In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. This missense change has been observed in individual(s) with dilated cardiomyopathy (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 18 of the TPM1 protein (p.Ala18Thr).
ClinVar Genomic variation as it relates to human health
NM_001018005.2(TPM1):c.52G>A (p.Ala18Thr)
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.
Likely pathogenic
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001018005.2(TPM1):c.52G>A (p.Ala18Thr)
Variation ID: 2850868 Accession: VCV002850868.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 15q22.2 15: 63042881 (GRCh38) [ NCBI UCSC ] 15: 63335080 (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 Aug 3, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001018005.2:c.52G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001018005.1:p.Ala18Thr missense NM_000366.6:c.52G>A NP_000357.3:p.Ala18Thr missense NM_001018004.2:c.52G>A NP_001018004.1:p.Ala18Thr missense NM_001018006.2:c.52G>A NP_001018006.1:p.Ala18Thr missense NM_001018007.2:c.52G>A NP_001018007.1:p.Ala18Thr missense NM_001018020.2:c.52G>A NP_001018020.1:p.Ala18Thr missense NM_001301244.2:c.52G>A NP_001288173.1:p.Ala18Thr missense NM_001365776.1:c.52G>A NP_001352705.1:p.Ala18Thr missense NM_001365777.1:c.52G>A NP_001352706.1:p.Ala18Thr missense NM_001365778.1:c.52G>A NP_001352707.1:p.Ala18Thr missense NM_001365779.1:c.52G>A NP_001352708.1:p.Ala18Thr missense NM_001407322.1:c.52G>A NP_001394251.1:p.Ala18Thr missense NM_001407323.1:c.52G>A NP_001394252.1:p.Ala18Thr missense NM_001407324.1:c.52G>A NP_001394253.1:p.Ala18Thr missense NM_001407325.1:c.52G>A NP_001394254.1:p.Ala18Thr missense NM_001407326.1:c.52G>A NP_001394255.1:p.Ala18Thr missense NM_001407327.1:c.52G>A NP_001394256.1:p.Ala18Thr missense NM_001407328.1:c.52G>A NP_001394257.1:p.Ala18Thr missense NM_001407329.1:c.52G>A NP_001394258.1:p.Ala18Thr missense NM_001407330.1:c.52G>A NP_001394259.1:p.Ala18Thr missense NM_001407331.1:c.52G>A NP_001394260.1:p.Ala18Thr missense NM_001407332.1:c.52G>A NP_001394261.1:p.Ala18Thr missense NM_001407333.1:c.52G>A NP_001394262.1:p.Ala18Thr missense NM_001407334.1:c.52G>A NP_001394263.1:p.Ala18Thr missense NM_001407335.1:c.52G>A NP_001394264.1:p.Ala18Thr missense NM_001407336.1:c.52G>A NP_001394265.1:p.Ala18Thr missense NM_001407337.1:c.52G>A NP_001394266.1:p.Ala18Thr missense NM_001407338.1:c.52G>A NP_001394267.1:p.Ala18Thr missense NR_176337.1:n.135G>A non-coding transcript variant NR_176338.1:n.135G>A non-coding transcript variant NR_176339.1:n.135G>A non-coding transcript variant NR_176340.1:n.135G>A non-coding transcript variant NR_176341.1:n.135G>A non-coding transcript variant NR_176342.1:n.135G>A non-coding transcript variant NR_176343.1:n.135G>A non-coding transcript variant NR_176344.1:n.135G>A non-coding transcript variant NR_176345.1:n.135G>A non-coding transcript variant NR_176346.1:n.135G>A non-coding transcript variant NR_176347.1:n.135G>A non-coding transcript variant NC_000015.10:g.63042881G>A NC_000015.9:g.63335080G>A NG_007557.1:g.5243G>A LRG_387:g.5243G>A LRG_387t1:c.52G>A LRG_387p1:p.Ala18Thr - Protein change
- A18T
- Other names
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- Canonical SPDI
- NC_000015.10:63042880:G:A
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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. |
|||
| TPM1 | No evidence available | No evidence available |
GRCh38 GRCh37 |
855 | 903 | |
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. |
|---|---|---|---|---|
| Likely pathogenic (1) |
criteria provided, single submitter
|
Aug 3, 2023 | RCV003750261.2 |
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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|---|---|---|---|---|---|
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Likely pathogenic
(Aug 03, 2023)
|
criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004451003.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has … (more)
In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. This missense change has been observed in individual(s) with dilated cardiomyopathy (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 18 of the TPM1 protein (p.Ala18Thr). (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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. This missense change has been observed in individual(s) with dilated cardiomyopathy (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 18 of the TPM1 protein (p.Ala18Thr).
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.