rs376846228
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_001267550.2(TTN):c.18680C>T(p.Pro6227Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,412 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P6227P) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.18680C>T | p.Pro6227Leu | missense_variant | 64/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.18680C>T | p.Pro6227Leu | missense_variant | 64/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-5028G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152052Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248406Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134746
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461360Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 726972
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152052Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74248
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 | Jan 19, 2018 | The p.Pro4983Leu variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 2/24004 African chromosomes by t he Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs376846228). Computational prediction tools and conservation analysis suggest that the p.Pro4983Leu variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical sign ificance of the p.Pro4983Leu variant is uncertain. ACMG/AMP Criteria applied: PM 2; PP3. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at