rs876658106
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_133379.5(TTN):c.16384G>T(p.Ala5462Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,198 control chromosomes in the GnomAD database, with no homozygous occurrence. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A5462T) has been classified as Uncertain significance.
Frequency
Consequence
NM_133379.5 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_133379.5 | c.16384G>T | p.Ala5462Ser | missense_variant | 46/46 | ENST00000360870.10 | |
TTN | NM_001267550.2 | c.11312-4095G>T | intron_variant | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000360870.10 | c.16384G>T | p.Ala5462Ser | missense_variant | 46/46 | 5 | NM_133379.5 | ||
TTN | ENST00000589042.5 | c.11312-4095G>T | intron_variant | 5 | NM_001267550.2 | P1 | |||
TTN-AS1 | ENST00000659121.1 | n.1223+3046C>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461198Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7AN XY: 726898
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
TTN-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 19, 2022 | The TTN c.16384G>T variant is predicted to result in the amino acid substitution p.Ala5462Ser. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at