NM_001267550.2(TTN):c.80858C>T (p.Thr26953Met) AND not specified

Germline classification:: Conflicting classifications of pathogenicity (3 submissions)
Last evaluated:: Feb 25, 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:: RCV000155780.15

Allele description [Variation Report for NM_001267550.2(TTN):c.80858C>T (p.Thr26953Met)]

NM_001267550.2(TTN):c.80858C>T (p.Thr26953Met)

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.80858C>T (p.Thr26953Met)

Other names:

p.T24385M:ACG>ATG

HGVS:

NC_000002.12:g.178565274G>A
NG_011618.3:g.270529C>T
NG_051363.1:g.47448G>A
NM_001256850.1:c.75935C>T
NM_001267550.2:c.80858C>TMANE SELECT
NM_003319.4:c.53663C>T
NM_133378.4:c.73154C>T
NM_133432.3:c.54038C>T
NM_133437.4:c.54239C>T
NP_001243779.1:p.Thr25312Met
NP_001254479.2:p.Thr26953Met
NP_003310.4:p.Thr17888Met
NP_596869.4:p.Thr24385Met
NP_597676.3:p.Thr18013Met
NP_597681.4:p.Thr18080Met
LRG_391t1:c.80858C>T
LRG_391:g.270529C>T
NC_000002.11:g.179430001G>A
NM_001267550.1:c.80858C>T

Protein change:

T17888M

Links:

dbSNP: rs377506142

Molecular consequence:

NM_001256850.1:c.75935C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.80858C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.53663C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.73154C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.54038C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.54239C>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
SCV000205491	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Aug 27, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001477173	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Benign (Feb 25, 2020)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001978987	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

SCV000205491

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Aug 27, 2014)

germline

clinical testing

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

SCV001477173

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Benign
(Feb 25, 2020)

unknown

clinical testing

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

SCV001978987

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	not provided	2	2	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	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, SCV000205491.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (1)

Description

The Thr24385Met variant in TTN has previously been identified by our laboratory in 1 adult with HCM, and was absent from large population studies. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein, though 1 mammal (pika) carries a methionine ( Met; this variant) at this position, raising the possibility that this change ma y be tolerated. In summary, the clinical significance of the Thr24385Met 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		2	not provided	2	not provided

From Athena Diagnostics, SCV001477173.1

#	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, SCV001978987.1

#	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: Jul 6, 2026

ClinVar

Relating variation to medicine