CMH6
MCID: CRD232
MIFTS: 38

Cardiomyopathy, Familial Hypertrophic, 6 (CMH6)

Categories: Blood diseases, Cardiovascular diseases, Genetic diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Cardiomyopathy, Familial Hypertrophic, 6

MalaCards integrated aliases for Cardiomyopathy, Familial Hypertrophic, 6:

Name: Cardiomyopathy, Familial Hypertrophic, 6 58 74
Cardiomyopathy, Familial Hypertrophic 6 12 76 13
Cmh6 58 12 76
Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome 76 6
Familial Hypertrophic Cardiomyopathy 6 30 6
Hypertrophic Cardiomyopathy 6 12 15
Cardiomyopathy, Hypertrophic, Familial, Type 6 41
Cardiomyopathy, Hypertrophic 6 58

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
genetic heterogeneity (see )


HPO:

33
cardiomyopathy, familial hypertrophic, 6:
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0110312
OMIM 58 600858
MeSH 45 D024741
MedGen 43 C1833236
UMLS 74 C1833236

Summaries for Cardiomyopathy, Familial Hypertrophic, 6

UniProtKB/Swiss-Prot : 76 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 wolff-parkinson-white syndrome and hypertrophic cardiomyopathy. An important gene associated with Cardiomyopathy, Familial Hypertrophic, 6 is PRKAG2 (Protein Kinase AMP-Activated Non-Catalytic Subunit Gamma 2), and among its related pathways/superpathways are Cardiac conduction and Dilated cardiomyopathy (DCM). Affiliated tissues include heart and skeletal muscle, 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 : 58 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)

Related Diseases for Cardiomyopathy, Familial Hypertrophic, 6

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:

33 (show all 9)
# Description HPO Frequency HPO Source Accession
1 hypertrophic cardiomyopathy 33 HP:0001639
2 atrioventricular block 33 HP:0001678
3 wolff-parkinson-white syndrome 33 HP:0001716
4 ventricular preexcitation 33 HP:0004309
5 atrial fibrillation 33 HP:0005110
6 sinus bradycardia 33 HP:0001688
7 asymmetric septal hypertrophy 33 HP:0001670
8 left bundle branch block 33 HP:0011713
9 myofiber disarray 33 HP:0031318

Symptoms via clinical synopsis from OMIM:

58
Cardiovascular Heart:
hypertrophic cardiomyopathy
atrioventricular block
atrial fibrillation
sinus bradycardia
wolff-parkinson-white ventricular preexcitation
more
Muscle Soft Tissue:
glycogenosis of skeletal muscle, mild (in some patients)

Clinical features from OMIM:

600858

MGI Mouse Phenotypes related to Cardiomyopathy, Familial Hypertrophic, 6:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.26 LMOD2 PRKAG2 TMOD1 TNNI3
2 muscle MP:0005369 8.92 LMOD2 PRKAG2 TMOD1 TNNI3

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 30 PRKAG2

Anatomical Context for Cardiomyopathy, Familial Hypertrophic, 6

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

42
Heart, Skeletal Muscle

Publications for Cardiomyopathy, Familial Hypertrophic, 6

Articles related to Cardiomyopathy, Familial Hypertrophic, 6:

(show all 16)
# Title Authors Year
1
Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. ( 27854360 )
2017
2
ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing. ( 25356965 )
2015
3
2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). ( 25173338 )
2014
4
ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. ( 23788249 )
2013
5
Clinical utility gene card for: hypertrophic cardiomyopathy (type 1-14). ( 21267010 )
2011
6
Severe hypertrophic cardiomyopathy in an infant with a novel PRKAG2 gene mutation: potential differences between infantile and adult onset presentation. ( 19787389 )
2009
7
Shared genetic causes of cardiac hypertrophy in children and adults. ( 18403758 )
2008
8
A new mutation in PRKAG2 gene causing hypertrophic cardiomyopathy with conduction system disease and muscular glycogenosis. ( 16487706 )
2006
9
Glycogen storage diseases presenting as hypertrophic cardiomyopathy. ( 15673802 )
2005
10
Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. ( 11827995 )
2002
11
A gene responsible for familial Wolff-Parkinson-White syndrome. ( 11586962 )
2001
12
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. ( 11371514 )
2001
13
Genetically transmitted ventricular pre-excitation in a family with hypertrophic cardiomyopathy. ( 10820940 )
2000
14
Electrophysiologic characteristics of accessory atrioventricular connections in an inherited form of Wolff-Parkinson-White syndrome. ( 10355918 )
1999
15
Familial hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome progressing to ventricular dilation. ( 8644606 )
1996
16
Familial Hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3. ( 7657794 )
1995

