rs397517522
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001267550.2(TTN):āc.2359A>Gā(p.Ile787Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 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. I787T) 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.2359A>G | p.Ile787Val | missense_variant | 14/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.2359A>G | p.Ile787Val | missense_variant | 14/46 | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.2359A>G | p.Ile787Val | missense_variant | 14/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.2359A>G | p.Ile787Val | missense_variant | 14/46 | 5 | NM_133379.5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461830Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727220
GnomAD4 genome ? Cov.: 32
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 | Jul 02, 2012 | Variant classified as Uncertain Significance - Favor Benign. The Ile787Val varia nt in TTN has not been reported in the literature, but has been identified in 1 individual with DCM tested by our laboratory. This variant has not been identifi ed in a very large and broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS). This low frequency is consistent with a diseas e causing role, but insufficient to establish this with confidence. However, thi s amino acid is not well conserved in evolution and other species (chicken and f rog) carry the mutant amino acid (valine), suggesting that this change may be to lerated. Computational analyses (biochemical amino acid properties, AlignGVGD, P olyPhen2, and SIFT) do not provide strong support for or against an impact to th e protein. In summary, this variant is more likely benign, but additional inform ation is needed to fully assess its clinical significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at