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NM_001267550.2(TTN):c.107840T>A (p.Ile35947Asn)

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Interpretation:
Conflicting interpretations of pathogenicity​

Pathogenic(1);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
4 (Most recent: Jan 7, 2021)
Last evaluated:
Jul 1, 2020
Accession:
VCV000012654.6
Variation ID:
12654
Description:
single nucleotide variant
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NM_001267550.2(TTN):c.107840T>A (p.Ile35947Asn)

Allele ID
27693
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2q31.2
Genomic location
2: 178527148 (GRCh38) GRCh38 UCSC
2: 179391875 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000002.11:g.179391875A>T
NC_000002.12:g.178527148A>T
NG_011618.3:g.308655T>A
... more HGVS
Protein change
I33379N, I34306N, I35947N, I27007N, I27074N, I26882N
Other names
293329T-A
AJ277892.2:g.293329T>A
Canonical SPDI
NC_000002.12:178527147:A:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00001
Links
ClinGen: CA341213
OMIM: 188840.0006
dbSNP: rs281864928
VarSome
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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, single submitter Feb 12, 2020 RCV000013490.22
Uncertain significance 1 criteria provided, single submitter Jul 1, 2020 RCV001319595.1
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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
7533 17646
TTN-AS1 - - - GRCh38 - 9887

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Jul 01, 2020)
criteria provided, single submitter
Method: clinical testing
Dilated cardiomyopathy 1G
Limb-girdle muscular dystrophy, type 2J
Allele origin: germline
Invitae
Accession: SCV001510348.1
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces isoleucine with asparagine at codon 35947 of the TTN protein (p.Ile35947Asn). There is a large physicochemical difference between isoleucine and asparagine. … (more)
Pathogenic
(Feb 12, 2020)
criteria provided, single submitter
Method: clinical testing
Tibial muscular dystrophy
(Autosomal dominant inheritance)
Allele origin: germline
Institute of Human Genetics, Klinikum rechts der Isar
Accession: SCV001149973.2
Submitted: (Aug 10, 2020)
Evidence details
Pathogenic
(Aug 01, 2003)
no assertion criteria provided
Method: literature only
TIBIAL MUSCULAR DYSTROPHY, TARDIVE
Allele origin: germline
OMIM
Accession: SCV000033737.1
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)
Pathogenic
(Dec 19, 2019)
no assertion criteria provided
Method: literature only
Tibial muscular dystrophy
Allele origin: germline
GeneReviews
Accession: SCV000054697.3
Submitted: (May 28, 2020)
Evidence details
Publications
PubMed (2)
BookShelf: NBK1323

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
Udd Distal Myopathy – Tibial Muscular Dystrophy Udd B - 2020 PMID: 20301498
Targeted Next-Generation Sequencing Reveals Novel TTN Mutations Causing Recessive Distal Titinopathy. Evilä A Molecular neurobiology 2017 PMID: 27796757
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
Tibial muscular dystrophy in a Belgian family. Van den Bergh PY Annals of neurology 2003 PMID: 12891679

Text-mined citations for rs281864928...

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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 Oct 16, 2021