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NM_001267550.2(TTN):c.33419-2A>C AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 8, 2022
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:
RCV001965474.6

Allele description [Variation Report for NM_001267550.2(TTN):c.33419-2A>C]

NM_001267550.2(TTN):c.33419-2A>C

Gene:
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.33419-2A>C
HGVS:
  • NC_000002.12:g.178680057T>G
  • NG_011618.3:g.155746A>C
  • NM_001256850.1:c.32468-2A>C
  • NM_001267550.2:c.33419-2A>CMANE SELECT
  • NM_003319.4:c.13283-37740A>C
  • NM_133378.4:c.29687-2A>C
  • NM_133432.3:c.13658-37740A>C
  • NM_133437.4:c.13859-37740A>C
  • LRG_391:g.155746A>C
  • NC_000002.11:g.179544784T>G
  • NM_133378.4:c.29687-2A>C
Links:
dbSNP: rs756841034
NCBI 1000 Genomes Browser:
rs756841034
Molecular consequence:
  • NM_003319.4:c.13283-37740A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133432.3:c.13658-37740A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133437.4:c.13859-37740A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001256850.1:c.32468-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001267550.2:c.33419-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_133378.4:c.29687-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV002219414Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 8, 2022) 		germlineclinical testing

PubMed (5)
[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

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

Prevalence of Titin Truncating Variants in General Population.

Akinrinade O, Koskenvuo JW, Alastalo TP.

PLoS One. 2015;10(12):e0145284. doi: 10.1371/journal.pone.0145284.

PubMed [citation]
PMID:
26701604
PMCID:
PMC4689403
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV002219414.3

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

Description

ClinVar contains an entry for this variant (Variation ID: 1440079). 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. This variant is located in the I band of TTN (PMID: 25589632). Truncating variants in this region have been shown to be highly prevalent in the general population and unaffected individuals (PMID: 26701604, 22335739). However, truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with TTN-related conditions. This variant is present in population databases (rs756841034, gnomAD 0.01%). This sequence change affects an acceptor splice site in intron 139 of the TTN gene. It is expected to disrupt RNA splicing and likely results in a truncated or disrupted TTN protein.

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

Last Updated: Mar 16, 2024