NM_001276345.2(TNNT2):c.838G>A (p.Asp280Asn) AND Dilated cardiomyopathy 1D

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 11, 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:: RCV000013229.24

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:: Dilated cardiomyopathy 1D
Synonyms:: Left ventricular noncompaction 6
Identifiers:: MONDO: MONDO:0011095; MedGen: C1832243; Orphanet: 154; Orphanet: 54260; OMIM: 601494

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000033476	OMIM	no assertion criteria provided	Pathogenic (Nov 16, 2004)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004180510	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 11, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000033476

OMIM

no assertion criteria provided

Pathogenic
(Nov 16, 2004)

germline

literature only

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

SCV004180510

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 11, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Severe disease expression of cardiac troponin C and T mutations in patients with idiopathic dilated cardiomyopathy.

Mogensen J, Murphy RT, Shaw T, Bahl A, Redwood C, Watkins H, Burke M, Elliott PM, McKenna WJ.

J Am Coll Cardiol. 2004 Nov 16;44(10):2033-40.

PubMed [citation]

PMID:: 15542288

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, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000033476.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 affected members of a family with dilated cardiomyopathy (CMD1D; 601494), Mogensen et al. (2004) identified heterozygosity for an asp270-to-asn (D270N) substitution at a conserved residue in exon 15 of the TNNT2 gene. The proband underwent cardiac transplantation at 38 years of age and died at age 44; his affected son was alive at 21 years of age. The mutation was not found in 2 unaffected children or in 200 ethnically matched control chromosomes. Functional studies showed significant impairment of mutated troponin interaction compared with wildtype control, indicating an altered regulation of myocardial contractility.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV004180510.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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