NM_001001430.2(TNNT2):c.421C>T (p.Arg141Trp) AND Left ventricular noncompaction 6

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 12, 2016
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000013225.27

Allele description

NM_001001430.2(TNNT2):c.421C>T (p.Arg141Trp)

Gene:

TNNT2:troponin T2, cardiac type [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q32.1

Genomic location:

Preferred name:

NM_001001430.2(TNNT2):c.421C>T (p.Arg141Trp)

Other names:

p.R141W:CGG>TGG

HGVS:

NC_000001.11:g.201364336G>A
NG_007556.1:g.18342C>T
NM_000364.3:c.451C>T
NM_001001430.2:c.421C>T
NP_000355.2:p.Arg151Trp
NP_001001430.1:p.Arg141Trp
NC_000001.10:g.201333464G>A
NM_000364.2:c.451C>T
NM_001001430.1:c.421C>T
P45379:p.Arg151Trp
p.(Arg141Trp)

Protein change:

R141W; ARG141TRP

Links:

UniProtKB: P45379#VAR_016198; OMIM: 191045.0007; dbSNP: rs74315379

GMAF:

0.0006(T), 74315379

NCBI 1000 Genomes Browser:

rs74315379

Molecular consequence:

NM_001001430.2:c.421C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Left ventricular noncompaction 6 (CMD1D)
Synonyms:: Dilated cardiomyopathy 1D
Identifiers:: 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
SCV000033472	OMIM	no assertion criteria provided	Pathogenic (Oct 30, 2001)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000299243	Center for Medical Genetics Ghent,University of Ghent	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 1, 2016)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11684629, 12923187, 15623536, 25741868
SCV000703511	EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	criteria provided, single submitter (EGL Classification Definitions)	Pathogenic (Dec 12, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000033472

OMIM

no assertion criteria provided

Pathogenic
(Oct 30, 2001)

germline

literature only

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

SCV000299243

Center for Medical Genetics Ghent,University of Ghent

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 1, 2016)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV000703511

EGL Genetic Diagnostics,Eurofins Clinical Diagnostics

criteria provided, single submitter

(EGL Classification Definitions)

Pathogenic
(Dec 12, 2016)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	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
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel cardiac troponin T mutation as a cause of familial dilated cardiomyopathy.

Li D, Czernuszewicz GZ, Gonzalez O, Tapscott T, Karibe A, Durand JB, Brugada R, Hill R, Gregoritch JM, Anderson JL, Quiñones M, Bachinski LL, Roberts R.

Circulation. 2001 Oct 30;104(18):2188-93.

PubMed [citation]

PMID:: 11684629

Different functional properties of troponin T mutants that cause dilated cardiomyopathy.

Venkatraman G, Harada K, Gomes AV, Kerrick WG, Potter JD.

J Biol Chem. 2003 Oct 24;278(43):41670-6. Epub 2003 Aug 14.

PubMed [citation]

PMID:: 12923187

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000033472.1

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

Description

Li et al. (2001) found a C-to-T transition at nucleotide position 471 of the TNNT2 gene, which was predicted to change the highly conserved basic amino acid arginine at residue 141 to the polar-neutral tryptophan (arg141 to trp; R141W). This sequence change cosegregated with dilated cardiomyopathy (601494) in the family, with 5 phenotypically normal mutation carriers in addition to 14 affected individuals. Evaluation of 200 control chromosomes and 219 individuals with familial hypertrophic cardiomyopathy failed to detect the variation, leading the authors to conclude that this was a pathogenic mutation.

#	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 Center for Medical Genetics Ghent,University of Ghent, SCV000299243.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

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

From EGL Genetic Diagnostics,Eurofins Clinical Diagnostics, SCV000703511.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	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	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Oct 18, 2018

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