rs377423256
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):c.11667G>T(p.Glu3889Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. E3889E) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.11667G>T | p.Glu3889Asp | missense_variant | 48/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.11667G>T | p.Glu3889Asp | missense_variant | 48/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.1134-1315C>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152070Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248516Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134784
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461576Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727082
GnomAD4 genome AF: 0.0000592 AC: 9AN: 152070Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74266
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2018 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 23, 2019 | - - |
Brugada syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Jul 12, 2019 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 30, 2019 | The p.E3526D variant (also known as c.10578G>T), located in coding exon 44 of the TTN gene, results from a G to T substitution at nucleotide position 10578. The glutamic acid at codon 3526 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, aspartic acid is the reference amino acid in other 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