NM_001276345.2(TNNT2):c.305G>A (p.Arg102Gln) AND Hypertrophic cardiomyopathy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 10, 2018
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:: RCV000211865.5

Allele description [Variation Report for NM_001276345.2(TNNT2):c.305G>A (p.Arg102Gln)]

NM_001276345.2(TNNT2):c.305G>A (p.Arg102Gln)

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.305G>A (p.Arg102Gln)

Other names:

p.R92Q:CGG>CAG

HGVS:

NC_000001.11:g.201365297C>T
NG_007556.1:g.17381G>A
NM_000364.4:c.305G>A
NM_001001430.3:c.275G>A
NM_001001431.3:c.275G>A
NM_001001432.3:c.260G>A
NM_001276345.2:c.305G>AMANE SELECT
NM_001276346.2:c.291+313G>A
NM_001276347.2:c.275G>A
NP_000355.2:p.Arg102Gln
NP_001001430.1:p.Arg92Gln
NP_001001431.1:p.Arg92Gln
NP_001001432.1:p.Arg87Gln
NP_001263274.1:p.Arg102Gln
NP_001263276.1:p.Arg92Gln
LRG_431t1:c.305G>A
LRG_431:g.17381G>A
LRG_431p1:p.Arg102Gln
NC_000001.10:g.201334425C>T
NM_001001430.1:c.275G>A
NM_001001430.2:c.275G>A
c.275G>A

Protein change:

R102Q; ARG92GLN

Links:

OMIM: 191045.0002; dbSNP: rs121964856

NCBI 1000 Genomes Browser:

rs121964856

Molecular consequence:

NM_001276346.2:c.291+313G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000364.4:c.305G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001001430.3:c.275G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001001431.3:c.275G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001001432.3:c.260G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276345.2:c.305G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276347.2:c.275G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Hypertrophic cardiomyopathy
Synonyms:: HYPERTROPHIC MYOCARDIOPATHY
Identifiers:: MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000060229	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Jul 10, 2018)	germline	clinical testing	PubMed (18) [See all records that cite these PMIDs] 10085122, 11606294, 7898523, 8205619, 18533079, 18403758, 19487599, 19087273, 9201030, 19150014, 12186860, 11158969, 22675533, 28735292, 27532257, 24691700, 26507537, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000060229

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Jul 10, 2018)

germline

clinical testing

PubMed (18)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	8	5	not provided	not provided	not provided	clinical testing

Citations

PubMed

Ca2+ sensitization and potentiation of the maximum level of myofibrillar ATPase activity caused by mutations of troponin T found in familial hypertrophic cardiomyopathy.

Yanaga F, Morimoto S, Ohtsuki I.

J Biol Chem. 1999 Mar 26;274(13):8806-12.

PubMed [citation]

PMID:: 10085122

Disease-causing mutations in cardiac troponin T: identification of a critical tropomyosin-binding region.

Palm T, Graboski S, Hitchcock-DeGregori SE, Greenfield NJ.

Biophys J. 2001 Nov;81(5):2827-37. Erratum in: Biophys J 2002 May;82(5):2826.

PubMed [citation]

PMID:: 11606294
PMCID:: PMC1301748

See all PubMed Citations (18)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000060229.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	8	not provided	not provided	clinical testing	PubMed (18)

Description

The p.Arg92Gln variant in TNNT2 has been reported in >15 individuals with HCM, i ncluding one de novo occurrence, and segregated with disease in >15 affected rel atives (Thierfelder 1994, Watkins 1995, Morita 2008, Olivotto 2008, Strijack 200 8, Ripoll-Vera 2016, Walsh, 2017, LMM data). In addition, this was absent from l arge population studies. In vitro functional studies have shown that the Arg92Gl n variant impacts protein function (Marian 1997, Yanaga 1999, Robinson 2002, Liu 2012) and transgenic mice carrying this variant develop HCM (Chandar 2001, Ferr antini 2017). In summary, this variant meets criteria to be classified as pathog enic for HCM in an autosomal dominant manner based on case observations, segrega tion studies, absence from controls, and functional evidence. ACMG/AMP Criteria applied: PS3, PS4, PP1_Strong, PM2.

#	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		8	not provided	5	not provided

Last Updated: Mar 5, 2024

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