chr2-178552209-G-A
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001267550.2(TTN):c.90691C>T(p.Pro30231Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,472 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P30231P) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.90691C>T | p.Pro30231Ser | missense_variant | Exon 335 of 363 | ENST00000589042.5 | NP_001254479.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.90691C>T | p.Pro30231Ser | missense_variant | Exon 335 of 363 | 5 | NM_001267550.2 | ENSP00000467141.1 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152120Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000363 AC: 9AN: 247906 AF XY: 0.0000372 show subpopulations
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461234Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 726856 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000131 AC: 20AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74430 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
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not specified Uncertain:1
Variant summary: TTN c.82987C>T (p.Pro27663Ser) results in a non-conservative amino acid change located in the A-band domain of the encoded protein sequence. Three of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 247906 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.82987C>T in individuals affected with Limb-Girdle Muscular Dystrophy, Type 2J and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 497188). Based on the evidence outlined above, the variant was classified as uncertain significance. -
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
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Cardiovascular phenotype Uncertain:1
The p.P21166S variant (also known as c.63496C>T), located in coding exon 162 of the TTN gene, results from a C to T substitution at nucleotide position 63496. The proline at codon 21166 is replaced by serine, an amino acid with 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