chr2-178604882-T-C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7
The NM_001267550.2(TTN):āc.54207A>Gā(p.Pro18069=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,611,714 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P18069P) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.54207A>G | p.Pro18069= | synonymous_variant | 281/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.4069T>C | non_coding_transcript_exon_variant | 17/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.54207A>G | p.Pro18069= | synonymous_variant | 281/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.502+7201T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000290 AC: 44AN: 151896Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000404 AC: 10AN: 247224Hom.: 0 AF XY: 0.0000373 AC XY: 5AN XY: 134138
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1459700Hom.: 0 Cov.: 32 AF XY: 0.0000207 AC XY: 15AN XY: 726044
GnomAD4 genome AF: 0.000289 AC: 44AN: 152014Hom.: 0 Cov.: 32 AF XY: 0.000256 AC XY: 19AN XY: 74324
ClinVar
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 19, 2012 | p.Pro15501Pro in Exon 230 of TTN: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence. It has been identified in 1/3094 African Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS;). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 01, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 15, 2015 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Sep 11, 2020 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 08, 2016 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at