NM_000363.5(TNNI3):c.599G>A (p.Gly200Glu) AND Hypertrophic cardiomyopathy

Clinical significance:Uncertain significance (Last evaluated: Feb 15, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000229066.1

Allele description [Variation Report for NM_000363.5(TNNI3):c.599G>A (p.Gly200Glu)]

NM_000363.5(TNNI3):c.599G>A (p.Gly200Glu)

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.599G>A (p.Gly200Glu)
HGVS:
  • NC_000019.10:g.55151868C>T
  • NG_007866.2:g.10865G>A
  • NG_011829.2:g.2371G>A
  • NM_000363.5:c.599G>AMANE SELECT
  • NP_000354.4:p.Gly200Glu
  • LRG_432t1:c.599G>A
  • LRG_432:g.10865G>A
  • LRG_679:g.2371G>A
  • NC_000019.9:g.55663236C>T
  • NM_000363.4:c.599G>A
Protein change:
G200E
Links:
dbSNP: rs878853957
NCBI 1000 Genomes Browser:
rs878853957
Molecular consequence:
  • NM_000363.5:c.599G>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
SCV000284661Invitaecriteria provided, single submitter
Uncertain significance
(Feb 15, 2016)
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, SCV000284661.2

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

Description

This sequence change replaces glycine with glutamic acid at codon 200 of the TNNI3 protein (p.Gly200Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change is located within exon 8 of the TNNI3 protein and a high percentage of previously reported TNNI3 missense mutations have been found within either exon 7 or exon 8 (PMID: 15607392). These observations suggest that a novel missense substitution within this exon may affect protein function, but experiments have not been done to test this possibility. In summary, this is a novel missense change with uncertain impact on protein function. It 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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