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NM_000257.4(MYH7):c.728G>A (p.Arg243His)

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Interpretation:
Uncertain significance​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
9 (Most recent: Sep 25, 2021)
Last evaluated:
Jun 16, 2021
Accession:
VCV000014126.9
Variation ID:
14126
Description:
single nucleotide variant
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NM_000257.4(MYH7):c.728G>A (p.Arg243His)

Allele ID
29165
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
14q11.2
Genomic location
14: 23431589 (GRCh38) GRCh38 UCSC
14: 23900798 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P12883:p.Arg243His
LRG_384t1:c.728G>A LRG_384p1:p.Arg243His
LRG_384:g.9073G>A
... more HGVS
Protein change
R243H
Other names
p.R243H:CGC>CAC
NM_000257.4(MYH7):c.728G>A
Canonical SPDI
NC_000014.9:23431588:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00001
Exome Aggregation Consortium (ExAC) 0.00001
Links
ClinGen: CA016701
UniProtKB: P12883#VAR_073876
OMIM: 160760.0040
dbSNP: rs267606910
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 reviewed by expert panel Jun 16, 2021 RCV001618213.1
Pathogenic/Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Oct 26, 2020 RCV000472129.6
Likely pathogenic 2 criteria provided, single submitter Aug 1, 2017 RCV000015186.27
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Nov 20, 2020 RCV000514633.5
Pathogenic 1 no assertion criteria provided Jun 3, 2008 RCV000015187.26
Likely pathogenic 1 no assertion criteria provided Jul 14, 2017 RCV000656213.1
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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
2412 2918

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Jun 16, 2021)
reviewed by expert panel
Method: curation
Cardiomyopathy
(Autosomal dominant inheritance)
Allele origin: germline
ClinGen Cardiomyopathy Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV001842666.1
Submitted: (Sep 08, 2021)
Evidence details
Other databases
https://erepo.clinicalgenome.org…
Comment:
The c.728G>A (p.Arg243His) variant in MYH7 has been identified in 3 individuals with HCM (Arad 2005 PMID:16267253; van Velzen 2016 PMID:27476098; GeneDx pers. comm.), 2 … (more)
Uncertain significance
(Apr 19, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics
Accession: SCV000611019.1
Submitted: (Oct 05, 2017)
Evidence details
Likely pathogenic
(Aug 01, 2017)
criteria provided, single submitter
Method: clinical testing
Familial hypertrophic cardiomyopathy 1
Allele origin: germline
Phosphorus, Inc.
Accession: SCV000679796.1
Submitted: (Sep 27, 2017)
Evidence details
Publications
PubMed (7)
Likely pathogenic
(Apr 20, 2018)
criteria provided, single submitter
Method: clinical testing
Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000967720.1
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (7)
Comment:
The p.Arg243His variant in MYH7 has been reported in 1 individual with hypertrop hic cardiomyopathy (Arad 2005), 1 with Ebstein anomaly (Sicko 2016), and 1 … (more)
Pathogenic
(Oct 26, 2020)
criteria provided, single submitter
Method: clinical testing
Hypertrophic cardiomyopathy
Allele origin: germline
Invitae
Accession: SCV000546234.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces arginine with histidine at codon 243 of the MYH7 protein (p.Arg243His). The arginine residue is highly conserved and there is a … (more)
Likely pathogenic
(Nov 20, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000208691.13
Submitted: (Sep 25, 2021)
Evidence details
Comment:
Identified in a patient with Ebstein's anomaly in the published literature (Sicko et al., 2016) and in another patient with Wolff-Parkinson-White (WPW) syndrome and LV … (more)
Pathogenic
(Jun 03, 2008)
no assertion criteria provided
Method: literature only
CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 1
Allele origin: germline
OMIM
Accession: SCV000035443.2
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (3)
Pathogenic
(Jun 03, 2008)
no assertion criteria provided
Method: literature only
LEFT VENTRICULAR NONCOMPACTION 5
Allele origin: germline
OMIM
Accession: SCV000035444.2
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (3)
Likely pathogenic
(Jul 14, 2017)
no assertion criteria provided
Method: research
Wolff-Parkinson-White pattern
Allele origin: inherited
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine
Study: Candidate_variants_in_patients_with_ Wolff-Parkinson-White Syndrome
Accession: SCV000678407.1
Submitted: (Aug 26, 2017)
Evidence details
Comment:
This variant was identified in an individual with Wolff-Parkinson-White syndrome

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
Hypertrophic cardiomyopathy clinical phenotype is independent of gene mutation and mutation dosage. Viswanathan SK PloS one 2017 PMID: 29121657
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
Genetic Variants in Isolated Ebstein Anomaly Implicated in Myocardial Development Pathways. Sicko RJ PloS one 2016 PMID: 27788187
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
The pathogenicity of genetic variants previously associated with left ventricular non-compaction. Abbasi Y Molecular genetics & genomic medicine 2015 PMID: 27066506
Genetic screening and double mutation in Japanese patients with hypertrophic cardiomyopathy. Kubo T Circulation journal : official journal of the Japanese Circulation Society 2011 PMID: 21799269
Sarcomere gene mutations in isolated left ventricular noncompaction cardiomyopathy do not predict clinical phenotype. Probst S Circulation. Cardiovascular genetics 2011 PMID: 21551322
Identification of a novel TPM1 mutation in a family with left ventricular noncompaction and sudden death. Chang B Molecular genetics and metabolism 2011 PMID: 20965760
Mutations in sarcomere protein genes in left ventricular noncompaction. Klaassen S Circulation 2008 PMID: 18506004
Gene mutations in apical hypertrophic cardiomyopathy. Arad M Circulation 2005 PMID: 16267253
Isolated noncompaction of the left ventricular myocardium in the adult is an autosomal dominant disorder in the majority of patients. Sasse-Klaassen S American journal of medical genetics. Part A 2003 PMID: 12749056
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/19ebffaf-dafb-4bb1-929f-9bc09049f137 - - - -

Text-mined citations for rs267606910...

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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 Sep 29, 2021