NM_001276345.2(TNNT2):c.692T>C (p.Ile231Thr) AND Cardiovascular phenotype

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Apr 9, 2025
Review status:: criteria provided, conflicting classifications

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:: RCV000619781.5

Allele description [Variation Report for NM_001276345.2(TNNT2):c.692T>C (p.Ile231Thr)]

NM_001276345.2(TNNT2):c.692T>C (p.Ile231Thr)

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.692T>C (p.Ile231Thr)

Other names:

p.I221T:ATT>ACT

HGVS:

NC_000001.11:g.201361940A>G
NG_007556.1:g.20738T>C
NM_000364.4:c.683T>C
NM_001001430.3:c.662T>C
NM_001001431.3:c.653T>C
NM_001001432.3:c.644T>C
NM_001276345.2:c.692T>CMANE SELECT
NM_001276346.2:c.563T>C
NM_001276347.2:c.662T>C
NP_000355.2:p.Ile228Thr
NP_001001430.1:p.Ile221Thr
NP_001001431.1:p.Ile218Thr
NP_001001432.1:p.Ile215Thr
NP_001263274.1:p.Ile231Thr
NP_001263275.1:p.Ile188Thr
NP_001263276.1:p.Ile221Thr
LRG_431t1:c.692T>C
LRG_431:g.20738T>C
LRG_431p1:p.Ile231Thr
NC_000001.10:g.201331068A>G
NM_000364.3:c.683T>C
NM_001001430.1:c.662T>C
NM_001001430.2:c.662T>C
NM_001276345.1:c.692T>C

Protein change:

I188T

Links:

dbSNP: rs45520032

NCBI 1000 Genomes Browser:

rs45520032

Molecular consequence:

NM_000364.4:c.683T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001001430.3:c.662T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001001431.3:c.653T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001001432.3:c.644T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276345.2:c.692T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276346.2:c.563T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276347.2:c.662T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000737050	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Aug 14, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22958901, 24093860, 26507537, 28255936 Citation Link,
SCV006066618	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 9, 2025)	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

SCV000737050

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Aug 14, 2023)

germline

clinical testing

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

Citation Link,

SCV006066618

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 9, 2025)

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	unknown	not provided	not provided	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

Burden of rare sarcomere gene variants in the Framingham and Jackson Heart Study cohorts.

Bick AG, Flannick J, Ito K, Cheng S, Vasan RS, Parfenov MG, Herman DS, DePalma SR, Gupta N, Gabriel SB, Funke BH, Rehm HL, Benjamin EJ, Aragam J, Taylor HA Jr, Fox ER, Newton-Cheh C, Kathiresan S, O'Donnell CJ, Wilson JG, Altshuler DM, Hirschhorn JN, et al.

Am J Hum Genet. 2012 Sep 7;91(3):513-9. doi: 10.1016/j.ajhg.2012.07.017.

PubMed [citation]

PMID:: 22958901
PMCID:: PMC3511985

Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy.

Marsiglia JD, Credidio FL, de Oliveira TG, Reis RF, Antunes Mde O, de Araujo AQ, Pedrosa RP, Barbosa-Ferreira JM, Mady C, Krieger JE, Arteaga-Fernandez E, Pereira Ada C.

Am Heart J. 2013 Oct;166(4):775-82. doi: 10.1016/j.ahj.2013.07.029. Epub 2013 Sep 18.

PubMed [citation]

PMID:: 24093860

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000737050.6

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

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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		not provided	not provided	not provided	not provided

From Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute, SCV006066618.1

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

Description

PS4_supp, PP2, PP3, BS1, BS3_supp

#	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: May 16, 2025

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