U.S. flag

An official website of the United States government

NM_000363.5(TNNI3):c.611G>A (p.Arg204His) AND Hypertrophic cardiomyopathy

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Feb 9, 2017
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000469008.1

Allele description

NM_000363.5(TNNI3):c.611G>A (p.Arg204His)

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.611G>A (p.Arg204His)
Other names:
p.R204H:CGC>CAC
HGVS:
  • NC_000019.10:g.55151856C>T
  • NG_007866.2:g.10877G>A
  • NG_011829.2:g.2383G>A
  • NM_000363.5:c.611G>A
  • NP_000354.4:p.Arg204His
  • LRG_432t1:c.611G>A
  • LRG_432:g.10877G>A
  • NC_000019.9:g.55663224C>T
  • NM_000363.4:c.611G>A
  • P19429:p.Arg204His
Protein change:
R204H
Links:
UniProtKB: P19429#VAR_042746; dbSNP: rs727504275
NCBI 1000 Genomes Browser:
rs727504275
Molecular consequence:
  • NM_000363.5:c.611G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Name:
Hypertrophic cardiomyopathy
Identifiers:
MedGen: C0007194; Human Phenotype Ontology: HP:0001639

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000551899Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Jul 31, 2016) 		germlineclinical testing

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

SCV000579527Center for Human Genetics,University of Leuven
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Feb 9, 2017) 		de novoclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
Asian-Africande novoyes11not providednot providednoclinical testing
Caucasiande novoyes11not providednot providednoclinical 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000551899.2

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

Description

This sequence change replaces arginine with histidine at codon 204 of the TNNI3 protein (p.Arg204His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in several individuals affected with hypertrophic cardiomyopathy (PMID: 15698845, 20569525) and restrictive cardiomyopathy (PMID: 23906401, 18801787). ClinVar contains an entry for this variant (Variation ID: 177679). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function that has been reported in several affected individuals. However further functional and/or genetic data will be needed to fully stablished pathogenicity for this variant. For these reasons, it has been classified as Likely Pathogenic.

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

From Center for Human Genetics,University of Leuven, SCV000579527.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Asian-African1not providednoclinical testingnot provided
2Caucasian1not providednoclinical testingnot provided

Description

Observed as de novo variant

Observed as de novo variant

Description

ACMG score likely pathogenic

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyesnot providednot providednot provided1not provided1not provided
2de novoyesnot providednot providednot provided1not provided1not provided

Last Updated: Aug 18, 2019