rs776953525
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):c.65158C>A(p.Pro21720Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict 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. P21720L) has been classified as Uncertain significance.
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.65158C>A | p.Pro21720Thr | missense_variant | 311/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2768-180G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.65158C>A | p.Pro21720Thr | missense_variant | 311/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-13203G>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152076Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000242 AC: 6AN: 248198Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134644
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461154Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726870
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152076Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74270
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 | Aug 12, 2015 | The p.Pro19152Thr variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 2/66502 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Prolin e (Pro) at position 19152 is poorly conserved in evolution and 12 fish species c arry a threonine (Thr), supporting that this change may be tolerated. In summary , the clinical significance of the p.Pro19152Thr variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at