rs769729114
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_001267550.2(TTN):c.75833G>A(p.Arg25278His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,613,164 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R25278C) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.75833G>A | p.Arg25278His | missense_variant | 326/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2044-12273C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.75833G>A | p.Arg25278His | missense_variant | 326/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-27297C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152054Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000485 AC: 12AN: 247634Hom.: 0 AF XY: 0.0000595 AC XY: 8AN XY: 134350
GnomAD4 exome AF: 0.0000370 AC: 54AN: 1461110Hom.: 0 Cov.: 40 AF XY: 0.0000440 AC XY: 32AN XY: 726858
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152054Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15AN XY: 74264
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 27, 2015 | The p.Arg22710His variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 3/66242 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Comput ational prediction tools and conservation analysis suggest that the p.Arg22710Hi s variant may impact the protein, though this information is not predictive enou gh to determine pathogenicity. In summary, the clinical significance of the p.Ar g22710His variant is uncertain. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 30, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at