NM_001267550.2(TTN):c.39539del (p.Pro13180fs) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 23, 2020
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:: RCV001350023.7

Allele description [Variation Report for NM_001267550.2(TTN):c.39539del (p.Pro13180fs)]

NM_001267550.2(TTN):c.39539del (p.Pro13180fs)

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.39539del (p.Pro13180fs)

HGVS:

NC_000002.12:g.178651462del
NG_011618.3:g.184342del
NM_001256850.1:c.35018del
NM_001267550.2:c.39539delMANE SELECT
NM_003319.4:c.13283-9144del
NM_133378.4:c.32237del
NM_133432.3:c.13658-9144del
NM_133437.4:c.13859-9144del
NP_001243779.1:p.Pro11673fs
NP_001254479.2:p.Pro13180fs
NP_596869.4:p.Pro10746fs
LRG_391:g.184342del
NC_000002.11:g.179516188del
NC_000002.11:g.179516189del

Protein change:

P10746fs

Links:

dbSNP: rs2062944024

NCBI 1000 Genomes Browser:

rs2062944024

Molecular consequence:

NM_001256850.1:c.35018del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001267550.2:c.39539del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_133378.4:c.32237del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003319.4:c.13283-9144del - intron variant - [Sequence Ontology: SO:0001627]
NM_133432.3:c.13658-9144del - intron variant - [Sequence Ontology: SO:0001627]
NM_133437.4:c.13859-9144del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

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

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2J (LGMDR10)
Synonyms:: Limb-girdle muscular dystrophy, type 2J; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 10
Identifiers:: MONDO: MONDO:0012127; MedGen: C1837342; Orphanet: 140922; OMIM: 608807

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001544395	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 23, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 25589632, 26701604, 22335739, 23975875, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001544395

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 23, 2020)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease.

Roberts AM, Ware JS, Herman DS, Schafer S, Baksi J, Bick AG, Buchan RJ, Walsh R, John S, Wilkinson S, Mazzarotto F, Felkin LE, Gong S, MacArthur JA, Cunningham F, Flannick J, Gabriel SB, Altshuler DM, Macdonald PS, Heinig M, Keogh AM, Hayward CS, et al.

Sci Transl Med. 2015 Jan 14;7(270):270ra6. doi: 10.1126/scitranslmed.3010134.

PubMed [citation]

PMID:: 25589632
PMCID:: PMC4560092

Prevalence of Titin Truncating Variants in General Population.

Akinrinade O, Koskenvuo JW, Alastalo TP.

PLoS One. 2015;10(12):e0145284. doi: 10.1371/journal.pone.0145284.

PubMed [citation]

PMID:: 26701604
PMCID:: PMC4689403

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001544395.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant has not been reported in the literature in individuals with TTN-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the TTN gene (p.Pro13180Leufs*17). While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant is located in the I band of TTN (PMID: 25589632). Truncating variants in this region have been shown to be highly prevalent in the general population and unaffected individuals (PMID: 26701604, 22335739). However, truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

ClinVar

Relating variation to medicine