2-178560660-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001267550.2(TTN):c.85472G>A(p.Arg28491His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 1,613,466 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. R28491C) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.85472G>A | p.Arg28491His | missense_variant | 326/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2043+18299C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.85472G>A | p.Arg28491His | missense_variant | 326/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-36936C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152094Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000968 AC: 24AN: 248024Hom.: 0 AF XY: 0.000104 AC XY: 14AN XY: 134558
GnomAD4 exome AF: 0.0000568 AC: 83AN: 1461372Hom.: 0 Cov.: 32 AF XY: 0.0000605 AC XY: 44AN XY: 726982
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152094Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74274
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 09, 2022 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 15, 2019 | The p.R19426H variant (also known as c.58277G>A), located in coding exon 153 of the TTN gene, results from a G to A substitution at nucleotide position 58277. The arginine at codon 19426 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 25, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Nov 15, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at