rs375944265
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001267550.2(TTN):c.52927C>T(p.Arg17643Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000533 in 1,613,036 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R17643L) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.52927C>T | p.Arg17643Trp | missense_variant | 276/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.52927C>T | p.Arg17643Trp | missense_variant | 276/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.502+10179G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000296 AC: 45AN: 151984Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000604 AC: 15AN: 248394Hom.: 0 AF XY: 0.0000668 AC XY: 9AN XY: 134744
GnomAD4 exome AF: 0.0000281 AC: 41AN: 1460934Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 726782
GnomAD4 genome ? AF: 0.000296 AC: 45AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74334
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 07, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 07, 2019 | This variant is associated with the following publications: (PMID: 31983221) - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 18, 2016 | The p.Arg15075Trp variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 6/9798 African chromosomes by t he Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs3 75944265).Computational prediction tools and conservation analysis suggest that the p.Arg15075Trp variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical signific ance of the p.Arg15075Trp variant is uncertain. - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 11, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at