rs727503629
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001267550.2(TTN):c.42649G>A(p.Glu14217Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.42649G>A | p.Glu14217Lys | missense_variant | 231/363 | ENST00000589042.5 | NP_001254479.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.42649G>A | p.Glu14217Lys | missense_variant | 231/363 | 5 | NM_001267550.2 | ENSP00000467141.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152102Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248488Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134800
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461136Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726864
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74274
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 | Mar 24, 2014 | Variant classified as Uncertain Significance - Favor Benign. The Glu11649Lys var iant in TTN has not been previously reported in individuals with cardiomyopathy or in large population studies. Computational prediction tools and conservation analysis suggest that this variant may not impact the protein, with most mammals and other species carrying a different amino acid at this position. However, th is information is not predictive enough to rule out pathogenicity. At this time, additional information is needed to fully assess the clinical significance of t he Glu11649Lys variant. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 11, 2019 | The p.E5152K variant (also known as c.15454G>A), located in coding exon 58 of the TTN gene, results from a G to A substitution at nucleotide position 15454. The glutamic acid at codon 5152 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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