NM_000363.5(TNNI3):c.555C>G (p.Asn185Lys) AND Dilated cardiomyopathy 1FF

Clinical significance:Pathogenic (Last evaluated: Aug 14, 2009)

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:
RCV000013244.23

Allele description [Variation Report for NM_000363.5(TNNI3):c.555C>G (p.Asn185Lys)]

NM_000363.5(TNNI3):c.555C>G (p.Asn185Lys)

Gene:
TNNI3:troponin I3, cardiac type [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.42
Genomic location:
Preferred name:
NM_000363.5(TNNI3):c.555C>G (p.Asn185Lys)
HGVS:
  • NC_000019.10:g.55151912G>C
  • NG_007866.2:g.10821C>G
  • NG_011829.2:g.2327C>G
  • NM_000363.5:c.555C>GMANE SELECT
  • NP_000354.4:p.Asn185Lys
  • LRG_432t1:c.555C>G
  • LRG_432:g.10821C>G
  • LRG_432p1:p.Asn185Lys
  • LRG_679:g.2327C>G
  • NC_000019.9:g.55663280G>C
  • P19429:p.Asn185Lys
Protein change:
N185K; ASN185LYS
Links:
UniProtKB: P19429#VAR_063549; OMIM: 191044.0013; dbSNP: rs267607129
NCBI 1000 Genomes Browser:
rs267607129
Molecular consequence:
  • NM_000363.5:c.555C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Dilated cardiomyopathy 1FF (CMD1FF)
Synonyms:
Cardiomyopathy, dilated, 1N
Identifiers:
MONDO: MONDO:0013211; MedGen: C2750091; Orphanet: 154; OMIM: 613286

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000033491OMIMno assertion criteria providedPathogenic
(Aug 14, 2009)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

Identification and functional characterization of cardiac troponin I as a novel disease gene in autosomal dominant dilated cardiomyopathy.

Carballo S, Robinson P, Otway R, Fatkin D, Jongbloed JD, de Jonge N, Blair E, van Tintelen JP, Redwood C, Watkins H.

Circ Res. 2009 Aug 14;105(4):375-82. doi: 10.1161/CIRCRESAHA.109.196055. Epub 2009 Jul 9.

PubMed [citation]
PMID:
19590045

Details of each submission

From OMIM, SCV000033491.2

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

Description

In a man who was diagnosed at age 24 years with severe dilated cardiomyopathy (CMD1FF; 613286), requiring implantation of a left ventricular assist device within 2 months and undergoing cardiac transplantation 13 months later, Carballo et al. (2009) identified heterozygosity for a 555C-G transversion in exon 7 of the TNNI3 gene, resulting in an asn185-to-lys (N185K) substitution at a highly conserved residue. Analysis of Ca(2+) regulation of actin-tropomyosin-activated myosin ATPase by troponin showed that troponin reconstituted with N185K had lower maximum ATPase rates and reduced Ca(2+) sensitivity compared to wildtype; in addition, mutant thin filaments had lower Ca(2+) affinity than normal. The mutation was not found in 280 chromosomes from ethnically matched controls or in the patient's asymptomatic mother and brother, who had normal ECGs and echocardiograms. However, it was detected in a stored DNA sample from his father, who was diagnosed with CMD at 50 years of age and died 4 years later from complications related to cardiac resynchronization therapy.

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

Last Updated: Oct 7, 2021

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