rs535876380
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):c.9770G>A(p.Arg3257His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000706 in 1,614,032 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. R3257S) 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 -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.9770G>A | p.Arg3257His | missense_variant | 42/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.9770G>A | p.Arg3257His | missense_variant | 42/46 | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.9770G>A | p.Arg3257His | missense_variant | 42/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.9770G>A | p.Arg3257His | missense_variant | 42/46 | 5 | NM_133379.5 | ||
TTN-AS1 | ENST00000659121.1 | n.1592+377C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250742Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135478
GnomAD4 exome AF: 0.0000753 AC: 110AN: 1461732Hom.: 0 Cov.: 34 AF XY: 0.0000729 AC XY: 53AN XY: 727162
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152300Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74476
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 15, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 19, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2023 | TTN: PM2 - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 14, 2017 | - - |
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 | Oct 15, 2021 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 08, 2018 | The p.R3211H variant (also known as c.9632G>A), located in coding exon 40 of the TTN gene, results from a G to A substitution at nucleotide position 9632. The arginine at codon 3211 is replaced by histidine, an amino acid with highly similar properties. 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