NM_001267550.2(TTN):c.5198C>T (p.Thr1733Met) AND not specified

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Jan 22, 2018
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:: RCV000152502.17

Allele description [Variation Report for NM_001267550.2(TTN):c.5198C>T (p.Thr1733Met)]

NM_001267550.2(TTN):c.5198C>T (p.Thr1733Met)

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.5198C>T (p.Thr1733Met)

HGVS:

NC_000002.12:g.178776666G>A
NG_011618.3:g.59137C>T
NM_001256850.1:c.5198C>T
NM_001267550.2:c.5198C>TMANE SELECT
NM_003319.4:c.5060C>T
NM_133378.4:c.5198C>T
NM_133379.5:c.5198C>T
NM_133432.3:c.5060C>T
NM_133437.4:c.5060C>T
NP_001243779.1:p.Thr1733Met
NP_001254479.2:p.Thr1733Met
NP_003310.4:p.Thr1687Met
NP_596869.4:p.Thr1733Met
NP_596870.2:p.Thr1733Met
NP_597676.3:p.Thr1687Met
NP_597681.4:p.Thr1687Met
LRG_391:g.59137C>T
NC_000002.11:g.179641393G>A

Protein change:

T1687M

Links:

dbSNP: rs367700246

NCBI 1000 Genomes Browser:

rs367700246

Molecular consequence:

NM_001256850.1:c.5198C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.5198C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.5060C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.5198C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133379.5:c.5198C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.5060C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.5060C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000201669	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Sep 25, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000859274	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Likely benign (Jan 22, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000201669

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Sep 25, 2014)

germline

clinical testing

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

SCV000859274

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Likely benign
(Jan 22, 2018)

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	not provided	1	1	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	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

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000201669.5

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

Description

The Thr1733Met variant in TTN gene has not been previously reported in individua ls with cardiomyopathy, but has been identified in 1/8600 European American chro mosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/ ; dbSNP rs367700246). Computational prediction tools and conservation analysis s uggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significa nce of the Thr1733Met variant is uncertain.

#	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		1	not provided	1	not provided

From Eurofins Ntd Llc (ga), SCV000859274.1

#	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

Last Updated: Mar 11, 2025

ClinVar

Relating variation to medicine