rs537578226
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1
The NM_001267550.2(TTN):c.40250C>T(p.Pro13417Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000575 in 1,547,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.40250C>T | p.Pro13417Leu | missense_variant | Exon 216 of 363 | ENST00000589042.5 | NP_001254479.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.40250C>T | p.Pro13417Leu | missense_variant | Exon 216 of 363 | 5 | NM_001267550.2 | ENSP00000467141.1 |
Frequencies
GnomAD3 genomes AF: 0.000132 AC: 20AN: 151906Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.000256 AC: 38AN: 148320Hom.: 0 AF XY: 0.000275 AC XY: 22AN XY: 79856
GnomAD4 exome AF: 0.0000494 AC: 69AN: 1395438Hom.: 0 Cov.: 28 AF XY: 0.0000567 AC XY: 39AN XY: 688320
GnomAD4 genome AF: 0.000132 AC: 20AN: 152022Hom.: 0 Cov.: 30 AF XY: 0.000162 AC XY: 12AN XY: 74300
ClinVar
Submissions by phenotype
TTN-related disorder Benign:1
This variant is classified as likely 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 Benign:1
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Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
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Early-onset myopathy with fatal cardiomyopathy Benign: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 Benign:1
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not provided Benign:1
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Tibial muscular dystrophy Benign:1
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Myopathy, myofibrillar, 9, with early respiratory failure Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at