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NM_001267550.2(TTN):c.53260T>C (p.Phe17754Leu) AND not specified

Germline classification:
Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:
Sep 13, 2016
Review status:
criteria provided, conflicting classifications
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000040345.16

Allele description [Variation Report for NM_001267550.2(TTN):c.53260T>C (p.Phe17754Leu)]

NM_001267550.2(TTN):c.53260T>C (p.Phe17754Leu)

Genes:
LOC126806425:BRD4-independent group 4 enhancer GRCh37_chr2:179471933-179473132 [Gene]
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.53260T>C (p.Phe17754Leu)
Other names:
p.F16113L:TTT>CTT
HGVS:
  • NC_000002.12:g.178607428A>G
  • NG_011618.3:g.228375T>C
  • NG_051363.1:g.89602A>G
  • NM_001256850.1:c.48337T>C
  • NM_001267550.2:c.53260T>CMANE SELECT
  • NM_003319.4:c.26065T>C
  • NM_133378.4:c.45556T>C
  • NM_133432.3:c.26440T>C
  • NM_133437.4:c.26641T>C
  • NP_001243779.1:p.Phe16113Leu
  • NP_001254479.2:p.Phe17754Leu
  • NP_003310.4:p.Phe8689Leu
  • NP_596869.4:p.Phe15186Leu
  • NP_597676.3:p.Phe8814Leu
  • NP_597681.4:p.Phe8881Leu
  • LRG_391:g.228375T>C
  • NC_000002.11:g.179472155A>G
  • NM_003319.4:c.26065T>C
  • c.45556T>C
Protein change:
F15186L
Links:
dbSNP: rs397517612
NCBI 1000 Genomes Browser:
rs397517612
Molecular consequence:
  • NM_001256850.1:c.48337T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.53260T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003319.4:c.26065T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.45556T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133432.3:c.26440T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133437.4:c.26641T>C - 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
SCV000064036Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)
Uncertain significance
(Aug 11, 2013)
germlineclinical testing

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

SCV000345541Eurofins Ntd Llc (ga)
criteria provided, single submitter

(EGL Classification Definitions 2015)
Likely benign
(Sep 13, 2016)
germlineclinical testing

Citation Link,

SCV001920364Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided
Benigngermlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided22not providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown1not 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, Mass General Brigham Personalized Medicine, SCV000064036.6

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

Description

Variant classified as Uncertain Significance - Favor Benign. The Phe15186Leu var iant in TTN has now been identified by our laboratory in 1 Indian individual wit h HCM and in 1 Afghan individual with Barth syndrome, who carried likely pathoge nic variants in other genes. This variant has not been identified in large popul ation studies. Computational analyses (biochemical amino acid properties, conser vation, AlignGVGD, PolyPhen2, and SIFT) suggest that this variant may not impact the protein, though this information is not predictive enough to rule out patho genicity. Additional information is needed to fully assess the clinical signific ance of this variant.

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

From Eurofins Ntd Llc (ga), SCV000345541.4

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

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001920364.1

#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 24, 2024