2-178597667-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001267550.2(TTN):āc.57415A>Cā(p.Ile19139Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I19139T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001267550.2 missense
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.57415A>C | p.Ile19139Leu | missense_variant | 294/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.3436T>G | non_coding_transcript_exon_variant | 13/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.57415A>C | p.Ile19139Leu | missense_variant | 294/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.488T>G | non_coding_transcript_exon_variant | 2/13 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152060Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152060Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74260
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 | May 31, 2012 | The Ile16571Leu variant in TTN has not been identified in large and broad popula tions screened by the NHLBI Exome Sequencing Project (http://evs.gs.washington.e du/EVS). This low frequency is consistent with a disease causing role but insuff icient to establish this with confidence. Computational analyses (biochemical am ino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Ile16571Leu variant may not impact the protein, though this information is n ot predictive enough to rule out pathogenicity. Additional information is needed to fully assess the clinical significance of the Ile16571Leu variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at