NM_000363.5(TNNI3):c.610C>A (p.Arg204Ser) AND Hypertrophic cardiomyopathy

Clinical significance:Uncertain significance (Last evaluated: Apr 14, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000554035.1

Allele description [Variation Report for NM_000363.5(TNNI3):c.610C>A (p.Arg204Ser)]

NM_000363.5(TNNI3):c.610C>A (p.Arg204Ser)

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.610C>A (p.Arg204Ser)
HGVS:
  • NC_000019.10:g.55151857G>T
  • NG_007866.2:g.10876C>A
  • NG_011829.2:g.2382C>A
  • NM_000363.5:c.610C>AMANE SELECT
  • NP_000354.4:p.Arg204Ser
  • LRG_432t1:c.610C>A
  • LRG_432:g.10876C>A
  • LRG_679:g.2382C>A
  • NC_000019.9:g.55663225G>T
  • NM_000363.4:c.610C>A
Protein change:
R204S
Links:
dbSNP: rs727504243
NCBI 1000 Genomes Browser:
rs727504243
Molecular consequence:
  • NM_000363.5:c.610C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hypertrophic cardiomyopathy
Identifiers:
MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; OMIM: PS192600; Human Phenotype Ontology: HP:0001639

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000623792Invitaecriteria provided, single submitter
Uncertain significance
(Apr 14, 2017)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000623792.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces arginine with serine at codon 204 of the TNNI3 protein (p.Arg204Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TNNI3-related disease. Different missense substitutions at this codon (p.Arg204His and p.Arg204Cys) have been determined to be pathogenic (PMID: 15698845, 20569525, 23906401, 27532257, 18801787, 27895589). This suggests that the arginine residue is critical for TNNI3 protein function and that other missense substitutions at this position may also be pathogenic. In summary, this variant is a rare missense change that affects a residue important for protein function. This evidence indicates that the variant is pathogenic, but additional clinical and functional data data is needed to prove that conclusively. Therefore, this variant has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 7, 2021

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