rs397517676
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001267550.2(TTN):c.68282C>T(p.Ser22761Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.68282C>T | p.Ser22761Phe | missense_variant | 321/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2044-3914G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.68282C>T | p.Ser22761Phe | missense_variant | 321/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-18938G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152060Hom.: 0 Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1460018Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726238
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152060Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74266
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 | Mar 11, 2013 | The Ser20193Phe variant in TTN has not been reported in the literature, but has been previously identified by our laboratory in 1 individual with HCM who carrie d a likely pathogenic variant in another gene (LMM unpublished data). This varia nt has also not been identified in large European American and African American populations by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/ EVS), though it may be present in other populations. Serine (Ser) at position 20 193 is not conserved in mammals, suggesting that a change at this position may b e tolerated. Additional computational analyses (biochemical amino acid propertie s, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. In summary, additional information is needed to fully assess the clinical significance of the Ser20193Phe variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at