NM_001267550.2(TTN):c.7619G>A (p.Arg2540His) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 30, 2013
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000242133.2

Allele description [Variation Report for NM_001267550.2(TTN):c.7619G>A (p.Arg2540His)]

NM_001267550.2(TTN):c.7619G>A (p.Arg2540His)

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.7619G>A (p.Arg2540His)

HGVS:

NC_000002.12:g.178773345C>T
NG_011618.3:g.62458G>A
NM_001256850.1:c.7619G>A
NM_001267550.2:c.7619G>AMANE SELECT
NM_003319.4:c.7481G>A
NM_133378.4:c.7619G>A
NM_133379.5:c.7619G>A
NM_133432.3:c.7481G>A
NM_133437.4:c.7481G>A
NP_001243779.1:p.Arg2540His
NP_001254479.2:p.Arg2540His
NP_003310.4:p.Arg2494His
NP_596869.4:p.Arg2540His
NP_596870.2:p.Arg2540His
NP_597676.3:p.Arg2494His
NP_597681.4:p.Arg2494His
LRG_391:g.62458G>A
NC_000002.11:g.179638072C>T
c.7619G>A

Protein change:

R2494H

Links:

dbSNP: rs397517725

NCBI 1000 Genomes Browser:

rs397517725

Molecular consequence:

NM_001256850.1:c.7619G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.7619G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.7481G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.7619G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133379.5:c.7619G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.7481G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.7481G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000319152	Ambry Genetics	criteria provided, single submitter (Ambry Autosomal Dominant and X-Linked criteria (10/2015))	Uncertain significance (Oct 30, 2013)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000319152

Ambry Genetics

criteria provided, single submitter

(Ambry Autosomal Dominant and X-Linked criteria (10/2015))

Uncertain significance
(Oct 30, 2013)

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	unknown	1	not provided	not provided	1	not provided	clinical testing

Details of each submission

From Ambry Genetics, SCV000319152.5

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

Description

The p.R2540H variant (also known as c.7619G>A) is located in coding exon 32 of the TTNgene. This alteration results from a G to A substitution at nucleotide position 7619. The arginine at codon 2540 is replaced by histidine, an amino acid with highly similar properties.This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), the 1000 Genomes Project and the NHLBI Exome Sequencing Project (ESP). In the ESP, this variant was not observed in 6501 samples (13002 alleles) with coverage at this position. Based on protein sequence alignment, this amino acid position isnot conserved in available vertebrate species, with histidine as the reference amino acid in numerous species.In addition, this alteration is predicted to be benignby PolyPhen in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.

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

Last Updated: Apr 20, 2025

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