rs727504757
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001267550.2(TTN):c.31391G>A(p.Arg10464Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000788 in 1,560,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict 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. R10464W) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.31391G>A | p.Arg10464Gln | missense_variant | Exon 117 of 363 | ENST00000589042.5 | NP_001254479.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.31391G>A | p.Arg10464Gln | missense_variant | Exon 117 of 363 | 5 | NM_001267550.2 | ENSP00000467141.1 |
Frequencies
GnomAD3 genomes AF: 0.0000922 AC: 14AN: 151844Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000344 AC: 6AN: 174408 AF XY: 0.0000434 show subpopulations
GnomAD4 exome AF: 0.0000774 AC: 109AN: 1408160Hom.: 0 Cov.: 30 AF XY: 0.0000820 AC XY: 57AN XY: 695328 show subpopulations
GnomAD4 genome AF: 0.0000922 AC: 14AN: 151844Hom.: 0 Cov.: 32 AF XY: 0.0000944 AC XY: 7AN XY: 74140 show subpopulations
ClinVar
Submissions by phenotype
not provided Uncertain:2
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not specified Uncertain:1
The Arg9220Gln variant in TTN has not been reported in any other families with c ardiomyopathy and data from large population studies is insufficient to assess t he frequency of this variant. Computational analyses are limited or unavailable for this variant. Additional information is needed to fully assess the clinical significance of the Arg9220Gln variant. -
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
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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
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at