rs368151971
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001267550.2(TTN):c.26468C>T(p.Thr8823Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,612,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T8823T) has been classified as Likely benign.
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.26468C>T | p.Thr8823Met | missense_variant | 91/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.26468C>T | p.Thr8823Met | missense_variant | 91/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-20198G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152098Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248438Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134788
GnomAD4 exome AF: 0.0000158 AC: 23AN: 1460262Hom.: 0 Cov.: 34 AF XY: 0.0000110 AC XY: 8AN XY: 726172
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74412
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 31, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | TTN: BP4 - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2018 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 13, 2013 | There is insufficient or conflicting evidence for classification of this alteration. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 03, 2015 | proposed classification - variant undergoing re-assessment, contact laboratory - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at