NM_001267550.2(TTN):c.35794G>T (p.Glu11932Ter) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(2) (Last evaluated: Aug 1, 2018)
Review status:1 star out of maximum of 4 stars
criteria provided, conflicting interpretations

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Based on:: 3 submissions [Details]
Record status:: current
Accession:: RCV000657941.3

Allele description [Variation Report for NM_001267550.2(TTN):c.35794G>T (p.Glu11932Ter)]

NM_001267550.2(TTN):c.35794G>T (p.Glu11932Ter)

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.35794G>T (p.Glu11932Ter)

HGVS:

NC_000002.12:g.178667239C>A
NG_011618.3:g.168564G>T
NM_001256850.1:c.34264+2979G>T
NM_001267550.2:c.35794G>TMANE SELECT
NM_003319.4:c.13283-24922G>T
NM_133378.4:c.31483+2979G>T
NM_133432.3:c.13658-24922G>T
NM_133437.4:c.13859-24922G>T
NP_001254479.2:p.Glu11932Ter
LRG_391:g.168564G>T
NC_000002.11:g.179531966C>A

Protein change:

E11932*

Links:

dbSNP: rs878854299

NCBI 1000 Genomes Browser:

rs878854299

Molecular consequence:

NM_001256850.1:c.34264+2979G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_003319.4:c.13283-24922G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_133378.4:c.31483+2979G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_133432.3:c.13658-24922G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_133437.4:c.13859-24922G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001267550.2:c.35794G>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000338622	EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	criteria provided, single submitter EGL Classification Definitions 2015	Uncertain significance (Feb 6, 2018)	germline	clinical testing	Citation Link,
SCV000779710	GeneDx	criteria provided, single submitter GeneDx Variant Classification (06012015)	Uncertain significance (May 18, 2018)	germline	clinical testing	Citation Link,
SCV001152960	CeGaT Praxis fuer Humangenetik Tuebingen	criteria provided, single submitter Praxis fuer Humangenetik Tuebingen - Variant Classification Criteria	Likely pathogenic (Aug 1, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000338622

EGL Genetic Diagnostics, Eurofins Clinical Diagnostics

criteria provided, single submitter

EGL Classification Definitions 2015

Uncertain significance
(Feb 6, 2018)

germline

clinical testing

Citation Link,

SCV000779710

GeneDx

criteria provided, single submitter

GeneDx Variant Classification (06012015)

Uncertain significance
(May 18, 2018)

germline

clinical testing

Citation Link,

SCV001152960

CeGaT Praxis fuer Humangenetik Tuebingen

criteria provided, single submitter

Praxis fuer Humangenetik Tuebingen - Variant Classification Criteria

Likely pathogenic
(Aug 1, 2018)

germline

clinical testing

Citation Link

Summary from all submissions

Help

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	2	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	4	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000338622.4

#	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	unknown	not provided	not provided	not provided		2	not provided	not provided	not provided

From GeneDx, SCV000779710.2

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

Description

The E11932X variant in the TTN gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The E11932X variant is not observed in large population cohorts (Lek et al., 2016). We interpret E11932X as a variant of uncertain significance.

#	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 CeGaT Praxis fuer Humangenetik Tuebingen, SCV001152960.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	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		4	not provided	not provided	not provided

Last Updated: Jul 10, 2021

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