NM_000363.5(TNNI3):c.428C>A (p.Thr143Asn) AND Cardiomyopathy

Clinical significance:Uncertain significance (Last evaluated: Nov 24, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001192353.2

Allele description [Variation Report for NM_000363.5(TNNI3):c.428C>A (p.Thr143Asn)]

NM_000363.5(TNNI3):c.428C>A (p.Thr143Asn)

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.428C>A (p.Thr143Asn)
Other names:
p.T143N:ACC>AAC
HGVS:
  • NC_000019.10:g.55154151G>T
  • NG_007866.2:g.8582C>A
  • NG_011829.2:g.88C>A
  • NM_000363.5:c.428C>AMANE SELECT
  • NP_000354.4:p.Thr143Asn
  • LRG_432t1:c.428C>A
  • LRG_432:g.8582C>A
  • LRG_679:g.88C>A
  • NC_000019.9:g.55665519G>T
  • NM_000363.4:c.428C>A
  • c.428C>A
Protein change:
T143N
Links:
dbSNP: rs397516348
NCBI 1000 Genomes Browser:
rs397516348
Molecular consequence:
  • NM_000363.5:c.428C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiomyopathy (CMYO)
Identifiers:
MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001360400Color Health, Inccriteria provided, single submitter
Uncertain significance
(Nov 24, 2020)
germlineclinical testing

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

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 Color Health, Inc, SCV001360400.2

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

Description

This missense variant replaces threonine with asparagine at codon 143 of the TNNI3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Computational splicing tools suggest that this variant may not impact RNA splicing. Experimental studies have suggested that this variant may abolish the phosphorylation site and may therefore have deleterious impact on the protein function (PMID: 15774859, 17010989, 17872964). However, clinical significance of these observations is unclear. This variant has been reported in 8 individuals affected with or referred for testing for hypertrophic cardiomyopathy (PMID: 23690394, 26936621, 27532257). Three of these individuals also carried pathogenic variants in the MYBPC3 and TPM1 gene (PMID: 26936621). This variant has also been identified in 9/248930 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 6, 2021

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