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NM_000363.5(TNNI3):c.575G>A (p.Arg192His) AND Dilated cardiomyopathy 2A

Germline classification:
Pathogenic (1 submission)
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:
RCV003388566.2

Allele description [Variation Report for NM_000363.5(TNNI3):c.575G>A (p.Arg192His)]

NM_000363.5(TNNI3):c.575G>A (p.Arg192His)

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.575G>A (p.Arg192His)
Other names:
p.R192H:CGC>CAC
HGVS:
  • NC_000019.10:g.55151892C>T
  • NG_007866.2:g.10841G>A
  • NG_011829.2:g.2347G>A
  • NM_000363.5:c.575G>AMANE SELECT
  • NP_000354.4:p.Arg192His
  • LRG_432t1:c.575G>A
  • LRG_432:g.10841G>A
  • LRG_679:g.2347G>A
  • NC_000019.9:g.55663260C>T
  • NM_000363.4:c.575G>A
  • P19429:p.Arg192His
Protein change:
R192H; ARG192HIS
Links:
UniProtKB: P19429#VAR_016084; OMIM: 191044.0006; dbSNP: rs104894729
NCBI 1000 Genomes Browser:
rs104894729
Molecular consequence:
  • NM_000363.5:c.575G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Dilated cardiomyopathy 2A (CMD2A)
Synonyms:
CARDIOMYOPATHY, CONGESTIVE, AUTOSOMAL RECESSIVE; CARDIOMYOPATHY, DILATED, AUTOSOMAL RECESSIVE
Identifiers:
MONDO: MONDO:0012746; MedGen: C2678474; Orphanet: 154; OMIM: 611880

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004100355Neuberg Centre For Genomic Medicine, NCGM
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenicgermlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Neuberg Centre For Genomic Medicine, NCGM, SCV004100355.1

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

Description

The missense variant p.R192H in TNNI3 (NM_000363.5) causes the same amino acid change as a previously established pathogenic variant. The p.Arg192His variant in TNNI3 (NM_000363.5) has been reported in 9 individuals with predominantly childhood onset RCM or HCM and occurred de novo in 4 of these cases (Mogensen 2003, Gomes 2005, Rai 2009, Yang 2013). The p.R192H variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The gene TNNI3 contains 38 pathogenic missense variants, indicating that missense variants are a common mechanism of disease in this gene. 9 variants within 6 amino acid positions of the variant p.R192H have been shown to be pathogenic, while none have been shown to be benign. The p.R192H missense variant is predicted to be damaging by both SIFT and PolyPhen2. The arginine residue at codon 192 of TNNI3 is conserved in all mammalian species. The nucleotide c.575 in TNNI3 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 19, 2024