Variations for Cardiomyopathy, Familial Hypertrophic, 6

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

76
# 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

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

6 (show top 50) (show all 214)
# Gene Variation Type Significance SNP ID Assembly Location
1 PRKAG2 NM_016203.3(PRKAG2): c.905G> A (p.Arg302Gln) single nucleotide variant Pathogenic rs121908987 GRCh37 Chromosome 7, 151273498: 151273498
2 PRKAG2 NM_016203.3(PRKAG2): c.905G> A (p.Arg302Gln) single nucleotide variant Pathogenic rs121908987 GRCh38 Chromosome 7, 151576412: 151576412
3 PRKAG2 NM_016203.3(PRKAG2): c.1148A> G (p.His383Arg) single nucleotide variant Uncertain significance rs121908988 GRCh37 Chromosome 7, 151265887: 151265887
4 PRKAG2 NM_016203.3(PRKAG2): c.1148A> G (p.His383Arg) single nucleotide variant Uncertain significance rs121908988 GRCh38 Chromosome 7, 151568801: 151568801
5 PRKAG2 NM_016203.3(PRKAG2): c.1050_1051insTTA (p.Arg350_Glu351insLeu) insertion Pathogenic rs587776643 GRCh37 Chromosome 7, 151269750: 151269751
6 PRKAG2 NM_016203.3(PRKAG2): c.1050_1051insTTA (p.Arg350_Glu351insLeu) insertion Pathogenic rs587776643 GRCh38 Chromosome 7, 151572664: 151572665
7 PRKAG2 NM_016203.3(PRKAG2): c.1199C> A (p.Thr400Asn) single nucleotide variant Likely pathogenic rs28938173 GRCh37 Chromosome 7, 151265836: 151265836
8 PRKAG2 NM_016203.3(PRKAG2): c.1199C> A (p.Thr400Asn) single nucleotide variant Likely pathogenic rs28938173 GRCh38 Chromosome 7, 151568750: 151568750
9 PRKAG2 NM_016203.3(PRKAG2): c.1463A> T (p.Asn488Ile) single nucleotide variant Pathogenic rs121908989 GRCh37 Chromosome 7, 151261285: 151261285
10 PRKAG2 NM_016203.3(PRKAG2): c.1463A> T (p.Asn488Ile) single nucleotide variant Pathogenic rs121908989 GRCh38 Chromosome 7, 151564199: 151564199
11 PRKAG2 NM_016203.3(PRKAG2): c.1459T> C (p.Tyr487His) single nucleotide variant Pathogenic rs267606976 GRCh37 Chromosome 7, 151261289: 151261289
12 PRKAG2 NM_016203.3(PRKAG2): c.1459T> C (p.Tyr487His) single nucleotide variant Pathogenic rs267606976 GRCh38 Chromosome 7, 151564203: 151564203
13 PRKAG2 NM_016203.3(PRKAG2): c.1589A> G (p.His530Arg) single nucleotide variant Pathogenic rs267606977 GRCh37 Chromosome 7, 151257699: 151257699
14 PRKAG2 NM_016203.3(PRKAG2): c.1589A> G (p.His530Arg) single nucleotide variant Pathogenic rs267606977 GRCh38 Chromosome 7, 151560613: 151560613
15 PRKAG2 NM_016203.3(PRKAG2): c.1516G> C (p.Glu506Gln) single nucleotide variant Likely pathogenic rs267606978 GRCh37 Chromosome 7, 151261232: 151261232
16 PRKAG2 NM_016203.3(PRKAG2): c.1516G> C (p.Glu506Gln) single nucleotide variant Likely pathogenic rs267606978 GRCh38 Chromosome 7, 151564146: 151564146
17 PRKAG2 NM_016203.3(PRKAG2): c.1642T> C (p.Ser548Pro) single nucleotide variant Pathogenic rs267606979 GRCh37 Chromosome 7, 151257646: 151257646
18 PRKAG2 NM_016203.3(PRKAG2): c.1642T> C (p.Ser548Pro) single nucleotide variant Pathogenic rs267606979 GRCh38 Chromosome 7, 151560560: 151560560
19 TNNI3 NM_000363.4(TNNI3): c.244C> T (p.Pro82Ser) single nucleotide variant risk factor rs77615401 GRCh37 Chromosome 19, 55667607: 55667607
20 TNNI3 NM_000363.4(TNNI3): c.244C> T (p.Pro82Ser) single nucleotide variant risk factor rs77615401 GRCh38 Chromosome 19, 55156239: 55156239
21 TNNI3; TNNT1 NM_003283.5(TNNT1): c.-20A> G single nucleotide variant Benign/Likely benign rs9636153 GRCh37 Chromosome 19, 55660537: 55660537
22 TNNI3; TNNT1 NM_003283.5(TNNT1): c.-20A> G single nucleotide variant Benign/Likely benign rs9636153 GRCh38 Chromosome 19, 55149169: 55149169
23 TNNI3; TNNT1 NM_003283.5(TNNT1): c.35A> G (p.Glu12Gly) single nucleotide variant Benign/Likely benign rs112562759 GRCh37 Chromosome 19, 55658387: 55658387
24 TNNI3; TNNT1 NM_003283.5(TNNT1): c.35A> G (p.Glu12Gly) single nucleotide variant Benign/Likely benign rs112562759 GRCh38 Chromosome 19, 55147019: 55147019
