ClinVar Genomic variation as it relates to human health
NM_002474.3(MYH11):c.739C>T (p.Arg247Cys)
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.
Uncertain significance(4); Benign(1); Likely benign(13)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_002474.3(MYH11):c.739C>T (p.Arg247Cys)
Variation ID: 161317 Accession: VCV000161317.56
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p13.11 16: 15778831 (GRCh38) [ NCBI UCSC ] 16: 15872688 (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 Dec 7, 2014 Apr 15, 2024 Mar 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002474.3:c.739C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002465.1:p.Arg247Cys missense NM_001040113.2:c.760C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001035202.1:p.Arg254Cys missense NM_001040114.2:c.760C>T NP_001035203.1:p.Arg254Cys missense NM_022844.3:c.739C>T NP_074035.1:p.Arg247Cys missense NC_000016.10:g.15778831G>A NC_000016.9:g.15872688G>A NG_009299.1:g.83200C>T LRG_1401:g.83200C>T LRG_1401t1:c.739C>T LRG_1401p1:p.Arg247Cys LRG_1401t2:c.760C>T LRG_1401p2:p.Arg254Cys - Protein change
- R254C, R247C
- Other names
- p.R247C:CGC>TGC
- Canonical SPDI
- NC_000016.10:15778830:G:A
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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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0.00060 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00060
1000 Genomes Project 30x 0.00078
Trans-Omics for Precision Medicine (TOPMed) 0.00144
The Genome Aggregation Database (gnomAD) 0.00174
The Genome Aggregation Database (gnomAD), exomes 0.00174
Exome Aggregation Consortium (ExAC) 0.00194
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00246
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
Help
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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MYH11 | No evidence available | No evidence available |
GRCh38 GRCh38 GRCh37 |
1786 | 3402 |
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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Likely benign (1) |
no assertion criteria provided
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Jun 1, 2014 | RCV000148692.10 | |
Uncertain significance (1) |
no assertion criteria provided
|
Apr 11, 2014 | RCV000157329.9 | |
Conflicting interpretations of pathogenicity (7) |
criteria provided, conflicting classifications
|
Jan 29, 2024 | RCV000206298.35 | |
Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Oct 22, 2019 | RCV000182546.18 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jun 5, 2014 | RCV000251088.12 | |
Uncertain significance (1) |
criteria provided, single submitter
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Nov 1, 2016 | RCV000659901.9 | |
Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Jan 25, 2023 | RCV000776119.16 | |
not provided (1) |
no classification provided
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- | RCV000844919.9 | |
Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2024 | RCV001092826.24 | |
Uncertain significance (1) |
criteria provided, single submitter
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Mar 30, 2021 | RCV003224171.8 | |
Likely benign (1) |
criteria provided, single submitter
|
Oct 5, 2020 | RCV003935256.1 | |
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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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Likely benign
(Mar 31, 2016)
|
criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000539829.1
First in ClinVar: Jan 07, 2017 Last updated: Jan 07, 2017 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.3% European; ClinVar: 2 VUS, 1 LB (less)
Method: Genome/Exome Filtration
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Likely benign
(Oct 19, 2016)
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criteria provided, single submitter
Method: clinical testing
|
Aortic aneurysm, familial thoracic 4
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000744026.1 First in ClinVar: Apr 19, 2018 Last updated: Apr 19, 2018 |
|
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Likely benign
(Jul 22, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Aortic aneurysm, familial thoracic 4
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000745486.1 First in ClinVar: Apr 19, 2018 Last updated: Apr 19, 2018 |
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Uncertain significance
(Nov 01, 2016)
|
criteria provided, single submitter
Method: clinical testing
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Connective tissue disorder
Affected status: yes
Allele origin:
germline
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Center for Human Genetics, Inc, Center for Human Genetics, Inc
Accession: SCV000781803.1
First in ClinVar: Jul 09, 2018 Last updated: Jul 09, 2018 |
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Uncertain significance
(Nov 30, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Aortic aneurysm, familial thoracic 4
Affected status: unknown
Allele origin:
germline
|
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV000898839.1
First in ClinVar: Apr 25, 2019 Last updated: Apr 25, 2019 |
Comment:
MYH11 NM_002474.2 exon 7 p.Arg247Cys (c.739C>T): This variant has been reported in the literature (also referred to as p.Arg254Cys) in at least one individual with … (more)
