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NM_001267550.2(TTN):c.107889del (p.Lys35963fs) AND Autosomal recessive titinopathy

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 26, 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:
RCV003234933.3

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:
Autosomal recessive titinopathy
Identifiers:
MONDO: MONDO:0100493; MedGen: CN315649

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003934122Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(May 26, 2023) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Early-Onset Atrial Fibrillation and the Prevalence of Rare Variants in Cardiomyopathy and Arrhythmia Genes.

Yoneda ZT, Anderson KC, Quintana JA, O'Neill MJ, Sims RA, Glazer AM, Shaffer CM, Crawford DM, Stricker T, Ye F, Wells Q, Stevenson LW, Michaud GF, Darbar D, Lubitz SA, Ellinor PT, Roden DM, Shoemaker MB.

JAMA Cardiol. 2021 Dec 1;6(12):1371-1379. doi: 10.1001/jamacardio.2021.3370.

PubMed [citation]
PMID:
34495297
PMCID:
PMC8427496

Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain.

Gonzalez-Quereda L, Rodriguez MJ, Diaz-Manera J, Alonso-Perez J, Gallardo E, Nascimento A, Ortez C, Natera-de Benito D, Olive M, Gonzalez-Mera L, Munain AL, Zulaica M, Poza JJ, Jerico I, Torne L, Riera P, Milisenda J, Sanchez A, Garrabou G, Llano I, Madruga-Garrido M, Gallano P.

Genes (Basel). 2020 May 11;11(5). doi:pii: E539. 10.3390/genes11050539.

PubMed [citation]
PMID:
32403337
PMCID:
PMC7288461
See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003934122.1

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

Description

Variant summary: TTN c.100185delA (p.Lys33395AsnfsX9) results in a premature termination codon within the last exon (M-band region, PSI 100%), predicted to cause a truncation of the encoded protein. The variant allele was found at a frequency of 4e-06 in 249174 control chromosomes (gnomAD). c.100185delA has been reported in the literature in multiple individuals affected with Autosomal Recessive Titinopathy and some individuals with a cardiac-related phenotype (e.g. Ceyhan-Birsoy_2013, Evila_2017, Gonzalez-Quereda_2020, Yoneda_2021, Barbosa-Gouveia_2022). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 35628876, 23975875, 27796757, 32403337, 34495297). Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Oct 20, 2024