ClinVar Genomic variation as it relates to human health
NM_001018005.2(TPM1):c.453C>A (p.Ala151=)
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_001018005.2(TPM1):c.453C>A (p.Ala151=)
Variation ID: 31888 Accession: VCV000031888.40
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 15q22.2 15: 63059641 (GRCh38) [ NCBI UCSC ] 15: 63351840 (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 May 1, 2024 Feb 5, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001018005.2:c.453C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001018005.1:p.Ala151= synonymous NM_000366.6:c.453C>A NP_000357.3:p.Ala151= synonymous NM_001018004.2:c.453C>A NP_001018004.1:p.Ala151= synonymous NM_001018006.2:c.453C>A NP_001018006.1:p.Ala151= synonymous NM_001018007.2:c.453C>A NP_001018007.1:p.Ala151= synonymous NM_001018008.2:c.345C>A NP_001018008.1:p.Ala115= synonymous NM_001018020.2:c.453C>A NP_001018020.1:p.Ala151= synonymous NM_001301244.2:c.453C>A NP_001288173.1:p.Ala151= synonymous NM_001301289.2:c.345C>A NP_001288218.1:p.Ala115= synonymous NM_001330344.2:c.345C>A NP_001317273.1:p.Ala115= synonymous NM_001330346.2:c.345C>A NP_001317275.1:p.Ala115= synonymous NM_001330351.2:c.345C>A NP_001317280.1:p.Ala115= synonymous NM_001365776.1:c.453C>A NP_001352705.1:p.Ala151= synonymous NM_001365777.1:c.453C>A NP_001352706.1:p.Ala151= synonymous NM_001365778.1:c.579C>A NP_001352707.1:p.Ala193= synonymous NM_001365779.1:c.453C>A NP_001352708.1:p.Ala151= synonymous NM_001365780.1:c.345C>A NP_001352709.1:p.Ala115= synonymous NM_001365781.2:c.345C>A NP_001352710.1:p.Ala115= synonymous NM_001365782.1:c.345C>A NP_001352711.1:p.Ala115= synonymous NC_000015.10:g.63059641C>A NC_000015.9:g.63351840C>A NG_007557.1:g.22003C>A LRG_387:g.22003C>A LRG_387t1:c.453C>A LRG_387p1:p.Ala151= - Protein change
- Other names
- p.A151A:GCC>GCA
- Canonical SPDI
- NC_000015.10:63059640:C:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- probably no functional consequence
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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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0.29433 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.63571
Trans-Omics for Precision Medicine (TOPMed) 0.64567
The Genome Aggregation Database (gnomAD) 0.64628
The Genome Aggregation Database (gnomAD), exomes 0.67040
Exome Aggregation Consortium (ExAC) 0.67368
1000 Genomes Project 30x 0.69706
1000 Genomes Project 0.70567
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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TPM1 | No evidence available | No evidence available |
GRCh38 GRCh37 |
848 | 898 |
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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not provided (1) |
no classification provided
|
Apr 15, 2012 | RCV000024584.7 | |
Benign (8) |
criteria provided, multiple submitters, no conflicts
|
Apr 10, 2023 | RCV000036332.20 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Sep 10, 2021 | RCV000280647.8 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 5, 2024 | RCV000373427.10 | |
Benign (1) |
criteria provided, single submitter
|
Mar 11, 2015 | RCV000248314.4 | |
Benign (1) |
criteria provided, single submitter
|
May 28, 2019 | RCV000989342.2 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Sep 27, 2022 | RCV001177325.5 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Sep 10, 2021 | RCV001094282.7 | |
TPM1-related disorder
|
Likely benign (1) |
criteria provided, single submitter
|
Dec 7, 2023 | RCV003891442.1 |
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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Benign
(Apr 03, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiomyopathy
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV001341519.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
|
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Benign
(Sep 27, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiomyopathy
Affected status: yes
Allele origin:
germline
|
Cohesion Phenomics
Accession: SCV003803072.1
First in ClinVar: Feb 18, 2023 Last updated: Feb 18, 2023 |
|
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Benign
(Apr 10, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003929102.1
First in ClinVar: Jun 03, 2023 Last updated: Jun 03, 2023 |
Comment:
Variant summary: TPM1 c.453C>A alters a conserved nucleotide resulting in a synonymous change. The variant allele was found at a frequency of 0.67 in 251338 … (more)
Variant summary: TPM1 c.453C>A alters a conserved nucleotide resulting in a synonymous change. The variant allele was found at a frequency of 0.67 in 251338 control chromosomes, suggesting that it is the major allele and therefore benign. The observed variant frequency is approximately 9000 fold of the estimated maximal expected allele frequency for a pathogenic variant in TPM1 causing Cardiomyopathy phenotype (7.5e-05), strongly suggesting that the variant is benign. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. (less)
|
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Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hypertrophic cardiomyopathy
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001000164.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024 |
|
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Likely benign
(Dec 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
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TPM1-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000305848.2
First in ClinVar: Oct 02, 2016 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
|
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Benign
(Feb 05, 2024)
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criteria provided, single submitter
Method: clinical testing
|
Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004815449.1
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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Number of individuals with the variant: 93147
|
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Benign
(Sep 25, 2012)
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criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000169032.11
First in ClinVar: Jun 23, 2014 Last updated: Oct 02, 2016 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
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Benign
(Jan 18, 2008)
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criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000059984.6
First in ClinVar: May 03, 2013 Last updated: Oct 02, 2016 |
Number of individuals with the variant: 4177
|
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Benign
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hypertrophic cardiomyopathy 1
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001139633.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
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Benign
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1Y
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000393208.3
First in ClinVar: Dec 06, 2016 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
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Benign
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hypertrophic cardiomyopathy 3
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000393207.3
First in ClinVar: Dec 06, 2016 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
|
Benign
(Sep 10, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Dilated cardiomyopathy 1Y
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002098675.1
First in ClinVar: Feb 26, 2022 Last updated: Feb 26, 2022 |
|
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Benign
(Sep 10, 2021)
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criteria provided, single submitter
Method: clinical testing
|
Hypertrophic cardiomyopathy 3
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002098676.1
First in ClinVar: Feb 26, 2022 Last updated: Feb 26, 2022 |
|
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Benign
(Mar 11, 2015)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000317582.7
First in ClinVar: Oct 02, 2016 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001927465.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
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: SCV001976124.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001742698.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
|
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001917009.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
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: SCV001953367.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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not provided
(Apr 15, 2012)
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no classification provided
Method: curation
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not specified
Affected status: not provided
Allele origin:
germline
|
Leiden Muscular Dystrophy (TPM1)
Accession: SCV000045893.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
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Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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probably no functional consequence
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Leiden Muscular Dystrophy (TPM1)
Accession: SCV000045893.1
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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 rs1071646 ...
HelpRecord last updated May 27, 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.