ClinVar Genomic variation as it relates to human health
NM_001018005.2(TPM1):c.479G>A (p.Arg160His)
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.479G>A (p.Arg160His)
Variation ID: 31899 Accession: VCV000031899.10
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 15q22.2 15: 63059667 (GRCh38) [ NCBI UCSC ] 15: 63351866 (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 Feb 14, 2024 Nov 27, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001018005.2:c.479G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001018005.1:p.Arg160His missense NM_000366.6:c.479G>A NP_000357.3:p.Arg160His missense NM_001018004.2:c.479G>A NP_001018004.1:p.Arg160His missense NM_001018006.2:c.479G>A NP_001018006.1:p.Arg160His missense NM_001018007.2:c.479G>A NP_001018007.1:p.Arg160His missense NM_001018008.2:c.371G>A NP_001018008.1:p.Arg124His missense NM_001018020.2:c.479G>A NP_001018020.1:p.Arg160His missense NM_001301244.2:c.479G>A NP_001288173.1:p.Arg160His missense NM_001301289.2:c.371G>A NP_001288218.1:p.Arg124His missense NM_001330344.2:c.371G>A NP_001317273.1:p.Arg124His missense NM_001330346.2:c.371G>A NP_001317275.1:p.Arg124His missense NM_001330351.2:c.371G>A NP_001317280.1:p.Arg124His missense NM_001365776.1:c.479G>A NP_001352705.1:p.Arg160His missense NM_001365777.1:c.479G>A NP_001352706.1:p.Arg160His missense NM_001365778.1:c.605G>A NP_001352707.1:p.Arg202His missense NM_001365779.1:c.479G>A NP_001352708.1:p.Arg160His missense NM_001365780.1:c.371G>A NP_001352709.1:p.Arg124His missense NM_001365781.2:c.371G>A NP_001352710.1:p.Arg124His missense NM_001365782.1:c.371G>A NP_001352711.1:p.Arg124His missense NC_000015.10:g.63059667G>A NC_000015.9:g.63351866G>A NG_007557.1:g.22029G>A LRG_387:g.22029G>A LRG_387t1:c.479G>A LRG_387p1:p.Arg160His - Protein change
- R160H, R202H, R124H
- Other names
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- Canonical SPDI
- NC_000015.10:63059666:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- functional variant Sequence Ontology [SO:0001536]
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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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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
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 |
835 | 884 |
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
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
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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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Pathogenic (2) |
criteria provided, single submitter
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Jun 18, 2020 | RCV000024595.3 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Sep 27, 2010 | RCV000036336.5 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Jan 11, 2020 | RCV001331475.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 27, 2023 | RCV003586127.1 |
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
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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
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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Likely pathogenic
(Jan 11, 2020)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1Y
Affected status: yes
Allele origin:
unknown
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Baylor Genetics
Accession: SCV001523517.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
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Pathogenic
(Jun 18, 2020)
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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: SCV000617285.3
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment:
Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; … (more)
Not observed in large population cohorts (Lek et al., 2016); 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: 25241052, 20530761, 28759816) (less)
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Likely pathogenic
(Sep 27, 2010)
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criteria provided, single submitter
Method: clinical testing
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Primary dilated cardiomyopathy
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000059988.6
First in ClinVar: May 03, 2013 Last updated: Jan 31, 2015 |
Number of individuals with the variant: 1
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Pathogenic
(Nov 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV004297269.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 160 of the TPM1 protein (p.Arg160His). … (more)
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 160 of the TPM1 protein (p.Arg160His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of TPM1-related conditions (PMID: 20530761, 34076677, 34935411; Invitae). In at least one individual the variant was observed to be de novo. This variant is also known as c.605G>A; p.R202H. ClinVar contains an entry for this variant (Variation ID: 31899). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic. (less)
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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:
de novo
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Leiden Muscular Dystrophy (TPM1)
Accession: SCV000045904.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
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Germline Functional Evidence
Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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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
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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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has functional consequence
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Leiden Muscular Dystrophy (TPM1)
Accession: SCV000045904.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Genotype and Cardiac Outcomes in Pediatric Dilated Cardiomyopathy. | Khan RS | Journal of the American Heart Association | 2022 | PMID: 34935411 |
Genetic Variants Associated With Unexplained Sudden Cardiac Death in Adult White and African American Individuals. | Guo L | JAMA cardiology | 2021 | PMID: 34076677 |
The importance of genetic counseling, DNA diagnostics, and cardiologic family screening in left ventricular noncompaction cardiomyopathy. | Hoedemaekers YM | Circulation. Cardiovascular genetics | 2010 | PMID: 20530761 |
Text-mined citations for rs199476311 ...
HelpRecord last updated Apr 06, 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.