2-178577602-C-G
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PM5PP2PP3_Strong
The NM_001267550.2(TTN):c.68824G>C(p.Glu22942Gln) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,437,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E22942K) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.68824G>C | p.Glu22942Gln | missense_variant, splice_region_variant | 323/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2044-4970C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.68824G>C | p.Glu22942Gln | missense_variant, splice_region_variant | 323/363 | 5 | NM_001267550.2 | P1 | |
ENST00000604215.1 | n.500C>G | non_coding_transcript_exon_variant | 1/1 | ||||||
TTN-AS1 | ENST00000659121.1 | n.417-19994C>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000861 AC: 2AN: 232160Hom.: 0 AF XY: 0.00000796 AC XY: 1AN XY: 125668
GnomAD4 exome AF: 6.96e-7 AC: 1AN: 1437756Hom.: 0 Cov.: 35 AF XY: 0.00000140 AC XY: 1AN XY: 712740
GnomAD4 genome ? Cov.: 32
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at