rs200321239
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_001267550.2(TTN):c.33367G>A(p.Ala11123Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,611,652 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
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 | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.33367G>A | p.Ala11123Thr | missense_variant | 139/363 | ENST00000589042.5 | |
LOC124906100 | XR_007087318.1 | n.2186-33449C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.33367G>A | p.Ala11123Thr | missense_variant | 139/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-54199C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 151930Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000769 AC: 19AN: 247164Hom.: 1 AF XY: 0.0000671 AC XY: 9AN XY: 134080
GnomAD4 exome AF: 0.0000288 AC: 42AN: 1459604Hom.: 1 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 726038
GnomAD4 genome ? AF: 0.000145 AC: 22AN: 152048Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74332
ClinVar
Submissions by phenotype
not provided Uncertain:3Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 12, 2016 | - - |
not provided, no classification provided | clinical testing | GeneDx | Feb 12, 2014 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 27, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 21, 2022 | The TTN c.33367G>A; p.Ala11123Thr variant (rs200321239; ClinVar Variation ID: 202579) is rare in the general population (<0.2% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p.Ala11123Thr variant cannot be determined with certainty. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 01, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at