NM_001267550.2(TTN):c.93166C>T (p.Arg31056Ter) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Aug 4, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000705561.4

Allele description [Variation Report for NM_001267550.2(TTN):c.93166C>T (p.Arg31056Ter)]

NM_001267550.2(TTN):c.93166C>T (p.Arg31056Ter)

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.93166C>T (p.Arg31056Ter)
HGVS:
  • NC_000002.12:g.178548460G>A
  • NG_011618.3:g.287343C>T
  • NG_051363.1:g.30634G>A
  • NM_001256850.1:c.88243C>T
  • NM_001267550.2:c.93166C>TMANE SELECT
  • NM_003319.4:c.65971C>T
  • NM_133378.4:c.85462C>T
  • NM_133432.3:c.66346C>T
  • NM_133437.4:c.66547C>T
  • NP_001243779.1:p.Arg29415Ter
  • NP_001254479.2:p.Arg31056Ter
  • NP_003310.4:p.Arg21991Ter
  • NP_596869.4:p.Arg28488Ter
  • NP_597676.3:p.Arg22116Ter
  • NP_597681.4:p.Arg22183Ter
  • LRG_391t1:c.93166C>T
  • LRG_391:g.287343C>T
  • NC_000002.11:g.179413187G>A
Protein change:
R21991*
Links:
dbSNP: rs72648250
NCBI 1000 Genomes Browser:
rs72648250
Molecular consequence:
  • NM_001256850.1:c.88243C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001267550.2:c.93166C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_003319.4:c.65971C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133378.4:c.85462C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133432.3:c.66346C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133437.4:c.66547C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Dilated cardiomyopathy 1G (CMD1G)
Identifiers:
MONDO: MONDO:0011400; MedGen: C1858763; Orphanet: 154; OMIM: 604145
Name:
Limb-girdle muscular dystrophy, type 2J (LGMDR10)
Synonyms:
MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 10
Identifiers:
MONDO: MONDO:0012127; MedGen: C1837342; Orphanet: 140922; OMIM: 608807

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000834562Invitaecriteria provided, single submitter
Pathogenic
(Aug 4, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Truncations of titin causing dilated cardiomyopathy.

Herman DS, Lam L, Taylor MR, Wang L, Teekakirikul P, Christodoulou D, Conner L, DePalma SR, McDonough B, Sparks E, Teodorescu DL, Cirino AL, Banner NR, Pennell DJ, Graw S, Merlo M, Di Lenarda A, Sinagra G, Bos JM, Ackerman MJ, Mitchell RN, Murry CE, et al.

N Engl J Med. 2012 Feb 16;366(7):619-28. doi: 10.1056/NEJMoa1110186.

PubMed [citation]
PMID:
22335739
PMCID:
PMC3660031

Titin Truncating Variants in Dilated Cardiomyopathy - Prevalence and Genotype-Phenotype Correlations.

Franaszczyk M, Chmielewski P, Truszkowska G, Stawinski P, Michalak E, Rydzanicz M, Sobieszczanska-Malek M, Pollak A, Szczygieł J, Kosinska J, Parulski A, Stoklosa T, Tarnowska A, Machnicki MM, Foss-Nieradko B, Szperl M, Sioma A, Kusmierczyk M, Grzybowski J, Zielinski T, Ploski R, Bilinska ZT.

PLoS One. 2017;12(1):e0169007. doi: 10.1371/journal.pone.0169007.

PubMed [citation]
PMID:
28045975
PMCID:
PMC5207678
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000834562.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change results in a premature translational stop signal in the TTN gene (p.Arg31056*). While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with dilated cardiomyopathy in a family (PMID: 22335739) and has been observed in several individuals with dilated cardiomyopathy (PMID: 22335739, 28045975). This variant is also known as p.R29415* in the literature. ClinVar contains an entry for this variant (Variation ID: 223326). This variant is located in the A band of TTN (PMID: 25589632). Truncating variants in this region are significantly overrepresented in patients affected with dilated cardiomyopathy (PMID: 25589632). Truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 20, 2021

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