NM_000363.5(TNNI3):c.582C>G (p.Asn194Lys) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Jun 23, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000159261.3

Allele description [Variation Report for NM_000363.5(TNNI3):c.582C>G (p.Asn194Lys)]

NM_000363.5(TNNI3):c.582C>G (p.Asn194Lys)

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.582C>G (p.Asn194Lys)
Other names:
p.N194K:AAC>AAG
HGVS:
  • NC_000019.10:g.55151885G>C
  • NG_007866.2:g.10848C>G
  • NG_011829.2:g.2354C>G
  • NM_000363.5:c.582C>GMANE SELECT
  • NP_000354.4:p.Asn194Lys
  • LRG_432t1:c.582C>G
  • LRG_432:g.10848C>G
  • LRG_679:g.2354C>G
  • NC_000019.9:g.55663253G>C
  • NM_000363.4:c.582C>G
Protein change:
N194K
Links:
dbSNP: rs730881090
NCBI 1000 Genomes Browser:
rs730881090
Molecular consequence:
  • NM_000363.5:c.582C>G - 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
SCV000209207GeneDxcriteria provided, single submitter
Likely pathogenic
(Jun 23, 2017)
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, SCV000209207.10

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

Description

The Asn194Lys variant in the TNNI3 gene has not been reported previously as pathogenic or as a benign polymorphism, to our knowledge. Asn194Lys results in a semi-conservative amino acid substitution of a neutral, polar Asparagine residue with a positively charged Lysine residue at a position that is conserved across species throughout evolution. In silico analysis predicts this change to be damaging to the structure/function of the protein and likely pathogenic. In addition, variants at surrounding residues (Arg192His, Arg192Cys, Ile195Met) have been reported in association with cardiomyopathy, further supporting the functional importance of this region of the protein. Furthermore, Asn194Lys was not detected in multiple control alleles of Caucasian ethnic backgrounds tested at GeneDx, indicating it is not a common benign polymorphism in this population. Based on currently available evidence, N194K is a strong candidate for a pathogenic variant. However, the possibility it is a rare benign variant cannot be excluded

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

Last Updated: Feb 27, 2021

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