ClinVar Genomic variation as it relates to human health
NM_170707.4(LMNA):c.872A>T (p.Glu291Val)
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_170707.4(LMNA):c.872A>T (p.Glu291Val)
Variation ID: 2502156 Accession: VCV002502156.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q22 1: 156135248 (GRCh38) [ NCBI UCSC ] 1: 156105039 (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 20, 2023 May 20, 2023 Apr 20, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_170707.4:c.872A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_733821.1:p.Glu291Val missense NM_005572.4:c.872A>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005563.1:p.Glu291Val missense NM_001257374.3:c.536A>T NP_001244303.1:p.Glu179Val missense NM_001282624.2:c.629A>T NP_001269553.1:p.Glu210Val missense NM_001282625.2:c.872A>T NP_001269554.1:p.Glu291Val missense NM_001282626.2:c.872A>T NP_001269555.1:p.Glu291Val missense NM_001406983.1:c.872A>T NP_001393912.1:p.Glu291Val missense NM_001406984.1:c.872A>T NP_001393913.1:p.Glu291Val missense NM_001406985.1:c.872A>T NP_001393914.1:p.Glu291Val missense NM_001406986.1:c.629A>T NP_001393915.1:p.Glu210Val missense NM_001406987.1:c.629A>T NP_001393916.1:p.Glu210Val missense NM_001406988.1:c.575A>T NP_001393917.1:p.Glu192Val missense NM_001406989.1:c.536A>T NP_001393918.1:p.Glu179Val missense NM_001406990.1:c.314A>T NP_001393919.1:p.Glu105Val missense NM_001406991.1:c.872A>T NP_001393920.1:p.Glu291Val missense NM_001406992.1:c.872A>T NP_001393921.1:p.Glu291Val missense NM_001406993.1:c.314A>T NP_001393922.1:p.Glu105Val missense NM_001406994.1:c.208A>T NP_001393923.1:p.Ser70Cys missense NM_001406995.1:c.314A>T NP_001393924.1:p.Glu105Val missense NM_001406996.1:c.314A>T NP_001393925.1:p.Glu105Val missense NM_001406997.1:c.314A>T NP_001393926.1:p.Glu105Val missense NM_001406998.1:c.536A>T NP_001393927.1:p.Glu179Val missense NM_001406999.1:c.208A>T NP_001393928.1:p.Ser70Cys missense NM_001407000.1:c.208A>T NP_001393929.1:p.Ser70Cys missense NM_001407001.1:c.208A>T NP_001393930.1:p.Ser70Cys missense NM_001407002.1:c.314A>T NP_001393931.1:p.Glu105Val missense NM_001407003.1:c.314A>T NP_001393932.1:p.Glu105Val missense NM_170708.4:c.872A>T NP_733822.1:p.Glu291Val missense NR_047544.1:n.1513A>T NR_047545.1:n.760A>T NC_000001.11:g.156135248A>T NC_000001.10:g.156105039A>T NG_008692.2:g.57676A>T LRG_254:g.57676A>T LRG_254t1:c.872A>T LRG_254p1:p.Glu291Val LRG_254t2:c.872A>T LRG_254p2:p.Glu291Val LRG_254t3:c.872A>T LRG_254p3:p.Glu291Val - Protein change
- E105V, E179V, E192V, E210V, E291V, S70C
- Other names
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- Canonical SPDI
- NC_000001.11:156135247:A: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.
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- Links
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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LMNA | Some evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1751 | 2024 |
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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Apr 20, 2022 | RCV003228574.1 |
Submissions - Germline
Classification
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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
(Apr 20, 2022)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1A
Affected status: yes
Allele origin:
germline
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New York Genome Center
Accession: SCV003925109.1
First in ClinVar: May 20, 2023 Last updated: May 20, 2023 |
Comment:
The c.872A>T (p.Glu291Val) variant identified in the LMNA gene substitutes a well conserved Glutamic Acid for Valine at amino acid291/665 (exon 5/12). This variant is … (more)
The c.872A>T (p.Glu291Val) variant identified in the LMNA gene substitutes a well conserved Glutamic Acid for Valine at amino acid291/665 (exon 5/12). This variant is absent from population databases (gnomADv3.1.2, BRAVO-TOPMed Freeze 8, All of Us) suggesting it is not a common benign variant in the populations represented in those databases. In silico algorithms predict this variant to be Pathogenic (REVEL; score:0.9509). While the p.Glu291Val variant identified here is absent from ClinVar, a different variant at the same amino acid position, p.Glu291Lys has been reported as Pathogenic in ClinVar(VarID:200942), and reported in multiple individuals in the literature with arrhythmias, dilated cardiomyopathy, and conduction disease or heart block [PMID:25498755, 32413188]. The p.Glu291Val variant has not been previously reported in the literature in affected individuals. The p.Glu291 residue is within the Coil 2 region of the Rod domain of LMNA (UniProtKB:P02545), and other missense variants in this region have been reported in individuals with LMNA-associated cardiac phenotypes [PMID:32413188, 30402260]. Given its absence in population databases, in silico algorithms strongly predict a damaging effect to the protein, and the presence of different pathogenic missense change at the same amino acid (p.Glu291Lys), the c.872A>T (p.Glu291Val) variant identified in the LMNA gene is reported as Likely Pathogenic. (less)
Clinical Features:
Atrioventricular block (present)
Secondary finding: no
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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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated May 27, 2023
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.