rs577298130
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBP6
The NM_001267550.2(TTN):c.4289C>A(p.Ala1430Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,613,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.4289C>A | p.Ala1430Glu | missense_variant | 25/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.4289C>A | p.Ala1430Glu | missense_variant | 25/46 | ENST00000360870.10 | |
LOC101927055 | NR_120594.1 | n.970G>T | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.4289C>A | p.Ala1430Glu | missense_variant | 25/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.4289C>A | p.Ala1430Glu | missense_variant | 25/46 | 5 | NM_133379.5 | ||
TTN-AS1 | ENST00000659121.1 | n.5322G>T | non_coding_transcript_exon_variant | 12/13 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152108Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000291 AC: 73AN: 250734Hom.: 0 AF XY: 0.000376 AC XY: 51AN XY: 135498
GnomAD4 exome AF: 0.000127 AC: 186AN: 1461566Hom.: 0 Cov.: 34 AF XY: 0.000179 AC XY: 130AN XY: 727100
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74438
ClinVar
Submissions by phenotype
not provided Uncertain:4Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 04, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | TTN: PM2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 09, 2022 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Mar 18, 2022 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 18, 2020 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at