NM_000363.5(TNNI3):c.509G>A (p.Arg170Gln) AND Hypertrophic cardiomyopathy

Clinical significance:Pathogenic (Last evaluated: Oct 5, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000540068.4

Allele description [Variation Report for NM_000363.5(TNNI3):c.509G>A (p.Arg170Gln)]

NM_000363.5(TNNI3):c.509G>A (p.Arg170Gln)

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.509G>A (p.Arg170Gln)
Other names:
p.R170Q:CGG>CAG
HGVS:
  • NC_000019.10:g.55154070C>T
  • NG_007866.2:g.8663G>A
  • NG_011829.2:g.169G>A
  • NM_000363.5:c.509G>AMANE SELECT
  • NP_000354.4:p.Arg170Gln
  • LRG_432t1:c.509G>A
  • LRG_432:g.8663G>A
  • LRG_679:g.169G>A
  • NC_000019.9:g.55665438C>T
  • NM_000363.4:c.509G>A
Protein change:
R170Q
Links:
dbSNP: rs727503503
NCBI 1000 Genomes Browser:
rs727503503
Molecular consequence:
  • NM_000363.5:c.509G>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
SCV000623788Invitaecriteria provided, single submitter
Pathogenic
(Oct 5, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Prevalence of sarcomere protein gene mutations in preadolescent children with hypertrophic cardiomyopathy.

Kaski JP, Syrris P, Esteban MT, Jenkins S, Pantazis A, Deanfield JE, McKenna WJ, Elliott PM.

Circ Cardiovasc Genet. 2009 Oct;2(5):436-41. doi: 10.1161/CIRCGENETICS.108.821314. Epub 2009 Jul 16.

PubMed [citation]
PMID:
20031618

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]
PMID:
27532257
PMCID:
PMC5116235
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000623788.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces arginine with glutamine at codon 170 of the TNNI3 protein (p.Arg170Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with hypertrophic cardiomyopathy (PMID: 20031618, 27532257). This variant has also been shown to arise de novo in an individual affected with restrictive cardiomyopathy (PMID: 25940119). ClinVar contains an entry for this variant (Variation ID: 165516). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Jul 7, 2021

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