CMH6
MCID: CRD232
MIFTS: 37

Cardiomyopathy, Familial Hypertrophic, 6 (CMH6)

Categories: Cardiovascular diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Cardiomyopathy, Familial Hypertrophic, 6

MalaCards integrated aliases for Cardiomyopathy, Familial Hypertrophic, 6:

Name: Cardiomyopathy, Familial Hypertrophic, 6 57 71
Cardiomyopathy, Familial Hypertrophic 6 12 73 13
Cmh6 57 12 73
Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome 73 6
Familial Hypertrophic Cardiomyopathy 6 29 6
Cardiomyopathy, Hypertrophic 6 57 29
Hypertrophic Cardiomyopathy 6 12 15
Cardiomyopathy, Hypertrophic, Familial, Type 6 39

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal dominant

Miscellaneous:
genetic heterogeneity (see )


HPO:

31
cardiomyopathy, familial hypertrophic, 6:
Inheritance autosomal dominant inheritance heterogeneous


Classifications:



External Ids:

Disease Ontology 12 DOID:0110312
OMIM® 57 600858
OMIM Phenotypic Series 57 PS192600
MeSH 44 D024741
MedGen 41 C1833236
UMLS 71 C1833236

Summaries for Cardiomyopathy, Familial Hypertrophic, 6

UniProtKB/Swiss-Prot : 73 Cardiomyopathy, familial hypertrophic 6: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. CMH6 patients present Wolff-Parkinson-White ventricular preexcitation, enlarged myocytes without myofiber disarray, and glycogen-containing cytosolic vacuoles within cardiomyocytes.

MalaCards based summary : Cardiomyopathy, Familial Hypertrophic, 6, also known as cardiomyopathy, familial hypertrophic 6, is related to cardiomyopathy, familial hypertrophic, 1 and atrial standstill 1. An important gene associated with Cardiomyopathy, Familial Hypertrophic, 6 is PRKAG2 (Protein Kinase AMP-Activated Non-Catalytic Subunit Gamma 2). Affiliated tissues include skeletal muscle and heart, and related phenotypes are hypertrophic cardiomyopathy and atrioventricular block

Disease Ontology : 12 A familial hypertrophic cardiomyopathy that has material basis in heterozygous mutation in the gene encoding the gamma-2 regulatory subunit of AMP-activated protein kinase (PRKAG2).

OMIM® : 57 Mutations in the PRKAG2 gene (602743) give rise to a moderate, essentially heart-specific, nonlysosomal glycogenosis with clinical onset typically in late adolescence or in the third decade of life, ventricular pre-excitation predisposing to supraventricular arrhythmias, mild to severe cardiac hypertrophy, enhanced risk of sudden cardiac death in midlife, and autosomal dominant inheritance with full penetrance (summary by Burwinkel et al., 2005). (600858) (Updated 05-Mar-2021)

Related Diseases for Cardiomyopathy, Familial Hypertrophic, 6

Diseases in the Hypertrophic Cardiomyopathy family:

Cardiomyopathy, Familial Hypertrophic, 2 Cardiomyopathy, Familial Hypertrophic, 3
Cardiomyopathy, Familial Hypertrophic, 4 Cardiomyopathy, Familial Hypertrophic, 1
Cardiomyopathy, Infantile Hypertrophic Cardiomyopathy, Familial Hypertrophic, 6
Cardiomyopathy, Familial Hypertrophic, 25 Cardiomyopathy, Familial Hypertrophic, 8
Cardiomyopathy, Familial Hypertrophic, 10 Cardiomyopathy, Familial Hypertrophic, 11
Cardiomyopathy, Familial Hypertrophic, 12 Cardiomyopathy, Familial Hypertrophic, 13
Cardiomyopathy, Familial Hypertrophic, 14 Cardiomyopathy, Familial Hypertrophic, 15
Cardiomyopathy, Familial Hypertrophic, 7 Cardiomyopathy, Familial Hypertrophic, 9
Cardiomyopathy, Familial Hypertrophic, 16 Cardiomyopathy, Familial Hypertrophic, 17
Cardiomyopathy, Familial Hypertrophic, 18 Cardiomyopathy, Familial Hypertrophic, 20
Cardiomyopathy, Familial Hypertrophic, 21 Cardiomyopathy, Familial Hypertrophic, 26
Cardiomyopathy, Familial Hypertrophic 27 Hypertrophic Cardiomyopathy Due to Intensive Athletic Training
Rare Familial Disorder with Hypertrophic Cardiomyopathy

