NM_001276345.2(TNNT2):c.764C>T (p.Ala255Val) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 12, 2023
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:: RCV002381490.3

Allele description [Variation Report for NM_001276345.2(TNNT2):c.764C>T (p.Ala255Val)]

NM_001276345.2(TNNT2):c.764C>T (p.Ala255Val)

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.764C>T (p.Ala255Val)

HGVS:

NC_000001.11:g.201361325G>A
NG_007556.1:g.21353C>T
NM_000364.4:c.755C>T
NM_001001430.3:c.734C>T
NM_001001431.3:c.725C>T
NM_001001432.3:c.716C>T
NM_001276345.2:c.764C>TMANE SELECT
NM_001276346.2:c.635C>T
NM_001276347.2:c.734C>T
NP_000355.2:p.Ala252Val
NP_001001430.1:p.Ala245Val
NP_001001431.1:p.Ala242Val
NP_001001432.1:p.Ala239Val
NP_001263274.1:p.Ala255Val
NP_001263275.1:p.Ala212Val
NP_001263276.1:p.Ala245Val
LRG_431t1:c.764C>T
LRG_431:g.21353C>T
LRG_431p1:p.Ala255Val
NC_000001.10:g.201330453G>A
NM_001001430.1:c.734C>T
NM_001001430.2:c.734C>T

Protein change:

A212V

Links:

dbSNP: rs369181536

NCBI 1000 Genomes Browser:

rs369181536

Molecular consequence:

NM_000364.4:c.755C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001001430.3:c.734C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001001431.3:c.725C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001001432.3:c.716C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276345.2:c.764C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276346.2:c.635C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276347.2:c.734C>T - 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
SCV002674970	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jun 12, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22958901, 24503780, 27532257 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002674970

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jun 12, 2023)

germline

clinical testing

PubMed (3)
[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	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

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 (3)

Details of each submission

From Ambry Genetics, SCV002674970.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.A245V variant (also known as c.734C>T), located in coding exon 13 of the TNNT2 gene, results from a C to T substitution at nucleotide position 734. The alanine at codon 245 is replaced by valine, an amino acid with similar properties. This alteration was reported in one individual with dilated cardiomyopathy (DCM) who also had variants in other cardiac-related genes, as well as in a DCM genetic testing cohort with limited clinical information provided (Pugh TJ et al. Genet. Med., 2014 Aug;16:601-8; Walsh R et al. Genet. Med., 2017 02;19:192-203). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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

Last Updated: May 7, 2024

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