NM_001276345.2(TNNT2):c.508GAG[3] (p.Glu173del) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 28, 2021
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:: RCV000620577.2

Allele description [Variation Report for NM_001276345.2(TNNT2):c.508GAG[3] (p.Glu173del)]

NM_001276345.2(TNNT2):c.508GAG[3] (p.Glu173del)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

1q32.1

Genomic location:

Preferred name:

NM_001276345.2(TNNT2):c.508GAG[3] (p.Glu173del)

HGVS:

NC_000001.10:g.201332505_201332507del
NC_000001.11:g.201363377CTC[3]
NG_007556.1:g.19290GAG[3]
NM_000364.4:c.508GAG[3]
NM_001001430.3:c.478GAG[3]
NM_001001431.3:c.478GAG[3]
NM_001001432.3:c.463GAG[3]
NM_001276345.2:c.508GAG[3]MANE SELECT
NM_001276346.2:c.388GAG[3]
NM_001276347.2:c.478GAG[3]
NP_000355.2:p.Glu173del
NP_001001430.1:p.Glu163del
NP_001001431.1:p.Glu163del
NP_001001432.1:p.Glu158del
NP_001263274.1:p.Glu173del
NP_001263275.1:p.Glu133del
NP_001263276.1:p.Glu163del
LRG_431t1:c.508GAG[3]
LRG_431:g.19290GAG[3]
LRG_431p1:p.Glu173del
NC_000001.10:g.201332505CTC[3]
NC_000001.10:g.201332505_201332507del
NC_000001.10:g.201332505_201332507delCTC
NC_000001.10:g.201332514_201332516del
NM_000364.2:c.517_519del
NM_000364.3:c.517_519delGAG
NM_001001430.1:c.487_489del
NM_001001430.1:c.487_489delGAG
NM_001001430.2:c.487_489del
NM_001001430.2:c.487_489delGAG
c.487_489delGAG

Protein change:

E133del

Links:

dbSNP: rs397516470

NCBI 1000 Genomes Browser:

rs397516470

Molecular consequence:

NM_000364.4:c.508GAG[3] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001001430.3:c.478GAG[3] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001001431.3:c.478GAG[3] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001001432.3:c.463GAG[3] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276345.2:c.508GAG[3] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276346.2:c.388GAG[3] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276347.2:c.478GAG[3] - inframe_deletion - [Sequence Ontology: SO:0001822]

Observations:

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000739945	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Pathogenic (Jan 28, 2021)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 21835320, 22144547, 22260945, 24480310, 27036851, 27532257, 27639548, 27662471, 31006259, 7898523 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000739945

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Pathogenic
(Jan 28, 2021)

germline

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Microvascular function is selectively impaired in patients with hypertrophic cardiomyopathy and sarcomere myofilament gene mutations.

Olivotto I, Girolami F, Sciagrà R, Ackerman MJ, Sotgia B, Bos JM, Nistri S, Sgalambro A, Grifoni C, Torricelli F, Camici PG, Cecchi F.

J Am Coll Cardiol. 2011 Aug 16;58(8):839-48. doi: 10.1016/j.jacc.2011.05.018.

PubMed [citation]

PMID:: 21835320

Long-term outcomes in hypertrophic cardiomyopathy caused by mutations in the cardiac troponin T gene.

Pasquale F, Syrris P, Kaski JP, Mogensen J, McKenna WJ, Elliott P.

Circ Cardiovasc Genet. 2012 Feb 1;5(1):10-7. doi: 10.1161/CIRCGENETICS.111.959973. Epub 2011 Dec 5.

PubMed [citation]

PMID:: 22144547

See all PubMed Citations (10)

Details of each submission

From Ambry Genetics, SCV000739945.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (10)

Description

The c.487_489delGAG pathogenic mutation (also known as p.E163del) is located in coding exon 10 of the TNNT2 gene. This alteration results from an in-frame deletion of 3 nucleotides at positions 487 to 489, causing the removal of a well-conserved glutamic acid residue at codon 163. Strong segregation of this alteration, also described as ΔGlu160, with hypertrophic cardiomyopathy has been demonstrated (Watkins H et al. N Engl J Med. 1995;332(16):1058-64). This alteration has also been detected in patients reported to have restrictive cardiomyopathy (Walsh MA et al. Circ Heart Fail. 2012;5(2):267-73). Additionally, a combination of in vitro and in vivo studies showed disrupted weak electrostatic actomyosin binding in motility assays and severe cardiac remodeling and myofilament disarray in transgenic mice (Moore RK et al. Arch Biochem Biophys. 2014;552-553:21-8). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 29, 2024

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