Diseases related to Cardiomyopathy, Familial Hypertrophic, 6 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 cardiomyopathy, familial hypertrophic, 1 30.1 TMOD1 PRKAG2 LMOD2
2 atrial standstill 1 10.3
3 wolff-parkinson-white syndrome 10.3
4 hypertrophic cardiomyopathy 10.3
5 congenital structural myopathy 9.8 TMOD1 LMOD2
6 congenital fiber-type disproportion 9.7 TMOD1 LMOD2
7 megacystis-microcolon-intestinal hypoperistalsis syndrome 9.7 TMOD1 LMOD2 LMOD1
8 cardiomyopathy, familial hypertrophic, 4 9.7 RNF144B DUSP11

Graphical network of the top 20 diseases related to Cardiomyopathy, Familial Hypertrophic, 6:



Diseases related to Cardiomyopathy, Familial Hypertrophic, 6

Symptoms & Phenotypes for Cardiomyopathy, Familial Hypertrophic, 6

Human phenotypes related to Cardiomyopathy, Familial Hypertrophic, 6:

31 (show all 9)
# Description HPO Frequency HPO Source Accession
1 hypertrophic cardiomyopathy 31 HP:0001639
2 atrioventricular block 31 HP:0001678
3 atrial fibrillation 31 HP:0005110
4 wolff-parkinson-white syndrome 31 HP:0001716
5 ventricular preexcitation 31 HP:0004309
6 sinus bradycardia 31 HP:0001688
7 left bundle branch block 31 HP:0011713
8 asymmetric septal hypertrophy 31 HP:0001670
9 myofiber disarray 31 HP:0031318

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Cardiovascular Heart:
hypertrophic cardiomyopathy
atrioventricular block
atrial fibrillation
sinus bradycardia
left bundle branch block
more
Muscle Soft Tissue:
glycogenosis of skeletal muscle, mild (in some patients)

Clinical features from OMIM®:

600858 (Updated 05-Mar-2021)

Drugs & Therapeutics for Cardiomyopathy, Familial Hypertrophic, 6

Search Clinical Trials , NIH Clinical Center for Cardiomyopathy, Familial Hypertrophic, 6

Genetic Tests for Cardiomyopathy, Familial Hypertrophic, 6

Genetic tests related to Cardiomyopathy, Familial Hypertrophic, 6:

# Genetic test Affiliating Genes
1 Familial Hypertrophic Cardiomyopathy 6 29 PRKAG2
2 Cardiomyopathy, Hypertrophic 6 29

Anatomical Context for Cardiomyopathy, Familial Hypertrophic, 6

MalaCards organs/tissues related to Cardiomyopathy, Familial Hypertrophic, 6:

40
Skeletal Muscle, Heart

Publications for Cardiomyopathy, Familial Hypertrophic, 6

Articles related to Cardiomyopathy, Familial Hypertrophic, 6:

