ClinVar Genomic variation as it relates to human health
NM_001018005.2(TPM1):c.574G>A (p.Glu192Lys)
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.574G>A (p.Glu192Lys)
Variation ID: 31882 Accession: VCV000031882.27
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 15q22.2 15: 63061723 (GRCh38) [ NCBI UCSC ] 15: 63353922 (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 Aug 25, 2024 Dec 30, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001018005.2:c.574G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001018005.1:p.Glu192Lys missense NM_000366.6:c.639+450G>A intron variant NM_001018004.2:c.574G>A NP_001018004.1:p.Glu192Lys missense NM_001018006.2:c.639+450G>A intron variant NM_001018007.2:c.574G>A NP_001018007.1:p.Glu192Lys missense NM_001018008.2:c.466G>A NP_001018008.1:p.Glu156Lys missense NM_001018020.2:c.639+450G>A intron variant NM_001301244.2:c.574G>A NP_001288173.1:p.Glu192Lys missense NM_001301289.2:c.466G>A NP_001288218.1:p.Glu156Lys missense NM_001330344.2:c.531+450G>A intron variant NM_001330346.2:c.466G>A NP_001317275.1:p.Glu156Lys missense NM_001330351.2:c.531+450G>A intron variant NM_001365776.1:c.574G>A NP_001352705.1:p.Glu192Lys missense NM_001365777.1:c.574G>A NP_001352706.1:p.Glu192Lys missense NM_001365778.1:c.700G>A NP_001352707.1:p.Glu234Lys missense NM_001365779.1:c.574G>A NP_001352708.1:p.Glu192Lys missense NM_001365780.1:c.466G>A NP_001352709.1:p.Glu156Lys missense NM_001365781.2:c.531+450G>A intron variant NM_001365782.1:c.466G>A NP_001352711.1:p.Glu156Lys missense NC_000015.10:g.63061723G>A NC_000015.9:g.63353922G>A NG_007557.1:g.24085G>A LRG_387:g.24085G>A LRG_387t1:c.574G>A LRG_387p1:p.Glu192Lys P09493:p.Glu192Lys - Protein change
- E192K, E156K, E234K
- Other names
- p.E192K:GAG>AAG
- Canonical SPDI
- NC_000015.10:63061722: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
Help
The frequency of the allele represented by this VCV record.
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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
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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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Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Nov 21, 2023 | RCV000024578.16 | |
Pathogenic (1) |
no assertion criteria provided
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Aug 1, 2011 | RCV000054795.24 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 5, 2015 | RCV000208146.4 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jul 16, 2023 | RCV000578109.5 | |
Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Dec 30, 2023 | RCV000526765.14 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 13, 2022 | RCV002345253.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 13, 2021 | RCV003149576.2 |
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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Pathogenic
(Nov 05, 2015)
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criteria provided, single submitter
Method: clinical testing
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Primary familial hypertrophic cardiomyopathy
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV000264261.2
First in ClinVar: Feb 27, 2016 Last updated: Sep 22, 2018 |
Number of individuals with the variant: 1
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Pathogenic
(Aug 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy 3
Affected status: unknown
Allele origin:
germline
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Phosphorus, Inc.
