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NM_000257.4(MYH7):c.740T>G (p.Phe247Cys)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(2);Pathogenic(2);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: Jan 7, 2021)
Last evaluated:
Mar 29, 2020
Accession:
VCV000181401.7
Variation ID:
181401
Description:
single nucleotide variant
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NM_000257.4(MYH7):c.740T>G (p.Phe247Cys)

Allele ID
179681
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
14q11.2
Genomic location
14: 23431474 (GRCh38) GRCh38 UCSC
14: 23900683 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_384:g.9188T>G
LRG_384t1:c.740T>G
NC_000014.8:g.23900683A>C
... more HGVS
Protein change
F247C
Other names
p.F247C:TTC>TGC
Canonical SPDI
NC_000014.9:23431473:A:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA016752
dbSNP: rs730880922
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 1 criteria provided, single submitter Dec 9, 2011 RCV000158881.1
Pathogenic 1 criteria provided, single submitter Feb 27, 2020 RCV000225905.6
Likely pathogenic 1 criteria provided, single submitter Mar 29, 2020 RCV000620575.2
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations May 15, 2018 RCV000507832.4
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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
Likely pathogenic
(May 15, 2018)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000604367.2
Submitted: (May 15, 2018)
Evidence details
Pathogenic
(Dec 09, 2011)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000208816.10
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This mutation is denoted p.Phe247Cys (F247C) at the protein level and c.740 T>G at the cDNA level. The Phe247Cys mutation in the MYH7 gene has … (more)
Uncertain significance
(Jan 27, 2017)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000731452.1
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (2)
Comment:
Variant classified as Uncertain Significance - Favor Pathogenic. The p.Phe247Cys variant in MYH7 has not been previously reported in individuals with cardiomyop athy, but has … (more)
Likely pathogenic
(Mar 29, 2020)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000737345.3
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (1)
Comment:
The p.F247C variant (also known as c.740T>G), located in coding exon 7 of the MYH7 gene, results from a T to G substitution at nucleotide … (more)
Pathogenic
(Feb 27, 2020)
criteria provided, single submitter
Method: clinical testing
Hypertrophic cardiomyopathy
Allele origin: germline
Invitae
Accession: SCV000284294.6
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change replaces phenylalanine with cysteine at codon 247 of the MYH7 protein (p.Phe247Cys). The phenylalanine residue is highly conserved and there is a … (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
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
Structural basis for drug-induced allosteric changes to human β-cardiac myosin motor activity. Winkelmann DA Nature communications 2015 PMID: 26246073
Resequencing the whole MYH7 gene (including the intronic, promoter, and 3' UTR sequences) in hypertrophic cardiomyopathy. Coto E The Journal of molecular diagnostics : JMD 2012 PMID: 22765922
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
Functional polymorphisms in genes of the Angiotensin and Serotonin systems and risk of hypertrophic cardiomyopathy: AT1R as a potential modifier. Coto E Journal of translational medicine 2010 PMID: 20594303
[Mutations in sarcomeric genes MYH7, MYBPC3, TNNT2, TNNI3, and TPM1 in patients with hypertrophic cardiomyopathy]. García-Castro M Revista espanola de cardiologia 2009 PMID: 19150014

Text-mined citations for rs730880922...

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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