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NM_000363.5(TNNI3):c.574C>T (p.Arg192Cys) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 30, 2021
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:
RCV003224802.3

Allele description [Variation Report for NM_000363.5(TNNI3):c.574C>T (p.Arg192Cys)]

NM_000363.5(TNNI3):c.574C>T (p.Arg192Cys)

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.574C>T (p.Arg192Cys)
HGVS:
  • NC_000019.10:g.55151893G>A
  • NG_007866.2:g.10840C>T
  • NG_011829.2:g.2346C>T
  • NM_000363.5:c.574C>TMANE SELECT
  • NP_000354.4:p.Arg192Cys
  • LRG_432t1:c.574C>T
  • LRG_432:g.10840C>T
  • LRG_679:g.2346C>T
  • NC_000019.9:g.55663261G>A
  • NM_000363.4:c.574C>T
Protein change:
R192C
Links:
dbSNP: rs727503499
NCBI 1000 Genomes Browser:
rs727503499
Molecular consequence:
  • NM_000363.5:c.574C>T - 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
Name:
Cardiomyopathy, familial restrictive, 1
Identifiers:
MONDO: MONDO:0007270; MedGen: C1861861; Orphanet: 75249; OMIM: 115210
Name:
Dilated cardiomyopathy 1FF (CMD1FF)
Identifiers:
MONDO: MONDO:0013211; MedGen: C2750091; Orphanet: 154; OMIM: 613286
Name:
Hypertrophic cardiomyopathy 7
Synonyms:
Familial hypertrophic cardiomyopathy 7; CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 7, MODIFIER OF; TNNI3-Related Familial Hypertrophic Cardiomyopathy
Identifiers:
MONDO: MONDO:0013369; MedGen: C1860752; OMIM: 613690

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003920894Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Mar 30, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot 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 Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV003920894.1

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

Description

TNNI3 NM_000363.4 exon 8 p.Arg192Cys (c.574C>T): This variant has been reported in the literature in 1 individual with restrictive cardiomyopathy (Van de Wijngaard 2011 PMID:21533915) and has been identified by our laboratory as de novo in 1 individual with sudden unexplained death. This variant is not present in large control databases. This variant is present in ClinVar (Variation ID:165510). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. Of note, other variants at this same codon have strong evidence for pathogenicity (p.Arg192His) and/or have been reported in the literature in individuals with disease (p.Arg192Leu), supporting that this region has significance. In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant classified as likely pathogenic.

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

Last Updated: Oct 20, 2024