NM_001267550.2(TTN):c.54874G>C (p.Gly18292Arg) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Dec 5, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000152304.2

Allele description [Variation Report for NM_001267550.2(TTN):c.54874G>C (p.Gly18292Arg)]

NM_001267550.2(TTN):c.54874G>C (p.Gly18292Arg)

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.54874G>C (p.Gly18292Arg)
HGVS:
  • NC_000002.12:g.178602528C>G
  • NG_011618.3:g.233275G>C
  • NG_051363.1:g.84702C>G
  • NM_001256850.1:c.49951G>C
  • NM_001267550.2:c.54874G>CMANE SELECT
  • NM_003319.4:c.27679G>C
  • NM_133378.4:c.47170G>C
  • NM_133432.3:c.28054G>C
  • NM_133437.4:c.28255G>C
  • NP_001243779.1:p.Gly16651Arg
  • NP_001254479.2:p.Gly18292Arg
  • NP_003310.4:p.Gly9227Arg
  • NP_596869.4:p.Gly15724Arg
  • NP_597676.3:p.Gly9352Arg
  • NP_597681.4:p.Gly9419Arg
  • LRG_391:g.233275G>C
  • NC_000002.11:g.179467255C>G
Protein change:
G15724R
Links:
dbSNP: rs377512675
NCBI 1000 Genomes Browser:
rs377512675
Molecular consequence:
  • NM_001256850.1:c.49951G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.54874G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003319.4:c.27679G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.47170G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133432.3:c.28054G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133437.4:c.28255G>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
SCV000201173Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Sep 19, 2013)
germlineclinical testing

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

SCV000725620GeneDxcriteria provided, single submitter
Likely benign
(Dec 5, 2017)
germlineclinical testing

Citation Link

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 Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000201173.5

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

Description

Variant classified as Uncertain Significance - Favor Benign. The Gly15724Arg var iant in TTN has not been reported in individuals with cardiomyopathy but has bee n identified in 1/8178 European American chromosomes by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS/; dbSNP rs377512675). Glycine (Gly) at position 15724 is not conserved across mammals and suggests that a change at this position may be tolerated despite high adjacent conservation. Additionally , computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen 2, and SIFT) do not provide strong support for or against an impact to the norma l function of the protein. In summary, additional information is needed to fully assess the clinical significance of the Gly15724Arg variant.

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

From GeneDx, SCV000725620.1

#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: Jul 7, 2021

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