NM_001267550.2(TTN):c.2228C>T (p.Ala743Val) AND Dilated cardiomyopathy 1G

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 22, 2002
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000013491.19

Allele description [Variation Report for NM_001267550.2(TTN):c.2228C>T (p.Ala743Val)]

NM_001267550.2(TTN):c.2228C>T (p.Ala743Val)

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.2228C>T (p.Ala743Val)

HGVS:

NC_000002.12:g.178785990G>A
NG_011618.3:g.49813C>T
NM_001256850.1:c.2228C>T
NM_001267550.2:c.2228C>TMANE SELECT
NM_003319.4:c.2090C>T
NM_133378.4:c.2228C>T
NM_133379.5:c.2228C>T
NM_133432.3:c.2090C>T
NM_133437.4:c.2090C>T
NP_001243779.1:p.Ala743Val
NP_001254479.2:p.Ala743Val
NP_003310.4:p.Ala697Val
NP_596869.4:p.Ala743Val
NP_596870.2:p.Ala743Val
NP_597676.3:p.Ala697Val
NP_597681.4:p.Ala697Val
LRG_391:g.49813C>T
NC_000002.11:g.179650717G>A
Q8WZ42:p.Ala743Val

Protein change:

A697V; ALA743VAL

Links:

UniProtKB: Q8WZ42#VAR_026688; OMIM: 188840.0007; dbSNP: rs267607157

NCBI 1000 Genomes Browser:

rs267607157

Molecular consequence:

NM_001256850.1:c.2228C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.2228C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.2090C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.2228C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133379.5:c.2228C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.2090C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.2090C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dilated cardiomyopathy 1G (CMD1G)
Identifiers:: MONDO: MONDO:0011400; MedGen: C1858763; Orphanet: 154; OMIM: 604145

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
SCV000033738	OMIM	no assertion criteria provided	Pathogenic (Feb 22, 2002)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000033738

OMIM

no assertion criteria provided

Pathogenic
(Feb 22, 2002)

germline

literature only

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Titin mutations as the molecular basis for dilated cardiomyopathy.

Itoh-Satoh M, Hayashi T, Nishi H, Koga Y, Arimura T, Koyanagi T, Takahashi M, Hohda S, Ueda K, Nouchi T, Hiroe M, Marumo F, Imaizumi T, Yasunami M, Kimura A.

Biochem Biophys Res Commun. 2002 Feb 22;291(2):385-93.

PubMed [citation]

PMID:: 11846417

Details of each submission

From OMIM, SCV000033738.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a father and daughter with dilated cardiomyopathy (CMD1G; 604145), Itoh-Satoh et al. (2002) identified a heterozygous C-to-T transition in the TTN gene, resulting in an ala743-to-val (A743V) substitution. Both patients had a history of cardiac arrhythmias (premature atrial or ventricular contraction and atrioventricular conduction block) before they developed dilated cardiomyopathy or congestive heart failure. The A743V mutation is located in the alpha-actinin (102575)-binding domain of titin, and functional studies showed that the mutation decreased the affinity of titin Z-repeats to alpha-actinin by about 40% compared to normal. The authors noted that the A743V mutation is located near the R740L (188840.0001) mutation, which was found in a patient with hypertrophic cardiomyopathy and results in increased titin-binding affinity to alpha-actinin.

#	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		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine