rs200284932
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_133379.5(TTN):c.10617T>C(p.His3539His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000438 in 1,613,206 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_133379.5 synonymous
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_133379.5 | c.10617T>C | p.His3539His | synonymous_variant | Exon 46 of 46 | ENST00000360870.10 | NP_596870.2 | |
TTN | NM_001267550.2 | c.11311+1341T>C | intron_variant | Intron 47 of 362 | ENST00000589042.5 | NP_001254479.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000360870.10 | c.10617T>C | p.His3539His | synonymous_variant | Exon 46 of 46 | 5 | NM_133379.5 | ENSP00000354117.4 | ||
TTN | ENST00000589042.5 | c.11311+1341T>C | intron_variant | Intron 47 of 362 | 5 | NM_001267550.2 | ENSP00000467141.1 |
Frequencies
GnomAD3 genomes AF: 0.000414 AC: 63AN: 152000Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000795 AC: 199AN: 250208Hom.: 2 AF XY: 0.000754 AC XY: 102AN XY: 135226
GnomAD4 exome AF: 0.000441 AC: 644AN: 1461088Hom.: 2 Cov.: 39 AF XY: 0.000473 AC XY: 344AN XY: 726830
GnomAD4 genome AF: 0.000414 AC: 63AN: 152118Hom.: 1 Cov.: 32 AF XY: 0.000403 AC XY: 30AN XY: 74358
ClinVar
Submissions by phenotype
not specified Benign:4
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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. -
His3539His in exon 45A of TTN: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 0.1% (6/7020) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS). His3539His in exon 45A of TTN (al lele frequency = 0.1%, 6/7020) ** -
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not provided Benign:2
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TTN: BP4, BP7 -
TTN-related disorder Benign:1
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). -
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 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at