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NM_001267550.2(TTN):c.583+5G>A

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: Aug 19, 2021)
Last evaluated:
Aug 19, 2019
Accession:
VCV000047232.6
Variation ID:
47232
Description:
single nucleotide variant
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NM_001267550.2(TTN):c.583+5G>A

Allele ID
56397
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2q31.2
Genomic location
2: 178800390 (GRCh38) GRCh38 UCSC
2: 179665117 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_391:g.35413G>A
NC_000002.11:g.179665117C>T
NC_000002.12:g.178800390C>T
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000002.12:178800389:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Links
ClinGen: CA140399
dbSNP: rs397517663
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 19, 2019 RCV000642802.4
Conflicting interpretations of pathogenicity 3 criteria provided, conflicting interpretations Oct 1, 2018 RCV000040502.4
Likely benign 1 no assertion criteria provided - RCV001573352.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
TTN Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
7416 17422

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Jan 25, 2018)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
GeneDx
Accession: SCV000727069.1
Submitted: (Mar 26, 2018)
Evidence details
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
Uncertain significance
(Jul 23, 2014)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000064193.6
Submitted: (Mar 21, 2019)
Evidence details
Comment:
The 583+5G>A variant in TTN has been identified by our laboratory in 1 Black ind ividual with LVNC. It was absent from large population studies. … (more)
Uncertain significance
(Oct 01, 2018)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV001159937.1
Submitted: (Aug 05, 2019)
Evidence details
Comment:
The TTN c.583+5G>A variant (rs397517663), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 47232). This variant … (more)
Uncertain significance
(Aug 19, 2019)
criteria provided, single submitter
Method: clinical testing
Dilated cardiomyopathy 1G
Limb-girdle muscular dystrophy, type 2J
Allele origin: germline
Invitae
Accession: SCV000764489.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change falls in intron 4 of the TTN gene. It does not directly change the encoded amino acid sequence of the TTN protein, … (more)
Likely benign
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001799111.1
Submitted: (Aug 19, 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
Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease. Roberts AM Science translational medicine 2015 PMID: 25589632
Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy. Ceyhan-Birsoy O Neurology 2013 PMID: 23975875
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. Buratti E Nucleic acids research 2007 PMID: 17576681
Statistical features of human exons and their flanking regions. Zhang MQ Human molecular genetics 1998 PMID: 9536098

Text-mined citations for rs397517663...

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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 Aug 25, 2021