rs376988498
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001267550.2(TTN):c.74063G>A(p.Arg24688His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,076 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R24688C) 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.74063G>A | p.Arg24688His | missense_variant | 326/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2044-10503C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.74063G>A | p.Arg24688His | missense_variant | 326/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-25527C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152014Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000282 AC: 7AN: 247808Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134450
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461062Hom.: 0 Cov.: 38 AF XY: 0.0000261 AC XY: 19AN XY: 726814
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152014Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74232
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1838244:Tibial muscular dystrophy;C1858763:Dilated cardiomyopathy 1G;C1861065:Hypertrophic cardiomyopathy 9;C1863599:Myopathy, myofibrillar, 9, with early respiratory failure;C2673677:Early-onset myopathy with fatal cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 08, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 22, 2018 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 20, 2017 | The p.R15623H variant (also known as c.46868G>A), located in coding exon 153 of the TTN gene, results from a G to A substitution at nucleotide position 46868. The arginine at codon 15623 is replaced by histidine, an amino acid with highly similar properties. This variant was reported (as NM_001267550.1:c.74063G>A p.Arg24688His) in one individual from an arrhythmogenic right ventricular cardiomyopathy (ARVC) cohort, who also had additional cardiac variants detected (Poloni G et al. Heart Rhythm, 2019 May;16:773-780). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at