NM_001267550.2(TTN):c.11311+3847G>T AND not provided

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

Germline classification:: Conflicting classifications of pathogenicity (8 submissions)
Last evaluated:: Jan 29, 2019
Review status:: criteria provided, conflicting classifications

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:: RCV000172716.10

Allele description

NM_001267550.2(TTN):c.11311+3847G>T

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.11311+3847G>T

Other names:

p.A4375S:GCA>TCA

HGVS:

NC_000002.12:g.178749277C>A
NG_011618.3:g.86526G>T
NM_001256850.1:c.10360+3847G>T
NM_001267550.2:c.11311+3847G>TMANE SELECT
NM_003319.4:c.10222+3847G>T
NM_133378.4:c.10360+3847G>T
NM_133379.5:c.13123G>T
NM_133432.3:c.10597+3847G>T
NM_133437.4:c.10798+3847G>T
NP_596870.2:p.Ala4375Ser
LRG_391:g.86526G>T
NC_000002.11:g.179614004C>A
NM_133379.3:c.13123G>T
c.13123G>T

Protein change:

A4375S

Links:

dbSNP: rs72647902

NCBI 1000 Genomes Browser:

rs72647902

Molecular consequence:

NM_001256850.1:c.10360+3847G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001267550.2:c.11311+3847G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_003319.4:c.10222+3847G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_133378.4:c.10360+3847G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_133432.3:c.10597+3847G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_133437.4:c.10798+3847G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_133379.5:c.13123G>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000051326	Biesecker Lab/Clinical Genomics Section,National Institutes of Health - ClinSeq	criteria provided, single submitter (Ng et al. (Circ Cardiovasc Genet. 2013))	Likely benign (Jun 24, 2013)	unknown	research	PubMed (1) [See all records that cite this PMID]
SCV000238112	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Jan 29, 2019)	germline	clinical testing	Citation Link,
SCV000855293	EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Nov 14, 2017)	germline	clinical testing	Citation Link,
SCV001153135	CeGaT Praxis fuer Humangenetik Tuebingen	criteria provided, single submitter (Praxis fuer Humangenetik Tuebingen - Variant Classification Criteria)	Uncertain significance (Apr 1, 2017)	germline	clinical testing	Citation Link,
SCV001744002	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Likely benign	germline	clinical testing
SCV001918615	Clinical Genetics,Academic Medical Center - 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
SCV001929919	Genome Diagnostics Laboratory, University Medical Center Utrecht - 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
SCV001953150	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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	3	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	2	not provided	not provided	not provided	not provided	research

Citations

PubMed

Interpreting secondary cardiac disease variants in an exome cohort.

Ng D, Johnston JJ, Teer JK, Singh LN, Peller LC, Wynter JS, Lewis KL, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG; NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program..

Circ Cardiovasc Genet. 2013 Aug;6(4):337-46. doi: 10.1161/CIRCGENETICS.113.000039. Epub 2013 Jul 16.

PubMed [citation]

PMID:: 23861362
PMCID:: PMC3887521

Details of each submission

From Biesecker Lab/Clinical Genomics Section,National Institutes of Health - ClinSeq, SCV000051326.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		2	not provided	not provided	not provided

From GeneDx, SCV000238112.6

#	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 large cohort of individuals with dilated cardiomyopathy; however, no details are provided (Haas et al., 2015); Observed in 0.0454% (57/125522) of alleles from individuals of European (non-Finnish) background in large population cohorts (Lek et al., 2016); Missense variant in a gene in which most reported pathogenic variants are truncating/loss-of-function; In silico analysis, which includes splice predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25163546)

#	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 EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000855293.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	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	unknown	not provided	not provided	not provided		3	not provided	not provided	not provided

From CeGaT Praxis fuer Humangenetik Tuebingen, SCV001153135.7

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

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001744002.3

#	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 Clinical Genetics,Academic Medical Center - VKGL Data-share Consensus, SCV001918615.1

#	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 Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001929919.1

#	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, SCV001953150.1

#	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

Relating variation to medicine