ClinVar Genomic variation as it relates to human health
NM_000256.3(MYBPC3):c.833G>A (p.Gly278Glu)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000256.3(MYBPC3):c.833G>A (p.Gly278Glu)
Variation ID: 42797 Accession: VCV000042797.44
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p11.2 11: 47347669 (GRCh38) [ NCBI UCSC ] 11: 47369220 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 30, 2017 Apr 20, 2024 Feb 5, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000256.3:c.833G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000247.2:p.Gly278Glu missense NC_000011.10:g.47347669C>T NC_000011.9:g.47369220C>T NG_007667.1:g.10034G>A LRG_386:g.10034G>A LRG_386t1:c.833G>A LRG_386p1:p.Gly278Glu Q14896:p.Gly278Glu - Protein change
- G278E
- Other names
- p.G278E:GGA>GAA
- Canonical SPDI
- NC_000011.10:47347668:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00379 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00427
Trans-Omics for Precision Medicine (TOPMed) 0.00449
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00518
The Genome Aggregation Database (gnomAD), exomes 0.00097
Exome Aggregation Consortium (ExAC) 0.00295
1000 Genomes Project 30x 0.00328
1000 Genomes Project 0.00379
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MYBPC3 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3892 | 3909 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Benign (4) |
criteria provided, multiple submitters, no conflicts
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Nov 17, 2020 | RCV000035673.28 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Feb 16, 2019 | RCV000512634.14 | |
Benign (1) |
criteria provided, single submitter
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Oct 20, 2017 | RCV000618768.10 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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May 28, 2019 | RCV000625031.11 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Feb 5, 2024 | RCV001086874.20 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Sep 20, 2022 | RCV001711096.16 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Benign
(Oct 20, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000736385.4
First in ClinVar: Apr 14, 2018 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Number of individuals with the variant: 1
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Benign
(Jan 07, 2014)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000203048.7
First in ClinVar: Jan 31, 2015 Last updated: Apr 09, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Benign
(Nov 17, 2020)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000059324.6
First in ClinVar: May 03, 2013 Last updated: May 29, 2021 |
Comment:
p.Gly278Glu in exon 8 of MYBPC3: This variant is not expected to have clinical significance because it has been identified in 2.6% (76/2968) of African … (more)
p.Gly278Glu in exon 8 of MYBPC3: This variant is not expected to have clinical significance because it has been identified in 2.6% (76/2968) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs147315081). (less)
Number of individuals with the variant: 27
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Benign
(Sep 20, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000885758.4
First in ClinVar: Feb 18, 2019 Last updated: Mar 04, 2023 |
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Benign
(Jun 07, 2016)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy 4
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000743570.1 First in ClinVar: Apr 20, 2018 Last updated: Apr 20, 2018 |
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Benign
(Oct 16, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cardiomyopathy
Affected status: unknown
Allele origin:
germline
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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Study: Canadian Open Genetics Repository
Accession: SCV000608291.2 First in ClinVar: Oct 30, 2017 Last updated: May 06, 2019 |
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Benign
(Apr 23, 2018)
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criteria provided, single submitter
Method: clinical testing
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Cardiomyopathy
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000911582.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
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Benign
(Feb 16, 2019)
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criteria provided, single submitter
Method: clinical testing
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Cardiomyopathy
Affected status: yes
Allele origin:
germline
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Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego
Accession: SCV000995359.1
First in ClinVar: Oct 11, 2019 Last updated: Oct 11, 2019 |
Number of individuals with the variant: 1
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Benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy 4
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001138313.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Benign
(Aug 27, 2019)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
Accession: SCV001433439.1
First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020 |
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Benign
(Nov 21, 2018)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000170453.13
First in ClinVar: Jun 23, 2014 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 12707239, 21310275, 26332594, 18403758, 20624503, 22763267, 23299917, 25525159, 27532831, 30871747)
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000558167.9
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
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Benign
(Feb 05, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004834716.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Number of individuals with the variant: 224
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001917872.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Benign
(Oct 10, 2022)
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no assertion criteria provided
Method: clinical testing
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Hypertrophic cardiomyopathy
Affected status: yes
Allele origin:
germline
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Cohesion Phenomics
Accession: SCV003800611.2
First in ClinVar: Feb 13, 2023 Last updated: Apr 15, 2023 |
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Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Identification of Medically Actionable Secondary Findings in the 1000 Genomes. | Olfson E | PloS one | 2015 | PMID: 26332594 |
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. | Xiong HY | Science (New York, N.Y.) | 2015 | PMID: 25525159 |
New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants. | Andreasen C | European journal of human genetics : EJHG | 2013 | PMID: 23299917 |
Population-based variation in cardiomyopathy genes. | Golbus JR | Circulation. Cardiovascular genetics | 2012 | PMID: 22763267 |
Prevalence and spectrum of mutations in a cohort of 192 unrelated patients with hypertrophic cardiomyopathy. | Millat G | European journal of medical genetics | 2010 | PMID: 20624503 |
Shared genetic causes of cardiac hypertrophy in children and adults. | Morita H | The New England journal of medicine | 2008 | PMID: 18403758 |
Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. | Richard P | Circulation | 2003 | PMID: 12707239 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MYBPC3 | - | - | - | - |
Text-mined citations for rs147315081 ...
HelpRecord last updated May 19, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.