rs397517672
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001267550.2(TTN):āc.6029A>Gā(p.Tyr2010Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y2010F) has been classified as Uncertain significance.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.6029A>G | p.Tyr2010Cys | missense_variant | 28/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.6029A>G | p.Tyr2010Cys | missense_variant | 28/46 | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.6029A>G | p.Tyr2010Cys | missense_variant | 28/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.6029A>G | p.Tyr2010Cys | missense_variant | 28/46 | 5 | NM_133379.5 | ||
TTN-AS1 | ENST00000659121.1 | n.3262T>C | non_coding_transcript_exon_variant | 12/13 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 250964Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135642
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461772Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727200
GnomAD4 genome ? Cov.: 32
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 Tyr2010Cys variant in TTN has not been reported in the literature nor previo usly identified by our laboratory. Computational analyses (biochemical amino aci d properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide stron g support for or against an impact to the protein. Additional information is nee ded to fully assess the clinical significance of the Tyr2010Cys variant. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 21, 2018 | The p.Y1964C variant (also known as c.5891A>G), located in coding exon 26 of the TTN gene, results from an A to G substitution at nucleotide position 5891. The tyrosine at codon 1964 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at