Supplemental Material
The MOGE(S) Classification of Cardiomyopathy for Clinicians
Eloisa Arbustini* MD, Navneet Narula† MD, Luigi Tavazzi‡ MD PHD, Alessandra Serio* MD, Maurizia Grasso* MD, Valentina Favalli* PHD, Riccardo
Bellazzix ME PHD, Jamil A.Tajik§ MD, Robert D. Bonow⌘MD, Valentin Fuster# MD PHD, and Jagat Narula# MD PHD
*Center for Inherited Cardiovascular Diseases, IRCCS Foundation Policlinico San Matteo, Pavia, Italy; †Weill Cornell Medical College, New York, New
York; ‡Maria Cecilia Hospital Health Science Foundation, Cotignola, Italy; xUniversity of Pavia, Pavia, Italy; §St. Luke’s Medical Center, Milwaukee, WI;
⌘Northwestern University School of Medicine, Chicago, IL, #Icahn School of Medicine at Mount Sinai, New York, New York
1
Table 1 suppl. List of genes associated to date with cardiomyopathies. The light blue filled cells in the column listing the sarcomeric genes indicate the most
common sarcomere genes in Hypertrophic Cardiomyopathy (HCM). The pink filled cells highlight the genes most commonly involved in Dilated
Cardiomyopathy (DCM). The light yellow filled cells highlight the genes most commonly involved in Arrhythmogenic Right Ventriculòar Cardiomyopathy
(ARVC). The light green shadowed cells highlight the genes most commonly involved in Left Ventricular Non Compaction (LVNC). The light violet filled cells
highlight the genes most commonly involved in Restrictive Cardiomyopathy (RCM).
Nuclear genes
MIM* Gene
Protein
HCM
RCM
ABCC9
601439
ATP-Binding Cassette, Subfamily C, Member 9

Cantu Syndrome; Hypertrichosis
AD
ABLIM1
602330
Limatin (actin-binding LIM domain protein)


LVNC
AD
ACTC1
102540
Cardiac actin alpha



Nemaline myopathy
AD
ACTN2
102573
Alpha-actinin 2

ALMS1
606844
ALMS1-C

ANO5
608662
Anoctamin 5

ANKRD1
609599
Ankyrin repeat domain-containing protein 1


DCM
ARVC
603883
BCL2-associated athanogene


CALR3
611414
Calreticulin 3


CASQ2
114251
Calsequestrin 2
AD

123590
Alpha B crystallin

CSRP3
CTF1
CTNNA3
600824
600435
607667
Cysteine- and glycine-rich protein 3
Cardiotrophin 1
Alpha3-catenin

DES
125660
Desmin
DMD
300377
Dystrophin
DMPK
605377
Dystrophia myotonica protein kinase gene
DOLK
610746
Dolichol Kinase

DSC2
125645
Desmocollin 2


DSG2
125671
Desmoglein 2


Dystrobrevin, alpha
300384
Emerin
AD
sCPK elevated; Long QT syndrome-9; Muscular dystrophy, limb-girdle;
Myopathy, distal, Tateyama type; Rippling muscle disease.
Posterior polar cataract
CRYAB
601239
AD
AD


EMD
AR
AD
Caveolin3
DTNA
AR
BAG3-related myofibrillar myopathy, CRYAB-related myofibrillar myopathy, fatal
infantile hypertrophy,
601253
Desmoplakin
Inheritance
Alstrom Syndrome (70%: DCM)
Limb girdle muscular dystrophy, Gnathodiaphyseal dysplasia, Miyoshi muscular
dystrophy 3; Dysphagia
CAV3
125647
Phenotypes/diseases /traits

BAG3
DSP
LVNC

AD








Susceptibility to Alzheimer disease




Des-related myofibrillar myopathy, Neurogenic scapuloperoneal syndrome,
Kaeser type; AVB, sCPK
AD

