NM_001267550.2(TTN):c.47875+4_47875+7del AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 15, 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:: RCV000548654.6

Allele description [Variation Report for NM_001267550.2(TTN):c.47875+4_47875+7del]

NM_001267550.2(TTN):c.47875+4_47875+7del

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.47875+4_47875+7del

HGVS:

NC_000002.12:g.178617115_178617118del
NG_011618.3:g.218687_218690del
NG_051363.1:g.99289_99292del
NM_001256850.1:c.42952+4_42952+7del
NM_001267550.2:c.47875+4_47875+7delMANE SELECT
NM_003319.4:c.20680+4_20680+7del
NM_133378.4:c.40171+4_40171+7del
NM_133432.3:c.21055+4_21055+7del
NM_133437.4:c.21256+4_21256+7del
LRG_391:g.218687_218690del
NC_000002.11:g.179481840_179481843del
NC_000002.11:g.179481842_179481845del
NM_001267550.2:c.47875+4_47875+7delAATAMANE SELECT
NM_003319.4:c.20680+4_20680+7delAATA

Links:

dbSNP: rs753206674

NCBI 1000 Genomes Browser:

rs753206674

Molecular consequence:

NM_001256850.1:c.42952+4_42952+7del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001267550.2:c.47875+4_47875+7del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_003319.4:c.20680+4_20680+7del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_133378.4:c.40171+4_40171+7del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_133432.3:c.21055+4_21055+7del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_133437.4:c.21256+4_21256+7del - splice donor variant - [Sequence Ontology: SO:0001575]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000643244	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 15, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17576681, 9536098, 25589632, 23975875, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000643244

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 15, 2023)

germline

clinical testing

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

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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000643244.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change falls in intron 255 of the TTN gene. It does not directly change the encoded amino acid sequence of the TTN protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs753206674, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 467193). Variants that disrupt 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. This variant is located in the A band of TTN (PMID: 25589632). Variants in this region may be relevant for cardiac or neuromuscular disorders (PMID: 25589632, 23975875). 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.

#	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: Sep 29, 2024

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