chr2-178621681-A-G
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4
The NM_001267550.2(TTN):c.45143T>C(p.Ile15048Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,612,120 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. I15048M) has been classified as Uncertain significance.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Likely_benign. The variant received -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.45143T>C | p.Ile15048Thr | missense_variant | Exon 245 of 363 | ENST00000589042.5 | NP_001254479.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.45143T>C | p.Ile15048Thr | missense_variant | Exon 245 of 363 | 5 | NM_001267550.2 | ENSP00000467141.1 |
Frequencies
GnomAD3 genomes AF: 0.0000198 AC: 3AN: 151870Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00000812 AC: 2AN: 246370 AF XY: 0.0000150 show subpopulations
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1460250Hom.: 0 Cov.: 32 AF XY: 0.00000964 AC XY: 7AN XY: 726400 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000198 AC: 3AN: 151870Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74140 show subpopulations
ClinVar
Submissions by phenotype
not specified Uncertain:1
The Ile12480Thr variant in TTN has not been previously reported in individuals w ith cardiomyopathy and was absent from large population studies. Computational p rediction tools and conservation analysis do not provide strong support for or a gainst an impact to the protein. In summary, the clinical significance of the Il e12480Thr variant is uncertain. -
TTN-related disorder Uncertain:1
The TTN c.45143T>C variant is predicted to result in the amino acid substitution p.Ile15048Thr. This variant was reported in an individual with left ventricular noncompaction (Table S2, Mazzarotto et al. 2021. PubMed ID: 33500567). This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Cardiomyopathy Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at