NM_001276345.2(TNNT2):c.835A>G (p.Asn279Asp) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 11, 2022
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:: RCV002415696.2

Allele description [Variation Report for NM_001276345.2(TNNT2):c.835A>G (p.Asn279Asp)]

NM_001276345.2(TNNT2):c.835A>G (p.Asn279Asp)

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.835A>G (p.Asn279Asp)

HGVS:

NC_000001.11:g.201359639T>C
NG_007556.1:g.23039A>G
NM_000364.4:c.826A>G
NM_001001430.3:c.805A>G
NM_001001431.3:c.796A>G
NM_001001432.3:c.787A>G
NM_001276345.2:c.835A>GMANE SELECT
NM_001276346.2:c.706A>G
NM_001276347.2:c.805A>G
NP_000355.2:p.Asn276Asp
NP_001001430.1:p.Asn269Asp
NP_001001431.1:p.Asn266Asp
NP_001001432.1:p.Asn263Asp
NP_001263274.1:p.Asn279Asp
NP_001263275.1:p.Asn236Asp
NP_001263276.1:p.Asn269Asp
LRG_431t1:c.835A>G
LRG_431:g.23039A>G
LRG_431p1:p.Asn279Asp
NC_000001.10:g.201328767T>C
NM_001001430.1:c.805A>G
NM_001001430.2:c.805A>G
NM_001001430.3:c.805A>G

Protein change:

N236D

Links:

dbSNP: rs4523540

NCBI 1000 Genomes Browser:

rs4523540

Molecular consequence:

NM_000364.4:c.826A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001001430.3:c.805A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001001431.3:c.796A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001001432.3:c.787A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276345.2:c.835A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276346.2:c.706A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276347.2:c.805A>G - 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
SCV002677538	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 11, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22958901, 27532257 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002677538

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 11, 2022)

germline

clinical testing

PubMed (2)
[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

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]

PMID:: 27532257
PMCID:: PMC5116235

Details of each submission

From Ambry Genetics, SCV002677538.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.N269D variant (also known as c.805A>G), located in coding exon 14 of the TNNT2 gene, results from an A to G substitution at nucleotide position 805. The asparagine at codon 269 is replaced by aspartic acid, an amino acid with highly similar properties. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort; however, clinical details were limited (Walsh R et al. Genet. Med. 2017;19:192-203). Another alteration affecting the same amino acid, p.N269K (c.807C>A), has been reported in association with HCM (Kassem HSh et al. J Cardiovasc Transl Res, 2013 Feb;6:65-80). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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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