25 PRKAG2 NM_016203.3(PRKAG2): c.1593G> A (p.Arg531=) single nucleotide variant Conflicting interpretations of pathogenicity rs148197254 GRCh37 Chromosome 7, 151257695: 151257695
26 PRKAG2 NM_016203.3(PRKAG2): c.1593G> A (p.Arg531=) single nucleotide variant Conflicting interpretations of pathogenicity rs148197254 GRCh38 Chromosome 7, 151560609: 151560609
27 PRKAG2 NM_016203.3(PRKAG2): c.298G> A (p.Gly100Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs79474211 GRCh37 Chromosome 7, 151478406: 151478406
28 PRKAG2 NM_016203.3(PRKAG2): c.298G> A (p.Gly100Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs79474211 GRCh38 Chromosome 7, 151781320: 151781320
29 TNNI3 NM_000363.4(TNNI3): c.12-7delC deletion Conflicting interpretations of pathogenicity rs370714315 GRCh37 Chromosome 19, 55668683: 55668683
30 TNNI3 NM_000363.4(TNNI3): c.12-7delC deletion Conflicting interpretations of pathogenicity rs370714315 GRCh38 Chromosome 19, 55157315: 55157315
31 DNAAF3; TNNI3 NM_000363.4(TNNI3): c.150+13G> A single nucleotide variant Benign/Likely benign rs73617692 GRCh37 Chromosome 19, 55667958: 55667958
32 DNAAF3; TNNI3 NM_000363.4(TNNI3): c.150+13G> A single nucleotide variant Benign/Likely benign rs73617692 GRCh38 Chromosome 19, 55156590: 55156590
33 TNNI3 NM_000363.4(TNNI3): c.198G> A (p.Glu66=) single nucleotide variant Benign/Likely benign rs3729710 GRCh37 Chromosome 19, 55667653: 55667653
34 TNNI3 NM_000363.4(TNNI3): c.198G> A (p.Glu66=) single nucleotide variant Benign/Likely benign rs3729710 GRCh38 Chromosome 19, 55156285: 55156285
35 DNAAF3; TNNI3 NM_000363.4(TNNI3): c.25-8T> A single nucleotide variant Benign/Likely benign rs3729836 GRCh37 Chromosome 19, 55668509: 55668509
36 DNAAF3; TNNI3 NM_000363.4(TNNI3): c.25-8T> A single nucleotide variant Benign/Likely benign rs3729836 GRCh38 Chromosome 19, 55157141: 55157141
37 PRKAG2 NM_016203.3(PRKAG2): c.*3G> A single nucleotide variant Benign/Likely benign rs113234987 GRCh37 Chromosome 7, 151254284: 151254284
38 PRKAG2 NM_016203.3(PRKAG2): c.*3G> A single nucleotide variant Benign/Likely benign rs113234987 GRCh38 Chromosome 7, 151557198: 151557198
39 PRKAG2 NM_016203.3(PRKAG2): c.111T> A (p.Ile37=) single nucleotide variant Conflicting interpretations of pathogenicity rs144426409 GRCh37 Chromosome 7, 151573595: 151573595
40 PRKAG2 NM_016203.3(PRKAG2): c.111T> A (p.Ile37=) single nucleotide variant Conflicting interpretations of pathogenicity rs144426409 GRCh38 Chromosome 7, 151876510: 151876510
41 PRKAG2 NM_016203.3(PRKAG2): c.114+12C> T single nucleotide variant Benign/Likely benign rs77902041 GRCh37 Chromosome 7, 151573580: 151573580
42 PRKAG2 NM_016203.3(PRKAG2): c.114+12C> T single nucleotide variant Benign/Likely benign rs77902041 GRCh38 Chromosome 7, 151876495: 151876495
43 PRKAG2 NM_016203.3(PRKAG2): c.123C> T (p.Ser41=) single nucleotide variant Conflicting interpretations of pathogenicity rs397517263 GRCh37 Chromosome 7, 151483619: 151483619
44 PRKAG2 NM_016203.3(PRKAG2): c.123C> T (p.Ser41=) single nucleotide variant Conflicting interpretations of pathogenicity rs397517263 GRCh38 Chromosome 7, 151786533: 151786533
45 PRKAG2 NM_016203.3(PRKAG2): c.1390G> A (p.Asp464Asn) single nucleotide variant Uncertain significance rs397517264 GRCh37 Chromosome 7, 151262815: 151262815
46 PRKAG2 NM_016203.3(PRKAG2): c.1390G> A (p.Asp464Asn) single nucleotide variant Uncertain significance rs397517264 GRCh38 Chromosome 7, 151565729: 151565729
47 PRKAG2 NM_016203.3(PRKAG2): c.1623T> C (p.Ile541=) single nucleotide variant Benign/Likely benign rs28763998 GRCh37 Chromosome 7, 151257665: 151257665
48 PRKAG2 NM_016203.3(PRKAG2): c.1623T> C (p.Ile541=) single nucleotide variant Benign/Likely benign rs28763998 GRCh38 Chromosome 7, 151560579: 151560579
49 PRKAG2 NM_016203.3(PRKAG2): c.207G> A (p.Pro69=) single nucleotide variant Benign/Likely benign rs144384573 GRCh37 Chromosome 7, 151478497: 151478497
50 PRKAG2 NM_016203.3(PRKAG2): c.207G> A (p.Pro69=) single nucleotide variant Benign/Likely benign rs144384573 GRCh38 Chromosome 7, 151781411: 151781411