MYH11 NM_002474.2 exon 7 p.Arg247Cys (c.739C>T): This variant has been reported in the literature (also referred to as p.Arg254Cys) in at least one individual with abdominal aortic aneurysm, segregating with disease in one affected family member (Van de Luijtgaarden 2015 PMID:26017485). This variant is present in 0.3% (393/129162) of European alleles in the Genome Aggregation Database, including 2 homozygotes (http://gnomad.broadinstitute.org/variant/16-15872688-G-A). This variant is also present in ClinVar, with several labs classifying this variant as likely benign (Variation ID:161317). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In addition, functional studies have shown a deleterious effect of this variant (Kuang 2012 PMID: 22511748; Bellini 2015 PMID: 25433566). However, these studies may not accurately represent in vivo biological function. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. (less)
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Likely benign
(Apr 16, 2018)
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criteria provided, single submitter
Method: clinical testing
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Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000910997.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
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Benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Aortic aneurysm, familial thoracic 4
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001139962.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Likely benign
(Mar 23, 2018)
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criteria provided, single submitter
Method: clinical testing
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Aortic aneurysm, familial thoracic 4
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001278181.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Likely benign
(Oct 22, 2019)
|
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: SCV001362299.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: MYH11 c.760C>T (p.Arg254Cys, also known as c.739C>T/p.Arg247Cys) results in a non-conservative amino acid change located in the Myosin head, motor domain (IPR001609) of … (more)
Variant summary: MYH11 c.760C>T (p.Arg254Cys, also known as c.739C>T/p.Arg247Cys) results in a non-conservative amino acid change located in the Myosin head, motor domain (IPR001609) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0017 in 282840 control chromosomes, predominantly at a frequency of 0.003 within the Non-Finnish European subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 2400 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYH11 causing Aortopathy phenotype (1.3e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. The variant, c.760C>T, has been reported in the literature in at least one family with 2 affected individuals (Van de Luijtgaarden_2015), and in patients with aortic disease and no family history (Kuang_2012). These reports however do not provide unequivocal conclusions about association of the variant with Aortopathy. Publications reported experimental evidence evaluating an impact on protein function, and demonstrated that the p.Arg247Cys substitution decreases the ATPase activity (actin-activated), and the rate of actin filament sliding, and in a knock-in mouse model the mutant aorta displayed a decreased contractile response, but there was no overall vascular phenotype under normal conditions in either homozygous or heterozygous mice (Kuang_2012, Huang_2018). However, the homozygous mutant knock-in mice were more vulnerable to alterations in hemodynamic loading (Bellini_2015), or developed aortic dilation when crossed with the ACTA2 +/- mice, indicating that two variants not known to cause disease may lead to aortic enlargement in combination (Kwartler_2018). Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (likely benign 7x, VUS 2x). Based on the evidence outlined above, the variant is unlikely to cause familial thoracic aortic disease, but more evidence is required to determine if it might represent a low penetrance risk variant, therefore it was classified as likely benign. (less)
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Likely benign
(Jun 02, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000234894.11
First in ClinVar: Jul 05, 2015 Last updated: Apr 09, 2018 |
Comment:
This variant is associated with the following publications: (PMID: 22968129, 16444274, 25407000, 24337657, 10854329, 22511748, 25433566, 26893369, 27879251, 27153395, 29494672, 17956658, 17666408, 14722581, 10199307, 7923625, … (more)
This variant is associated with the following publications: (PMID: 22968129, 16444274, 25407000, 24337657, 10854329, 22511748, 25433566, 26893369, 27879251, 27153395, 29494672, 17956658, 17666408, 14722581, 10199307, 7923625, 26792327, 25424711, 24676022, 27418595, 26017485, 25637381, 26332594, 27535533, 29961567, 32220188, 32068640) (less)
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Uncertain significance
(Jun 05, 2014)
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criteria provided, single submitter
Method: clinical testing
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Hereditary disease
Affected status: yes
Allele origin:
germline
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Ambry Genetics
Accession: SCV000318112.4
First in ClinVar: Oct 02, 2016 Last updated: Dec 11, 2022 |
Comment:
Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected
Clinical Features:
MR/ID/DD (present) , Phenotype is progressive (present) , Dysmorphic features (present) , Cardiovascular (child onset) (present) , Musculoskeletal/Structural (child onset) (present) , Neurologic (child onset) … (more)
MR/ID/DD (present) , Phenotype is progressive (present) , Dysmorphic features (present) , Cardiovascular (child onset) (present) , Musculoskeletal/Structural (child onset) (present) , Neurologic (child onset) (present) , Craniofacial (child onset) (present) (less)
