rs376616067
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_001267550.2(TTN):āc.82684T>Cā(p.Tyr27562His) variant causes a missense change. The variant allele was found at a frequency of 0.0000595 in 1,613,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.82684T>C | p.Tyr27562His | missense_variant | 326/363 | ENST00000589042.5 | NP_001254479.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.82684T>C | p.Tyr27562His | missense_variant | 326/363 | 5 | NM_001267550.2 | ENSP00000467141.1 |
Frequencies
GnomAD3 genomes AF: 0.000316 AC: 48AN: 152064Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000644 AC: 16AN: 248348Hom.: 0 AF XY: 0.0000520 AC XY: 7AN XY: 134712
GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461446Hom.: 0 Cov.: 37 AF XY: 0.0000344 AC XY: 25AN XY: 727006
GnomAD4 genome AF: 0.000315 AC: 48AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.000229 AC XY: 17AN XY: 74392
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 07, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 26, 2021 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 25, 2016 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 15, 2018 | The p.Y18497H variant (also known as c.55489T>C), located in coding exon 153 of the TTN gene, results from a T to C substitution at nucleotide position 55489. The tyrosine at codon 18497 is replaced by histidine, an amino acid with some similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at