2-178784084-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBP6
The NM_001267550.2(TTN):c.2761G>A(p.Gly921Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 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. G921G) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.2761G>A | p.Gly921Arg | missense_variant | 16/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.2761G>A | p.Gly921Arg | missense_variant | 16/46 | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.2761G>A | p.Gly921Arg | missense_variant | 16/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.2761G>A | p.Gly921Arg | missense_variant | 16/46 | 5 | NM_133379.5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000639 AC: 16AN: 250566Hom.: 0 AF XY: 0.0000590 AC XY: 8AN XY: 135492
GnomAD4 exome AF: 0.0000376 AC: 55AN: 1461192Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 726920
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74322
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 14, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | TTN: BP4 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 30, 2015 | p.Gly921Arg in exon 16 of TTN: This variant is not expected to have clinical sig nificance due to a lack of conservation across species, including mammals. Of no te, 8 mammals have an arginine (Arg) at this position. It has also been identifi ed in 4/16510 South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at