Duchenne Muscle Dystrophy, Becker Muscle dystrophy; >sCPK/myopathy
XLR

(Dystrophia Myotonica type 1) or Steinert's disease; AVB
Congenital disorder of glycosylation, type Im; Myopathy, possible ichthyosiform
dermatitis
With and without mild palmoplantar keratoderma and woolly hair
AD

AD
AD
AD
AR
AD
AD



AD
Lethal acantholytic epidermolysis bullosa, Keratosis palmoplantaris striata II, Skin
fragility-woolly hair syndrome
With or without congenital heart defects
EDMD1, X-linked; AVB, Myopathy, sCPK
AD
AD
XLR
2

EYA4
603550
Eyes absent 4
FHL1
300163
Four-and –a-half LIM domains 1
GATAD1
614518
GATA Zinc Finger Domain Containing Protein 1

ILK
602366
Integrin-linked kinase

JUP (DP3)
173325
Plakoglobin, Desmoplakin III


LMNA
150330
Lamin AC


LAMA2
156225
Laminin Alpha, 2

LAMA4
600133
Laminin Alpha, 4

LDB3
605906
LIM domain-binding 3



MIB1
608677
Midbomb, homolog of , Drosophila



MYBPC3
600958
Myosin-binding protein C



MYH6
160710
Alpha-myosin heavy chain 6


MYH7
160760
Beta-myosin heavy chain 7

MYH7B
609928
Myosin Heavy Chain 7B

MYL2
160781
Myosin Light Chain 2

MYL3
160790
Myosin Light Chain 3

MYOZ1
605603
Myozenin 1,

MYOZ2
605602
Myozenin 2

MYPN
608517
Myopalladin

NEBL
605491
Nebulette
NEXN
613121
Nexilin
NKX2-5
600584
NK2 homeobox 5; cardiac specific homeobox 1

PDLIM3
605889
PDZ and LIM domain protein 3

PLN
172405
Phospholamban


AR
PKP2
602861
Plakophilin 2


AD
PSEN1
104311
Presenilin 1

PSEN2
600759
Presenilin 2

RBM20
613171
RNA-binding motif protein 20

RYR2
180902
SCN5A
600163
SGCD
601411
Ryanodine receptor 2
Sodium channel, voltage gated, type V, alpha
subunit
Delta-sarcoglycan
SYNE1
608441
Nesprin 1, Synaptic nuclear envelop protein 1
TCAP
604488
Titin-cap; telethonin
TCF21
603306
Transcription factor 21, epicardin


Deafness, autosomal dominant
EMDM 6, X-linked, Myopathy, reducing body, childhood-onset and severe earlyonset, Myopathy with postural muscle atrophy, Scapuloperoneal myopathy, XLD


XLR,XLD
AD
AD

Naxos traits
DCM with conduction disease plus 11 additional phenotypes; AVB; possible
sCPK
Congenital merosin-deficient muscular dystrophy type 1A
AD, AR
AD
AR
AD



AD
ZASP-related myofibrillar myopathy; LVNC, possiblesCPK; Hypertrabeculation;
AD
Atrial septal defect, Sick sinus syndrome
Laing distal myopathy; Myosin storage myopathy; Scapuloperoneal syndrome,
myopathic type; possible sCPK
Congenital myopathy?
AD
AD
AD, AR
AD

AD, AR

AD
AD


AD

AD

Possible conduction system disease; congenital heart diseases; hypothyroidism,
congenital nongoitrous
AD
AD
Acne inversa, familial, 3, Alzheimer disease, type 3, Frontotemporal dementia,
Pick disease
Alzheimer disease, type 4
AD
AD
AD


