NM_001267550.2(TTN):c.21332T>C (p.Met7111Thr) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Nov 12, 2015)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000220902.2

Allele description [Variation Report for NM_001267550.2(TTN):c.21332T>C (p.Met7111Thr)]

NM_001267550.2(TTN):c.21332T>C (p.Met7111Thr)

Gene:
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.21332T>C (p.Met7111Thr)
Other names:
p.M6794T:ATG>ACG
HGVS:
  • NC_000002.12:g.178723927A>G
  • NG_011618.3:g.111876T>C
  • NM_001256850.1:c.20381T>C
  • NM_001267550.2:c.21332T>CMANE SELECT
  • NM_003319.4:c.13282+14155T>C
  • NM_133378.4:c.17600T>C
  • NM_133432.3:c.13657+14155T>C
  • NM_133437.4:c.13858+14155T>C
  • NP_001243779.1:p.Met6794Thr
  • NP_001254479.2:p.Met7111Thr
  • NP_596869.4:p.Met5867Thr
  • LRG_391:g.111876T>C
  • NC_000002.11:g.179588654A>G
Protein change:
M5867T
Links:
dbSNP: rs374408615
NCBI 1000 Genomes Browser:
rs374408615
Molecular consequence:
  • NM_003319.4:c.13282+14155T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133432.3:c.13657+14155T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133437.4:c.13858+14155T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001256850.1:c.20381T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.21332T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.17600T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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
SCV000238293GeneDxcriteria provided, single submitter
Uncertain significance
(Apr 9, 2013)
germlineclinical testing

Citation Link,

SCV000270986Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely benign
(Nov 12, 2015)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not 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 GeneDx, SCV000238293.6

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

Description

Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in DCM panel(s).

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

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000270986.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

p.Met5867Thr in exon 70 of TTN: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including mammals. Of n ote, nine mammals have a Threonine (Thr) at this position. It has also been iden tified in 2/66616 European chromosomes by the Exome Aggregation Consortium (ExAC , http://exac.broadinstitute.org/; dbSNP rs374408615).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Jul 7, 2021

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