NM_001267550.2(TTN):c.84965G>A (p.Arg28322His) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 30, 2018
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:: RCV002354370.2

Allele description [Variation Report for NM_001267550.2(TTN):c.84965G>A (p.Arg28322His)]

NM_001267550.2(TTN):c.84965G>A (p.Arg28322His)

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.84965G>A (p.Arg28322His)

HGVS:

NC_000002.12:g.178561167C>T
NG_011618.3:g.274636G>A
NG_051363.1:g.43341C>T
NM_001256850.1:c.80042G>A
NM_001267550.2:c.84965G>AMANE SELECT
NM_003319.4:c.57770G>A
NM_133378.4:c.77261G>A
NM_133432.3:c.58145G>A
NM_133437.4:c.58346G>A
NP_001243779.1:p.Arg26681His
NP_001254479.2:p.Arg28322His
NP_003310.4:p.Arg19257His
NP_596869.4:p.Arg25754His
NP_597676.3:p.Arg19382His
NP_597681.4:p.Arg19449His
LRG_391:g.274636G>A
NC_000002.11:g.179425894C>T
NM_003319.4:c.57770G>A
p.Arg26681His

Protein change:

R19257H

Links:

dbSNP: rs373532064

NCBI 1000 Genomes Browser:

rs373532064

Molecular consequence:

NM_001256850.1:c.80042G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.84965G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.57770G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.77261G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.58145G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.58346G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002652111	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (May 30, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002652111

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(May 30, 2018)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Interpreting secondary cardiac disease variants in an exome cohort.

Ng D, Johnston JJ, Teer JK, Singh LN, Peller LC, Wynter JS, Lewis KL, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG; NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program.

Circ Cardiovasc Genet. 2013 Aug;6(4):337-46. doi: 10.1161/CIRCGENETICS.113.000039. Epub 2013 Jul 16.

PubMed [citation]

PMID:: 23861362
PMCID:: PMC3887521

Details of each submission

From Ambry Genetics, SCV002652111.2

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

Description

The p.R19257H variant (also known as c.57770G>A), located in coding exon 153 of the TTN gene, results from a G to A substitution at nucleotide position 57770. The arginine at codon 19257 is replaced by histidine, an amino acid with highly similar properties. This alteration (reported as p.R25754H) has been detected as a secondary cardiac variant in an exome cohort (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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