2-178558485-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001267550.2(TTN):c.86974T>C(p.Cys28992Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,704 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001267550.2 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_001267550.2 | c.86974T>C | p.Cys28992Arg | missense_variant | Exon 327 of 363 | ENST00000589042.5 | NP_001254479.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.86974T>C | p.Cys28992Arg | missense_variant | Exon 327 of 363 | 5 | NM_001267550.2 | ENSP00000467141.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152134Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248506Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134780
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461570Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727076
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152134Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74296
ClinVar
Submissions by phenotype
not specified Uncertain:1
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Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain: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 Uncertain:1
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Congenital long QT syndrome Uncertain:1
The c.86974T>C missense variant in TTN is reported in ClinVar as VUS (SCV000317996) and is absent from population databases like gnomAD, indicating rarity (PM2). However, there is insufficient evidence supporting its pathogenicity (BP1). Due to the lack of conclusive data, this variant is classified as a VUS (ACMG codes: PM2, BP1). -
Cardiovascular phenotype Uncertain:1
The p.C19927R variant (also known as c.59779T>C), located in coding exon 154 of the TTN gene, results from a T to C substitution at nucleotide position 59779. The cysteine at codon 19927 is replaced by arginine, an amino acid with highly dissimilar properties. Based on data from ExAC, the C allele was reported in 2 of 120394 total alleles (Exome Aggregation Consortium (ExAC), Cambridge, MA (URL: http://exac.broadinstitute.org) [Accessed September 29, 2015]). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6028 samples (12056 alleles) with coverage at this position. 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 variant remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at