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NM_000363.5(TNNI3):c.428C>A (p.Thr143Asn)

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Interpretation:
Uncertain significance​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6 (Most recent: Oct 1, 2021)
Last evaluated:
Nov 24, 2020
Accession:
VCV000043382.9
Variation ID:
43382
Description:
single nucleotide variant
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NM_000363.5(TNNI3):c.428C>A (p.Thr143Asn)

Allele ID
52552
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
19q13.42
Genomic location
19: 55154151 (GRCh38) GRCh38 UCSC
19: 55665519 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_679:g.88C>A
NC_000019.10:g.55154151G>T
NC_000019.9:g.55665519G>T
... more HGVS
Protein change
T143N
Other names
p.T143N:ACC>AAC
Canonical SPDI
NC_000019.10:55154150:G:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00004
Links
ClinGen: CA021641
dbSNP: rs397516348
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Aug 30, 2017 RCV000036291.3
Uncertain significance 3 criteria provided, single submitter Jan 16, 2020 RCV000159221.4
Uncertain significance 1 criteria provided, single submitter Apr 17, 2019 RCV000628944.4
Uncertain significance 1 criteria provided, single submitter Nov 24, 2020 RCV001192353.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
TNNI3 Little evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
438 493

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Aug 30, 2017)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000059943.6
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (5)
Comment:
The p.Thr143Asn variant in TNNI3 has been reported in 1 individual with HCM and 3 individuals with early onset HCM, 2 of whom carried an … (more)
Uncertain significance
(Apr 17, 2019)
criteria provided, single submitter
Method: clinical testing
Hypertrophic cardiomyopathy
Allele origin: germline
Invitae
Accession: SCV000749852.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (8)
Comment:
This sequence change replaces threonine with asparagine at codon 143 of the TNNI3 protein (p.Thr143Asn). The threonine residue is highly conserved and there is a … (more)
Uncertain significance
(Nov 24, 2020)
criteria provided, single submitter
Method: clinical testing
Cardiomyopathy
Allele origin: germline
Color Health, Inc
Accession: SCV001360400.2
Submitted: (Jun 11, 2021)
Evidence details
Comment:
This missense variant replaces threonine with asparagine at codon 143 of the TNNI3 protein. Computational prediction suggests that this variant may not impact protein structure … (more)
Uncertain significance
(Jan 16, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000209167.11
Submitted: (Oct 01, 2021)
Evidence details
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the … (more)
Uncertain significance
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Clinical Genetics,Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001922074.1
Submitted: (Sep 23, 2021)
Evidence details
Uncertain significance
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Human Genetics - Radboudumc,Radboudumc
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001951831.1
Submitted: (Sep 30, 2021)
Evidence details

Functional evidence

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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 this variant

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
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
Comprehensive Versus Targeted Genetic Testing in Children with Hypertrophic Cardiomyopathy. Bales ND Pediatric cardiology 2016 PMID: 26936621
Comparison of echocardiographic and cardiac magnetic resonance imaging in hypertrophic cardiomyopathy sarcomere mutation carriers without left ventricular hypertrophy. Valente AM Circulation. Cardiovascular genetics 2013 PMID: 23690394
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
Negative charges at protein kinase C sites of troponin I stabilize the inactive state of actin. Mathur MC Biophysical journal 2008 PMID: 17872964
PKC-betaII sensitizes cardiac myofilaments to Ca2+ by phosphorylating troponin I on threonine-144. Wang H Journal of molecular and cellular cardiology 2006 PMID: 17010989
Functional effects of rho-kinase-dependent phosphorylation of specific sites on cardiac troponin. Vahebi S Circulation research 2005 PMID: 15774859
Cardiac troponin I mutants. Phosphorylation by protein kinases C and A and regulation of Ca(2+)-stimulated MgATPase of reconstituted actomyosin S-1. Noland TA Jr The Journal of biological chemistry 1995 PMID: 7592712

Text-mined citations for rs397516348...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 06, 2021