rs73036368
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBP6
The NM_001267550.2(TTN):c.88028G>A(p.Arg29343His) variant causes a missense change. The variant allele was found at a frequency of 0.000182 in 1,613,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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. R29343P) 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.88028G>A | p.Arg29343His | missense_variant | 330/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2043+14765C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.88028G>A | p.Arg29343His | missense_variant | 330/363 | 5 | NM_001267550.2 | P1 | |
ENST00000624360.1 | n.2566C>T | non_coding_transcript_exon_variant | 1/1 | ||||||
TTN-AS1 | ENST00000659121.1 | n.416+33490C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000453 AC: 69AN: 152176Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000125 AC: 31AN: 247548Hom.: 0 AF XY: 0.000134 AC XY: 18AN XY: 134404
GnomAD4 exome AF: 0.000153 AC: 224AN: 1461282Hom.: 0 Cov.: 33 AF XY: 0.000140 AC XY: 102AN XY: 726934
GnomAD4 genome ? AF: 0.000453 AC: 69AN: 152294Hom.: 0 Cov.: 33 AF XY: 0.000510 AC XY: 38AN XY: 74450
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 17, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 28, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 13, 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 specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 10, 2018 | The p.Arg26775His variant in TTN is classified as benign because it has been ide ntified in 0.1% (29/23976) of African chromosomes by gnomAD (http://gnomad.broad institute.org). ACMG/AMP Criteria applied: BA1. - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Nov 26, 2019 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 01, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at