AD

Ventricular tachycardia, catecholaminergic polymorphic, 1
AD

LQT3, Brugada1, Atrial Fibrillation, Sick Sinus Syndrome, Familial VF
AD

Limb-girdle muscular dystrophy

EMD4, AD; Spinocerebellar ataxia, autosomal recessive

Muscular dystrophy, limb-girdle, type 2G; sCPK
AD

Hearing loss
AD
AD
AD;AR
3
TGFB3
190230


Rienhoff Syndrome
AD
TMEM43
612048
Transmembrane Protein 43


Emery-Dreifuss muscular dystrophy, AD
AD
TMEM70
612418
Mitochondrial complex V (ATP synthase) deficiency,

nuclear type 2


TMPO
188380
Thymopoietin
TNNC1
191040
Cardiac troponin C



TNNI3
191044
Cardiac troponin I3




AD
TNNT2
191045
Cardiac troponin T2




AD
TPM1
191010
Tropomyosin 1




TTN
VCL
188840
193065

Titin


Vinculin


Nuclear genes coding mitochondrial proteins
ANT1 (PEOA2)
Adenin Nucleotide Translocator 1
103220
AR
Neonatal mitochondrial encephalocardiomyopathy with ATP synthase deficiency
AD
AD
AD
Limb-girdle muscular dystrophy ,Early-onset myopathy with fatal
cardiomyopathy, Proximal Myopathy with early respiratory muscle involvement,
Tardive tibial muscular dystrophy

AD
AD


AD-PEO with multiple mtDNA deletions
AD
AGK
610345
Acylglycerol Kinase


Cataract, Myopathy, Senger Syndrome
AR
NDUFS2
602985
NAD-Ubiquinone Oxidoreductase Fe-S Protein 2


Encephalopathy, Mt complex I deficiency
AR
NDUFV2
SCO2
600532
NAD-Ubiquinone Oxidoreductase Flavoprotein2


604272
Homolog of S Cervisiae, 2


Hypotonia, encephalopathy, Mt complex I deficiency
Neonatal cardio-encephalomyopathy, COX1 deficiency
AR
AR
COX10
602125
Cytochome C Oxidase Assembly Protein, 10

Neonatal tubulopathy and encephalopathy, LS, MtCOX4 Deficiency
AR
COX15
603646
608977
Cytochome C Oxidase Assembly Protein, 15

Early-onset HCM, LS
Early onset, anemia, ataxia, male genital anomalies and methylglutaconic
aciduria type V
Alpers-type syndrome, MNGIE-type, AD-PEO and AR-PEO, SANDO syndrome,
SCAE
Friedreich ataxia
Barth Syndrome, LVNC, cyclic granulocytopenia, hypocholesterolemia
AR
DNAJC19
POLG (PEOA1)
FXN
G4.5
174763
606829
300394
Disorders of the glycogen metabolism
LAMP2
309060
PRKAG2
602743
AGL
610860
GAA
606800
GBE1
607839
GYS1
PYGM


DNAJ/HSP40 Homolog, Subfamily C, Member 19

DNA Polymerase 


Frataxin
Tafazzin





Lysosome-associated membrane protein 2



Protein Kinase AMP activated noncatalytic 2

Amylo-1,6-glucosidase 4-alpha-glucanotransferase
AR
AD-AR
AR
XLR

Danon disease; myopathy, cognitive impairment in males, pigmentary
retinopathy in females; WPW, Short PR
Lethal congenital glycogen storage disease of heart, PRKAG2-related HCM; WPW
XL
AD


GSDIII (Forbes or Cori disease, glycogen debranching enzyme)
AR
Alpha Glucosidase


AR
Glycogen Branching Enzyme


138570
Glycogen Synthase 1


GSDII (Pompe disease, Glycogen storage disease II, acid α-glucosidase /acid
maltase deficiency)
GSD IV (Anderson disease, glycogen branching enzyme) Polyglucosan body
disease, adult form
GSD 0 (muscle) (muscle glycogen synthase
608455
Muscle glycogen phosphorylase


GSD V (McArdle disease, glycogen phosphorylase)
AR
α-galactosidase


Anderson-Fabry Disease (α-galactosidase deficiency); Anderson-Fabry Disease Later onset, cardiac variant
XL
AR
AR
Lysosomal storage diseases
GLA
300644
4

GM1 gangliosidosis (β-galactosidase deficiency)
AR

Metachromatic leucodystrophy. MVD, CAD
AD


GM2 gangliosidosis (Sandhoff disease)
AR


MPS Ih (Hurler), Ih/s (Hurler/Scheie), Is (Scheie) (iduronidase deficiency)
AR
Iduronate 2-Sulfatase


