NM_001267550.2(TTN):c.81037C>T (p.Arg27013Ter) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Mar 2, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000256162.3

Allele description [Variation Report for NM_001267550.2(TTN):c.81037C>T (p.Arg27013Ter)]

NM_001267550.2(TTN):c.81037C>T (p.Arg27013Ter)

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.81037C>T (p.Arg27013Ter)
HGVS:
  • NC_000002.12:g.178565095G>A
  • NG_011618.3:g.270708C>T
  • NG_051363.1:g.47269G>A
  • NM_001256850.1:c.76114C>T
  • NM_001267550.2:c.81037C>TMANE SELECT
  • NM_003319.4:c.53842C>T
  • NM_133378.4:c.73333C>T
  • NM_133432.3:c.54217C>T
  • NM_133437.4:c.54418C>T
  • NP_001243779.1:p.Arg25372Ter
  • NP_001254479.2:p.Arg27013Ter
  • NP_003310.4:p.Arg17948Ter
  • NP_596869.4:p.Arg24445Ter
  • NP_597676.3:p.Arg18073Ter
  • NP_597681.4:p.Arg18140Ter
  • LRG_391:g.270708C>T
  • NC_000002.11:g.179429822G>A
Protein change:
R17948*
Links:
dbSNP: rs869038795
NCBI 1000 Genomes Browser:
rs869038795
Molecular consequence:
  • NM_001256850.1:c.76114C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001267550.2:c.81037C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_003319.4:c.53842C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133378.4:c.73333C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133432.3:c.54217C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133437.4:c.54418C>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000322337GeneDxcriteria provided, single submitter
Pathogenic
(Mar 2, 2018)
germlineclinical testing

Citation Link,

SCV000335307EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Likely pathogenic
(Sep 11, 2015)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown1not providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000322337.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The R25372X pathogenic variant in the TTN gene has been reported previously in association with DCM in two individuals from a French Canadian family (Chami et al., 2014). This variant has also been identified independently and/or in conjunction with additional cardiogenetic variants in individuals referred for cardiomyopathy genetic testing at GeneDx. So far, segregation data is limited or absent for this individual due to the lack of clinical information provided and/or insufficient participation by informative family members. The R25372X variant is predicted to cause loss of normal protein function either due to production of an abnormal, prematurely truncated protein, or by absence of protein product due to nonsense mediated mRNA decay. Other truncating TTN variants have been reported in approximately 3% of control alleles (Herman et al., 2012). However, R25372X is located in the A-band region of titin, where the majority of truncating pathogenic variants associated with DCM have been reported (Herman et al., 2012). Furthermore, the R25372X variant is not observed in large population cohorts (Lek et al., 2016).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000335307.4

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

Last Updated: Oct 8, 2021

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