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Relating variation to medicine
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NM_001267550.2(TTN):c.74987_74991dup (p.Ser24998fs) AND multiple conditions
- Germline classification:
- Likely pathogenic (1 submission)
- Last evaluated:
- Dec 6, 2018
- Review status:
- 1 star out of maximum of 4 stars
criteria provided, single submitter
- Somatic classification
of clinical impact: - None
- Review status:
- (0/4)
no assertion criteria provided
- Somatic classification
of oncogenicity: - None
- Review status:
- (0/4)
no assertion criteria provided
- Record status:
- current
- Accession:
- RCV000810190.6
Allele description [Variation Report for NM_001267550.2(TTN):c.74987_74991dup (p.Ser24998fs)]
NM_001267550.2(TTN):c.74987_74991dup (p.Ser24998fs)
- Genes:
- TTN-AS1:TTN antisense RNA 1 [Gene - HGNC]
TTN:titin [Gene - OMIM - HGNC] - Variant type:
- Duplication
- Cytogenetic location:
- 2q31.2
- Genomic location:
- Chr2: 178571140 - 178571141 (on Assembly GRCh38)
- Chr2: 179435867 - 179435868 (on Assembly GRCh37)
- Preferred name:
- NM_001267550.2(TTN):c.74987_74991dup (p.Ser24998fs)
- HGVS:
- NC_000002.12:g.178571145_178571149dup
- NG_011618.3:g.264658_264662dup
- NG_051363.1:g.53319_53323dup
- NM_001256850.1:c.70064_70068dup
- NM_001267550.2:c.74987_74991dupMANE SELECT
- NM_003319.4:c.47792_47796dup
- NM_133378.4:c.67283_67287dup
- NM_133432.3:c.48167_48171dup
- NM_133437.4:c.48368_48372dup
- NP_001243779.1:p.Ser23357fs
- NP_001254479.2:p.Ser24998fs
- NP_003310.4:p.Ser15933fs
- NP_596869.4:p.Ser22430fs
- NP_597676.3:p.Ser16058fs
- NP_597681.4:p.Ser16125fs
- LRG_391:g.264658_264662dup
- NC_000002.11:g.179435867_179435868insTACTT
- NC_000002.11:g.179435872_179435876dup
- NM_001256850.1:c.70064_70068dupAAGTA
- NM_001267550.2:c.74987_74991dupAAGTAMANE SELECT
- Protein change:
- S15933fs
- Links:
- dbSNP: rs1553604316
- NCBI 1000 Genomes Browser:
- rs1553604316
- Molecular consequence:
- NM_001256850.1:c.70064_70068dup - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_001267550.2:c.74987_74991dup - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_003319.4:c.47792_47796dup - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_133378.4:c.67283_67287dup - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_133432.3:c.48167_48171dup - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_133437.4:c.48368_48372dup - frameshift variant - [Sequence Ontology: SO:0001589]
Condition(s)
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Assertion and evidence details
- Clinical assertions
- Evidence
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| Submission Accession | Submitter | Review Status (Assertion method) | Clinical Significance (Last evaluated) | Origin | Method | Citations |
|---|---|---|---|---|---|---|
| SCV000950383 | Invitae | criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) | Likely pathogenic (Dec 6, 2018) | germline | clinical testing | PubMed (3) |
Help
Summary from all submissions
| Ethnicity | Origin | Affected | Individuals | Families | Chromosomes tested | Number Tested | Family history | Method |
|---|---|---|---|---|---|---|---|---|
| not provided | germline | unknown | not provided | not provided | not provided | not provided | not provided | clinical testing |
Citations
PubMed
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
Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy.
Ceyhan-Birsoy O, Agrawal PB, Hidalgo C, Schmitz-Abe K, DeChene ET, Swanson LC, Soemedi R, Vasli N, Iannaccone ST, Shieh PB, Shur N, Dennison JM, Lawlor MW, Laporte J, Markianos K, Fairbrother WG, Granzier H, Beggs AH.
Neurology. 2013 Oct 1;81(14):1205-14. doi: 10.1212/WNL.0b013e3182a6ca62. Epub 2013 Aug 23.
PubMed [citation]
- PMID:
- 23975875
- PMCID:
- PMC3795603
See all PubMed Citations (3)
Details of each submission
From Invitae, SCV000950383.4
| # | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
|---|---|---|---|---|---|---|
| 1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (3) |
Description
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. 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). This variant has not been reported in the literature in individuals with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 452835). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the TTN gene (p.Ser24998Lysfs*28). While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein.
| # | Sample | Method | Observation | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
| 1 | germline | unknown | not provided | not provided | not provided | not provided | not provided | not provided | not provided | |
Last Updated: Mar 5, 2024
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