(show all 17)
# Title Authors PMID Year
1
Severe hypertrophic cardiomyopathy in an infant with a novel PRKAG2 gene mutation: potential differences between infantile and adult onset presentation. 57 6
19787389 2009
2
Shared genetic causes of cardiac hypertrophy in children and adults. 6 57
18403758 2008
3
A new mutation in PRKAG2 gene causing hypertrophic cardiomyopathy with conduction system disease and muscular glycogenosis. 6 57
16487706 2006
4
Glycogen storage diseases presenting as hypertrophic cardiomyopathy. 6 57
15673802 2005
5
Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. 57 6
11827995 2002
6
Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis. 57 6
11371514 2001
7
Genetically transmitted ventricular pre-excitation in a family with hypertrophic cardiomyopathy. 57 6
10820940 2000
8
Familial Hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3. 57 6
7657794 1995
9
High risk of sudden death associated with a PRKAG2-related familial Wolff-Parkinson-White syndrome. 6
20381067 2011
10
Clinical, electrocardiographic, and electrophysiologic characteristics of patients with a fasciculoventricular pathway: the role of PRKAG2 mutation. 6
20888928 2011
11
Nodoventricular accessory pathways in PRKAG2-dependent familial preexcitation syndrome reveal a disorder in cardiac development. 6
19808419 2008
12
Ventricular pre-excitation and cardiac hypertrophy mimicking hypertrophic cardiomyopathy in a Turkish family with a novel PRKAG2 mutation. 57
16716659 2006
13
Fatal congenital heart glycogenosis caused by a recurrent activating R531Q mutation in the gamma 2-subunit of AMP-activated protein kinase (PRKAG2), not by phosphorylase kinase deficiency. 57
15877279 2005
14
Transgenic mice overexpressing mutant PRKAG2 define the cause of Wolff-Parkinson-White syndrome in glycogen storage cardiomyopathy. 57
12782567 2003
15
Identification of a gene responsible for familial Wolff-Parkinson-White syndrome. 6
11407343 2001
16
Electrophysiologic characteristics of accessory atrioventricular connections in an inherited form of Wolff-Parkinson-White syndrome. 6
10355918 1999
17
Leiomodins: larger members of the tropomodulin (Tmod) gene family. 61
11318603 2001

Variations for Cardiomyopathy, Familial Hypertrophic, 6

ClinVar genetic disease variations for Cardiomyopathy, Familial Hypertrophic, 6:

