2-178733515-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001267550.2(TTN):c.15778C>A(p.Pro5260Thr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,608,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. P5260S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001267550.2 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.15778C>A | p.Pro5260Thr | missense_variant, splice_region_variant | 54/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.15778C>A | p.Pro5260Thr | missense_variant, splice_region_variant | 54/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-989G>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152130Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246410Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 133640
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1456594Hom.: 0 Cov.: 36 AF XY: 0.00000414 AC XY: 3AN XY: 723774
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152130Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74300
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 05, 2014 | The Pro4016Thr 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 Pro4016Thr varian t is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at