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 cytoskeleton GO:0005856 9.5 LMOD1 LMOD2 TMOD1
2 actin filament GO:0005884 9.43 LMOD1 LMOD2 TMOD1
3 striated muscle thin filament GO:0005865 9.33 LMOD1 LMOD2 TMOD1
4 sarcomere GO:0030017 9.26 LMOD1 LMOD2 TMOD1 TNNI3
5 myofibril GO:0030016 8.92 LMOD1 LMOD2 TMOD1 TNNI3

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

# Name GO ID Score Top Affiliating Genes
1 muscle contraction GO:0006936 9.46 LMOD1 LMOD2 TMOD1 TNNI3
2 positive regulation of actin filament polymerization GO:0030838 9.37 LMOD1 LMOD2
3 muscle filament sliding GO:0030049 9.32 TMOD1 TNNI3
4 actin nucleation GO:0045010 9.26 LMOD1 LMOD2
5 myofibril assembly GO:0030239 9.13 LMOD1 LMOD2 TMOD1
6 pointed-end actin filament capping GO:0051694 8.8 LMOD1 LMOD2 TMOD1

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 9.26 LMOD1 LMOD2 TMOD1 TNNI3
2 actin filament binding GO:0051015 9.16 TMOD1 TNNI3
3 tropomyosin binding GO:0005523 8.8 LMOD1 LMOD2 TMOD1

Sources for Cardiomyopathy, Familial Hypertrophic, 6

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