Accession: SCV000679817.1
First in ClinVar: Jan 28, 2018 Last updated: Jan 28, 2018 |
Number of individuals with the variant: 1
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Pathogenic
(Jun 01, 2023)
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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: SCV000209318.17
First in ClinVar: Feb 24, 2015 Last updated: Nov 25, 2023 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; … (more)
Not observed at significant frequency in large population cohorts (gnomAD); 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: 27532257, 12858563, 12860912, 25241052, 23700264, 21415410, 24510615, 20031602, 21551322, 26960954, 27639548, 21310275, 16365313, 25524337, 18409188, 23771913, 27376658, 25611685, 23396983, 24033266, 31006259, 34319370, 28193612, 35176663, 33297573, 34540771, 28615295) (less)
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Likely pathogenic
(Oct 29, 2015)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000060282.6
First in ClinVar: May 03, 2013 Last updated: Aug 26, 2019 |
Comment:
The p.Glu192Lys variant in TPM1 has been reported in more than 20 individuals wi th HCM (Van Driest 2003, Ho 2009, Probst 2011, Deva 2013, … (more)
The p.Glu192Lys variant in TPM1 has been reported in more than 20 individuals wi th HCM (Van Driest 2003, Ho 2009, Probst 2011, Deva 2013, Kapplinger 2014, Coppi ni 2014, LMM unpublished data) and segregated with disease in 4 affected relativ es from 4 different families (LMM unpublished data). It is absent from large pop ulation studies. Glutamic acid (Glu) at position 192 is highly conserved in mamm als and across evolutionarily distant species and the change to Lysine (Lys) was predicted to be pathogenic using a computational tool clinically validated by o ur laboratory. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jordan 2011). In summary, this variant is likely to be pathogenic, though additional studies are required to fully establish its clinical significa nce. (less)
Number of individuals with the variant: 27
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Pathogenic
(Mar 21, 2017)
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criteria provided, single submitter
Method: research
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Hypertrophic cardiomyopathy
Affected status: yes
Allele origin:
germline
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Agnes Ginges Centre for Molecular Cardiology, Centenary Institute
Accession: SCV000996338.2
First in ClinVar: Nov 02, 2019 Last updated: Jan 09, 2020 |
Comment:
This TPM1 Glu192Lys has since been identified in numerous HCM cases and co-segregated in affected family members (Ho CY, et al., 2009; Probst S, et … (more)
This TPM1 Glu192Lys has since been identified in numerous HCM cases and co-segregated in affected family members (Ho CY, et al., 2009; Probst S, et al., 2011; Deva DP, et al., 2013; Kapplinger JD, et al., 2014; Mango R, et al., 2016; ClinVar:SCV000209318, SCV000220120; https://cardiodb.org/ACGV/acgv_variant.php?id=5992). Interestingly, Mango et al., (2016) identified this variant co-segregating with HCM in 4 affected family members who also had signs of Brugada Syndrome. Furthermore, this variant is absent in population databases including the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/). Glutamic acid (Glu) at position 192 is highly conserved across distantly related species and in silico tools (SIFT, MutationTaster, PolyPhen-2) predict this variant to be disease-causing. We have identified this variant in one HCM patient with moderate asymmetric hypertrophy. There is no family history of HCM or SCD. In summary, based on its absence in the general population, observation in multiple unrelated HCM cases, strong segregation data and in silico predictions, we classify TPM1 Glu192Lys as "pathogenic". (less)
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Likely pathogenic
(May 28, 2021)
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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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AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002501209.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 1
Secondary finding: no
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Pathogenic
(Oct 13, 2021)
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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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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV003837751.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
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Pathogenic
(Oct 19, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002020269.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Dec 30, 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: SCV000623807.9
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 192 of the TPM1 protein … (more)
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 192 of the TPM1 protein (p.Glu192Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hypertrophic cardiomyopathy (HCM) and left-ventricular non-compaction (LVNC) and HCM (PMID: 18409188, 20031602, 21551322, 23771913, 24510615, 26960954, 27639548). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 31882). An algorithm developed specifically for the TPM1 gene suggests that this missense change is likely to be deleterious (PMID: 21310275). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jul 13, 2022)
