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NM_001276345.2(TNNT2):c.502C>G (p.Arg168Gly) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 23, 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:
RCV000646065.7

Allele description [Variation Report for NM_001276345.2(TNNT2):c.502C>G (p.Arg168Gly)]

NM_001276345.2(TNNT2):c.502C>G (p.Arg168Gly)

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.502C>G (p.Arg168Gly)
Other names:
p.R158G:CGA>GGA
HGVS:
  • NC_000001.11:g.201363394G>C
  • NG_007556.1:g.19284C>G
  • NM_000364.4:c.502C>G
  • NM_001001430.3:c.472C>G
  • NM_001001431.3:c.472C>G
  • NM_001001432.3:c.457C>G
  • NM_001276345.2:c.502C>GMANE SELECT
  • NM_001276346.2:c.382C>G
  • NM_001276347.2:c.472C>G
  • NP_000355.2:p.Arg168Gly
  • NP_001001430.1:p.Arg158Gly
  • NP_001001431.1:p.Arg158Gly
  • NP_001001432.1:p.Arg153Gly
  • NP_001263274.1:p.Arg168Gly
  • NP_001263275.1:p.Arg128Gly
  • NP_001263276.1:p.Arg158Gly
  • LRG_431t1:c.502C>G
  • LRG_431:g.19284C>G
  • LRG_431p1:p.Arg168Gly
  • NC_000001.10:g.201332522G>C
  • NM_001001430.1:c.472C>G
  • NM_001001430.2:c.472C>G
Protein change:
R128G
Links:
dbSNP: rs730881103
NCBI 1000 Genomes Browser:
rs730881103
Molecular consequence:
  • NM_000364.4:c.502C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001430.3:c.472C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001431.3:c.472C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001432.3:c.457C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276345.2:c.502C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276346.2:c.382C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276347.2:c.472C>G - 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
SCV000767822Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Mar 23, 2023) 		germlineclinical testing

PubMed (3)
[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

Multiple gene mutations, not the type of mutation, are the modifier of left ventricle hypertrophy in patients with hypertrophic cardiomyopathy.

Zou Y, Wang J, Liu X, Wang Y, Chen Y, Sun K, Gao S, Zhang C, Wang Z, Zhang Y, Feng X, Song Y, Wu Y, Zhang H, Jia L, Wang H, Wang D, Yan C, Lu M, Zhou X, Song L, Hui R.

Mol Biol Rep. 2013 Jun;40(6):3969-76. doi: 10.1007/s11033-012-2474-2. Epub 2013 Jan 3.

PubMed [citation]
PMID:
23283745

Genetic Risk of Arrhythmic Phenotypes in Patients With Dilated Cardiomyopathy.

Gigli M, Merlo M, Graw SL, Barbati G, Rowland TJ, Slavov DB, Stolfo D, Haywood ME, Dal Ferro M, Altinier A, Ramani F, Brun F, Cocciolo A, Puggia I, Morea G, McKenna WJ, La Rosa FG, Taylor MRG, Sinagra G, Mestroni L.

J Am Coll Cardiol. 2019 Sep 17;74(11):1480-1490. doi: 10.1016/j.jacc.2019.06.072.

PubMed [citation]
PMID:
31514951
PMCID:
PMC6750731
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000767822.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 181620). This missense change has been observed in individual(s) with dilated or hypertrophic cardiomyopathy (PMID: 23283745, 31514951; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 158 of the TNNT2 protein (p.Arg158Gly).

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

Last Updated: Sep 29, 2024