rs886042115
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001267550.2(TTN):c.29024C>A(p.Ser9675Ter) variant causes a stop gained 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. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S9675S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001267550.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.29024C>A | p.Ser9675Ter | stop_gained | 100/363 | ENST00000589042.5 | |
LOC124906100 | XR_007087318.1 | n.2186-6211G>T | intron_variant, non_coding_transcript_variant | ||||
LOC124907912 | XR_007087321.1 | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.29024C>A | p.Ser9675Ter | stop_gained | 100/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-26961G>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 33
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 | Feb 19, 2018 | This sequence change results in a premature translational stop signal in the TTN gene (p.Ser9675*). While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TTN-related disease. ClinVar contains an entry for this variant (Variation ID: 281227). In summary, although this is a novel truncating variant, truncating variants in this region of the TTN gene have been shown to be highly prevalent in the TTN gene in the general population and unaffected individuals (PMID: 26701604, 22335739). However, truncating mutations in this region have also been reported to cause autosomal recessive congenital myopathy (PMID: 23975875). Therefore without additional functional and/or genetic data, this variant has been classified as a Variant of Uncertain Significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 08, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at