chr2-178540145-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001267550.2(TTN):c.98021G>A(p.Arg32674His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,613,364 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 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. R32674C) 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.98021G>A | p.Arg32674His | missense_variant | 351/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.1879C>T | non_coding_transcript_exon_variant | 6/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.98021G>A | p.Arg32674His | missense_variant | 351/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.416+16509C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152156Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000362 AC: 9AN: 248512Hom.: 0 AF XY: 0.0000445 AC XY: 6AN XY: 134804
GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461208Hom.: 1 Cov.: 33 AF XY: 0.0000303 AC XY: 22AN XY: 726862
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152156Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74322
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 23, 2020 | Missense variant in a gene in which most reported pathogenic variants are truncating/loss-of-function; In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 10, 2019 | - - |
Likely pathogenic, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at