rs369292052
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001267550.2(TTN):c.71699G>A(p.Arg23900Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,386 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R23900W) has been classified as Uncertain significance.
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.71699G>A | p.Arg23900Gln | missense_variant | 326/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2044-8139C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.71699G>A | p.Arg23900Gln | missense_variant | 326/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-23163C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152092Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248408Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134732
GnomAD4 exome AF: 0.0000506 AC: 74AN: 1461294Hom.: 0 Cov.: 38 AF XY: 0.0000633 AC XY: 46AN XY: 726918
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152092Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74278
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 21, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 02, 2021 | In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 18, 2022 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2018 | - - |
Dilated cardiomyopathy 1G;C1861065:Hypertrophic cardiomyopathy 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Dec 10, 2021 | The c.71699G>A (p.Arg23900Gln) variant identified in the TTN gene substitutes a well conserved Arginine for Glutamine at amino acid 23900/35992(coding exon 326/364) in transcript NM_001267550. This variant is found with low frequency in gnomAD(v3.1.2)(8 heterozygotes, 0 homozygotes; allele frequency:5.26e-5) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Damaging (SIFT;score:0.00) and Pathogenic (REVEL; score:0.6119) to the function of the canonical transcript. This variant is reported as a Variant of Uncertain Significance in ClinVar(VarID:498625), and to our current knowledge has not been reported in an affected individual in the literature. The p.Arg23900 residue is within the A-Band of TTN (http://cardiodb.org/titin/). Given the lack of compelling evidence for its pathogenicity, the c.71699G>A (p.Arg23900Gln) variant identified in the TTN gene is reported as a Variant of Uncertain Significance. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 15, 2018 | The p.R14835Q variant (also known as c.44504G>A), located in coding exon 153 of the TTN gene, results from a G to A substitution at nucleotide position 44504. The arginine at codon 14835 is replaced by glutamine, 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