rs201510986
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):c.55306G>A(p.Glu18436Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000025 in 1,603,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. E18436E) 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 -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.55306G>A | p.Glu18436Lys | missense_variant | 286/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.3917+1117C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.55306G>A | p.Glu18436Lys | missense_variant | 286/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.502+4103C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 151870Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000125 AC: 3AN: 239378Hom.: 0 AF XY: 0.00000771 AC XY: 1AN XY: 129648
GnomAD4 exome AF: 0.00000965 AC: 14AN: 1451182Hom.: 0 Cov.: 32 AF XY: 0.00000832 AC XY: 6AN XY: 721202
GnomAD4 genome ? AF: 0.000171 AC: 26AN: 151870Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17AN XY: 74150
ClinVar
Submissions by phenotype
not provided Uncertain:5Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 18, 2020 | This variant is associated with the following publications: (PMID: 25447171) - |
Uncertain significance, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 30, 2023 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 22, 2014 | The Glu15868Lys variant in TTN has not been previously reported in individuals w ith cardiomyopathy, but has been identified in 2/3642 African American chromosom es by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbS NP rs201510986). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the Glu15868Lys variant is uncertain. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 15, 2016 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 30, 2019 | The p.E9371K variant (also known as c.28111G>A and under NM_133378.4: p.E15868K), located in coding exon 113 of the TTN gene, results from a G to A substitution at nucleotide position 28111. The glutamic acid at codon 9371 is replaced by lysine, an amino acid with similar properties. This alteration has been reported in a sudden cardiac death cohort in one subject who also had alterations in other cardiac-related genes (Campuzano O et al. Forensic Sci. Int., 2014 12;245:30-7). This amino acid position is highly 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