rs727504757
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_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. 11/18 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
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.31391G>A | p.Arg10464Gln | missense_variant | 117/363 | ENST00000589042.5 | |
LOC124907912 | XR_007087321.1 | n.6497C>T | non_coding_transcript_exon_variant | 1/2 | |||
LOC124906100 | XR_007087318.1 | n.2186-19120C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.31391G>A | p.Arg10464Gln | missense_variant | 117/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-39870C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000922 AC: 14AN: 151844Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000344 AC: 6AN: 174408Hom.: 0 AF XY: 0.0000434 AC XY: 4AN XY: 92190
GnomAD4 exome AF: 0.0000774 AC: 109AN: 1408160Hom.: 0 Cov.: 30 AF XY: 0.0000820 AC XY: 57AN XY: 695328
GnomAD4 genome ? AF: 0.0000922 AC: 14AN: 151844Hom.: 0 Cov.: 32 AF XY: 0.0000944 AC XY: 7AN XY: 74140
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 30, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 21, 2022 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 04, 2013 | 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
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 12, 2016 | - - |
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 02, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at