rs397517729
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001267550.2(TTN):c.84553C>T(p.Arg28185Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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.84553C>T | p.Arg28185Ter | stop_gained | 326/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2043+19218G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.84553C>T | p.Arg28185Ter | stop_gained | 326/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-36017G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1460948Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726712
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 26, 2012 | Variant classified as Uncertain Significance - Favor Pathogenic. The Arg25617X v ariant in TTN has not been reported in the literature but has been detected by o ur laboratory in 1 infant with RCM of Arab ancestry who carried another cardiomy opathy variant of unknown significance. The Arg25617X variant leads to a prematu re termination codon at position 25617, which is predicted to lead to a truncate d or absent protein. Loss of function of the TTN gene is strongly associated wit h cardiomyopathy (DCM; Herman 2012). The Arg25617X variant is likely to severely impact the protein, but given that it has been detected in an individual with R CM (which is currently not associated with variants in TTN), additional studies are needed to determine its clinical significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at