rs565140436
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_133379.5(TTN):c.14399G>A(p.Gly4800Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,612,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G4800W) has been classified as Likely benign.
Frequency
Consequence
NM_133379.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_133379.5 | c.14399G>A | p.Gly4800Glu | missense_variant | 46/46 | ENST00000360870.10 | NP_596870.2 | |
TTN | NM_001267550.2 | c.11311+5123G>A | intron_variant | ENST00000589042.5 | NP_001254479.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000360870.10 | c.14399G>A | p.Gly4800Glu | missense_variant | 46/46 | 5 | NM_133379.5 | ENSP00000354117 | ||
TTN | ENST00000589042.5 | c.11311+5123G>A | intron_variant | 5 | NM_001267550.2 | ENSP00000467141 | P1 | |||
TTN-AS1 | ENST00000659121.1 | n.1223+5031C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 151910Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000879 AC: 22AN: 250316Hom.: 0 AF XY: 0.0000813 AC XY: 11AN XY: 135290
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1460904Hom.: 0 Cov.: 35 AF XY: 0.00000963 AC XY: 7AN XY: 726746
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152028Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74324
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 22, 2015 | p.Gly4800Glu in exon 45A of TTN: This variant is not expected to have clinical s ignificance due to a lack of conservation across species, including mammals. Of note, chimp, cat, and armadillo have a glutamic acid (Glu) at this position. It has also been identified 0.1% (12/8464) of East Asian chromosomes by the Exome A ggregation Consortium (http://exac.broadinstitute.org). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at