rs727503601
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001267550.2(TTN):c.54812T>G(p.Phe18271Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. F18271L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001267550.2 missense, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.54812T>G | p.Phe18271Cys | missense_variant, splice_region_variant | 283/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.3917+1923A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.54812T>G | p.Phe18271Cys | missense_variant, splice_region_variant | 283/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.502+4909A>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
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 | Jun 30, 2014 | The Phe15703Cys variant in TTN has not been previously reported in individuals w ith cardiomyopathy. Data from large population studies is insufficient to assess the frequency of this variant. Phenylalanine at position 15703 is not conserved in mammals or evolutionarily distant species, raising the possibility that a ch ange at this position may be tolerated. Additional computational prediction too ls do not provide strong support for or against an impact to the protein. In ad dition, this variant is located in the first base of the exon, which is part of the 3? splice region. Computational tools do not suggest an impact to splicing, though this information is not predictive enough to rule out pathogenicity. In s ummary, the clinical significance of the Phe15703Cys variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at