NM_000363.5(TNNI3):c.509G>A (p.Arg170Gln) AND not provided

Clinical significance:Pathogenic (Last evaluated: Apr 21, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000159232.4

Allele description [Variation Report for NM_000363.5(TNNI3):c.509G>A (p.Arg170Gln)]

NM_000363.5(TNNI3):c.509G>A (p.Arg170Gln)

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.509G>A (p.Arg170Gln)
Other names:
p.R170Q:CGG>CAG
HGVS:
  • NC_000019.10:g.55154070C>T
  • NG_007866.2:g.8663G>A
  • NG_011829.2:g.169G>A
  • NM_000363.5:c.509G>AMANE SELECT
  • NP_000354.4:p.Arg170Gln
  • LRG_432t1:c.509G>A
  • LRG_432:g.8663G>A
  • LRG_679:g.169G>A
  • NC_000019.9:g.55665438C>T
  • NM_000363.4:c.509G>A
Protein change:
R170Q
Links:
dbSNP: rs727503503
NCBI 1000 Genomes Browser:
rs727503503
Molecular consequence:
  • NM_000363.5:c.509G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
8

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000209178GeneDxcriteria provided, single submitter
Pathogenic
(Apr 21, 2017)
germlineclinical testing

Citation Link,

SCV000280510Stanford Center for Inherited Cardiovascular Disease, Stanford Universityno assertion criteria providedLikely pathogenic
(Oct 16, 2013)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot provided8not providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000209178.13

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

Description

The Arg170Gln mutation in the TNNI3 gene has been published previously in one individual with HCM (Kaski J et al., 2009). This study reported that Arg170Gln, which is located within the actin-binding domain of the troponin I protein, is predicted to increase the inhibitory effect of troponin I. Mutations affecting neighboring codons (Lys164Thr, Ser166Phe, Lys167Pro, Ala171Thr, Lys178Glu) have been reported in association with HCM and restrictive cardiomyopathy, further supporting the functional importance of this region of the protein. Furthermore, the NHLBI ESP Exome Variant Server reports Arg170Gln was not observed in approximately 6000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. The Arg170Gln mutation has been observed in multiple other unrelated individual tested for HCM at GeneDx.Therefore, Arg170Gln in the TNNI3 gene is interpreted as a disease-causing mutation.The variant is found in HCM panel(s).

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

From Stanford Center for Inherited Cardiovascular Disease, Stanford University, SCV000280510.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided8not providednot providedclinical testingnot provided

Description

Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Arg170Gln (c.509 G>A) in the TNNI3 gene We have seen this variant in a patient diagnosed at age 3 with RCM, s/p heart transplant. p.Arg170Gln has been reported in 1 pediatric HCM proband (Kaski 2009) and at the testing lab has been seen it in 7 individuals with early-onset RCM (including our patient). Two were de novo. TNNI3 is a gene strongly associated with RCM (Kubo 2007). This variant was not identified in large population studies, also supporting pathogenicity.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided8not providednot providednot provided

Last Updated: Jul 7, 2021

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