NM_001001430.2(TNNT2):c.416G>A (p.Arg139His) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Jul 31, 2014)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000036590.3

Allele description [Variation Report for NM_001001430.2(TNNT2):c.416G>A (p.Arg139His)]

NM_001001430.2(TNNT2):c.416G>A (p.Arg139His)

Gene:
TNNT2:troponin T2, cardiac type [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q32.1
Genomic location:
Preferred name:
NM_001001430.2(TNNT2):c.416G>A (p.Arg139His)
Other names:
p.R139H:CGC>CAC
HGVS:
  • NC_000001.11:g.201364341C>T
  • NG_007556.1:g.18337G>A
  • NM_000364.3:c.446G>A
  • NM_001001430.2:c.416G>A
  • NM_001276347.1:c.416G>A
  • NP_000355.2:p.Arg149His
  • NP_001001430.1:p.Arg139His
  • NP_001263276.1:p.Arg139His
  • NC_000001.10:g.201333469C>T
  • NM_001001430.1:c.416G>A
  • c.416G>A
Protein change:
R139H
Links:
dbSNP: 397516466
NCBI 1000 Genomes Browser:
rs397516466
Molecular consequence:
  • NM_001001430.2:c.416G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
4

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000060245Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Jul 31, 2014)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided84not providednot providednot providedclinical testing

Citations

PubMed

Late onset sporadic dilated cardiomyopathy caused by a cardiac troponin T mutation.

Morales A, Pinto JR, Siegfried JD, Li D, Norton N, Hofmeyer M, Vallin M, Morales AR, Potter JD, Hershberger RE.

Clin Transl Sci. 2010 Oct;3(5):219-26. doi: 10.1111/j.1752-8062.2010.00228.x.

PubMed [citation]
PMID:
20973921
PMCID:
PMC2965560

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,Partners HealthCare Personalized Medicine, SCV000060245.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided8not providednot providedclinical testing PubMed (2)

Description

The Arg139His variant in TNNT2 has been identified by our laboratory in 1 adult with DCM, who also carried the 690-6G>A varint in TNNT2 on the same copy of the gene (in cis; Morales 2010), as well as in 2 infants with DCM who inherited this variant from an unaffected parent (LMM unpublished). One of these infants carried a second variant in TNNT2 on the other copy of the gene (in trans) that may also be contributing to disease. In addition, this variant was absent from large population studies. Arginine (Arg) at position 139 is highly conserved in evolution and the change to histidine (His) was predicted to be pathogenic using a computational tool clinically validated by our laboratory. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jordan 2011). In addition, another variant at the same position (Arg139Cys) as been identified in 1 family with DCM suggesting that changes to this residue are not tolerated. Studies have shown that this variant affects the protein’s function, though it is unclear if this effect would result in disease (Morales 2010). In summary, while there is some suspicion for a pathogenic role, the clinical significance of the Arg139His variant is uncertain.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided8not provided4not provided

Last Updated: May 7, 2017