ClinVar Genomic variation as it relates to human health
NM_170707.4(LMNA):c.749C>T (p.Ala250Val)
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.749C>T (p.Ala250Val)
Variation ID: 48078 Accession: VCV000048078.25
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q22 1: 156134914 (GRCh38) [ NCBI UCSC ] 1: 156104705 (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 Jan 31, 2015 May 1, 2024 Aug 15, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_170707.4:c.749C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_733821.1:p.Ala250Val missense NM_005572.4:c.749C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005563.1:p.Ala250Val missense NM_001257374.3:c.413C>T NP_001244303.1:p.Ala138Val missense NM_001282624.2:c.506C>T NP_001269553.1:p.Ala169Val missense NM_001282625.2:c.749C>T NP_001269554.1:p.Ala250Val missense NM_001282626.2:c.749C>T NP_001269555.1:p.Ala250Val missense NM_170708.4:c.749C>T NP_733822.1:p.Ala250Val missense NC_000001.11:g.156134914C>T NC_000001.10:g.156104705C>T NG_008692.2:g.57342C>T LRG_254:g.57342C>T LRG_254t1:c.749C>T LRG_254p1:p.Ala250Val LRG_254t2:c.749C>T - Protein change
- A250V, A138V, A169V
- Other names
- -
- Canonical SPDI
- NC_000001.11:156134913: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.
The Genome Aggregation Database (gnomAD), exomes 0.00000
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00002
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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LMNA | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1818 | 2095 |
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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Uncertain significance (1) |
criteria provided, single submitter
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Jun 28, 2019 | RCV000041363.6 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 7, 2019 | RCV000237089.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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May 5, 2023 | RCV000707020.6 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 12, 2018 | RCV001100067.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 12, 2018 | RCV001100069.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 12, 2018 | RCV001100063.4 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Jan 12, 2018 | RCV001100064.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 12, 2018 | RCV001100065.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 12, 2018 | RCV001098298.4 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Jan 12, 2018 | RCV001100066.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 12, 2018 | RCV001100068.4 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Jan 12, 2018 | RCV001100070.4 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Jan 12, 2018 | RCV001102065.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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- | RCV001174245.1 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jun 22, 2023 | RCV001186222.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jun 3, 2021 | RCV002390179.2 | |
Uncertain significance/Uncertain risk allele (2) |
criteria provided, multiple submitters, no conflicts
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Aug 15, 2023 | RCV003231111.3 | |
Uncertain significance (1) |
criteria provided, single submitter
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Sep 8, 2021 | RCV002490579.1 | |
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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
(Sep 08, 2021)
|
criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1A
Familial partial lipodystrophy, Dunnigan type Hutchinson-Gilford syndrome Emery-Dreifuss muscular dystrophy 2, autosomal dominant Emery-Dreifuss muscular dystrophy 2, autosomal dominant Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome Mandibuloacral dysplasia with type A lipodystrophy Charcot-Marie-Tooth disease type 2B1 Heart-hand syndrome, Slovenian type Congenital muscular dystrophy due to LMNA mutation Emery-Dreifuss muscular dystrophy 3, autosomal recessive Restrictive dermopathy 2
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002779069.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Jan 07, 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: SCV000293879.10
First in ClinVar: Jul 25, 2016 Last updated: Apr 17, 2019 |
Comment:
While the A250V variant has not been published as a pathogenic variant or a benign variant, it has been classified as a likely pathogenic variant … (more)
While the A250V variant has not been published as a pathogenic variant or a benign variant, it has been classified as a likely pathogenic variant by another clinical laboratory in ClinVar (Landrum et al., 2014). The A250V variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, the A250V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved only in mammals. Finally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. (less)
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Uncertain significance
(-)
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criteria provided, single submitter
Method: clinical testing
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Charcot-Marie-Tooth disease
Affected status: yes
Allele origin:
germline
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Molecular Genetics Laboratory, London Health Sciences Centre
Accession: SCV001337375.1
First in ClinVar: Jun 14, 2020 Last updated: Jun 14, 2020 |
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Uncertain significance
(Jun 28, 2019)
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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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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000065056.6
First in ClinVar: May 03, 2013 Last updated: Jul 03, 2020 |
Comment:
The p.Ala250Val variant in LMNA has been identified in 1 individual with tachybrady syndrome with skeletal muscle weakness and 1 individual with cardiomyopathy and peripheral … (more)
The p.Ala250Val variant in LMNA has been identified in 1 individual with tachybrady syndrome with skeletal muscle weakness and 1 individual with cardiomyopathy and peripheral neuropathy (LMM data, UPenn pers. comm.). This variant has also been reported in ClinVar (Variation ID 48078) and has been identified in 1/113716 European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Ala250Val variant is uncertain. ACMG/AMP criteria applied: PM2. (less)
Number of individuals with the variant: 1
|
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Uncertain risk allele
(-)
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criteria provided, single submitter
(K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)
Method: research
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Primary dilated cardiomyopathy
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
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Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic
Accession: SCV003928183.1
First in ClinVar: Jun 10, 2023 Last updated: Jun 10, 2023 |
Comment:
