2-178634818-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.42056G>A(p.Arg14019His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,611,684 control chromosomes in the GnomAD database, including 1 homozygotes. 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. R14019C) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.42056G>A | p.Arg14019His | missense_variant | 229/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.42056G>A | p.Arg14019His | missense_variant | 229/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.502+37137C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 152034Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000223 AC: 55AN: 246758Hom.: 0 AF XY: 0.000291 AC XY: 39AN XY: 133802
GnomAD4 exome AF: 0.000135 AC: 197AN: 1459532Hom.: 1 Cov.: 32 AF XY: 0.000200 AC XY: 145AN XY: 725942
GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74368
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 01, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 17, 2018 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 19, 2014 | The Arg11451His variant in TTN has not been previously reported in individuals w ith cardiomyopathy, but has been identified in 1/8184 European American chromoso mes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). C omputational prediction tools and conservation analysis suggest that this varian t may impact the protein, though this information is not predictive enough to de termine pathogenicity. Additional information is needed to fully assess the clin ical significance of this variant. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at