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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: SCV002651645.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.E192K pathogenic mutation (also known as c.574G>A), located in coding exon 6 of the TPM1 gene, results from a G to A substitution at … (more)
The p.E192K pathogenic mutation (also known as c.574G>A), located in coding exon 6 of the TPM1 gene, results from a G to A substitution at nucleotide position 574. The glutamic acid at codon 192 is replaced by lysine, an amino acid with similar properties. This alteration has been reported in numerous individuals with hypertrophic cardiomyopathy (HCM) and was shown to co-segregate with disease in one family (Deva DP et al. Radiology. 2013;269:68-76; Coppini R et al. J. Am. Coll. Cardiol. 2014;64:2589-2600; Kapplinger JD et al. J Cardiovasc Transl Res. 2014;7:347-61; Lopes LR et al. Heart. 2015;101:294-301; Mango R et al. Circ. J. 2016;80:938-49; Ross SB et al. Circ Cardiovasc Genet. 2017;10(3):e001671; Walsh R et al. Genet. Med. 2017;19:192-203). This variant has also been detected in one patient with left ventricular noncompaction (LVNC) (Probst S et al. Circ Cardiovasc Genet. 2011;4:367-74). This missense alteration is located in a region that has a low rate of benign missense variation (Lek M et al. Nature. 2016 Aug 18;536(7616):285-91; DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. Firth H.V. et al. 2009. Am.J.Hum.Genet. 84, 524-533 (DOI: dx.doi.org/10/1016/j.ajhg.2009.03.010)). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by BayesDel in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Jul 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy 3
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002769399.2
First in ClinVar: Dec 24, 2022 Last updated: Jul 23, 2024 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0105 - The mechanism of disease for this gene … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0105 - The mechanism of disease for this gene is not clearly established, although it has been suggested that that HCM is caused by gain of function missense variants while DCM is caused by loss of function missense variants (PMID: 31270709). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0112 - The condition associated with this gene has incomplete penetrance. Variants in this gene have been associated with late-onset disease or incomplete penetrance (PMIDs: 33642254; 32882290, 32731933). (I) 0200 - Variant is predicted to result in a missense amino acid change from glutamic acid to lysine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated tropomyosin domain (DECIPHER). (I) 0801 - This variant has very strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in multiple individuals or families with HCM and is the most common TPM1 pathogenic variant associated with HCM (ClinVar, PMIDs: 24510615, 27532257; 21551322, 26960954, 34638741). (SP) 1208 - Inheritance information is currently unavailable for this individual. (I) Legend: (SP) - Supporting Pathogenic, (I) – Information, (SB) – Supporting Benign (less)
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Likely pathogenic
(Nov 21, 2023)
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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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Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005198858.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
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Pathogenic
(Aug 01, 2011)
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no assertion criteria provided
Method: literature only
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LEFT VENTRICULAR NONCOMPACTION 9
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000083040.1
First in ClinVar: Sep 05, 2013 Last updated: Sep 05, 2013 |
Comment on evidence:
In a 55-year-old white man of western European descent with left ventricular noncompaction (LVNC9; see 611878), Probst et al. (2011) identified heterozygosity for a c.765G-A … (more)
In a 55-year-old white man of western European descent with left ventricular noncompaction (LVNC9; see 611878), Probst et al. (2011) identified heterozygosity for a c.765G-A transition in exon 6 of the TPM1 gene, resulting in a glu192-to-lys (E192K) substitution at a highly conserved residue. Echocardiography revealed pronounced noncompaction of the apex and left midventricular wall, as well as increased right ventricular trabeculations. His son, who did not carry the mutation, showed normal left ventricular morphology and function on echocardiogram. (less)
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Likely pathogenic
(Aug 05, 2016)
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no assertion criteria provided
Method: provider interpretation
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not provided
Affected status: unknown
Allele origin:
germline
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Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000280539.2
First in ClinVar: Jun 01, 2016 Last updated: Nov 08, 2018 |
Comment:
p.Glu192Lys (c.574G>A) in the TPM1 gene. Seen in our center in an adult with HCM with a family history of HCM and sudden death. We … (more)
