rs181957743
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBP6
The NM_001267550.2(TTN):c.57073G>A(p.Val19025Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000584 in 1,608,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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. V19025A) 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.57073G>A | p.Val19025Ile | missense_variant | 292/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.3451-12C>T | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.57073G>A | p.Val19025Ile | missense_variant | 292/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.502+863C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 151958Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000184 AC: 45AN: 244382Hom.: 0 AF XY: 0.000113 AC XY: 15AN XY: 132552
GnomAD4 exome AF: 0.0000529 AC: 77AN: 1456728Hom.: 0 Cov.: 32 AF XY: 0.0000359 AC XY: 26AN XY: 724400
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152076Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74308
ClinVar
Submissions by phenotype
not specified Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Jul 01, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 17, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 20, 2017 | Variant classified as Uncertain Significance - Favor Benign. The p.Val16457Ile v ariant in TTN has not been previously reported in individuals with cardiomyopath y, but has been reported in ClinVar (Variation ID 212474). This variant has been identified in 0.14% (16/11350) of Latino chromosomes by the Exome Aggregation C onsortium (ExAC, http://exac.broadinstitute.org; dbSNP rs181957743). Computation al prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, while the clinical significance of the p.Val16457Ile variant is uncertain, its frequency suggests that it is mo re likely to be benign. - |
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 23, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 23, 2020 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at