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NM_001276345.2(TNNT2):c.838G>A (p.Asp280Asn) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 4, 2022
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:
RCV001851816.4

Allele description [Variation Report for NM_001276345.2(TNNT2):c.838G>A (p.Asp280Asn)]

NM_001276345.2(TNNT2):c.838G>A (p.Asp280Asn)

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.838G>A (p.Asp280Asn)
HGVS:
  • NC_000001.11:g.201359636C>T
  • NG_007556.1:g.23042G>A
  • NM_000364.4:c.829G>A
  • NM_001001430.3:c.808G>A
  • NM_001001431.3:c.799G>A
  • NM_001001432.3:c.790G>A
  • NM_001276345.2:c.838G>AMANE SELECT
  • NM_001276346.2:c.709G>A
  • NM_001276347.2:c.808G>A
  • NP_000355.2:p.Asp277Asn
  • NP_001001430.1:p.Asp270Asn
  • NP_001001431.1:p.Asp267Asn
  • NP_001001432.1:p.Asp264Asn
  • NP_001263274.1:p.Asp280Asn
  • NP_001263275.1:p.Asp237Asn
  • NP_001263276.1:p.Asp270Asn
  • LRG_431t1:c.838G>A
  • LRG_431:g.23042G>A
  • LRG_431p1:p.Asp280Asn
  • NC_000001.10:g.201328764C>T
  • NM_001001430.1:c.808G>A
Protein change:
D237N; ASP270ASN
Links:
OMIM: 191045.0010; dbSNP: rs121964861
NCBI 1000 Genomes Browser:
rs121964861
Molecular consequence:
  • NM_000364.4:c.829G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001430.3:c.808G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001431.3:c.799G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001432.3:c.790G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276345.2:c.838G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276346.2:c.709G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276347.2:c.808G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002196538Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 4, 2022) 		germlineclinical testing

PubMed (4)
[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

Dilated cardiomyopathy mutations in three thin filament regulatory proteins result in a common functional phenotype.

Mirza M, Marston S, Willott R, Ashley C, Mogensen J, McKenna W, Robinson P, Redwood C, Watkins H.

J Biol Chem. 2005 Aug 5;280(31):28498-506. Epub 2005 May 27.

PubMed [citation]
PMID:
15923195

Dilated and hypertrophic cardiomyopathy mutations in troponin and alpha-tropomyosin have opposing effects on the calcium affinity of cardiac thin filaments.

Robinson P, Griffiths PJ, Watkins H, Redwood CS.

Circ Res. 2007 Dec 7;101(12):1266-73. Epub 2007 Oct 11.

PubMed [citation]
PMID:
17932326
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002196538.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects TNNT2 function (PMID: 15542288, 15923195, 17932326). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TNNT2 protein function. ClinVar contains an entry for this variant (Variation ID: 12417). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 15542288). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 270 of the TNNT2 protein (p.Asp270Asn).

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

Last Updated: Sep 29, 2024