rs727504767
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001267550.2(TTN):c.52406-6T>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,420,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001267550.2 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.52406-6T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.52406-6T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001267550.2 | P1 | |||
TTN-AS1 | ENST00000659121.1 | n.502+10802A>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 7.04e-7 AC: 1AN: 1420206Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1AN XY: 703482
GnomAD4 genome ? Cov.: 33
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 | Sep 27, 2013 | The 44702-6T>A variant in TTN has not been previously reported in individuals wi th cardiomyopathy. Data from large population studies is insufficient to assess the frequency of this variant. This variant is located in the 3' splice region. Computational tools do not suggest an impact to splicing. However, this informa tion is not predictive enough to rule out pathogenicity. Additional information is needed to fully assess the clinical significance of the 44702-6T>A variant. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 16, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at