Potent mutations in LMNA gene can lead to structural alteration in skeletal and cardiac muscle by altering the structure of Lamin A and Lamin C. … (more)
Potent mutations in LMNA gene can lead to structural alteration in skeletal and cardiac muscle by altering the structure of Lamin A and Lamin C. It is associated with dilated cardiomyopathy and skeletal muscle dystrophies. However no sufficient evidence is found to ascertain the role of this particular variant rs397517907, yet. (less)
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Uncertain significance
(Jun 22, 2023)
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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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Color Diagnostics, LLC DBA Color Health
Accession: SCV001352588.3
First in ClinVar: Jun 22, 2020 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces alanine with valine at codon 250 of the LMNA protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
This missense variant replaces alanine with valine at codon 250 of the LMNA protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with dyslipidemia (PMID: 32041611). This variant has been identified in 1/251422 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)
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Uncertain significance
(May 05, 2023)
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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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Invitae
Accession: SCV000836098.4
First in ClinVar: Oct 10, 2018 Last updated: Feb 28, 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. ClinVar contains an entry for this variant (Variation ID: 48078). This missense change has been observed in individual(s) with clinical features of LMNA-related conditions (PMID: 32041611). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 250 of the LMNA protein (p.Ala250Val). (less)
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Uncertain Significance
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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Primary dilated cardiomyopathy
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004844332.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
This missense variant replaces alanine with valine at codon 250 of the lamin A/C proteins. Computational prediction is inconclusive regarding the impact of this variant … (more)
This missense variant replaces alanine with valine at codon 250 of the lamin A/C proteins. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/251422 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)
Number of individuals with the variant: 3
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Uncertain significance
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1A
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001254652.1
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)
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Uncertain significance
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
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Mandibuloacral dysplasia with type A lipodystrophy
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001256564.1
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)
|
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Uncertain significance
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Familial partial lipodystrophy, Dunnigan type
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001256565.1
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)
|
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Uncertain significance
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital muscular dystrophy due to LMNA mutation
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001256568.1
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)
|
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Uncertain significance
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Emery-Dreifuss muscular dystrophy 2, autosomal dominant
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001256566.1
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)
|
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Uncertain significance
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hutchinson-Gilford syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001256567.1
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)
|
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Uncertain significance
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Emery-Dreifuss muscular dystrophy
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001256570.1
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)
|
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Uncertain significance
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001256569.1
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
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Charcot-Marie-Tooth disease type 2B1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001256571.1
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
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Restrictive dermopathy 1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001258713.1
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)
|
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Uncertain significance
(Jun 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002672726.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.A250V variant (also known as c.749C>T), located in coding exon 4 of the LMNA gene, results from a C to T substitution at nucleotide … (more)
The p.A250V variant (also known as c.749C>T), located in coding exon 4 of the LMNA gene, results from a C to T substitution at nucleotide position 749. The alanine at codon 250 is replaced by valine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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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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Integrated analysis reveals the alterations that LMNA interacts with euchromatin in LMNA mutation-associated dilated cardiomyopathy. | Zhang X | Clinical epigenetics | 2021 | PMID: 33407844 |
LMNA Missense Mutation Causes Nonsense-Mediated mRNA Decay and Severe Dilated Cardiomyopathy. | Kato K | Circulation. Genomic and precision medicine | 2020 | PMID: 32818388 |
Six years' experience with LipidSeq: clinical and research learnings from a hybrid, targeted sequencing panel for dyslipidemias. | Dron JS | BMC medical genomics | 2020 | PMID: 32041611 |
Inherited dilated cardiomyopathy in a large Moroccan family caused by LMNA mutation. | Adadi N | Anatolian journal of cardiology | 2018 | PMID: 29952368 |
Gene-Based Risk Stratification for Cardiac Disorders in LMNA Mutation Carriers. | Nishiuchi S | Circulation. Cardiovascular genetics | 2017 | PMID: 29237675 |
Mutations in the LMNA gene encoding lamin A/C. | Genschel J | Human mutation | 2000 | PMID: 11102973 |
Text-mined citations for rs397517907 ...
HelpRecord last updated May 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.