ClinVar Genomic variation as it relates to human health
NM_001267550.2(TTN):c.59315C>T (p.Pro19772Leu)
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_001267550.2(TTN):c.59315C>T (p.Pro19772Leu)
Variation ID: 47148 Accession: VCV000047148.32
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q31.2 2: 178592804 (GRCh38) [ NCBI UCSC ] 2: 179457531 (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 Oct 2, 2016 Feb 28, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001267550.2:c.59315C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001254479.2:p.Pro19772Leu missense NM_001256850.1:c.54392C>T NP_001243779.1:p.Pro18131Leu missense NM_003319.4:c.32120C>T NP_003310.4:p.Pro10707Leu missense NM_133378.4:c.51611C>T NP_596869.4:p.Pro17204Leu missense NM_133432.3:c.32495C>T NP_597676.3:p.Pro10832Leu missense NM_133437.4:c.32696C>T NP_597681.4:p.Pro10899Leu missense NC_000002.12:g.178592804G>A NC_000002.11:g.179457531G>A NG_011618.3:g.242999C>T NG_051363.1:g.74978G>A LRG_391:g.242999C>T LRG_391t1:c.59315C>T - Protein change
- P19772L, P17204L, P18131L, P10832L, P10707L, P10899L
- Other names
- p.P18131L:CCG>CTG
- Canonical SPDI
- NC_000002.12:178592803: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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0.00240 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00085
Exome Aggregation Consortium (ExAC) 0.00095
1000 Genomes Project 30x 0.00219
1000 Genomes Project 0.00240
The Genome Aggregation Database (gnomAD) 0.00274
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00282
Trans-Omics for Precision Medicine (TOPMed) 0.00376
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
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. |
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TTN | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
11725 | 31212 | |
LOC126806424 | - | - | - | GRCh38 | - | 257 |
TTN-AS1 | - | - | - | GRCh38 | - | 17885 |
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/Likely benign (7) |
criteria provided, multiple submitters, no conflicts
|
Aug 8, 2021 | RCV000040418.33 | |
Benign (1) |
criteria provided, single submitter
|
Sep 18, 2013 | RCV000241577.9 | |
Benign (1) |
criteria provided, single submitter
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Jan 31, 2024 | RCV000476235.19 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Oct 10, 2023 | RCV001572698.12 | |
Benign (1) |
criteria provided, single submitter
|
Sep 10, 2021 | RCV001839647.10 | |
Benign (1) |
criteria provided, single submitter
|
Sep 10, 2021 | RCV001839644.10 | |
Benign (1) |
criteria provided, single submitter
|
Sep 10, 2021 | RCV001839645.10 | |
Benign (1) |
criteria provided, single submitter
|
Sep 10, 2021 | RCV001839646.10 |
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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Benign
(May 06, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000064109.6
First in ClinVar: May 03, 2013 Last updated: May 03, 2018 |
Comment:
p.Pro17204Leu in exon 249 of TTN: This variant is not expected to have clinical significance because it has been identified in 1.0% (99/9780) of African … (more)
p.Pro17204Leu in exon 249 of TTN: This variant is not expected to have clinical significance because it has been identified in 1.0% (99/9780) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs72646840). (less)
Number of individuals with the variant: 8
|
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Benign
(Oct 10, 2023)
|
criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV004564976.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
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Likely benign
(Aug 24, 2015)
|
criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000597649.1
First in ClinVar: Aug 27, 2017 Last updated: Aug 27, 2017 |
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Benign
(May 05, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000616113.1
First in ClinVar: Aug 27, 2017 Last updated: Aug 27, 2017 |
|
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Likely benign
(Aug 08, 2021)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001821477.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
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Likely benign
(Nov 27, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000237353.6
First in ClinVar: Jul 05, 2015 Last updated: Apr 09, 2018 |
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Benign
(Sep 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Myopathy, myofibrillar, 9, with early respiratory failure
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002101126.1
First in ClinVar: Mar 05, 2022 Last updated: Mar 05, 2022 |
|
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Benign
(Sep 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Early-onset myopathy with fatal cardiomyopathy
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002101127.1
First in ClinVar: Mar 05, 2022 Last updated: Mar 05, 2022 |
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Benign
(Sep 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2J
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002101124.1
First in ClinVar: Mar 05, 2022 Last updated: Mar 05, 2022 |
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Benign
(Sep 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Tibial muscular dystrophy
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002101128.1
First in ClinVar: Mar 05, 2022 Last updated: Mar 05, 2022 |
|
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Benign
(Mar 12, 2013)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000114415.8
First in ClinVar: Jan 17, 2014 Last updated: May 03, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
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Benign
(Sep 18, 2013)
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criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000319192.5
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1G
Autosomal recessive limb-girdle muscular dystrophy type 2J
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000555374.9
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001744791.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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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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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001797463.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001924592.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001966368.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 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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Recessive Inactivating Mutations in TBCK, Encoding a Rab GTPase-Activating Protein, Cause Severe Infantile Syndromic Encephalopathy. | Chong JX | American journal of human genetics | 2016 | PMID: 27040692 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TTN | - | - | - | - |
Text-mined citations for rs72646840 ...
HelpRecord last updated May 12, 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.