57 unrelated Chinese patients with LVNC were recruited at Fuwai Hospital, Beijing, China. Detailed clinical evaluation was performed on the probands and available family members. DNA samples isolated from the peripheral blood of the index cases were screened for 10 sarcomeric genes, including MYH7, MYBPC3, MYL2, MYL3, MYH6, TNNC1, TNNT2, TNNI3, TPM1, and ACTC1
Four MYH7 variants mentioned using reference transcript NM_000257.2
c.464_466delTCT
c.745C>G
c.1106G>A
c.2785G>A
In a small cohort of HCM patients (n = 8), we searched for mutations in the two most common genes responsible for HCM and found four missense mutations in the MYH7 gene encoding cardiac β-myosin heavy chain (R204H, M493V, R719W, and R870H) and three mutations in the myosin-binding protein C3 gene (MYBPC3) including one missense (A848V) and two frameshift mutations (c.3713delTG and c.702ins26bp).
4 mutations in MYH7 reported but no case information
(R204H, M493V, R719W, and R870H)
Cardiomyopathy Mutations in the Tail of β-Cardiac Myosin Modify the Coiled-coil Structure and Affect Integration into Thick Filaments in Muscle Sarcomeres in Adult Cardiomyocytes*
PMID: 24047955
Gene: MYH7
HGNC: 7577
"It is unclear why mutations in the filament-forming tail of myosin heavy chain (MHC) cause hypertrophic or dilated cardiomyopathy as these mutations should not directly affect contraction. To investigate this, we first investigated the impact of five hypertrophic cardiomyopathy-causing (N1327K, E1356K, R1382W, E1555K, and R1768K) and one dilated cardiomyopathy-causing (R1500W) tail mutations on their ability to incorporate into muscle sarcomeres in vivo."
Results suggest that small effects of mutations on helicity translate into a reduced ability to incorporate into sarcomeres, which may elicit compensatory hypertrophy.
Effects of renal sympathetic denervation and angiotensin-converting enzyme inhibitor on left ventricular hypertrophy
PMID: 24924395
Gene: MYH7
"RSD had a significant antihypertensive effect and inhibited hypertensive-induced cardiac hypertrophy in SHRs and showed advantages compared with ACEI in decreasing BP in the early stage and in inhibiting myocardial fibrosis"
Digenic mutational inheritance of the integrin alpha 7 and the myosin heavy chain 7B genes causes congenital myopathy with left ventricular non-compact cardiomyopathy
PMID: 23800289
Gene: MYH7
HGNC: 7577
"This is the first indication that a mutation in the MYH7B gene causes LVNC cardiomyopathy. We demonstrated that the arginine at position 890 of the MYH7B gene is highly conserved in all species; this region is also conserved in the MYH7 gene, which, when mutated, causes LVNC. These data further support the concept that sarcomere genes are associated with LVNC."
DNA analyses were performed in 141 patients with HCM, including 137 survivors and 4 consented, deceased patients
No Case Info
MultipleGeneVariant:
Variant2191 NM_000257.4:c.2191C>T
ClinVar: 181176
CAID: CA011922
gnomAD: not found
Variant2606: NM_000257.4:c.2606G>A
ClinVar: 177667
CAID: CA012723
gnomAD: https://gnomad.broadinstitute.org/variant/14-23894051-C-T
0.0001230 African
Mutation that causes hypertrophic cardiomyopathy increases force production in human β-cardiac myosin
PMID: 23852727
Gene: MYH7
HGNC: 7577
"So, how do we stop a genetic heartbreaker like R453C? The identification of a biochemical and biophysical phenotype is the first step. Now that we know that this mutation causes a subtle decrease in ATPase cycling and an increase in force production by changing the stiffness of the myosin motor domain, we can investigate how these changes affect heart function and development."
Determining pathogenicity of genetic variants in hypertrophic cardiomyopathy: importance of periodic reassessment
PMID: 24113344
Gene: MYH7
HGNC: 7577
This study sought to reassess single-nucleotide variant classification in hypertrophic cardiomyopathy probands. a total of 136 unrelated hypertrophic cardiomyopathy probands had genetic testing, of which 63 (46%) carried at least one pathogenic mutation. MYBPC3 (n = 34; 47%) and MYH7 (n = 23; 32%)
MYH7-R1053Q was found in 17 of 306 patients (5.6%). No carriers of MYH7-R719W or N696S were found. A novel TPM1-D175G mutation was found in a single patient.
Case1: n/a
DiseaseAssertion: HCM
FamilyInfo: n/a
CasePresentingHPOs: n/a
CaseHPOFreeText: n/a
CaseNotHPOs: n/a
CaseNotHPOFreeText: n/a
CasePreviousTesting: n/a
GenotypingMethod: Ten mutations in the beta-myosin heavy chain gene (MYH7), TPM1, and MYBPC3 were screened.
Variant: NM_000257.4:c.3158G>A
ClinVar: 155814
CAID: CA013417
gnomAD: https://gnomad.broadinstitute.org/variant/14-23891476-C-T
0.0006368 European - Finnish
Poor Prognosis of Rare Sarcomeric Gene Variants in Patients with Dilated Cardiomyopathy
PMID: 24119082
Gene: MYH7
HGNC: 7577
24 rare variants (3 in MYH6, 3 in MYH7, 3 in MYBPC3, 2 in TNNT2, and 13 in TTN) affecting 52 subjects in 25 families:
MYH7 (c.2945 T>C, p.M982T; c.4300 C>T, p.R1434C; c.4498 C>T, p.R1500W)
Among these are the 25-nucleotide deletions in MYBPC3, p.R453C and p.G716R in MYH7, and p.R92W inTNNT2, all of which are clearly pathogenic and associated with a poor prognosis.
Variant(1) NM_000257.4:c.1357C>T
ClinVar: 14089
CAID: CA010630
Variant(2) NM_000257.4:c.2146G>A
ClinVar: 14105
CAID: CA011770