NM_000363.5(TNNI3):c.526G>A (p.Val176Met) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 23, 2019
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:: RCV001036762.15

Allele description [Variation Report for NM_000363.5(TNNI3):c.526G>A (p.Val176Met)]

NM_000363.5(TNNI3):c.526G>A (p.Val176Met)

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.526G>A (p.Val176Met)

HGVS:

NC_000019.10:g.55154053C>T
NG_007866.2:g.8680G>A
NG_011829.2:g.186G>A
NM_000363.5:c.526G>AMANE SELECT
NP_000354.4:p.Val176Met
LRG_432t1:c.526G>A
LRG_432:g.8680G>A
LRG_679:g.186G>A
NC_000019.9:g.55665421C>T
NM_000363.4:c.526G>A

Protein change:

V176M

Links:

dbSNP: rs727503501

NCBI 1000 Genomes Browser:

rs727503501

Molecular consequence:

NM_000363.5:c.526G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypertrophic cardiomyopathy
Synonyms:: HYPERTROPHIC MYOCARDIOPATHY
Identifiers:: MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

Recent activity

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kunitz-type protease inhibitor 3 precursor [Homo sapiens]
kunitz-type protease inhibitor 3 precursor [Homo sapiens]
gi|189571689|ref|NP_006643.1|

Protein
JGI_XZT60653.rev NIH_XGC_tropTad5 Xenopus tropicalis cDNA clone IMAGE:7635190 3'...
JGI_XZT60653.rev NIH_XGC_tropTad5 Xenopus tropicalis cDNA clone IMAGE:7635190 3', mRNA sequence
gi|57075611|gnl|dbEST|26961003|gb|C 39.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001200142	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 23, 2019)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 25524337, 27532257, 30384889, 23396983, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001200142

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 23, 2019)

germline

clinical testing

PubMed (5)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical phenotype and outcome of hypertrophic cardiomyopathy associated with thin-filament gene mutations.

Coppini R, Ho CY, Ashley E, Day S, Ferrantini C, Girolami F, Tomberli B, Bardi S, Torricelli F, Cecchi F, Mugelli A, Poggesi C, Tardiff J, Olivotto I.

J Am Coll Cardiol. 2014 Dec 23;64(24):2589-2600. doi: 10.1016/j.jacc.2014.09.059.

PubMed [citation]

PMID:: 25524337
PMCID:: PMC4270453

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]

PMID:: 27532257
PMCID:: PMC5116235

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001200142.5

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 25524337, 27532257, 30384889, 23396983, Invitae). ClinVar contains an entry for this variant (Variation ID: 165513). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with methionine at codon 176 of the TNNI3 protein (p.Val176Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine.

#	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: Oct 13, 2024

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