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ONLINE APPENDIX
The genes detailed in these supplemental tables represent those associated with a given cardiomyopathy phenotype in the literature. Genes with high-quality evidence that meet all criteria for
defining disease pathogenicity listed in Table 1 of the manuscript are defined as “definitive”
disease-causing genes. All others are listed as “putative” disease genes. With advances in nextgeneration sequencing and molecular genetics technologies, great efforts are being made at
confirming the pathogenicity of specific genes. Thus, we expect these data to change rapidly in
the next several years, causing some putative disease genes to be reclassified as definitive
disease-causing genes and others to be recognized as genes that do no cause cardiomyopathy. It
is also important to recognize that not all novel variants found in a gene, even those that
definitively cause disease, will be causative. Hence, new mutations identified in known diseasecausing genes still require careful validation.
Supplemental Table 1. Genes associated with hypertrophic cardiomyopathy
Gene Symbol
Encoded protein
Definitive disease causing genes
MYBPC3 (1,2)
Cardiac myosin binding protein C
MYH7 (3,4)
-myosin heavy chain
MYL2 (5)
Regulatory myosin light chain
MYL3 (5)
Essential myosin light chain
TNNI3 (6)
Cardiac troponin I
TNNT2 (7,8)
Cardiac troponin T
TPM1 (7,8)
-tropomyosin
ACTC1 (9,10)
Cardiac -actin
Putative disease genes
ACTN2 (11,12)
-actinin 2
MYOZ2 (13)
Myozenin 2
CSRP3 (11,14Cardiac LIM protein
17)
MYPN (18)
Myopalladin
TNNC1 (19-21)
Cardiac troponin C
MYH6 (17,22)
-myosin heavy chain
NEXN (23)
Nexilin
TCAP (15,24)
Telethonin
ANKRD1 (25)
Cardiac ankyrin repeat protein
LDB3 (11)
LIM binding domain 3 protein*
VCL (26,27)
Vinculin
Cellular Location
Sarcomere, thick filament
Sarcomere, thick filament
Sarcomere, thick filament
Sarcomere, thick filament
Sarcomere, thin filament
Sarcomere, thin filament
Sarcomere, thin filament
Sarcomere, thin filament
Sarcomere, Z-disc
Sarcomere, Z-disc
Sarcomere, Z-disc
Sarcomere, Z-disc
Sarcomere, thin filament
Sarcomere, thick filament
Sarcomere, Z-disc
Sarcomere, Z-disc
Sarcomere, Z-disc
Sarcomere, Z-disc
Sarcomere, Z-disc, intercalated
disc and sarcolemma
JPH2 (28)
Junctophilin 2
Sarcolemma
CAV3 (24)
Caveolin-3
Sarcolemma
PLN (29,30)
Phospholamban
Sarcoplasmic reticulum
CALR3 (29)
Calreticulin 3
Sarcoplasmic reticulum
*LIM binding domain 3 protein is also commonly known as Cypher/ZASP
Supplemental Table 2. Genes associated with metabolic cardiomyopathies
Gene
GLA
(31,32)
LAMP2
(33,34)
PRKAG2
(34-36)
GAA(37)
Encoded Protein
-galactosidase A
Disease
Fabry disease
Inheritance
X-linked
Lysosome-associated membrane
protein 2
AMP-activated protein kinase, 2
subunit (noncatalytic)
-glucosidase
Danon disease
X-linked
PRKAG2
cardiomyopathy
Pompe disease
Autosomal
dominant
Autosomal
recessive
Supplemental Table 3. Genes associated with dilated cardiomyopathy
Gene
Encoded Protein
Definitive disease causing genes
TTN(38,39)
Titin
MYH7(40,41)
-myosin heavy chain
ACTC1(42)
Cardiac -actin
TNNT2(40)
Cardiac troponin T
TPM1(43)
-tropomyosin
TNNI3(44,45)
Cardiac troponin I
BAG3 (46-48)
Bcl2-associated athanogene 3
DES (49-51)
Desmin
DMD (52-55)
Dystrophin
DNAJC19
(56,57)
EMD (1,58)
DNAJ (Hsp40) homolog
LMNA (59)
Lamin A/C
Emerin
PLN (60-62)
RBM20 (63-66)
SCN5A (67-69)
Phospholamban
RNA-binding protein, 20
Voltage gated sodium channel type
V, -subunit
TAZ (70)
Tafazzin
Putative disease genes
MYBPC3(71,72) Cardiac myosin binding protein C
TNNC1(73,74)
Cardiac troponin C
ANKRD1
Cardiac ankyrin repeat protein
(75,76)
LDB3 (77)
LIM binding domain 3 protein
NEXN (78)
Nexilin
SGCD (79,80)
-sarcoglycan
EYA4 (81)
PSEN1 (82)
MYPN
(18,83,84)
FBXO32 (85)
GATAD1 (86)
GATA4 (87)
CHRM2 (88)
Eyes absent homolog 4
Presenilin-1
Myopalladin
F-box protein 32/atrogin-1
GATA zinc finger domain