p.Glu192Lys (c.574G>A) in the TPM1 gene. Seen in our center in an adult with HCM with a family history of HCM and sudden death. We re-reviewed the results August 4th, 2016. We had initially classified this as a VUS. Given the strong case data and absence in controls we now consider the variant likely pathogenic and we do feel it is appropriate for assessing risk in healthy relatives (predictive genetic testing). Seen in at least 18 presumably unrelated cases of HCM (7 published, 11 unpublished) and one case of LVNC. It has segregated with disease in at least three affected relatives. Deva et al. (2013) reported this variant in one out of 300 patients with HCM that were cared for in Toronto, Canada, who underwent analysis of unreported genes. Ancestry was not reported. Ho et al. (2009) reported this variant in one out of 40 patients with HCM that were cared for in Boston, MA, Minneapolis, MN, and Copenhagen, Denmark, who underwent analysis of at least the MYH7, MYBPC3, TNNT2, TNNI3, and TPM1 genes. Kapplinger et al. (2013) reported this variant in four out of 2,178 patients with HCM that were cared for in Mayo Clinic in Rochester, Minnesota or tested by Transgenomic Inc. Patients underwent analysis of the MYH7, MYL2, MYL3, MYBPC3, ACTC, TNNC1, TNNI3, TNNT2, and TPM1 genes. Patient specific ancestry was not reported. Fokstuen et al. (2008) reported this variant in one out of 8 patients with HCM of unreported ancestry that were cared for in University College London Hospitals, London, United Kingdom. They performed analysis of HCM associated genes including: MYH7, MYBPC3, TNNT2, TPM1, TNNI3, MYL3, MYL2, CSRP3, PLN, ACTC, TNNC1, and PRKAG2. Probst et al. (2011) reported this variant in one out of 63 LVNC cases of western European ancestry that were cared for in University Hospital Zurich, Switzerland, and the German Heart Institute Berlin, Germany, who underwent analysis of MYH7, ACTC1, TNNT2, TNNI3, MYL2, MYL3, TPM1 and MYBPC3 genes. The proband is a 55-year-old male, who presented with sudden chest pain, dyspnea, pronounced midventricular wall LVNC and increased right ventricular trabeculations. In LMM's summary report submitted to ClinVar (4/10/2014), they note that they have identified this variant in at least 11 presumably unrelated cases of HCM and 3 affected family members (unclear if they are from the same family or different families). These cases likely overlap with others, including those reported by Ho et al. In silico analysis with PolyPhen-2 predicts the variant to be benign and SIFT predicts the variant to be not tolerated. Glutamic acid at position 192 is highly conserved in mammals and across evolutionarily distant species. No other variants have been reported in association with disease at this codon. This variant lies in the troponin T binding region of alpha-tropomyosin, as do several other TPM1 variants that have been observed in patients with primary cardiomyopathies (p.Ile172Thr; p.Asp175Asn; p.Glu180Gly; p.Glu180Val; p.Leu185Arg) (Jagatheesan, 2010). It has been suggested that variants in this domain may disrupt calcium signaling and tropomyosin - troponin T binding (Wieczorek, 2008). LMM notes that a computational tool clinically validated by their laboratory predicts this variant to be pathogenic. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jordan, 2011). In total the variant has not been seen in ~61,476 individuals from published controls and publicly available datasets that approximate the general population. The variant was absent in 60,335 individuals in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/), which currently includes variant calls on ~64,000 individuals of European, African, Latino and Asian descent (as of April 22nd, 2015). The phenotype of those individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population; others were enriched for common cardiovascular disease. Median coverage in ExAC is >70. The variant was not observed in the following lab control samples: 400 by Familion labs. The variant was not observed in the following published control samples: 38 in Ho (2009), 96 in Fokstuen (2008), and 427 in Kapplinger (2013), 180 in Probst (2011). (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: research
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Hypertrophic cardiomyopathy 3
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
somatic
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Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences
Accession: SCV002499630.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Comment:
The TPM1 gene encodes Tropomyosin 1 which involves in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. Mutations in … (more)
The TPM1 gene encodes Tropomyosin 1 which involves in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. Mutations in TPM1 result in Hypertrophic cardiomyopathy with an autosomal dominant inheritance (OMIM: 115196). (less)
Age: 50-59 years
Sex: male
Ethnicity/Population group: Iranian
Geographic origin: Iran
Testing laboratory: Whole exome sequencing
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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
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Leiden Muscular Dystrophy (TPM1)
Accession: SCV000045887.1
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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has functional consequence
