rs397517704
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):āc.76199G>Cā(p.Cys25400Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,612,890 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 (ā ā ). Synonymous variant affecting the same amino acid position (i.e. C25400C) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.76199G>C | p.Cys25400Ser | missense_variant | 326/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2044-12639C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.76199G>C | p.Cys25400Ser | missense_variant | 326/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-27663C>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152010Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1460880Hom.: 0 Cov.: 40 AF XY: 0.0000138 AC XY: 10AN XY: 726710
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152010Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74260
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 10, 2021 | The p.Cys22832Ser variant in TTN has been identified in 1 individual with hypertrophic cardiomyopathy (HCM; LMM data) and has also been reported in 0.006% (1/15416) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Cys22832Ser variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at