ClinVar Genomic variation as it relates to human health
NM_001276345.2(TNNT2):c.143C>T (p.Thr48Ile)
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_001276345.2(TNNT2):c.143C>T (p.Thr48Ile)
Variation ID: 1805009 Accession: VCV001805009.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q32.1 1: 201368182 (GRCh38) [ NCBI UCSC ] 1: 201337310 (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 Dec 24, 2022 Dec 24, 2022 May 6, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001276345.2:c.143C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001263274.1:p.Thr48Ile missense NM_000364.4:c.143C>T NP_000355.2:p.Thr48Ile missense NM_001001430.3:c.113C>T NP_001001430.1:p.Thr38Ile missense NM_001001431.3:c.113C>T NP_001001431.1:p.Thr38Ile missense NM_001001432.3:c.98C>T NP_001001432.1:p.Thr33Ile missense NM_001276346.2:c.143C>T NP_001263275.1:p.Thr48Ile missense NM_001276347.2:c.113C>T NP_001263276.1:p.Thr38Ile missense NM_001406723.1:c.143C>T NP_001393652.1:p.Thr48Ile missense NM_001406724.1:c.113C>T NP_001393653.1:p.Thr38Ile missense NM_001406725.1:c.113C>T NP_001393654.1:p.Thr38Ile missense NM_001406726.1:c.113C>T NP_001393655.1:p.Thr38Ile missense NM_001406727.1:c.113C>T NP_001393656.1:p.Thr38Ile missense NM_001406728.1:c.98C>T NP_001393657.1:p.Thr33Ile missense NC_000001.11:g.201368182G>A NC_000001.10:g.201337310G>A NG_007556.1:g.14496C>T LRG_431:g.14496C>T LRG_431t1:c.143C>T LRG_431p1:p.Thr48Ile - Protein change
- T33I, T38I, T48I
- Other names
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- Canonical SPDI
- NC_000001.11:201368181: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
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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 | ||
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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
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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TNNT2 | No evidence available | No evidence available |
GRCh38 GRCh37 |
898 | 917 |
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
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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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Uncertain significance (1) |
criteria provided, single submitter
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May 6, 2021 | RCV002471427.1 |
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
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
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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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Uncertain significance
(May 06, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy 2
(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: SCV002768061.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3C. 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 VUS-3C. Following criteria are met: 0105 - The mechanism of disease for this gene is not clearly established. Functional studies have suggested loss-of-function, gain-of-function and dominant-negative mechanisms based on calcium sensitivity, contractibility and mouse models (PMID: 18612386, 32098556, 33025817, ClinGen). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Variants in this gene have been reported to cause both HCM and dilated cardiomyopathy (PMID: 26507537). (I) 0200 - Variant is predicted to result in a missense amino acid change from threonine to isoleucine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0504 - Same amino acid change has been observed in placental mammals. (SB) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. This alternative missense variant (p.(Thr48Asn)) has been reported as pathogenic, and observed in an individual with hypertrophic cardiomyopathy (HCM). However, this individual also had a pathogenic variant in the MYBPC3 gene, which results in a premature termination codon (PMID: 25132132). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
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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 |
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Development of a Cardiac Sarcomere Functional Genomics Platform to Enable Scalable Interrogation of Human TNNT2 Variants. | Pettinato AM | Circulation | 2020 | PMID: 33025817 |
Variant R94C in TNNT2-Encoded Troponin T Predisposes to Pediatric Restrictive Cardiomyopathy and Sudden Death Through Impaired Thin Filament Relaxation Resulting in Myocardial Diastolic Dysfunction. | Ezekian JE | Journal of the American Heart Association | 2020 | PMID: 32098556 |
Clinical and Prognostic Profiles of Cardiomyopathies Caused by Mutations in the Troponin T Gene. | Ripoll-Vera T | Revista espanola de cardiologia (English ed.) | 2016 | PMID: 26507537 |
Malignant effects of multiple rare variants in sarcomere genes on the prognosis of patients with hypertrophic cardiomyopathy. | Wang J | European journal of heart failure | 2014 | PMID: 25132132 |
The role of cardiac troponin T quantity and function in cardiac development and dilated cardiomyopathy. | Ahmad F | PloS one | 2008 | PMID: 18612386 |
Text-mined citations for this variant ...
HelpRecord last updated Dec 24, 2022
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.