ClinVar Genomic variation as it relates to human health
NM_033118.4(MYLK2):c.284C>A (p.Ala95Glu)
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_033118.4(MYLK2):c.284C>A (p.Ala95Glu)
Variation ID: 4244 Accession: VCV000004244.30
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 20q11.21 20: 31820357 (GRCh38) [ NCBI UCSC ] 20: 30408160 (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 Apr 4, 2013 Feb 20, 2024 Jan 28, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_033118.4:c.284C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_149109.1:p.Ala95Glu missense NC_000020.11:g.31820357C>A NC_000020.10:g.30408160C>A NG_012847.1:g.5983C>A LRG_392:g.5983C>A LRG_392t1:c.284C>A LRG_392p1:p.Ala95Glu Q9H1R3:p.Ala95Glu - Protein change
- A95E
- Other names
- p.A95E:GCA>GAA
- Canonical SPDI
- NC_000020.11:31820356:C: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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0.00280 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00058
Exome Aggregation Consortium (ExAC) 0.00078
The Genome Aggregation Database (gnomAD) 0.00202
Trans-Omics for Precision Medicine (TOPMed) 0.00219
1000 Genomes Project 30x 0.00265
1000 Genomes Project 0.00280
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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MYLK2 | - | - |
GRCh38 GRCh37 |
600 | 623 |
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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Pathogenic (1) |
no assertion criteria provided
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Nov 30, 2001 | RCV000004466.2 | |
Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Aug 15, 2022 | RCV000154782.13 | |
Benign (1) |
criteria provided, single submitter
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Nov 4, 2019 | RCV001170850.3 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Jan 28, 2024 | RCV000467194.18 | |
Benign (4) |
criteria provided, single submitter
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Aug 5, 2019 | RCV001701560.4 |
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. |
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Likely benign
(Apr 09, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000229245.5
First in ClinVar: Jun 28, 2015 Last updated: Apr 09, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Likely benign
(Jan 27, 2017)
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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: SCV000204462.4
First in ClinVar: Jan 31, 2015 Last updated: Apr 09, 2018 |
Comment:
p.Ala95Glu in exon 3 of MYLK2: This variant is not expected to have clinical sig nificance because it has been identified in 0.8% (75/9276) of … (more)
p.Ala95Glu in exon 3 of MYLK2: This variant is not expected to have clinical sig nificance because it has been identified in 0.8% (75/9276) of African chromosome s by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbS NP rs121908108). (less)
Number of individuals with the variant: 3
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Benign
(Aug 05, 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: SCV000236026.9
First in ClinVar: Jul 05, 2015 Last updated: Apr 09, 2018 |
Comment:
This variant is associated with the following publications: (PMID: 23299917, 22995991, 11733062, 27884173, 25910212)
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Benign
(Nov 04, 2019)
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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
Accession: SCV001333470.2
First in ClinVar: May 31, 2020 Last updated: Dec 29, 2021 |
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Benign
(Jan 20, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy 1
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002049182.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
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Likely benign
(Aug 15, 2022)
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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: SCV002572058.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
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Benign
(Jan 28, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy 1
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000556767.9
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
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Pathogenic
(Nov 30, 2001)
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no assertion criteria provided
Method: literature only
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CARDIOMYOPATHY, HYPERTROPHIC, MIDVENTRICULAR, DIGENIC
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000024639.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
See 606566.0001 and Davis et al. (2001).
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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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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001931317.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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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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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: SCV001951201.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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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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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: SCV001975838.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 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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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 |
An informatics approach to analyzing the incidentalome. | Berg JS | Genetics in medicine : official journal of the American College of Medical Genetics | 2013 | PMID: 22995991 |
The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation. | Davis JS | Cell | 2001 | PMID: 11733062 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MYLK2 | - | - | - | - |
Text-mined citations for rs121908108 ...
HelpRecord last updated Feb 28, 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.