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NM_000363.5(TNNI3):c.568G>T (p.Asp190Tyr) AND Hypertrophic cardiomyopathy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 11, 2019
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000152073.6

Allele description [Variation Report for NM_000363.5(TNNI3):c.568G>T (p.Asp190Tyr)]

NM_000363.5(TNNI3):c.568G>T (p.Asp190Tyr)

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.568G>T (p.Asp190Tyr)
HGVS:
  • NC_000019.10:g.55151899C>A
  • NG_007866.2:g.10834G>T
  • NG_011829.2:g.2340G>T
  • NM_000363.5:c.568G>TMANE SELECT
  • NP_000354.4:p.Asp190Tyr
  • LRG_432t1:c.568G>T
  • LRG_432:g.10834G>T
  • LRG_679:g.2340G>T
  • NC_000019.9:g.55663267C>A
  • NM_000363.4:c.568G>T
Protein change:
D190Y
Links:
dbSNP: rs727503500
NCBI 1000 Genomes Browser:
rs727503500
Molecular consequence:
  • NM_000363.5:c.568G>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Hypertrophic cardiomyopathy
Synonyms:
HYPERTROPHIC MYOCARDIOPATHY
Identifiers:
MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000200711Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Likely pathogenic
(Jul 11, 2019) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown51not providednot providednot providedclinical testing

Citations

PubMed

Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations.

Mogensen J, Kubo T, Duque M, Uribe W, Shaw A, Murphy R, Gimeno JR, Elliott P, McKenna WJ.

J Clin Invest. 2003 Jan;111(2):209-16. Erratum in: J Clin Invest. 2003 Mar;111(6):925.

PubMed [citation]
PMID:
12531876
PMCID:
PMC151864

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000200711.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided5not providednot providedclinical testing PubMed (2)

Description

The p.Asp190Tyr variant in TNNI3 has been identified by our laboratory in 1 adult with HCM and segregated with disease in 4 affected relatives. It was absent from large population studies. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. Another HCM-associated variant meeting our criteria for pathogenicity has been reported at this same position (p.Asp190Gly; Mogensen 2003) suggesting that variation at this amino acid may not be tolerated. In summary, although additional studies are required to fully establish its clinical significance, the p.Asp190Tyr variant meets criteria to be classified as likely pathogenic for autosomal dominant HCM. ACMG/AMP Criteria applied: PM2, PM5, PP1, PP3.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided5not provided1not provided

Last Updated: Dec 24, 2022