NM_000363.5(TNNI3):c.331A>G (p.Arg111Gly) AND Cardiomyopathy

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 9, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001190439.5

Allele description [Variation Report for NM_000363.5(TNNI3):c.331A>G (p.Arg111Gly)]

NM_000363.5(TNNI3):c.331A>G (p.Arg111Gly)

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.331A>G (p.Arg111Gly)

Other names:

p.R111G:AGA>GGA

HGVS:

NC_000019.10:g.55154782T>C
NG_007866.2:g.7951A>G
NM_000363.5:c.331A>GMANE SELECT
NP_000354.4:p.Arg111Gly
LRG_432t1:c.331A>G
LRG_432:g.7951A>G
NC_000019.9:g.55666150T>C
NM_000363.4:c.331A>G

Protein change:

R111G

Links:

dbSNP: rs730881088

NCBI 1000 Genomes Browser:

rs730881088

Molecular consequence:

NM_000363.5:c.331A>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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Homo sapiens keratin 40 (KRT40), transcript variant 1, mRNA
Homo sapiens keratin 40 (KRT40), transcript variant 1, mRNA
gi|1632519222|ref|NM_182497.4|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001357932	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 9, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004239771	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 23, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001357932

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 9, 2023)

germline

clinical testing

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

SCV004239771

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 23, 2023)

germline

clinical testing

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

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

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 Diagnostics, LLC DBA Color Health, SCV001357932.3

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

Description

This missense variant replaces arginine with glycine at codon 111 of the TNNI3 protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TNNI3-related disorders in the literature. This variant has been identified in 6/249460 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.

#	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

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, SCV004239771.1

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

#	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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