rs200972189
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBP6
The NM_001267550.2(TTN):c.25087G>T(p.Ala8363Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,607,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 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. A8363P) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.25087G>T | p.Ala8363Ser | missense_variant | 87/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.25087G>T | p.Ala8363Ser | missense_variant | 87/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-16717C>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000789 AC: 120AN: 152084Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000206 AC: 50AN: 242328Hom.: 0 AF XY: 0.000144 AC XY: 19AN XY: 131660
GnomAD4 exome AF: 0.0000742 AC: 108AN: 1455162Hom.: 0 Cov.: 34 AF XY: 0.0000608 AC XY: 44AN XY: 723166
GnomAD4 genome ? AF: 0.000788 AC: 120AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.000739 AC XY: 55AN XY: 74416
ClinVar
Submissions by phenotype
not specified Uncertain:2Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 20, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 16, 2012 | Variant classified as Uncertain Significance - Favor Benign. The Ala7119Ser vari ant in TTN has been identified in 0.2% (7/2996) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS). Computational analyses (biochemical amino acid properties, con servation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. While this frequency suggests that Ala7119Ser variant is more likely benign, it is too low to confidently rule out a disease c ausing role. Additional information is needed to fully assess its clinical signi ficance. - |
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 26, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 03, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 24, 2020 | - - |
TTN-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 27, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at