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

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 4, 2023
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:
RCV001850074.4

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]

Condition(s)

Name:
Hypertrophic cardiomyopathy 2
Synonyms:
Familial hypertrophic cardiomyopathy 2; TNNT2-Related Familial Hypertrophic Cardiomyopathy
Identifiers:
MONDO: MONDO:0007266; MedGen: C1861864; OMIM: 115195
Name:
Dilated cardiomyopathy 1D
Synonyms:
Left ventricular noncompaction 6
Identifiers:
MONDO: MONDO:0011095; MedGen: C1832243; Orphanet: 154; Orphanet: 54260; OMIM: 601494
Name:
Cardiomyopathy, familial restrictive, 3
Identifiers:
MONDO: MONDO:0012900; MedGen: C2676271; Orphanet: 75249; OMIM: 612422

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002234279Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 4, 2023) 		germlineclinical testing

PubMed (13)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy.

Watkins H, McKenna WJ, Thierfelder L, Suk HJ, Anan R, O'Donoghue A, Spirito P, Matsumori A, Moravec CS, Seidman JG, et al.

N Engl J Med. 1995 Apr 20;332(16):1058-64.

PubMed [citation]
PMID:
7898523

Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere.

Thierfelder L, Watkins H, MacRae C, Lamas R, McKenna W, Vosberg HP, Seidman JG, Seidman CE.

Cell. 1994 Jun 3;77(5):701-12.

PubMed [citation]
PMID:
8205619
See all PubMed Citations (13)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002234279.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (13)

Description

This sequence change falls in intron 15 of the TNNT2 gene. It does not directly change the encoded amino acid sequence of the TNNT2 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 7898523, 8205619, 25611685, 27532257). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 165533). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects TNNT2 function (PMID: 9637714, 10617660, 10850966, 15568820, 21245263, 27036851). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024