NM_001267550.2(TTN):c.11312-5194_11312-5162dup AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Benign/Likely benign (5 submissions)
Last evaluated:: Aug 1, 2021
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:: RCV000786262.8

Allele description

NM_001267550.2(TTN):c.11312-5194_11312-5162dup

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.11312-5194_11312-5162dup

Other names:

p.Thr5102_Glu5112dup; p.Glu5112_Ala5113insThrLeuGluArgTyrSerThrProProGlyGlu

HGVS:

NC_000002.12:g.178747087_178747119dup
NG_011618.3:g.88688_88720dup
NM_001256850.1:c.10361-5194_10361-5162dup
NM_001267550.2:c.11312-5194_11312-5162dupMANE SELECT
NM_003319.4:c.10223-5194_10223-5162dup
NM_133378.4:c.10360+6009_10360+6041dup
NM_133379.5:c.15285_15317dup
NM_133432.3:c.10598-5194_10598-5162dup
NM_133437.4:c.10799-5194_10799-5162dup
NP_596870.2:p.5058TLERYSTPPGE[6]
LRG_391:g.88688_88720dup
NC_000002.11:g.179611809_179611810insTATCGCTCTAGAGTCTCTCCTGGGGGTGTGGAG
NC_000002.11:g.179611814_179611846dup
NM_133379.3:c.15285_15317dup
c.15285_15317dup

Links:

dbSNP: rs397517815

NCBI 1000 Genomes Browser:

rs397517815

Molecular consequence:

NM_133379.5:c.15285_15317dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001256850.1:c.10361-5194_10361-5162dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001267550.2:c.11312-5194_11312-5162dup - intron variant - [Sequence Ontology: SO:0001627]
NM_003319.4:c.10223-5194_10223-5162dup - intron variant - [Sequence Ontology: SO:0001627]
NM_133378.4:c.10360+6009_10360+6041dup - intron variant - [Sequence Ontology: SO:0001627]
NM_133432.3:c.10598-5194_10598-5162dup - intron variant - [Sequence Ontology: SO:0001627]
NM_133437.4:c.10799-5194_10799-5162dup - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000925013	Stanford Center for Inherited Cardiovascular Disease, Stanford University	no assertion criteria provided	Uncertain significance (Jul 27, 2016)	germline	provider interpretation
SCV001334681	CeGaT Praxis fuer Humangenetik Tuebingen	criteria provided, single submitter (Praxis fuer Humangenetik Tuebingen - Variant Classification Criteria)	Likely benign (Aug 1, 2021)	germline	clinical testing	Citation Link,
SCV001800155	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus	no assertion criteria provided	Likely benign	germline	clinical testing
SCV001847297	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Benign (Oct 23, 2019)	germline	clinical testing	Citation Link,
SCV001953317	Human Genetics - Radboudumc,Radboudumc - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Likely benign	germline	clinical testing

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	provider interpretation

Details of each submission

From Stanford Center for Inherited Cardiovascular Disease, Stanford University, SCV000925013.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	provider interpretation	not provided

Description

p.Thr5102_Glu5112dup (T5102_E5112dup, c.15285_15317dup33:) in exon 46 of the TTN gene (NM_133379.3, alternate transcript). Seen in a patient in our center with LVNC and reduced systolic function. Given the location, lack of case data, and frequency in ExAC, we consider this variant a variant of uncertain significance, probably benign and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). The variant has not been reported in association with disease. Based on the genomic position (hg19 ) and https://cardiodb.org/titin/ it appears the variant is in the I-band distant from the A band. To date it appears that pathogenic variants in TTN are in the A band (or the I band near the A band). ExAC: 0.6% (376/66452) European chromosomes.

#	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 CeGaT Praxis fuer Humangenetik Tuebingen, SCV001334681.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	not provided

#	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		2	not provided	not provided	not provided

From Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus, SCV001800155.1

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

#	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

From GeneDx, SCV001847297.1

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

#	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

From Human Genetics - Radboudumc,Radboudumc - VKGL Data-share Consensus, SCV001953317.1

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

#	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: Nov 29, 2021

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