rs10580462
Positions:
- chr2-178647040-GTATATATATA-G
- chr2-178647040-GTATATATATA-GTATA
- chr2-178647040-GTATATATATA-GTATATA
- chr2-178647040-GTATATATATA-GTATATATA
- chr2-178647040-GTATATATATA-GTATATATATATA
- chr2-178647040-GTATATATATA-GTATATATATATATA
- chr2-178647040-GTATATATATA-GTATATATATATATATA
- chr2-178647040-GTATATATATA-GTATATATATATATATATA
- chr2-178647040-GTATATATATA-GTATATATATATATATATATA
- chr2-178647040-GTATATATATA-GTATATATATATATATATATATA
- chr2-178647040-GTATATATATA-GTATATATATATATATATATATATA
- chr2-178647040-GTATATATATA-GTATATATATATATATATATATATATA
- chr2-178647040-GTATATATATA-GTATATATATATATATATATATATATATA
- chr2-178647040-GTATATATATA-GTATATATATATATATATATATATATATATA
- chr2-178647040-GTATATATATA-GTATATATATATATATATATATATATATATATA
- chr2-178647040-GTATATATATA-GTATATATATATATATATATATATATATATATATA
- chr2-178647040-GTATATATATA-GTATATATATATATATATATATATATATATATATATA
- chr2-178647040-GTATATATATA-GTATATATATATATATATATATATATATATATATATATA
- chr2-178647040-GTATATATATA-GTATATATATATATATATATATATATATATATATATATATATA
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate
The NM_001267550.2(TTN):c.40222+14_40222+23del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 731,396 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000070 ( 0 hom., cov: 21)
Exomes 𝑓: 0.0000017 ( 0 hom. )
Consequence
TTN
NM_001267550.2 intron
NM_001267550.2 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.346
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]
TTN-AS1 (HGNC:44124): (TTN antisense RNA 1) This gene encodes a non-coding RNA transcribed from the opposite strand to the titin gene. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 2-178647040-GTATATATATA-G is Benign according to our data. Variant chr2-178647040-GTATATATATA-G is described in ClinVar as [Likely_benign]. Clinvar id is 2168350.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.40222+14_40222+23del | intron_variant | ENST00000589042.5 | |||
LOC124906100 | XR_007087318.1 | n.2185+2552_2185+2561del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.40222+14_40222+23del | intron_variant | 5 | NM_001267550.2 | P1 | |||
TTN-AS1 | ENST00000659121.1 | n.502+49372_502+49381del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000698 AC: 1AN: 143282Hom.: 0 Cov.: 21
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GnomAD4 exome AF: 0.00000170 AC: 1AN: 588114Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 292410
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GnomAD4 genome ? AF: 0.00000698 AC: 1AN: 143282Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 69468
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2022 | - - |
Computational scores
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Name
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at