rs727503684
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001267550.2(TTN):c.8953A>T(p.Thr2985Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,750 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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Synonymous variant affecting the same amino acid position (i.e. T2985T) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.8953A>T | p.Thr2985Ser | missense_variant | 38/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.8953A>T | p.Thr2985Ser | missense_variant | 38/46 | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.8953A>T | p.Thr2985Ser | missense_variant | 38/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.8953A>T | p.Thr2985Ser | missense_variant | 38/46 | 5 | NM_133379.5 | ||
TTN-AS1 | ENST00000659121.1 | n.1593-4392T>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251100Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135730
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461750Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727170
GnomAD4 genome Cov.: 31
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 | Jan 31, 2014 | The Thr2985Ser variant in TTN has not been previously reported in individuals wi th cardiomyopathy or in large population studies. Computational analyses (amino acid biochemical properties, conservation, SIFT, PolyPhen-2, AlignGVGD) suggest this variant may impact the protein, though this information is not predictive e nough to determine pathogenicity. In summary, additional information is needed to fully assess the clinical significance of this variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at