rs370135800
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):āc.89893A>Gā(p.Ile29965Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,611,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
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.89893A>G | p.Ile29965Val | missense_variant | 335/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2043+10646T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.89893A>G | p.Ile29965Val | missense_variant | 335/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.416+29371T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152208Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246756Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 133994
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459476Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 726132
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74352
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 | Dec 08, 2016 | Variant classified as Uncertain Significance - Favor Benign. The p.Ile27397Val v ariant in TTN has not been previously reported in individuals with cardiomyopath y, but has been identified in 2/9770 African chromosomes by the Exome Aggregatio n Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs370135800). Isoleuci ne (Ile) at position 27397 is not conserved in mammals or evolutionarily distant species, and 17 species (including 2 mammals) carry a valine (Val) at this posi tion, supporting that this change may be tolerated. Additional computational pre diction tools suggest that the p.Ile27397Val variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Ile27397Val variant is uncerta in, these data suggest that it is more likely to be benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at