2-178573644-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001267550.2(TTN):c.72488G>A(p.Arg24163His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000493 in 1,499,946 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. R24163C) 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.72488G>A | p.Arg24163His | missense_variant | 326/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2044-8928C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.72488G>A | p.Arg24163His | missense_variant | 326/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-23952C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152064Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000294 AC: 5AN: 169990Hom.: 0 AF XY: 0.0000222 AC XY: 2AN XY: 90016
GnomAD4 exome AF: 0.0000482 AC: 65AN: 1347764Hom.: 0 Cov.: 38 AF XY: 0.0000410 AC XY: 27AN XY: 657950
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74384
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 20, 2015 | The p.Arg21595His variant in TTN has been identified by our laboratory in 1 indi vidual with DCM who carried another, likely pathogenic TTN variant. This variant has also been identified in 3/64008 European chromosomes by the Exome Aggregati on Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs374712231). Computa tional prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance o f the p.Arg21595His variant is uncertain. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 03, 2017 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 02, 2018 | This variant is associated with the following publications: (PMID: 24503780) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at