NM_001267550.2(TTN):c.64245G>A (p.Trp21415Ter) AND Dilated cardiomyopathy 1G

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 3, 2023
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:: RCV003111528.3

Allele description [Variation Report for NM_001267550.2(TTN):c.64245G>A (p.Trp21415Ter)]

NM_001267550.2(TTN):c.64245G>A (p.Trp21415Ter)

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.64245G>A (p.Trp21415Ter)

HGVS:

NC_000002.12:g.178586656C>T
NG_011618.3:g.249147G>A
NG_051363.1:g.68830C>T
NM_001256850.1:c.59322G>A
NM_001267550.2:c.64245G>AMANE SELECT
NM_003319.4:c.37050G>A
NM_133378.4:c.56541G>A
NM_133432.3:c.37425G>A
NM_133437.4:c.37626G>A
NP_001243779.1:p.Trp19774Ter
NP_001254479.1:p.Trp21415Ter
NP_001254479.2:p.Trp21415Ter
NP_003310.4:p.Trp12350Ter
NP_596869.4:p.Trp18847Ter
NP_597676.3:p.Trp12475Ter
NP_597681.4:p.Trp12542Ter
LRG_391t1:c.64245G>A
LRG_391:g.249147G>A
LRG_391p1:p.Trp21415Ter
NC_000002.11:g.179451383C>T
NM_001267550.1:c.64245G>A

Protein change:

W12350*

Molecular consequence:

NM_001256850.1:c.59322G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001267550.2:c.64245G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_003319.4:c.37050G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_133378.4:c.56541G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_133432.3:c.37425G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_133437.4:c.37626G>A - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Dilated cardiomyopathy 1G (CMD1G)
Identifiers:: MONDO: MONDO:0011400; MedGen: C1858763; Orphanet: 154; OMIM: 604145

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003762208	Servicio Canario de Salud, Hospital Universitario Nuestra Sra. de Candelaria	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 3, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003762208

Servicio Canario de Salud, Hospital Universitario Nuestra Sra. de Candelaria

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 3, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
caucasian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Servicio Canario de Salud, Hospital Universitario Nuestra Sra. de Candelaria, SCV003762208.2

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

Description

The c.64245G>A (p.Trp21415Ter) TTN variant has been reported in our laboratory in a 41-year-old male patient (diagnosis with 29 years) and his father (64 years, diagnosis with 60 years), both with a clinical diagnosis of Dilated CardioMyopathy. His 34-year-old brother, asymptomatic, did not have the variant. This variant has never been reported in TTN related-disorders. This variant was absent from large population studies (gnomAD no frequency). In summary, the available evidence for c.64245G>A (p.Trp21415Ter) TTN variant meets our criteria to be classified as Likely Pathogenic based upon its absence from controls and the clinical correlation in this patient´s phenotype

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Mar 5, 2024

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