NM_001267550.2(TTN):c.583+5G>A AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Aug 19, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000642802.4

Allele description [Variation Report for NM_001267550.2(TTN):c.583+5G>A]

NM_001267550.2(TTN):c.583+5G>A

Gene:
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.583+5G>A
HGVS:
  • NC_000002.12:g.178800390C>T
  • NG_011618.3:g.35413G>A
  • NM_001256850.1:c.583+5G>A
  • NM_001267550.2:c.583+5G>AMANE SELECT
  • NM_003319.4:c.583+5G>A
  • NM_133378.4:c.583+5G>A
  • NM_133379.5:c.583+5G>A
  • NM_133432.3:c.583+5G>A
  • NM_133437.4:c.583+5G>A
  • LRG_391:g.35413G>A
  • NC_000002.11:g.179665117C>T
  • c.583+5G>A
Links:
dbSNP: rs397517663
NCBI 1000 Genomes Browser:
rs397517663
Molecular consequence:
  • NM_001256850.1:c.583+5G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001267550.2:c.583+5G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_003319.4:c.583+5G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133378.4:c.583+5G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133379.5:c.583+5G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133432.3:c.583+5G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133437.4:c.583+5G>A - intron variant - [Sequence Ontology: SO:0001627]

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
SCV000764489Invitaecriteria provided, single submitter
Uncertain significance
(Aug 19, 2019)
germlineclinical testing

PubMed (5)
[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

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

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 (5)

Details of each submission

From Invitae, SCV000764489.4

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

Description

This sequence change falls in intron 4 of the TTN gene. It does not directly change the encoded amino acid sequence of the TTN protein, but it affects a nucleotide within the consensus splice site of the intron. 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. Variants in this region of the TTN gene are typically not causative for cardiac disease, but may be relevant for neuromuscular disorders (PMID: 23975875). ClinVar contains an entry for this variant (Variation ID: 47232). This variant identified in the TTN gene is located in the Z band of the resulting protein (PMID: 25589632). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Aug 25, 2021

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