rs750806089
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):āc.89515A>Gā(p.Ile29839Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,593,676 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 Conflicting classifications of pathogenicity (no stars).
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.89515A>G | p.Ile29839Val | missense_variant | 335/363 | ENST00000589042.5 | NP_001254479.2 | |
TTN-AS1 | NR_038272.1 | n.2043+11024T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.89515A>G | p.Ile29839Val | missense_variant | 335/363 | 5 | NM_001267550.2 | ENSP00000467141 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.416+29749T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000296 AC: 7AN: 236354Hom.: 0 AF XY: 0.0000234 AC XY: 3AN XY: 128374
GnomAD4 exome AF: 0.0000118 AC: 17AN: 1441470Hom.: 0 Cov.: 33 AF XY: 0.0000112 AC XY: 8AN XY: 715012
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74356
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 21, 2023 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 14, 2019 | - - |
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 30, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 22, 2015 | The p.Ile27271Val variant in TTN has not been previously reported in individuals with cardiomyopathy but has been identified in 2/11502 Latino chromosomes and 1 /9636 African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac .broadinstitute.org). Computational prediction tools and conservation analysis d o not provide strong support for or against an impact to the protein. In summary , the clinical significance of the p.Ile27271Val variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at