2-178679958-CTCTTCT-CTCT
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM4_Supporting
The NM_001267550.2(TTN):c.33513_33515delAGA(p.Glu11172del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000942 in 1,613,002 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001267550.2 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.33513_33515delAGA | p.Glu11172del | disruptive_inframe_deletion | Exon 140 of 363 | ENST00000589042.5 | NP_001254479.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.33513_33515delAGA | p.Glu11172del | disruptive_inframe_deletion | Exon 140 of 363 | 5 | NM_001267550.2 | ENSP00000467141.1 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 151904Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000125 AC: 31AN: 248470Hom.: 0 AF XY: 0.000148 AC XY: 20AN XY: 134786
GnomAD4 exome AF: 0.0000883 AC: 129AN: 1460980Hom.: 1 AF XY: 0.0000936 AC XY: 68AN XY: 726794
GnomAD4 genome AF: 0.000151 AC: 23AN: 152022Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74328
ClinVar
Submissions by phenotype
not provided Uncertain:6Benign:1
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This variant is associated with the following publications: (PMID: 23861362) -
not specified Uncertain:1
Variant summary: TTN c.29781_29783delAGA (p.Glu9928del) results in an in-frame deletion that is predicted to remove one amino acid from the I-band region of the encoded protein. The variant allele was found at a frequency of 0.00012 in 248470 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in TTN causing Dilated Cardiomyopathy (0.00012 vs 0.00039), allowing no conclusion about variant significance. c.29781_29783delAGA has been reported in the literature in a cohort of individuals with a spectrum of coronary artery disease risk (Ng_2013), however without strong evidence for causality (e.g., lack of clinical and co-segregation data). This report therefore does not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication was ascertained in the context of this evaluation (PMID: 23861362). Four submitters have reported clinical-significance assessments for this variant to ClinVar after 2014 with conflicting interpretations (VUS, n = 3; likely benign, n = 1). Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at