NM_000363.5(TNNI3):c.592C>G (p.Leu198Val) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Dec 20, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000518842.2

Allele description [Variation Report for NM_000363.5(TNNI3):c.592C>G (p.Leu198Val)]

NM_000363.5(TNNI3):c.592C>G (p.Leu198Val)

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.592C>G (p.Leu198Val)
Other names:
p.L198V:CTG>GTG
HGVS:
  • NC_000019.10:g.55151875G>C
  • NG_007866.2:g.10858C>G
  • NG_011829.2:g.2364C>G
  • NM_000363.5:c.592C>GMANE SELECT
  • NP_000354.4:p.Leu198Val
  • LRG_432t1:c.592C>G
  • LRG_432:g.10858C>G
  • LRG_679:g.2364C>G
  • NC_000019.9:g.55663243G>C
  • NM_000363.4:c.592C>G
Protein change:
L198V
Links:
dbSNP: rs727504285
NCBI 1000 Genomes Browser:
rs727504285
Molecular consequence:
  • NM_000363.5:c.592C>G - 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
SCV000209193GeneDxcriteria provided, single submitter
Likely pathogenic
(Dec 20, 2018)
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, SCV000209193.8

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

Description

The L198V likely pathogenic variant in the TNNI3 gene has been identified in multiple unrelated individuals with HCM referred for genetic testing at GeneDx and reported in published literature (Maron et al., 2012; Otsuka et al., 2012; Ng et al., 2013; Arad et al., 2014; Coppini et al., 2014; Lopes et al., 2015; Walsh et al., 2017). Moreover, this variant has segregated with disease in affected relatives from several families referred for testing at GeneDx and in the published literature (Otsuka et al., 2012). The L198V variant is not observed in large population cohorts (Lek et al., 2016). Furthermore, missense variants in nearby residues (N194K, D196N, S199N) are independently classified as pathogenic or likely pathogenic by GeneDx. Nonetheless, the L198V variant is a conservative amino acid substitution which is not likely to impact secondary protein structure as these residues share similar properties and in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. In summary, L198V in the TNNI3 gene is interpreted as a likely pathogenic variant.

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

Last Updated: Sep 29, 2021

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