NM_001267550.2(TTN):c.52731_52732del (p.Arg17577fs) AND Dilated cardiomyopathy 1G

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 18, 2016
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:: RCV000227749.2

Allele description [Variation Report for NM_001267550.2(TTN):c.52731_52732del (p.Arg17577fs)]

NM_001267550.2(TTN):c.52731_52732del (p.Arg17577fs)

Genes:

LOC126806425:BRD4-independent group 4 enhancer GRCh37_chr2:179471933-179473132 [Gene]
TTN-AS1:TTN antisense RNA 1 [Gene - HGNC]
TTN:titin [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.52731_52732del (p.Arg17577fs)

HGVS:

NC_000002.11:g.179472782_179472783del
NC_000002.12:g.178608055CT[1]
NG_011618.3:g.227745AG[1]
NG_051363.1:g.90229CT[1]
NM_001256850.1:c.47808_47809del
NM_001267550.2:c.52731_52732delMANE SELECT
NM_003319.4:c.25536_25537del
NM_133378.4:c.45027_45028del
NM_133432.3:c.25911_25912del
NM_133437.4:c.26112_26113del
NP_001243779.1:p.Arg15936fs
NP_001254479.2:p.Arg17577fs
NP_003310.4:p.Arg8512fs
NP_596869.4:p.Arg15009fs
NP_597676.3:p.Arg8637fs
NP_597681.4:p.Arg8704fs
LRG_391t1:c.52731_52732del
LRG_391:g.227745AG[1]
NC_000002.11:g.179472782CT[1]
NC_000002.11:g.179472782_179472783del
NC_000002.11:g.179472782_179472783delCT
NM_001256850.1:c.47808_47809delAG
NM_001267550.1:c.52731_52732del
NM_001267550.2:c.52731_52732delAGMANE SELECT
NM_003319.4:c.25536_25537delAG

Protein change:

R15009fs

Links:

dbSNP: rs878854315

NCBI 1000 Genomes Browser:

rs878854315

Molecular consequence:

NM_001256850.1:c.47808_47809del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001267550.2:c.52731_52732del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003319.4:c.25536_25537del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_133378.4:c.45027_45028del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_133432.3:c.25911_25912del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_133437.4:c.26112_26113del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000286710	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Feb 18, 2016)	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

SCV000286710

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Feb 18, 2016)

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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000286710.2

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

Description

This sequence change deletes 2 nucleotides from exon 276 of the TTN mRNA (c.52731_52732del), causing a frameshift at codon 17577. This creates a premature translational stop signal (p.Arg17577Serfs*3) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in this region of TTN are likely pathogenic (PMID: 25589632). For these reasons, this variant has been classified as Likely Pathogenic.

#	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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