NM_001267550.2(TTN):c.30196G>C (p.Glu10066Gln) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Sep 28, 2023
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:: RCV000733860.8

Allele description [Variation Report for NM_001267550.2(TTN):c.30196G>C (p.Glu10066Gln)]

NM_001267550.2(TTN):c.30196G>C (p.Glu10066Gln)

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.30196G>C (p.Glu10066Gln)

HGVS:

NC_000002.12:g.178704174C>G
NG_011618.3:g.131629G>C
NM_001256850.1:c.29245G>C
NM_001267550.2:c.30196G>CMANE SELECT
NM_003319.4:c.13282+33908G>C
NM_133378.4:c.26464G>C
NM_133432.3:c.13657+33908G>C
NM_133437.4:c.13858+33908G>C
NP_001243779.1:p.Glu9749Gln
NP_001254479.2:p.Glu10066Gln
NP_596869.4:p.Glu8822Gln
LRG_391:g.131629G>C
NC_000002.11:g.179568901C>G
NM_001256850.1:c.29245G>C
NM_133378.4:c.26464G>C

Protein change:

E10066Q

Links:

dbSNP: rs370072382

NCBI 1000 Genomes Browser:

rs370072382

Molecular consequence:

NM_003319.4:c.13282+33908G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_133432.3:c.13657+33908G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_133437.4:c.13858+33908G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001256850.1:c.29245G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.30196G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.26464G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000861962	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions)	Uncertain significance (Jun 21, 2018)	germline	clinical testing	Citation Link,
SCV003826568	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 22, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004563364	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Uncertain significance (Sep 28, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000861962

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL ClinVar v180209 classification definitions)

Uncertain significance
(Jun 21, 2018)

germline

clinical testing

Citation Link,

SCV003826568

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 22, 2021)

germline

clinical testing

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

SCV004563364

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)

Uncertain significance
(Sep 28, 2023)

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	unknown	1	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 Eurofins Ntd Llc (ga), SCV000861962.1

#	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	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV003826568.2

#	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 ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV004563364.1

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

Description

The TTN c.30196G>C; p.Glu10066Gln variant (rs370072382; ClinVar Variation ID: 404868) is rare in the general population (<0.2% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p.Glu10066Gln variant cannot be determined with certainty. References: Begay RL et al. Role of Titin Missense Variants in Dilated Cardiomyopathy. J Am Heart Assoc. 2015 Nov 13;4(11). PMID: 26567375. Herman DS et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012 Feb 16;366(7):619-28. PMID: 22335739. Linke WA and Hamdani N. Gigantic business: titin properties and function through thick and thin. Circ Res 2014; 114(6): 1052-1068. PMID: 24625729.

#	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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