NM_001267550.2(TTN):c.68329+2_68329+3insTT AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 10, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001784466.5

Allele description [Variation Report for NM_001267550.2(TTN):c.68329+2_68329+3insTT]

NM_001267550.2(TTN):c.68329+2_68329+3insTT

Genes:

LOC126806423:CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:179443309-179444508 [Gene]
TTN-AS1:TTN antisense RNA 1 [Gene - HGNC]
TTN:titin [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.68329+2_68329+3insTT

HGVS:

NC_000002.12:g.178578608_178578609insAA
NC_000002.12:g.178578609_178578610insAA
NG_011618.3:g.257194_257195insTT
NG_051363.1:g.60783_60784insAA
NM_001256850.1:c.63406+2_63406+3insTT
NM_001267550.2:c.68329+2_68329+3insTTMANE SELECT
NM_003319.4:c.41134+2_41134+3insTT
NM_133378.4:c.60625+2_60625+3insTT
NM_133432.3:c.41509+2_41509+3insTT
NM_133437.4:c.41710+2_41710+3insTT
LRG_391t1:c.68329+2_68329+3insTT
LRG_391:g.257194_257195insTT
NC_000002.11:g.179443335_179443336insAA
NC_000002.11:g.179443336_179443337insAA
NM_001267550.1:c.68329+2_68329+3insTT

Links:

dbSNP: rs536078303

NCBI 1000 Genomes Browser:

rs536078303

Molecular consequence:

NM_001256850.1:c.63406+2_63406+3insTT - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001267550.2:c.68329+2_68329+3insTT - splice donor variant - [Sequence Ontology: SO:0001575]
NM_003319.4:c.41134+2_41134+3insTT - splice donor variant - [Sequence Ontology: SO:0001575]
NM_133378.4:c.60625+2_60625+3insTT - splice donor variant - [Sequence Ontology: SO:0001575]
NM_133432.3:c.41509+2_41509+3insTT - splice donor variant - [Sequence Ontology: SO:0001575]
NM_133437.4:c.41710+2_41710+3insTT - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002021492	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 14, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005328169	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jan 10, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002021492

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 14, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV005328169

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jan 10, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Revvity Omics, Revvity, SCV002021492.3

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

#	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

From GeneDx, SCV005328169.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Identified in a patient with pediatric-onset restrictive cardiomyopathy; the variant was inherited from an unaffected parent (PMID: 31568572); In silico analysis supports a deleterious effect on splicing; Located in the A-band region of TTN in which the majority of loss of function variants have been associated with autosomal dominant titinopathies (PMID: 22335739); This variant is associated with the following publications: (PMID: 22335739, 31333075, 31568572)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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Relating variation to medicine