rs754325718
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):āc.81517C>Gā(p.Pro27173Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,613,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.81517C>G | p.Pro27173Ala | missense_variant | 326/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2044-17957G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.81517C>G | p.Pro27173Ala | missense_variant | 326/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-32981G>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152034Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000604 AC: 15AN: 248266Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134690
GnomAD4 exome AF: 0.0000636 AC: 93AN: 1461264Hom.: 0 Cov.: 37 AF XY: 0.0000619 AC XY: 45AN XY: 726924
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152034Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74252
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 20, 2017 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 24, 2016 | The p.P18108A variant (also known as c.54322C>G), located in coding exon 153 of the TTN gene, results from a C to G substitution at nucleotide position 54322. The proline at codon 18108 is replaced by alanine, an amino acid with highly similar properties. Based on data from ExAC, the G allele has an overall frequency of approximately 0.008% (9/119946). The highest observed frequency was 0.03% (2/6550) of European (Finnish) alleles (Exome Aggregation Consortium (ExAC), Cambridge, MA (URL: http://exac.broadinstitute.org) [Accessed February 24, 2016]). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6090 samples (12180 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at