rs727504986
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4BP6
The NM_001267550.2(TTN):c.49366C>T(p.Arg16456Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000933 in 1,608,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R16456H) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.49366C>T | p.Arg16456Cys | missense_variant | 263/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.49366C>T | p.Arg16456Cys | missense_variant | 263/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.502+16236G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 151908Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000820 AC: 2AN: 244030Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132286
GnomAD4 exome AF: 0.00000824 AC: 12AN: 1456170Hom.: 0 Cov.: 32 AF XY: 0.0000111 AC XY: 8AN XY: 723874
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 151908Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74164
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 | Mar 19, 2014 | The Arg13888Cys variant in TTN has not been previously reported in individuals w ith cardiomyopathy or in large population studies. Computational prediction tool s and conservation analysis do not provide strong support for or against an impa ct to the protein. Additional information is needed to fully assess the clinical significance of the variant. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 23, 2018 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at