rs563369722
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):āc.1049A>Gā(p.Tyr350Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. Y350Y) 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.1049A>G | p.Tyr350Cys | missense_variant | 7/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.1049A>G | p.Tyr350Cys | missense_variant | 7/46 | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.1049A>G | p.Tyr350Cys | missense_variant | 7/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.1049A>G | p.Tyr350Cys | missense_variant | 7/46 | 5 | NM_133379.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251146Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135734
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461822Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727218
GnomAD4 genome ? AF: 0.00000656 AC: 1AN: 152330Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74490
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 26, 2021 | The p.Tyr350Cys variant in TTN has not been previously reported in individuals with cardiomyopathy but has been identified in 0.003% (1/30616) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at