NM_001267550.2(TTN):c.52852C>T (p.Arg17618Cys) AND not specified

Germline classification:: Conflicting classifications of pathogenicity (3 submissions)
Last evaluated:: Oct 19, 2020
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:: RCV000040336.17

Allele description [Variation Report for NM_001267550.2(TTN):c.52852C>T (p.Arg17618Cys)]

NM_001267550.2(TTN):c.52852C>T (p.Arg17618Cys)

Genes:

LOC126806425:BRD4-independent group 4 enhancer GRCh37_chr2:179471933-179473132 [Gene]
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.52852C>T (p.Arg17618Cys)

HGVS:

NC_000002.12:g.178607935G>A
NG_011618.3:g.227868C>T
NG_051363.1:g.90109G>A
NM_001256850.1:c.47929C>T
NM_001267550.2:c.52852C>TMANE SELECT
NM_003319.4:c.25657C>T
NM_133378.4:c.45148C>T
NM_133432.3:c.26032C>T
NM_133437.4:c.26233C>T
NP_001243779.1:p.Arg15977Cys
NP_001254479.2:p.Arg17618Cys
NP_003310.4:p.Arg8553Cys
NP_596869.4:p.Arg15050Cys
NP_597676.3:p.Arg8678Cys
NP_597681.4:p.Arg8745Cys
LRG_391:g.227868C>T
NC_000002.11:g.179472662G>A
NM_001267550.1:c.52852C>T
NM_003319.4:c.25657C>T
c.45148C>T

Protein change:

R15050C

Links:

dbSNP: rs201213901

NCBI 1000 Genomes Browser:

rs201213901

Molecular consequence:

NM_001256850.1:c.47929C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.52852C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.25657C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.45148C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.26032C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.26233C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000064027	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (May 21, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001879658	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics criteria)	Benign (Oct 19, 2020)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001923367	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	Benign	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000064027

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(May 21, 2015)

germline

clinical testing

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

SCV001879658

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics criteria)

Benign
(Oct 19, 2020)

unknown

clinical testing

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

SCV001923367

Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided

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	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	3	3	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000064027.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (1)

Description

Variant classified as Uncertain Significance - Favor Benign. The p.Arg15050Cys v ariant in TTN has been previously identified by our laboratory in 1 adult with D CM, who carried a likely pathogenic variant in another gene, and in 1 adult with HCM. This variant has been identified in 0.2% (146/66698) of European chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs201213901). Computational prediction tools and conservation analysis sugge st that this variant may impact the protein, though this information is not pred ictive enough to determine pathogenicity. In summary, while the clinical signifi cance of the p.Arg15050Cys variant is uncertain, its frequency in the general po pulation suggests that it is more likely to be benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		3	not provided	3	not provided

From Athena Diagnostics, SCV001879658.1

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

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001923367.2

#	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: Mar 11, 2025

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