NM_001267550.2(TTN):c.11311+1799G>C AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(2) (Last evaluated: Oct 16, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000041001.4

Allele description [Variation Report for NM_001267550.2(TTN):c.11311+1799G>C]

NM_001267550.2(TTN):c.11311+1799G>C

Gene:
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.11311+1799G>C
Other names:
p.S3692T:AGT>ACT
HGVS:
  • NC_000002.12:g.178751325C>G
  • NG_011618.3:g.84478G>C
  • NM_001256850.1:c.10360+1799G>C
  • NM_001267550.2:c.11311+1799G>CMANE SELECT
  • NM_003319.4:c.10222+1799G>C
  • NM_133378.4:c.10360+1799G>C
  • NM_133379.5:c.11075G>C
  • NM_133432.3:c.10597+1799G>C
  • NM_133437.4:c.10798+1799G>C
  • NP_596870.2:p.Ser3692Thr
  • LRG_391t2:c.11075G>C
  • LRG_391:g.84478G>C
  • NC_000002.11:g.179616052C>G
  • NM_133379.3:c.11075G>C
  • NM_133379.4:c.11075G>C
  • c.11075G>C
Protein change:
S3692T
Links:
dbSNP: rs147314430
NCBI 1000 Genomes Browser:
rs147314430
Molecular consequence:
  • NM_001256850.1:c.10360+1799G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001267550.2:c.11311+1799G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_003319.4:c.10222+1799G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133378.4:c.10360+1799G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133432.3:c.10597+1799G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133437.4:c.10798+1799G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133379.5:c.11075G>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
SCV000064692Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Oct 24, 2012)
germlineclinical testing

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

SCV000238090GeneDxcriteria provided, single submitter
Uncertain significance
(Jun 8, 2015)
germlineclinical testing

Citation Link,

SCV000702040EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Likely benign
(Oct 16, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown1not providednot providednot providednot providedclinical testing
not providedgermlinenot provided11not 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, SCV000064692.6

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

Description

Variant classified as Uncertain Significance - Favor Benign. The Ser3692Thr vari ant in TTN has not been reported in the literature nor previously identified by our laboratory. This variant has been identified in 0.1% (11/8598) of European A merican chromosomes from a broad population by the NHLBI Exome Sequencing Projec t (http://evs.gs.washington.edu/EVS; dbSNP rs147314430). Computational analyses are limited or unavailable for this variant. In summary, the low frequency of th is variant suggest that it is likely benign, though this is insufficient to esta blish this with certainty. Additional information is needed to fully assess the clinical significance of this variant.

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

From GeneDx, SCV000238090.7

#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 CARDIOMYOPATHY panel(s).

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

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000702040.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

Last Updated: Sep 6, 2021

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