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NM_001267550.2(TTN):c.59926C>T (p.His19976Tyr)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(2);Uncertain significance(4)

Review status:
criteria provided, conflicting interpretations
Submissions:
6 (Most recent: Sep 24, 2021)
Last evaluated:
Mar 31, 2021
Accession:
VCV000165933.6
Variation ID:
165933
Description:
single nucleotide variant
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NM_001267550.2(TTN):c.59926C>T (p.His19976Tyr)

Allele ID
172863
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2q31.2
Genomic location
2: 178591978 (GRCh38) GRCh38 UCSC
2: 179456705 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_001256850.1:c.55003C>T NP_001243779.1:p.His18335Tyr missense
NM_003319.4:c.32731C>T NP_003310.4:p.His10911Tyr missense
NM_133378.4:c.52222C>T NP_596869.4:p.His17408Tyr missense
... more HGVS
Protein change
H17408Y, H19976Y, H18335Y, H10911Y, H11036Y, H11103Y
Other names
p.H18335Y:CAT>TAT
Canonical SPDI
NC_000002.12:178591977:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00004
The Genome Aggregation Database (gnomAD), exomes 0.00005
Links
ClinGen: CA178643
dbSNP: rs727503588
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Mar 1, 2019 RCV000152270.3
Uncertain significance 1 criteria provided, single submitter Dec 25, 2016 RCV000474565.1
Likely benign 1 criteria provided, single submitter Mar 26, 2020 RCV000618262.2
Uncertain significance 1 criteria provided, single submitter Oct 31, 2018 RCV000765563.1
Likely benign 1 criteria provided, single submitter Mar 31, 2021 RCV001704100.1
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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
7498 17579
TTN-AS1 - - - GRCh38 - 9855

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(May 01, 2014)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000201115.5
Submitted: (Mar 21, 2019)
Evidence details
Comment:
Variant classified as Uncertain Significance - Favor Benign. The His17408Tyr var iant in TTN has not been previously reported in individuals with cardiomyopathy or in … (more)
Likely benign
(Mar 31, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000237359.5
Submitted: (Sep 24, 2021)
Evidence details
Uncertain significance
(Dec 25, 2016)
criteria provided, single submitter
Method: clinical testing
Dilated cardiomyopathy 1G
Limb-girdle muscular dystrophy, type 2J
Allele origin: germline
Invitae
Accession: SCV000542908.2
Submitted: (Mar 14, 2017)
Evidence details
Uncertain significance
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Tibial muscular dystrophy
Myopathy, myofibrillar, 9, with early respiratory failure
Dilated cardiomyopathy 1G
Limb-girdle muscular dystrophy, type 2J
Myopathy, early-onset, with fatal cardiomyopathy
Familial hypertrophic cardiomyopathy 9
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000896878.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Uncertain significance
(Mar 01, 2019)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV001160292.1
Submitted: (Aug 05, 2019)
Evidence details
Comment:
The c.52222C>T; p.His17408Tyr variant (rs727503588) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our … (more)
Likely benign
(Mar 26, 2020)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000735257.3
Submitted: (Nov 30, 2020)
Evidence details
Comment:
In silico models in agreement (benign);Last nucleotide of exon;Other strong data supporting benign classification

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
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Richards S Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868

Text-mined citations for rs727503588...

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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 Sep 26, 2021