ClinVar Genomic variation as it relates to human health
NM_000501.4(ELN):c.647G>T (p.Gly216Val)
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(5); Benign(1); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000501.4(ELN):c.647G>T (p.Gly216Val)
Variation ID: 213192 Accession: VCV000213192.21
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q11.23 7: 74047678 (GRCh38) [ NCBI UCSC ] 7: 73462008 (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 19, 2017 Oct 8, 2024 Aug 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000501.4:c.647G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000492.2:p.Gly216Val missense NM_001081752.3:c.617G>T NP_001075221.1:p.Gly206Val missense NM_001081753.3:c.662G>T NP_001075222.1:p.Gly221Val missense NM_001081754.3:c.662G>T NP_001075223.1:p.Gly221Val missense NM_001081755.3:c.647G>T NP_001075224.1:p.Gly216Val missense NM_001278912.2:c.647G>T NP_001265841.1:p.Gly216Val missense NM_001278913.2:c.578-464G>T intron variant NM_001278914.2:c.632G>T NP_001265843.1:p.Gly211Val missense NM_001278915.2:c.647G>T NP_001265844.1:p.Gly216Val missense NM_001278916.2:c.644-464G>T intron variant NM_001278917.2:c.617G>T NP_001265846.1:p.Gly206Val missense NM_001278918.2:c.515G>T NP_001265847.1:p.Gly172Val missense NM_001278939.2:c.647G>T NP_001265868.1:p.Gly216Val missense NC_000007.14:g.74047678G>T NC_000007.13:g.73462008G>T NG_009261.1:g.24582G>T - Protein change
- G216V, G172V, G206V, G211V, G221V
- Other names
- p.G216V:GGC>GTC
- Canonical SPDI
- NC_000007.14:74047677:G: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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Allele frequency
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The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00046
Exome Aggregation Consortium (ExAC) 0.00028
The Genome Aggregation Database (gnomAD), exomes 0.00029
The Genome Aggregation Database (gnomAD) 0.00034
Trans-Omics for Precision Medicine (TOPMed) 0.00036
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
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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
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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ELN | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
838 | 1158 |
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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Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Jan 31, 2024 | RCV000531891.11 | |
Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Aug 1, 2024 | RCV000728083.13 | |
Uncertain significance (1) |
criteria provided, single submitter
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Oct 31, 2018 | RCV000765972.2 | |
Benign (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV001161674.4 |
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
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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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Uncertain significance
(Jul 13, 2017)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000855615.1
First in ClinVar: Dec 16, 2018 Last updated: Dec 16, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Uncertain significance
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Cutis laxa, autosomal dominant 1
Supravalvar aortic stenosis Williams syndrome
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000897394.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cutis laxa, autosomal dominant 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001323567.1
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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Supravalvar aortic stenosis
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001325207.1
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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Uncertain significance
(Sep 05, 2020)
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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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Revvity Omics, Revvity
Accession: SCV003831890.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Uncertain significance
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Supravalvar aortic stenosis
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000622214.4
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 216 of the ELN protein (p.Gly216Val). … (more)
This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 216 of the ELN protein (p.Gly216Val). This variant is present in population databases (rs145612009, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ELN-related conditions. ClinVar contains an entry for this variant (Variation ID: 213192). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ELN protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Jan 12, 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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GeneDx
Accession: SCV000250061.11
First in ClinVar: Oct 11, 2015 Last updated: Sep 16, 2024 |
Comment:
Reported in two German individuals with a dilated aortic root and a biscuspid aortic valve (PMID: 28387797); however, it is unclear which reference transcript was … (more)
Reported in two German individuals with a dilated aortic root and a biscuspid aortic valve (PMID: 28387797); however, it is unclear which reference transcript was used in this study and whether this represents the same variant identified here due to discrepant c. nomenclature provided (c.515G>T); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25256751, 28387797, 19029017) (less)
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Likely benign
(Aug 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: SCV005331144.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
ELN: BS2
Number of individuals with the variant: 1
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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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Analysis of exonic elastin variants in severe, early-onset chronic obstructive pulmonary disease. | Cho MH | American journal of respiratory cell and molecular biology | 2009 | PMID: 19029017 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ELN | - | - | - | - |
Text-mined citations for rs145612009 ...
HelpRecord last updated Oct 08, 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.