chr2-178774011-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001267550.2(TTN):c.7157G>A(p.Gly2386Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,614,068 control chromosomes in the GnomAD database, including 1 homozygotes. 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. G2386S) has been classified as Uncertain significance.
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.7157G>A | p.Gly2386Asp | missense_variant | 31/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.7157G>A | p.Gly2386Asp | missense_variant | 31/46 | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.7157G>A | p.Gly2386Asp | missense_variant | 31/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.7157G>A | p.Gly2386Asp | missense_variant | 31/46 | 5 | NM_133379.5 | ||
TTN-AS1 | ENST00000659121.1 | n.1654-216C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251008Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135630
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461810Hom.: 1 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727208
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74448
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 18, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 01, 2016 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 30, 2014 | The Gly2386Asp variant in TTN has not been previously reported in individuals wi th cardiomyopathy, but has been identified in 2/4406 African American chromosome s by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSN P rs142926566). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predic tive enough to determine pathogenicity. In summary, the clinical significance of the Gly2386Asp variant is uncertain. - |
TTN-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 13, 2023 | The TTN c.7157G>A variant is predicted to result in the amino acid substitution p.Gly2386Asp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.028% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2013 | There is insufficient or conflicting evidence for classification of this alteration. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at