NM_000363.5(TNNI3):c.521A>C (p.Lys174Thr) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: May 24, 2013)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000159234.2

Allele description [Variation Report for NM_000363.5(TNNI3):c.521A>C (p.Lys174Thr)]

NM_000363.5(TNNI3):c.521A>C (p.Lys174Thr)

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.521A>C (p.Lys174Thr)
Other names:
p.K174T:AAG>ACG
HGVS:
  • NC_000019.10:g.55154058T>G
  • NG_007866.2:g.8675A>C
  • NG_011829.2:g.181A>C
  • NM_000363.5:c.521A>CMANE SELECT
  • NP_000354.4:p.Lys174Thr
  • LRG_432t1:c.521A>C
  • LRG_432:g.8675A>C
  • LRG_679:g.181A>C
  • NC_000019.9:g.55665426T>G
  • NM_000363.4:c.521A>C
Protein change:
K174T
Links:
dbSNP: rs730881076
NCBI 1000 Genomes Browser:
rs730881076
Molecular consequence:
  • NM_000363.5:c.521A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000209180GeneDxcriteria provided, single submitter
Likely pathogenic
(May 24, 2013)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000209180.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The Lys174Thr variant in the TNNI3 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Lys174Thr results in a non-conservative amino acid substitution of a positively charged Lysine with a neutral, polar Threonine at a position that is mostly conserved across species. In silico analysis predicts Lys174Thr is probably damaging to the protein structure/function. Mutations in nearby residues (Arg170Gln, Ala171Thr, Lys178Glu, Asp180Gly) have been reported in association with cardiomyopathy, supporting the functional importance of this region of the protein. Furthermore, the Lys174Thr variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In summary, while Lys174Thr is a good candidate for a disease-causing mutation, with the clinical and molecular information available at this time we cannot unequivocally determine the clinical significance of this variant.The variant is found in HCM panel(s).

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

Last Updated: Feb 27, 2021

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