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Leiden Muscular Dystrophy (TPM1)
Accession: SCV000045887.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Genotype-phenotype correlations in hypertrophic cardiomyopathy: a multicenter study in Portugal and Spain of the TPM1 p.Arg21Leu variant. | Lamounier Junior A | Revista espanola de cardiologia (English ed.) | 2022 | PMID: 33642254 |
Genetic Testing in Patients with Hypertrophic Cardiomyopathy. | Bonaventura J | International journal of molecular sciences | 2021 | PMID: 34638741 |
The effect of tropomyosin variants on cardiomyocyte function and structure that underlie different clinical cardiomyopathy phenotypes. | Dorsch LM | International journal of cardiology | 2021 | PMID: 32882290 |
Yield of Rare Variants Detected by Targeted Next-Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy. | Micheu MM | Diagnostics (Basel, Switzerland) | 2020 | PMID: 33297573 |
Penetrance of Hypertrophic Cardiomyopathy in Sarcomere Protein Mutation Carriers. | Lorenzini M | Journal of the American College of Cardiology | 2020 | PMID: 32731933 |
Thin filament dysfunctions caused by mutations in tropomyosin Tpm3.12 and Tpm1.1. | Moraczewska J | Journal of muscle research and cell motility | 2020 | PMID: 31270709 |
Yield of Clinical Screening for Hypertrophic Cardiomyopathy in Child First-Degree Relatives. | Norrish G | Circulation | 2019 | PMID: 31006259 |
Care in Specialized Centers and Data Sharing Increase Agreement in Hypertrophic Cardiomyopathy Genetic Test Interpretation. | Furqan A | Circulation. Cardiovascular genetics | 2017 | PMID: 28986452 |
Burden of Recurrent and Ancestral Mutations in Families With Hypertrophic Cardiomyopathy. | Ross SB | Circulation. Cardiovascular genetics | 2017 | PMID: 28615295 |
Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. | Walsh R | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 27532257 |
Multiplexed Reference Materials as Controls for Diagnostic Next-Generation Sequencing: A Pilot Investigating Applications for Hypertrophic Cardiomyopathy. | Kudalkar EM | The Journal of molecular diagnostics : JMD | 2016 | PMID: 27639548 |
Investigating the effects of tropomyosin mutations on its flexibility and interactions with filamentous actin using molecular dynamics simulation. | Zheng W | Journal of muscle research and cell motility | 2016 | PMID: 27376658 |
Next Generation Sequencing and Linkage Analysis for the Molecular Diagnosis of a Novel Overlapping Syndrome Characterized by Hypertrophic Cardiomyopathy and Typical Electrical Instability of Brugada Syndrome. | Mango R | Circulation journal : official journal of the Japanese Circulation Society | 2016 | PMID: 26960954 |
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. | Alfares AA | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25611685 |
Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy. | Lopes LR | Heart (British Cardiac Society) | 2015 | PMID: 25351510 |
Clinical phenotype and outcome of hypertrophic cardiomyopathy associated with thin-filament gene mutations. | Coppini R | Journal of the American College of Cardiology | 2014 | PMID: 25524337 |
Energy landscapes reveal the myopathic effects of tropomyosin mutations. | Orzechowski M | Archives of biochemistry and biophysics | 2014 | PMID: 25241052 |
Distinguishing hypertrophic cardiomyopathy-associated mutations from background genetic noise. | Kapplinger JD | Journal of cardiovascular translational research | 2014 | PMID: 24510615 |
A systematic approach to assessing the clinical significance of genetic variants. | Duzkale H | Clinical genetics | 2013 | PMID: 24033266 |
Deep basal inferoseptal crypts occur more commonly in patients with hypertrophic cardiomyopathy due to disease-causing myofilament mutations. | Deva DP | Radiology | 2013 | PMID: 23771913 |
Genetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing. | Lopes LR | Journal of medical genetics | 2013 | PMID: 23396983 |
Sarcomere gene mutations in isolated left ventricular noncompaction cardiomyopathy do not predict clinical phenotype. | Probst S | Circulation. Cardiovascular genetics | 2011 | PMID: 21551322 |
Development and validation of a computational method for assessment of missense variants in hypertrophic cardiomyopathy. | Jordan DM | American journal of human genetics | 2011 | PMID: 21310275 |
Echocardiographic strain imaging to assess early and late consequences of sarcomere mutations in hypertrophic cardiomyopathy. | Ho CY | Circulation. Cardiovascular genetics | 2009 | PMID: 20031602 |
ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007. | Richards CS | Genetics in medicine : official journal of the American College of Medical Genetics | 2008 | PMID: 18414213 |
A DNA resequencing array for pathogenic mutation detection in hypertrophic cardiomyopathy. | Fokstuen S | Human mutation | 2008 | PMID: 18409188 |
Structure of the mid-region of tropomyosin: bending and binding sites for actin. | Brown JH | Proceedings of the National Academy of Sciences of the United States of America | 2005 | PMID: 16365313 |
Prevalence and spectrum of thin filament mutations in an outpatient referral population with hypertrophic cardiomyopathy. | Van Driest SL | Circulation | 2003 | PMID: 12860912 |
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Text-mined citations for rs199476315 ...
HelpRecord last updated Aug 25, 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.