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NM_001276345.2(TNNT2):c.294T>A (p.Asp98Glu) AND Primary dilated cardiomyopathy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 14, 2019
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:
RCV000825476.6

Allele description [Variation Report for NM_001276345.2(TNNT2):c.294T>A (p.Asp98Glu)]

NM_001276345.2(TNNT2):c.294T>A (p.Asp98Glu)

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.294T>A (p.Asp98Glu)
HGVS:
  • NC_000001.11:g.201365610A>T
  • NG_007556.1:g.17068T>A
  • NM_000364.4:c.294T>A
  • NM_001001430.3:c.264T>A
  • NM_001001431.3:c.264T>A
  • NM_001001432.3:c.249T>A
  • NM_001276345.2:c.294T>AMANE SELECT
  • NM_001276346.2:c.291T>A
  • NM_001276347.2:c.264T>A
  • NP_000355.2:p.Asp98Glu
  • NP_001001430.1:p.Asp88Glu
  • NP_001001431.1:p.Asp88Glu
  • NP_001001432.1:p.Asp83Glu
  • NP_001263274.1:p.Asp98Glu
  • NP_001263275.1:p.Asp97Glu
  • NP_001263276.1:p.Asp88Glu
  • LRG_431t1:c.294T>A
  • LRG_431:g.17068T>A
  • LRG_431p1:p.Asp98Glu
  • NC_000001.10:g.201334738A>T
  • NM_001001430.1:c.264T>A
  • p.Asp88Glu
Protein change:
D83E
Links:
dbSNP: rs397516454
NCBI 1000 Genomes Browser:
rs397516454
Molecular consequence:
  • NM_000364.4:c.294T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001430.3:c.264T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001431.3:c.264T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001432.3:c.249T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276345.2:c.294T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276346.2:c.291T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276347.2:c.264T>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Primary dilated cardiomyopathy (DCM)
Synonyms:
Dilated Cardiomyopathy
Identifiers:
EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000966778Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Likely pathogenic
(May 14, 2019) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown11not providednot providednot providedclinical testing

Citations

PubMed

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, SCV000966778.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The p.Asp88Glu (c.264T>A) variant in TNNT2 has been identified as a de novo change in 1 individual with infantile-onset DCM (LMM data), but was absent from large population studies. Additionally, a different variant resulting in the same amino acid change, c.264T>G, has been identified as a de novo change in another individual with infantile-onset DCM (LMM data). Computational prediction tools and conservation analysis suggest that the p.Asp88Glu variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In addition, this variant is located in the last three bases of the exon, which is part of the 5’ splice region. While computational tools do not predict an impact on splicing, these tools may not accurately predict biological function. In summary, although additional studies are required to fully establish its clinical significance, the p.Asp88Glu (c.264T>A) variant meets criteria to be classified as likely pathogenic for autosomal dominant dilated cardiomyopathy. ACMG/AMP Criteria applied: PM2, PM6, PP3, PS1_Supporting.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not provided1not provided

Last Updated: Jun 23, 2024