rs779064623
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001267550.2(TTN):c.101890C>T(p.Arg33964Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,613,646 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. R33964H) has been classified as Likely benign.
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.101890C>T | p.Arg33964Cys | missense_variant | 358/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.220-1007G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.101890C>T | p.Arg33964Cys | missense_variant | 358/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.416+11089G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152098Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000804 AC: 2AN: 248802Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134980
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461548Hom.: 0 Cov.: 38 AF XY: 0.0000124 AC XY: 9AN XY: 727052
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152098Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74312
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 01, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); Missense variant in a gene in which most reported pathogenic variants are truncating/loss-of-function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26582918) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 16, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 22, 2019 | - - |
TTN-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 10, 2022 | The TTN c.101890C>T variant is predicted to result in the amino acid substitution p.Arg33964Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0046% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-179399452-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at