NM_000363.5(TNNI3):c.585C>G (p.Ile195Met) AND Hypertrophic cardiomyopathy

Clinical significance:Uncertain significance (Last evaluated: Mar 25, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000363.5(TNNI3):c.585C>G (p.Ile195Met)]

NM_000363.5(TNNI3):c.585C>G (p.Ile195Met)

TNNI3:troponin I3, cardiac type [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000363.5(TNNI3):c.585C>G (p.Ile195Met)
  • NC_000019.10:g.55151882G>C
  • NG_007866.2:g.10851C>G
  • NG_011829.2:g.2357C>G
  • NM_000363.5:c.585C>GMANE SELECT
  • NP_000354.4:p.Ile195Met
  • LRG_432t1:c.585C>G
  • LRG_432:g.10851C>G
  • LRG_679:g.2357C>G
  • NC_000019.9:g.55663250G>C
  • NM_000363.4:c.585C>G
Protein change:
Molecular consequence:
  • NM_000363.5:c.585C>G - missense variant - [Sequence Ontology: SO:0001583]


Hypertrophic cardiomyopathy
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)
SCV001234713Invitaecriteria provided, single submitter
Uncertain significance
(Mar 25, 2020)
germlineclinical testing

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

Summary from all submissions

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



Cellular and molecular aspects of familial hypertrophic cardiomyopathy caused by mutations in the cardiac troponin I gene.

Gomes AV, Potter JD.

Mol Cell Biochem. 2004 Aug;263(1-2):99-114. doi: 10.1023/B:MCBI.0000041852.42291.aa. Review.

PubMed [citation]

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]

Details of each submission

From Invitae, SCV001234713.2

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


This sequence change replaces isoleucine with methionine at codon 195 of the TNNI3 protein (p.Ile195Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with clinical features of hypertrophic cardiomyopathy (PMID: 15524171, Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 7, 2021

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