rs756091180
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001267550.2(TTN):c.60008G>A(p.Arg20003His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,156 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. R20003G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.60008G>A | p.Arg20003His | missense_variant | 303/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.3364+497C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.60008G>A | p.Arg20003His | missense_variant | 303/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-5785C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152038Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248064Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134554
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461118Hom.: 0 Cov.: 35 AF XY: 0.0000316 AC XY: 23AN XY: 726858
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152038Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74254
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 15, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 15, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 13, 2018 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2017 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 13, 2013 | The p.R17435H variant (also known as c.52304G>A) is located in coding exon 251 of the TTN gene. This alteration results from a G to A substitution at nucleotide position 52304. The arginine at codon 17435 is replaced by histidine, an amino acid with some highly similar properties.​This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project.This amino acid position is highly conserved on sequence alignment.This variant is predicted to be probably damaging by PolyPhen in silico analyses. Since supporting evidence is limited at this time, the clinical significance of p.R17435H remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at