TNNT2, 3-BP DEL, 285GGA AND Familial restrictive cardiomyopathy 3

Clinical significance:Pathogenic (Last evaluated: Jan 25, 2008)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000013230.24

Allele description [Variation Report for TNNT2, 3-BP DEL, 285GGA]

TNNT2, 3-BP DEL, 285GGA

Gene:
TNNT2:troponin T2, cardiac type [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
1q32
Preferred name:
TNNT2, 3-BP DEL, 285GGA
HGVS:
    Nucleotide change:
    3-BP DEL, 285GGA
    Links:
    OMIM: 191045.0011

    Condition(s)

    Name:
    Familial restrictive cardiomyopathy 3 (RCM3)
    Identifiers:
    MedGen: C2676271; Orphanet: 75249; OMIM: 612422

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    Assertion and evidence details

    Submission AccessionSubmitterReview Status
    (Assertion method)
    Clinical Significance
    (Last evaluated)
    OriginMethodCitations
    SCV000033477OMIMno assertion criteria providedPathogenic
    (Jan 25, 2008)
    germlineliterature only

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

    Summary from all submissions

    EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
    not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

    Citations

    PubMed

    Infantile restrictive cardiomyopathy resulting from a mutation in the cardiac troponin T gene.

    Peddy SB, Vricella LA, Crosson JE, Oswald GL, Cohn RD, Cameron DE, Valle D, Loeys BL.

    Pediatrics. 2006 May;117(5):1830-3.

    PubMed [citation]
    PMID:
    16651346

    A troponin T mutation that causes infantile restrictive cardiomyopathy increases Ca2+ sensitivity of force development and impairs the inhibitory properties of troponin.

    Pinto JR, Parvatiyar MS, Jones MA, Liang J, Potter JD.

    J Biol Chem. 2008 Jan 25;283(4):2156-66. Epub 2007 Nov 21.

    PubMed [citation]
    PMID:
    18032382

    Details of each submission

    From OMIM, SCV000033477.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedliterature only PubMed (2)

    Description

    In a 12-month-old girl with restrictive cardiomyopathy (612422), Peddy et al. (2006) identified a 3-bp deletion (285delGGA) in exon 9 the TNNT2 gene, resulting in the deletion of glutamic acid at codon 96 (glu96del) in a highly conserved segment of the main tropomyosin-binding region in the N-terminal half of troponin T. The deletion was not found in either parent, who had normal echocardiograms at ages 28 and 34 years, respectively. The girl also carried a known MYBPC3 (600958) polymorphism, V896M, which was also found in her unaffected father; the authors suggested that the V896M variant may have acted as a modifier, exacerbating the phenotypic expression of the TNNT2 mutation and causing an unusually early onset of RMC.

    Pinto et al. (2008) analyzed the effects of the 3-bp TNNT2 deletion in both the adult and fetal human cardiac TNNT2 isoforms, in order to evaluate the disease progression after birth when the isoform switch occurs. Both mutant isoforms showed a large increase in Ca(2+) sensitivity compared to their respective wildtypes, but there was no significant change in force recovery in any of the experiments. Both mutants showed an impaired ability to inhibit actomyosin ATPase activity, and the capacity of troponin complexes to fully relax fibers after troponin T displacement was also compromised. Experiments with fetal troponin isoforms showed a less severe impact compared with adult isoforms, consistent with a cardioprotective role for slow skeletal isoforms and with the rapid onset of RCM after birth following the isoform switch.

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

    Last Updated: Sep 5, 2017