XLR
N-Sulfoglucosamine-Sulfohydrolase


MPS II (Hunter syndrome) (iduronate 2-sulfatase deficiency)
MPS III A (Sanfilippo syndrome A)
N-Acetylglucosaminidase


MPS III B (Sanfilippo syndrome B)
AR
610453
Heparan-alpha-glucosaminide N-Acetyltransferase


MPS III C (Sanfilippo syndrome C)
AR
607664
N-Acetylglucosamine-6-Sulfatase


MPS III D (Sanfilippo syndrome D)
AR
GALNS
612222
Galactosamine-6-Sulfate Sulfatase


MPS IV A (Morquio syndrome)
AR
GLB1
611458
Galactosidase beta 1


MPS IV B (Morquio syndrome)
AR
GUSB
611499
Beta-Glucuronidase


MPS VII (Sly syndrome)
AR
ARSB
AGA
611542
Arylsulfatase B


613228
Aspartylglucosaminidase


MPS VI (Maroteux-Lamy syndrome)
Aspartylglucosaminuria
AR
AR
CTSA
613111


Galatosialidosis ,Goldberg syndrome (cathepsin A defect)
AR
GNPTAB
607840


Mucolipidosis II, Alpha-Beta
AR
FUCA1
612280
Cathepsin A
N-Acetylglucosamine-1-Phosphotransferase,
alpha/beta subunit
AlphaL-1-Fucosidase


Fucosidosis
AR
NAGA
104170
N-Acetyl-Alpha-D-Galactosaminidase
Disorders of amino acid and organic acid metabolism


Schindler disease, I and III; Kanzaki Disease
AR
ACAT1
607809
Acetyl-CoA-Acetyltransferase 1


β-ketothiolase deficiency
AGXT
604285
Alanine-Glyoxylate Aminotransferase


Hyperoxaluria I (Oxalosis I)
AR
FAH
613871
Fumarylacetoacetate Hydrolase


Tyrosinemia I
AR
GRHPR
604296
Glyoxylate Reductase/Hydroxypyrivate Reductase


Hyperoxaluria II (Oxalosis II)
AR
MUT
609058
Methylmalonyl-CoA Mutase


Methylmalonic aciduria
AR
HGD
607474
Homogentisate 1,2-Dioxygenase


Alkaptonuria (homogentisate 1,2-dehydrogenase deficit)
AR
Noonan Syndrome
Gene
Protein


PTPN11
176876
Noonan Syndrome type 1; LEOPARD type 1
AD
190070

Noonan Syndrome type 3; Cardio-facio-cutaneous syndrome 2
AD
RAF1
164760

164790

Noonan syndrome 5,
LEOPARD syndrome 2
Noonan syndrome 6
AD
NRAS
Protein Tyrosin Phosphatase, non receptor type11
V-KI-RAS2 Kirsten Rat Sarcoma Viral Oncogene
Homolog
V-RAF-1 Murine Leukemia Viral Oncogene
Homolog1
Neuroblastoma RAS Viral Oncogene Homolog

KRAS
RIT1
609591
Ric-Like Protein without CAAX Motif1

Noonan syndrome 8
AD
MtDNA genes*
MTTL1
Gene
tRNALeu(UUR)
Allele
MTTL1
MTTL1
GLB1
611458
β-galactosidase
ARSA
607574
Arylsulfatase
HEXB
606873
Hexosaminidase B
IDUA
252800
Alpha-L-Iduronidase
IDS
300823
SGSH
605270
NAGLU
609701
HGSNAT
GNS


AR
AD


A3260G


MMC/MELAS
Matrilineal
tRNALeu(UUR)
C3303T


MMC
Matrilineal
tRNALeu(UUR)
A3243G

MELAS / LS / DMDF / MIDD / SNHL / CPEO / MM / FSGS / Cardiac+multiorgan
dysfunction
Matrilineal


