rs577114038
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001267550.2(TTN):c.65986C>T(p.Arg21996Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,612,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R21996H) 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.65986C>T | p.Arg21996Cys | missense_variant | 314/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2044-102G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.65986C>T | p.Arg21996Cys | missense_variant | 314/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-15126G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152034Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000113 AC: 28AN: 247876Hom.: 0 AF XY: 0.0000595 AC XY: 8AN XY: 134490
GnomAD4 exome AF: 0.0000493 AC: 72AN: 1460756Hom.: 0 Cov.: 32 AF XY: 0.0000289 AC XY: 21AN XY: 726688
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152152Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74358
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 | Jun 15, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 05, 2020 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Jul 22, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at