rs876657672
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_001267550.2(TTN):c.99866-1G>A variant causes a splice acceptor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_001267550.2 splice_acceptor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.99866-1G>A | splice_acceptor_variant, intron_variant | Intron 355 of 362 | ENST00000589042.5 | NP_001254479.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.99866-1G>A | splice_acceptor_variant, intron_variant | Intron 355 of 362 | 5 | NM_001267550.2 | ENSP00000467141.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Primary dilated cardiomyopathy Pathogenic:1
The c.92162-1G>A variant in TTN has not been previously reported in individuals with cardiomyopathy or in large population studies. This variant occurs in the i nvariant region (+/- 1,2) of the splice consensus sequence and is predicted to c ause altered splicing leading to an abnormal or absent protein. Splice and other truncating variants in TTN are strongly associated with DCM if they are located in the exons encoding for the A-band region (exons 201-306) of the protein (Her man 2012, Pugh 2014), where this variant is located. In summary, although additi onal studies are required to fully establish its clinical significance, the c.92 162-1G>A variant is likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at