5
MTTL1
tRNALeu(UUR)
A3243T

MTTL1
tRNALeu(UUR)
G3244A

MTTL1
tRNALeu(UUR)
G3242A

MTTL1
tRNALeu(UUR)
A3252G
MTTL1
tRNALeu(UUR)
T3258C
MTTL1
tRNALeu(UUR)
A3280G
MTTL2
tRNALeu(CUN)
T12297C
MTTI
tRNAIle
A4295G

MTTI
tRNAIle
A4300G

MTTI
tRNAIle
A4269G

MTTI
tRNAIle
A4316G

MTTI
tRNAIle
A4317G

MTTI
tRNAIle
G4284A
MTTI
tRNAIle
MTTI

MM / MELAS / SNHL / CPEO
Matrilineal
MELAS
Matrilineal

MM / HCM+renal tubular dysfunction
Matrilineal


EXIT: Exercise Intolerance
Matrilineal


MELAS/myopathy
Matrilineal


MELAS
Matrilineal


DCM / Leight Syndrome/ Failure to Thrive & LA
Matrilineal
MHCM / Maternally inherited hypertension
Matrilineal

MICM
Matrilineal

Leigh Syndrome
Matrilineal
HCM with hearing loss/poss. hypertension factor
Matrilineal

FICP
Matrilineal


Varied familial presentation/spastic paraparesis
Matrilineal
A4317G


FICP / poss. hypertension factor
Matrilineal
tRNAIle
C4320T

Mitochondrial Encephalocardiomyopathy
Matrilineal
MTTK
tRNALys
A8348G


Cardiomyopathy / SNHL / poss. hypertension factor
Matrilineal
MTTK
tRNALys
A8344G


MERRF Other - LD / Depressive mood disorder / leukoencephalopathy / HiCM
Matrilineal
MTTK
tRNALys
G8363A


MERRF/MICM+DEAF/Autism/ LS / Ataxia+Lipomas
Matrilineal
MTTG
tRNAGly
T9997C


MHCM
Matrilineal
MTTH
tRNAHis
G12192A


MICM
Matrilineal
MTTP
tRNAPro
T16032TTCTCTGTTCTTTCAT (15 bp dup)


DCM
Matrilineal
MTTQ
tRNA Gln
T4373C


Possibly LVNC-associated
Matrilineal
MTTV
tRNAVal
C1624T


Leigh syndrome
Matrilineal
MTTV
tRNAVal
G1644T

Adult Leigh Syndrome
Matrilineal
MTTV
tRNAVal
G1644A

HCM/MELAS
Matrilineal
MTRNR2
16S rRNA
C3093G

MELAS
Matrilineal
MTRNR1
12S rRNA
T1391C

Found in 1 HCM patient
Matrilineal
MTRNR1
12S rRNA
C1556T

Found in 1 HCM patient
Matrilineal
MTCYB
MTCYB
G15243A (G166E)


HCM
Matrilineal
MTCYB
MTCYB
G15498A (G251D)


HCM / WPW, DEAF
Matrilineal
MTCYB
MTCYB
T15693C (M-T


MTCO1
MTCO1
T6721C ( M273T)


Idiopathic Sideroblastic Anemia
Matrilineal
MTCO1
MTCO1
T6742C ( I280T)


Idiopathic Sideroblastic Anemia
Matrilineal
MTND4
MTND4
A12026G (I423V)


Diabetes Mellitus
Matrilineal
T921C



Possibly LVNC-associated
Matrilineal
T850C



Possibly LVNC-associated
Matrilineal
T961C



DEAF, possibly LVNC-associated
Matrilineal
MTRNR1
MTRNR1
MTRNR1
12S rRNA
12S rRNA
12S rRNA


