rs745323281
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PP2PP3BP6
The NM_001267550.2(TTN):āc.63743T>Cā(p.Leu21248Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,612,040 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L21248F) has been classified as Uncertain significance.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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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.63743T>C | p.Leu21248Pro | missense_variant | 306/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.3188+2573A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.63743T>C | p.Leu21248Pro | missense_variant | 306/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-10030A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151992Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000324 AC: 8AN: 246672Hom.: 0 AF XY: 0.0000373 AC XY: 5AN XY: 133876
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1460048Hom.: 0 Cov.: 33 AF XY: 0.0000275 AC XY: 20AN XY: 726264
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151992Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74206
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 21, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 09, 2012 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at