NM_000363.5(TNNI3):c.539A>G (p.Asp180Gly) AND Cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 19, 2023
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:: RCV003532121.1

Allele description [Variation Report for NM_000363.5(TNNI3):c.539A>G (p.Asp180Gly)]

NM_000363.5(TNNI3):c.539A>G (p.Asp180Gly)

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.539A>G (p.Asp180Gly)

HGVS:

NC_000019.10:g.55154040T>C
NG_007866.2:g.8693A>G
NG_011829.2:g.199A>G
NM_000363.5:c.539A>GMANE SELECT
NP_000354.4:p.Asp180Gly
LRG_432t1:c.539A>G
LRG_432:g.8693A>G
LRG_679:g.199A>G
NC_000019.9:g.55665408T>C
NM_000363.4:c.539A>G

Protein change:

D180G

Links:

dbSNP: rs1060499912

NCBI 1000 Genomes Browser:

rs1060499912

Molecular consequence:

NM_000363.5:c.539A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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actin-binding Rho-activating protein [Homo sapiens]
actin-binding Rho-activating protein [Homo sapiens]
gi|21040251|ref|NP_631905.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004359896	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 19, 2023)	germline	clinical testing	PubMed (12) [See all records that cite these PMIDs] 20215591, 20530761, 21483645, 21533915, 23785128, 25163546, 29447731, 30847666, 31112419, 31737537, 31771441, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004359896

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 19, 2023)

germline

clinical testing

PubMed (12)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Coding sequence rare variants identified in MYBPC3, MYH6, TPM1, TNNC1, and TNNI3 from 312 patients with familial or idiopathic dilated cardiomyopathy.

Hershberger RE, Norton N, Morales A, Li D, Siegfried JD, Gonzalez-Quintana J.

Circ Cardiovasc Genet. 2010 Apr;3(2):155-61. doi: 10.1161/CIRCGENETICS.109.912345. Epub 2010 Mar 9.

PubMed [citation]

PMID:: 20215591
PMCID:: PMC2908892

The importance of genetic counseling, DNA diagnostics, and cardiologic family screening in left ventricular noncompaction cardiomyopathy.

Hoedemaekers YM, Caliskan K, Michels M, Frohn-Mulder I, van der Smagt JJ, Phefferkorn JE, Wessels MW, ten Cate FJ, Sijbrands EJ, Dooijes D, Majoor-Krakauer DF.

Circ Cardiovasc Genet. 2010 Jun;3(3):232-9. doi: 10.1161/CIRCGENETICS.109.903898. Epub 2010 Jun 8.

PubMed [citation]

PMID:: 20530761

See all PubMed Citations (12)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV004359896.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (12)

Description

This missense variant replaces aspartic acid with glycine at codon 180 of the TNNI3 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with dilated cardiomyopathy (PMID: 20215591, 21483645, 23785128, 25163546, 30847666, 31112419, 31737537). It has also been reported in an individual affected with left ventricular noncompaction (PMID: 20530761, 21533915, 31771441) and in an individual affected with noncompaction cardiomyopathy (PMID: 29447731). This variant has not been identified 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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