ClinVar Genomic variation as it relates to human health
NM_001276345.2(TNNT2):c.298A>G (p.Ile100Val)
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_001276345.2(TNNT2):c.298A>G (p.Ile100Val)
Variation ID: 1794769 Accession: VCV001794769.3
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 1q32.1 1: 201365304 (GRCh38) [ NCBI UCSC ] 1: 201334432 (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 Nov 29, 2022 Dec 24, 2023 Apr 11, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001276345.2:c.298A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001263274.1:p.Ile100Val missense NM_000364.4:c.298A>G NP_000355.2:p.Ile100Val missense NM_001001430.3:c.268A>G NP_001001430.1:p.Ile90Val missense NM_001001431.3:c.268A>G NP_001001431.1:p.Ile90Val missense NM_001001432.3:c.253A>G NP_001001432.1:p.Ile85Val missense NM_001276346.2:c.291+306A>G intron variant NM_001276347.2:c.268A>G NP_001263276.1:p.Ile90Val missense NM_001406723.1:c.298A>G NP_001393652.1:p.Ile100Val missense NM_001406724.1:c.268A>G NP_001393653.1:p.Ile90Val missense NM_001406725.1:c.265A>G NP_001393654.1:p.Ile89Val missense NM_001406726.1:c.268A>G NP_001393655.1:p.Ile90Val missense NM_001406727.1:c.268A>G NP_001393656.1:p.Ile90Val missense NM_001406728.1:c.253A>G NP_001393657.1:p.Ile85Val missense NC_000001.11:g.201365304T>C NC_000001.10:g.201334432T>C NG_007556.1:g.17374A>G LRG_431:g.17374A>G LRG_431t1:c.298A>G LRG_431p1:p.Ile100Val - Protein change
- I90V, I100V, I85V, I89V
- Other names
- -
- Canonical SPDI
- NC_000001.11:201365303:T:C
-
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. |
|||
TNNT2 | No evidence available | No evidence available |
GRCh38 GRCh37 |
946 | 964 |
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. |
---|---|---|---|---|
Uncertain significance (1) |
criteria provided, single submitter
|
Sep 7, 2021 | RCV002453174.1 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Apr 11, 2023 | RCV002471287.2 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Apr 11, 2023 | RCV003455490.1 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Apr 11, 2023 | RCV003455491.1 |
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
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. |
|
---|---|---|---|---|---|
Uncertain significance
(Sep 07, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002739115.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
The p.I90V variant (also known as c.268A>G), located in coding exon 8 of the TNNT2 gene, results from an A to G substitution at nucleotide … (more)
The p.I90V variant (also known as c.268A>G), located in coding exon 8 of the TNNT2 gene, results from an A to G substitution at nucleotide position 268. The isoleucine at codon 90 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
Number of individuals with the variant: 1
|
|
Uncertain significance
(Feb 02, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hypertrophic cardiomyopathy 2
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002768248.1
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-3A. 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-3A. 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). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity. p.(Arg92Gln) has been described in families which has both DCM and HCM (PMID: 26507537). (I) 0200 - Variant is predicted to result in a missense amino acid change from isoleucine to valine. (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) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0708 - Other missense variants comparable to the one identified in this case have limited previous evidence for pathogenicity. The p.(Ile100Asn) variant has been reported as a VUS in an individual with hypertrophic cardiomyopathy (HCM; PMID: 27532257). Another variant p.(Ile100Met) has been reported as a VUS in ClinVar, and has been shown to segregate with HCM in a large family, however several unaffected individuals were heterozygous for the variant (PMID: 19061534). (I) 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. Variant was not detected in the mother during segregation, however father was not tested. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
|
|
Uncertain significance
(Apr 11, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Dilated cardiomyopathy 1D
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV004181501.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
|
|
Uncertain significance
(Apr 11, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hypertrophic cardiomyopathy 2
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV004181503.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
|
|
Uncertain significance
(Apr 11, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiomyopathy, familial restrictive, 3
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV004181502.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
|
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 |
---|---|---|---|---|
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 |
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 |
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 |
Ile90Met, a novel mutation in the cardiac troponin T gene for familial hypertrophic cardiomyopathy in a Chinese pedigree. | Xu C | Genetics research | 2008 | PMID: 19061534 |
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 30, 2023
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.