ClinVar Genomic variation as it relates to human health
NM_000363.5(TNNI3):c.235C>T (p.Arg79Cys)
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.
Uncertain significance(1); Benign(5); Likely benign(8)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000363.5(TNNI3):c.235C>T (p.Arg79Cys)
Variation ID: 43367 Accession: VCV000043367.31
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19q13.42 19: 55156248 (GRCh38) [ NCBI UCSC ] 19: 55667616 (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 9, 2018 Feb 28, 2024 Jan 26, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000363.5:c.235C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000354.4:p.Arg79Cys missense NC_000019.10:g.55156248G>A NC_000019.9:g.55667616G>A NG_007866.2:g.6485C>T LRG_432:g.6485C>T LRG_432t1:c.235C>T P19429:p.Arg79Cys - Protein change
- R79C
- Other names
- p.R79C:CGC>TGC
- Canonical SPDI
- NC_000019.10:55156247: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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0.00120 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00043
The Genome Aggregation Database (gnomAD), exomes 0.00046
The Genome Aggregation Database (gnomAD) 0.00048
Trans-Omics for Precision Medicine (TOPMed) 0.00056
1000 Genomes Project 0.00120
1000 Genomes Project 30x 0.00141
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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TNNI3 | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
- | 723 |
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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Benign (1) |
criteria provided, single submitter
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Nov 22, 2017 | RCV000036275.13 | |
Benign (1) |
criteria provided, single submitter
|
Mar 20, 2019 | RCV000253834.3 | |
Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 26, 2024 | RCV000464815.12 | |
Benign (1) |
criteria provided, single submitter
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May 28, 2019 | RCV000991060.1 | |
Likely benign (6) |
criteria provided, multiple submitters, no conflicts
|
Oct 18, 2023 | RCV000721099.11 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Oct 11, 2018 | RCV001170622.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 13, 2018 | RCV001135030.4 | |
Likely benign (1) |
criteria provided, single submitter
|
Jan 13, 2018 | RCV001135032.4 | |
Likely benign (1) |
criteria provided, single submitter
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Jan 13, 2018 | RCV001135029.4 | |
Likely benign (1) |
criteria provided, single submitter
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Jan 13, 2018 | RCV001135031.4 |
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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Likely benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
Accession: SCV000987480.1
First in ClinVar: Sep 08, 2019 Last updated: Sep 08, 2019 |
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Likely benign
(Nov 20, 2019)
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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: SCV000209157.9
First in ClinVar: Feb 24, 2015 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 24510615, 15607392, 26506446, 21310275, 9241277, 32815737, 33078954)
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Benign
(Nov 22, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000059927.5
First in ClinVar: May 03, 2013 Last updated: Nov 08, 2018 |
Comment:
p.Arg79Cys in exon 5 of TNNI3: This variant is not expected to have clinical sig nificance because it has been identified in 0.6% (115/18670) of … (more)
p.Arg79Cys in exon 5 of TNNI3: This variant is not expected to have clinical sig nificance because it has been identified in 0.6% (115/18670) of East Asian chrom osomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute. org; dbSNP rs3729712). BA1 (less)
Number of individuals with the variant: 5
|
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Likely benign
(May 08, 2018)
|
criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy
Affected status: yes
Allele origin:
germline
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Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego
Accession: SCV000995486.1
First in ClinVar: Oct 11, 2019 Last updated: Oct 11, 2019 |
Number of individuals with the variant: 1
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Uncertain significance
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 2A
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001294796.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Likely benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy 7
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001294797.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
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Likely benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Cardiomyopathy, familial restrictive, 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001294795.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
|
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Likely benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001294798.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
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Benign
(Jul 03, 2018)
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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: SCV001333213.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
|
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Likely benign
(Oct 18, 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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV004564544.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
|
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Benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy 1
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001142165.1
First in ClinVar: Jan 10, 2020 Last updated: Jan 10, 2020 |
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Benign
(Oct 11, 2018)
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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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Color Diagnostics, LLC DBA Color Health
Accession: SCV001339283.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
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Benign
(Mar 20, 2019)
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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: SCV000319767.6
First in ClinVar: Oct 02, 2016 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Number of individuals with the variant: 1
|
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Likely benign
(Jan 26, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000562162.9
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001932501.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Likely benign
(Sep 06, 2017)
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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: SCV000280498.2
First in ClinVar: Jun 01, 2016 Last updated: Nov 08, 2018 |
Comment:
p.Arg79Cys (c.235C>T) in the TNNI3 gene. Given the frequency (0.1%) in Asian individuals unselected for HCM and the failure to segregate, we consider this variant … (more)
p.Arg79Cys (c.235C>T) in the TNNI3 gene. Given the frequency (0.1%) in Asian individuals unselected for HCM and the failure to segregate, we consider this variant likely benign, with potential to be a modifier. The variant has been seen in at least 6 unrelated cases of HCM (not including this patient's family). The p.Arg79Cys variant in TNNI3 was first reported by Kimura et al (1997) as a polymorphism in five unrelated patients with HCM and in healthy control individuals (detailed control data not provided). This cohort is likely of East Asian descent as the study was conducted in Japan. It was also noted the p.Arg79Cys variant did not segregate with cardiomyopathy in these five families. Subsequently, Mogensen et al. (2004) reported the p.Arg79Cys variant in an individual of Asian decent with HCM and considered it a polymorphism based on the previous report by Kimura et al. Segregation analysis was not performed in this family. In silico analysis with PolyPhen-2 predicts the variant to be probably damaging to the protein structure/function and mutationtaster predicts it to be disease-causing. The p.Arg79Cys variant at codon 79 is conserved across mammals, but not in x tropicalis (western clawed frog). Other variants have been reported in the Human Gene Mutation Database in association with disease at nearby codons (p.Arg74Pro, p.Pro82Ser) in association with cardiomyopathy (Stenson et al., 2009). In total the variant has been seen in 50 of ~53,696 published controls and individuals from publicly available population datasets. This variant is listed in dbSNP and 1000 genomes (rs3729712, as of 01/21/2015). The variant was observed in the following published control samples: Murakami et al. (2010) reported the p.Arg79Cys variant in 2 controls in a cohort that is likely of Asian ancestry. Kapplinger et al. (2014) also reported the variant in 2 individuals of a control cohort of 427 individuals of various ethnic backgrounds. The variant was reported online in 46 of 53,269 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 01/21/2015). Specifically, the variant was observed in 43 of 4026 individuals (0.1%) of the East Asian ancestry. 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. (less)
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Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001951550.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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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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Frequency and clinical expression of cardiac troponin I mutations in 748 consecutive families with hypertrophic cardiomyopathy. | Mogensen J | Journal of the American College of Cardiology | 2004 | PMID: 15607392 |
Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy. | Kimura A | Nature genetics | 1997 | PMID: 9241277 |
Text-mined citations for rs3729712 ...
HelpRecord last updated Mar 05, 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.