2-178751841-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_133379.5(TTN):c.10559C>A(p.Pro3520Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,612,612 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P3520P) has been classified as Likely benign.
Frequency
Consequence
NM_133379.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_133379.5 | c.10559C>A | p.Pro3520Gln | missense_variant | Exon 46 of 46 | ENST00000360870.10 | NP_596870.2 | |
TTN | NM_001267550.2 | c.11311+1283C>A | 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.10559C>A | p.Pro3520Gln | missense_variant | Exon 46 of 46 | 5 | NM_133379.5 | ENSP00000354117.4 | ||
TTN | ENST00000589042.5 | c.11311+1283C>A | intron_variant | Intron 47 of 362 | 5 | NM_001267550.2 | ENSP00000467141.1 |
Frequencies
GnomAD3 genomes AF: 0.0000725 AC: 11AN: 151802Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250062Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135180
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460810Hom.: 0 Cov.: 39 AF XY: 0.00000138 AC XY: 1AN XY: 726664
GnomAD4 genome AF: 0.0000725 AC: 11AN: 151802Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 3AN XY: 74130
ClinVar
Submissions by phenotype
not specified Uncertain:1
Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in CARDIOMYOPATHY panel(s). -
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
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at