rs397517501
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_001267550.2(TTN):c.22241-5T>C 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 0.000064 in 1,609,132 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
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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.22241-5T>C | 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.22241-5T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001267550.2 | P1 | |||
TTN-AS1 | ENST00000659121.1 | n.503-11953A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152142Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000408 AC: 10AN: 245080Hom.: 0 AF XY: 0.0000451 AC XY: 6AN XY: 132928
GnomAD4 exome AF: 0.0000652 AC: 95AN: 1456990Hom.: 0 Cov.: 34 AF XY: 0.0000552 AC XY: 40AN XY: 724238
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152142Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74304
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 | May 01, 2012 | The 18509-5T>C variant (TTN) has not been reported in the literature nor previou sly identified by our laboratory. It was absent from >3,000 European American in dividuals sequenced by the NHLBI exome sequencing project (http://evs.gs.washing ton.edu/EVS). This low frequency is consistent with a disease causing role but i nsufficient to establish this with confidence. This variant is located in the 3 ' splice region. Computational tools do not predict altered splicing. However, t his information is not predictive enough to rule out pathogenicity. In summary, additional information is needed to fully assess the clinical significance of th e 18509-5T>C variant. - |
TTN-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 09, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 11, 2019 | This variant is associated with the following publications: (PMID: 24503780) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at