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NM_001256850.1(TTN):c.39893-1G>A

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Interpretation:
Conflicting interpretations of pathogenicity​

Pathogenic(2);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
4 (Most recent: Jan 7, 2021)
Last evaluated:
Oct 30, 2020
Accession:
VCV000202368.5
Variation ID:
202368
Description:
single nucleotide variant
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NM_001256850.1(TTN):c.39893-1G>A

Allele ID
199342
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2q31.2
Genomic location
2: 178622768 (GRCh38) GRCh38 UCSC
2: 179487495 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000002.11:g.179487495C>T
NC_000002.12:g.178622768C>T
NM_001267550.2:c.44816-1G>A MANE Select splice acceptor
... more HGVS
Protein change
-
Other names
IVS192-1 G>A
Canonical SPDI
NC_000002.12:178622767:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00000
Links
ClinGen: CA309215
dbSNP: rs749705939
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 1 criteria provided, single submitter Oct 30, 2020 RCV000476723.7
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Apr 23, 2018 RCV000184214.6
not provided 1 no assertion provided - RCV000509547.1

Clinical features observed in individuals with this variant

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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 - - GRCh38
GRCh37
7377 17355

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Mar 09, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000338272.4
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(Apr 23, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000236836.10
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The c.39893-1 G>A pathogenic variant in the TTN gene has been reported in a patient with centronuclear myopathy and a normal cardiac evaluation who also … (more)
Pathogenic
(Oct 30, 2020)
criteria provided, single submitter
Method: clinical testing
Dilated cardiomyopathy 1G
Limb-girdle muscular dystrophy, type 2J
Allele origin: germline
Invitae
Accession: SCV000542917.7
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change affects an acceptor splice site in intron 242 of the TTN gene. It is expected to disrupt RNA splicing and likely results … (more)
not provided
(-)
no assertion provided
Method: phenotyping only
Cardiomyopathy
Allele origin: unknown
GenomeConnect, ClinGen
Accession: SCV000607336.1
Submitted: (Aug 22, 2017)
Evidence details
Comment:
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical … (more)

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
Prevalence of Titin Truncating Variants in General Population. Akinrinade O PloS one 2015 PMID: 26701604
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
Truncations of titin causing dilated cardiomyopathy. Herman DS The New England journal of medicine 2012 PMID: 22335739
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TTN - - - -

Text-mined citations for rs749705939...

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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 May 10, 2021