NM_001267550.2(TTN):c.95242C>T (p.Arg31748Cys) AND not provided

Germline classification:: Conflicting classifications of pathogenicity (4 submissions)
Last evaluated:: Feb 1, 2025
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:: RCV000172617.40

Allele description [Variation Report for NM_001267550.2(TTN):c.95242C>T (p.Arg31748Cys)]

NM_001267550.2(TTN):c.95242C>T (p.Arg31748Cys)

Genes:

TTN-AS1:TTN antisense RNA 1 [Gene - HGNC]
TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.95242C>T (p.Arg31748Cys)

Other names:

p.R30107C:CGC>TGC

HGVS:

NC_000002.12:g.178545994G>A
NG_011618.3:g.289809C>T
NG_051363.1:g.28168G>A
NM_001256850.1:c.90319C>T
NM_001267550.2:c.95242C>TMANE SELECT
NM_003319.4:c.68047C>T
NM_133378.4:c.87538C>T
NM_133432.3:c.68422C>T
NM_133437.4:c.68623C>T
NP_001243779.1:p.Arg30107Cys
NP_001254479.2:p.Arg31748Cys
NP_003310.4:p.Arg22683Cys
NP_596869.4:p.Arg29180Cys
NP_597676.3:p.Arg22808Cys
NP_597681.4:p.Arg22875Cys
LRG_391:g.289809C>T
NC_000002.11:g.179410721G>A
c.87538C>T

Protein change:

R22683C

Links:

dbSNP: rs142525903

NCBI 1000 Genomes Browser:

rs142525903

Molecular consequence:

NM_001256850.1:c.90319C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.95242C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.68047C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.87538C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.68422C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.68623C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000051307	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]
SCV000237802	GeneDx	no classification provided (GeneDx Variant Classification (06012015))	not provided	germline	clinical testing	Citation Link,
SCV000333343	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Jul 20, 2015)	germline	clinical testing	Citation Link,
SCV001152642	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Benign (Feb 1, 2025)	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	38	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	6	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	4	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, SCV000051307.1

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

From GeneDx, SCV000237802.2

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

Description

Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in DCM,CARDIOMYOPATHY panel(s).

#	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 Eurofins Ntd Llc (ga), SCV000333343.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	6	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		6	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV001152642.29

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	38	not provided	not provided	clinical testing	not provided

Description

TTN: BS1, BS2

#	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		38	not provided	not provided	not provided

Last Updated: Mar 22, 2025

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