NM_001276345.2(TNNT2):c.260C>T (p.Pro87Leu) AND multiple conditions

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

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 23, 2022
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:: RCV000646057.6

Allele description

NM_001276345.2(TNNT2):c.260C>T (p.Pro87Leu)

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.260C>T (p.Pro87Leu)

HGVS:

NC_000001.11:g.201365644G>A
NG_007556.1:g.17034C>T
NM_000364.4:c.260C>T
NM_001001430.3:c.230C>T
NM_001001431.3:c.230C>T
NM_001001432.3:c.215C>T
NM_001276345.2:c.260C>TMANE SELECT
NM_001276346.2:c.257C>T
NM_001276347.2:c.230C>T
NP_000355.2:p.Pro87Leu
NP_001001430.1:p.Pro77Leu
NP_001001431.1:p.Pro77Leu
NP_001001432.1:p.Pro72Leu
NP_001263274.1:p.Pro87Leu
NP_001263275.1:p.Pro86Leu
NP_001263276.1:p.Pro77Leu
LRG_431t1:c.260C>T
LRG_431:g.17034C>T
LRG_431p1:p.Pro87Leu
NC_000001.10:g.201334772G>A
NM_000364.2:c.260C>T
NM_001001430.1:c.230C>T
NM_001001430.2:c.230C>T
NM_001276345.2:c.260C>T
c.230C>T

Protein change:

P72L

Links:

dbSNP: rs144900708

NCBI 1000 Genomes Browser:

rs144900708

Molecular consequence:

NM_000364.4:c.260C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001001430.3:c.230C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001001431.3:c.230C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001001432.3:c.215C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276345.2:c.260C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276346.2:c.257C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276347.2:c.230C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypertrophic cardiomyopathy 2
Synonyms:: Familial hypertrophic cardiomyopathy 2; TNNT2-Related Familial Hypertrophic Cardiomyopathy
Identifiers:: MONDO: MONDO:0007266; MedGen: C1861864; OMIM: 115195

Name:: Dilated cardiomyopathy 1D
Synonyms:: Left ventricular noncompaction 6
Identifiers:: MONDO: MONDO:0011095; MedGen: C1832243; Orphanet: 154; Orphanet: 54260; OMIM: 601494

Name:: Cardiomyopathy, familial restrictive, 3
Identifiers:: MONDO: MONDO:0012900; MedGen: C2676271; Orphanet: 75249; OMIM: 612422

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000767814	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 23, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11560853, 20530761, 33025817, 28492532
SCV002784510	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 8, 2021)	unknown	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

SCV000767814

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 23, 2022)

germline

clinical testing

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

SCV002784510

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 8, 2021)

unknown

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Hypertrophic cardiomyopathy: histopathological features of sudden death in cardiac troponin T disease.

Varnava AM, Elliott PM, Baboonian C, Davison F, Davies MJ, McKenna WJ.

Circulation. 2001 Sep 18;104(12):1380-4.

PubMed [citation]

PMID:: 11560853

The importance of genetic counseling, DNA diagnostics, and cardiologic family screening in left ventricular noncompaction cardiomyopathy.

Hoedemaekers YM, Caliskan K, Michels M, Frohn-Mulder I, van der Smagt JJ, Phefferkorn JE, Wessels MW, ten Cate FJ, Sijbrands EJ, Dooijes D, Majoor-Krakauer DF.

Circ Cardiovasc Genet. 2010 Jun;3(3):232-9. doi: 10.1161/CIRCGENETICS.109.903898. Epub 2010 Jun 8.

PubMed [citation]

PMID:: 20530761

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000767814.5

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

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 77 of the TNNT2 protein (p.Pro77Leu). This variant is present in population databases (rs144900708, gnomAD 0.02%). This missense change has been observed in individual(s) with TNNT2-related conditions (PMID: 11560853, 20530761). This variant is also known as p.Pro87Leu. ClinVar contains an entry for this variant (Variation ID: 43619). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TNNT2 protein function. Experimental studies have shown that this missense change does not substantially affect TNNT2 function (PMID: 33025817). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 Fulgent Genetics, Fulgent Genetics, SCV002784510.1

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

Last Updated: Sep 16, 2024

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