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NM_001276345.2(TNNT2):c.321G>T (p.Lys107Asn) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 18, 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:
RCV000791922.5

Allele description [Variation Report for NM_001276345.2(TNNT2):c.321G>T (p.Lys107Asn)]

NM_001276345.2(TNNT2):c.321G>T (p.Lys107Asn)

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.321G>T (p.Lys107Asn)
HGVS:
  • NC_000001.11:g.201365281C>A
  • NG_007556.1:g.17397G>T
  • NM_000364.4:c.321G>T
  • NM_001001430.3:c.291G>T
  • NM_001001431.3:c.291G>T
  • NM_001001432.3:c.276G>T
  • NM_001276345.2:c.321G>TMANE SELECT
  • NM_001276346.2:c.291+329G>T
  • NM_001276347.2:c.291G>T
  • NP_000355.2:p.Lys107Asn
  • NP_001001430.1:p.Lys97Asn
  • NP_001001431.1:p.Lys97Asn
  • NP_001001432.1:p.Lys92Asn
  • NP_001263274.1:p.Lys107Asn
  • NP_001263276.1:p.Lys97Asn
  • LRG_431t1:c.321G>T
  • LRG_431:g.17397G>T
  • LRG_431p1:p.Lys107Asn
  • NC_000001.10:g.201334409C>A
  • NM_001001430.1:c.291G>T
  • NM_001001430.2:c.291G>T
  • NM_001001430.3:c.291G>T
  • NM_001001431.2:c.291G>T
  • c.291G>T
Protein change:
K107N
Links:
dbSNP: rs397516459
NCBI 1000 Genomes Browser:
rs397516459
Molecular consequence:
  • NM_001276346.2:c.291+329G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000364.4:c.321G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001430.3:c.291G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001431.3:c.291G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001432.3:c.276G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276345.2:c.321G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276347.2:c.291G>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000931191Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 18, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Clinical challenges of genotype positive (+)-phenotype negative (-) family members in hypertrophic cardiomyopathy.

Maron BJ, Yeates L, Semsarian C.

Am J Cardiol. 2011 Feb 15;107(4):604-8. doi: 10.1016/j.amjcard.2010.10.022. Epub 2010 Dec 22. No abstract available.

PubMed [citation]
PMID:
21185001

Clinical phenotype and outcome of hypertrophic cardiomyopathy associated with thin-filament gene mutations.

Coppini R, Ho CY, Ashley E, Day S, Ferrantini C, Girolami F, Tomberli B, Bardi S, Torricelli F, Cecchi F, Mugelli A, Poggesi C, Tardiff J, Olivotto I.

J Am Coll Cardiol. 2014 Dec 23;64(24):2589-2600. doi: 10.1016/j.jacc.2014.09.059.

PubMed [citation]
PMID:
25524337
PMCID:
PMC4270453
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000931191.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 97 of the TNNT2 protein (p.Lys97Asn). This variant is present in population databases (rs397516459, gnomAD 0.0009%). This missense change has been observed in individuals with TNNT2-related conditions (PMID: 21185001, 25524337, 27532257; Invitae). ClinVar contains an entry for this variant (Variation ID: 43631). 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 affects TNNT2 function (PMID: 33025817). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 3, 2024