NM_000363.5(TNNI3):c.554A>G (p.Asn185Ser) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Jun 25, 2012)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000159238.2

Allele description [Variation Report for NM_000363.5(TNNI3):c.554A>G (p.Asn185Ser)]

NM_000363.5(TNNI3):c.554A>G (p.Asn185Ser)

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.554A>G (p.Asn185Ser)
Other names:
p.N185S:AAC>AGC
HGVS:
  • NC_000019.10:g.55151913T>C
  • NG_007866.2:g.10820A>G
  • NG_011829.2:g.2326A>G
  • NM_000363.5:c.554A>GMANE SELECT
  • NP_000354.4:p.Asn185Ser
  • LRG_432t1:c.554A>G
  • LRG_432:g.10820A>G
  • LRG_679:g.2326A>G
  • NC_000019.9:g.55663281T>C
  • NM_000363.4:c.554A>G
Protein change:
N185S
Links:
dbSNP: rs730881079
NCBI 1000 Genomes Browser:
rs730881079
Molecular consequence:
  • NM_000363.5:c.554A>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
SCV000209184GeneDxcriteria provided, single submitter
Likely pathogenic
(Jun 25, 2012)
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, SCV000209184.10

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

Description

The Asn185Ser variant in the TNNI3 gene has not been reported as a disease-causing mutation or as a benign polymorphism, to our knowledge. However, a mutation at the same position, Asn185Lys, has been reported in a 24 year-old patient with DCM and the patient's affected father, and the mutation was absent from 280 ethnically matched control chromosomes (Carballo S et al., 2009). Furthermore, mutations in nearby codons (Lys183Asn, Lys183Glu, Arg186Gln, Asp190Gly) have been reported in association with cardiomyopathy, supporting the functional importance of this region of the protein. The NHLBI ESP Exome Variant Server reports Asn185Ser was not observed in approximately 5,900 samples from individuals of European and African American backgrounds, indicating it is not a common variant in these populations. However, Asn185Ser is a conservative amino acid substitution of a larger, neutral, polar Asparagine with a smaller, neutral, polar Serine at a position that is not well conserved through evolution.In summary, with the clinical and molecular information available at this time, we cannot unequivocally determine the clinical significance of Asn185Ser in the TNNI3 gene, although evidence suggests it is likely disease-causing. 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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