6 (show top 50) (show all 165)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PRKAG2 NM_016203.4(PRKAG2):c.1050_1051insTTA (p.Glu351_Leu352insLeu) Insertion Pathogenic 6848 rs587776643 7:151269750-151269751 7:151572664-151572665
2 PRKAG2 NM_016203.4(PRKAG2):c.1463A>T (p.Asn488Ile) SNV Pathogenic 6850 rs121908989 7:151261285-151261285 7:151564199-151564199
3 PRKAG2 NM_016203.4(PRKAG2):c.1642T>C (p.Ser548Pro) SNV Pathogenic 6856 rs267606979 7:151257646-151257646 7:151560560-151560560
4 PRKAG2 NM_016203.4(PRKAG2):c.1148A>G (p.His383Arg) SNV Pathogenic 6847 rs121908988 7:151265887-151265887 7:151568801-151568801
5 PRKAG2 NM_016203.4(PRKAG2):c.905G>A (p.Arg302Gln) SNV Pathogenic 6846 rs121908987 7:151273498-151273498 7:151576412-151576412
6 PRKAG2 NM_016203.4(PRKAG2):c.1199C>A (p.Thr400Asn) SNV Pathogenic 6849 rs28938173 7:151265836-151265836 7:151568750-151568750
7 PRKAG2 NM_016203.4(PRKAG2):c.1459T>C (p.Tyr487His) SNV Pathogenic 6853 rs267606976 7:151261289-151261289 7:151564203-151564203
8 PRKAG2 NM_016203.4(PRKAG2):c.1589A>G (p.His530Arg) SNV Pathogenic 6854 rs267606977 7:151257699-151257699 7:151560613-151560613
9 PRKAG2 NM_016203.4(PRKAG2):c.1516G>C (p.Glu506Gln) SNV Pathogenic 6855 rs267606978 7:151261232-151261232 7:151564146-151564146
10 PRKAG2 NM_016203.4(PRKAG2):c.620C>G (p.Ser207Cys) SNV Uncertain significance 45729 rs397517277 7:151372570-151372570 7:151675484-151675484
11 PRKAG2 NM_016203.3(PRKAG2):c.-520C>T SNV Uncertain significance 359364 rs73160072 7:151574225-151574225 7:151877140-151877140
12 PRKAG2 NM_016203.3(PRKAG2):c.-517G>T SNV Uncertain significance 359363 rs886062107 7:151574222-151574222 7:151877137-151877137
13 PRKAG2 NM_016203.3(PRKAG2):c.-575C>T SNV Uncertain significance 359366 rs886062108 7:151574280-151574280 7:151877195-151877195
14 PRKAG2 NM_016203.3(PRKAG2):c.-580C>T SNV Uncertain significance 359367 rs886062109 7:151574285-151574285 7:151877200-151877200
15 PRKAG2 NM_016203.4(PRKAG2):c.240C>A (p.Gly80=) SNV Uncertain significance 45710 rs142482217 7:151478464-151478464 7:151781378-151781378
16 TNNI3 NM_000363.5(TNNI3):c.550-11C>T SNV Uncertain significance 330198 rs886054635 19:55663296-55663296 19:55151928-55151928
17 PRKAG2 NM_016203.4(PRKAG2):c.1454A>C (p.Lys485Thr) SNV Uncertain significance 438860 rs1554453641 7:151261294-151261294 7:151564208-151564208
18 PRKAG2 NM_016203.4(PRKAG2):c.278T>C (p.Val93Ala) SNV Uncertain significance 908128 7:151478426-151478426 7:151781340-151781340
19 PRKAG2 NM_016203.4(PRKAG2):c.*771C>T SNV Uncertain significance 909038 7:151253516-151253516 7:151556430-151556430
20 PRKAG2 NM_016203.4(PRKAG2):c.*471T>C SNV Uncertain significance 909898 7:151253816-151253816 7:151556730-151556730
21 PRKAG2-AS1 NM_016203.4(PRKAG2):c.-481G>A SNV Uncertain significance 910143 7:151574186-151574186 7:151877101-151877101
22 PRKAG2 NM_016203.4(PRKAG2):c.*1043G>A SNV Uncertain significance 910745 7:151253244-151253244 7:151556158-151556158
23 PRKAG2 NM_016203.4(PRKAG2):c.*1030T>G SNV Uncertain significance 910746 7:151253257-151253257 7:151556171-151556171
24 PRKAG2 NM_016203.4(PRKAG2):c.*1021T>G SNV Uncertain significance 910747 7:151253266-151253266 7:151556180-151556180
25 PRKAG2 NM_016203.4(PRKAG2):c.*450T>C SNV Uncertain significance 910801 7:151253837-151253837 7:151556751-151556751
26 PRKAG2 NM_016203.4(PRKAG2):c.*419C>T SNV Uncertain significance 910802 7:151253868-151253868 7:151556782-151556782
27 PRKAG2 NM_016203.4(PRKAG2):c.119T>A (p.Leu40Gln) SNV Uncertain significance 910975 7:151483623-151483623 7:151786537-151786537
28 PRKAG2 NM_016203.4(PRKAG2):c.*953T>A SNV Uncertain significance 911968 7:151253334-151253334 7:151556248-151556248
29 PRKAG2 NM_016203.4(PRKAG2):c.*398C>T SNV Uncertain significance 910804 7:151253889-151253889 7:151556803-151556803
30 PRKAG2 NM_016203.4(PRKAG2):c.*256T>G SNV Uncertain significance 912012 7:151254031-151254031 7:151556945-151556945
31 PRKAG2 NM_016203.4(PRKAG2):c.*156A>G SNV Uncertain significance 909098 7:151254131-151254131 7:151557045-151557045
32 PRKAG2 NM_016203.4(PRKAG2):c.1324G>A (p.Asp442Asn) SNV Uncertain significance 912070 7:151262881-151262881 7:151565795-151565795
33 PRKAG2 NM_016203.4(PRKAG2):c.90G>T (p.Arg30Ser) SNV Uncertain significance 912206 7:151573616-151573616 7:151876531-151876531
34 PRKAG2 NM_016203.4(PRKAG2):c.*887G>A SNV Uncertain significance 359330 rs886062096 7:151253400-151253400 7:151556314-151556314
35 PRKAG2 NM_016203.4(PRKAG2):c.787C>A (p.Arg263=) SNV Uncertain significance 359344 rs886062100 7:151292508-151292508 7:151595422-151595422
36 PRKAG2 NM_016203.4(PRKAG2):c.*1040dup Duplication Uncertain significance 359322 rs56898021 7:151253246-151253247 7:151556160-151556161
37 PRKAG2 NM_016203.4(PRKAG2):c.-249G>C SNV Uncertain significance 359355 rs534059998 7:151573954-151573954 7:151876869-151876869
38 PRKAG2 NM_016203.4(PRKAG2):c.*1029dup Duplication Uncertain significance 359324 rs1554444891 7:151253257-151253258 7:151556171-151556172
39 PRKAG2 NM_016203.4(PRKAG2):c.*365G>A SNV Uncertain significance 359338 rs886062098 7:151253922-151253922 7:151556836-151556836
40 PRKAG2 NM_016203.4(PRKAG2):c.-397G>C SNV Uncertain significance 359362 rs886062106 7:151574102-151574102 7:151877017-151877017
41 PRKAG2 NM_016203.4(PRKAG2):c.-252C>T SNV Uncertain significance 359356 rs546312513 7:151573957-151573957 7:151876872-151876872
42 PRKAG2 NM_016203.4(PRKAG2):c.*1021_*1022delinsGT Indel Uncertain significance 359325 rs886062094 7:151253265-151253266 7:151556179-151556180
43 PRKAG2 NM_016203.4(PRKAG2):c.*1040del Deletion Uncertain significance 359323 rs56898021 7:151253247-151253247 7:151556161-151556161
44 PRKAG2 NM_016203.4(PRKAG2):c.*1012T>G SNV Uncertain significance 359327 rs886062095 7:151253275-151253275 7:151556189-151556189
45 PRKAG2 NM_016203.4(PRKAG2):c.-40C>T SNV Uncertain significance 359353 rs148715621 7:151573745-151573745 7:151876660-151876660
46 PRKAG2 NM_016203.4(PRKAG2):c.-262C>T SNV Uncertain significance 359357 rs886062103 7:151573967-151573967 7:151876882-151876882
47 PRKAG2 NM_016203.4(PRKAG2):c.*964G>A SNV Uncertain significance 359328 rs75512992 7:151253323-151253323 7:151556237-151556237
48 PRKAG2 NM_016203.4(PRKAG2):c.*1041dup Duplication Uncertain significance 359321 rs886062093 7:151253245-151253246 7:151556159-151556160
49 PRKAG2 NM_016203.4(PRKAG2):c.-16A>G SNV Uncertain significance 359352 rs200468798 7:151573721-151573721 7:151876636-151876636
50 PRKAG2 NM_016203.4(PRKAG2):c.*612G>A SNV Uncertain significance 359333 rs371404960 7:151253675-151253675 7:151556589-151556589

