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NM_001267550.2(TTN):c.104421_104425del (p.Arg34807fs) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 6, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002035637.6

Allele description [Variation Report for NM_001267550.2(TTN):c.104421_104425del (p.Arg34807fs)]

NM_001267550.2(TTN):c.104421_104425del (p.Arg34807fs)

Genes:
TTN-AS1:TTN antisense RNA 1 [Gene - HGNC]
TTN:titin [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.104421_104425del (p.Arg34807fs)
HGVS:
  • NC_000002.12:g.178532193_178532197del
  • NG_011618.3:g.303609_303613del
  • NG_051363.1:g.14367_14371del
  • NM_001256850.1:c.99498_99502del
  • NM_001267550.2:c.104421_104425delMANE SELECT
  • NM_003319.4:c.77226_77230del
  • NM_133378.4:c.96717_96721del
  • NM_133432.3:c.77601_77605del
  • NM_133437.4:c.77802_77806del
  • NP_001243779.1:p.Arg33166fs
  • NP_001254479.2:p.Arg34807fs
  • NP_003310.4:p.Arg25742fs
  • NP_596869.4:p.Arg32239fs
  • NP_597676.3:p.Arg25867fs
  • NP_597681.4:p.Arg25934fs
  • LRG_391:g.303609_303613del
  • NC_000002.11:g.179396917_179396921del
  • NC_000002.11:g.179396920_179396924del
Protein change:
R25742fs
Links:
dbSNP: rs1689427568
NCBI 1000 Genomes Browser:
rs1689427568
Molecular consequence:
  • NM_001256850.1:c.99498_99502del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001267550.2:c.104421_104425del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_003319.4:c.77226_77230del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_133378.4:c.96717_96721del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_133432.3:c.77601_77605del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_133437.4:c.77802_77806del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Dilated cardiomyopathy 1G (CMD1G)
Identifiers:
MONDO: MONDO:0011400; MedGen: C1858763; Orphanet: 154; OMIM: 604145
Name:
Autosomal recessive limb-girdle muscular dystrophy type 2J (LGMDR10)
Synonyms:
Limb-girdle muscular dystrophy, type 2J; 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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002278250Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Dec 6, 2023) 		germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Genetics, Clinical Features, and Long-Term Outcome of Noncompaction Cardiomyopathy.

van Waning JI, Caliskan K, Hoedemaekers YM, van Spaendonck-Zwarts KY, Baas AF, Boekholdt SM, van Melle JP, Teske AJ, Asselbergs FW, Backx APCM, du Marchie Sarvaas GJ, Dalinghaus M, Breur JMPJ, Linschoten MPM, Verlooij LA, Kardys I, Dooijes D, Lekanne Deprez RH, IJpma AS, van den Berg MP, Hofstra RMW, van Slegtenhorst MA, et al.

J Am Coll Cardiol. 2018 Feb 20;71(7):711-722. doi: 10.1016/j.jacc.2017.12.019.

PubMed [citation]
PMID:
29447731

Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease.

Roberts AM, Ware JS, Herman DS, Schafer S, Baksi J, Bick AG, Buchan RJ, Walsh R, John S, Wilkinson S, Mazzarotto F, Felkin LE, Gong S, MacArthur JA, Cunningham F, Flannick J, Gabriel SB, Altshuler DM, Macdonald PS, Heinig M, Keogh AM, Hayward CS, et al.

Sci Transl Med. 2015 Jan 14;7(270):270ra6. doi: 10.1126/scitranslmed.3010134.

PubMed [citation]
PMID:
25589632
PMCID:
PMC4560092
See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002278250.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This sequence change creates a premature translational stop signal (p.Arg34807Serfs*8) in the TTN gene. 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 (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with dilated cardiomyopathy (PMID: 29447731). ClinVar contains an entry for this variant (Variation ID: 1498821). This variant is located in the M band of TTN (PMID: 25589632). Truncating variants in this region have been previously reported in individuals affected with autosomal recessive myopathy and muscular dystrophy (PMID: 18948003, 23975875, 24395473). Truncating variants in this region have also been identified in individuals affected with autosomal dominant dilated cardiomyopathy and/or cardio-related conditions (PMID: 27869827, 32964742). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Sep 29, 2024