ClinVar Genomic variation as it relates to human health
NM_001018005.2(TPM1):c.538G>A (p.Glu180Lys)
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
-
NM_001018005.2(TPM1):c.538G>A (p.Glu180Lys)
Variation ID: 1002513 Accession: VCV001002513.6
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 15q22.2 15: 63060914 (GRCh38) [ NCBI UCSC ] 15: 63353113 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Mar 7, 2021 Feb 28, 2024 Mar 16, 2021 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001018005.2:c.538G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001018005.1:p.Glu180Lys missense NM_000366.6:c.538G>A NP_000357.3:p.Glu180Lys missense NM_001018004.2:c.538G>A NP_001018004.1:p.Glu180Lys missense NM_001018006.2:c.538G>A NP_001018006.1:p.Glu180Lys missense NM_001018007.2:c.538G>A NP_001018007.1:p.Glu180Lys missense NM_001018008.2:c.430G>A NP_001018008.1:p.Glu144Lys missense NM_001018020.2:c.538G>A NP_001018020.1:p.Glu180Lys missense NM_001301244.2:c.538G>A NP_001288173.1:p.Glu180Lys missense NM_001301289.2:c.430G>A NP_001288218.1:p.Glu144Lys missense NM_001330344.2:c.430G>A NP_001317273.1:p.Glu144Lys missense NM_001330346.2:c.430G>A NP_001317275.1:p.Glu144Lys missense NM_001330351.2:c.430G>A NP_001317280.1:p.Glu144Lys missense NM_001365776.1:c.538G>A NP_001352705.1:p.Glu180Lys missense NM_001365777.1:c.538G>A NP_001352706.1:p.Glu180Lys missense NM_001365778.1:c.664G>A NP_001352707.1:p.Glu222Lys missense NM_001365779.1:c.538G>A NP_001352708.1:p.Glu180Lys missense NM_001365780.1:c.430G>A NP_001352709.1:p.Glu144Lys missense NM_001365781.2:c.430G>A NP_001352710.1:p.Glu144Lys missense NM_001365782.1:c.430G>A NP_001352711.1:p.Glu144Lys missense NC_000015.10:g.63060914G>A NC_000015.9:g.63353113G>A NG_007557.1:g.23276G>A LRG_387:g.23276G>A LRG_387t1:c.538G>A LRG_387p1:p.Glu180Lys - Protein change
- E144K, E180K, E222K
- Other names
- -
- Canonical SPDI
- NC_000015.10:63060913:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
- 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 |
797 | 846 |
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
|
Mar 16, 2021 | RCV001298950.6 |
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. |
|
---|---|---|---|---|---|
Likely pathogenic
(Mar 16, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hypertrophic cardiomyopathy
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001488021.4
First in ClinVar: Mar 07, 2021 Last updated: Feb 28, 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. This variant disrupts the p.Glu180 amino acid residue in TPM1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8205619, 22155441, 9245729, 11603924, 22789852). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with clinical features of restrictive cardiomyopathy (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 180 of the TPM1 protein (p.Glu180Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. (less)
|
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 |
---|---|---|---|---|
The flexibility of two tropomyosin mutants, D175N and E180G, that cause hypertrophic cardiomyopathy. | Li XE | Biochemical and biophysical research communications | 2012 | PMID: 22789852 |
The effect of the Asp175Asn and Glu180Gly TPM1 mutations on actin-myosin interaction during the ATPase cycle. | Rysev NA | Biochimica et biophysica acta | 2012 | PMID: 22155441 |
A familial hypertrophic cardiomyopathy alpha-tropomyosin mutation causes severe cardiac hypertrophy and death in mice. | Prabhakar R | Journal of molecular and cellular cardiology | 2001 | PMID: 11603924 |
Effects of two hypertrophic cardiomyopathy mutations in alpha-tropomyosin, Asp175Asn and Glu180Gly, on Ca2+ regulation of thin filament motility. | Bing W | Biochemical and biophysical research communications | 1997 | PMID: 9245729 |
Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. | Thierfelder L | Cell | 1994 | PMID: 8205619 |
Text-mined citations for rs1555409132 ...
HelpRecord last updated Mar 05, 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.