gln), NCI-TCGA Cosmic COSV5175, Variant assessed as somatic; moderate impact.
- R41W (p.Arg41Trp), NCI-TCGA Cosmic COSV5175, MetaLR 0.85, MetaSVM 0.92, Variant assessed as somatic; moderate impact.
- H42Y (p.His42Tyr), rs2140433161, ClinGen CA391633022, ClinVar RCV001946513, Ensembl rs2140433161, AlphaMissense 0.73, MetaLR 0.69, Uncertain significance, Atrial septal defect 5; Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1
- G44* (p.Gly44Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- G44=, NCI-TCGA TCGA novel, Variant assessed as somatic; low impact.
- V45A (p.Val45Ala), rs1555418924, ClinGen CA391632289, ClinVar RCV000554419, Ensembl rs1555418924, AlphaMissense 0.96, MetaLR 0.70, Uncertain significance, Atrial septal defect 5; Dilated cardiomyopathy 1R; Hypertrophic cardiomyopathy 1
- M46K (p.Met46Lys), gnomAD 15-34793562-A-T, REVEL 0.90, MetaLR 0.81
- V47V (p.Val47Val), gnomAD 15-34793558-C-T, CADD 10.70
- V47A (p.Val47Ala), gnomAD 15-34793559-A-G, REVEL 0.83, MetaLR 0.87
- G48C (p.Gly48Cys), Ensembl rs76508081
- G48V (p.Gly48Val), NCI-TCGA Cosmic COSV9929, MetaLR 0.93, MetaSVM 1.07, Variant assessed as somatic; moderate impact.
- G48G (p.Gly48Gly), gnomAD 15-34793555-A-T, CADD 9.70, SIFT 0.01
- M49I (p.Met49Ile), NCI-TCGA TCGA novel, MetaLR 0.63, MetaSVM 0.11, Variant assessed as somatic; moderate impact.
- G50S (p.Gly50Ser), rs1555418921, ClinGen CA391632221, ClinVar RCV003767820, ClinVar RCV005400735, AlphaMissense 0.85, MetaLR 0.87, Conflicting interpretations, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- Q51* (p.Gln51Ter), rs2504183400, ClinGen CA391632213, ClinVar RCV002870949, Uncertain significance
- K52Q (p.Lys52Gln), NCI-TCGA Cosmic COSV5176, Variant assessed as somatic; moderate impact.
- K52T (p.Lys52Thr), rs2140432240, ClinGen CA391632191, ClinVar RCV001961500, Ensembl rs2140432240, AlphaMissense 0.99, MetaLR 0.92, Likely pathogenic, Dilated cardiomyopathy 1R; Atrial septal defect 5; Hypertrophic cardiomyopathy 1
- K52K (p.Lys52Lys), gnomAD 15-34793543-C-T, CADD 13.20, SIFT 0.00
- D53N (p.Asp53Asn), rs2504183375, ClinGen CA391632181, ClinVar RCV003070263, Uncertain significance, Dilated cardiomyopathy 1R; Atrial septal defect 5; Hypertrophic cardiomyopathy 1
- D53V (p.Asp53Val), rs1555418919, ClinGen CA391632176, ClinVar RCV000617708, ClinVar RCV001764728, AlphaMissense 0.99, MetaLR 0.89, Uncertain significance, Cardiovascular phenotype; Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy
- S54A (p.Ser54Ala), gnomAD rs1478666795
- S54F (p.Ser54Phe), rs730880391, ClinGen CA019669, ClinVar RCV000157778, ClinVar RCV005222787, AlphaMissense 0.83, MetaLR 0.81, Uncertain significance, Atrial septal defect 5; Dilated cardiomyopathy 1R; Hypertrophic cardiomyopathy 1
- S54T (p.Ser54Thr), gnomAD rs1478666795, REVEL 0.56, MetaLR 0.76
- S54S (p.Ser54Ser), rs748909803, gnomAD 15-34793537-G-A, CADD 14.00
- S54C (p.Ser54Cys), gnomAD 15-34793538-G-C, REVEL 0.73, MetaLR 0.81
- Y55Y (p.Tyr55Tyr), rs149432225, gnomAD 15-34793534-G-A, CADD 5.14
- Y55C (p.Tyr55Cys), gnomAD 15-34793535-T-C, REVEL 0.96, MetaLR 0.92
- V56I (p.Val56Ile), rs944740404, ClinGen CA268663502, NCI-TCGA Cosmic COSV5175, ClinVar RCV001178519, REVEL 0.59, MetaLR 0.83, Uncertain significance, Primary dilated cardiomyopathy
- V56L (p.Val56Leu), rs944740404, ClinGen CA391632137, ClinVar RCV001863893, TOPMed rs944740404, REVEL 0.81, MetaLR 0.93, Uncertain significance, Dilated cardiomyopathy 1R; Atrial septal defect 5; Hypertrophic cardiomyopathy 1
- G57S (p.Gly57Ser), TOPMed rs1891752230, gnomAD rs1891752230, REVEL 0.93, MetaLR 0.94, Uncertain significance, Atrial septal defect 5; Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1
- D58Y (p.Asp58Tyr), NCI-TCGA Cosmic COSV9929, Variant assessed as somatic; moderate impact.