containing 1 protein
GATA binding protein 4
Muscarinic cholinergic receptor
Possible Coexistant Phenotypes
None
None
None
None
None
None
None
Skeletal myopathy, conduction
system disease
Duchenne’s muscular dystrophy,
Becker’s muscular dystrophy
DCMA
Emery-Dreifuss muscular dystrophy
type 1
Conduction system disease, EmeryDreifuss muscular dystrophy type 2
None
None
Supraventricular and ventricular
arrhythmias
Barth syndrome
None
None
None
Myofibrillar myopathy
None
Limb-girdle muscular dystrophy,
type 2F
Sensorineural hearing loss
None*
None
None
None
None
Supraventricular and ventricular
arrhythmias
MYH6 (22)
ACTN2 (89)
CSRP3 (89,90)
TCAP (24,91)
ABCC9 (92)
TBX20 (93)
NKX2-5 (94)
CTF1 (95)
VCL (96)
SGCB (97)
-myosin heavy chain
-actinin 2
Cardiac LIM protein
Telethonin
Sulfonylurea receptor 2
T-box 20
NK2 homeobox 5
Cardiotrophin-1
Vinculin
-sarcoglycan
SGCA (98)
-sarcoglycan
FHL2 (99)
Four and a half limb domains 2
FKTN (100,101) Fukutin
FOXD4 (102)
Forkhead box protein D4
None
None
Limb girdle muscular dystrophy
None
Cantú syndrome
CHD
CHD
None
None
Limb-girdle muscular dystrophy,
type 2E
Limb-girdle muscular dystrophy,
type 2D
None
Fukuyama-type muscular dystrophy
Obsessive compulsive disorder and
suicidality
None
None
None*
LAMA4 (103)
Laminin, 4
ILK (103)
Integrin-linked kinase
PSEN2 (82)
Presenilin-2
SDHA (104)
Succinate dehydrogenase subunit A
CRYAB
Skeletal myopathy
-B crystallin
(105,106)
MURC (107)
Muscle-related coiled-coil protein
None
SYNE1
Nesprin-1
Emery-Dreifuss muscular dystrophy
(108,109)
type 4
PRDM16 (110) PR domain containing 16
LVNC
PGM1 (111)
Phosphoglucomutase 1
Glycogenosis type XIV
TMPO (112)
Thymopoietin
None
DSC2 (113,114) Desmocollin 2
None
DSG2 (113)
Desmoglein 2
None
DSP (115)
Desmoplakin
Plantopalmar keratoderma
PKP2 (113)
Plakophilin 2
None
Genetic loci linked to DCM without a known disease-associated mutation
9q13-q22 (116)
MIM CMD1B
None
2q14-q22 (117)
MIM CMD1H
Conduction system disease
6q12-q16 (118)
MIM CMD1K
None
7q22-q31 (119)
MIM CMD1Q
None
1p36.13 (48)
Unknown
None
* - Allelic variants in Alzheimer’s dementia
DCMA – dilated cardiomyopathy with ataxia; MIM – Mendelian Inheritance in Man; CHD –
congenital heart disease
Supplemental Table 4. Genes associated with left ventricular non-compaction cardiomyopathy
Gene
Encoded Protein
Associated findings or syndromes*
Definitive disease genes
TAZ(120,121)
Tafazzin
DCM, Barth syndrome
MIB1 (122)
Mindbomb homolog 1
None
MYH7(123,124) Myosin heavy chain
None
Putative disease genes
LDB3(77,125)
LIM binding domain 3 protein
DCM, myofibrillar myopathy
DTNA(121)
None
-dystrobrevin
ACTC1(126,127) Cardiac -actin
Apical HCM
TNNT2(127,128) Cardiac troponin T
None
NKX2.5(129)
NK2 homeobox 5
None
TPM1(130,131) -tropomyosin
None
MYBPC3(131)
Cardiac myosin binding protein C
None
PRDM16(110)
PR domain containing 16
1p36 deletion syndrome
Genetic loci linked to LVNC without a known disease-associated mutation
11p15(132)
MIM LVNC2
None
* All LVNC-associated genes are also associated with a variety of other congenital heart defects,
which are not listed here
MIM – Mendelian Inheritance in Man
Supplemental Table 5. Genes associated with arrhythmogenic right ventricular
dysplasia/cardiomyopathy
Gene
Encoded Protein
Associated syndromes
Definitive disease genes
JUP(133-135)
Plakoglobin
Naxos syndrome
DSP(115,136,137) Desmoplakin
Carvajal syndrome
PKP2 (138-140)
Plakophilin 2
None
DSG2 (141,142)
Desmoglein 2
None
DSC2 (143,144)
Desmocollin 2
None
TMEM43 (145Transmembrane protein 43
None
147)
Putative disease genes
TGFB3 (148)
None
Transforming growth factor 3
PLN (149)
Phospholamban
None
TTN (150)
Titin
None
Genetic loci linked to ARVC without a known disease-associated mutation
14q12-q22 (151)
MIM ARVD3
None
2q32.1-q32.3 (152)
MIM ARVD4
None
10p14-p12 (153)
MIM ARVD6
None
MIM – Mendelian Inheritance in Man
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