NM_001267550.2(TTN):c.58072C>T (p.Arg19358Cys) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(2);Uncertain significance(1) (Last evaluated: Oct 10, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000194123.3

Allele description [Variation Report for NM_001267550.2(TTN):c.58072C>T (p.Arg19358Cys)]

NM_001267550.2(TTN):c.58072C>T (p.Arg19358Cys)

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.58072C>T (p.Arg19358Cys)
HGVS:
  • NC_000002.12:g.178594422G>A
  • NG_011618.3:g.241381C>T
  • NG_051363.1:g.76596G>A
  • NM_001256850.1:c.53149C>T
  • NM_001267550.2:c.58072C>TMANE SELECT
  • NM_003319.4:c.30877C>T
  • NM_133378.4:c.50368C>T
  • NM_133432.3:c.31252C>T
  • NM_133437.4:c.31453C>T
  • NP_001243779.1:p.Arg17717Cys
  • NP_001254479.2:p.Arg19358Cys
  • NP_003310.4:p.Arg10293Cys
  • NP_596869.4:p.Arg16790Cys
  • NP_597676.3:p.Arg10418Cys
  • NP_597681.4:p.Arg10485Cys
  • LRG_391:g.241381C>T
  • NC_000002.11:g.179459149G>A
  • p.Arg16790Cys
Protein change:
R10293C
Links:
dbSNP: rs371973579
NCBI 1000 Genomes Browser:
rs371973579
Molecular consequence:
  • NM_001256850.1:c.53149C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.58072C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003319.4:c.30877C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.50368C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133432.3:c.31252C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133437.4:c.31453C>T - 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
SCV000249270Genetic Services Laboratory, University of Chicagocriteria provided, single submitter
Uncertain significance
(Apr 29, 2014)
germlineclinical testing

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

SCV000729583GeneDxcriteria provided, single submitter
Likely benign
(Sep 13, 2017)
germlineclinical testing

Citation Link,

SCV000967323Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely benign
(Oct 10, 2018)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007.

Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE; Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee..

Genet Med. 2008 Apr;10(4):294-300. doi: 10.1097/GIM.0b013e31816b5cae.

PubMed [citation]
PMID:
18414213

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 Genetic Services Laboratory, University of Chicago, SCV000249270.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From GeneDx, SCV000729583.1

#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

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000967323.1

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

Description

The p.Arg16790Cys variant in TTN is classified as likely benign because it has b een identified in 0.08% (15/18656) of East Asian chromosomes and 0.07% (16/23994 ) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BS1, PP3.

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

Last Updated: Jul 7, 2021

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