rs367914610
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):āc.70102A>Gā(p.Ile23368Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000899 in 1,613,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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
Genome browser will be placed here
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.70102A>G | p.Ile23368Val | missense_variant | 326/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2044-6542T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.70102A>G | p.Ile23368Val | missense_variant | 326/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-21566T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152108Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000101 AC: 25AN: 248540Hom.: 0 AF XY: 0.0000890 AC XY: 12AN XY: 134814
GnomAD4 exome AF: 0.0000938 AC: 137AN: 1461094Hom.: 0 Cov.: 36 AF XY: 0.0000936 AC XY: 68AN XY: 726772
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74296
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 26, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 31, 2021 | This variant is associated with the following publications: (PMID: 31983221) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Aug 18, 2020 | - - |
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 05, 2013 | The Ile20800Val variant in TTN has not been previously reported in individuals w ith cardiomyopathy, but has been identified in 1/8230 European American chromoso mes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). Co mputational analyses (biochemical amino acid properties, conservation, PolyPhen2 , and SIFT) suggest that this variant may impact the protein, though this inform ation is not predictive enough to determine pathogenicity. Additional informatio n is needed to fully assess the clinical significance of this variant. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 15, 2024 | Variant summary: TTN c.62398A>G (p.Ile20800Val) results in a conservative amino acid change located in the the A-band region of the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0001 in 248540 control chromosomes. c.62398A>G has been reported in the literature in one unspecified individual affected with dilated Cardiomyopathy (Mazzarotto_2020). These report(s) do not provide unequivocal conclusions about association of the variant with Limb-Girdle Muscular Dystrophy, Type 2J and other TTN-related diseases. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 31983221). ClinVar contains an entry for this variant (Variation ID: 165860). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 28, 2017 | - - |
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Jan 19, 2021 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 06, 2017 | The p.I14303V variant (also known as c.42907A>G), located in coding exon 153 of the TTN gene, results from an A to G substitution at nucleotide position 42907. The isoleucine at codon 14303 is replaced by valine, an amino acid with highly 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