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NM_000257.4(MYH7):c.5326A>G (p.Ser1776Gly)

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Interpretation:
Uncertain significance​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
14
First in ClinVar:
Apr 1, 2019
Most recent Submission:
May 16, 2022
Last evaluated:
Dec 15, 2016
Accession:
VCV000177629.19
Variation ID:
177629
Description:
single nucleotide variant
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NM_000257.4(MYH7):c.5326A>G (p.Ser1776Gly)

Allele ID
175442
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
14q11.2
Genomic location
14: 23415228 (GRCh38) GRCh38 UCSC
14: 23884437 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_000257.4:c.5326A>G MANE Select NP_000248.2:p.Ser1776Gly missense
NC_000014.9:g.23415228T>C
NC_000014.8:g.23884437T>C
... more HGVS
Protein change
S1776G
Other names
NM_000257.3(MYH7):c.5326A>G
Canonical SPDI
NC_000014.9:23415227:T:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00002
Exome Aggregation Consortium (ExAC) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00005
The Genome Aggregation Database (gnomAD), exomes 0.00003
The Genome Aggregation Database (gnomAD) 0.00006
The Genome Aggregation Database (gnomAD) 0.00016
Links
ClinGen: CA015944
UniProtKB: P12883#VAR_020821
dbSNP: rs369437262
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 3 reviewed by expert panel Dec 15, 2016 RCV000462813.8
Uncertain significance 3 criteria provided, multiple submitters, no conflicts Apr 15, 2021 RCV000154209.6
Uncertain significance 3 criteria provided, multiple submitters, no conflicts Sep 30, 2021 RCV000514376.5
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Apr 7, 2021 RCV001170485.5
Uncertain significance 1 criteria provided, single submitter May 18, 2016 RCV000168915.4
Uncertain significance 1 criteria provided, single submitter Aug 4, 2020 RCV000620185.2
Uncertain significance 1 criteria provided, single submitter Oct 31, 2018 RCV000765157.1
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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
2863 3456

