rs34706803
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2
The NM_001267550.2(TTN):c.13976A>G(p.Tyr4659Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000809 in 1,608,126 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. Y4659Y) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.13976A>G | p.Tyr4659Cys | missense_variant | 48/363 | ENST00000589042.5 | |
LOC124906101 | XR_007087319.1 | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.13976A>G | p.Tyr4659Cys | missense_variant | 48/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.1133+964T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000788 AC: 120AN: 152226Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00145 AC: 358AN: 246586Hom.: 1 AF XY: 0.00146 AC XY: 195AN XY: 133748
GnomAD4 exome AF: 0.000811 AC: 1181AN: 1455900Hom.: 10 Cov.: 30 AF XY: 0.000837 AC XY: 605AN XY: 723196
GnomAD4 genome ? AF: 0.000788 AC: 120AN: 152226Hom.: 2 Cov.: 32 AF XY: 0.000740 AC XY: 55AN XY: 74358
ClinVar
Submissions by phenotype
not specified Benign:6
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 10, 2019 | proposed classification - variant undergoing re-assessment, contact laboratory - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 06, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 24, 2017 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 01, 2020 | - - |
Benign, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | TTN: BS1 - |
Autosomal recessive limb-girdle muscular dystrophy type 2J Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | May 02, 2018 | - - |
Early-onset myopathy with fatal cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Tibial muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Myopathy, myofibrillar, 9, with early respiratory failure Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
TTN-related condition Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 14, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Primary dilated cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego | Apr 06, 2018 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 22, 2018 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at