2-178751117-C-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_133379.5(TTN):c.11283G>A(p.Lys3761Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
TTN
NM_133379.5 synonymous
NM_133379.5 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.47
Publications
0 publications found
Genes affected
TTN (HGNC:12403): (titin) This gene encodes a large abundant protein of striated muscle. The product of this gene is divided into two regions, a N-terminal I-band and a C-terminal A-band. The I-band, which is the elastic part of the molecule, contains two regions of tandem immunoglobulin domains on either side of a PEVK region that is rich in proline, glutamate, valine and lysine. The A-band, which is thought to act as a protein-ruler, contains a mixture of immunoglobulin and fibronectin repeats, and possesses kinase activity. An N-terminal Z-disc region and a C-terminal M-line region bind to the Z-line and M-line of the sarcomere, respectively, so that a single titin molecule spans half the length of a sarcomere. Titin also contains binding sites for muscle associated proteins so it serves as an adhesion template for the assembly of contractile machinery in muscle cells. It has also been identified as a structural protein for chromosomes. Alternative splicing of this gene results in multiple transcript variants. Considerable variability exists in the I-band, the M-line and the Z-disc regions of titin. Variability in the I-band region contributes to the differences in elasticity of different titin isoforms and, therefore, to the differences in elasticity of different muscle types. Mutations in this gene are associated with familial hypertrophic cardiomyopathy 9, and autoantibodies to titin are produced in patients with the autoimmune disease scleroderma. [provided by RefSeq, Feb 2012]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP7
Synonymous conserved (PhyloP=-1.47 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_133379.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TTN | TSL:5 MANE Select | c.11311+2007G>A | intron | N/A | ENSP00000467141.1 | Q8WZ42-12 | |||
| TTN | TSL:1 | c.11311+2007G>A | intron | N/A | ENSP00000408004.2 | A0A1B0GXE3 | |||
| TTN | TSL:1 | c.11035+2007G>A | intron | N/A | ENSP00000405517.2 | A0A0C4DG59 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460732Hom.: 0 Cov.: 73 AF XY: 0.00000138 AC XY: 1AN XY: 726654 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1460732
Hom.:
Cov.:
73
AF XY:
AC XY:
1
AN XY:
726654
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33442
American (AMR)
AF:
AC:
0
AN:
44650
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26072
East Asian (EAS)
AF:
AC:
0
AN:
39638
South Asian (SAS)
AF:
AC:
1
AN:
86204
European-Finnish (FIN)
AF:
AC:
0
AN:
53212
Middle Eastern (MID)
AF:
AC:
0
AN:
5750
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111428
Other (OTH)
AF:
AC:
0
AN:
60336
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.