UniProtKB/Swiss-Prot genetic disease variations for Cardiomyopathy, Familial Hypertrophic, 6:

73
# Symbol AA change Variation ID SNP ID
1 PRKAG2 p.Arg302Gln VAR_013264 rs121908987
2 PRKAG2 p.His383Arg VAR_013266 rs121908988
3 PRKAG2 p.Thr400Asn VAR_013267 rs28938173
4 PRKAG2 p.Asn488Ile VAR_013268 rs121908989

Expression for Cardiomyopathy, Familial Hypertrophic, 6

Search GEO for disease gene expression data for Cardiomyopathy, Familial Hypertrophic, 6.

Pathways for Cardiomyopathy, Familial Hypertrophic, 6

GO Terms for Cardiomyopathy, Familial Hypertrophic, 6

Cellular components related to Cardiomyopathy, Familial Hypertrophic, 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 sarcomere GO:0030017 9.43 TMOD1 LMOD2 LMOD1
2 myofibril GO:0030016 9.33 TMOD1 LMOD2 LMOD1
3 actin filament GO:0005884 9.26 TMOD1 RCSD1 LMOD2 LMOD1
4 striated muscle thin filament GO:0005865 8.8 TMOD1 LMOD2 LMOD1

Biological processes related to Cardiomyopathy, Familial Hypertrophic, 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 actin filament organization GO:0007015 9.5 TMOD1 LMOD2 LMOD1
2 positive regulation of actin filament polymerization GO:0030838 9.37 LMOD2 LMOD1
3 muscle contraction GO:0006936 9.33 TMOD1 LMOD2 LMOD1
4 actin nucleation GO:0045010 9.26 LMOD2 LMOD1
5 myofibril assembly GO:0030239 9.13 TMOD1 LMOD2 LMOD1
6 pointed-end actin filament capping GO:0051694 8.8 TMOD1 LMOD2 LMOD1

Molecular functions related to Cardiomyopathy, Familial Hypertrophic, 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 actin binding GO:0003779 9.13 TMOD1 LMOD2 LMOD1
2 tropomyosin binding GO:0005523 8.8 TMOD1 LMOD2 LMOD1

Sources for Cardiomyopathy, Familial Hypertrophic, 6

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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