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NM_000364.4(TNNT2):c.508_510GAG[3] (p.Glu173del)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6 (Most recent: May 8, 2019)
Last evaluated:
Dec 26, 2018
Accession:
VCV000043648.5
Variation ID:
43648
Description:
3bp microsatellite
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NM_000364.4(TNNT2):c.508_510GAG[3] (p.Glu173del)

Allele ID
52817
Variant type
Microsatellite
Variant length
3 bp
Cytogenetic location
1q32.1
Genomic location
1: 201363377-201363379 (GRCh38) GRCh38 UCSC
1: 201332505-201332507 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000001.10:g.201332505_201332507CTC[3]
NC_000001.11:g.201363377_201363379CTC[3]
NM_000364.4:c.508_510GAG[3] NP_000355.2:p.Glu173del
... more HGVS
Protein change
E163del
Other names
-
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA004651
dbSNP: rs397516470
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 3 criteria provided, multiple submitters, no conflicts Mar 16, 2018 RCV000624557.3
Pathogenic 1 criteria provided, single submitter Oct 8, 2012 RCV000211867.5
Pathogenic 1 criteria provided, single submitter Dec 26, 2018 RCV000459834.5
Pathogenic 1 criteria provided, single submitter Jul 26, 2017 RCV000620577.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
TNNT2 No evidence available No evidence available GRCh38
GRCh37
384 397

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Jul 26, 2017)
criteria provided, single submitter
Method: clinical testing
cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000739945.2
Submitted: (Jul 30, 2018)
Evidence details
Publications
PubMed (6)
Comment:
Lines of evidence used in support of classification: Strong segregation with disease (lod >3 = >10 meioses),Significant disease association in appropriately sized case-control study(ies),Detected in ... (more)
Pathogenic
(Dec 26, 2018)
criteria provided, single submitter
Method: clinical testing
Familial restrictive cardiomyopathy 3
Familial hypertrophic cardiomyopathy 2
Left ventricular noncompaction 6
Allele origin: germline
Invitae
Accession: SCV000541933.5
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (10)
Comment:
This sequence change deletes 3 nucleotides from exon 11 of the TNNT2 mRNA (c.487_489delGAG). This leads to the deletion of 1 amino acid residue in ... (more)
Pathogenic
(Nov 28, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute
Accession: SCV000740431.1
Submitted: (Aug 02, 2017)
Evidence details
Pathogenic
(Mar 16, 2018)
criteria provided, single submitter
Method: clinical testing
Not provided
Allele origin: germline
Blueprint Genetics
Accession: SCV000927600.1
Submitted: (May 08, 2019)
Comment:
Patient analyzed with Hypertrophic Cardiomyopathy (HCM) Panel
Evidence details
Pathogenic
(Oct 08, 2012)
criteria provided, single submitter
Method: clinical testing
Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine
Accession: SCV000060251.6
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (8)
Comment:
The p.Glu163del variant in TNNT2 has been previously reported in multiple famili es with HCM, segregated with disease in >10 affected family members, and was ... (more)
Pathogenic
(Apr 12, 2017)
no assertion criteria provided
Method: provider interpretation
not provided
Allele origin: germline
Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000924966.1
Submitted: (Aug 15, 2018)
Evidence details
Comment:
Testing for our patients was performed at the Invitae laboratory. Given the strong case data, supportive functional studies, and absence in general population databases, we ... (more)

Citations for this variant

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
Genetic Spectrum of Idiopathic Restrictive Cardiomyopathy Uncovered by Next-Generation Sequencing. Kostareva A PloS one 2016 PMID: 27662471
Mutations in troponin T associated with Hypertrophic Cardiomyopathy increase Ca(2+)-sensitivity and suppress the modulation of Ca(2+)-sensitivity by troponin I phosphorylation. Messer AE Archives of biochemistry and biophysics 2016 PMID: 27036851
Hypertrophic cardiomyopathy: one gene … but many phenotypes. Maron BJ The American journal of cardiology 2014 PMID: 24792744
Allosteric effects of cardiac troponin TNT1 mutations on actomyosin binding: a novel pathogenic mechanism for hypertrophic cardiomyopathy. Moore RK Archives of biochemistry and biophysics 2014 PMID: 24480310
Molecular effects of familial hypertrophic cardiomyopathy-related mutations in the TNT1 domain of cTnT. Manning EP Journal of molecular biology 2012 PMID: 22579624
Conduction abnormalities in pediatric patients with restrictive cardiomyopathy. Walsh MA Circulation. Heart failure 2012 PMID: 22260945
Long-term outcomes in hypertrophic cardiomyopathy caused by mutations in the cardiac troponin T gene. Pasquale F Circulation. Cardiovascular genetics 2012 PMID: 22144547
Prevalence and spectrum of mutations in a cohort of 192 unrelated patients with hypertrophic cardiomyopathy. Millat G European journal of medical genetics 2010 PMID: 20624503
Hypertrophic cardiomyopathy--molecular genetic analysis of exons 9 and 11 of the TNNT2 gene in Czech patients. Capek P Methods of information in medicine 2006 PMID: 16538283
Prevalence and clinical profile of troponin T mutations among patients with hypertrophic cardiomyopathy in tuscany. Torricelli F The American journal of cardiology 2003 PMID: 14636924
Comparison of fluorescent SSCP and denaturing HPLC analysis with direct sequencing for mutation screening in hypertrophic cardiomyopathy. Mogensen J Journal of medical genetics 2003 PMID: 12746413
Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Richard P Circulation 2003 PMID: 12707239
Disease-causing mutations in cardiac troponin T: identification of a critical tropomyosin-binding region. Palm T Biophysical journal 2001 PMID: 11606294
Functional consequences of the deletion mutation deltaGlu160 in human cardiac troponin T. Harada K Journal of biochemistry 2000 PMID: 10731693
Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy. Watkins H The New England journal of medicine 1995 PMID: 7898523

Record last updated Dec 15, 2019