rs397517829
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBP6
The NM_001267550.2(TTN):c.12181G>A(p.Ala4061Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000861 in 1,613,742 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).
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.12181G>A | p.Ala4061Thr | missense_variant | 48/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.12181G>A | p.Ala4061Thr | missense_variant | 48/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.1134-1829C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000125 AC: 31AN: 248188Hom.: 0 AF XY: 0.000134 AC XY: 18AN XY: 134630
GnomAD4 exome AF: 0.0000876 AC: 128AN: 1461596Hom.: 0 Cov.: 32 AF XY: 0.0000894 AC XY: 65AN XY: 727090
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74306
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 31, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 24, 2012 | The Ala3823Thr variant in TTN has not been reported in the literature nor previo usly identified by our laboratory. Computational analyses (biochemical amino aci d properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide stron g support for or against an impact to the protein. Additional information is nee ded to fully assess the clinical significance of this variant. - |
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 10, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2022 | 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 | Oct 12, 2016 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 08, 2019 | The p.A3698T variant (also known as c.11092G>A), located in coding exon 44 of the TTN gene, results from a G to A substitution at nucleotide position 11092. The alanine at codon 3698 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at