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NM_000257.4(MYH7):c.958G>A (p.Val320Met)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(4);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
8 (Most recent: Jan 7, 2021)
Last evaluated:
Apr 5, 2020
Accession:
VCV000161328.7
Variation ID:
161328
Description:
single nucleotide variant
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NM_000257.4(MYH7):c.958G>A (p.Val320Met)

Allele ID
171165
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
14q11.2
Genomic location
14: 23430601 (GRCh38) GRCh38 UCSC
14: 23899810 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P12883:p.Val320Met
LRG_384:g.10061G>A
LRG_384t1:c.958G>A
... more HGVS
Protein change
V320M
Other names
p.V320M:GTG>ATG
Canonical SPDI
NC_000014.9:23430600:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00010
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
Links
ClinGen: CA017003
UniProtKB: P12883#VAR_020803
dbSNP: rs376897125
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Mar 10, 2020 RCV000201440.2
Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Apr 5, 2020 RCV000549661.6
Uncertain significance 1 criteria provided, single submitter Jan 12, 2017 RCV000158772.4
Conflicting interpretations of pathogenicity 2 no assertion criteria provided Jun 9, 2014 RCV000148711.4
Likely pathogenic 1 no assertion criteria provided Aug 6, 2012 RCV000223879.1
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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
2444 2958

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(-)
criteria provided, single submitter
Method: clinical testing
Familial hypertrophic cardiomyopathy 1
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory of Genetics and Molecular Cardiology, University of São Paulo
Study: Sarcomeric Human Cardiomyopathy Registry (ShaRe)
Accession: SCV000256154.1
Submitted: (Oct 30, 2015)
Evidence details
Other databases
http://researchpub.org/journal/j…
Uncertain significance
(Jan 12, 2017)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
GeneDx
Accession: SCV000208707.12
Submitted: (Nov 28, 2017)
Evidence details
Comment:
A variant of uncertain significance has been identified in the MYH7 gene. The V320M variant has previously been reported in association with HCM (Havndrup et … (more)
Likely pathogenic
(Feb 08, 2019)
criteria provided, single submitter
Method: clinical testing
Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000710839.2
Submitted: (Jun 03, 2020)
Evidence details
Publications
PubMed (8)
Comment:
The p.Val320Met variant in MYH7 has been reported in over 20 individuals with hypertrophic cardiomyopathy (HCM) (Brito 2012, Fokstuen 2011, Havndrup 2003, Homburger 2016, Jensen … (more)
Likely pathogenic
(Mar 10, 2020)
criteria provided, single submitter
Method: research
Familial hypertrophic cardiomyopathy 1
Allele origin: unknown
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology
Study: AGHI_GT
Accession: SCV001423552.1
Submitted: (Apr 07, 2020)
Evidence details
Likely pathogenic
(Apr 05, 2020)
criteria provided, single submitter
Method: clinical testing
Hypertrophic cardiomyopathy
Allele origin: germline
Invitae
Accession: SCV000623763.6
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (8)
Comment:
This sequence change replaces valine with methionine at codon 320 of the MYH7 protein (p.Val320Met). The valine residue is highly conserved and there is a … (more)
Uncertain significance
(Jun 01, 2014)
no assertion criteria provided
Method: research
Cardiomyopathy, hypertrophic
(Autosomal dominant inheritance)
Allele origin: germline
CSER _CC_NCGL, University of Washington
Study: ESP 6500 variant annotation
Accession: SCV000190441.1
Submitted: (Aug 28, 2014)
Comment:
Variants classified for the Actionable exomic incidental findings in 6503 participants: challenges of variant classification manuscript
Evidence details
Likely pathogenic
(Jun 09, 2014)
no assertion criteria provided
Method: clinical testing
Primary familial hypertrophic cardiomyopathy
Allele origin: germline
Blueprint Genetics
Accession: SCV000207090.1
Submitted: (Feb 02, 2015)
Evidence details
Likely pathogenic
(Aug 06, 2012)
no assertion criteria provided
Method: clinical testing
Not provided
Allele origin: germline
Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000280360.1
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)

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
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
A Variant Detection Pipeline for Inherited Cardiomyopathy-Associated Genes Using Next-Generation Sequencing. Oliveira TG The Journal of molecular diagnostics : JMD 2015 PMID: 25937619
Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy. Marsiglia JD American heart journal 2013 PMID: 24093860
Penetrance of hypertrophic cardiomyopathy in children and adolescents: a 12-year follow-up study of clinical screening and predictive genetic testing. Jensen MK Circulation 2013 PMID: 23197161
Sarcomeric hypertrophic cardiomyopathy: genetic profile in a Portuguese population. Brito D Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology 2012 PMID: 22857948
Rapid detection of genetic variants in hypertrophic cardiomyopathy by custom DNA resequencing array in clinical practice. Fokstuen S Journal of medical genetics 2011 PMID: 21239446
Echocardiographic strain imaging to assess early and late consequences of sarcomere mutations in hypertrophic cardiomyopathy. Ho CY Circulation. Cardiovascular genetics 2009 PMID: 20031602
Outcome of clinical versus genetic family screening in hypertrophic cardiomyopathy with focus on cardiac beta-myosin gene mutations. Havndrup O Cardiovascular research 2003 PMID: 12566107
http://researchpub.org/journal/jcvd/number/vol2-no2/vol2-no2-7.pdf - - - -

Text-mined citations for rs376897125...

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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