rs765930349
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):c.69227T>C(p.Ile23076Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,613,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict 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. I23076K) 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.69227T>C | p.Ile23076Thr | missense_variant | 324/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2044-5464A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.69227T>C | p.Ile23076Thr | missense_variant | 324/363 | 5 | NM_001267550.2 | P1 | |
ENST00000604215.1 | n.6A>G | non_coding_transcript_exon_variant | 1/1 | ||||||
TTN-AS1 | ENST00000659121.1 | n.417-20488A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 151984Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000242 AC: 6AN: 248270Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134666
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461186Hom.: 0 Cov.: 35 AF XY: 0.0000138 AC XY: 10AN XY: 726890
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 151984Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74210
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jul 09, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 04, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 31, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 02, 2018 | The p.Ile20508Thr variant in TTN has not been previously reported in individuals with cardiomyopathy but it has been identified in 1/15274 African chromosomes b y the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbS NP rs765930349). Computational prediction tools and conservation analysis sugges t that the p.Ile20508Thr variant may not impact the protein, though this informa tion is not predictive enough to rule out pathogenicity. In summary, the clinica l significance of the p.Ile20508Thr variant is uncertain. ACMG/AMP Criteria appl ied: BP4. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at