NM_001267550.2(TTN):c.96069dup (p.Val32024fs) AND Dilated cardiomyopathy 1G

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 1, 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:: RCV000232804.1

Allele description [Variation Report for NM_001267550.2(TTN):c.96069dup (p.Val32024fs)]

NM_001267550.2(TTN):c.96069dup (p.Val32024fs)

Genes:

LOC126806421:CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:179407630-179408829 [Gene]
TTN-AS1:TTN antisense RNA 1 [Gene - HGNC]
TTN:titin [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.96069dup (p.Val32024fs)

HGVS:

NC_000002.12:g.178544075dup
NG_011618.3:g.291728dup
NG_051363.1:g.26249dup
NM_001256850.1:c.91146dup
NM_001267550.2:c.96069dupMANE SELECT
NM_003319.4:c.68874dup
NM_133378.4:c.88365dup
NM_133432.3:c.69249dup
NM_133437.4:c.69450dup
NP_001243779.1:p.Val30383fs
NP_001254479.2:p.Val32024fs
NP_003310.4:p.Val22959fs
NP_596869.4:p.Val29456fs
NP_597676.3:p.Val23084fs
NP_597681.4:p.Val23151fs
LRG_391:g.291728dup
NC_000002.11:g.179408801_179408802insA
NC_000002.11:g.179408802dup
NM_001267550.2:c.96069dupTMANE SELECT

Protein change:

V22959fs

Links:

dbSNP: rs878854432

NCBI 1000 Genomes Browser:

rs878854432

Molecular consequence:

NM_001256850.1:c.91146dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001267550.2:c.96069dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003319.4:c.68874dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_133378.4:c.88365dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_133432.3:c.69249dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_133437.4:c.69450dup - 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
SCV000286938	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 1, 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

SCV000286938

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 1, 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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000286938.2

#	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 duplicates 1 nucleotide in exon 346 of the TTN mRNA (c.96069dupT), causing a frameshift at codon 32024. This creates a premature translational stop signal (p.Val32024Cysfs*31) and is expected to result in an absent or disrupted protein product. This variant is found in the A-band of this gene. While this particular variant has not been reported in the literature, truncating variants in the A-band 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: Feb 28, 2024

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