- E59E (p.Glu59Glu), rs755858258, gnomAD 15-34793522-T-C, CADD 12.20
- A60S (p.Ala60Ser), rs1555418912, ClinGen CA391632078, ClinVar RCV004521291, AlphaMissense 0.99, MetaLR 0.93, Uncertain significance, Cardiovascular phenotype
- A60T (p.Ala60Thr), rs1555418912, ClinGen CA391632082, ClinVar RCV000648296, ClinVar RCV000769473, AlphaMissense 0.99, MetaLR 0.93, Uncertain significance, Cardiomyopathy; Atrial septal defect 5; Dilated cardiomyopathy 1R
- A60A (p.Ala60Ala), rs370322510, gnomAD 15-34793519-G-A, CADD 13.30
- S62G (p.Ser62Gly), Ensembl rs1891751811, Uncertain significance, Atrial septal defect 5; Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1
- S62I (p.Ser62Ile), Ensembl rs2140432196
- S62N (p.Ser62Asn), NCI-TCGA Cosmic COSV5176, MetaLR 0.83, MetaSVM 0.61, Variant assessed as somatic; moderate impact.
- K63N (p.Lys63Asn), rs2140432188, NCI-TCGA Cosmic COSV5176, ClinGen CA391632024, ClinVar RCV003328084, Uncertain significance, Dilated cardiomyopathy 1R
- K63R (p.Lys63Arg), rs794727502, ClinGen CA019679, ClinVar RCV000177225, ClinVar RCV000530584, AlphaMissense 0.51, MetaLR 0.86, Uncertain significance, Atrial septal defect 5; Dilated cardiomyopathy 1R; Hypertrophic cardiomyopathy 1
- R64K (p.Arg64Lys), rs869025353, ClinGen CA351904, ClinVar RCV000208267, ClinVar RCV002295289, AlphaMissense 0.97, MetaLR 0.84, Uncertain significance, Cardiovascular phenotype; Atrial septal defect 5; Hypertrophic cardiomyopathy 11
- I66M (p.Ile66Met), rs780724030, ClinGen CA391631983, ClinVar RCV002423800, Uncertain significance, Cardiovascular phenotype
- I66I (p.Ile66Ile), rs780724030, gnomAD 15-34793501-G-T, CADD 12.00
- L67M (p.Leu67Met), NCI-TCGA Cosmic COSV5175, Variant assessed as somatic; moderate impact.