Family history: yes
Sex: male
Ethnicity/Population group: European-origin,Asian-origin
Segregation observed: yes
|
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Uncertain significance
(Mar 30, 2021)
|
criteria provided, single submitter
Method: clinical testing
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Megacystis-microcolon-intestinal hypoperistalsis syndrome 2
Aortic aneurysm, familial thoracic 4 Visceral myopathy 2
Affected status: unknown
Allele origin:
germline
|
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV003920234.1
First in ClinVar: Apr 30, 2023 Last updated: Apr 30, 2023 |
Comment:
MYH11 NM_002474.2 exon 7 p.Arg247Cys (c.739C>T): This variant has been reported in the literature (also referred to as p.Arg254Cys) in at least one individual with … (more)
MYH11 NM_002474.2 exon 7 p.Arg247Cys (c.739C>T): This variant has been reported in the literature (also referred to as p.Arg254Cys) in at least one individual with abdominal aortic aneurysm, segregating with disease in one affected family member (Van de Luijtgaarden 2015 PMID:26017485). This variant is present in 0.3% (393/129162) of European alleles in the Genome Aggregation Database, including 2 homozygotes (http://gnomad.broadinstitute.org/variant/16-15872688-G-A). This variant is also present in ClinVar, with several labs classifying this variant as likely benign (Variation ID:161317). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In addition, functional studies have shown a deleterious effect of this variant (Kuang 2012 PMID: 22511748; Bellini 2015 PMID: 25433566). However, these studies may not accurately represent in vivo biological function. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. (less)
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Likely benign
(Jan 25, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV001332918.4
First in ClinVar: May 31, 2020 Last updated: Feb 04, 2024 |
|
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Likely benign
(Nov 15, 2023)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000604349.5
First in ClinVar: Sep 28, 2017 Last updated: Feb 20, 2024 |
|
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Likely benign
(Oct 05, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
MYH11-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004756302.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
|
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Likely benign
(Mar 19, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002673954.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, … (more)
This alteration is classified as likely 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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Likely benign
(Jan 29, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Aortic aneurysm, familial thoracic 4
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000261650.11
First in ClinVar: Jan 31, 2016 Last updated: Feb 20, 2024 |
|
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Likely benign
(Mar 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001249520.13
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Comment:
MYH11: PP3, BS2
Number of individuals with the variant: 2
|
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Likely benign
(Jun 01, 2014)
|
no assertion criteria provided
Method: research
|
Altered myosin contractile function
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
CSER _CC_NCGL, University of Washington
Study: ESP 6500 variant annotation
Accession: SCV000190419.1 First in ClinVar: Dec 07, 2014 Last updated: Dec 07, 2014 |
|
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Likely benign
(Feb 04, 2014)
|
no assertion criteria provided
Method: clinical testing
|
Aortic aneurysm, familial thoracic 4
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000745975.1 First in ClinVar: Apr 19, 2018 Last updated: Apr 19, 2018 |
|
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Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001799022.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Uncertain significance
(Apr 11, 2014)
|
no assertion criteria provided
Method: clinical testing
|
Loeys-Dietz syndrome
Affected status: yes
Allele origin:
germline
|
Blueprint Genetics
Accession: SCV000207066.1
First in ClinVar: Feb 07, 2015 Last updated: Feb 07, 2015 |
Number of individuals with the variant: 1
|
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not provided
(-)
|
no classification provided
Method: phenotyping only
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Aortic aneurysm, familial thoracic 4
Congenital aneurysm of ascending aorta
Affected status: unknown
Allele origin:
unknown
|
GenomeConnect, ClinGen
Accession: SCV000986726.1
First in ClinVar: Aug 31, 2019 Last updated: Aug 31, 2019 |
Comment:
Variant interpretted as Uncertain significance and reported on 03/28/2017 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report … (more)
Variant interpretted as Uncertain significance and reported on 03/28/2017 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Abnormality of the mouth (present) , Oral-pharyngeal dysphagia (present) , Abnormality of the nose (present) , Abnormality of globe size (present) , Abnormality of vision … (more)
