rs878854432
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001267550.2(TTN):c.96069_96070insT(p.Val32024CysfsTer31) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,070 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. T32023T) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001267550.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.96069_96070insT | p.Val32024CysfsTer31 | frameshift_variant | 346/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2043+1714dup | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.96069_96070insT | p.Val32024CysfsTer31 | frameshift_variant | 346/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.416+20439dup | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461070Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 726780
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 01, 2016 | For these reasons, this variant has been classified as Likely Pathogenic. This variant is found in the A-band of this gene. While this particular variant has not been reported in the literature, truncating variants in the A-band of TTN are likely pathogenic (PMID: 25589632). This sequence change duplicates 1 nucleotide in exon 346 of the TTN mRNA (c.96069dupT), causing a frameshift at codon 32024. This creates a premature translational stop signal (p.Val32024Cysfs*31) and is expected to result in an absent or disrupted protein product. - |
Dilated cardiomyopathy 1G Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 01, 2016 | This sequence change duplicates 1 nucleotide in exon 346 of the TTN mRNA (c.96069dupT), causing a frameshift at codon 32024. This creates a premature translational stop signal (p.Val32024Cysfs*31) and is expected to result in an absent or disrupted protein product. This variant is found in the A-band of this gene. While this particular variant has not been reported in the literature, truncating variants in the A-band of TTN are likely pathogenic (PMID: 25589632). For these reasons, this variant has been classified as Likely Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at