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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:
9 (Most recent: Mar 28, 2019)
Last evaluated:
Dec 15, 2016
Accession:
VCV000177629.2
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
NC_000014.8:g.23884437T>C
NC_000014.9:g.23415228T>C
LRG_384t1:c.5326A>G
... more HGVS
Protein change
S1776G
Other names
NM_000257.3(MYH7):c.5326A>G
Functional consequence
-
Global minor allele frequency (GMAF)
-

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

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 reviewed by expert panel Dec 15, 2016 RCV000462813.5
Uncertain significance 3 criteria provided, multiple submitters, no conflicts Nov 29, 2018 RCV000154209.3
Uncertain significance 1 criteria provided, single submitter May 18, 2016 RCV000168915.3
Uncertain significance 1 criteria provided, single submitter Apr 19, 2017 RCV000514376.1
Uncertain significance 1 criteria provided, single submitter Jun 11, 2016 RCV000620185.1
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
1630 1931

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Dec 15, 2016)
reviewed by expert panel
Method: curation
Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Allele origin: germline
ClinGen Inherited Cardiomyopathy Variant Curation Expert Panel,
FDA Recognized Database
Accession: SCV000564457.4
Submitted: (Feb 25, 2019)
Evidence details
Publications
PubMed (1)
Other databases
https://erepo.clinicalgenome.o...
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
Allele origin: germline
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics
Accession: SCV000609658.1
Submitted: (Oct 05, 2017)
Evidence details
Uncertain significance
(May 09, 2017)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
GeneDx
Accession: SCV000208629.9
Submitted: (Nov 28, 2017)
Evidence details
Comment:
The S1776G variant was identified in two siblings with HCM but failed to segregate in a third sibling, and was absent from 400 population-matched control ... (more)
Uncertain significance
(May 18, 2016)
criteria provided, single submitter
Method: clinical testing
None
Allele origin: germline
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute
Accession: SCV000740371.1
Submitted: (Aug 02, 2017)
Evidence details
Uncertain significance
(Jun 11, 2016)
criteria provided, single submitter
Method: clinical testing
cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000736987.2
Submitted: (Jul 30, 2018)
Evidence details
Publications
PubMed (6)
Comment:
Lines of evidence used in support of classification: Insufficient evidence
Uncertain significance
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Myopathy, distal, 1
Scapuloperoneal myopathy, MYH7-related
Familial hypertrophic cardiomyopathy 1
Myopathy, myosin storage, autosomal recessive
Congenital myopathy with fiber type disproportion
Myosin storage myopathy
Dilated cardiomyopathy 1S
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000896386.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Uncertain significance
(Dec 28, 2018)
criteria provided, single submitter
Method: clinical testing
Hypertrophic cardiomyopathy
Allele origin: germline
Invitae
Accession: SCV000546233.4
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (6)
Comment:
This sequence change replaces serine with glycine at codon 1776 of the MYH7 protein (p.Ser1776Gly). The serine residue is highly conserved and there is a ... (more)
Uncertain significance
(Nov 29, 2018)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000203861.4
Submitted: (Mar 21, 2019)
Evidence details
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)
Uncertain significance
(Jan 06, 2015)
no assertion criteria provided
Method: clinical testing
not specified
Allele origin: germline
Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000280364.1
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)

Citations for this variant

Title Author Journal Year Link
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
The sarcomeric M-region: a molecular command center for diverse cellular processes. Hu LY BioMed research international 2015 PMID: 25961035
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
Cardiac structural and sarcomere genes associated with cardiomyopathy exhibit marked intolerance of genetic variation. Pan S Circulation. Cardiovascular genetics 2012 PMID: 23074333
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 - - - -

Record last updated Feb 17, 2020