NM_001267550.2(TTN):c.14302G>A (p.Gly4768Ser) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Feb 12, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000152410.6

Allele description [Variation Report for NM_001267550.2(TTN):c.14302G>A (p.Gly4768Ser)]

NM_001267550.2(TTN):c.14302G>A (p.Gly4768Ser)

Gene:
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.14302G>A (p.Gly4768Ser)
Other names:
p.G4451S:GGC>AGC
HGVS:
  • NC_000002.12:g.178738151C>T
  • NG_011618.3:g.97652G>A
  • NM_001256850.1:c.13351G>A
  • NM_001267550.2:c.14302G>AMANE SELECT
  • NM_003319.4:c.13213G>A
  • NM_133378.4:c.10570G>A
  • NM_133432.3:c.13588G>A
  • NM_133437.4:c.13789G>A
  • NP_001243779.1:p.Gly4451Ser
  • NP_001254479.2:p.Gly4768Ser
  • NP_003310.4:p.Gly4405Ser
  • NP_596869.4:p.Gly3524Ser
  • NP_597676.3:p.Gly4530Ser
  • NP_597681.4:p.Gly4597Ser
  • LRG_391:g.97652G>A
  • NC_000002.11:g.179602878C>T
Protein change:
G3524S
Links:
dbSNP: rs727503652
NCBI 1000 Genomes Browser:
rs727503652
Molecular consequence:
  • NM_001256850.1:c.13351G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.14302G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003319.4:c.13213G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.10570G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133432.3:c.13588G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133437.4:c.13789G>A - 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
SCV000201435Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Oct 15, 2013)
germlineclinical testing

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

SCV000238195GeneDxcriteria provided, single submitter
Likely benign
(Feb 12, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot 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, SCV000201435.5

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

Description

The Gly3524Ser variant in TTN has not been previously reported in individuals wi th cardiomyopathy or in large population studies. Computational analyses (bioche mical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do no t provide strong support for or against an impact to the protein. Additional inf ormation is needed to fully assess the clinical significance of the Gly3524Ser v ariant.

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

From GeneDx, SCV000238195.7

#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

Last Updated: Nov 27, 2021

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