rs754182768
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001267550.2(TTN):c.427G>A(p.Glu143Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,614,004 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E143E) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.427G>A | p.Glu143Lys | missense_variant | 4/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.427G>A | p.Glu143Lys | missense_variant | 4/46 | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.427G>A | p.Glu143Lys | missense_variant | 4/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.427G>A | p.Glu143Lys | missense_variant | 4/46 | 5 | NM_133379.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251330Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135824
GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461840Hom.: 0 Cov.: 31 AF XY: 0.0000454 AC XY: 33AN XY: 727224
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74330
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 10, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 18, 2020 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 16, 2017 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 09, 2019 | The p.E143K variant (also known as c.427G>A), located in coding exon 3 of the TTN gene, results from a G to A substitution at nucleotide position 427. The glutamic acid at codon 143 is replaced by lysine, an amino acid with similar 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