ClinVar Genomic variation as it relates to human health
NM_002471.4(MYH6):c.2946G>A (p.Glu982=)
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_002471.4(MYH6):c.2946G>A (p.Glu982=)
Variation ID: 44475 Accession: VCV000044475.55
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 14q11.2 14: 23393501 (GRCh38) [ NCBI UCSC ] 14: 23862710 (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 2, 2016 Sep 29, 2024 Jul 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002471.4:c.2946G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002462.2:p.Glu982= synonymous NC_000014.9:g.23393501C>T NC_000014.8:g.23862710C>T NG_023444.1:g.19777G>A LRG_389:g.19777G>A LRG_389t1:c.2946G>A LRG_389p1:p.Glu982= - Protein change
- Other names
- -
- Canonical SPDI
- NC_000014.9:23393500: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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0.00419 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00419
1000 Genomes Project 30x 0.00437
Trans-Omics for Precision Medicine (TOPMed) 0.00731
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00861
Exome Aggregation Consortium (ExAC) 0.00985
The Genome Aggregation Database (gnomAD) 0.01048
The Genome Aggregation Database (gnomAD), exomes 0.01061
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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MYH6 | - | - |
GRCh38 GRCh37 |
1867 | 2382 |
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 (6) |
criteria provided, multiple submitters, no conflicts
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May 29, 2018 | RCV000037466.22 | |
Benign (1) |
criteria provided, single submitter
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Jan 31, 2024 | RCV000234739.21 | |
Benign (1) |
criteria provided, single submitter
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Dec 18, 2014 | RCV000244702.11 | |
Benign (1) |
criteria provided, single submitter
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Nov 18, 2015 | RCV000770447.10 | |
Benign (4) |
criteria provided, multiple submitters, no conflicts
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Jul 1, 2024 | RCV001529419.31 | |
Benign (1) |
criteria provided, single submitter
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Feb 17, 2022 | RCV002477093.8 |
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
(Nov 08, 2016)
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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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GeneDx
Accession: SCV000515357.4
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Benign
(Nov 18, 2015)
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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: SCV000901890.1 First in ClinVar: May 06, 2019 Last updated: May 06, 2019 |
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Benign
(May 29, 2018)
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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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000917839.1
First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019 |
Comment:
Variant summary: MYH6 c.2946G>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these … (more)
Variant summary: MYH6 c.2946G>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.011 in 277200 control chromosomes in the gnomAD database, including 37 homozygotes. The observed variant frequency is approximately 439-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in MYH6 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. The variant, c.2946G>A, has been reported in the literature in individuals affected with Cardiomyopathy (Posch_2011). This report does not provide an unequivocal conclusion about the association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely benign/benign." Based on the evidence outlined above, the variant was classified as benign. (less)
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Benign
(Jan 27, 2012)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000061124.5
First in ClinVar: May 03, 2013 Last updated: Mar 08, 2017 |
Comment:
Glu982Glu in exon 23 of MYH6: This variant is classified as benign based on its high frequency in the general population (dbSNP rs145274612; NHLBI Exome … (more)
Glu982Glu in exon 23 of MYH6: This variant is classified as benign based on its high frequency in the general population (dbSNP rs145274612; NHLBI Exome Sequenc ing Project, http://evs.gs.washington.edu/EVS). (less)
Number of individuals with the variant: 29
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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 14
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000287402.10
First in ClinVar: Jul 01, 2016 Last updated: Feb 14, 2024 |
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Benign
(Nov 09, 2023)
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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: SCV001157077.6
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
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Benign
(Jul 01, 2024)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002545159.14
First in ClinVar: Jul 09, 2022 Last updated: Aug 04, 2024 |
Comment:
MYH6: BP4, BP7, BS1, BS2
Number of individuals with the variant: 10
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Benign
(-)
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criteria provided, single submitter
Method: not provided
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not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005232864.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
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Benign
(Feb 17, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy 1
Hypertrophic cardiomyopathy 14 Dilated cardiomyopathy 1EE Atrial septal defect 3 Sick sinus syndrome 3, susceptibility to
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002803350.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Benign
(Dec 18, 2014)
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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: SCV000317890.7
First in ClinVar: Oct 02, 2016 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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)
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001742849.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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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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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001955571.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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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 DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001968156.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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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: SCV001923960.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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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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Cardiac alpha-myosin (MYH6) is the predominant sarcomeric disease gene for familial atrial septal defects. | Posch MG | PloS one | 2011 | PMID: 22194935 |
Text-mined citations for rs145274612 ...
HelpRecord last updated Sep 29, 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.