rs727505345
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001267550.2(TTN):c.60002C>T(p.Pro20001Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,108 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 (★★). Synonymous variant affecting the same amino acid position (i.e. P20001P) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
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.60002C>T | p.Pro20001Leu | missense_variant | 303/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.3364+503G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.60002C>T | p.Pro20001Leu | missense_variant | 303/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-5779G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152000Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000242 AC: 6AN: 248070Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134550
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461108Hom.: 0 Cov.: 35 AF XY: 0.00000825 AC XY: 6AN XY: 726854
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152000Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74224
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 | Dec 03, 2014 | The p.Pro17433Leu variant in TTN has not been previously reported in individual with cardiomyopathy and was absent from large population studies. Computational prediction tools and conservation analysis suggest that the p.Pro17433Leu varian t may impact the protein, though this information is not predictive enough to de termine pathogenicity. In summary, the clinical significance of the p.Pro17433Le u variant is uncertain. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at