NM_000363.5(TNNI3):c.5C>T (p.Ala2Val) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 28, 2021
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:: RCV001753445.3

Allele description [Variation Report for NM_000363.5(TNNI3):c.5C>T (p.Ala2Val)]

NM_000363.5(TNNI3):c.5C>T (p.Ala2Val)

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.5C>T (p.Ala2Val)

HGVS:

NC_000019.10:g.55157585G>A
NG_007866.2:g.5148C>T
NG_032759.1:g.14138C>T
NM_000363.5:c.5C>TMANE SELECT
NP_000354.4:p.Ala2Val
LRG_432t1:c.5C>T
LRG_432:g.5148C>T
NC_000019.9:g.55668953G>A
NM_000363.4:c.5C>T
P19429:p.Ala2Val
c.5C>T

Protein change:

A2V

Links:

LOVD 3: TNNI3_000039; UniProtKB: P19429#VAR_043989; OMIM: 191044.0009; dbSNP: rs397516359

NCBI 1000 Genomes Browser:

rs397516359

Molecular consequence:

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

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
SCV001985384	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Nov 19, 2019)	germline	clinical testing	Citation Link,
SCV002501800	AiLife Diagnostics, AiLife Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 28, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15070570, 22940544, 31534214, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001985384

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Nov 19, 2019)

germline

clinical testing

Citation Link,

SCV002501800

AiLife Diagnostics, AiLife Diagnostics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 28, 2021)

germline

clinical testing

PubMed (4)
[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	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel mutation in cardiac troponin I in recessive idiopathic dilated cardiomyopathy.

Murphy RT, Mogensen J, Shaw A, Kubo T, Hughes S, McKenna WJ.

Lancet. 2004 Jan 31;363(9406):371-2.

PubMed [citation]

PMID:: 15070570

New insights into the functional significance of the acidic region of the unique N-terminal extension of cardiac troponin I.

Henze M, Patrick SE, Hinken A, Scruggs SB, Goldspink P, de Tombe PP, Kobayashi M, Ping P, Kobayashi T, Solaro RJ.

Biochim Biophys Acta. 2013 Apr;1833(4):823-32. doi: 10.1016/j.bbamcr.2012.08.012. Epub 2012 Aug 25.

PubMed [citation]

PMID:: 22940544
PMCID:: PMC3548050

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV001985384.2

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

Description

Reported as a homozygous variant in two siblings with DCM; both heterozygous parents and one heterozygous sibling were reported to have a normal cardiac work-up (Murphy et al., 2004); Functional studies have demonstrated conflicting results regarding the impact on ATPase regulation and troponin function (Murphy et al., 2004; Carballo et al., 2009; Henze et al., 2013); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 43397; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 19590045, 31568572, 22940544, 15070570, 31534214, 32870709)

#	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

From AiLife Diagnostics, AiLife Diagnostics, SCV002501800.1

#	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

Last Updated: May 1, 2024

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