rs189431308
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP2PP3
The NM_001267550.2(TTN):c.28466G>A(p.Arg9489Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,609,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R9489W) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.28466G>A | p.Arg9489Gln | missense_variant | 99/363 | ENST00000589042.5 | |
LOC124906100 | XR_007087318.1 | n.2186-3901C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.28466G>A | p.Arg9489Gln | missense_variant | 99/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-24651C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 151924Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000485 AC: 12AN: 247596Hom.: 0 AF XY: 0.0000372 AC XY: 5AN XY: 134424
GnomAD4 exome AF: 0.0000172 AC: 25AN: 1457076Hom.: 0 Cov.: 31 AF XY: 0.0000166 AC XY: 12AN XY: 724394
GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 152042Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7AN XY: 74292
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 21, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 29, 2017 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 13, 2014 | The Arg8245Gln variant in TTN has not been previously reported in individuals wi th cardiomyopathy, but has been identified in 1/120 Colombian chromosomes by the 1000 Genomes Project (http://evs.gs.washington.edu/EVS/; dbSNP rs189431308). Co mputational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to det ermine pathogenicity. In summary, the clinical significance of the Arg8245Gln va riant is uncertain. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at