rs1021479898
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong
The NM_001267550.2(TTN):c.1662+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,611,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001267550.2 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.1662+5G>A | splice_donor_5th_base_variant, intron_variant | ENST00000589042.5 | |||
TTN | NM_133379.5 | c.1662+5G>A | splice_donor_5th_base_variant, intron_variant | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000360870.10 | c.1662+5G>A | splice_donor_5th_base_variant, intron_variant | 5 | NM_133379.5 | ||||
TTN | ENST00000589042.5 | c.1662+5G>A | splice_donor_5th_base_variant, intron_variant | 5 | NM_001267550.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1459262Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 725880
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74350
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | This sequence change falls in intron 10 of the TTN gene. It does not directly change the encoded amino acid sequence of the TTN protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 466843). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant is located in the Z band of TTN (PMID: 25589632). Non-truncating variants in this region may be clinically relevant, but have not been definitively shown to cause cardiomyopathy or neuromuscular disease (PMID: 27493940, 32778822). 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. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1838244:Tibial muscular dystrophy;C1858763:Dilated cardiomyopathy 1G;C1861065:Hypertrophic cardiomyopathy 9;C1863599:Myopathy, myofibrillar, 9, with early respiratory failure;C2673677:Early-onset myopathy with fatal cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 19, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at