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. 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 expected to disrupt LMNA protein function. This variant has not been reported in the literature in individuals affected with LMNA-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 516 of the LMNA protein (p.Ala516Val).
ClinVar Genomic variation as it relates to human health
NM_170707.4(LMNA):c.1547C>T (p.Ala516Val)
Germline
Classification
Help
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.
(1)
Help
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
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_170707.4(LMNA):c.1547C>T (p.Ala516Val)
Variation ID: 2813118 Accession: VCV002813118.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q22 1: 156137171 (GRCh38) [ NCBI UCSC ] 1: 156106962 (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 Feb 20, 2024 Feb 20, 2024 Nov 9, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_170707.4:c.1547C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_733821.1:p.Ala516Val missense NM_005572.4:c.1547C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005563.1:p.Ala516Val missense NM_001257374.3:c.1211C>T NP_001244303.1:p.Ala404Val missense NM_001282624.2:c.1304C>T NP_001269553.1:p.Ala435Val missense NM_001282625.2:c.1547C>T NP_001269554.1:p.Ala516Val missense NM_001282626.2:c.1547C>T NP_001269555.1:p.Ala516Val missense NM_001406983.1:c.1547C>T NP_001393912.1:p.Ala516Val missense NM_001406984.1:c.1547C>T NP_001393913.1:p.Ala516Val missense NM_001406985.1:c.1547C>T NP_001393914.1:p.Ala516Val missense NM_001406986.1:c.1304C>T NP_001393915.1:p.Ala435Val missense NM_001406987.1:c.1304C>T NP_001393916.1:p.Ala435Val missense NM_001406988.1:c.1250C>T NP_001393917.1:p.Ala417Val missense NM_001406989.1:c.1211C>T NP_001393918.1:p.Ala404Val missense NM_001406990.1:c.989C>T NP_001393919.1:p.Ala330Val missense NM_001406991.1:c.1547C>T NP_001393920.1:p.Ala516Val missense NM_001406992.1:c.1547C>T NP_001393921.1:p.Ala516Val missense NM_001406993.1:c.989C>T NP_001393922.1:p.Ala330Val missense NM_001406994.1:c.923C>T NP_001393923.1:p.Ala308Val missense NM_001406995.1:c.989C>T NP_001393924.1:p.Ala330Val missense NM_001406996.1:c.989C>T NP_001393925.1:p.Ala330Val missense NM_001406997.1:c.989C>T NP_001393926.1:p.Ala330Val missense NM_001406998.1:c.1211C>T NP_001393927.1:p.Ala404Val missense NM_001406999.1:c.923C>T NP_001393928.1:p.Ala308Val missense NM_001407000.1:c.923C>T NP_001393929.1:p.Ala308Val missense NM_001407001.1:c.923C>T NP_001393930.1:p.Ala308Val missense NM_001407002.1:c.989C>T NP_001393931.1:p.Ala330Val missense NM_001407003.1:c.989C>T NP_001393932.1:p.Ala330Val missense NM_170708.4:c.1547C>T NP_733822.1:p.Ala516Val missense NR_047544.1:n.2188C>T NR_047545.1:n.1435C>T NC_000001.11:g.156137171C>T NC_000001.10:g.156106962C>T NG_008692.2:g.59599C>T LRG_254:g.59599C>T LRG_254t1:c.1547C>T LRG_254p1:p.Ala516Val LRG_254t2:c.1547C>T LRG_254p2:p.Ala516Val LRG_254t3:c.1547C>T LRG_254p3:p.Ala516Val - Protein change
- A308V, A516V, A330V, A404V, A435V, A417V
- Other names
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- Canonical SPDI
- NC_000001.11:156137170:C: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
Help
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
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. |
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| LMNA | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1845 | 2125 | |
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 (1) |
criteria provided, single submitter
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Nov 9, 2022 | RCV003744095.2 |
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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Uncertain significance
(Nov 09, 2022)
|
criteria provided, single submitter
Method: clinical testing
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Charcot-Marie-Tooth disease type 2
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004410521.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
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 … (more)
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. 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 expected to disrupt LMNA protein function. This variant has not been reported in the literature in individuals affected with LMNA-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 516 of the LMNA protein (p.Ala516Val). (less)
|
Comment:
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. |
Comment:
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. 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 expected to disrupt LMNA protein function. This variant has not been reported in the literature in individuals affected with LMNA-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 516 of the LMNA protein (p.Ala516Val).
Citations for germline classification of this variant
Help| There 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 Sep 30, 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.