NM_001267550.2(TTN):c.11984C>T (p.Thr3995Ile) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 28, 2024
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:: RCV004690132.1

Allele description [Variation Report for NM_001267550.2(TTN):c.11984C>T (p.Thr3995Ile)]

NM_001267550.2(TTN):c.11984C>T (p.Thr3995Ile)

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.11984C>T (p.Thr3995Ile)

HGVS:

NC_000002.12:g.178741249G>A
NG_011618.3:g.94554C>T
NM_001256850.1:c.11033C>T
NM_001267550.2:c.11984C>TMANE SELECT
NM_003319.4:c.10895C>T
NM_133378.4:c.10361-2889C>T
NM_133432.3:c.11270C>T
NM_133437.4:c.11471C>T
NP_001243779.1:p.Thr3678Ile
NP_001254479.2:p.Thr3995Ile
NP_003310.4:p.Thr3632Ile
NP_597676.3:p.Thr3757Ile
NP_597681.4:p.Thr3824Ile
LRG_391t1:c.11984C>T
LRG_391:g.94554C>T
NC_000002.11:g.179605976G>A
NM_001267550.1:c.11984C>T
NM_133378.4:c.10361-2889C>T

Protein change:

T3632I

Links:

dbSNP: rs749320093

NCBI 1000 Genomes Browser:

rs749320093

Molecular consequence:

NM_133378.4:c.10361-2889C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001256850.1:c.11033C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.11984C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.10895C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.11270C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.11471C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005184467	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (May 28, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005184467

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(May 28, 2024)

germline

clinical testing

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005184467.1

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

Description

Variant summary: TTN c.10361-2889C>T (NM_133378.4) is located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. In addition, this variant results in a missense change in a different transcript (NM_001267550.2), c.11984C>T (p.Thr3995Ile), which is located to the I-band region of the encoded protein sequence. The variant allele was found at a frequency of 1.2e-05 in 248358 control chromosomes (gnomAD v2.1). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.10361-2889C>T in individuals affected with Limb-Girdle Muscular Dystrophy, Type 2J and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1328760). Based on the evidence outlined above, the variant was classified as 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: Aug 18, 2024

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