rs727503600
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):āc.55378A>Gā(p.Thr18460Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000659 in 1,609,554 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T18460I) 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.55378A>G | p.Thr18460Ala | missense_variant | 286/363 | ENST00000589042.5 | NP_001254479.2 | |
TTN-AS1 | NR_038272.1 | n.3917+1045T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.55378A>G | p.Thr18460Ala | missense_variant | 286/363 | 5 | NM_001267550.2 | ENSP00000467141 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.502+4031T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152066Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000695 AC: 17AN: 244736Hom.: 0 AF XY: 0.0000754 AC XY: 10AN XY: 132652
GnomAD4 exome AF: 0.0000611 AC: 89AN: 1457488Hom.: 0 Cov.: 32 AF XY: 0.0000593 AC XY: 43AN XY: 724742
GnomAD4 genome AF: 0.000112 AC: 17AN: 152066Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74276
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 15, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 01, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 03, 2017 | - - |
Cardiomyopathy Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego | May 28, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Sep 21, 2017 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 28, 2014 | The Thr15892Ala variant in TTN has not been reported in individuals with cardiom yopathy or in large population studies. The affected amino acid is well conserve d in evolution, suggesting that a change would not be tolerated. Other computati onal analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT ) do not provide strong support for or against an impact to the protein. Additio nal information is needed to fully assess the clinical significance of the Thr15 892Ala variant. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 28, 2017 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2019 | The p.T9395A variant (also known as c.28183A>G), located in coding exon 113 of the TTN gene, results from an A to G substitution at nucleotide position 28183. The threonine at codon 9395 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly 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