NM_001267550.2(TTN):c.835C>T (p.Arg279Trp) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 13, 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:: RCV000617531.4

Allele description [Variation Report for NM_001267550.2(TTN):c.835C>T (p.Arg279Trp)]

NM_001267550.2(TTN):c.835C>T (p.Arg279Trp)

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.835C>T (p.Arg279Trp)

Other names:

p.R279W:CGG>TGG

HGVS:

NC_000002.12:g.178799566G>A
NG_011618.3:g.36237C>T
NM_001256850.1:c.835C>T
NM_001267550.2:c.835C>TMANE SELECT
NM_003319.4:c.835C>T
NM_133378.4:c.835C>T
NM_133379.5:c.835C>T
NM_133432.3:c.835C>T
NM_133437.4:c.835C>T
NP_001243779.1:p.Arg279Trp
NP_001254479.2:p.Arg279Trp
NP_003310.4:p.Arg279Trp
NP_596869.4:p.Arg279Trp
NP_596870.2:p.Arg279Trp
NP_597676.3:p.Arg279Trp
NP_597681.4:p.Arg279Trp
LRG_391t1:c.835C>T
LRG_391:g.36237C>T
NC_000002.11:g.179664293G>A
NM_001267550.1:c.835C>T
Q8WZ42:p.Arg279Trp

Protein change:

R279W; ARG279TRP

Links:

UniProtKB: Q8WZ42#VAR_026634; OMIM: 188840.0011; dbSNP: rs138060032

NCBI 1000 Genomes Browser:

rs138060032

Molecular consequence:

NM_001256850.1:c.835C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.835C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.835C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.835C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133379.5:c.835C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.835C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.835C>T - 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
SCV000735597	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 13, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23861362, 24558114, 27930701 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000735597

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 13, 2018)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Titin gene mutations are common in families with both peripartum cardiomyopathy and dilated cardiomyopathy.

van Spaendonck-Zwarts KY, Posafalvi A, van den Berg MP, Hilfiker-Kleiner D, Bollen IA, Sliwa K, Alders M, Almomani R, van Langen IM, van der Meer P, Sinke RJ, van der Velden J, Van Veldhuisen DJ, van Tintelen JP, Jongbloed JD.

Eur Heart J. 2014 Aug 21;35(32):2165-73. doi: 10.1093/eurheartj/ehu050. Epub 2014 Feb 20.

PubMed [citation]

PMID:: 24558114

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000735597.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.R279W variant (also known as c.835C>T), located in coding exon 5 of the TTN gene, results from a C to T substitution at nucleotide position 835. The arginine at codon 279 is replaced by tryptophan, an amino acid with dissimilar properties. This variant was reported in cis with a truncating TTN alteration in a family with both dilated cardiomyopathy and peripartum cardiomyopathy (van Spaendonck-Zwarts KY et al. Eur Heart J. 2014;35:2165-73). This alteration has also been reported as a secondary cardiac variant in an exome cohort, and was detected in a sudden unexplained death case with variants in other cardiac-related genes (Ng D et al. Circ Cardiovasc Genet. 2013;6:337-46; Sanchez O et al. PLoS ONE. 2016;11(12):e0167358). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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: Oct 20, 2024

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