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NM_000257.4(MYH7):c.1750G>A (p.Gly584Ser)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6 (Most recent: Jan 7, 2021)
Last evaluated:
Oct 20, 2020
Accession:
VCV000042862.9
Variation ID:
42862
Description:
single nucleotide variant
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NM_000257.4(MYH7):c.1750G>A (p.Gly584Ser)

Allele ID
52032
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
14q11.2
Genomic location
14: 23427723 (GRCh38) GRCh38 UCSC
14: 23896932 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P12883:p.Gly584Ser
LRG_384:g.12939G>A
LRG_384t1:c.1750G>A
... more HGVS
Protein change
G584S
Other names
-
Canonical SPDI
NC_000014.9:23427722:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00001
Links
ClinGen: CA011178
UniProtKB: P12883#VAR_029436
dbSNP: rs121913626
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Oct 20, 2020 RCV000229519.6
Pathogenic 1 criteria provided, single submitter Oct 1, 2018 RCV000035743.6
Likely pathogenic 1 criteria provided, single submitter Nov 12, 2019 RCV000242011.2
Likely pathogenic 1 criteria provided, single submitter Feb 8, 2018 RCV000709746.1
Pathogenic 1 criteria provided, single submitter Jul 19, 2018 RCV000788633.1
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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
2445 2959

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Oct 20, 2020)
criteria provided, single submitter
Method: clinical testing
Hypertrophic cardiomyopathy
Allele origin: germline
Invitae
Accession: SCV000284258.6
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (10)
Comment:
This sequence change replaces glycine with serine at codon 584 of the MYH7 protein (p.Gly584Ser). The glycine residue is highly conserved and there is a … (more)
Likely pathogenic
(Aug 07, 2017)
criteria provided, single submitter
Method: clinical testing
Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000059394.6
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (4)
Comment:
The p.Gly584Ser variant in MYH7 has been reported in >5 individuals with HCM (Er dmann 2003, Zou 2013, Kapplinger 2014, Homburger 2016, LMM unpublished), and … (more)
Likely pathogenic
(Feb 08, 2018)
criteria provided, single submitter
Method: clinical testing
Familial hypertrophic cardiomyopathy 1
Allele origin: germline
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV000840023.1
Submitted: (Jun 14, 2018)
Evidence details
Comment:
The c.1750G>A (p.Gly584Ser) variant in the MYH7 gene has been reported in multiple unrelated individuals with hypertrophic cardiomyopathy (HCM) (PMID: 12974739, 23283745, 24510615, 27247418). This … (more)
Pathogenic
(Oct 01, 2018)
criteria provided, single submitter
Method: clinical testing
Primary familial hypertrophic cardiomyopathy
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000917844.1
Submitted: (Apr 24, 2019)
Evidence details
Publications
PubMed (7)
Comment:
Variant summary: MYH7 c.1750G>A (p.Gly584Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Pathogenic
(Jul 19, 2018)
criteria provided, single submitter
Method: clinical testing
Not provided
Allele origin: germline
Blueprint Genetics
Accession: SCV000927812.1
Submitted: (May 08, 2019)
Comment:
Patient analyzed with Hypertrophic Cardiomyopathy (HCM) Panel
Evidence details
Likely pathogenic
(Nov 12, 2019)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000319779.5
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (7)
Comment:
The p.G584S variant (also known as c.1750G>A), located in coding exon 14 of the MYH7 gene, results from a G to A substitution at nucleotide … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Presence of Hypertrophic Cardiomyopathy Related Gene Mutations and Clinical Manifestations in Vietnamese Patients With Hypertrophic Cardiomyopathy. Tran Vu MT Circulation journal : official journal of the Japanese Circulation Society 2019 PMID: 31308319
Genetic testing impacts the utility of prospective familial screening in hypertrophic cardiomyopathy through identification of a nonfamilial subgroup. Ko C Genetics in medicine : official journal of the American College of Medical Genetics 2018 PMID: 28640247
Whole Exome Sequencing Identifies Truncating Variants in Nuclear Envelope Genes in Patients With Cardiovascular Disease. Haskell GT Circulation. Cardiovascular genetics 2017 PMID: 28611029
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
Utility and limitations of exome sequencing as a genetic diagnostic tool for conditions associated with pediatric sudden cardiac arrest/sudden cardiac death. Li MH Human genomics 2015 PMID: 26187847
Characterization of a phenotype-based genetic test prediction score for unrelated patients with hypertrophic cardiomyopathy. Bos JM Mayo Clinic proceedings 2014 PMID: 24793961
Distinguishing hypertrophic cardiomyopathy-associated mutations from background genetic noise. Kapplinger JD Journal of cardiovascular translational research 2014 PMID: 24510615
Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy. Marsiglia JD American heart journal 2013 PMID: 24093860
Multiple gene mutations, not the type of mutation, are the modifier of left ventricle hypertrophy in patients with hypertrophic cardiomyopathy. Zou Y Molecular biology reports 2013 PMID: 23283745
Development and validation of a computational method for assessment of missense variants in hypertrophic cardiomyopathy. Jordan DM American journal of human genetics 2011 PMID: 21310275
Array-based resequencing assay for mutations causing hypertrophic cardiomyopathy. Waldmüller S Clinical chemistry 2008 PMID: 18258667
Mutation spectrum in a large cohort of unrelated consecutive patients with hypertrophic cardiomyopathy. Erdmann J Clinical genetics 2003 PMID: 12974739
Prognostic implications of novel beta cardiac myosin heavy chain gene mutations that cause familial hypertrophic cardiomyopathy. Anan R The Journal of clinical investigation 1994 PMID: 8282798
Left ventricular hypertrophy and morphology in familial hypertrophic cardiomyopathy associated with mutations of the beta-myosin heavy chain gene. Solomon SD Journal of the American College of Cardiology 1993 PMID: 8335820
Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. Watkins H The New England journal of medicine 1992 PMID: 1552912

Text-mined citations for rs121913626...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021