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NM_001267550.2(TTN):c.107889del (p.Lys35963fs) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 25, 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:
RCV001216397.8

Allele description [Variation Report for NM_001267550.2(TTN):c.107889del (p.Lys35963fs)]

NM_001267550.2(TTN):c.107889del (p.Lys35963fs)

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.107889del (p.Lys35963fs)
HGVS:
  • NC_000002.12:g.178527101del
  • NG_011618.3:g.308704del
  • NG_051363.1:g.9275del
  • NM_001256850.1:c.102966del
  • NM_001267550.2:c.107889delMANE SELECT
  • NM_003319.4:c.80694del
  • NM_133378.4:c.100185del
  • NM_133432.3:c.81069del
  • NM_133437.4:c.81270del
  • NP_001243779.1:p.Lys34322fs
  • NP_001254479.2:p.Lys35963fs
  • NP_003310.4:p.Lys26898fs
  • NP_596869.4:p.Lys33395fs
  • NP_597676.3:p.Lys27023fs
  • NP_597681.4:p.Lys27090fs
  • LRG_391t1:c.107889del
  • LRG_391:g.308704del
  • NC_000002.11:g.179391826del
  • NC_000002.11:g.179391828del
  • NM_001256850.1:c.102966delA
  • NM_001267550.1:c.107889del
  • NM_001267550.2:c.107889delAMANE SELECT
  • NM_003319.4:c.80694delA
  • NM_133378.4:c.100185del
  • NM_133378.4:c.100185delA
  • p.K34322NfsX9
  • p.Lys35963AsnfsTer9
Nucleotide change:
AJ277892.2:g.293378delA
Protein change:
K26898fs
Links:
dbSNP: rs281864930
NCBI 1000 Genomes Browser:
rs281864930
Molecular consequence:
  • NM_001256850.1:c.102966del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001267550.2:c.107889del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_003319.4:c.80694del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_133378.4:c.100185del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_133432.3:c.81069del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_133437.4:c.81270del - 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
SCV001388193Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 25, 2023) 		germlineclinical testing

PubMed (10)
[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

Rare Titin (TTN) Variants in Diseases Associated with Sudden Cardiac Death.

Campuzano O, Sanchez-Molero O, Mademont-Soler I, Riuró H, Allegue C, Coll M, Pérez-Serra A, Mates J, Picó F, Iglesias A, Brugada R.

Int J Mol Sci. 2015 Oct 27;16(10):25773-87. doi: 10.3390/ijms161025773.

PubMed [citation]
PMID:
26516846
PMCID:
PMC4632826

Targeted next-generation sequencing assay for detection of mutations in primary myopathies.

Evilä A, Arumilli M, Udd B, Hackman P.

Neuromuscul Disord. 2016 Jan;26(1):7-15. doi: 10.1016/j.nmd.2015.10.003. Epub 2015 Nov 25.

PubMed [citation]
PMID:
26627873
See all PubMed Citations (10)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001388193.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (10)

Description

This sequence change creates a premature translational stop signal (p.Lys35963Asnfs*9) 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 present in population databases (rs281864930, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with autosomal recessive centronuclear myopathy, autosomal recessive tibial muscular dystrophy and/or dilated cardiomyopathy and atrial fibrillation (PMID: 23975875, 24395473, 26516846, 26627873, 34495297). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as p.K33395NfsX9. ClinVar contains an entry for this variant (Variation ID: 38439). 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). 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: Oct 20, 2024