rs201490999
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PP2PP3_Strong
The NM_001267550.2(TTN):c.17C>T(p.Pro6Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,613,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P6P) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.17C>T | p.Pro6Leu | missense_variant | 2/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.17C>T | p.Pro6Leu | missense_variant | 2/46 | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.17C>T | p.Pro6Leu | missense_variant | 2/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.17C>T | p.Pro6Leu | missense_variant | 2/46 | 5 | NM_133379.5 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152106Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250928Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135608
GnomAD4 exome AF: 0.0000376 AC: 55AN: 1461600Hom.: 0 Cov.: 32 AF XY: 0.0000399 AC XY: 29AN XY: 727112
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152106Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74302
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 | Aug 21, 2014 | The Pro6Leu variant in TTN gene has not been previously reported in individuals with cardiomyopathy or in large population studies. This variant is listed in db SNP (rs201490999) without frequency information. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, thou gh this information is not predictive enough to determine pathogenicity. In summ ary, the clinical significance of the Pro6Leu 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 | Sep 20, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at