U.S. flag

An official website of the United States government

NM_001276345.2(TNNT2):c.422G>A (p.Arg141Gln) AND Primary dilated cardiomyopathy

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 2, 2015
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:
RCV000036585.6

Allele description [Variation Report for NM_001276345.2(TNNT2):c.422G>A (p.Arg141Gln)]

NM_001276345.2(TNNT2):c.422G>A (p.Arg141Gln)

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.422G>A (p.Arg141Gln)
HGVS:
  • NC_000001.11:g.201364365C>T
  • NG_007556.1:g.18313G>A
  • NM_000364.4:c.422G>A
  • NM_001001430.3:c.392G>A
  • NM_001001431.3:c.392G>A
  • NM_001001432.3:c.377G>A
  • NM_001276345.2:c.422G>AMANE SELECT
  • NM_001276346.2:c.302G>A
  • NM_001276347.2:c.392G>A
  • NP_000355.2:p.Arg141Gln
  • NP_001001430.1:p.Arg131Gln
  • NP_001001431.1:p.Arg131Gln
  • NP_001001432.1:p.Arg126Gln
  • NP_001263274.1:p.Arg141Gln
  • NP_001263275.1:p.Arg101Gln
  • NP_001263276.1:p.Arg131Gln
  • LRG_431t1:c.422G>A
  • LRG_431:g.18313G>A
  • LRG_431p1:p.Arg141Gln
  • NC_000001.10:g.201333493C>T
  • NM_001001430.1:c.392G>A
  • NM_001001430.2:c.392G>A
  • c.392G>A
Protein change:
R101Q
Links:
dbSNP: rs397516464
NCBI 1000 Genomes Browser:
rs397516464
Molecular consequence:
  • NM_000364.4:c.422G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001430.3:c.392G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001431.3:c.392G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001432.3:c.377G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276345.2:c.422G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276346.2:c.302G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276347.2:c.392G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

Condition(s)

Name:
Primary dilated cardiomyopathy (DCM)
Synonyms:
Dilated Cardiomyopathy
Identifiers:
EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000060240Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Feb 2, 2015) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided33not providednot providednot providedclinical testing

Citations

PubMed

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

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000060240.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (2)

Description

The p.Arg131Gln variant in TNNT2 has been identified by our laboratory as de nov o in 1 infant and in 1 child with DCM. This variant was absent from large popula tion studies. Additionally, other likely pathogenic amino acid alterations at th is position (p.Arg131Trp and p.Arg131Pro) have been reported, suggesting variati on at this position is not tolerated. Arginine (Arg) at position 131 is highly c onserved in mammals and across evolutionarily distant species and the change to glutamine (Gln) was predicted to be pathogenic using a computational tool clinic ally validated by our laboratory. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jordan 2011). In summary, this variant meets our criteria to be classified as pathogenic for DCM in an autosomal dominant manner (http://www.partners.org/personalizedmedicine/LMM) based upon multiple de novo occurrences and absence from controls.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided3not provided3not provided

Last Updated: May 19, 2024