Abnormality of the mouth (present) , Oral-pharyngeal dysphagia (present) , Abnormality of the nose (present) , Abnormality of globe size (present) , Abnormality of vision (present) , Tinnitus (present) , Hyperacusis (present) , Vertigo (present) , Morphological abnormality of the central nervous system (present) , Abnormality of coordination (present) , Stereotypy (present) , Anxiety (present) , Depressivity (present) , Short attention span (present) , Atrophic scars (present) , Hypohidrosis (present) , Generalized abnormality of skin (present) , Epidermal thickening (present) , Hyperextensible skin (present) , Abnormality of limb bone morphology (present) , Abnormality of the curvature of the vertebral column (present) , Joint hypermobility (present) , Hip dysplasia (present) , Abnormality of muscle physiology (present) , Abnormality of the musculature of the limbs (present) , Abnormality of the musculature of the thorax (present) , Arrhythmia (present) , Syncope (present) , Abnormality of cardiovascular system morphology (present) , Hypertension (present) , Asthma (present) , Abnormality of the upper respiratory tract (present) , Abnormality of esophagus morphology (present) , Abnormality of the stomach (present) , Gastrointestinal dysmotility (present) , Abnormal large intestine physiology (present) , Abnormality of the bladder (present) , Abnormal renal physiology (present) , Abnormality of urine homeostasis (present) , Autoimmunity (present) , Immunodeficiency (present) , Abnormal inflammatory response (present) , Recurrent infections (present) , Bleeding with minor or no trauma (present) , Bruising susceptibility (present) , Persistent bleeding after trauma (present) , Abnormality of the musculature (present) (less)
Age: 30-39 years
Sex: female
Testing laboratory: GeneDx
Date variant was reported to submitter: 2017-03-28
Testing laboratory interpretation: Uncertain significance
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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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Variants of Unknown Significance in Genes Associated with Heritable Thoracic Aortic Disease Can Be Low Penetrant "Risk Variants". | Kwartler CS | American journal of human genetics | 2018 | PMID: 29961567 |
Genetic approaches to identify pathological limitations in aortic smooth muscle contraction. | Huang J | PloS one | 2018 | PMID: 29494672 |
Altered Smooth Muscle Cell Force Generation as a Driver of Thoracic Aortic Aneurysms and Dissections. | Milewicz DM | Arteriosclerosis, thrombosis, and vascular biology | 2017 | PMID: 27879251 |
Utilization of Whole Exome Sequencing to Identify Causative Mutations in Familial Congenital Heart Disease. | LaHaye S | Circulation. Cardiovascular genetics | 2016 | PMID: 27418595 |
Myosin isoforms and the mechanochemical cross-bridge cycle. | Walklate J | The Journal of experimental biology | 2016 | PMID: 26792327 |
Identification of Medically Actionable Secondary Findings in the 1000 Genomes. | Olfson E | PloS one | 2015 | PMID: 26332594 |
First genetic analysis of aneurysm genes in familial and sporadic abdominal aortic aneurysm. | van de Luijtgaarden KM | Human genetics | 2015 | PMID: 26017485 |
Myh11(R247C/R247C) mutations increase thoracic aorta vulnerability to intramural damage despite a general biomechanical adaptivity. | Bellini C | Journal of biomechanics | 2015 | PMID: 25433566 |
Further delineation of the KAT6B molecular and phenotypic spectrum. | Gannon T | European journal of human genetics : EJHG | 2015 | PMID: 25424711 |
A homozygous loss-of-function variant in MYH11 in a case with megacystis-microcolon-intestinal hypoperistalsis syndrome. | Gauthier J | European journal of human genetics : EJHG | 2015 | PMID: 25407000 |
Heterozygous de novo and inherited mutations in the smooth muscle actin (ACTG2) gene underlie megacystis-microcolon-intestinal hypoperistalsis syndrome. | Wangler MF | PLoS genetics | 2014 | PMID: 24676022 |
De novo ACTG2 mutations cause congenital distended bladder, microcolon, and intestinal hypoperistalsis. | Thorson W | Human genetics | 2014 | PMID: 24337657 |
Incomplete segregation of MYH11 variants with thoracic aortic aneurysms and dissections and patent ductus arteriosus. | Harakalova M | European journal of human genetics : EJHG | 2013 | PMID: 22968129 |
Rare, nonsynonymous variant in the smooth muscle-specific isoform of myosin heavy chain, MYH11, R247C, alters force generation in the aorta and phenotype of smooth muscle cells. | Kuang SQ | Circulation research | 2012 | PMID: 22511748 |
De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction. | Milewicz DM | American journal of medical genetics. Part A | 2010 | PMID: 20734336 |
Investigation of the MYH11 gene in sporadic patients with an isolated persistently patent arterial duct. | Zhu L | Cardiology in the young | 2007 | PMID: 17956658 |
MYH11 mutations result in a distinct vascular pathology driven by insulin-like growth factor 1 and angiotensin II. | Pannu H | Human molecular genetics | 2007 | PMID: 17666408 |
Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus. | Zhu L | Nature genetics | 2006 | PMID: 16444274 |
Familial thoracic aortic aneurysm/dissection with patent ductus arteriosus: genetic arguments for a particular pathophysiological entity. | Khau Van Kien P | European journal of human genetics : EJHG | 2004 | PMID: 14722581 |
Smooth-muscle contraction without smooth-muscle myosin. | Morano I | Nature cell biology | 2000 | PMID: 10854329 |
Familial patterns of thoracic aortic aneurysms. | Coady MA | Archives of surgery (Chicago, Ill. : 1960) | 1999 | PMID: 10199307 |
Smooth muscle myosin heavy chain exclusively marks the smooth muscle lineage during mouse embryogenesis. | Miano JM | Circulation research | 1994 | PMID: 7923625 |
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Text-mined citations for rs150759461 ...
HelpRecord last updated Apr 15, 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.