ClinVar Genomic variation as it relates to human health
NM_002474.3(MYH11):c.5516C>T (p.Ala1839Val)
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(9); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_002474.3(MYH11):c.5516C>T (p.Ala1839Val)
Variation ID: 197069 Accession: VCV000197069.27
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 16p13.11 16: 15715261 (GRCh38) [ NCBI UCSC ] 16: 15809118 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 6, 2016 Feb 20, 2024 Jan 24, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_002474.3:c.5516C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002465.1:p.Ala1839Val missense NM_017668.3:c.948-8930G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_001040113.2:c.5537C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001035202.1:p.Ala1846Val missense NM_001040114.2:c.5537C>T NP_001035203.1:p.Ala1846Val missense NM_001143979.2:c.948-8930G>A intron variant NM_022844.3:c.5516C>T NP_074035.1:p.Ala1839Val missense NC_000016.10:g.15715261G>A NC_000016.9:g.15809118G>A NG_009299.1:g.146770C>T NG_021210.1:g.76995G>A LRG_1401:g.146770C>T LRG_1401t1:c.5516C>T LRG_1401p1:p.Ala1839Val LRG_1401t2:c.5537C>T LRG_1401p2:p.Ala1846Val - Protein change
- A1846V, A1839V
- Other names
- -
- Canonical SPDI
- NC_000016.10:15715260:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
0.00020 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00014
The Genome Aggregation Database (gnomAD), exomes 0.00022
Trans-Omics for Precision Medicine (TOPMed) 0.00023
1000 Genomes Project 30x 0.00031
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00031
1000 Genomes Project 0.00020
Exome Aggregation Consortium (ExAC) 0.00021
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 | ||
---|---|---|---|---|---|---|
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. |
|||
MYH11 | No evidence available | No evidence available |
GRCh38 GRCh38 GRCh37 |
1988 | 3711 | |
NDE1 | - | - |
GRCh38 GRCh38 GRCh37 |
175 | 1898 |
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. |
---|---|---|---|---|
Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
|
Apr 26, 2023 | RCV000252424.22 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Jun 14, 2016 | RCV000390537.12 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Jan 24, 2024 | RCV000456952.16 | |
Likely benign (1) |
criteria provided, single submitter
|
Nov 1, 2016 | RCV000659928.8 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
|
Sep 22, 2023 | RCV000724061.17 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Mar 9, 2023 | RCV003407656.4 |
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. |
|
---|---|---|---|---|---|
Uncertain significance
(Jun 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Lissencephaly, Recessive
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000395208.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
|
|
Uncertain significance
(Jun 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Thoracic Aortic Aneurysms and Aortic Dissections
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000395207.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
|
|
Likely benign
(Nov 01, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Connective tissue disorder
Affected status: yes
Allele origin:
germline
|
Center for Human Genetics, Inc, Center for Human Genetics, Inc
Accession: SCV000781832.1
First in ClinVar: Jul 09, 2018 Last updated: Jul 09, 2018 |
|
|
Uncertain significance
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Aortic aneurysm, familial thoracic 4
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001274136.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
|
|
Uncertain significance
(Oct 01, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000319243.6
First in ClinVar: Oct 02, 2016 Last updated: Nov 29, 2022 |
Comment:
The p.A1839V variant (also known as c.5516C>T), located in coding exon 38 of the MYH11 gene, results from a C to T substitution at nucleotide … (more)
The p.A1839V variant (also known as c.5516C>T), located in coding exon 38 of the MYH11 gene, results from a C to T substitution at nucleotide position 5516. The alanine at codon 1839 is replaced by valine, an amino acid with similar properties, and is located in the coiled coil domain. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
Number of individuals with the variant: 1
|
|
Uncertain significance
(Mar 09, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
MYH11-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004115299.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The MYH11 c.5537C>T variant is predicted to result in the amino acid substitution p.Ala1846Val. To our knowledge, this variant has not been reported in the … (more)
The MYH11 c.5537C>T variant is predicted to result in the amino acid substitution p.Ala1846Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.087% of alleles in individuals of Ashkenazi Jewish descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-15809118-G-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less)
|
|
Uncertain significance
(Sep 22, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000536457.8
First in ClinVar: Mar 08, 2017 Last updated: Nov 25, 2023 |
Comment:
In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; … (more)
In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 21529752) (less)
|
|
Uncertain significance
(Nov 09, 2022)
|
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: SCV004239429.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
|
|
Likely benign
(Jan 24, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Aortic aneurysm, familial thoracic 4
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000543719.5
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
|
|
Uncertain significance
(Sep 03, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000229950.5
First in ClinVar: Jun 29, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
Uncertain significance
(Apr 26, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000904490.5
First in ClinVar: May 20, 2019 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces alanine with valine at codon 1846 of the MYH11 protein. Computational prediction suggests that this variant may not impact protein structure … (more)
This missense variant replaces alanine with valine at codon 1846 of the MYH11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 60/282598 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
|
|
Uncertain significance
(Jul 22, 2016)
|
no assertion criteria provided
Method: provider interpretation
|
not provided
Affected status: unknown
Allele origin:
germline
|
Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000925174.1
First in ClinVar: Jun 29, 2019 Last updated: Jun 29, 2019 |
Comment:
p.Ala1846Val (c.5537C>T) in the MYH11 gene (NM_001040113.1) Given the lack of case data and allele frequency in ExAC we consider this variant a variant of … (more)
p.Ala1846Val (c.5537C>T) in the MYH11 gene (NM_001040113.1) Given the lack of case data and allele frequency in ExAC we consider this variant a variant of uncertain significance, probably benign and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). MYH11 has been associated with autosomal dominant thoracic aortic aneurysms and dissection. Per the lab report and our own searches, the variant has not been reported in individuals with aneurysms and dissections. The variant was reported online in 26 of 60536 individuals in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/), which currently includes variant calls on ~64,000 individuals of European, African, Latino and Asian descent (as of July 20th, 2016). Specifically, the variant was observed in Latinos, Europeans, East Asians, and Africans. The highest allele frequency was in the "other" group (0.002217). The phenotype of those individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease. (less)
|
|
click to load more click to collapse |
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 |
---|---|---|---|---|
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MYH11 | - | - | - | - |
Text-mined citations for rs112948385 ...
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.