Possibly LVNC cardiomyopathy-associated
6
MTRNR2
16S rRNA
T2352C



Possibly LVNC-associated
Matrilineal
MTRNR2
16S rRNA
G2361A



Possibly LVNC-associated
Matrilineal



Matrilineal
16S rRNA
A2755G
Possibly LVNC-associated
AD = Autosomal Dominant; AR = Autosomal Recessive; XL = X-linked; XLR = XL Recessive; XLD = XL Dominant; MVD = Mitral Valve Disease; CAD = Coronary Artery Disease;* http://www.mitomap.org/MITOMAP; MMC = Maternal
Myopathy and Cardiomyopathy; MHCM = Maternally Inherited Hypertrophic Cardiomyopthy (?). MICM = Maternally Inherited Cardiomyopathy; FICP: Fatal Infantile Cardiomyopathy Plus, a MELAS associated cardiomyopathy; LD or
LS = Leigh Disease or Syndrome; MERRF: Myoclonic Epilepsy and Ragged Red Muscle Fibers; MELAS = Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes; LVNC = Ventricular Non Compaction; DEAF:
Maternally inherited DEAFness or aminoglycoside-induced DEAFness; PEO = Progressive External Opthalmoplegia. SANDO = Sensory ataxic neuropathy with dysarthria/dysphagia and ophthalmoplegia; SCAE = spinocerebellar ataxia
with epilepsy.
MTRNR2
7
Figure 1 Suppl.
The figure shows a family with dilated cardiolaminopathy.
I:1
MD OH GAD EG-NA SC-IV
I:2
M0 O0 GAD EG-Neg SA-I
II:1
MD(AVB) OH+M GAD EG-LMNA[p.Arg190Trp] SC-III
II:2
M0 O0 GAD EG-LMNA[p.Arg190Trp] SA-I
II:3
ME[D] OH GAD EG-LMNA[p.Arg190Trp] SB-I
8
Figure 2 Suppl.
Matrilineal Cardiomyopathy
I:1
II:2
II:1
III:1
I:2
II:3
III:2
Family member
MOGES
I:1
M0 O0 GU EG-0
I:2
M0 O0 GM EG-OC
II:1
M0 OA,O(Diabetes) GM EG-MTDNA[A3243G]+GJB2[c.35DelG+/-] SA-I
II:2
M0 OA,O(Diabetes) GM EG-MTDNA[A3243G]+GJB2[c.35DelG+/-] SA-I
II:3
MH+DOH,M,N,A,O(Diabetes)GM EG-MTDNA[A3243G]+GJB2[c.35DelG+/-] SD-IV
III:1
M0OAGMEG-MtDNA [A3243G] SA-I
III:2
M0O0GMEG-MtDNA [A3243G] SA-I
9
Figure 3 Suppl.
ARVC associated with 2 genetic Variants of Unknown Significance Inheritance (VUS): the
inheritance of the phenotype is probably autosomal recessive, but still undetermied, due to the
uncertain significance of the two VUS, which are given in yellow-orange in the App. In this family
the genetic diagnosis is still open.
Family
member
MOGES
I:1
M0(AVB) O0 GU EG-LDB3p.Thr507Asn SA-I
I:2
M0 O0 GU EG-DSG2p.Lys479Glu SA-I
II:1
MA(M2x2)-AVB-Trab OH GUndet EG-LDB3p.Thr507Asn + DSG2p.Lys479Glu SB-I
II:3
M0 O0 GUndet EG-Neg S A-I
II:5
M0 O0 GUndet EG-p.Lys479Glu SA-I
II:7
M0 O0 GUndet EG-Neg SA-I
III:1
M0 O0 GUndet EG-p.Thr507Asn SA-I
III:2
M0 O0 GUndet EG-LDB3p.Thr507Asn + DSG2p.Lys479Glu SA-I
III:5
M0 O0 GUndet EG-Neg SA-I
10
Figure 4 Suppl.
De novo Danon Disease.
I
I:2
I:1
II
II:1
II:2
II:3
Family member
MOGE(S)
I:1
M0 O0 GN EG-Neg SA-I
I:2
M0 O0 GN EG-Neg SA-I
II:1
M0 O0 GN EG-0 SA-I
II:2
M0 O0 GN EG-0 SA-I
II:3
MR OH+M+Li+N GN EG-DN-LAMP2[p.His260Pro fs22] SC-II
11