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NM_000257.4(MYH7):c.2221G>T (p.Gly741Trp)

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Interpretation:
Pathogenic​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
9 (Most recent: Feb 25, 2019)
Last evaluated:
Dec 15, 2016
Accession:
VCV000177665.1
Variation ID:
177665
Description:
single nucleotide variant
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NM_000257.4(MYH7):c.2221G>T (p.Gly741Trp)

Allele ID
175480
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
14q11.2
Genomic location
14: 23425760 (GRCh38) GRCh38 UCSC
14: 23894969 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000014.8:g.23894969C>A
NC_000014.9:g.23425760C>A
LRG_384t1:c.2221G>T LRG_384p1:p.Gly741Trp
... more HGVS
Protein change
G741W
Other names
p.G741W:GGG>TGG
NM_000257.3(MYH7):c.2221G>T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
UniProtKB: P12883#VAR_004589
dbSNP: rs121913632
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 3 reviewed by expert panel Dec 15, 2016 RCV000678722.3
Pathogenic 3 criteria provided, multiple submitters, no conflicts Jan 20, 2017 RCV000158523.5
Likely pathogenic 1 criteria provided, single submitter Apr 17, 2014 RCV000154255.2
Pathogenic 1 criteria provided, single submitter Jan 9, 2015 RCV000162338.3
Likely pathogenic 1 criteria provided, single submitter Jan 18, 2017 RCV000619837.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
MYH7 No evidence available No evidence available GRCh38
GRCh37
1406 1673

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Dec 15, 2016)
reviewed by expert panel
Method: curation
Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Allele origin: germline
ClinGen Inherited Cardiomyopathy Variant Curation Expert Panel,
FDA Recognized Database
Accession: SCV000564428.4
Submitted: (Feb 25, 2019)
Evidence details
Publications
PubMed (4)
Other databases
https://erepo.clinicalgenome.o...
Comment:
The c.2221G>T (p.Gly741Trp) variant in MYH7 has been reported in >15 individuals with hypertrophic cardiomyopathy (PS4; PMID: 8533830; PMID:15856146; PMID:27532257; Partners LMM ClinVar SCV000203910.4; AGCMC ... (more)
Pathogenic
(Jan 09, 2015)
criteria provided, single submitter
Method: research
Familial hypertrophic cardiomyopathy 1
(Autosomal dominant inheritance)
Allele origin: germline
Agnes Ginges Centre for Molecular Cardiology,Centenary Institute
Accession: SCV000212638.1
Submitted: (Mar 03, 2015)
Evidence details
Publications
PubMed (7)
Comment:
This MYH7 Gly741Trp variant has been reported in both sporadic and familial HCM cases (Arai S, et al., 1995; Perrot A, et al., 2005). Parents ... (more)
Pathogenic
(Jan 20, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000208458.9
Submitted: (Nov 28, 2017)
Evidence details
Comment:
The G741W variant in the MYH7 gene has been previously reported in multiple individuals diagnosed with HCM. In at least two families, the G741W variant ... (more)
Likely pathogenic
(Apr 17, 2014)
criteria provided, single submitter
Method: clinical testing
Primary familial hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine
Accession: SCV000203910.4
Submitted: (Feb 23, 2018)
Evidence details
Publications
PubMed (3)
Comment:
The Gly741Trp variant in MYH7 has been reported in at least 3 individuals with HCM (Arai 1995, Perrot 2005, Pan 2012) and segregated with disease ... (more)
Pathogenic
(May 17, 2018)
criteria provided, single submitter
Method: clinical testing
Hypertrophic cardiomyopathy
Allele origin: germline
Invitae
Accession: SCV000813145.1
Submitted: (Aug 29, 2018)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces glycine with tryptophan at codon 741 of the MYH7 protein (p.Gly741Trp). The glycine residue is highly conserved and there is a ... (more)
Likely pathogenic
(Jan 18, 2017)
criteria provided, single submitter
Method: clinical testing
cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000739985.2
Submitted: (Jul 30, 2018)
Evidence details
Publications
PubMed (8)
Comment:
Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Well-characterized mutation at same ... (more)
Pathogenic
(Jan 15, 2015)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics
Accession: SCV000226869.5
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/em...
Likely pathogenic
(Sep 09, 2015)
no assertion criteria provided
Method: clinical testing
Not provided
Allele origin: germline
Stanford Center for Inherited Cardiovascular Disease,Stanford University
Accession: SCV000280319.1
Submitted: (May 06, 2016)
Evidence details
Comment:
Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case ... (more)
Likely pathogenic
(Mar 16, 2016)
no assertion criteria provided
Method: clinical testing
Hypertrophic cardiomyopathy
Allele origin: germline
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital
Accession: SCV000804893.1
Submitted: (Jul 17, 2018)
Evidence details

Citations for this variant

Title Author Journal Year Link
Adaptation and validation of the ACMG/AMP variant classification framework for MYH7-associated inherited cardiomyopathies: recommendations by ClinGen's Inherited Cardiomyopathy Expert Panel. Kelly MA Genetics in medicine : official journal of the American College of Medical Genetics 2018 PMID: 29300372
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Walsh R Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 27532257
Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation. Homburger JR Proceedings of the National Academy of Sciences of the United States of America 2016 PMID: 27247418
Evaluation of the Mayo Clinic Phenotype-Based Genotype Predictor Score in Patients with Clinically Diagnosed Hypertrophic Cardiomyopathy. Murphy SL Journal of cardiovascular translational research 2016 PMID: 26914223
Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy. Lopes LR Heart (British Cardiac Society) 2015 PMID: 25351510
Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy. Marsiglia JD American heart journal 2013 PMID: 24093860
Cardiac structural and sarcomere genes associated with cardiomyopathy exhibit marked intolerance of genetic variation. Pan S Circulation. Cardiovascular genetics 2012 PMID: 23074333
High resolution melting: improvements in the genetic diagnosis of hypertrophic cardiomyopathy in a Portuguese cohort. Santos S BMC medical genetics 2012 PMID: 22429680
Prevalence and distribution of sarcomeric gene mutations in Japanese patients with familial hypertrophic cardiomyopathy. Otsuka H Circulation journal : official journal of the Japanese Circulation Society 2012 PMID: 22112859
Prevalence of cardiac beta-myosin heavy chain gene mutations in patients with hypertrophic cardiomyopathy. Perrot A Journal of molecular medicine (Berlin, Germany) 2005 PMID: 15856146
Mutations profile in Chinese patients with hypertrophic cardiomyopathy. Song L Clinica chimica acta; international journal of clinical chemistry 2005 PMID: 15563892
Comprehensive analysis of the beta-myosin heavy chain gene in 389 unrelated patients with hypertrophic cardiomyopathy. Van Driest SL Journal of the American College of Cardiology 2004 PMID: 15358028
Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Richard P Circulation 2003 PMID: 12707239
Missense mutation of the beta-cardiac myosin heavy-chain gene in hypertrophic cardiomyopathy. Arai S American journal of medical genetics 1995 PMID: 8533830
Missense mutations in the beta-myosin heavy-chain gene cause central core disease in hypertrophic cardiomyopathy. Fananapazir L Proceedings of the National Academy of Sciences of the United States of America 1993 PMID: 8483915
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MYH7 - - - -
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/6c7676cc-a729-42ee-bc9c-580feb015c57 - - - -

Record last updated Jun 24, 2019