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NM_001276345.2(TNNT2):c.851+1G>T AND Hypertrophic cardiomyopathy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 4, 2015
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000152095.5

Allele description [Variation Report for NM_001276345.2(TNNT2):c.851+1G>T]

NM_001276345.2(TNNT2):c.851+1G>T

Gene:
TNNT2:troponin T2, cardiac type [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q32.1
Genomic location:
Preferred name:
NM_001276345.2(TNNT2):c.851+1G>T
HGVS:
  • NC_000001.11:g.201359622C>A
  • NG_007556.1:g.23056G>T
  • NM_000364.4:c.842+1G>T
  • NM_001001430.3:c.821+1G>T
  • NM_001001431.3:c.812+1G>T
  • NM_001001432.3:c.803+1G>T
  • NM_001276345.2:c.851+1G>TMANE SELECT
  • NM_001276346.2:c.722+1G>T
  • NM_001276347.2:c.821+1G>T
  • NM_001406723.1:c.842+1G>T
  • NM_001406724.1:c.821+1G>T
  • NM_001406725.1:c.818+1G>T
  • NM_001406726.1:c.812+1G>T
  • NM_001406727.1:c.812+1G>T
  • NM_001406728.1:c.806+1G>T
  • LRG_431t1:c.851+1G>T
  • LRG_431:g.23056G>T
  • NC_000001.10:g.201328750C>A
  • NM_001001430.1:c.821+1G>T
Links:
dbSNP: rs111377893
NCBI 1000 Genomes Browser:
rs111377893
Molecular consequence:
  • NM_000364.4:c.842+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001001430.3:c.821+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001001431.3:c.812+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001001432.3:c.803+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001276345.2:c.851+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001276346.2:c.722+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001276347.2:c.821+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406723.1:c.842+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406724.1:c.821+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406725.1:c.818+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406726.1:c.812+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406727.1:c.812+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406728.1:c.806+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
Observations:
2

Condition(s)

Name:
Hypertrophic cardiomyopathy
Synonyms:
HYPERTROPHIC MYOCARDIOPATHY
Identifiers:
MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000200746Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Likely pathogenic
(Dec 4, 2015) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided22not providednot providednot providedclinical testing

Citations

PubMed

Human cardiomyopathy mutations induce myocyte hyperplasia and activate hypertrophic pathways during cardiogenesis in zebrafish.

Becker JR, Deo RC, Werdich AA, Panàkovà D, Coy S, MacRae CA.

Dis Model Mech. 2011 May;4(3):400-10. doi: 10.1242/dmm.006148. Epub 2011 Jan 18.

PubMed [citation]
PMID:
21245263
PMCID:
PMC3097461

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000200746.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (2)

Description

The c.821+1G>T variant in TNNT2 has been previously identified by our laboratory in 1 Caucasian teenager with HCM. It was absent from large population studies. Another substitution at the same nucleotide position (c.821+1G>A), which is clas sified as pathogenic, was shown to result in an abnormal protein with impaired f unction (Watkins 1995, Watkins 1996, Mukherjea 1999, Szczesna 2000, Gafurov 2004 ). The c.821+1G>T variant occurs in the same invariant region (+/- 1,2) of the s plice consensus sequence and is expected to result in an altered splicing leadin g to an abnormal protein similarly to the c.821+1G>A variant. In addition, block ing splicing at the zebrafish equivalent of this splice site provides some evide nce for a causative role (Becker 2011). In summary, although additional studies are required to fully establish its clinical significance, the c.821+1G>T varia nt is likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided2not provided2not provided

Last Updated: Sep 29, 2024