chr2-178729503-A-C
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3
The NM_001267550.2(TTN):c.18653T>G(p.Leu6218Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. L6218L) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.18653T>G | p.Leu6218Arg | missense_variant | Exon 64 of 363 | ENST00000589042.5 | NP_001254479.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.18653T>G | p.Leu6218Arg | missense_variant | Exon 64 of 363 | 5 | NM_001267550.2 | ENSP00000467141.1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152100Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000121 AC: 3AN: 248380 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461340Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 726964 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152100Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74282 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Uncertain:1
The Leu4974Arg variant in TTN has not been previously reported in individuals wi th cardiomyopathy or in large population studies. Computational prediction tools and conservation analysis do not provide strong support for or against an impac t to the protein. In summary, the clinical significance of the Leu4974Arg varian t is uncertain. -
not provided Uncertain:1
Not observed at significant frequency in large population cohorts (gnomAD); Missense variant in a gene in which most reported pathogenic variants are truncating/loss of function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23975875) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at