rs372384272
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):c.43702G>A(p.Val14568Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000497 in 1,608,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V14568V) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.43702G>A | p.Val14568Ile | missense_variant | 236/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.43702G>A | p.Val14568Ile | missense_variant | 236/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.502+34511C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152078Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000416 AC: 1AN: 240552Hom.: 0 AF XY: 0.00000767 AC XY: 1AN XY: 130362
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1456774Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2AN XY: 724224
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152078Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74250
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 | Apr 08, 2015 | The p.Val12000Ile variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 1/3734 African American chromos omes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; d bSNP rs372384272). Computational prediction tools and conservation analysis do n ot provide strong support for or against an impact to the protein, though 2 mamm als (tenrec and aardvark) carry an isoleucine (Ile) at this position raising the possibility that this change would be tolerated. In summary, the clinical signi ficance of the p.Val12000Ile variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at