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter More information
Uncertain significance
(Dec 15, 2016)
reviewed by expert panel
Method: curation
Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin: germline
ClinGen Cardiomyopathy Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV000564457.4
First in ClinVar: Apr 27, 2017
Last updated: Mar 04, 2019
Publications:
PubMed (1)
PubMed: 29300372
Other databases
https://erepo.clinicalgenome.org… https://erepo.clinicalgenome.org/evrepo/ui/interpretation/5d9a840f-4e17-4378-a41d-341cf6eab7b8
Comment:
The c.5326A>G (p.Ser1776Gly) variant in MYH7 has been reported in 12 individuals with hypertrophic cardiomyopathy (PMID:27532257; PMID:11861413; PMID:21239446; Partners LMM ClinVar SCV000203861.4; SHaRe consortium, PMID: … (more)
Uncertain significance
(Apr 19, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Affected status: not provided
Allele origin: germline
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics
Accession: SCV000609658.1
First in ClinVar: Nov 04, 2017
Last updated: Nov 04, 2017
Uncertain significance
(May 18, 2016)
criteria provided, single submitter
Method: clinical testing
Primary familial hypertrophic cardiomyopathy
Affected status: yes
Allele origin: germline
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute
Accession: SCV000740371.1
First in ClinVar: Apr 14, 2018
Last updated: Apr 14, 2018
Uncertain significance
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
MYH7-related skeletal myopathy
MYH7-related late-onset scapuloperoneal muscular dystrophy
Hypertrophic cardiomyopathy 1
Myopathy, myosin storage, autosomal recessive
Congenital myopathy with fiber type disproportion
Myosin storage myopathy
Dilated cardiomyopathy 1S
Affected status: unknown
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000896386.1
First in ClinVar: Mar 31, 2019
Last updated: Mar 31, 2019
Publications:
PubMed (1)
PubMed: 25741868
Uncertain significance
(Nov 29, 2018)
criteria provided, single submitter
Method: clinical testing
not specified
Affected status: not provided
Allele origin: germline
Laboratory for Molecular Medicine,Mass General Brigham Personalized Medicine
Accession: SCV000203861.4
First in ClinVar: Jan 30, 2015
Last updated: Apr 09, 2018
Publications:
PubMed (11)
Comment:
The p.Ser1776Gly variant in MYH7 has been identified in at least 12 individuals with HCM (Blair 2002, Fokstuen 2010, Homburger 2016, Walsh 2017, Kelly 2018, … (more)
Number of individuals with the variant: 8
Uncertain significance
(-)
criteria provided, single submitter
Method: research
Hypertrophic cardiomyopathy
Affected status: yes
Allele origin: unknown
Genetics and Genomics Program,Sidra Medicine
Accession: SCV001434151.1
First in ClinVar: Feb 27, 2021
Last updated: Feb 27, 2021
Number of individuals with the variant: 1
Uncertain significance
(Aug 04, 2020)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Affected status: unknown
Allele origin: germline
Ambry Genetics
Accession: SCV000736987.3
First in ClinVar: Apr 13, 2018
Last updated: Mar 25, 2020
Publications:
PubMed (6)
Comment:
The p.S1776G variant (also known as c.5326A>G), located in coding exon 35 of the MYH7 gene, results from an A to G substitution at nucleotide … (more)
Number of individuals with the variant: 1
Uncertain significance
(Apr 15, 2021)
criteria provided, single submitter
Method: clinical testing
not specified
Affected status: unknown
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001572358.1
First in ClinVar: Apr 29, 2021
Last updated: Apr 29, 2021
Publications:
PubMed (10)
Comment:
Variant summary: MYH7 c.5326A>G (p.Ser1776Gly) results in a non-conservative amino acid change located in the Myosin tail domain of the encoded protein sequence. Five of … (more)
Uncertain significance
(Sep 30, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Affected status: yes
Allele origin: germline
GeneDx
Accession: SCV000208629.10
First in ClinVar: Feb 24, 2015
Last updated: Dec 12, 2021
Comment:
In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance by the ClinGen … (more)
Uncertain significance
(Nov 24, 2020)
criteria provided, single submitter
Method: clinical testing
Cardiomyopathy
Affected status: unknown
Allele origin: germline
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario
Accession: SCV001333066.2
First in ClinVar: May 31, 2020
Last updated: Dec 29, 2021
Uncertain significance
(Apr 07, 2021)
criteria provided, single submitter
Method: clinical testing
Cardiomyopathy
Affected status: unknown
Allele origin: germline
Color Health, Inc
Accession: SCV001359756.3
First in ClinVar: Jun 22, 2020
Last updated: Jan 08, 2022
Comment:
This missense variant replaces serine with glycine at codon 1776 of the MYH7 protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
Uncertain significance
(Dec 11, 2021)
criteria provided, single submitter
Method: clinical testing
Hypertrophic cardiomyopathy
Affected status: unknown
Allele origin: germline
Invitae
Accession: SCV000546233.6
First in ClinVar: Apr 16, 2017
Last updated: May 16, 2022
Publications:
PubMed (7)
Comment:
This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 1776 of the MYH7 protein (p.Ser1776Gly). … (more)
Uncertain significance
(May 18, 2020)
criteria provided, single submitter
Method: clinical testing
Not provided
Affected status: yes
Allele origin: germline
AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002503353.1
First in ClinVar: Apr 23, 2022
Last updated: Apr 23, 2022
Publications:
PubMed (6)
Number of individuals with the variant: 1
Secondary finding: no
Uncertain significance
(Jan 06, 2015)
no assertion criteria provided
Method: clinical testing
not specified
Affected status: not provided
Allele origin: germline
Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000280364.1
First in ClinVar: Jun 01, 2016
Last updated: Jun 01, 2016
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)
Number of individuals with the variant: 17

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 in a lupus patient: a case of hydroxychloroquine cardiotoxicity. Chang A ESC heart failure 2019 PMID: 31493341
Defining genotype-phenotype relationships in patients with hypertrophic cardiomyopathy using cardiovascular magnetic resonance imaging. Miller RJH PloS one 2019 PMID: 31199839
Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance. van Lint FHM Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 2019 PMID: 30847666
Genetic Diagnostic Testing for Inherited Cardiomyopathies: Considerations for Offering Multi-Gene Tests in a Health Care Setting. Daoud H The Journal of molecular diagnostics : JMD 2019 PMID: 30731207
Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Ho CY Circulation 2018 PMID: 30297972
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
Hypertrophic cardiomyopathy clinical phenotype is independent of gene mutation and mutation dosage. Viswanathan SK PloS one 2017 PMID: 29121657
Using high-resolution variant frequencies to empower clinical genome interpretation. Whiffin N Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28518168
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
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Richards S Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
Distinguishing hypertrophic cardiomyopathy-associated mutations from background genetic noise. Kapplinger JD Journal of cardiovascular translational research 2014 PMID: 24510615
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
Localization of the binding site of the C-terminal domain of cardiac myosin-binding protein-C on the myosin rod. Flashman E The Biochemical journal 2007 PMID: 16918501
Mutation of the slow myosin heavy chain rod domain underlies hyaline body myopathy. Bohlega S Neurology 2004 PMID: 15136674
Mutations of the light meromyosin domain of the beta-myosin heavy chain rod in hypertrophic cardiomyopathy. Blair E Circulation research 2002 PMID: 11861413
Beta-myosin heavy chain gene mutations in familial hypertrophic cardiomyopathy: the usual suspect? McNally EM Circulation research 2002 PMID: 11861410
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/5d9a840f-4e17-4378-a41d-341cf6eab7b8 - - - -

Text-mined citations for rs369437262...

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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 May 28, 2022