NM_000363.5(TNNI3):c.544G>A (p.Glu182Lys) AND Primary dilated cardiomyopathy

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 10, 2014
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:: RCV000036303.6

Allele description [Variation Report for NM_000363.5(TNNI3):c.544G>A (p.Glu182Lys)]

NM_000363.5(TNNI3):c.544G>A (p.Glu182Lys)

Gene:

TNNI3:troponin I3, cardiac type [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.42

Genomic location:

Preferred name:

NM_000363.5(TNNI3):c.544G>A (p.Glu182Lys)

Other names:

p.E182K:GAG>AAG

HGVS:

NC_000019.10:g.55154035C>T
NG_007866.2:g.8698G>A
NG_011829.2:g.204G>A
NM_000363.5:c.544G>AMANE SELECT
NP_000354.4:p.Glu182Lys
LRG_432t1:c.544G>A
LRG_432:g.8698G>A
LRG_679:g.204G>A
NC_000019.9:g.55665403C>T
NM_000363.4:c.544G>A
c.544G>A

Protein change:

E182K

Links:

dbSNP: rs397516355

NCBI 1000 Genomes Browser:

rs397516355

Molecular consequence:

NM_000363.5:c.544G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000059955	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Sep 10, 2014)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22464770, 24503780, 27532257, 24033266
SCV000804930	Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	no assertion criteria provided	Likely pathogenic (Oct 12, 2015)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000059955

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Sep 10, 2014)

germline

clinical testing

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

SCV000804930

Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital

no assertion criteria provided

Likely pathogenic
(Oct 12, 2015)

germline

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	2	2	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic testing for dilated cardiomyopathy in clinical practice.

Lakdawala NK, Funke BH, Baxter S, Cirino AL, Roberts AE, Judge DP, Johnson N, Mendelsohn NJ, Morel C, Care M, Chung WK, Jones C, Psychogios A, Duffy E, Rehm HL, White E, Seidman JG, Seidman CE, Ho CY.

J Card Fail. 2012 Apr;18(4):296-303. doi: 10.1016/j.cardfail.2012.01.013. Epub 2012 Feb 15.

PubMed [citation]

PMID:: 22464770
PMCID:: PMC3666099

The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing.

Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH.

Genet Med. 2014 Aug;16(8):601-8. doi: 10.1038/gim.2013.204. Epub 2014 Feb 6.

PubMed [citation]

PMID:: 24503780

See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000059955.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (4)

Description

The Glu182Lys variant in TNNI3 has been identified by our laboratory as de novo in 1 African American neonate with DCM and 1 Caucasian infant with DCM. In addit ion, it has not been identified in large population studies. Computational predi ction tools and conservation analysis do not provide strong support for or again st an impact to the protein. In summary, this variant meets our criteria to be c lassified as pathogenic (http://www.partners.org/personalizedmedicine/LMM) based upon de novo occurrence in multiple cases.

#	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		2	not provided	2	not provided

From Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital, SCV000804930.1

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

#	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

Last Updated: Sep 29, 2024

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