NM_001267550.2(TTN):c.51525del (p.Ser17177fs) AND multiple conditions

Clinical significance:Likely pathogenic (Last evaluated: Oct 12, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000642790.1

Allele description [Variation Report for NM_001267550.2(TTN):c.51525del (p.Ser17177fs)]

NM_001267550.2(TTN):c.51525del (p.Ser17177fs)

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.51525del (p.Ser17177fs)
HGVS:
  • NC_000002.12:g.178609898del
  • NG_011618.3:g.225905del
  • NG_051363.1:g.92072del
  • NM_001256850.1:c.46602del
  • NM_001267550.2:c.51525delMANE SELECT
  • NM_003319.4:c.24330del
  • NM_133378.4:c.43821del
  • NM_133432.3:c.24705del
  • NM_133437.4:c.24906del
  • NP_001243779.1:p.Ser15536fs
  • NP_001254479.2:p.Ser17177fs
  • NP_003310.4:p.Ser8112fs
  • NP_596869.4:p.Ser14609fs
  • NP_597676.3:p.Ser8237fs
  • NP_597681.4:p.Ser8304fs
  • LRG_391:g.225905del
  • NC_000002.11:g.179474625del
  • NM_001267550.2:c.51525delAMANE SELECT
Protein change:
S14609fs
Links:
dbSNP: rs1553692435
NCBI 1000 Genomes Browser:
rs1553692435
Molecular consequence:
  • NM_001256850.1:c.46602del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001267550.2:c.51525del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_003319.4:c.24330del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_133378.4:c.43821del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_133432.3:c.24705del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_133437.4:c.24906del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000764477Invitaecriteria provided, single submitter
Likely pathogenic
(Oct 12, 2017)
germlineclinical testing

PubMed (2)
[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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000764477.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change results in a premature translational stop signal in the TTN gene (p.Ser17177Alafs*3). It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TTN-related disease. This variant is found in the A-band of this gene. While this particular variant has not been reported in the literature, truncating variants in the A-band of TTN are significantly overrepresented in patients with dilated cardiomyopathy and are considered to be likely pathogenic for the disease (PMID: 25589632). 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: Nov 27, 2021

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