ClinVar Genomic variation as it relates to human health
NM_000257.4(MYH7):c.2785GAG[2] (p.Glu931del)
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_000257.4(MYH7):c.2785GAG[2] (p.Glu931del)
Variation ID: 42934 Accession: VCV000042934.13
- Type and length
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Microsatellite, 3 bp
- Location
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Cytogenetic: 14q11.2 14: 23424036-23424038 (GRCh38) [ NCBI UCSC ] 14: 23893245-23893247 (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 May 29, 2016 Apr 20, 2024 Nov 23, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000257.4:c.2785GAG[2] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000248.2:p.Glu931del inframe deletion NM_000257.2:c.2791_2793delGAG NM_000257.3:c.2791_2793del NC_000014.9:g.23424036CTC[2] NC_000014.8:g.23893245CTC[2] NG_007884.1:g.16618GAG[2] LRG_384:g.16618GAG[2] LRG_384t1:c.2791_2793del - Protein change
- E931del
- Other names
- NM_000257.3(MYH7):c.2791_2793delGAG
- NM_000257.4(MYH7):c.2785_2787GAG[2]
- Canonical SPDI
- NC_000014.9:23424035:CTCCTCCTC:CTCCTC
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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MYH7 | No evidence available | No evidence available |
GRCh38 GRCh37 |
3578 | 4827 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Likely pathogenic (1) |
criteria provided, single submitter
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Oct 24, 2019 | RCV000158830.3 | |
Likely pathogenic (3) |
reviewed by expert panel
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Nov 23, 2021 | RCV000707732.12 |
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
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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
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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
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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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Likely pathogenic
(Nov 23, 2021)
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reviewed by expert panel
Method: curation
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Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen Cardiomyopathy Variant Curation Expert Panel
Accession: SCV000564439.5
First in ClinVar: May 29, 2016 Last updated: Dec 25, 2021 |
Comment:
The NM_000257.3(MYH7):c.2791_2793delGAG (p.Glu931del) variant has been reported in at least 8 individuals with HCM (PS4_Moderate; Tesson 1998 PMID:9829907; Richard 2013 PMID:12707239; Walsh 2017 PMID:27532257; Norrish … (more)
The NM_000257.3(MYH7):c.2791_2793delGAG (p.Glu931del) variant has been reported in at least 8 individuals with HCM (PS4_Moderate; Tesson 1998 PMID:9829907; Richard 2013 PMID:12707239; Walsh 2017 PMID:27532257; Norrish 2019 PMID:31006259; GeneDx pers. comm., Invitae pers. comm., LMM pers. comm., OMGL pers.comm.) and segregated with disease in 5 affected individuals with HCM in 1 family (PP1_Moderate; Tesson 1998 PMID:9829907). This variant was absent from large population studies (PM2; gnomAD v2.1.1, http://gnomad.broadinstitute.org). This variant is a deletion of 1 amino acid at position 931 and is not predicted to alter the protein reading-frame. Given that only 1 amino acid has been deleted, the expert panel felt that adjusting to supporting evidence would be more appropriate in this case (PM4_Supporting). In summary, this variant meets criteria to be classified as likely pathogenic for hypertrophic cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (Kelly 2018 PMID:29300372): PS4_ Moderate; PP1_Moderate; PM2; PM4_Supporting. (less)
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Pathogenic
(Dec 20, 2023)
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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: SCV000836841.6
First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant, c.2791_2793del, results in the deletion of 1 amino acid(s) of the MYH7 protein (p.Glu931del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.2791_2793del, results in the deletion of 1 amino acid(s) of the MYH7 protein (p.Glu931del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with hypertrophic cardiomyopathy (HCM) (PMID: 9829907, 27532257). It has also been observed to segregate with disease in related individuals. This variant is also known as Glu930 codon deletion. ClinVar contains an entry for this variant (Variation ID: 42934). This variant disrupts the p.Glu931 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15358028, 24111713, 25351510). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
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Likely Pathogenic
(Jun 05, 2023)
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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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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000059478.6
First in ClinVar: May 03, 2013 Last updated: Apr 20, 2024 |
Comment:
The p.Glu931del variant has been reported in at least 8 individuals with hypertrophic cardiomyopathy (HCM; Tesson 1998 PMID:9829907; Richard 2013 PMID:12707239; Walsh 2017 PMID:27532257; Norrish … (more)
The p.Glu931del variant has been reported in at least 8 individuals with hypertrophic cardiomyopathy (HCM; Tesson 1998 PMID:9829907; Richard 2013 PMID:12707239; Walsh 2017 PMID:27532257; Norrish 2019 PMID:31006259; GeneDx pers. comm., Invitae pers. comm., LMM pers. comm., OMGL pers.comm.) and segregated with disease in 5 affected individuals (Tesson 1998 PMID:9829907). This variant was absent from large population studies (gnomAD v3.2.1, http://gnomad.broadinstitute.org). In vitro functional studies provide some evidence that this variant impacts protein function (Singh 2021 PMID: 34051236). This variant is a deletion of 1 amino acid at position 931 and is not predicted to alter the protein reading-frame. In summary, this variant meets criteria to be classified as likely pathogenic for autosomal dominant HCM. ACMG/AMP criteria applied: PS4_ Moderate, PP1_Moderate, PM2_Supporting, PM4_Supporting, PS3_Supporting. (less)
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Likely pathogenic
(Oct 24, 2019)
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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: SCV000208765.10
First in ClinVar: Feb 24, 2015 Last updated: May 29, 2016 |
Comment:
In-frame deletion of one amino acid, also referred to as E930del in the published literature due to alternate nomenclature; Not observed in large population cohorts … (more)
In-frame deletion of one amino acid, also referred to as E930del in the published literature due to alternate nomenclature; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in ClinVar as likely pathogenic by the ClinGen Inherited Cardiomyopathy Variant Curation Expert Panel (ClinVar Variant ID 42934 ; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 9829907, 31006259, 12707239, 29300372, 27532257) (less)
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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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Mutations in myosin S2 alter cardiac myosin-binding protein-C interaction in hypertrophic cardiomyopathy in a phosphorylation-dependent manner. | Singh RR | The Journal of biological chemistry | 2021 | PMID: 34051236 |
Yield of Clinical Screening for Hypertrophic Cardiomyopathy in Child First-Degree Relatives. | Norrish G | Circulation | 2019 | PMID: 31006259 |
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 |
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 |
Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy. | Lopes LR | Heart (British Cardiac Society) | 2015 | PMID: 25351510 |
Genetics of hypertrophic cardiomyopathy in Norway. | Berge KE | Clinical genetics | 2014 | PMID: 24111713 |
Comprehensive analysis of the beta-myosin heavy chain gene in 389 unrelated patients with hypertrophic cardiomyopathy. | Van Driest SL | Journal of the American College of Cardiology | 2004 | PMID: 15358028 |
Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. | Richard P | Circulation | 2003 | PMID: 12707239 |
Low-density DNA microarrays are versatile tools to screen for known mutations in hypertrophic cardiomyopathy. | Waldmüller S | Human mutation | 2002 | PMID: 11968089 |
Genotype-phenotype analysis in four families with mutations in beta-myosin heavy chain gene responsible for familial hypertrophic cardiomyopathy. | Tesson F | Human mutation | 1998 | PMID: 9829907 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/5fe5fef0-e52a-4616-8e14-0b7ae7e8da51 | - | - | - | - |
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Text-mined citations for rs397516172 ...
HelpRecord last updated Apr 20, 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.