NM_001267550.2(TTN):c.92780T>A (p.Ile30927Lys) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Nov 16, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
5 submissions [Details]
Record status:
current
Accession:
RCV000156609.7

Allele description [Variation Report for NM_001267550.2(TTN):c.92780T>A (p.Ile30927Lys)]

NM_001267550.2(TTN):c.92780T>A (p.Ile30927Lys)

Genes:
TTN-AS1:TTN antisense RNA 1 [Gene - HGNC]
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.92780T>A (p.Ile30927Lys)
Other names:
p.I29286K:ATA>AAA
HGVS:
  • NC_000002.12:g.178548846A>T
  • NG_011618.3:g.286957T>A
  • NG_051363.1:g.31020A>T
  • NM_001256850.1:c.87857T>A
  • NM_001267550.2:c.92780T>AMANE SELECT
  • NM_003319.4:c.65585T>A
  • NM_133378.4:c.85076T>A
  • NM_133432.3:c.65960T>A
  • NM_133437.4:c.66161T>A
  • NP_001243779.1:p.Ile29286Lys
  • NP_001254479.2:p.Ile30927Lys
  • NP_003310.4:p.Ile21862Lys
  • NP_596869.4:p.Ile28359Lys
  • NP_597676.3:p.Ile21987Lys
  • NP_597681.4:p.Ile22054Lys
  • LRG_391:g.286957T>A
  • NC_000002.11:g.179413573A>T
Protein change:
I21862K
Links:
dbSNP: rs531432790
NCBI 1000 Genomes Browser:
rs531432790
Molecular consequence:
  • NM_001256850.1:c.87857T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.92780T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003319.4:c.65585T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.85076T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133432.3:c.65960T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133437.4:c.66161T>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

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
SCV000206329Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Jun 27, 2014)
germlineclinical testing

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

SCV000237770GeneDxcriteria provided, single submitter
Likely benign
(Nov 16, 2017)
germlineclinical testing

Citation Link,

SCV001922264Clinical Genetics,Academic Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria providedBenigngermlineclinical testing

SCV001928362Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus

See additional submitters

no assertion criteria providedBenigngermlineclinical testing

SCV001971771Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria providedBenigngermlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided22not providednot providednot providedclinical testing
not providedgermlineyesnot providednot 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

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000206329.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (1)

Description

The Ile28359Lys variant in TTN has not been previously reported in individuals w ith cardiomyopathy or in large population studies. Computational prediction too ls and conservation analysis do not provide strong support for or against an imp act to the protein. In summary, the clinical significance of the Ile28359Lys var iant is uncertain.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided2not provided2not provided

From GeneDx, SCV000237770.7

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

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Clinical Genetics,Academic Medical Center - VKGL Data-share Consensus, SCV001922264.1

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

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001928362.1

#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, SCV001971771.1

#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: Nov 27, 2021

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