- L67L (p.Leu67Leu), rs1440918499, gnomAD 15-34793500-G-A, CADD 13.40
- T68N (p.Thr68Asn), gnomAD rs1270699898, REVEL 0.67, MetaLR 0.89
- T68T (p.Thr68Thr), rs1891751214, gnomAD 15-34793495-G-A, CADD 8.96
- L69L (p.Leu69Leu), gnomAD 15-34793492-C-G, CADD 11.00
- K70K (p.Lys70Lys), rs758865091, gnomAD 15-34793489-C-T, CADD 13.20
- P72S (p.Pro72Ser), rs2140432138, ClinGen CA391631915, ClinVar RCV001555263, Ensembl rs2140432138, AlphaMissense 1.00, MetaLR 0.98, Uncertain significance, not provided
- P72P (p.Pro72Pro), rs1346123657, gnomAD 15-34793483-G-T, CADD 12.40
- I73V (p.Ile73Val), rs750951965, ClinGen CA041260, ClinVar RCV000216183, ClinVar RCV001179800, REVEL 0.69, MetaLR 0.81, Uncertain significance, Cardiovascular phenotype; Cardiomyopathy; not specified
- I73I (p.Ile73Ile), gnomAD 15-34793480-G-T, CADD 1.70
- E74D (p.Glu74Asp), gnomAD rs1298902768, REVEL 0.73, MetaLR 0.92
- E74K (p.Glu74Lys), gnomAD rs1352413131, REVEL 0.88, AlphaMissense 0.98
- E74Q (p.Glu74Gln), rs1352413131, ClinGen CA391631891, ClinVar RCV003801817, AlphaMissense 0.98, MetaLR 0.95, Uncertain significance, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- H75H (p.His75His), rs1441829438, gnomAD 15-34793474-A-G, CADD 2.16
- G76D (p.Gly76Asp), NCI-TCGA Cosmic COSV9929, MetaLR 0.98, MetaSVM 1.05, Variant assessed as somatic; moderate impact.
- I77T (p.Ile77Thr), NCI-TCGA TCGA novel, MetaLR 0.94, MetaSVM 1.06, Variant assessed as somatic; moderate impact.
- I77V (p.Ile77Val), rs397517056, ClinGen CA019696, ClinVar RCV000038322, ClinVar RCV004018868, REVEL 0.70, MetaLR 0.81, Uncertain significance, Cardiovascular phenotype; not specified
- I78V (p.Ile78Val), Ensembl rs2140432101, MetaLR 0.96, MetaSVM 1.06, Uncertain significance, Hypertrophic cardiomyopathy
- T79S (p.Thr79Ser), Ensembl rs2140432094, MetaLR 0.87, MetaSVM 0.72
- T79T (p.Thr79Thr), rs1595761422, gnomAD 15-34793462-G-T, CADD 12.30
- N80N (p.Asn80Asn), rs1178754602, gnomAD 15-34793459-G-A, CADD 13.30
- W81* (p.Trp81Ter), rs1891749863, ClinGen CA391631779, ClinVar RCV003992009, TOPMed rs1891749863, Uncertain significance
- W81C (p.Trp81Cys), NCI-TCGA TCGA novel, MetaLR 0.98, MetaSVM 1.02, Variant assessed as somatic; moderate impact.
- D82E (p.Asp82Glu), rs373261583, ClinGen CA391631762, ClinVar RCV002288370, ClinVar RCV004808246, Uncertain significance, Hypertrophic cardiomyopathy; Dilated cardiomyopathy 1R
- D82N (p.Asp82Asn), rs2504183112, ClinGen CA391631772, ClinVar RCV003808263, Uncertain significance, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- D82D (p.Asp82Asp), rs373261583, gnomAD 15-34793453-G-A, CADD 1.10
- D82G (p.Asp82Gly), gnomAD 15-34793454-T-C, REVEL 0.95, MetaLR 0.95
- D83N (p.Asp83Asn), Ensembl rs867127535
- D83V (p.Asp83Val), NCI-TCGA Cosmic COSV9929, MetaLR 0.96, MetaSVM 1.10, Variant assessed as somatic; moderate impact.
