rs553988103
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001267550.2(TTN):c.66778G>C(p.Glu22260Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000081 in 1,605,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign 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. E22260D) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.66778G>C | p.Glu22260Gln | missense_variant | 317/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2044-1971C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.66778G>C | p.Glu22260Gln | missense_variant | 317/363 | 5 | NM_001267550.2 | P1 | |
ENST00000603521.1 | n.1812C>G | non_coding_transcript_exon_variant | 1/1 | ||||||
TTN-AS1 | ENST00000659121.1 | n.417-16995C>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152082Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000417 AC: 10AN: 239868Hom.: 0 AF XY: 0.0000308 AC XY: 4AN XY: 130010
GnomAD4 exome AF: 0.00000826 AC: 12AN: 1453576Hom.: 0 Cov.: 33 AF XY: 0.00000692 AC XY: 5AN XY: 722632
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152082Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74268
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 | Oct 10, 2017 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 28, 2018 | 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