NM_000363.5(TNNI3):c.167T>C (p.Ile56Thr) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 13, 2022
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:: RCV003162619.2

Allele description [Variation Report for NM_000363.5(TNNI3):c.167T>C (p.Ile56Thr)]

NM_000363.5(TNNI3):c.167T>C (p.Ile56Thr)

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.167T>C (p.Ile56Thr)

HGVS:

NC_000019.10:g.55156316A>G
NG_007866.2:g.6417T>C
NM_000363.5:c.167T>CMANE SELECT
NP_000354.4:p.Ile56Thr
LRG_432t1:c.167T>C
LRG_432:g.6417T>C
NC_000019.9:g.55667684A>G
NM_000363.4:c.167T>C

Protein change:

I56T

Links:

dbSNP: rs545441942

NCBI 1000 Genomes Browser:

rs545441942

Molecular consequence:

NM_000363.5:c.167T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003869211	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 13, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 21533915, 25611685, 27532257, 33495596, 33495597 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003869211

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 13, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

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

Recurrent and founder mutations in the Netherlands: cardiac Troponin I (TNNI3) gene mutations as a cause of severe forms of hypertrophic and restrictive cardiomyopathy.

van den Wijngaard A, Volders P, Van Tintelen JP, Jongbloed JD, van den Berg MP, Lekanne Deprez RH, Mannens MM, Hofmann N, Slegtenhorst M, Dooijes D, Michels M, Arens Y, Jongbloed R, Smeets BJ.

Neth Heart J. 2011 Aug;19(7-8):344-51. doi: 10.1007/s12471-011-0135-z.

PubMed [citation]

PMID:: 21533915
PMCID:: PMC3144325

Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity.

Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, Shen J, McLaughlin HM, Clark EH, Babb LJ, Cox SW, DePalma SR, Ho CY, Seidman JG, Seidman CE, Rehm HL.

Genet Med. 2015 Nov;17(11):880-8. doi: 10.1038/gim.2014.205. Epub 2015 Jan 22. Erratum in: Genet Med. 2015 Apr;17(4):319. doi: 10.1038/gim.2015.16.

PubMed [citation]

PMID:: 25611685

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV003869211.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The p.I56T variant (also known as c.167T>C), located in coding exon 5 of the TNNI3 gene, results from a T to C substitution at nucleotide position 167. The isoleucine at codon 56 is replaced by threonine, an amino acid with similar properties. This alteration has been reported in association with hypertrophic cardiomyopathy (HCM) (van den Wijngaard A et al. Neth Heart J, 2011 Aug;19:344-51; Alfares AA et al. Genet Med, 2015 Nov;17:880-8; Walsh R et al. Genet Med, 2017 Feb;19:192-203; Tadros R et al. Nat Genet, 2021 Feb;53:128-134). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Jul 7, 2024

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