- K86del (p.Lys86del), gnomAD 15-34793439-ATCT-, CADD 21.90
- I87S (p.Ile87Ser), ExAC rs764208251, gnomAD rs764208251, REVEL 0.96, MetaLR 0.97
- I87V (p.Ile87Val), rs1891749269, ClinVar RCV004588808, Ensembl rs1891749269, AlphaMissense 0.20, MetaLR 0.82, Uncertain significance, not provided
- I87I (p.Ile87Ile), rs1174917816, gnomAD 15-34793438-G-A, CADD 12.60
- I87N (p.Ile87Asn), gnomAD 15-34793439-A-T, REVEL 0.93, MetaLR 0.97
- H90P (p.His90Pro), gnomAD rs1253423096, REVEL 0.96, MetaLR 0.98
- H90Y (p.His90Tyr), rs121912676, ClinGen CA019710, ClinVar RCV000019991, ClinVar RCV000038323, REVEL 0.87, MetaLR 0.94, Conflicting interpretations, Cardiovascular phenotype; Dilated cardiomyopathy 1R; Atrial septal defect 5
- H90H (p.His90His), rs138812333, gnomAD 15-34793429-G-A, CADD 6.67
- T91N (p.Thr91Asn), rs730880037, ClinGen CA019720, ClinVar RCV000157092, Ensembl rs730880037, AlphaMissense 0.91, MetaLR 0.98, Likely benign
- T91T (p.Thr91Thr), gnomAD 15-34793426-G-A, CADD 11.70
- T91I (p.Thr91Ile), gnomAD 15-34793427-G-A, REVEL 0.87, MetaLR 0.94
- F92Y (p.Phe92Tyr), gnomAD rs1480127658, REVEL 0.87, MetaLR 0.96
- Y93C (p.Tyr93Cys), rs1595761404, ClinGen CA391631596, NCI-TCGA Cosmic COSV5175, ClinVar RCV001184876, REVEL 0.95, MetaLR 0.94, Uncertain significance, Cardiomyopathy; Hypertrophic cardiomyopathy 11; Cardiovascular phenotype
- Y93Y (p.Tyr93Tyr), gnomAD 15-34793420-G-A, CADD 11.90
- N94S (p.Asn94Ser), rs767734253, ClinGen CA041504, ClinVar RCV000201495, ClinVar RCV003114362, REVEL 0.75, MetaLR 0.90, Conflicting interpretations, Cardiovascular phenotype; Dilated cardiomyopathy 1R; Hypertrophic cardiomyopathy
- E95E (p.Glu95Glu), rs1211913373, gnomAD 15-34793414-C-T, CADD 13.10
- L96F (p.Leu96Phe), rs2140431992, ClinGen CA391631565, ClinVar RCV003804071, ClinVar RCV005412600, AlphaMissense 0.99, MetaLR 0.97, Uncertain significance, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- L96I (p.Leu96Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R97C (p.Arg97Cys), rs759495229, ClinGen CA041519, ClinVar RCV002040431, UniProt VAR 045925, REVEL 0.96, MetaLR 0.95, Uncertain significance, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- R97G (p.Arg97Gly), NCI-TCGA Cosmic COSV5175, NCI-TCGA Cosmic COSV9929, Variant assessed as somatic; moderate impact., in CMH11
- R97H (p.Arg97His), rs2504182967, ClinGen CA391631559, NCI-TCGA Cosmic COSV5175, ClinVar RCV002303950, Uncertain significance, Dilated cardiomyopathy 1R; Atrial septal defect 5; Hypertrophic cardiomyopathy 1
- R97P (p.Arg97Pro), gnomAD 15-34793399-GGGAG, CADD 33.00
- R97R (p.Arg97Arg), gnomAD 15-34793408-A-G, CADD 5.69
- V98A (p.Val98Ala), rs1555418891, ClinGen CA391631552, ClinVar RCV000648297, TOPMed rs1555418891, AlphaMissense 0.80, MetaLR 0.96, Uncertain significance, Atrial septal defect 5; Dilated cardiomyopathy 1R; Hypertrophic cardiomyopathy 1
- V98V (p.Val98Val), rs397517058, gnomAD 15-34793405-C-T, CADD 10.80
