2-178777923-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001267550.2(TTN):c.4261C>T(p.Arg1421Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000613 in 1,613,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 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. R1421Q) 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.4261C>T | p.Arg1421Trp | missense_variant | 25/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.4261C>T | p.Arg1421Trp | missense_variant | 25/46 | ENST00000360870.10 | |
LOC101927055 | NR_120594.1 | n.998G>A | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.4261C>T | p.Arg1421Trp | missense_variant | 25/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.4261C>T | p.Arg1421Trp | missense_variant | 25/46 | 5 | NM_133379.5 | ||
TTN-AS1 | ENST00000659121.1 | n.5350G>A | non_coding_transcript_exon_variant | 12/13 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152176Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000639 AC: 16AN: 250374Hom.: 0 AF XY: 0.0000665 AC XY: 9AN XY: 135346
GnomAD4 exome AF: 0.0000554 AC: 81AN: 1461628Hom.: 0 Cov.: 34 AF XY: 0.0000550 AC XY: 40AN XY: 727114
GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152294Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74468
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 10, 2018 | The p.Arg1421Trp variant in TTN is classified as likely benign because it has be en identified in 0.05% (12/24020) of African chromosomes by gnomAD (http://gnoma d.broadinstitute.org). ACMG/AMP Criteria applied: BS1. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 29, 2014 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 06, 2017 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at