NM_015978.3(TNNI3K):c.1538T>C (p.Leu513Pro) AND Arrhythmogenic right ventricular dysplasia 2

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 20, 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:: RCV001807868.1

Allele description [Variation Report for NM_015978.3(TNNI3K):c.1538T>C (p.Leu513Pro)]

NM_015978.3(TNNI3K):c.1538T>C (p.Leu513Pro)

Genes:

FPGT-TNNI3K:FPGT-TNNI3K readthrough [Gene - HGNC]
TNNI3K:TNNI3 interacting kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p31.1

Genomic location:

Preferred name:

NM_015978.3(TNNI3K):c.1538T>C (p.Leu513Pro)

HGVS:

NC_000001.11:g.74369456T>C
NG_032939.2:g.176204T>C
NM_001112808.3:c.1841T>C
NM_001199327.2:c.1841T>C
NM_015978.3:c.1538T>CMANE SELECT
NP_001106279.3:p.Leu614Pro
NP_001186256.3:p.Leu614Pro
NP_057062.1:p.Leu513Pro
LRG_678t1:c.1538T>C
LRG_678:g.176204T>C
LRG_678p1:p.Leu513Pro
NC_000001.10:g.74835140T>C
NM_015978.2:c.1538T>C

Protein change:

L513P

Links:

dbSNP: rs1294489336

NCBI 1000 Genomes Browser:

rs1294489336

Molecular consequence:

NM_001112808.3:c.1841T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001199327.2:c.1841T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_015978.3:c.1538T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Arrhythmogenic right ventricular dysplasia 2
Identifiers:: MedGen: C1832931

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002054099	Clinical Center for Gene Diagnosis and Therapy, Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 20, 2021)	unknown	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002054099

Clinical Center for Gene Diagnosis and Therapy, Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 20, 2021)

unknown

research

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	unknown	yes	not provided	not provided	not provided	not provided	not provided	research

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 Clinical Center for Gene Diagnosis and Therapy, Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, SCV002054099.1

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

Description

A novel mutation (c.1538T>C) of TNNI3K was identified in a 6-year-old chineses man, with phenotypes of dominant RV disease fulfilling ’definite’ diagnosis of ARVC according to the 2010 Task Force Criteria and was absent from 1000 Genomes and ExAC, and only one from gnomeAD. The comprehensive assessment of the mutation was pathogenic. We found that this mutation would lead to a decrease in the level of TNNI3K mRNA and protein, as well as a decrease in the expression of RYR2 gene, which further proves that TNNI3K plays an important role in cardiomyopathy and expands the spectrum of TNNI3K mutation.

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

Last Updated: Dec 24, 2023

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