rs397517784
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001267550.2(TTN):c.101250C>G(p.Ile33750Met) variant causes a missense 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. 14/19 in silico tools predict a benign outcome for this variant. 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. I33750F) has been classified as Uncertain significance.
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.101250C>G | p.Ile33750Met | missense_variant | 358/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.220-367G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.101250C>G | p.Ile33750Met | missense_variant | 358/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.416+11729G>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 38
GnomAD4 genome Cov.: 33
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 | Apr 03, 2012 | Variant classified as Uncertain Significance - Favor Benign. The Ile31182Met var iant in TTN has not been reported in the literature nor previously identified by our laboratory. Ile at position 31182 is conserved in mammals, but not in more distantly related species. Computational analyses (biochemical amino acid proper ties, AlignGVGD, and SIFT) do not provide strong support for or against an impac t to the protein. In summary, additional information is needed to fully assess t he clinical significance of this variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at