NM_001267550.2(TTN):c.6927T>A (p.Asn2309Lys) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 18, 2019
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:: RCV002362887.2

Allele description [Variation Report for NM_001267550.2(TTN):c.6927T>A (p.Asn2309Lys)]

NM_001267550.2(TTN):c.6927T>A (p.Asn2309Lys)

Genes:

LOC126806433:BRD4-independent group 4 enhancer GRCh37_chr2:179638309-179639508 [Gene]
TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.6927T>A (p.Asn2309Lys)

HGVS:

NC_000002.12:g.178774337A>T
NG_011618.3:g.61466T>A
NM_001256850.1:c.6927T>A
NM_001267550.2:c.6927T>AMANE SELECT
NM_003319.4:c.6789T>A
NM_133378.4:c.6927T>A
NM_133379.5:c.6927T>A
NM_133432.3:c.6789T>A
NM_133437.4:c.6789T>A
NP_001243779.1:p.Asn2309Lys
NP_001254479.2:p.Asn2309Lys
NP_003310.4:p.Asn2263Lys
NP_596869.4:p.Asn2309Lys
NP_596870.2:p.Asn2309Lys
NP_597676.3:p.Asn2263Lys
NP_597681.4:p.Asn2263Lys
LRG_391:g.61466T>A
NC_000002.11:g.179639064A>T
NM_003319.4:c.6789T>A

Protein change:

N2263K

Links:

dbSNP: rs147580120

NCBI 1000 Genomes Browser:

rs147580120

Molecular consequence:

NM_001256850.1:c.6927T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.6927T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.6789T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.6927T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133379.5:c.6927T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.6789T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.6789T>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
SCV002662491	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jun 18, 2019)	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

SCV002662491

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jun 18, 2019)

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, SCV002662491.2

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

Description

The p.N2263K variant (also known as c.6789T>A), located in coding exon 28 of the TTN gene, results from a T to A substitution at nucleotide position 6789. The asparagine at codon 2263 is replaced by lysine, an amino acid with similar properties. This alteration has been reported (as NM_133378.4:c.6927T>A p.N2309K) 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 not 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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