NM_001267550.2(TTN):c.14152A>G (p.Lys4718Glu) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 12, 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:: RCV002381621.9

Allele description [Variation Report for NM_001267550.2(TTN):c.14152A>G (p.Lys4718Glu)]

NM_001267550.2(TTN):c.14152A>G (p.Lys4718Glu)

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.14152A>G (p.Lys4718Glu)

Other names:

p.K4401E:AAA>GAA

HGVS:

NC_000002.12:g.178738301T>C
NG_011618.3:g.97502A>G
NM_001256850.1:c.13201A>G
NM_001267550.2:c.14152A>GMANE SELECT
NM_003319.4:c.13063A>G
NM_133378.4:c.10420A>G
NM_133432.3:c.13438A>G
NM_133437.4:c.13639A>G
NP_001243779.1:p.Lys4401Glu
NP_001254479.2:p.Lys4718Glu
NP_003310.4:p.Lys4355Glu
NP_596869.4:p.Lys3474Glu
NP_597676.3:p.Lys4480Glu
NP_597681.4:p.Lys4547Glu
LRG_391:g.97502A>G
NC_000002.11:g.179603028T>C
NM_003319.4:c.13063A>G

Protein change:

K3474E

Links:

dbSNP: rs757119133

NCBI 1000 Genomes Browser:

rs757119133

Molecular consequence:

NM_001256850.1:c.13201A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.14152A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.13063A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.10420A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.13438A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.13639A>G - 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
SCV002693755	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 12, 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

SCV002693755

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 12, 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

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

Details of each submission

From Ambry Genetics, SCV002693755.2

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

Description

The p.K4355E variant (also known as c.13063A>G), located in coding exon 45 of the TTN gene, results from an A to G substitution at nucleotide position 13063. The lysine at codon 4355 is replaced by glutamic acid, an amino acid with similar properties. This variant (reported as p.Lys4401Glu, c.13201A>G) was reported to co-occur with a TTN frameshift alteration in an individual with peripartum cardiomyopathy (van Spaendonck-Zwarts KY et al. Eur. Heart J., 2014 Aug;35:2165-73). 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: Nov 24, 2024

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