NM_001267550.2(TTN):c.64916G>A (p.Arg21639Gln) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 25, 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:: RCV002350422.2

Allele description [Variation Report for NM_001267550.2(TTN):c.64916G>A (p.Arg21639Gln)]

NM_001267550.2(TTN):c.64916G>A (p.Arg21639Gln)

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.64916G>A (p.Arg21639Gln)

Other names:

p.Arg19071Gln

HGVS:

NC_000002.12:g.178584725C>T
NG_011618.3:g.251078G>A
NG_051363.1:g.66899C>T
NM_001256850.1:c.59993G>A
NM_001267550.2:c.64916G>AMANE SELECT
NM_003319.4:c.37721G>A
NM_133378.4:c.57212G>A
NM_133432.3:c.38096G>A
NM_133437.4:c.38297G>A
NP_001243779.1:p.Arg19998Gln
NP_001254479.2:p.Arg21639Gln
NP_003310.4:p.Arg12574Gln
NP_596869.4:p.Arg19071Gln
NP_597676.3:p.Arg12699Gln
NP_597681.4:p.Arg12766Gln
LRG_391:g.251078G>A
NC_000002.11:g.179449452C>T
NM_003319.4:c.37721G>A
NR_038272.1:n.2920C>T

Protein change:

R12574Q

Links:

dbSNP: rs373282633

NCBI 1000 Genomes Browser:

rs373282633

Molecular consequence:

NM_001256850.1:c.59993G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.64916G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.37721G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.57212G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.38096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.38297G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_038272.1:n.2920C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV002620754	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Oct 25, 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

SCV002620754

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Oct 25, 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

Titin Truncating Variants in Dilated Cardiomyopathy - Prevalence and Genotype-Phenotype Correlations.

Franaszczyk M, Chmielewski P, Truszkowska G, Stawinski P, Michalak E, Rydzanicz M, Sobieszczanska-Malek M, Pollak A, Szczygieł J, Kosinska J, Parulski A, Stoklosa T, Tarnowska A, Machnicki MM, Foss-Nieradko B, Szperl M, Sioma A, Kusmierczyk M, Grzybowski J, Zielinski T, Ploski R, Bilinska ZT.

PLoS One. 2017;12(1):e0169007. doi: 10.1371/journal.pone.0169007.

PubMed [citation]

PMID:: 28045975
PMCID:: PMC5207678

Details of each submission

From Ambry Genetics, SCV002620754.2

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

Description

The p.R12574Q variant (also known as c.37721G>A), located in coding exon 137 of the TTN gene, results from a G to A substitution at nucleotide position 37721. The arginine at codon 12574 is replaced by glutamine, an amino acid with highly similar properties. This variant has been detected in a dilated cardiomyopathy cohort; however, details were not provided (Franaszczyk M et al. PLoS ONE, 2017 Jan;12:e0169007). This amino acid position is highly 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: Apr 13, 2025

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