NM_000363.5(TNNI3):c.562G>A (p.Val188Met) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Dec 24, 2015)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000159240.2

Allele description [Variation Report for NM_000363.5(TNNI3):c.562G>A (p.Val188Met)]

NM_000363.5(TNNI3):c.562G>A (p.Val188Met)

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.562G>A (p.Val188Met)
Other names:
p.V188M:GTG>ATG
HGVS:
  • NC_000019.10:g.55151905C>T
  • NG_007866.2:g.10828G>A
  • NG_011829.2:g.2334G>A
  • NM_000363.5:c.562G>AMANE SELECT
  • NP_000354.4:p.Val188Met
  • LRG_432t1:c.562G>A
  • LRG_432:g.10828G>A
  • LRG_679:g.2334G>A
  • NC_000019.9:g.55663273C>T
  • NM_000363.4:c.562G>A
Protein change:
V188M
Links:
dbSNP: rs193922409
NCBI 1000 Genomes Browser:
rs193922409
Molecular consequence:
  • NM_000363.5:c.562G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000209186GeneDxcriteria provided, single submitter
Likely pathogenic
(Dec 24, 2015)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000209186.12

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The Val188Met variant in the TNNI3 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Val188Met results in a conservative amino acid substitution of one non-polar amino acid with another at a position that is conserved across species. In silico analysis predicts Val188Met is damaging to the protein structure/function. Mutations in nearby residues (Asn185Lys, Arg186Gln, Asp190Gly, Arg192Cys) have been reported in association with cardiomyopathy, further supporting the functional importance of this region of the protein. Furthermore, the Val188Met variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In summary, while Val188Met is a good candidate for a disease-causing mutation, with the clinical and molecular information available at this time we cannot unequivocally determine the clinical significance of this variant.The variant is found in HCM panel(s).

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

Last Updated: Jun 14, 2021

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