rs397517486
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001267550.2(TTN):c.1399-3C>T 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 0.0000372 in 1,613,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.1399-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000589042.5 | |||
TTN | NM_133379.5 | c.1399-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000360870.10 | c.1399-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_133379.5 | ||||
TTN | ENST00000589042.5 | c.1399-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001267550.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152122Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250878Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135642
GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461196Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 726926
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74426
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 14, 2012 | The 1399-3C>T variant in TTN has not been reported in the literature nor previou sly identified by our laboratory. This variant is located in the 3' splice regio n. Computational tools do not suggest an impact to splicing, though this informa tion is not predictive enough to rule out pathogenicity. Additional information is needed to fully assess the clinical significance of this variant. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2017 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 14, 2021 | The c.1399-3C>T intronic variant results from a C to T substitution 3 nucleotides upstream from coding exon 8 in the TTN gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 21, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at