NM_001267550.2(TTN):c.102737G>A (p.Arg34246His) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Sep 12, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000040923.3

Allele description [Variation Report for NM_001267550.2(TTN):c.102737G>A (p.Arg34246His)]

NM_001267550.2(TTN):c.102737G>A (p.Arg34246His)

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.102737G>A (p.Arg34246His)
HGVS:
  • NC_000002.12:g.178533878C>T
  • NG_011618.3:g.301925G>A
  • NG_051363.1:g.16052C>T
  • NM_001256850.1:c.97814G>A
  • NM_001267550.2:c.102737G>AMANE SELECT
  • NM_003319.4:c.75542G>A
  • NM_133378.4:c.95033G>A
  • NM_133432.3:c.75917G>A
  • NM_133437.4:c.76118G>A
  • NP_001243779.1:p.Arg32605His
  • NP_001254479.2:p.Arg34246His
  • NP_003310.4:p.Arg25181His
  • NP_596869.4:p.Arg31678His
  • NP_597676.3:p.Arg25306His
  • NP_597681.4:p.Arg25373His
  • LRG_391:g.301925G>A
  • NC_000002.11:g.179398605C>T
  • c.95033G>A
Protein change:
R25181H
Links:
dbSNP: rs372716177
NCBI 1000 Genomes Browser:
rs372716177
Molecular consequence:
  • NM_001256850.1:c.97814G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.102737G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003319.4:c.75542G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.95033G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133432.3:c.75917G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133437.4:c.76118G>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
SCV000064614Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Apr 19, 2012)
germlineclinical testing

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

SCV000713901GeneDxcriteria provided, single submitter
Likely benign
(Sep 12, 2017)
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, SCV000064614.6

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

Description

The Arg31678His variant (TTN) has not been reported in the literature nor previo usly identified by our laboratory. Computational analyses (biochemical amino aci d properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide stron g support for or against an impact to the protein. This variant has been identif ied in 0.01% (1/6620) of European American chromosomes from a broad population b y the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP ) ; however, this frequency is too low to rule out a disease causing role. In summ ary, additional information is needed to fully assess the clinical significance of the Arg31678His variant.

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

From GeneDx, SCV000713901.1

#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 29, 2021

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