NM_000363.5(TNNI3):c.529AAG[1] (p.Lys178del) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: May 4, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV001781349.9

Allele description [Variation Report for NM_000363.5(TNNI3):c.529AAG[1] (p.Lys178del)]

NM_000363.5(TNNI3):c.529AAG[1] (p.Lys178del)

Gene:

TNNI3:troponin I3, cardiac type [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

19q13.42

Genomic location:

Preferred name:

NM_000363.5(TNNI3):c.529AAG[1] (p.Lys178del)

HGVS:

NC_000019.10:g.55154046TTC[1]
NC_000019.9:g.55665413_55665415del
NG_007866.2:g.8683AAG[1]
NG_011829.2:g.189AAG[1]
NM_000363.5:c.529AAG[1]MANE SELECT
NP_000354.4:p.Lys178del
LRG_432t1:c.532_534del
LRG_432:g.8683AAG[1]
LRG_679:g.189AAG[1]
NC_000019.9:g.55665413_55665415del
NC_000019.9:g.55665413_55665415delCTT
NC_000019.9:g.55665414TTC[1]
NM_000363.4:c.532_534del
NM_000363.4:c.532_534delAAG
NM_000363.5:c.532_534delMANE SELECT
c.532_534delAAG

Protein change:

K178del

Links:

dbSNP: rs397516351

NCBI 1000 Genomes Browser:

rs397516351

Molecular consequence:

NM_000363.5:c.529AAG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002022365	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 2, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002501406	AiLife Diagnostics, AiLife Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 28, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12707239, 21533915, 27532257, 25741868
SCV002526371	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (May 4, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002022365

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 2, 2023)

germline

clinical testing

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

SCV002501406

AiLife Diagnostics, AiLife Diagnostics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 28, 2021)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002526371

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(May 4, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy.

Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, Benaiche A, Isnard R, Dubourg O, Burban M, Gueffet JP, Millaire A, Desnos M, Schwartz K, Hainque B, Komajda M; EUROGENE Heart Failure Project..

Circulation. 2003 May 6;107(17):2227-32. Epub 2003 Apr 21. Erratum in: Circulation. 2004 Jun 29;109(25):3258.

PubMed [citation]

PMID:: 12707239

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

See all PubMed Citations (4)

Details of each submission

From Revvity Omics, Revvity, SCV002022365.3

#	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

From AiLife Diagnostics, AiLife Diagnostics, SCV002501406.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

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

From GeneDx, SCV002526371.4

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

Description

In-frame deletion of one amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21533915, 27532257, 18402758, 35456187, 12707239, 18403758)

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

Last Updated: Mar 16, 2024

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