- A99V (p.Ala99Val), rs2504182948, ClinGen CA391631547, ClinVar RCV003795208, Uncertain significance, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- P100L (p.Pro100Leu), rs876661195, ClinGen CA10577511, ClinVar RCV000218970, gnomAD rs876661195, REVEL 0.82, MetaLR 0.97, Uncertain significance, not provided
- P100T (p.Pro100Thr), rs2504182941, ClinGen CA391631544, ClinVar RCV002927518, Uncertain significance, Dilated cardiomyopathy 1R; Atrial septal defect 5; Hypertrophic cardiomyopathy 1
- P100P (p.Pro100Pro), rs141322728, gnomAD 15-34793399-G-A, CADD 5.83
- E101G (p.Glu101Gly), rs1891748027, ClinGen CA391631536, ClinVar RCV002435971, AlphaMissense 0.97, MetaLR 0.95, Uncertain significance, Cardiovascular phenotype
- E101K (p.Glu101Lys), rs193922680, ClinGen CA019743, NCI-TCGA Cosmic COSV5175, ClinVar RCV000019996, REVEL 0.87, MetaLR 0.92, Pathogenic, Hypertrophic cardiomyopathy
- E101V (p.Glu101Val), rs1891748027, ClinGen CA391631535, ClinVar RCV001044723, Ensembl rs1891748027, AlphaMissense 0.97, MetaLR 0.95, Uncertain significance, Dilated cardiomyopathy 1R; Atrial septal defect 5; Hypertrophic cardiomyopathy 1
- E101E (p.Glu101Glu), rs1391018363, gnomAD 15-34793396-C-T, CADD 12.80
- E101Q (p.Glu101Gln), gnomAD 15-34793398-C-G, REVEL 0.80, MetaLR 0.93
- E102E (p.Glu102Glu), rs773112383, gnomAD 15-34793393-C-T, CADD 11.50
- H103Q (p.His103Gln), rs769303249, ClinGen CA16607774, ClinVar RCV000418492, ClinVar RCV000699207, AlphaMissense 0.81, MetaLR 0.95, Uncertain significance, not provided; Atrial septal defect 5; Hypertrophic cardiomyopathy 11
- H103R (p.His103Arg), Ensembl rs796286204, MetaLR 0.96, MetaSVM 1.08
- H103H (p.His103His), rs769303249, gnomAD 15-34793390-G-A, AlphaMissense 0.81, MetaLR 0.95
- P104L (p.Pro104Leu), rs1405829098, ClinGen CA391631514, ClinVar RCV000788301, ClinVar RCV001319564, REVEL 0.87, MetaLR 0.98, Uncertain significance, Dilated cardiomyopathy 1R; Hypertrophic cardiomyopathy 11; Atrial septal defect
- P104R (p.Pro104Arg), TOPMed rs1405829098, gnomAD rs1405829098, REVEL 0.95, MetaLR 0.97, Uncertain significance
- P104S (p.Pro104Ser), rs397517059, ClinGen CA019747, ClinVar RCV000038325, ClinVar RCV000484679, AlphaMissense 0.61, MetaLR 0.96, Conflicting interpretations, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- P104T (p.Pro104Thr), gnomAD rs397517059, REVEL 0.94, AlphaMissense 0.61, Likely pathogenic
- T105I (p.Thr105Ile), rs1368192263, ClinGen CA391631510, NCI-TCGA Cosmic COSV5175, ClinVar RCV003799116, AlphaMissense 0.17, MetaLR 0.62, Uncertain significance, Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect
- T105S (p.Thr105Ser), TOPMed rs1368192263, MetaLR 0.87, MetaSVM 0.76, Uncertain significance
- L106L (p.Leu106Leu), rs1335305223, gnomAD 15-34793381-C-T, CADD 11.80
- L107F (p.Leu107Phe), gnomAD 15-34793380-G-A, REVEL 0.89, MetaLR 0.97
- T108T (p.Thr108Thr), gnomAD 15-34793375-T-C, CADD 4.30
- E109E (p.Glu109Glu), gnomAD 15-34793372-C-T, CADD 12.70
- A110T (p.Ala110Thr), rs1057523500, ClinGen CA16607773, ClinVar RCV000445116, Ensembl rs1057523500, AlphaMissense 0.95, MetaLR 0.97, Uncertain significance, not provided
Public ACTC1 analysis runs
- ACTC1 analysis run — ACTC1 (684 variants) — completed 2026-08-10