rs727503635
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001267550.2(TTN):c.32515G>T(p.Ala10839Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,609,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A10839A) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.32515G>T | p.Ala10839Ser | missense_variant | 130/363 | ENST00000589042.5 | |
LOC124906100 | XR_007087318.1 | n.2186-28809C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.32515G>T | p.Ala10839Ser | missense_variant | 130/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-49559C>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152068Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000416 AC: 1AN: 240428Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 130440
GnomAD4 exome AF: 0.0000281 AC: 41AN: 1457006Hom.: 0 Cov.: 31 AF XY: 0.0000304 AC XY: 22AN XY: 724322
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152068Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74268
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jun 06, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 22, 2018 | p.Ala9595Ser in exon 127 of TTN: This variant classified as likely benign becaus e computational prediction tools and conservation analysis do not predict an imp act on the protein. In addition, the majority of pathogenic variants reported in the TTN gene are loss-of-function variants located in the A-band or in other hi ghly expressed exons. This is a missense variant located in the I-band, in an ex on that is not highly expressed in the heart. It has also been identified in 1/1 07056 European chromosomes by the Genome Aggregation Database (gnomAD, http://gn omad.broadinstitute.org; dbSNP rs727503635); however, coverage of this region wa s poor. ACMG/AMP Criteria applied: BP1; BP4. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at