rs765913263
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001267550.2(TTN):c.64826C>T(p.Thr21609Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,236 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 (★★). Synonymous variant affecting the same amino acid position (i.e. T21609T) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.64826C>T | p.Thr21609Met | missense_variant | 310/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.3010G>A | non_coding_transcript_exon_variant | 11/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.64826C>T | p.Thr21609Met | missense_variant | 310/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-12781G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151960Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248328Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134694
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461276Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 726920
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151960Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74178
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 18, 2016 | The p.Thr19041Met variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 2/9782 African chromosomes by t he Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs7 65913263). Computational prediction tools and conservation analysis suggest that the p.Thr19041Met variant may impact the protein, though this information is no t predictive enough to determine pathogenicity. In summary, the clinical signifi cance of the p.Thr19041Met variant is uncertain. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1838244:Tibial muscular dystrophy;C1858763:Dilated cardiomyopathy 1G;C1861065:Hypertrophic cardiomyopathy 9;C1863599:Myopathy, myofibrillar, 9, with early respiratory failure;C2673677:Early-onset myopathy with fatal cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 20, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at