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NM_000363.5(TNNI3):c.12-7del AND not specified

Germline classification:
Benign/Likely benign (5 submissions)
Last evaluated:
Sep 5, 2017
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:
RCV000036269.16

Allele description [Variation Report for NM_000363.5(TNNI3):c.12-7del]

NM_000363.5(TNNI3):c.12-7del

Gene:
TNNI3:troponin I3, cardiac type [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
19q13.42
Genomic location:
Preferred name:
NM_000363.5(TNNI3):c.12-7del
HGVS:
  • NC_000019.10:g.55157316del
  • NC_000019.9:g.55668683del
  • NG_007866.2:g.5418del
  • NG_032759.1:g.14408del
  • NM_000363.5:c.12-7delMANE SELECT
  • LRG_432t1:c.12-7del
  • LRG_432:g.5418del
  • NC_000019.9:g.55668683del
  • NC_000019.9:g.55668683delG
  • NC_000019.9:g.55668684del
  • NM_000363.4:c.12-7del
  • NM_000363.4:c.12-7delC
  • c.12-7delC
Links:
dbSNP: rs370714315
NCBI 1000 Genomes Browser:
rs370714315
Molecular consequence:
  • NM_000363.5:c.12-7del - intron variant - [Sequence Ontology: SO:0001627]
Observations:
7

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000059921Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)
Likely benign
(Aug 1, 2012)
germlineclinical testing

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

SCV000227105Eurofins Ntd Llc (ga)
criteria provided, single submitter

(EGL Classification Definitions 2015)
Benign
(Apr 10, 2015)
germlineclinical testing

Citation Link,

SCV000920308Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Benign
(Sep 5, 2017)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV001924816Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided
Benigngermlineclinical testing

SCV001972526Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided
Benigngermlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided77not providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown1not providednot providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Sarcomere protein gene mutations in patients with apical hypertrophic cardiomyopathy.

Gruner C, Care M, Siminovitch K, Moravsky G, Wigle ED, Woo A, Rakowski H.

Circ Cardiovasc Genet. 2011 Jun;4(3):288-95. doi: 10.1161/CIRCGENETICS.110.958835. Epub 2011 Apr 21.

PubMed [citation]
PMID:
21511876
See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000059921.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided7not providednot providedclinical testing PubMed (1)

Description

12-7delC in intron 1 of TNNI3: This variant is unlikely to have clinical signifi cance because it is not located within the conserved splice consensus sequence. In addition, there are no reports of disease-causing splicing variants in the TN NI3 gene. Of note, the variant has been detected by our laboratory in 5 individu als with various cardiomyopathies (HCM or LVNC), 4 of whom were of confirmed Bla ck ancestry. This raises the possibility that this variant is common in the Bla ck population. A modifying effect cannot be excluded.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided7not provided7not provided

From Eurofins Ntd Llc (ga), SCV000227105.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000920308.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: The TNNI3 c.12-7delC variant involves the alteration of a non-conserved intronic nucleotide. MutationTaster predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 52/108562 control chromosomes from all ethnicities, but was predominantly observed in the African subpopulation at a frequency of 0.005965 (50/8382). This frequency is about 48 times the estimated maximal expected allele frequency of a pathogenic TNNI3 variant (0.000125), strongly suggesting this is likely a benign polymorphism found primarily in populations of African origin. In addition, nn an internal LCA sample, the variant was found to co-occur with a pathogenic DSP mutation (c.1dupA), suggesting the variant is not responsible for disease in this individual. Multiple clinical diagnostic laboratories/reputable databases have classified this variant with differing interpretations, including uncertain significance, likely benign, and benign, with a classification of benign being the most recent. Taken together, this variant is classified as benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001924816.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001972526.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 5, 2024