2-178605488-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001267550.2(TTN):c.53807G>A(p.Arg17936His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000614 in 1,611,826 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. R17936R) 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.53807G>A | p.Arg17936His | missense_variant | 279/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.53807G>A | p.Arg17936His | missense_variant | 279/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.502+7807C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000659 AC: 10AN: 151834Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000928 AC: 23AN: 247858Hom.: 0 AF XY: 0.0000744 AC XY: 10AN XY: 134432
GnomAD4 exome AF: 0.0000610 AC: 89AN: 1459992Hom.: 0 Cov.: 32 AF XY: 0.0000551 AC XY: 40AN XY: 726236
GnomAD4 genome AF: 0.0000659 AC: 10AN: 151834Hom.: 0 Cov.: 32 AF XY: 0.0000944 AC XY: 7AN XY: 74134
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 22, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 14, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 24, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 04, 2014 | The Arg15368His variant in TTN has not been previously reported in individuals w ith cardiomyopathy or in large population studies. Computational prediction too ls and conservation analysis do not provide strong support for or against an imp act to the protein. Additional information is needed to fully assess the clinica l significance of the Arg15368His variant. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 25, 2016 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 06, 2018 | The p.R8871H variant (also known as c.26612G>A), located in coding exon 106 of the TTN gene, results from a G to A substitution at nucleotide position 26612. The arginine at codon 8871 is replaced by histidine, an amino acid with highly 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