rs397517556
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_001267550.2(TTN):c.39419C>T(p.Ala13140Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,613,216 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/19 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. A13140S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.39419C>T | p.Ala13140Val | missense_variant | 206/363 | ENST00000589042.5 | |
LOC124906100 | XR_007087318.1 | n.2185+7209G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.39419C>T | p.Ala13140Val | missense_variant | 206/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.502+54029G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152094Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000105 AC: 26AN: 247980Hom.: 1 AF XY: 0.000126 AC XY: 17AN XY: 134534
GnomAD4 exome AF: 0.0000486 AC: 71AN: 1461122Hom.: 1 Cov.: 33 AF XY: 0.0000647 AC XY: 47AN XY: 726838
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152094Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74294
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, 2012 | The Ala10706Val variant in TTN has not been reported in the literature nor previ ously identified by our laboratory. Computational analyses (biochemical amino ac id properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the va riant may not impact the protein and another mammal (rabbit) carries a valine (V al; this variant) at this position despite high nearby amino acid conservation. However, this information is not predictive enough to rule out pathogenicity. Ad ditional information is needed to fully assess the clinical significance of this variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at