2-178557987-T-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):āc.87367A>Cā(p.Ser29123Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000108 in 1,613,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict 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. S29123G) has been classified as Uncertain significance.
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 | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.87367A>C | p.Ser29123Arg | missense_variant | 328/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2043+15626T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.87367A>C | p.Ser29123Arg | missense_variant | 328/363 | 5 | NM_001267550.2 | P1 | |
ENST00000624360.1 | n.3427T>G | non_coding_transcript_exon_variant | 1/1 | ||||||
TTN-AS1 | ENST00000659121.1 | n.416+34351T>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152208Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000925 AC: 23AN: 248516Hom.: 0 AF XY: 0.000104 AC XY: 14AN XY: 134820
GnomAD4 exome AF: 0.000110 AC: 161AN: 1461382Hom.: 0 Cov.: 33 AF XY: 0.000124 AC XY: 90AN XY: 726994
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74352
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 30, 2019 | This variant is associated with the following publications: (PMID: 30453078) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 21, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jan 22, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 11, 2023 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 07, 2012 | The Ser26555Arg variant (TTN) has not been reported in the literature nor previo usly identified by our laboratory. Computational analyses (biochemical amino aci d properties, conservation, AlignGVGD, and SIFT) do not provide strong support f or or against an impact to the protein. Additional information is needed to full y assess the clinical significance of the Ser26555Arg 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 08, 2017 | - - |
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Apr 27, 2021 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 24, 2019 | The p.S20058R variant (also known as c.60172A>C), located in coding exon 155 of the TTN gene, results from an A to C substitution at nucleotide position 60172. The serine at codon 20058 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is well 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